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https://f1000research.com/articles/13-187/v1
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11 Mar 24
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{
"type": "Research Article",
"title": "Risk assessment based on fault tree analysis and analytic hierarchy process in rural areas of Thailand",
"authors": [
"Ratchanee Joomjee",
"Momthicha Raksin",
"Yanitha Paengprakhon",
"Jaruporn Duangsri",
"Niruwan Turnbull",
"Ratchanee Joomjee",
"Momthicha Raksin",
"Yanitha Paengprakhon",
"Jaruporn Duangsri"
],
"abstract": "Introduction The importance of understanding the factors contributing to road accidents at schools cannot be overstated. This study aims to determine the risk of accidents in situations that could lead to accidents near schools.\n\nMethods A total of 10 kindergarten to junior high schools were selected for the study. The research used the Haddon Matrix to classify factors at risk of accidents, risk assessment through fault tree analysis, and the analytic hierarchy process (FTA-AHP) techniques. Fourteen sub-criteria were defined for risk identification, risk probability analysis, and risk assessment of the 10 roads. The likelihood of each event was analyzed using the AHP technique for all schools with an expert choice program. RI (random index) was calculated, and CR (consistency ratio) < 0.10 was considered satisfactory.\n\nResults The possibility of human accidents ranked highest in three areas: 1) Risk perception in SC 01, 03, and 02, with probabilities of 69.30%, 61.90%, and 57.4%, respectively. 2) The likelihood of accidents from vehicles/equipment, with the highest probabilities in a) Handling (SC01) at 64.70%, b) Braking (SC07) at 61.90%, and c) Lighting (SC03) at 57.80%. 3) The likelihood of accidents from the environment, with the highest probabilities in 1) driving at excessive speeds in areas SC01, 06, 03, and 09, which were 43.60%, 40.90%, and 40.00%, respectively.\n\nConclusions The impacts of all three main factors were as follows: a) humans had the highest impact in the SC01 area (77.90%), b) vehicles/equipment had the highest impact in the SC01 area (75.90%), and c) the highest environmental impact in the SC01 area was 69.90%. The accident risk assessment revealed the highest risk score in three areas: 1) human risk perception, 2) environment with driving at excessive speeds, and 3) vehicle/equipment, including lighting, braking, and handling.",
"keywords": [
"Risk assessment",
"School road",
"Traffic accident",
"(FTA-AHP) techniques",
"Analytic Hierarchy Process"
],
"content": "Introduction\n\nIn 2018, 1.35 million people died due to crashes involving motor vehicles, most of which were young people between the ages of five to 29 years old, and the majority of victims were pedestrians, cyclists, motorcyclists, and animals. Most accidents occur in developing countries.1,2 Accidents affect victims, both directly and indirectly. Direct effects include death, injury, loss of medical expenses, and property damage. Some indirect effects of road accidents include loss of income, changes in the mental health of the victim and those involved, and impact on the country’s business and society.3,4 The global death toll from traffic accidents is increasing. Registration statistics indicate that vehicle incidents have increased annually.5 Accidents directly and indirectly impact victims, their families, society, and the nation, as well as injuries, medical costs, and road safety campaign budgets.3 According to the World Bank Country and Lending Groups, Thailand is a developing country with a middle-income6 economy, which ranks first in Southeast Asia and eighth in the world for road fatalities, with an average of 32.7 deaths per 100,000 residents.1 Road environments can contribute to this tragedy, which kills young adults worldwide. Thailand has one of the highest accident rates worldwide.1,2,7 There have been reports of road traffic injuries and fatalities among 12–14-year-old children in the southern region of Thailand, resulting in severe disability and mortality, especially among those with pediatric traumatic brain injuries (TBI).8 The most hazardous environment was rural roads with intersections. In rural areas, the accident rate is approximately 30%, 6% of all severe accidents.5\n\nThe Haddon Matrix principle was devised to investigate accidents and road traffic injuries. It was evaluated from three vantage points: pre-event, event, and post-event phases, as well as three factors:1) human variables, 2) equipment/vehicle variables, and 3) environmental variables.9 Fault tree analysis was used to analyze the risk of accidents to identify risk factors and the primary cause of public safety accidents by defining the potentially severe impact as the top event and identifying the fundamental event leading to a potentially powerful impact. For example, the evaluation of road accidents at the severity level that will impact catastrophe revealed the following risk factors:1) internal system failures, including battery failures, mechanical failures, and flight control system failures; 2) pilot factors, including unqualified knowledge and skills, poor safety awareness, violations, and lack of legal understanding; and 3) external environmental impacts, including obstacles, route planning issues, and unclear airspace. The Analytical Hierarchy Process (AHP) is also used to rank risky events to create a risk management plan that can be influenced by accidents.10,11 The Haddon Matrix method classifies the causes of road incidents into three factors: driver behavior (41%), road environment (26%), and condition of the vehicle (33%). Males constituted a more significant proportion of road traffic casualties (RTCs) than females (61.39 vs. 38.61, P <0.05). The male mortality rate was 63.23 percent, with an average age of 33.65 and 16.76 years. Secondary school students had the highest morbidity and mortality rate (40.25%). Male adolescents are approximately three times more likely to experience road accidents than females, and mobile phone use while driving is typical at this age.12 The percentage of individuals injured everywhere on their bodies (16.57%), upper or lower bodies (17.84%), skulls (20.77%), and abdomen (15.75%) varied considerably.13 Road accidents are more common among drivers aged 17–25 years old. There is a correlation between severe accidents and excessive pace. Therefore, natural control measures exist. To prevent and reduce the number of casualties, stopping at intersections (T-intersections), controlling the road environment (e.g., the number of lanes, slope adjustment, and speed limit with a stop), traffic control devices, driver safety controls (age, gender, and speed), and prevention of accidents caused by natural disasters (e.g., providing weather forecasts and specifying the day and time of storms and rain)14 are needed.\n\nThis study investigates main road safety in Ubon Ratchathani Province, Thailand. A total of 17 Ubon Ratchathani town schools with routes to other districts were studied. It studied three pre-accident risk factors:1) in humans to analyze road user hazards to kindergarten and lower secondary students (6–15 years old). 2) Vehicle/equipment characteristics of cars that drive across the road in front of all ten schools. 3) How the school’s road environment may affect children’s ability to prioritize road risk mitigation actions. This study employed fault tree analysis and the analytic hierarchy process (AHP) to identify risk variables and road accident prevention techniques in the following order.\n\nTo assess the road accident risk factors for each event resulting in an accident on a school road.\n\n\nMethods\n\nThe study design was approved by the Ethical Review Committee for Human Research, Ubon Ratchathani Rajabhat University (Study No. 015/2563-HE632027) on 7 March 2020. Written informed consent forms were completed by all participants.\n\nA cross-sectional study utilized a checklist to effectively gather information for assessing the probability and risk of incidents on selected school main roads in Ubon Rattanathi, Thailand, from April to December 2020. We engaged stakeholders, including schoolteachers, community leaders, and parents of students, representing 17 schools. Our selection process focused on the main roads adjacent to those schools, involving 10 kindergartens to junior high schools in Ubon Rattanathi. There were 125 participants in the risk assessment model for road accidents near schools, and this assessment took place from April to December 2020.\n\nThe study was conducted in three phases. The initial phase, spanning from April to May 2020, involved data collection from three schools: Ban Dampra School, Ban Thabor School, and Ban Namean School. Subsequently, the second phase took place from June to July 2020, during which data was gathered from three different schools: Ban Khamyai School, Ban Tungkunnoi-Nongjan Wittaya School, and Ban Pladuk School. The final phase, covering September to October 2020, involved data collection from four schools: Ban Yang Lum School and Ban Nonglai School. Following the completion of the data collection phases, three months were allocated for data gathering, culminating in data analysis conducted in November and December 2020 (Figure 1).\n\nData collection for this study occurred at different times for various schools, potentially introducing temporal bias or seasonal variations. However, during data analysis, we addressed this concern by accounting for seasonal differences in traffic patterns and weather conditions. One potential issue with this study is selection bias since it focused on specific schools in the province of Ubon Rattanathi, Thailand, which may only be representative of regional schools. We selected schools with diverse characteristics and locations to minimize bias to ensure a more representative sample. We also addressed measurement bias by employing standardized incident reporting protocols and training personnel for data collection. To account for potentially confounding factors like traffic volume, speed limits, road conditions, and weather conditions, we used AHP with FTA-AHP analysis to adjust for their influence. Subgroup analyses were conducted to examine effect modifiers, such as whether the relationship between outcomes and exposure varied based on school type or other factors.\n\nInclusion criteria included schools under the Ubon Ratchathani Primary Educational Service Area Office’s authority in high-risk areas and on main thoroughfares. Institutions not cooperating with the study during the research period were also excluded.\n\nThe data collection instrument used in this study was derived from the Haddon Matrix, a highly acknowledged and influential framework in injury prevention. The matrix, developed by William Haddon in 1970,15 analyses a range of factors related to individual characteristics, features of the vector or agent, and environmental variables before, during, and after an injury or fatality. Hence, the risk assessment form successfully identifies three distinct elements. The three categories considered in this study were as follows: 1) human/student, in humans to analyze road user hazards to kindergarten and lower secondary students (6–15 years old), 2) Vehicle/equipment characteristics of cars that drive across the road in front of all ten schools, and 3) the school’s road environment may affect children’s ability to prioritize road risk mitigation actions. These categories are derived from the Haddon Matrix. All 14 accidents underwent risk probability analysis and risk assessment for 10 roads based on the following factors: age, playing on the road, use of mobile phones, risk perception, vehicle/equipment, roadworthiness, lighting, braking, handling, environment, clear traffic signs, expressways, sidewalks, bus stops, school gates, and driving at excessive speeds. These accidents with similar characteristics were identified in a few studies.5,16,17 Subsequently, a risk analysis was conducted, and risks were prioritized using the FTA-AHP technique in the following order.\n\nWe conducted data collection activities from 2020 to 2022 by using a risk assessment approach for road accidents around schools. This assessment consists of three parts, which are information about students, vehicles/equipment, and the environment. Subsequently, the assessment was tested on a pilot group and implemented in a pilot school. Data from the pilot test was collected and feedback was used to make improvements during February 2020. Then, the assessment tool that had undergone quality checks was sent to experts for review in March 2020, before using it for risk assessment with a sample of 10 schools in the next phase. The risk assessment model for road accidents near schools, which has undergone quality checks, was used to assess the risk in 10 schools, namely: 1) Ban Dampra School 2) Ban Thabor School 3) Ban Namean School 4) Ban Khamyai School 5) Ban Tungkunnoi-Nongjan Wittaya 6) Ban Pladuk School 7) Ban Yang Lum School 8) Ban Nonglai School 9) Ban Huakam School and 10) Ban Phakaew School. This process was carried out in collaboration with the Education Committee in each school, including community leaders, community management committees, and school management committees, totaling 25 people. Therefore, there were 125 participants in the risk assessment model for road accidents near schools, and this assessment took place from April to December 2020. The first group of three schools collected data within the time frame covering April to May 2020. These particular schools encompassed Ban Dampra School, Ban Thabor School, and Ban Namean School. The second cohort of three schools gathered information from June to July 2020. The schools under consideration included Ban Khamyai School, Ban Tungkunnoi-Nongjan Wittaya School, and Ban Pladuk School. The final group of four schools that gathered data during a time frame covering from September to October 2020 consisted of Ban Yang Lum School and Ban Nonglai School. Following this, three months were allocated for data collection, which was later subjected to analysis during November and December 2020.\n\nFault tree analysis (FTA) quantifies a qualitatively identified risk from a relevant primary system as the top event in the tree for deductive reasoning based on risk factor probabilities.16,17 FTA has considered three factors that cause school road traffic accidents: 1) Human/Student, such as age 6-15 years old, playing on the road, using a mobile phone, and risk perception; 2) Vehicle/Equipment, such as roadworthiness, lighting, braking, handling, and 3) Environment, such as clear traffic sign, motorway, sidewalk way, bus stop, school gates, driving at excessive speeds), The hazard conditions in front of 10 schools within a two-kilometer radius were recorded (Figure 2).\n\nThe values of each factor were categorized into five ranks (very low, low, moderate, high, and very high) according to the value ranges encountered for each layer. Subsequently, the weight for each factor was estimated based on Saaty’s AHP18,19 (Table 1). The consistency index (CI) and the consistency ratio (CR) were calculated based on equation (1) in (Figure 3).18,19\n\nThe likelihood of each event was analyzed using the AHP technique of all ten schools with an expert choice program, RI=random index, and CR≤0.10 was considered acceptable, and the weights calculated for risk school road areas were considered statistically acceptable.\n\nThe Analytic Hierarchy Process (AHP) were impact (I) and probability (P) from the FTA equation, which was obtained from equations 3 and 417 (Figure 4).\n\nThe data29 were validated and analyzed using the AHP technique of all 10 schools with the Expert Choice program version 11 to determine the chance of each event (Open source alternative: DecisionBuilderTM, Minitab). RI=random index and CR<0.10 was regarded satisfactory.\n\nThe probability and impact rating of the risk assessment with a five-level risk matrix (Tables 2 and 3) were based on the event’s probability. There are four risk score levels: negligible (1 to 5), tolerable (6 to 9), undesirable (10 to 16), and intolerable (17 to 25) (Figure 5).17\n\n\nResults\n\nUsing the FTA-AHP technique to analyze the likelihood of incidents in 10 areas, the study determined that the likelihood of an accident from each of the three main factors (Human/Student, Vehicle/Equipment, and Environment) is as follows: 1) The highest three rankings from Risk Perception in area SC 01,03, 02,05 for the effect of an accident involving human/student were 69.30%, 61.90%, and 57.4%, respectively. The highest three vehicle/equipment rankings for the likelihood of an accident were\n\n• 64.70 percent for Handling in the SC 01 area,\n\n• 61.90 percent for braking in the SC 07 area, and\n\n• 57.80 percent for lighting in the SC 03 area.\n\nThe likelihood of an accident owing to the environment was 43.60%, 40.9%, and 40% in areas SC 01, 06, 03, and 09, respectively. The combined probabilities of the three primary factors, SC 01, SC 03, SC 02, and SC 05, had the greatest effects on humans/students (77.90%, 74.90%, and 73.40%, respectively). 74.90%, 74.90%, and 73.40% of SC 01, SC07, and SC06, respectively, were affected by vehicles or equipment. The cumulative effect on the environment in sectors SC 01, SC 07, and SC 06 was 100% (69.90, 69.30, and 69.10, respectively) (Figure 6).\n\nIn 10 schools, Human/Student (Risk Perception) and Environment (Driving at excessive rates) had the highest risk score of level 3 (Undesirable 10–16). 1) Lighting zone SC 03 (Ban Namean School), SC 04 (Ban Khamyai School), SC 05 (Ban Tungkunnoi-Nongjan Wittaya), SC 08 (Ban Nonglai School), SC 09 (Ban Huakam School). 2) Braking zone SC 07 (Ban Yang Lum School), SC 10 (Ban Phakaew School). 3) Handling zone SC 01 (Ban Dampra School), SC 02 (Ban Thabor School), SC 06 (Ban Pladuk School) (Figure 7, Table 4).\n\n\nDiscussion\n\nFor the 10 school road traffic accidents in 10 areas classified by the Haddon Matrix method, the risk levels of all three factors were at level 3 (undesirable). Depending on students and road users, it was found that for Human/Student, the highest probability was 77.90%, Vehicle/Equipment was 75.90%, and environment was 69.90% (found in area SC 01). The highest probability was found in 69.30% of risk perception, 64.70% of handling, and 43.60% of driving at excessive speeds, consistent with educational road traffic accidents, among the leading causes of injury and death worldwide. This resulted in a 100% risk of mortality and injury for road users, particularly for 81% of vulnerable road users and 36% of drivers. Accident-causing factors include human characteristics, vehicles, road characteristics, and environmental conditions, such as rush hour and school term time in the morning.20–23\n\nTransportation Research Information Services (TRIS)\n\nTransportation Research Information Services (TRIS) found human behavioral factors to be at the highest risk of road accidents at 41%, environmental factors at 26%, and vehicle factors at 33% (5). Behaviors can contribute to the risk of accidents, such as not crossing the road on a pedestrian crossing or a designated route and crossing during heavy traffic. Risky environmental factors are infrastructures such as sidewalks, zebra crossing, pedestrian-protected space at the exit, two-way streets, protected routes/corridors for pedestrian children, and 30 km/h zones. We also found that the density of cars in road environments with speed driving is a major factor causing accidents and the severity of the accidents.24–26 According to this study, lack of road user safety awareness (69.30%), driving at high speeds in school zones (46.30%), and utilizing cars in incomplete situations (e.g., damaged) had the most significant impact on road accidents. Inadequate lighting on roads and vehicles was identified as an essential factor in road accidents, accounting for 57.80% of all incidents. Poor visibility owing to insufficient lighting can lead to increased risk for drivers and pedestrians. Braking issues accounted for 61.90% of road accidents. Problems with vehicle braking systems, such as worn-out brakes or delayed response times, can lead to collisions and a reduced ability to avoid accidents. Handling-related factors contributed to 64.70% of road accidents. Difficulties in maneuvering and controlling vehicles, particularly in emergencies, can increase the likelihood of accidents.\n\nActive school travel\n\nPersonal safety, traffic safety, distance to school, school factors, and social factors are essential for student traffic safety, and we have analyzed the risk of road accidents and established proactive preventive measures in the area to reduce the risk of traffic on the road, including legislation to regulate driving speed and response to road infrastructure. Safe crossing measures are essential to protect students while walking across the roads, especially in nearby schools. This includes providing pedestrian crossings and designated routes with proper signage and traffic signals. Educating students about the importance of using designated crossings and following traffic rules is crucial to instilling road safety awareness from a young age. Ensuring a safe road environment for motorcycles and bicycles involves several aspects. First, establishing dedicated lanes and routes for bikes and motorbikes can separate them from faster-moving vehicular traffic, reducing the risk of collisions.23,27 In addition, the government should support road safety through public education. Personal safety, traffic safety, distance to school, school factors, and social factors are essential for student traffic safety, and we have analyzed the risk of road accidents and established proactive preventive measures in the area to reduce the risk of traffic on the road, including legislation to regulate driving speed and response to road infrastructure.\n\nSafe crossing measures are essential to protect students while they crossroads, especially in areas near schools. This includes providing pedestrian crossings and designated routes with proper signage and traffic signals. Educating students about the importance of using designated crossings and following traffic rules is also crucial to instilling road safety awareness from a young age. Ensuring a safe road environment for motorcycles and bicycles involves several aspects. First, establishing dedicated lanes and routes for bikes and motorbikes can separate them from faster-moving vehicular traffic, reducing the risk of collisions.23,27 In addition, the government should support road safety through public education. Strict enforcement of the law, especially regarding driving faster than the law, and improving the road environment is considered safer to ensure road user safety.28\n\n\nConclusion\n\nThe FTA-AHP technique was selected for the study on the school’s main highways in the Ubon Ratchathani Province of Thailand. In terms of human/student (Risk Perception), environment (driving at excessive speeds), and vehicle/equipment (Lighting, Braking, Handling), the highest risk score was level 3. The area surrounding SC01 had the highest accident probability for all 10 schools owing to risk perception (69.30%), handling (64.70%), and driving at excessive velocities (43.60%). Human/student (77.90%), vehicle/equipment (75.90%), and environment (69.90%) had the most significant influence in area SC 01. Therefore, it is necessary to prevent or reduce the risk of road accidents. First, road users must be aware of risks and adhere rigorously to traffic regulations. Regarding traffic knowledge, a safe road environment, and strict adherence to traffic laws, schools, communities, and government organizations must support them.\n\n\nAuthor contributions\n\nRatchanee Joomjee: Conceptualization, Investigation, Writing – Original Draft Preparation\n\nMomthicha Raksin: Resources, Supervision\n\nYanitha Paengprakhon: Formal Analysis, Investigation\n\nJaruporn Duangsri: Methodology, Project Administration, Software\n\nNiruwan Turnbull: Project Administration, Validation, Writing – Review & Editing",
"appendix": "Data availability\n\nFigshare: Risk Assessment Factors of Road Accident at School Based on Fault Tree Analysis and Analytic Hierarchy Process in Rural of Thailand. https://doi.org/10.6084/m9.figshare.23626425. 29\n\nThis project contains the following underlying data:\n\n• Underlying data.xlsx. (Results of the survey conducted on various aspects of road safety)\n\nFigshare: Risk Assessment Factors of Road Accident at School Based on Fault Tree Analysis and Analytic Hierarchy Process in Rural of Thailand. https://doi.org/10.6084/m9.figshare.23626425. 29\n\nThis project contains the following extended data:\n\n• Risk Assessment Form - English.pdf. (The data used to assess and manage potential risks to students and staff at various schools)\n\n• Risk Assessment Form - Thai.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nQUVAE Research & Publications provided guidance and support during the submission process for this article and data deposition.\n\n\nReferences\n\nGlobal Status Report on Road Safety: 2018. Reference Source\n\nAbra FD, Granziera BM, Huijser MP, et al.: Pay or prevent? Human safety, costs to society and legal perspectives on animal-vehicle collisions in São Paulo state, Brazil. PLoS One. 2019; 14(4): e0215152. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRizzi LI, de Dios O ; xfa, zar J: Road Safety Valuation under a Stated Choice Framework. JTEP. 2006; 40(1): 69–94.\n\nTrawén A, Maraste P, Persson U: International comparison of costs of a fatal casualty of road accidents in 1990 and 1999. Accid. Anal. 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Technol. 2018; 13: 208–221. Publisher Full Text\n\nBocage C, Mashalla Y, Motshome P, et al.: Applying the Haddon matrix conceptual model to guide motor vehicle crash injury research and prevention in Botswana. Afr. J. Emerg. Med. 2020; 10: S38–S43. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTao L, Chen L, Long P, et al.: Integrated risk assessment method for spent fuel road transportation accident under complex environment. Nucl. Eng. Technol. 2021; 53(2): 393–398. Publisher Full Text\n\nHyun K-C, Min S, Choi H, et al.: Risk analysis using fault-tree analysis (FTA) and analytic hierarchy process (AHP) applicable to shield TBM tunnels. Tunn. Undergr. Space Technol. 2015; 49: 121–129. Publisher Full Text\n\nKanuganti S, Agarwala R, Dutta B, et al.: Road safety analysis using multi criteria approach: A case study in India. Transp. Res. Procedia. 2017; 25: 4649–4661. Publisher Full Text\n\nFernandez JJ, Paringit MC, Salvador JR, et al.: Driver’s Road Accident Factor Prioritization using AHP in Relation to Mastery of Traffic Signs in the City of Manila. Transp. Res. Procedia. 2020; 48: 1316–1324. Publisher Full Text\n\nChand A, Jayesh S, Bhasi AB: Road traffic accidents: An overview of data sources, analysis techniques and contributing factors. Mater. Today: Proc. 2021; 47: 5135–5141.\n\nYang T, Zeng H, Yang X, et al.: Characteristics of road traffic accident types and casualties in Guangzhou, China, from 2007 to 2020: A retrospective cohort study based on the general population. Heliyon. 2023; 9(1): e12822. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhao L, Wang C, Yang H, et al.: Exploring injury severity of Non-Motor vehicle riders involving in traffic accidents using the generalized ordered logit model. Ain Shams Eng. J. 2023; 14(5): 101962. Publisher Full Text\n\nKingham S, Sabel CE, Bartie P: The impact of the ‘school run’ on road traffic accidents: A spatio-temporal analysis. J. Transp. Geogr. 2011; 19(4): 705–711. Publisher Full Text\n\nBina M, Confalonieri F, Abati D, et al.: Analysis of traffic upon school departure: Environment, behaviour, well-being and risk factors for road crashes. J. Transp. Health. 2021; 22: 101119. Publisher Full Text\n\nPei X, Wong SC, Sze NN: The roles of exposure and speed in road safety analysis. Accid. Anal. Prev. 2012; 48: 464–471. PubMed Abstract | Publisher Full Text\n\nAhmed S, Hossain MA, Ray SK, et al.: A study on road accident prediction and contributing factors using explainable machine learning models: analysis and performance. Transp. Res. Interdiscip. Perspect. 2023; 19: 100814. Publisher Full Text\n\nSmith M, Ikeda E, Hawley G, et al.: An integrated conceptual model of environmental needs for New Zealand children’s active travel to school. J. Transp. Health. 2020; 16: 100814. Publisher Full Text\n\nZhang Q, Lu Y, Feng F, et al.: Causal analysis of coach and bus accidents in China based on road alignments. Heliyon. 2023; 9(4): e15231. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJoomjee R, Raksin M, Paengprakhon Y, et al.: Risk Assessment Factors of Road Accident at School Based on Fault Tree Analysis and Analytic Hierarchy Process in Rural of Thailand. [Dataset]. Figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "261889",
"date": "14 May 2024",
"name": "Shehzad Saleem",
"expertise": [
"Reviewer Expertise Public Health"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study's conclusions and suggestions may influence and enhance safety protocols, legislative choices, and instructional programs, thereby lowering the chance of traffic accidents and fostering a safer atmosphere for communities and students. The scholars' commitment to this significant subject is really admirable! Description about significance of study:\nThe Haddon Matrix and other methods were utilized in a study on traffic accidents near schools in Ubon Rattanathi, Thailand, in order to identify and evaluate risk factors.The study discovered that the biggest risk factors were human perception of risk, the environment (particularly speeding), and problems with vehicles and equipment, with human conduct accounting for the most important portion (77.90%). The survey also found that utilizing defective vehicles, speeding in school zones, and a lack of safety knowledge were key causes of accidents. These results are consistent with earlier studies that found behavioral aspects of human conduct to be the greatest risk factor (41%), followed by environmental and vehicle components.\nComments: 1. The writers skipped over 'accidents' in the title. (The title could be changed to: Risk assessment of Road accidents in rural Thailand: A fault tree analysis) 2. The authors have describes ''The most hazardous environment was rural roads'' - So, why they have conducted this study in urban settings ''involving 10 kindergartens to junior high schools in Urbon Rattanathi'' and not in rural roads? 3. Please explain why was a variable not included in the FTA hierarchy. 4. Please find spelling mistakes such as: (Ubon=Urban; Risk Risk level of school=Risk level of School) 5. The last 2 lines of the conclusion give recommendations for the drivers and not for the environmental changes which can reduce accidents 6. The study design is appropriate, and suitable for the research question or objective.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "267027",
"date": "22 May 2024",
"name": "Arroon Ketsakorn",
"expertise": [
"Reviewer Expertise Occupational Health and Safety"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAccording to the title, the manuscript describes the risk assessment by applying the fault tree analysis and analytic hierarchy process in rural areas of Thailand. Partly due to language issues, the manuscript is not easy to read and understand, especially regarding the fault tree analysis and analytic hierarchy process. It is unclear how to use both fault tree analysis and analytic hierarchy process. Why did the authors choose to use those tools? However, this study has many good and important aspects, but the manuscript needs some major, but I view, very “do-able” revisions.\n\nTitle\nPlease specific the study area in the title. It's too spacious for rural areas.\n\nAbstract\nPlease adjust the writing of the introduction to be consistent with what you want to study. Please check typo error entire the manuscript. Authors need to determine the factors for assessing the risk. Please rewrite of the methods section. The authors should explain the details of study. Fourteen sub-criteria? What are the main criteria? “RI (random index) was calculated” This sentence is not correct. Please revise it. The conclusion should not be written in duplicate with the results of the study. This “traffic accident” does not reflect research study. The FTA-AHP techniques duplicated with Analytic Hierarchy Process.\nIntroduction\nLack of explanation on the area of study and the issues/problems. The authors need to elaborate more on the issues towards road traffic accident at school. Please support the road traffic accident at school with citations or literature sources when elaborating the aspects. This is important step to find out the gap of research. Due to language issues, the manuscript is not easy to read and understand. Please send the manuscript to a native speaker to check before submission. What are the advantage and disadvantage of using AHP? Why did the authors choose the fault tree analysis? Please provide supporting reasons.\nObjective\nPlease adjust the objective to be consistent with the research title.\nMethods\nWhere does the checklist form come from? Who made it? Please give details. Please add more details of FTA and AHP including risk assessment How does the authors prove the FTA diagram? Please add the details The method for doing AHP should be explained in detail. In the case where there are many evaluators, what is the method for doing it? Please add the reference in Table 3 and Figure 5. “Figure 5 Risk scoring matrix” This is a table, not a figure. Please give the meaning the risk class; negligible 1-5; Tolerable 6-9; Undesirable 10-16; Intolerable 17-25.\nResults\nPlease give an example of manual calculation for AHP. Please show the results from Expert Choice program.\nDiscussion\nThe results should be discussed in the section FTA; AHP and risk assessment. The discussion part should not be written in duplicate with the results of the study. Authors must first discuss the study's findings and then explain how the study's results are similar or different from other studies.\nConclusion\nThe conclusion should not be written in duplicate with the results of the study.\nReferences\nHarmonize format with F1000Research style requirements.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-187
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https://f1000research.com/articles/13-185/v1
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11 Mar 24
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{
"type": "Systematic Review",
"title": "Distributing Zakatu Kasbil 'Amal as an Alternative to Student Funding, Evidence in Indonesia’s Universities",
"authors": [
"Marliyah Marliyah",
"Budi Dharma",
"Ahmad Muhaisin B. Syarbaini",
"Budi Dharma",
"Ahmad Muhaisin B. Syarbaini"
],
"abstract": "Background The purpose of this paper is to clarify the use of zakat as an alternative funding for students to pay their tuition fees. Apart from that, this paper also explains how zakat collected from muzakki fixed income known as zakatu kasbil 'amal, which is known as income zakat and is still controversial in Indonesia.\n\nMethod The study uses a systematic literature review with an inductive approach to find out the theoretical basis of the research questions. The analysis uses a qualitative method that explores significant findings from various literature sources. The findings will combine with the exploration results of several universities in Indonesia that use social funds as a tool for helping students.\n\nResult The income zakat controversy mediates using the precautionary principle, which ensures that the projected income indeed exceeds the nisab (1 year) of the income. Some Islamic universities in Indonesia carry out this zakat withdrawal and even use an auto debit system. On the other hand, the distribution of zakat to students is also controversial because zakat is part of worship whose distribution is regulated into nine asnaf. Nevertheless, students may be equated with one of the asnaf so that it becomes permissible to be the subject of zakat distribution. Observation findings at Indonesian Islamic universities even show that the results of zakat distribution strongly influence the success of students’ studies, even if only in aid of tuition fees.",
"keywords": [
"Improving University Quality",
"Income Zakat",
"Indonesian Universities",
"Student Funding."
],
"content": "1. Introduction\n\nOne of the root problems in Indonesian higher education is student funding. Providing alternative student funding will significantly contribute to higher education improvement in Indonesia. The basis for the emergence of student funding problems is the increasing costs of higher education, which stem from the university’s expectation to grow in an era of technological disruption and high competition.1 Even though universities can obtain operational funding assistance from various parties,2 more is needed to ease the burden transferred to students. The educational costs charged to students tend to increase yearly.3\n\nEven though Indonesian people’s participation in higher education tends to increase yearly,4,5 it is dominated by communities with the highest per capita income in Indonesia.6,7 BPS-Statistics Indonesia reports (2022b) show that the average cost of pursuing higher education has increased by 85.51% from the costs incurred during high school (almost two times high school cost). So, it is natural that higher education tends to be expensive.\n\nWhy is Indonesian higher education increasing its tuition fees? The research results of Marliyah & Dharma (2022) inform that the most critical risk for Indonesian Islamic universities is the risk of standardizing the higher education system,8,9 which must be “Unggul” (DIKTI version) and have an international ranking. Therefore, various improvements need to be made, such as improving college facilities and infrastructure and improving the quality of students.10 This impact increasing university operational costs, and with the current university business model,11–13 the most straightforward choice to take is to pass it on to students.\n\nBPS-Statistics Indonesia (2022b) reports an increase in participation of the lowest economic community by 1.34 times from 2016. The main factor causing that phenomenon is funding assistance schemes, including scholarships for poor people, paving the way for students to study in universities. Popular schemes in various countries are Scholarships and endowment Funds.14 In Indonesia, the Government provides higher education subsidies known as KIP (Kartu Indonesia Pintar). Apart from these schemes, popular funding at various universities in Indonesia comes from social financial assistance, including zakat.\n\nKompas (2022), in an investigation, stated that people with middle to lower economic levels in Indonesia need assistance to obtain higher education,3 and the distribution of zakat is one alternative assistance. Zakat is one of the Islamic pillars aiming to fulfil the primary needs of Muslims, one of which is gaining access to higher education. It is because Islam realizes that although all humans have the same opportunity to work and earn an income, not everyone can earn a decent and sufficient income to fulfil their life’s needs. On the other hand, zakat is an Islamic mechanism for withdrawing part of the rich’s wealth to distribute to people in need so that everyone has the same right to access and enjoy the results of the country’s development. The findings of BAZNAS Center Of Strategic Studies & Zaenal (2019) that for two consecutive years (2018-2019),15 the distribution of zakat had a good impact on mustahik and confirmed by Abdullah et al. (2012) and Beik et al. (2017) concluded that one of the solutions to improving human quality in Indonesia is the distribution of zakat.16,17\n\nApart from that, there is a complicated problem that requires logical and accurate research, namely whether zakat can be distributed to students. It is said to be complicated because, in Islam, the criteria or groups of people who are entitled to receive zakat have been determined in the Al Quran. In Surah At-Taubah verse 60, Allah SWT said: \"Indeed, zakat is only for the needy, the poor, the amils, those whose hearts are softened and then convert to Islam, to free those who are enslaved, to free those who are in debt, for (jihad) in the way of Allah and for those who are in a journey that requires help as an obligation from Allah. Allah is knowing and wise.\"\n\nThe verse above explains that those who are entitled to receive zakat distribution are only eight groups “asnaf,” namely the needy, the poor, the amil, Muslim converts, for freeing enslaved people, people who are in debt for mujahid (jihad) defending Islam and travellers who need accommodation assistance. If we look carefully, there is no explicit information from this verse, which shows that students have the right to receive zakat distribution. It is a significant discussion that requires sufficient attention, considering that education is an essential instrument in human development, especially in Indonesia.\n\nThe researcher seeks to explore the origin of assistance from income zakat and its distribution to students for higher education purposes, both in the form of previous research findings and actual exploration in several universities in Indonesia. These findings will help universities to use zakat as alternative funding for students and provide recommendations on how to integrate them into strategic policies for the development of universities.\n\n\n2. Theoretical framework and literature review\n\nThe terminology of zakat begins with a review of its etymology, defined as an-nama', which means blessing, cleanliness, and growth, or a process that will provide incredible wealth and protect it from danger. This reference is based on Ibn Taymiyah's translation, which states that zakat payers will have their hearts guarded to become pure. The zakat terminology is defined as an obligation from Allah to a certain amount of wealth with a specific size (nisab) which must be given to those who need it/mustahik, or it is called a certain level of certain wealth which must distributed to entitled people who have determined (in the Alquran) when they meet the conditions.\n\nAccording to Dieb et al. (2012), \"This wealth is called zakat because the original wealth (which has been given as zakat) grows because of the blessings of zakat wealth and the prayers from the people who receive it.\" Likewise, zakat is a cleanser of all wealth from syubhat (doubts) and a cleanser from the rights of other people attached to them. As Allah commanded, zakat is a form of worship that Muslims must carry out. It has a transcendental (unseen) side and a real side, following the Islamic view of wealth that contains the rights of people experiencing poverty attached to it, then must be paid out as a form of zakat.\n\nZakat is one of the Islamic laws obligatory for its well-off adherents, where the goal is the same as other goals of Islamic philanthropy so that wealth does not only circulate in certain circles, as stated in the seventh verse of Surah Al-Hasyr. Zakat is an effort so that people have sufficient financial capacity to meet basic needs such as food, clothing, and shelter, not to mention the need for a decent education.\n\nTherefore, it includes the distribution of zakat in Islamic law, which covers an extensive group, as explained in Qs. At-Taubah: 60. However, apart from the aim of meeting people’s basic needs, if we look closely at how Allah determines who is entitled to receive zakat in the Al Quran, it turns out that zakat is not only intended to meet basic needs alone. Furthermore, zakat will be distributed to those who have contributed to developing the country broadly. For example, among the asnaf of zakat who are not necessarily included in the poor category are fisabilillah and mualaf.\n\nFor example, Fisabilillah are those in the army fighting for Islam who are assigned to guard the borders and protect the Muslim territory from enemy attacks. Fisabilillah still gets zakat even if they are rich.18 The inclusion of the fisabilillah group in the asnaf category (those who are entitled to receive zakat) is a strong indication that those who contribute to religion are entitled to receive zakat as a form of appreciation for those who are willing to serve their religion. So, among contemporary Fiqh (Islamic law) scholars, the asnaf category of zakat receives a fairly extensive portion of discourse and discussion in order to maximize the potential and influence of zakat in building an advanced and sustainable Islamic civilization.\n\n\n3. Methods\n\nThe research seeks to explore contextual views in finding solutions to the complexity of background phenomena. On this basis, the recommended research approach is qualitative.19–21 Because researchers seek to present theoretical fundamentals that can provide a comprehensive understanding of zakat in a specific context, this requires finding historical data from time to time,22 which according to Fowler & Christakis (2010) must be able to be linked to broader needs,23 and in line with Fisher et al. (2017) recommend a systematic literature review approach.24\n\nA systematic literature review is carried out by analysing literature related to zakat, both in the context of its collection and in the context of its distribution. The research uses the concept of inductive analysis in exploring specific evidence so that findings emerge naturally from published literature.25 For this reason, the appraisal/'Amid concept was developed Marliyah et al. (2023)26 to reduce the data into essential findings.27\n\nThe research begins with data collection from relevant literature.28 Moseley et al. (2009) imply the need for a quality and structure selection process (framework) that explores the constructs of the theme variable builders.29 The premise underlying the unit of analysis is a thesaurus database set formed from the results of literature searches.28,30,31\n\nRelevant literature is divided into a thesaurus database of recent findings32 sourced from reputable journals (Scopus, WOS, and Sinta), applicable regulation,33 and a thesaurus database originating from classical and contemporary Islamic reference books as a record of events from the previous Islamic era. Researchers build an analytical framework as follows:\n\n1) Developing a search string31 with subsequent filtering, which focuses on a “search question” to identify the database.28 Collecting data as search string: collecting zakat from income or zakatu kasbil 'amal (زكاة كسب العمل) and distributing zakat as student funds.\n\n2) The database is screening to potentially relevant articles by title and abstract32,33 The potential paper will be carried out by selecting books or articles that focus on and contrast with the search string.\n\n3) Eligibility and sensitivity analysis. Sensitivity analysis performs by configuring inclusion and exclusion criteria,25 then the potentially relevant articles screening by inclusion and exclusion criteria.34 The following criteria (Table 1):\n\nNotes for Eligible articles to be screened for data abstraction.25\n\n4) Qualitative synthesis analysis was done by data abstraction and reduction using triangulation tables.\n\nTo obtain empirical findings on how universities in Indonesia use zakat, researchers conducted a deep interview and FGD (Focus Group Discussion) with philanthropic organizations formed by universities with the same aim as the research theme “using social funds as an alternative to student funding.” Sources of informants came from UPZ UIN Sumatera Utara, UPZ UIN Walisongo Semarang, Puspas Unair, and Ziswaf UNIDA. The selection (as informants) was based on the fact that they have the best image in Indonesia in collecting social funds. For example, Puspas is an organization that has long been active and plays a crucial role for Universitas Airlangga students35 and managing finances very well, as reflected in the unqualified opinion acquisition for the last three years. UPZ UIN Walisongo Semarang is the best UPZ in Indonesia, according to the Ministry of Religion.36 The data and information obtained will be analyzed using qualitative analysis tools such as coding analysis for data reduction and content analysis for systematically identify the meaning.\n\n\n4. Research findings\n\nIncome zakat is a controversial type of zakat. Until now, the legal status or position of income zakat is still being debated, which covers comprehensive aspects. If simplified, the debate can be concluded in two aspects. First, is it permissible to determine the type of zakat whose determination does not come directly from the Al Quran or Hadith? Second, if it is permitted, then what are the provisions for determining the requirements for income zakat obligations both in terms of nisab (minimum level) and haul (period)?\n\nAs previously explained, the zakat required in Islam, whether it comes from the Al Quran or the Hadith, is limited to six types, namely zakat on gold and silver (including) money, zakat on livestock, zakat on staple foods, zakat on trade, zakat on mining products, and the last is zakat fitrah. All types of zakat mentioned above have transparent sources and arguments in the Al Quran and Hadith.\n\nBased on the explicit provisions related to the types of zakat mentioned above, not a single ulama since the time of the Prophet Muhammad until many later generations carried out ijtihad or reform to determine other types of zakat outside of what is stated in the Al Quran or the Hadith. It is because zakat is a mahdhah (ritual/form of worship) where a Muslim must obey and follow the rules without adding or subtracting from the rules. This attitude is based on the rules agreed upon by the ulama, namely:\n\nالاصل في العباده التوقيف\n\n“The original law in determining worship is to follow standard rules.”\n\nSo based on this rule, since the zakat law was introduced by Islam, not a single Muslim researcher has modified the law, both from the type of zakat to the determination of the minimum level (nisab) and the mandatory period for paying zakat (haul). The zakat law is implemented following the provisions of the Al Quran and Hadith.\n\nDiscourse regarding income zakat was first raised in the 60s. The researcher who published the first work related to income zakat (professional zakat) was Yusuf Al Qardhawi. Through his work entitled Fiqh Az-Zakah (Fiqh Zakat) in 1969.37 Al Qadhawy was the person who first made issues related to income zakat. It became widespread with challenging discussions throughout the Islamic world, both in meetings, scientific writings, and research, both pros and cons.\n\nEven though discussions about income zakat have emerged since the late 60s, according to Riyadi (2016), the study and practice of it began to spread in Indonesia around the late 90s and early 2000s.38 After Al Qardhawi’s book was translated into Indonesian by Didin Hafidhuddin with the title “Fikih Zakat” in 1999, income zakat began to be widely implemented by zakat management institutions in Indonesia, both BAZ (Badan Amil Zakat) owned by the government (either BAZDA or BASNAZ), or privately owned LAZ (Lembaga Amil Zakat), such as PKPU, Dompet Dhuafa.\n\nThe emergence of the idea of income zakat gave rise to widespread controversy. There are quite a few scholars who support Al Qardhawi’s ideas and even wrote many works to strengthen what he had initiated. However, there are also quite a few who oppose it and refute it with various scientific arguments for the ideas put forward by Qardhawy. In the Indonesian context, the same thing also happens. Not all fatwa institutions agree with the idea of income zakat.\n\nNahdatul Ulama (NU) in Bahtsul Masail Maudlu'iyyah activities at the East Java PWNU Regional Conference at Lirboyo (15-28-29 July 2018) confirmed NU’s official opinion that there is no income zakat obligation in the four mahzab. However, every person in any profession with money that reaches the nisab and haul must pay zakat, considering that this money has the same exchange rate as gold and silver (nuqud). It differs from the Fatwa of the Indonesian Ulema Council (MUI/Majelis Ulama Indonesia). MUI (2003) stated that all forms of halal income must be paid zakat on condition that they have reached the nisab in one year, namely 85 grams of gold. In this fatwa, what is meant by “income” is any income such as salary, honorarium, service fees, and other things that are obtained in a halal way, whether routine, such as state officials, employees, or non-routine, such as doctors, lawyers, consultants, and the like, as well as income earned from other freelance work.\n\nHowever, it should be noted that even though the MUI agrees with Al Qardhawi’s ideas regarding income zakat obligations, if we look more carefully, the MUI fatwa takes a different legal perspective from several points that Al Qardhawi initiated. Among these differences is that the MUI fatwa states that all forms of halal income must paid zakat if they have reached the nisab, namely 85 grams of gold. It means that the minimum level of assets that requires income zakat is analogous (qiyas) to zakat on gold and silver. It is different from Al Qardhawi’s initial idea, where the nisab of income zakat is debiased/analogous (qiyas) to the nisab of agricultural zakat, namely 653 kg of dry grain or 520 kg of rice.\n\nThe MUI goes further than Al Qardhawi’s original idea, where the MUI believes that even if a person’s income has not reached the nisab, he can already pay zakat if, in his calculations, the amount of salary or income he receives in one year (even if it is still in the calculation above paper) and has not been received, can reach the nisab value without taking into account daily or monthly expenses that must be excluded from the income or salary received.\n\nHowever, regardless of the debate regarding the law or the status of professional zakat itself, according to Baidowi (2018), even though the law regarding professional zakat is still controversial and not yet well known by the Muslim community in general and Muslim professional circles in the country in particular, awareness and enthusiasm to set aside a portion of income as zakat which he believes is a religious obligation that must be paid relatively high.39\n\nMoreover, the Indonesian government has issued various regulations related to zakat. However, according to Cahyani (2020), the legal position of professional zakat has not been strengthened by adequate regulations, at least in Law No. 38 of 1999 concerning Zakat Management, in Chapter IV Article 11 Paragraph 2, states the types of assets subject to zakat, and one of the types is income and services. So, indirectly, the issue of professional zakat already has rules to adhere to as a legal reference.40\n\nStudents are one of the groups that are still being debated whether they are one of the eight groups entitled to receive zakat. This is because, in Surah At-Taubah verse 60, no sentence explicitly indicates that students or those seeking knowledge have the right to receive zakat.\n\nThis causes not all Muslim scientists to agree that students have the right to receive zakat. However, this debate came to light when the MUI issued a fatwa in 1996 regarding providing zakat for scholarships. The fatwa states that “Giving zakat money for educational purposes, especially in the form of scholarships, is legal because it is included in asnaf fi sabilillah”.41\n\nLooking at the fatwa, the main opinion is that students or people who are studying are included in the fisabilillah group or people who are fighting in the way of Allah. MUI issued this fatwa regarding the general rules in the method of interpreting the Al Quran, namely:\n\nيبقى العموم على عمومه\n\n“The general text is applied as is its generality.”\n\nThe meaning of the rules of interpretation above is that if the text of the Al Quran and Hadith is universal without any particular meaning that limits its universality, then the text is applied universally without certain limits. In the context of Surah At-Taubah verse 60, one of the groups entitled to receive zakat mentioned by Allah SWT in that verse is fisabilillah, namely people who are fighting jihad in the way of Allah. However, the verse above does not clearly or explicitly explain what jihad means in the way of Allah.\n\nThe rules of interpretation above are: As long as the text of the Koran and Hadith is universal without any particular meaning that limits its universality, then the text is applied universally without certain limits. In the context of Surah At-Taubah verse 60, one of the groups entitled to receive zakat mentioned by Allah SWT in that verse is fisabilillah, namely people who are fighting jihad in the way of Allah. However, the verse above needs to clearly or explicitly explain what jihad means in the way of Allah.\n\nIt is true that during the time of Rasulullah SAW, the groups included in this category were war volunteers who did not have a fixed salary.42 However, if viewed in general terms, jihad does not limit the scope of its meaning to troops or soldiers fighting to defend and defend the country. However, in general terms, without specifying the person in those who are fighting in the way of Allah.43 So, in the logic of this fatwa, MUI sees that students or students of knowledge are people who are also fighting jihad in the way of Allah, and with their knowledge, they can defend religion and advance the nation and state so that they can include as the fisabilillah category.\n\nIt is just that the Indonesian Ulema Council (MUI), in its fatwa, provides strict limits or categories regarding what kind of students are entitled to receive scholarships through zakat distribution. The fatwa provides three categories that must be fulfilled by pupils or university students in order to be entitled to receive a scholarship from zakat, namely: 1) academic achievement, 2) priority for those who are less fortunate, and 3) studying knowledge that is useful for the Indonesian nation.\n\nThe Indonesian Ulema Council is not the only fatwa institution that has stated that zakat funds can distribute scholarships for students. One of the international fatwa institutions that is a reference for Muslims around the world, namely Darul Ifta' Egypt, 2007 issued a similar fatwa in fatwa sheet number 175, which contained:\n\nيجوزُ شرعًا صرفُ الزكاة في الإنفاقِ على تدريبِ طلبة العلم، خاصَّةً إذا كانوا محتاجين، حتى إن الحنفية أجازوا نقل الزكاة من بلد إلى آخر لطالب العلم. والإنفاق على طلبة العلم يشمل تدريبهم على المهارات الضرورية؛ لأنهم يحتاجون إليها\n\n“It is legally permissible to distribute zakat for scholarships for science passports, especially if they are in need. Even the Hanafi Madhab allows the transfer of zakat from one country to another for distribution to seekers of knowledge. Scholarships for students include (among other things) to train them in necessary skills because they are very shaky” (dar-alifta.org/ar/fatawa).\n\nLikewise, the official fatwa institution of the Islamic State of Jordan, namely Dairah Al-Ifta, issued a similar fatwa in 2013 in fatwa sheet number 2847. However, in this case, the fatwa from Dairah Al Ifta' provides strict limits regarding students entitled to receive zakat. The contents of the fatwa state that: 1) He must be a student who is proven to be serious about studying so that his activities in studying cause him to be unable to work and make money. 2) The knowledge the studies are fardhu kifayah, whose orientation is the good of the people, both Shar'i knowledge, such as fiqh and interpretation, and general knowledge, such as medicine, economics, chemistry, and others. 3) Zakat does not come from relatives or family obliged to provide for their needs.\n\nFrom the description above, contemporary ulama is more inclined to the opinion that allows zakat to be distributed through scholarships to students. Of course, this fatwa is a breath of fresh air both for the government of the Unitary State of the Republic of Indonesia and for the students themselves. For the government, this will help accelerate the human development index (HDI)44 and improve the quality of human resources for the nation’s children, considering that access to higher education among young people is still very low. Alawiyah (2016) concluded that one of the leading causes is the high cost of higher education, which causes many young people of productive learning age to be unable to access it due to limited costs.45,46 Quoting from official data on the Central Statistics Agency (BPS) website, it shows that the percentage of poor people in March 2022 is 9.54 percent. The number of poor people in our country in March 2022 is 26.16 million. The number of urban poor people in March 2022 was 11.82 million people, while the number of rural poor people in March 2022 was 14.34 million people.\n\nEducation is the right of all groups, from the lower middle class to the upper middle class, with supportive socio-economic conditions; of course, there will be no difficulty in reaching education up to the upper level, but this is not the case with the lower middle class, which is why there is a need for equal distribution of opportunities to obtain education. Many weak people do not continue their education to a higher level because the cost of education is expensive.47\n\nThe facts of the exchange show that the ulama’s fatwa regarding the legality of distributing zakat in the form of scholarships to students was welcomed by the National Zakat Amil Agency (Baznas). Baznas distribute part of the zakat from muzakki (people obliged to pay zakat) through educational scholarships. Baznas even formed a particular unit to handle the distribution of zakat through student scholarships. The institution is called LBB or Baznas Scholarship Institute. LBB is a program from the Distribution and Utilization Division tasked with providing educational funds to ensure the continuity of educational programs for underprivileged/poor students as an intergenerational responsibility.48\n\nEven some of the Amil Zakat Institutions affiliated with mass organizations have also started taking steps or taking part in distributing zakat to students. Prakoso, in his research in 2022, discovered the fact that the Amil Zakat Infaq Sadaqoh Muhammadiyah Institute (LAZISMU) has distributed scholarships to students since 2016. In the 2017/2018 academic year, LAZISMU provided scholarships of IDR 818,448,000 to 508 students, while in 2021, it will provide scholarships for 6,600 students.49\n\nSo, for students or prospective students who come from lower middle-class economic backgrounds, this fatwa is undoubtedly a bright hope for being able to continue higher education, provided that this fatwa can open people’s minds to distribute their zakat assets in the education sector.\n\nThe findings might be in the light of some of its limitations, where the main limitation of this research is universities in Indonesia as a locus for seeing the impact of using zakat as a mechanism to help universities, in this case, helping students in need. The combination of Indonesian culture of helping each other with the dominance of Islamic thought has resulted in the growth of the model of using zakat in universities in Indonesia.\n\nFuture research may focus on models of collecting social funds in Islamic corridors such as alms/infaq and even waqf. The researchers’ initial findings on the waqf model led to the emergence of a well-known university in Indonesia, namely UNIDA Gontor. It is quite an initial treatise for researching the waqf model in higher education, especially in Indonesia. Currently, both alms/infaq and waqf are still predominantly used in religious activities, although specifically for waqf, various higher education foundations have emerged that source their funds from waqf.\n\nThe research results can provide essential implications for managing Islamic-based social funds (especially zakat). The research results can be used as a reference and alternative for zakat collection in universities to build zakat collection units that focus on helping improve the quality of students, then the combination of higher education interests solely for achieving benefits, namely education for all levels of society. This finding also encourages universities to carry out zakat collection activities, which are then synchronized with the needs of universities to help students unable to complete their studies.",
"appendix": "Data availability\n\nAll data underlying the results is available as part of the article and no additional source data are required.\n\n\nReferences\n\nNasution L, Rapono M: Strategi Dalam Menghadapi Persaingan Perguruan Tinggi Di Propinsi Sumatera Utara Melalui Analisis SWOT (Studi Kasus UMN Al Washliyah Medan). JKBM (Jurnal Konsep Bisnis dan Manajemen). Nov. 2018; 5(1): 9. Publisher Full Text\n\nHanim Z, Anggal N, Sanda Y: Strategi Pembiayaan Pendidikan Pada Perguruan Tinggi Keagamaan Katolik Swasta Untuk Pemenuhan Capaian Kinerja. Jurnal Penelitian Pendidikan Indonesia. Jun. 2023; 9(2): 604–614. Publisher Full Text\n\nRosalina MP, Krisna A, Wisanggeni SP: Orangtua Indonesia Makin Sulit Biayai Kuliah Anak. Kompas.\n\nBPS-Statistics Indonesia: Data Survei Sosial Ekonomi Nasional 2020. Jakarta: 2021.\n\nBPS-Statistics Indonesia: Data Survei Sosial Ekonomi Nasional 2021. Jakarta: 2022.\n\nBPS-Statistics Indonesia: Indonesian Economic Report, 2020. Jakarta: 2021.\n\nBPS-Statistics Indonesia: Indonesian Economic Report, 2021. Jakarta: 2022.\n\nMarliyah, Dharma B: Desain Manajemen Risiko Dengan Pendekatan Transdisipliner di Universitas Islam Negeri Sumatera Utara Medan. Medan: 2022.\n\nMarliyah, Dharma B, Syarbaini AMB: The Maturity Of Risk Management In Indonesian Islamic Universities. Jurnal Riset Bisnis dan Manajemen. Aug. 2023; 16(2): 117–125. Publisher Full Text\n\nMarliyah B, Dharma MY, Syarbaini AMB: Analisis Kebutuhan Industri Keuangan Syariah Terhadap Kompetensi Luaran Pendidikan Tinggi Islam. HUMAN FALAH: Jurnal Studi Ekonomi dan Bisnis Islam. Dec. 2022; 9(2): 10. Publisher Full Text\n\nIbrohim B: Pembiyaan Pendidikan Tinggi. Tarbawi: Jurnal Keilmuan Manajemen Pendidikan. 2017; 3(1): 15–23.\n\nIrawan DE, et al.: Kajian Pendidikan Tinggi IDRI untuk DPR RI dan Ristek Dikti 2018. Bandung: ITB Press; 2018.\n\nZuhairi A, Riana KE, Maria M, et al.: Model Ekonomi dan Manajemen Pembiayaan Pendidikan Tinggi pada PTBHMN, PTN, PTS, dan PTJJ di Indonesia.2008.\n\nMunadi M: Pengelolaan Endowment Fund di Perguruan Tinggi Malaysia: Studi Kasus di Universitas Teknologi Malaysia. Al-Ulum. Dec. 2017; 17(2). Publisher Full Text\n\nBAZNAS Center Of Strategic StudiesZaenal MH: Dampak Zakat Terhadap Kesejahteraan Mustahik Evaluasi Program Zakat Produktif 2018. Jakarta: Puskas Baznas; 2019.\n\nAbdullah N, Yusop MM, Awang COH: A Technical Note on The Derivation of Zakat Effectiveness Index (Zein). International Journal of Economics, Management and Accounting. 2012; 20(1).\n\nBeik IS, et al.: National Zakat Index: Framework and Methodology. Puskas Working Paper Series. 2017; 1–22.\n\nDieb M, Al-Khin M, Asy-Syarbaji A: Al-Fiqh al-Manhaji ‘ala Mazhab al-Imam asy-Syafi’I. 13th ed.Damaskus: Darul Qolam; 2012.\n\nDenzin NK, Lincoln YS: Handbook of Qualitative Research. Yogyakarta: Pustaka Pelajar; 2009.\n\nBungin B: Penelitian kualitatif: Komunikasi, ekonomi, kebijakan publik, dan ilmu sosial lainnya. Ketiga ed.Jakarta: Kencana; 2021.\n\nBungin B: Post-Qualitative Social Research Methods. Ketiga ed.Jakarta: Kencana; 2022.\n\nEsendorfer J, Lehner OM: Islamic Banking And Finance As An Ethical Alternative: A Systematic Literature Review. ACRN Oxford Journal of Finance and Risk Perspectives. 2016; 5(2): 42–64.\n\nFowler JH, Christakis NA: Cooperative Behavior Cascades in Human Social Networks. Proceedings of the National Academy of Sciences. Mar. 2010; 107(12): 5334–5338. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFisher M, Qureshi H, Hardyman W, et al.: Using Qualitative Research in Systematic Reviews: Older People’s Views of Hospital Discharge. London (England): Social Care Institute foe Exellence; 2017.\n\nYob FSC, et al.: Children’s emotion regulation strategies in facing the Volatile, Uncertain, Complex, and Ambiguous (VUCA) World: A systematic narrative review. Masyarakat, Kebudayaan dan Politik. 2023; 36(2): 185–200. Publisher Full Text\n\nMarliyah M, Yafiz BD, Syarbaini AMB: ’Amid: Islamic Integrative Approach as Survey Model. Indonesian Journal of Islamic Literature and Muslim Society. Mar. 2023; 7(1): 17–32. Publisher Full Text\n\nMurphy CM: Writing an Effective Review Article. Journal of Medical Toxicology. Jun. 2012; 8(2): 89–90. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcFadden P, Taylor BJ, Campbell A, et al.: Systematically Identifying Relevant Research. Research on Social Work Practice. Nov. 2012; 22(6): 626–636. Publisher Full Text\n\nMoseley AM, Sherrington C, Elkins MR, et al.: Indexing of randomised controlled trials of physiotherapy interventions: a comparison of AMED, CENTRAL, CINAHL, EMBASE, Hooked on Evidence, PEDro, PsycINFO and PubMed. Physiotherapy. Sep. 2009; 95(3): 151–156. PubMed Abstract | Publisher Full Text\n\nFlatley RK, Lilla R, Widner J: Choosing a Database for Social Work: A Comparison of Social Work Abstracts and Social Service Abstracts. The Journal of Academic Librarianship. Jan. 2007; 33(1): 47–55. Publisher Full Text\n\nLee E, Dobbins M, DeCorby K, et al.: An optimal search filter for retrieving systematic reviews and meta-analyses. BMC Medical Research Methodology. Dec. 2012; 12(1): 51. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHolden G, Barker K, Covert-Vail L, et al.: Sosial Abstracts fails again: A Replication and Extension. Research on Social Practice. 2009; 19: 715–721. Publisher Full Text\n\nHolden G, Barker K, Covert-Vail L, et al.: Does Sosial Abstract works? Research on Social Practice. 2008; 18: 487–499. Publisher Full Text\n\nMcFadden P, Taylor BJ, Campbel A, et al.: Systematically Identifying Relevant Research: Case Study on Child Protection Social Workers’ Resilience. Research on Social Practice. 2012; 22(6): 626–636. Publisher Full Text\n\nBagus: Wisudawan Beprestasi: Ini Berkat PUSPAS. PUSPAS UNAIR;\n\npendis.kemenag: Berhasil Kelola Zakat untuk Sejahterakan Ummat, Prof. Imam Taufiq terima Baznas Award 2023. Kementrian Agama RI;\n\nal-Qaradawi Y: Fiqh Az-Zakat: A Comparative Study. UK: Dar Al Taqwa; 1991.\n\nRiyadi F: Kontroversi zakat profesi pesrpektif ulama kontemporer. ZISWAF: Jurnal Zakat dan Wakaf. 2016; 2(1): 109–132.\n\nBaidowi I: Zakat Profesi (Zakat Penghasilan). Tazkiya. 2018; 19(01): 40–54.\n\nCahyani AI: Zakat Profesi Dalam Era Kontemporer. El-Iqthisadi: Jurnal Hukum Ekonomi Syariah Fakultas Syariah dan Hukum. Dec. 2020; 2(2). Publisher Full Text\n\nMajelis Ulama Indonesia: Pemberian Zakat Untuk Beasiswa Nomor Kep.-120/MU/II/1996. Jakarta: Feb. 1996.\n\nZabir M: Manajemen Pendistribusian Zakat Melalui Program Unggulan Beasiswa Oleh Baitul Mal Aceh. Al-Idarah: Jurnal Manajemen dan Administrasi Islam. Jul. 2017; 1(1): 131–151. Publisher Full Text\n\nAhmed BO: Identifying the poor and the needy among the beneficiaries of zakat Need for a zakat-based poverty threshold in Nigeria. International Journal of Social Economics. 2017; 44(4): 446–458. Publisher Full Text\n\nHerianingrum S: The impact of zakat, education expenditure, and health expenditure towards poverty reduction. Systematic Reviews in Pharmacy. 2020; 11(12): 235–239. Publisher Full Text\n\nAlawiyah F: Akses Pendidikan Tinggi dan Penyebabnya. Kajian. 2016; 17(3): 301–328. Publisher Full Text\n\nPiliyanti I: Transformasi Tradisi Filantropi Islam: Studi Model Pendayagunaan Zakat, Infaq, Sadaqah Wakaf Di Indonesia. Jurnal Pemikiran dan Penelitian Ekonomi Islam. 2010; 11(2).\n\nAminah S: Pendistribusian Dana Zakat Untuk Beasiswa Pendidikan Mahasiswa Di Badan Amil Zakat Nasional (Baznas) Kota Cirebon. AKSIOMA AL-MUSAQOH: Journal of Islamic Economics and Business Studies. 2021; 4(2).\n\nBaznas: Lembaga Beasiswa Baznas.\n\nPrakoso YA, Masruchin: Zakat Profesi dalam Meningkatkan Kemampuan Lanjut Studi Mahasiswa UMSIDA (Studi Kasus LAZISMU Cabang UMSIDA). Syarikat: Jurnal Rumpun Ekonomi Syariah. Jun. 2022; 5(1): 128–139. Publisher Full Text"
}
|
[
{
"id": "355629",
"date": "17 Jan 2025",
"name": "Ade Nur Rohim",
"expertise": [
"Reviewer Expertise Islamic Economics",
"Zakat",
"Waqf"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 is quite relevant to the current phenomenon of zakat distribution which has been widely implemented in various zakat institutions.\nHowever, some notes for the author to consider include:\n1. The abstract does not contain a sufficient statement of the research problem, especially related to the distribution of zakat to the scholarship scheme. This has implications for the bias of the approach used, whether using a fatwa approach, or regulation, or an interpretation (tafseer) approach or indeed only limited to a review of several of these provisions.\n2. There are terms in the abstract that trigger fundamental errors, such as nisab which is interpreted as \"1 year\", and also the number of asnaf mentioned as 9 asnaf. The use of the term \"Baznas\" also needs to comply with the provisions of the Zakat Law which no longer uses the term \"BAZ\".\n3. The research results presented in the abstract are not relevant enough to the discussion. The author states the practice in \"several universities\" related to zakat distribution, but this is not specifically reviewed in the discussion, including its impact on the success of student studies which has not been described in depth.\n4. Reviews of several previous studies related to the research topic have not been clearly stated in the introduction. The author needs to describe them to strengthen the justification of the novelty of this research, including by describing academic debates related to this research topic.\n5. There needs to be a comprehensive explanation regarding the terms used, whether zakat kasbil 'amal or income zakat, by reviewing the similarities or differences, or the relationship between the two terms.\n6. The author needs to review several practices of implementing zakat distribution at several universities in Indonesia in a separate subsection in the discussion section, so that it can be relevant to the title of this research which captures a portrait of zakat distribution at various universities in Indonesia.\n7. There is no final conclusion to answer the research questions.\nBased on these notes, this study is expected to reconstruct the systematic discussion in this study to make it in line between the research title, methods and approaches used, and the findings and results of the study that answer the research questions.\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? No\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-185
|
https://f1000research.com/articles/13-184/v1
|
11 Mar 24
|
{
"type": "Systematic Review",
"title": "Scoping review of international relations theories in health security: A cue for health diplomacy",
"authors": [
"Sanjay Pattanshetty",
"Aniruddha Inamdar",
"Viola Savy Dsouza",
"Kiran Bhatt",
"Amrita Jash",
"Nachiket Gudi",
"Helmut Brand",
"Aniruddha Inamdar",
"Viola Savy Dsouza",
"Kiran Bhatt",
"Amrita Jash",
"Nachiket Gudi",
"Helmut Brand"
],
"abstract": "Background Health security as a domain has gained tremendous importance in the recent past. Emerging and re-emerging diseases globally, coupled with the derailment of the determinants of health mainly the socio-political environment, has made health security a cross-cutting entity in diverse fields including International Relations (IR). With the ongoing global polycrisis, the health-related issues which were previously sidelined as a concept of less strategic importance in the IR field, are now contributing to the shift of the world order. This has instilled an increased participation of IR scholars in the discussions and debates on health security concerns. The field of IR contains numerous theoretical lenses through which scholars analyze such situations, policies, and systems of the world.\n\nMethods In this paper, we use a scoping review method to inspect how IR theories have been applied in analyzing health security concerns.\n\nResults We observed that various diverging IR theories have been used to deliberate on states’ actions in tackling the recent pandemic and have also been prescriptive about the changing notions of multilateralism and international governing organizations. Realism, liberalism, and securitization were among the most frequently applied IR theories in the context of health security discussions.\n\nConclusions This work provides an impetus to enhance the interaction among interdisciplinary teams leading to evolving solutions that can address issues of global importance in the contemporary world.",
"keywords": [
"Health security",
"international relations theories",
"realism",
"liberalism",
"securitization"
],
"content": "Introduction\n\nThe COVID-19 pandemic has compelled us to reimagine the existing world order and inspect the nature of the shift that can be expected.1–3 With health security becoming the forefront of the discussion in national security and foreign policy concerns, governments worldwide had to balance their act of protecting their people while having a global outlook. This situation was further aggravated by tensions between the USA and China on the origin of the COVID-19 virus, China’s contention over Taiwan’s accession to the World Health Organization (WHO), and the Russia-Ukraine conflict. There is also a resounding agreement among the countries on the reformation of multilateral systems due to the challenges it brought in mitigating the health and geopolitical crises.4 These situations have ignited discussions and debates among International Relations (IR) scholars who have tried to analyze the world’s situations, policies, and systems.5\n\nIR scholars generally use the theoretical knowledge base of the field to understand and elaborate on how countries respond to changes and challenges at the global level and navigate inter-state dynamics. Theories are instruments designed to help understand a particular phenomenon that function as a guide for research to explain a specific event or predict the occurrence of something.6 These theories are also utilized by political leaders and policymakers in articulating solutions at the national and international levels which later translate into policies framed to obtain national objectives, which vary in their strategic importance. While states have been the primary focus of IR, the role played by other actors, such as international organizations, civil society groups, and even individuals, has gained prominence in the discourse. However, in the pursuit of peace and security, IR as a field has broadened its horizon by interacting with dynamic fields like global health to analyze how the context of conflicts, development inequity, socio-economic conditions, environmental volatility, and global governance affect health security.7\n\nWHO defines global public health security “as the activities required, both proactive and reactive, to minimize the danger and impact of acute public health events that endanger people’s health across geographical regions and international boundaries.” The pandemic magnified national conflicts and challenges impacting the lives of billions globally. In many countries, the crisis turned into a political test.8 The polycrisis nature of the pandemic has created tensions in international relations and health security.9 Historically, health issues largely remained outside the purview of most traditional IR scholarly works as it was treated with lesser strategic significance. However, the importance of discussing health security in the IR field was recognized during the post-Cold War period with the emergence of new security threats, particularly the prospects of pandemics related to emerging/re-remerging diseases and the increased perils of bioterrorism. This led to the issue of health security being dealt with under the ambit of foreign, national, and security policies. Ever since, the aspects of health security have been studied in IR concerning governance, inter-governmental institutions, globalization, diplomacy, and others.\n\nWhile health-related debates have gradually made their way into IR scholarly works, there is a need for deeper engagement among IR scholars on health. The changing context of the health and foreign policy interface has emphasized health security as a valid concern for IR and could find a place within the traditional boundaries of IR theories. Thus, this scoping review intends to understand how IR scholars have debated and discussed health concerns through a theoretical lens to gauge its potential impact on the international world order.\n\n\nMethods\n\nA scoping review approach enables us to understand emerging evidence and is regarded as a first step to research evidence development.10 We have followed the framework espoused by Arskey and O’Malley (2005) to inform the methods of this review.11 The PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist was followed to report the review.11,12\n\nThe research question was identified by SP in consultation with the subject matter expert (HB) and further refined with the consensus of the research team. Since this is an emerging domain, we inquired about the following research question:\n\n“How have International Relations scholars discussed and debated on health security concerns”?\n\nSince our objective is to understand the discussions on how these IR scholars have discussed health issues and that the discussion would be informed by a theoretical underpinning in the health security domain, we have adapted the health policy triangle framework instead of other frameworks.13,14\n\nKeyword searches were conducted in the English language in PubMed (NCBI), Web of Science (Elsevier), Scopus (Elsevier), and Embase (Elsevier) databases on November 5th, 2023, to cover a range of literature using the following search terms: “international relations theories” AND “health security”. The search strategy used for the study is provided in Appendix 1 of the Extended data.15 We further performed a search on Google Scholar with the aforementioned terms and screened the first five pages (with 10 entries in a page) for possible inclusion. The more detailed search strategy is in an online supplementary document. The search terms were based on the focus of the various IR theories and commonly used terms related to health security. Searches were limited to peer-reviewed journal articles they were not limited to any period. All the records were exported to Rayyan.Ai, a reference management software, and deduplication was carried out.16\n\nStep 3: Study Selection\n\nThe study selection was carried out at two stages, namely Title-abstract (Ti-Ab) and full-text stages. Ti-Ab screening was conducted by SP, KB, NG, and AI independently while screening at the full-text stage was conducted by SP, AI, and KB based on the following selection criteria: The inclusion criteria comprised of two aspects: (1) the articles needed to reference international relations theories explicitly, and (2) they should extensively apply these theories to offer valuable insights into understanding positions, negotiations, and outcomes in health security. In disagreements, a resolution was sought through discussion and consensus involving a third review author (VD).\n\nThree review authors independently extracted information from the articles, utilizing a pre-piloted electronic data extraction form. When discrepancies arose, the two review authors engaged in discussions to reach a consensus. The third author participated in further deliberations if a resolution could not be reached. The records at each review stage are presented in the PRISMA flow diagram. The data synthesis process incorporated principles derived from Walt and Gilson’s Health Policy Triangle framework model.14 The framework was employed because it offers a perspective that allows for the analysis of the interactions between actors, context, content, and processes. This framework facilitates an insightful approach to understanding the application and influence of different International Relations (IR) theories in the realm of health security. In this structure, the columns were categorized into distinct components such as “condition” “context” and “content”. The gathered data is then synthesized for a theme, along with a comprehensive analysis of the supporting evidence within each theme.\n\n\nResults\n\nA total of 12,889 records were retrieved from a database search Web of Science (Clarivate) – 2802, PubMed (NBCI) – 1362, Scopus (Elsevier) -6275, and Embase (Elsevier)- 2560. We removed 5227 duplicates from the list of articles. After the screening, 10 studies that met the eligibility criteria were included in the synthesis. We screened 50 records from Google Scholar (from the first five pages) and included 14 records for the synthesis. The PRISMA flow chart which is available as part of extended data, depicts the detailed study selection.15 Characteristics of the included studies and the arguments made by the authors are presented in Appendix 2 and Appendix 3 of the extended data.15\n\nThe data synthesis table involved extracting the IR theories discussed during the discussion of health security, health conditions presented in the paper, the context discussed, and the contents of the application of the theory. The detailed data synthesis table is provided in Table 1. The selected studies showed that a few papers used multiple theories in a single study and often presented arguments from various points of view to make a case. The theory of realism, securitization, and liberalism were the most frequently applied theories discussing health security.\n\n\n\n- International cooperation and liberalism have fallen into a crisis\n\n- Lack of global leadership\n\n- Opposing political ideologies\n\n- Vaccine nationalism\n\n\n\n- United States-led liberal international order\n\n- Emergence of a post-liberal international order\n\n- International cooperation\n\n- Middle-power countries in the East Asian region\n\n\n\n- Need for emergency policies\n\n- Neoliberal governments to roll out unpopular economic reforms\n\n- The securitization lens is prominently used in analyzing Global Health Security (GHS)\n\n- Difficulty of de-securitizing\n\n\n\n- Meanings, purposes, and objectives associated with technological development.\n\n- Understanding global and national policy responses to the crisis\n\n- To examine the problem of why states fail to cooperate\n\n\n\n- To investigate the intertwining nature of national health policies and provisions with international considerations.\n\n\n\n- Investigation of the geostrategic developments\n\n\n\n- Understanding and analysis of global health diplomacy from a relational view of power\n\n\n\n- Security-based international order to establish global justice\n\n\n\n- Identifying the drivers of global health diplomacy\n\n\n\n- To theorize (and practice) anti-hegemonic alternatives to mainstream international relations\n\n\n\n- Examining the key concepts and ideas within Neo-Marxist class analysis\n\n- Utilized to analyze and explain health disparities.\n\n\n\n- Grasping global and national policy responses to the crisis\n\n- To understand the problem of why states fail to cooperate in the pursuit of common interests\n\n\n\n- The etiological multifactorial character of the elements involved in disease pathogens\n\n- New protagonists are manifesting at the international level, The interest in state problems gets diminished\n\n\n\n- Use of the proposed conceptual model to predict the future international order\n\n\n\n- Positioning global health better within foreign policy\n\nThe increased relevance of discussions on international relations and health security during the recent COVID-19 pandemic was reflected in our scoping review with a majority of articles focusing on it. These papers primarily deliberated on how states across the world handled the pandemic and how we can anticipate a shift in the existing world order using the existing IR theories. However, one theory that stood out with its application in various global health challenges is the theory of securitization. This theory has been not only applied during COVID-19 but also in HIV, Pandemic influenza, SARS, H5N1, H1N1, infant deaths, diarrheal diseases, tobacco, ‘lifestyle diseases’, and ‘mental health’. The prominent global health concern of non-communicable diseases (NCDs) was discussed in a paper that discussed the role of Post-modernist IR theory in health security. The IR discussions have also taken place on determinants of health such as food, housing, and education through the lens of constructivism. Additionally, social justice and health inequalities concerns have been dealt with by IR scholars. Thus, IR theories have tried to emphasize the relevance of health security’s geopolitical and geoeconomic determinants.\n\nThe data on the context and content built by a particular IR theory is imperative to understanding the divergence and similarities in viewing health security. The papers that highlight the realist theory emphasize that the liberal world order that promotes global cooperation has failed during the COVID-19 crisis. They view that nations’ self-centered and self-interest-promoting actions in mitigating the pandemic’s risks and the rise of vaccine nationalism were the primary reasons for the lack of practical global cooperation and leadership. They foresee a shift in the US-led liberal world order that has been prevalent after the end of the Cold War.\n\nIn contrast to the realists, there is a greater emphasis on the liberal approach as being more relevant to the challenges of COVID-19. Liberals recognized the current world order’s limitations and highlighted the need for new geopolitical and geoeconomic players such as the middle-power countries in the East Asian region to enhance cooperation and fill the global leadership void. Despite the national interests becoming prominent in mitigating the pandemic, there has been an unprecedented rise in effective scientific collaborations for addressing the global health challenge. Thus, the liberals emphasize that strengthening cooperation and defying nationalistic measures is vital to tackling future global health crises.\n\n‘Securitization theory’ has been the most recurring theory of IR that has contributed to the discussions of health security with its application across various global health concerns. The studies using this theory have stressed the importance of the securitization of health, which places ‘health’ as a foreign and defense policy domain and prioritizes its deliberation and action towards mitigating global health concerns. By making health a foreign policy priority, it challenges the liberal world order with an augmented tendency of states acting in self-interests above a global vision (statist approach). However, it is important to examine whether the securitization of health indeed translates to ‘health security’. The analytical demarcation of social and international security of the securitization theory must be addressed as the prolonged securitizing of health threats’ has become a concern for efficient resource re-allocation.\n\nThe studies that used constructivism theory have used it to understand the reasons for the lack of effective cooperation despite common interests among nations. It emphasizes that an interlinkage between global and national policies is imperative to address health crises. It diverges from the realist and liberal views of the objectivity of states’ actions and highlights its subjective and complex nature. According to the theory, the consensus of the reality in which states function affects the state’s responses to a common concern and interest.\n\nThe critical security theory has been utilized to highlight the need for a globalist approach in which health policies focus on well-being and individual rights. The application of critical and decolonization theory was made to understand the inequitable nature of the world in terms of economic and political power and its effects on the management of the pandemic. With the rise of scrutiny on international organizations and the shift in the world order, liberal institutionalists who examine their determinants have emphasized the importance of domestic regimes and international norms for collective action against global health challenges. Modern Socialist and Marxist Theories were highlighted in a study that endorsed South-South cooperation in health through the lens of social justice. The Neo-Marxist theory, predominantly used to explain health inequity, was also used to explain the divergence in understanding social class.\n\nHealth security has also been looked at through the normative theory, which is prescriptive on the existence of effective international agreements and cooperation. However, the study that discusses it also highlighted its limitation of inability to explain the crumbling nature of international cooperation that deterred a comprehensive mechanism to address health challenges. While liberals argued for new developing state actors to cooperate for collective action, the post-modernists argued that such cooperation must also involve the voice of all stakeholders. The discussion of new actors becomes prevalent when the discussions by the theory of hegemonic rise and fall highlight the cyclical nature of great powers and the lack of global leadership in mitigating health risks. This brings importance to why health has to become a foreign policy priority in all countries as deliberated by the theory of relational justice which emphasizes that states should not only assist in treating a health concern that affects them but also in preventing any future harm to other countries.\n\n\nDiscussions\n\nThe global health challenge of the COVID-19 pandemic has invariably threatened the primary functions of foreign policy, such as international security, economic stability, human dignity, and social justice. The lapse of the existing global health systems, governing structures, and geopolitical tensions across the world, have made it relevant for international relations scholars to discuss health security and the future direction of the global world order. In this scoping review, we witnessed increased instances of applying IR theories in health security discussions to explain the complex nature of the shifting world order. Various diverging theories have been used to deliberate on states’ actions in tackling the recent pandemic and have also been prescriptive about the changing notions of multilateralism and international governing organizations. Additionally, the IR theories have also discussed other health concerns such as communicable and non-communicable diseases, and the determinants of health such as food, housing, education, social justice, and inequalities. Thus, it has become more imperative than ever before to understand how health is evolving into a critical concern in IR.\n\nThe contentious issues with the geopolitical dimension are mainly linked to equity and human rights, the sharing of knowledge, technology, and innovation, and the financing of global public goods for health.8 The lack of global solidarity is the major barrier to achieving equity in access to vaccines, therapeutics, and diagnostics. According to WHO Director-General, Dr Tedros Adhanom Ghebreyesus, from the human rights lens, “[t] he enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being without distinction of race, religion, political belief, economic or social condition”. The central principle of the 2030 Agenda for Sustainable Development is to ensure that no one is left behind. For instance, inequity and lack of international cooperation to access COVID-19 tools threatened global public health security.\n\nThe involvement of IR theories in discussions on health has evolved post-Cold War caused by the shift in the lens through which policymakers view health. Security discussions during the Cold War period focused predominantly on military-based national security concerns. According to the WHO Regional Committee for the Eastern Mediterranean, the security dimensions in the 21st century are characterized by increasing complexity, the fourth industrial revolution, economic polarization, global interdependence in the supply chain, international conflicts, and a wide range of threats, including emerging and re-emerging diseases. The growing insecurity is not adequately addressed by the traditional mechanisms used to pursue national security. In the current scenario, people’s security depends on factors beyond a particular state’s control and demands a global approach to tackle fundamental issues and mutual vulnerability. The complexity of the global problems and the need for collective action have made it relevant for a multidisciplinary approach to tackle global concerns.\n\nThe increased securitization of global public goods and services, such as health, has provided the impetus for IR scholars to contribute to its discussions. The gradual shift of health from being of ‘low politics’ (humanitarian endeavor) to ‘high politics’ (national and international security concerns) and its increased discussions in foreign policy matters have provided a perfect segway for applying IR theories in such conditions.35 The results of this study show that the IR theories deliberating on health concerns have disease-specific and system-oriented elements. The theories have been applied to understand the state’s action or inaction during a health crisis and relate it to the geopolitical environment in which they function. Interestingly, despite their differences in their approach to tackling a crisis, most theoretical applications concur that the world can expect a shift in the world order after the COVID-19 pandemic. Thus, by looking at geopolitical and geoeconomic determinants of health, the theories have emphasized the need for health to be considered a foreign policy issue.\n\nThis scoping review intended to understand how IR theories were applied in health security, why it is relevant in the current geopolitical and health context, and what difference they can make. The results have extensively shown the overlaps and the variance in the theoretical approach to health security. While the wake-up call for IR scholars to deliberate on health security issues became prominent with the COVID-19 pandemic, health as a non-traditional security issue evolved in the post-Cold War era to be included and prioritized in foreign policy. The momentum that health security has gained in the IR space must be further pushed forward by IR scholars using the existing theories in post facto analysis and predicting and prescribing states’ actions. Thus, by combining the two disciplines of IR and health, the world can be prepared to tackle a future global health crisis that implies geopolitics. We included studies published only in the English language and we acknowledge this as a limitation. Future studies can include literature from other languages.\n\n\nConclusions\n\nThis scoping review brings into perspective the need for adopting an interdisciplinary as well as a multidisciplinary approach in bridging the gap between health and international relations. The COVID-19 pandemic brought to the surface that health crisis is not just a single state’s problem and demands a global approach to finding solutions to such crisis. Pandemics thereby are a ‘global health issue’ and very much linked to states ‘security’ and ‘survivability’. This makes it imperative to view and discuss ‘health’ in the larger confines of IR. Given this, the paper attempts to further expand the security discourse of IR by focusing on ‘health’ as a core issue of security. Here, the intention lies in creating the scope for further research to bridge the existing gap between ‘health’ and ‘IR’.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nOpen Science Framework: Scoping Review of International Relations Theories in Health Security: A Cue for Health Diplomacy. https://doi.org/10.17605/OSF.IO/NY9WZ. 15\n\nThis project contains the following underlying data:\n\n• Appendices.pdf (Appendix 1 - Literature Search, Appendix 2 - Reason for excluding studies, Appendix 3 - Data Extraction Table)\n\n• PRISMA Flowchart.jpg\n\nPRISMA-ScR checklist for ‘Scoping Review of International Relations Theories in Health Security: A Cue for Health Diplomacy’. https://doi.org/10.17605/OSF.IO/NY9WZ. 15\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 acknowledge Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, for the logistics and administrative support.\n\n\nReferences\n\nKim Y, Park Y: International Health Cooperation in the Post-Pandemic Era: Possibilities for and Limitations of Middle Powers in International Cooperation. Soc. Sci. 2022; 11(6). Publisher Full Text\n\nBenyera E: Covid-19 Vaccine Nationalism and Vaccine Diplomacy: A New Currency in Soft Power? Strateg. Rev. S. Afr. 2021; 43(2): 200–224. Publisher Full Text\n\nAbabakr A: The Coronavirus Pandemic and the Transformation of International Order: A Short Overview. Journal of Liberty and International Affairs. 2022; 8(2): 266–280. Publisher Full Text\n\nGupta N, Singh B, Kaur J, et al.: COVID-19 Pandemic and Reimagination of Multilateralism through Global Health Diplomacy. Sustainability. 2021; 13(20): 11551. Publisher Full Text\n\nBasrur R, Kliem F: Covid-19 and international cooperation: IR paradigms at odds. SN Soc. Sci. 2021; 1(1): 7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDougherty JE, Pfaltzgraff RL: Contending Theories of International Relations: A Comprehensive Survey. 5th ed.Longman; 2001.\n\nStoeva P: International Relations and the Global Politics of Health: A State of the Art. Glob. Health Gov. 2016; 10(3).\n\nKickbusch I, Holzscheiter A: Can geopolitics derail the pandemic treaty? BMJ. 2021; 375: e069129. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDavies M, Hobson C: An embarrassment of changes: International Relations and the COVID-19 pandemic. Aust. J. Int. Aff. 2023; 77(2): 150–168. Publisher Full Text\n\nPeterson J, Pearce PF, Ferguson LA, et al.: Understanding scoping reviews: Definition, purpose, and process. J. Am. Assoc. Nurse Pract. 2017; 29(1): 12–16. Publisher Full Text\n\nArksey H, O’Malley L: Scoping studies: Towards a methodological framework. Int. J. Soc. Res. Methodol. 2005; 8(1): 19–32. Publisher Full Text\n\nTricco AC, Lillie E, Zarin W, et al.: PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann. Intern. Med. 2018; 169(7): 467–473. Publisher Full Text\n\nDavies SE: What contribution can International Relations make to the evolving global health agenda? Int. Aff. 2010; 86(5): 1167–1190. PubMed Abstract | Publisher Full Text\n\nWalt G, Gilson L: Reforming the health sector in developing countries: the central role of policy analysis. Health Policy Plan. 1994; 9(4): 353–370. PubMed Abstract | Publisher Full Text\n\nPattanshetty S, Inamdar A, Dsouza V, et al.: Scoping Review of International Relations Theories in Health Security: A Cue for Health Diplomacy. [Dataset]. OSF. 2024. Publisher Full Text\n\nOuzzani M, Hammady H, Fedorowicz Z, et al.: Rayyan-a web and mobile app for systematic reviews. Syst. Rev. 2016; 5(1): 1–10. Publisher Full Text\n\nLabonté R, Gagnon ML: Framing health and foreign policy: lessons for global health diplomacy. Global Health. 2010; 6: 14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSaniabadi ER: COVID-19 and International Order: A Case Study of China’s Role. J. World Sociopolitical Stud. 2022; 6(2): 273–303. Publisher Full Text\n\nBirn AE, Muntaner C, Afzal Z: South-South cooperation in health: bringing in theory, politics, history, and social justice. Cad. Saude Publica. 2017; 33(2). Publisher Full Text\n\nKoblentz GD: From biodefence to biosecurity: The Obama administration’s strategy for countering biological threats. Int. Aff. 2012; 88(1): 131–148. Publisher Full Text\n\nDuarte DE, Valença MM: Securitising Covid-19? The Politics of Global Health and the Limits of the Copenhagen School. Contexto Internacional. 2021; 43(2): 235–257. Publisher Full Text\n\nHowell A: The Global Politics of Medicine: Beyond global health, against securitisation theory. Rev. Int. Stud. 2014; 40(5): 961–987. Publisher Full Text\n\nMcInnes C, Rushton S: HIV/AIDS and securitization theory. Eur. J. Int. Rel. 2012; 19(1): 115–138. Publisher Full Text\n\nKickbusch I, Liu A: Global health diplomacy-reconstructing power and governance. Lancet. 2022; 399(10341): 2156–2166. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWishnick E: Dilemmas of securitization and health risk management in the People’s Republic of China: the cases of SARS and avian influenza. Health Policy Plan. 2010; 25(6): 454–466. PubMed Abstract | Publisher Full Text\n\nCrick E: Drugs as an existential threat: An analysis of the international securitization of drugs. Int. J. Drug Policy. 2012; 23(5): 407–414. PubMed Abstract | Publisher Full Text\n\nLo Yuk-Ping C, Thomas N: How is health a security issue? Politics, responses and issues. Health Policy Plan. 2010; 25(6): 447–453. PubMed Abstract | Publisher Full Text\n\nLiu FK: Human security in the Asia Pacific: perspective of food and health security. Asia Pac. J. Clin. Nutr. 2009; 18(4): 669–673. PubMed Abstract\n\nDavies S: Securitizing Infectious Disease. Int. Affairs (Royal Institute of International Affairs 1944-). 2008; 84(2): 295–313. Publisher Full Text\n\nLarsson OL: The Swedish Covid-19 strategy and voluntary compliance: Failed securitisation or constitutional security management? Eur. J. Int. Secur. 2022; 7(2): 226–247. Publisher Full Text\n\nHanrieder T, Kreuder-Sonnen C: WHO decides on the exception? Securitization and emergency governance in global health. Secur. Dialogue. 2014; 45(4): 331–348. Publisher Full Text\n\nPathak T: Engagement of Constructivism with the Human Security Theory. J. Manag. Public Policy 2021; 13(1): 49–61. Publisher Full Text\n\nMuntaner C, Ng E, Chung H, et al.: Two decades of Neo-Marxist class analysis and health inequalities: A critical reconstruction. Soc. Theory Health. 2015; 13(3-4): 267–287. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBalan A, Savin C, Balan GG, et al.: Health Protection and International Relations. A Postmodernist Approach. Revista de Cercetare si Interventie Sociala. 2014; 45: 160–174.\n\nFidler DP: Health as foreign policy: harnessing globalization for health. Health Promot. Int. 2006; 21(suppl_1): 51–58. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "263570",
"date": "10 Apr 2024",
"name": "Rahul Jindal",
"expertise": [
"Reviewer Expertise Transplant surgery",
"Global Surgery",
"Global Health Diplomacy and development."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors have carried out a scoping review to dissect the question “How have International Relations scholars discussed and debated on health security concerns”?\nThe review has been carried out appropriately by employing standard methods adapting the health policy triangle framework.\nA few minor points will enhance the manuscript:\n1. The authors need to clarify if gray literature was examined.\n2. The authors could add a few lines on the increasing geo-political influence of India and its’ potential role of leadership of the Global South as it relates to international relations and health security.\n3. The authors could also discuss the role of South-South collaboration in the new international world order.\n4. The authors have touched on ‘Modern Socialist and Marxist Theories’ and how this could be reconciled with universal human rights, a topic of great interest in liberal democracies.\n5. The authors briefly mention “The application of critical and decolonization theory” – they could perhaps expand on how decolonization of global health intersects with security concerns?\nOverall, this scoping review brings a new perspective in bridging the gap between health security and international relations. It is clearly important to understand international relations, security, global health, and diplomacy via a theoretical lens.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "263573",
"date": "09 May 2024",
"name": "Anders Nordström",
"expertise": [
"Reviewer Expertise Public health policy"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n-The article is focused with a clear question as well as results. I have only three comments 1. The fact that health security has been interpreted in different ways in IR - what does that mean? Any implications? Recommendations for the future? 2. The article indicates that health treated as a security issue is (or was?) now higher up on the political agenda. It would be useful with some comments on the fact that that interest has now disappeared i.e. lack of sustainable political interest 3. Are the risks and limitations applying an IR perspective and analysis of health?\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) No",
"responses": []
},
{
"id": "263569",
"date": "21 May 2024",
"name": "Garry Aslanyan",
"expertise": [
"Reviewer Expertise health policy and systems",
"global health diplomacy"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAs a scoping review, this article provides a useful overview of theories used in IR and it is applied in analyzing health security. The paper can be further strengthened by clearly outlining which stakeholders in IR (academia, think tanks, governments, lobby groups, NGOs) need to do what differently to adjust to the realities of the 21st century and the need for multidisciplinary approaches in these theories going forward.\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": []
}
] | 1
|
https://f1000research.com/articles/13-184
|
https://f1000research.com/articles/13-181/v1
|
11 Mar 24
|
{
"type": "Case Report",
"title": "Case Report: Ofloxacin-induced fixed drug eruption",
"authors": [
"Anuj R. Varma",
"Ashish R. Varma",
"Sakshi P. Arora",
"Waqar M. Naqvi",
"Anuj R. Varma",
"Ashish R. Varma",
"Sakshi P. Arora"
],
"abstract": "Background Fixed Drug Eruption (FDE) is a rare form of drug-induced dermatoses that appears as well-defined, erythematous patches occurring within hours of medication’s administration with or without blistering and resolves with post-inflammatory residual hyperpigmentation.\n\nCase presentation A 50-year-old male patient visited the outpatient department with chief complaints of burning micturition, increased urine frequency, and high-grade fever with chills lasting three days. Blood and urine investigations indicated leukocytosis and remnants of pus cells, respectively, confirming the diagnosis of urinary tract infection intervened with a tablet ofloxacin. Two hours after drug consumption, intense itching was noticed over the body, which soon progressed to blackening discoloration; blisters developed with a burning sensation over the webs of the palm and on the arm, with hyperpigmentation of the lower lip. Furthermore, painful patches with serous discharge developed in the oral cavity and penile tip. He had encountered a similar episode seven years before, which confirmed the diagnosis of fixed drug eruption (FDE). Immediate treatment included injectable steroids, antihistamines, cephalosporin antibiotics, and intravenous fluids with discontinuation of the ofloxacin drug. He adhered well to the treatment and had a remarkable improvement after 72 hours with residual hyperpigmentation, following which, the patient was advised to avoid similar medicine in the future to prevent a recurrence.\n\nConclusions This case report concludes that the adverse drug reactions should be considered mandatorily with antibiotic audits on a regular basis to ensure that the course of treatment is appropriate and adequate, and any inappropriate reaction should be reported immediately. The rationality of the treatment and inappropriate prescriptions must be reported.",
"keywords": [
"Fixed Drug Eruption",
"Ofloxacin",
"Dermatoses",
"Fluoroquinolone",
"Urinary Tract Infection"
],
"content": "Introduction\n\nFixed drug eruption (FDE) or “eruption érythémato-pigmentée fixe” was initially reported and described by Bourns in 1889 and Brocq in 1894, respectively.1 FDE is a specific type of drug-induced dermatoses that emerges as clearly defined, erythematous (eryth) patches occurring with or without blisters within hours of the administration of the triggering medication and resolves with post inflammatory persisting hyperpigmentation.2 When exposed again to the same or a comparable class of medications, it typically occurs at the same area of the skin or mucous membrane.2\n\nOfloxacin (OF), a fluoroquinolone (FQ) of second generation, is quite efficient against a variety of bacterial infections with some adverse effects that include gastrointestinal disorders, skin reactions, and neurological reactions.3 They are commonly used antibiotics that can cause dermatological adverse drug reactions (ADRs) in about 1-2% of individuals.4 Rare hypersensitivity events due to OF include itching, skin rashes, urticaria, erythema and shock, and their frequency ranges from 0.4% to 2%.5\n\nFDE can affect people of any age, however it most frequently affects individuals with documented median ages ranging from 35 to 60 years, and both men and women are equally susceptible to it.1 Recurrence of FDE is regulated by CD8+ memory T-cells, which are found in the basal layer of the epidermis of dormant FDE lesions.6 These cells drift upwards in the epidermis within 24 hours of ingesting the triggering medicine,6 generate cytokines such interferon-gamma and TNF-alpha (1), acquire the features of a natural killer cell, and express the cytotoxic chemicals granzyme B and perforin along with cell surface molecule CD56.6 This natural killer feature that the cells acquired during FDE subsides once the acute stage of the condition has passed and they remain dormant in the epidermis in the region of prior eruption for a long time.6 Bullous FDE, however, is not frequently recorded. Thus, this case report emphasizes a rare instance of FDE brought on by the administration of the drug OF.\n\n\nCase report\n\nThe case report was amended according to the CARE guidelines.\n\nA 50-year-old South-Asian male patient presented at the Acharya Vinoba Bhave Rural Hospital, Sawangi, India, with the main complaints of burning micturition, increased frequency of urination, nausea, vomiting, pain in low back and high-grade fever with chills lasting three days at the medicine outpatient department (OPD). The patient described a past history of urinary tract infection (UTI) seven years before for which he had taken unknown medicine that he was not able to recollect that caused him intense itching along with blackening of skin of upper and lower limbs and gluteal region along with development of blisters.\n\nOn examination, the patient was coherent, well-oriented and stable with blood pressure 110/70 mmHg, for investigations the patient’s blood and urine sample were sent for laboratory investigation, which revealed increased C-reactive protein, raised blood creatinine, leukocytosis with neutrophilia and increased number of pus cells that confirmed the diagnosis of UTI caused by the bacteria Escherichia coli. As the bacteria was found sensitive to the drug OF it was prescribed to the patient along with the advice of consumption of plenty of water. The first dose of OF was taken by the patient on the same evening.\n\nAt midnight, after 2 hours of drug consumption, intense itching started all over the body, especially involving upper and lower limbs and gluteal region, which soon progressed to blackening of skin on these parts. Additionally, physical examination revealed development of five blisters with burning sensation measuring 2–2.5 cm in diameter that were well circumscribed having an erythematous base over webs of palm (Figure 1) and on arm with negative Nikolsky sign7 along with hyperpigmentation of the lower lip. Furthermore, the patient developed painful erosions with serous discharge formation in oral cavity (Figure 2), penile tip, and prepuce (Figure 3). Based on the above presentation following the administration of the drug OF, the patient was referred to dermatology OPD where a diagnosis of fixed drug eruption was confirmed.\n\nBefore commencing medical intervention, the objective of the treatment was described to the patient and written informed consent was obtained. Following which immediate medical treatment was started with injectable steroids, injection ceftriaxone and levocetirizine, intravenous fluids, and topical betamethasone butyrate propionate ointment along with discontinuation of OF.\n\nThe patient adhered well to the above mentioned treatment as the outcomes of the intervention demonstrated subsiding of itching after 3 to 4 hours, oral and penile ulceration healed in 48 hours and overall condition of the patient improved after 72 hours with the presence of residual hyperpigmentation. Patient was advised to avoid similar medicine in future to avoid recurrence.\n\n\nDiscussion\n\nOF is a FQ prescribed to treat diseases of the prostate, skin, urinary system, and lungs caused due to bacteria. Anaphylactic responses and incidences of shock related to hypersensitivity have been documented during post-marketing surveillance.8 The terminology FDE indicates formation of eryth patches as a consequence of administration of a medication. Based on the location of the lesion and their clinical characteristics, various morphological forms of FDE, such as pigmenting, non-pigmenting, and bullous FDE, are known.3 According to a systematic review, antibiotics are responsible for 28% of ADRs, and the estimated prevalence rate of ADRs caused by ofloxacin is 4.27%.9\n\nThe basic presentation of the OF-related FDE seen in this case was intense itching all over the body. In particular, it involved upper and lower limbs and gluteal region, which soon progressed to blackening of skin on these parts. Development of blisters with burning sensation were well circumscribed with an erythematous base over webs of palm and on arm along with hyperpigmentation of the lower lip, and painful erosions with serous discharge formation in oral cavity, penile tip and prepuce. Development of blisters made the condition of this patient more severe. These related findings were published in a study that characterized generalized bullous FDE as standard FDE lesions occur at three of six different anatomic regions with blisters covering and accounting for not less than 10% surface area of the body. It was referred as Stevens-Johnson syndrome, which was basically differentiated on the basis of morphological characteristics of the eruption and the site of onset.10\n\nThe pathophysiological process consists of cell-mediated cytotoxic reaction, which is antibody-dependent, and CD8+ effector or memory T cells play a critical role in reactivating the reaction when exposed to the triggering medication again, however the precise mechanism is still unknown.3 However, the evidence indicates that these cells are primarily responsible for the occurrence of localized tissue destruction in FDE, and arousal of these cells triggers skin lesion.1,3 OF and other quinolones can cause both the IgE-mediated as well as delayed form of hypersensitivity reaction.2,11\n\nIn this case the patient was diagnosed with UTI for which OF was prescribed that resulted in FDE. Similarly, a previous review demonstrated various ADRs of OF that involved angioedema when given in case of diarrhea,9 cutaneous vasculitis in diabetic foot and UTI, intense erythema with sub-corneal pustulation, fever, and neutrophil leukocytosis in bronchitis and pharyngitis.9 The ADRs improved when OF that was being administered was discontinued, as there was no other cause that might have independently caused the reaction, and it was therefore, confirmed to be an FDE. Treatment for these reactions should primarily focus on cessation of the triggering drug and consumption of topical corticosteroids or antihistamines, and cephalosporin antibiotics.3 In this case, injectable steroids, injection ceftriaxone, and levocetirizine and intravenous fluids, topical betamethasone butyrate propionate ointment along with discontinuation of OF was commenced. When the patient returned for follow-up one month later, the lesions had subsided and the patient had responded well to the treatment.\n\nThe primary take away lessons involve strict avoidance of the culprit drug, which can protect the patient from recurrence, for diagnosis of fixed drug reactions the patient can be rechallenged by oral or patch test with the offending drug causing eruptions repeatedly at the identical skin site (that is fixed), and a note can be written on the discharge card with mention of offending drug molecule along with patient education for future prescription by other doctors.\n\n\nConclusions\n\nThis case report highlights fixed drug eruption caused due to ofloxacin drug during treatment of UTI and concludes that all hospitals should be mandated to track ADRs along with conduction of antibiotic audits on a regular basis to ensure that the course of treatment is appropriate and adequate, and any inappropriate prescription should be reported. A regular antibiotic audit must be done to check the rationality of the treatment and in case of inappropriate prescribing, errors must be reported. Additionally, ofloxacin must be included in the differential diagnosis of FDE and healthcare providers need to be made aware of illogical drug combinations.\n\nI had this tendency of increased urination for 15 years. But this time it was with burning micturition and fever. I visited a nearby hospital. They admitted me and initiated with some medication. After two hours of consuming my first dosage, I felt itching everywhere on my body. Then I noticed weird black stains over my lower lip and palms, so I immediately called the medical staff on duty who immediately took my concern into consideration and called for further help. Again, I got prescribed with some other medications and after three days, I was relieved a bit with the symptoms.\n\n\nConsent\n\nWritten informed consent for publication of clinical details and images was obtained from the patient.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nReferences\n\nAnderson HJ, Lee JB: A Review of Fixed Drug Eruption with a Special Focus on Generalized Bullous Fixed Drug Eruption. Medicina. 2021; 57: 925. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKameswari PD, Selvaraj N, Adhimoolam M: Fixed drug eruptions caused by cross-reactive quinolones. J Basic Clin Pharm. 2014; 5: 54–55. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGohel KH, Shah KV, Patel S, et al.: Ofloxacin-induced fixed drug eruptions. Int. J. Integr. Health Sci. 2020; 8: 22. Publisher Full Text\n\nJain SP, Jain PA: Bullous Fixed Drug Eruption to Ciprofloxacin: A Case Report. J. Clin. Diagn. Res. 2013; 7: 744–745. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRamineni HB, Eluri P, Vipparla K, et al.: Ofloxacin induced hypersensitivity reaction. Int. J. Res. Med. Sci. 2017; 3: 349–351. Publisher Full Text\n\nMizukawa Y, Yamazaki Y, Shiohara T: In vivo dynamics of intraepidermal CD8+ T cells and CD4+ T cells during the evolution of fixed drug eruption. Br. J. Dermatol. 2008; 158: 1230–1238. PubMed Abstract | Publisher Full Text\n\nMaity S, Banerjee I, Sinha R, et al.: Nikolsky’s sign: A pathognomic boon. J. Family Med. Prim. Care. 2020; 9: 526–530. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSarkar MK, Dey S: A Fixed-Dose Combination of Ofloxacin-Ornidazole Induced Fixed Drug Eruption: A Case Report. Cureus. 2023; 15: e35630. eCollection 2023 Mar. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKamdi AS, Kokane SD, Bohra PN, et al.: Systematic review of adverse drug reactions of ofloxacin. International Journal of Basic & Clinical. Pharmacology. 2018; 7: 2277–2280. Publisher Full Text\n\nCho Y-T, Lin J-W, Chen Y-C, et al.: Generalized bullous fixed drug eruption is distinct from Stevens-Johnson syndrome/toxic epidermal necrolysis by immunohistopathological features. J. Am. Acad. Dermatol. 2014; 70: 539–548. PubMed Abstract | Publisher Full Text\n\nSánchez-Morillas L, Rojas Pérez-Ezquerra P, González Morales ML, et al.: Fixed drug eruption due to norfloxacin and cross-reactivity with other quinolones. Allergol. Immunopathol. 2013; 41: 60–61. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "287834",
"date": "10 Jun 2024",
"name": "Esen Özkaya",
"expertise": [
"Reviewer Expertise Allergic contact dermatitis",
"fixed drug eruption"
],
"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 case report on ofloxacin-induced fixed drug eruption on skin and mucosa. I have the following comments and suggestions for improvement (page numbers refer to the PDF):\nPage 3, Introduction: Please focus on the background information of ofloxacin-induced fixed drug eruption in the literature. Also, please add information on common clinical forms of quinolone-induced FDE. The last 2 sentences of the introduction need revising to be more specific to the presented case. Move the pathophysiology to the discussion section. Page 3, Patient information: Please add the Fitzpatrick skin type of the patient. Page 3, Clinical findings and diagnostic assessment: Was the patient diagnosed with generalized bullous FDE or not? Please revise accordingly. Include the Naranjo drug reaction probability score of the patient. The diagnosis of FDE needs to be confirmed by systemic or topical provocation. Was a topical provocation test performed? Please add this to the text. Was this the second attack of FDE? Please add the information to the text. Also, include details of any similar episodes in the past. Page 4, Follow-up and outcomes: How long was the patient followed-up for recurrences? What does “similar medicine” mean? Please be more specific. Page 5, Discussion: Was the patient diagnosed with generalized bullous FDE or not? Please add this to the discussion along with the reasons. Please revise “It was referred as Stevens-Johnson syndrome, which was basically differentiated on the basis of morphological characteristics of the eruption and the site of onset.” as “It was differentiated from Stevens-Johnson syndrome on the basis of morphological characteristics of the eruption, such as ………, and the site of onset, particularly, ……” Page 5, Discussion: Please discuss other quinolone-induced FDEs published in the literature along with their cross-reactivity. Was this patient checked for cross-reactivity to other quinolones? Page 4, Conclusion: Please revise the conclusion to focus on the major outcomes for this patient. What does this case add to the literature, and why is it significant?\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-181
|
https://f1000research.com/articles/13-178/v1
|
11 Mar 24
|
{
"type": "Study Protocol",
"title": "A prospective observational study of red cell distribution width (RDW) as an outcome marker in Critically ill children admitted to a Pediatric Intensive Care Unit in a tertiary care hospital in central India",
"authors": [
"nimmanagoti nagaraju",
"Ashish Verma",
"DR AMAR TAKSANDE",
"Ashish Verma",
"DR AMAR TAKSANDE"
],
"abstract": "Background Critically ill pediatric patients often present with a broad spectrum of conditions, and early prognostic markers are essential for guiding clinical decisions. Red Cell Distribution Width (RDW), a measure of the variability in red blood cell size, has been associated with various health conditions.\n\nMethods The study will be conducted over two years at a tertiary care hospital in Central India. Critically ill children between the ages of 1 month and 18 years admitted to the PICU will be consecutively enrolled after obtaining informed consent. Demographic data, vital signs, diagnoses, laboratory results, and relevant scores (PELOD-2 and SOFA) will be recorded. Outcome variables will be documented, including ICU stay duration, mechanical ventilation days, ionotrope usage, development of Acute Kidney Injury (AKI), renal replacement therapy, and outcome (death or discharge). Statistical analysis will involve t-tests, chi-square tests, ROC curve analysis, sensitivity, specificity, positive predictive value, and negative predictive value calculations.\n\nExpected results The study aims to provide insights into the potential of RDW as a predictor of morbidity and mortality in critically ill pediatric patients. Comparison with established scoring systems will contribute to understanding the practical significance of RDW in clinical decision-making.",
"keywords": [
"RDW",
"Pediatric Intensive Care",
"Critically Ill Children",
"Outcome Predictors",
"Tertiary Care Hospital",
"Central India"
],
"content": "Introduction\n\nCritically ill children admitted to the Pediatric Intensive Care Unit (PICU) represent a diverse and vulnerable patient population, spanning a broad spectrum of medical conditions and clinical severity.1 Predicting the course and outcomes of these patients early in their PICU stay is paramount for clinical decision-making, resource allocation, and improved patient care.2\n\nRed Cell Distribution Width (RDW), a routine hematological parameter that reflects the variability in red blood cell size, has recently gained attention as a potential prognostic marker in various clinical settings.3 While RDW is traditionally used to assess anemia, emerging evidence suggests its broader utility in predicting morbidity and mortality in critically ill adults. However, its applicability in the pediatric population, especially in the context of the PICU, still needs to be explored.4\n\nConsidering this knowledge gap, this study protocol outlines a prospective observational study designed to investigate the role of RDW as a predictor of outcomes in critically ill children admitted to a tertiary care hospital in Central India. By assessing RDW’s association with morbidity and mortality in this specific patient cohort, we aim to provide valuable insights into its potential as a prognostic tool.\n\nMoreover, this study compares RDW with well-established scoring systems, such as the Pediatric Logistic Organ Dysfunction 2 (PELOD-2) and Sequential Organ Failure Assessment (SOFA) scores, to evaluate its clinical significance. Such a comparative analysis can help clarify RDW’s place in clinical decision-making. The findings of this study are expected to have important implications for PICU healthcare providers, as a reliable prognostic marker could enhance the early identification of patients at higher risk and guide therapeutic interventions. Ultimately, this research aims to contribute to improved patient care and outcomes in the challenging environment of the PICU.\n\nTo investigate the utility of Red Cell Distribution Width (RDW) as a predictive marker for the outcome of critically ill children admitted to the Pediatric Intensive Care Unit (PICU).\n\n\n\n1. To evaluate RDW as a predictor of morbidity in critically ill children.\n\n2. To assess RDW as a predictor of mortality in critically ill children.\n\n3. To compare the predictive value of RDW with Pediatric Sequential Organ Failure Assessment (pSOFA) and Pediatric Logistic Organ Dysfunction 2 (PELOD2) scores in predicting the outcome of patients in the PICU.\n\n\nMethods\n\nProspective Observational Study.\n\nCritically ill children between the ages of 1 month and 18 years were admitted to the Pediatric Intensive Care Unit (PICU) of Acharya Vinoba Bhave Rural Hospital (AVBRH) in Central India set 2023-2024.\n\nThe study will be conducted in the Pediatric Intensive Care Unit (PICU) of the Department of Pediatrics at Acharya Vinoba Bhave Rural Hospital (AVBRH), a 1525-bedded tertiary care hospital located in Sawangi (Meghe), Wardha, Maharashtra, Central India.\n\n\n\n1. Critically ill children aged between 1 month to 18 years.\n\n2. Admitted to the Pediatric Intensive Care Unit (PICU).\n\n3. PICU stays more than 24 hours.\n\n\n\n1. Refusal of consent from the patient or guardian.\n\n2. Admission for scheduled procedures that are typically managed outside the PICU.\n\n3. PICU stay of less than 24 hours.\n\n4. Patients with pre-existing hematological disorders.\n\n5. Patients who have received a blood transfusion within the past seven days.\n\n\n\n1. Selection bias: There will be a potential for selection bias in the study, as only critically ill children admitted to the Pediatric Intensive Care Unit (PICU) will be included. This may not represent the entire spectrum of pediatric patients, leading to a bias toward more severe cases.\n\n2. Sampling bias: The study will use consecutive sampling, which may introduce bias if certain patients are systematically excluded or underrepresented during specific periods.\n\n3. Information bias: Information bias could occur due to variations in data collection methods and interpretations of laboratory results, especially when multiple individuals are involved in data collection and recording.\n\n\n\n1. Eligibility criteria: Patients who satisfy the predefined inclusion criteria, which include critically ill children aged between 1 month to 18 years and having Pediatric Intensive Care Unit (PICU) stays exceeding 24 hours, are eligible for enrollment in the study. This criterion-based approach is fundamental for maintaining the study’s relevance and applicability to the target population.\n\n2. Informed consent: Enrollment into the study occurs only after obtaining written informed consent from the patient (if of an appropriate age and capacity) or from their legal guardians. This practice is essential for ensuring the ethical conduct of the research, respecting patient autonomy, and upholding the principles of informed and voluntary participation in medical research.\n\n3. Consecutive sampling: To minimize the potential for selection bias and enhance the representativeness of the study population, consecutive sampling is employed. This systematic approach ensures that eligible patients are enrolled in the study continuously and unbiasedly throughout the two-year study period.\n\n4. Data collection: Each patient undergoes a comprehensive data collection process once enrolled. This involves gathering detailed information, including demographic data, vital signs, specific diagnoses, results of laboratory tests, and the calculation of scores such as Pediatric Logistic Organ Dysfunction 2 (PELOD-2) and Sequential Organ Failure Assessment (SOFA). The data collected for each patient forms the basis for the subsequent Red Cell Distribution Width (RDW) analysis and its association with various outcome variables.\n\nThe data collection process described in the study will be a systematic and methodical approach aimed at gathering critical information from critically ill children who will be admitted to the Pediatric Intensive Care Unit (PICU) at Acharya Vinoba Bhave Rural Hospital (AVBRH) in Central India.\n\nUpon a patient’s admission to the PICU, a structured process will be initiated to ensure consistent data collection. Patients who will meet the inclusion criteria, including those aged between 1 month and 18 years and expected to stay in the PICU for more than 24 hours, will be enrolled in the study after obtaining informed consent, either from the patient (if of an appropriate age) or their legal guardians.\n\nThe data collection process will encompass several key aspects:\n\n1. Demographic data: Detailed demographic information, including age, gender, and weight, will be meticulously recorded for each enrolled patient. This information will be fundamental for characterizing the study population and analyzing how RDW may relate to patient profiles.\n\n2. Clinical assessment: Vital signs, such as heart rate, blood pressure, respiratory rate, and temperature, will be carefully monitored and documented. This clinical assessment will aid in understanding the patients’ overall health status upon admission to the PICU.\n\n3. Diagnosis: The specific diagnosis or reason for admission to the PICU will be noted. This information will help categorize and analyze patient populations with different underlying conditions, which may affect the study’s outcomes.\n\n4. Laboratory investigations: A comprehensive set of laboratory tests will be conducted, including a complete blood count, Red Cell Distribution Width (RDW), Kidney Function Test (KFT), Liver Function Test (LFT), C-reactive protein (CRP), and blood culture. These tests will provide valuable insights into the patients’ hematological and organ function status, as well as the presence of any infectious agents.\n\n5. Additional investigations: Supplementary investigations, such as serum lactate and 2D echocardiography, will be performed when necessary to collect further clinical data relevant to the patient’s condition.\n\n6. Scoring systems: The Pediatric Logistic Organ Dysfunction 2 (PELOD-2)5 and Sequential Organ Failure Assessment (SOFA)6 scores will be calculated within 24 hours of PICU admission. These scoring systems will be instrumental in assessing organ dysfunction’s severity and disease progression.\n\n7. Outcome variables: Crucial outcome variables, including the length of ICU stay, the number of days of mechanical ventilation, ionotrope usage, the development of Acute Kidney Injury (AKI), the need for renal replacement therapy, and the outcome (death or discharge), will be meticulously documented.\n\nThe study protocol specifies a sample size of 129. This means that the study aims to include 129 critically ill children meeting the inclusion criteria (aged between 1 month to 18 years and with PICU stays exceeding 24 hours). This sample size has been determined to provide sufficient statistical power to assess the relationship between Red Cell Distribution Width (RDW) and the outcomes of interest in critically ill children in the Pediatric Intensive Care Unit (PICU) at Acharya Vinoba Bhave Rural Hospital (AVBRH) in Central India.\n\n\n\n1. Morbidity: This refers to being diseased or unhealthy. In the context of the study, researchers are interested in understanding how RDW is related to the morbidity or disease severity of critically ill children in the Pediatric Intensive Care Unit (PICU).\n\n2. Mortality: In this context, mortality refers to death among critically ill children during their PICU stay. Researchers aim to investigate whether RDW can serve as a predictor of mortality in this population.\n\n3. Length of ICU stay: This outcome variable measures each patient’s duration in the Pediatric Intensive Care Unit. Researchers seek to determine whether RDW is associated with longer or shorter ICU stays.\n\n4. Mechanical ventilation days: This outcome assesses the number of days a patient requires mechanical ventilation during their stay in the PICU. Researchers aim to examine whether RDW is linked to a greater need for mechanical ventilation.\n\n5. Ionotrope usage: Ionotropes are medications that support the heart’s function. Researchers will explore the relationship between RDW and the usage of ionotropes in critically ill children.\n\n6. Acute Kidney Injury (AKI): This outcome focuses on developing acute kidney injury during the PICU stay. Researchers intend to investigate whether RDW is associated with a higher likelihood of AKI.\n\n7. Renal Replacement Therapy: Researchers will assess if RDW is linked to the need for renal replacement therapy, a medical procedure to support kidney function in cases of severe renal dysfunction.\n\n8. Outcome (Death or Discharge): This outcome variable categorizes patients into two groups: those who either succumb to their illness and pass away during their PICU stay or those who recover and are discharged. The study aims to determine if RDW can predict these outcomes.\n\nThe study protocol delineates the application of specific statistical methods that will be used to analyze the collected data. These methods are pivotal in unraveling the relationships between Red Cell Distribution Width (RDW) and the various outcome variables of interest; for quantitative variables such as age, weight, and laboratory values, unpaired t-tests or Mann-Whitney tests will be employed to compare and identify statistically significant differences among groups. For qualitative variables, including gender and specific diagnostic categories, statistical tests like Chi-square or Fisher’s exact tests will evaluate proportions and assess associations in categorical data. To evaluate the diagnostic accuracy of RDW as a predictor of outcomes, the study will employ the Receiver Operating Characteristic (ROC) curve analysis. This will determine the optimal cut-off value for RDW, balancing sensitivity and specificity, and calculate the area under the curve (AUC) to gauge RDW’s overall performance as a diagnostic marker. Additionally, confidence intervals will provide insight into the range of likely values, while sensitivity, specificity, positive predictive value, and negative predictive value will gauge the diagnostic capability of RDW. A significance level of p < 0.05 will be considered statistically significant in assessing the relationships between RDW and various outcomes by using R studio version 9.1.\n\nThe Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research (DU) has granted its approval to the study protocol (Reference number: DMIHER (DU)/IEC/2022/1076. Date:27-06-2022). Before commencing the study, we will obtain written informed consent from all participants, providing them with a comprehensive explanation of the study’s objectives.\n\nAfter the completion of the study, we will publish it in an indexed journal or conference.\n\nThe study has yet to start. After the publication of the protocol, we will start recruitment in the study.\n\n\nDiscussion\n\nRDW, a measure of the variability in red blood cell size, has garnered growing attention recently as a potential biomarker for various health conditions. Elevated RDW has been associated with inflammation, oxidative stress, and chronic diseases in adult and pediatric populations.7 In critically ill patients, monitoring and predicting outcomes is paramount, and novel biomarkers such as RDW offer a non-invasive and readily available option for assessment.\n\nThis study aims to assess whether RDW can predict morbidity and mortality in critically ill children. Morbidity and mortality prediction is a critical aspect of clinical care in the PICU, as early identification of patients at higher risk can lead to tailored interventions and improved outcomes. Several studies have demonstrated the potential of RDW as a prognostic marker for morbidity and mortality in various medical conditions.8 However, its application in the context of critically ill children still needs to be well-established.\n\nIn addition to examining RDW’s predictive value, this study will compare it with widely used scoring systems, namely Pediatric Logistic Organ Dysfunction 2 (PELOD-2) and Sequential Organ Failure Assessment (SOFA). These scoring systems assess organ dysfunction and disease severity, and their performance in the PICU setting is well-documented.5,9 A direct comparison with RDW can help elucidate whether this routine hematological parameter offers similar or complementary predictive insights.\n\nRDW may have significant clinical implications if it is a reliable predictor of morbidity and mortality. Physicians can use this readily available parameter to enhance risk stratification and make more informed decisions regarding patient care. Moreover, the comparative analysis with established scoring systems will provide valuable insights into the practical significance of incorporating RDW into clinical practice.\n\nIt is essential to acknowledge the limitations of this study, including its single-center design and the specific population of critically ill children. Furthermore, the study will not explore the underlying mechanisms connecting RDW to outcomes, which remain subjects for future investigation.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nMurphy Salem S, Graham RJ: Chronic Illness in Pediatric Critical Care. Front. Pediatr. 2021; 9: 686206. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBauer A, Korten I, Juchem G, et al.: EuroScore and IL-6 predict the course in ICU after cardiac surgery. Eur. J. Med. Res. 2021; 26: 29. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYousefi B, Sanaie S, Ghamari AA, et al.: Red Cell Distribution Width as a Novel Prognostic Marker in Multiple Clinical Studies. Indian J. Crit. Care Med. 2020; 24: 49–54. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSaid AS, Spinella PC, Hartman ME, et al.: Red blood cell distribution width: biomarker for red cell dysfunction and critical illness outcome? Pediatr. Crit. Care Med. 2017; 18: 134–142. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLeteurtre S, Duhamel A, Salleron J, et al.: Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP): PELOD-2: an update of the PEdiatric logistic organ dysfunction score. Crit. Care Med. 2013; 41: 1761–1773. Publisher Full Text\n\nJones AE, Trzeciak S, Kline JA: The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation. Crit. Care Med. 2009; 37: 1649–1654. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi N, Zhou H, Tang Q: Red Blood Cell Distribution Width: A Novel Predictive Indicator for Cardiovascular and Cerebrovascular Diseases. Dis. Markers. 2017; 2017: 7089423–7089493. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSalvagno GL, Sanchis-Gomar F, Picanza A, et al.: Red blood cell distribution width: A simple parameter with multiple clinical applications. Crit. Rev. Clin. Lab. Sci. 2015; 52: 86–105. Publisher Full Text\n\nVincent JL, Moreno R, Takala J, et al.: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996; 22: 707–710. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "268379",
"date": "30 Apr 2024",
"name": "Nermina Rizvanović",
"expertise": [
"Reviewer Expertise anaesthesiology and intensive care"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Authors, This is a well-designed study. I would like consider some questions. 1.Please, explain the sample size! How did you get the number of 129 patients? What statistical program/test did you use? Power analysis or ....? What did you consider the clinically relevant difference for the primary outcome? What was the variability (standard deviation) of the primary outcome? 2. Please explain whether you will calculate the mean RDW in your cohort and then the predictive significance of that value? Will you use the RDW \"cut-off\" value from the earlier study (eg. RDW 14.5), then divide your cohort based on that earlier \"cut-off\" value (>14.5 group vs. <14.5 group) and compare study objectives? This is unclear.\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": []
},
{
"id": "258284",
"date": "22 May 2024",
"name": "Seema Rai",
"expertise": [
"Reviewer Expertise Pediatric Endocrinology",
"intensive care"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 The article is well written, however there are few suggestions from my side.\nIn introduction please mention how RDW is associated with IDA and how you will tackle bias. The results are not written. I could not access any table and figures. In material and methods write full forms of all abbreviations. The manuscript needs to rewritten by a fellow whose native language is English else use some software to correct the language. Please write confidence interval in the results. Please highlight the factors which are already known and what we are adding by doing this study in discussion.\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? No\n\nAre the datasets clearly presented in a useable and accessible format? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-178
|
https://f1000research.com/articles/13-177/v1
|
11 Mar 24
|
{
"type": "Review",
"title": "Epidemiological behavior of childhood obesity: A continental point of view",
"authors": [
"Maricarmen Chacin",
"Sandra Carrillo-Sierra",
"Pablo Duran",
"Bermany Garrido",
"Ruben Carrasquero",
"Manuel Nava",
"Juan Salazar",
"Lisse Angarita",
"Hazel Anderson",
"Henry Garcia-Pacheco",
"Ana Checa-Ros",
"Luis D’Marco",
"Diego Rivera-Porras",
"Valmore Bermúdez",
"Sandra Carrillo-Sierra",
"Pablo Duran",
"Bermany Garrido",
"Ruben Carrasquero",
"Manuel Nava",
"Juan Salazar",
"Lisse Angarita",
"Hazel Anderson",
"Henry Garcia-Pacheco",
"Ana Checa-Ros",
"Luis D’Marco",
"Diego Rivera-Porras",
"Valmore Bermúdez"
],
"abstract": "Weight excess during the childhood has been one of the most critical public health problems worldwide in the past few decades. It is considered a significant predictor of adulthood obesity, increased cardiometabolic diseases, and premature mortality. Since the Industrial Revolution, childhood obesity has risen due to sedentary lifestyles and poor eating habits, contributing to the development of obesogenic environments around children in different parts of the world. In this regard, Oceania is positioned as the continent with the highest prevalence globally; however, these results did not consider Australia and New Zealand’s data, probably due to the significant differences in population sizes. America has the second highest percentage of children under five who are overweight. Curiously, Asia’s obesity rates are more significant in higher socioeconomic statuses and urban areas than in children aged 2-4 years. Likewise, Africa displays similar epidemiologic behaviour. Qatar and Kuwait are the countries with the highest obesity prevalence on the continent. Moreover, Europe exhibits a notable South-North gradient, which establishes a higher prevalence of obesity in Mediterranean countries than the Nordic ones. In this regard, various prevention and interventional programs have been developed to combat this silent epidemic, focusing their efforts on nutritional education, improving children’s and parents’ lifestyles, and fighting the influence of the media on their behaviour, and decisions. Therefore, the objective of this review was to describe the epidemiological behaviour of childhood obesity from a continental perspective.",
"keywords": [
"Childhood obesity",
"overweight",
"diabetes mellitus",
"hypertension",
"public health."
],
"content": "Introduction\n\nIn the past few decades, the prevalence of childhood obesity has increased dangerously, reaching epidemic proportions in several regions worldwide.1 In that sense, between 2000 and 2018, overweight prevalence rose from 10% to 18% in children and teenagers between 5 and 19 years old; meanwhile, by 2018, 41 million kids under five years old had overweight globally. Moreover, according to the World Health Organization (WHO), the childhood obesity prevalence worldwide was 5.6%, the equivalent to 38.3 million children (excluding Europe), of which 45% were located in Asia and 24% in Africa.2–4\n\nThe progressive industrialization interplaying with environmental and genetic factors has been considered the leading contributor to childhood obesity in Westernized countries.5,6 Likewise, emotional and psychosocial stress, parents’ dietary habits, maternal breastfeeding history, environmental chemicals, and adverse life situations could increase childhood obesity risk factors.7–11 Accordingly, it has been noticed that childhood obesity, especially in children with severe obesity or with a relevant family history of obesity, tends to be strongly associated with overweight persistence during adulthood.12,13 Thus, implementing a proper and timely approach to addressing childhood obesity is of paramount importance.\n\nObesity profoundly influences public health dynamics since its comorbidities cause a substantial economic burden on the health systems.14–18 In this context, weight excess is responsible for significantly high health costs in the United States, accounting for about $147 billion in 2008; and approximately 6% of the medical expenses in Europe.19,20 Given these circumstances, the epidemiological surveillance of childhood obesity acquires paramount importance in preventing its more fearful cardiometabolic complications and other psychosocial problems like anxiety, depression, sleep disorders, low self-esteem, disturbing social relations, and learning process in childhood.17–19\n\nAs a result, epidemiological researchers, governmental and non-governmental entities have monitored the temporal changes in childhood overweight and obesity prevalence worldwide.12,21 Therefore, it is convenient to recognize the factors linked to excessive weight in children, its epidemiological evolution, and future trends. Hence, recognizing the critical importance of identifying the factors contributing to excess weight in children, tracking how these trends evolve, and predicting future patterns is essential. Therefore, the primary aim of this review is to provide a comprehensive understanding of how childhood obesity behaves from a continental perspective, which involves analyzing its prevalence and associated factors across different continents or regions.\n\n\nMethods\n\nThis is a narrative review in which an extensive literature search was performed on Scopus, EMBASE, PubMed, ISI Web of Science, and Google Scholar databases, from their inception to August 2022. The terms “childhood obesity,” “childhood overweight,” “Europe,” “Asia,” “America,” “Middle Eastern countries” and “Africa” were the keywords used in the search. The quality assessment of the studies used in this review was performed by 3 of the authors, and studies with minimal risk of bias were used.\n\nObesity and overweight in European children have increased in the last 20 years. The collaboration between the WHO, International Obesity Taskforce (IOTF), European Union (EU), and several research institutes, made it possible to gather a considerable amount of representative data of the European nations.22 According to the IOTF criteria, 17.9% of the European children (between 2 and 7 years old) have excessive weight, while 5.3% are obese.23 For that reason, the WHO started a surveillance system to study childhood obesity (Childhood Obesity Surveillance Initiative, COSI) to assess the epidemiological behavior of overweight and obesity in European children between 6 and 9 years old (Figure 1).\n\nAbbreviation: N/A: not available. Source: Food Group Consumption, 2019.23 Epidemiological behavior of obesity in European children with IOTF criteria.\n\nSince the beginning of this initiative in 2007, 21 countries have participated in at least one data gathering round between 2007 and 2013. The 2013 round had a sample size of 636,933 children (323,648 boys and 313,285 girls) and demonstrated considerable fluctuation in overweight and obesity prevalence between the enlisted countries exhibiting a pronounced south-to-north gradient in which the southernmost countries like Greece, Spain, Italy, San Marino, Portugal, Malta and The Republic of North Macedonia had the highest overweight and obesity prevalence in contrast to those located in the north, such as Latvia, Lithuania, Norway and Ireland.24 In this vein, data extracted from the third data collection round (2012-2013) from COSI shows that Greece exhibited the highest prevalence of overweight and obesity with 52% for boys and 43% for girls, and 28% and 20% for boys and girls, respectively; followed by Italy with 44% overweight for boys and 40% for girls, and 23% obesity for boy and 15% for girls. Contrarily, Norway stands out among the countries with the lowest prevalence, with 24% overweight and only 7% obesity for boys and girls.24\n\nMoreover, the fourth COSI round (2015-2017) showed the highest overweight, and obesity rates continued to be a significant concern in the southern European region. Nonetheless, although some countries such as Greece, Italy, Spain, Portugal, and Slovenia, decreased their obesity prevalence, they still hold the top ten leading countries with childhood obesity in this continent (Table 1).25 Likewise, the Mediterranean countries with the highest prevalence were Cyprus and Greece; moreover, the above list includes Italy, San Marino and Malta. Predominantly, Nordic countries achieved the lowest prevalence; notably, Denmark had 18% overweight for boys and 20% for girls, and 5% obesity for both. Additionally, Sweden with 10% for boys and 7% for girls, Finland with 11% for boys and 9% for girls, and Norway with 7 % for boys and 5% for girls follow the list of countries with the lowest obesity rates.25 In addition, very few insular European countries participated in the latter study. Notably, Ireland has exhibited a decreasing trend in the prevalence of childhood obesity compared to the last data gathering.\n\nWHO European Childhood Obesity Surveillance Initiative: Overweight and obesity among 6–9-year-old children. Report of the third round of data collection 2012–2013.24,25\n\n* Countries that did not participate in COSI studies are denoted as follows: a: Countries that did not participate in the COSI 2012/2013 studies; d: Refers to 8-year-olds in the COSI 2012/2013 study; e: Refers to 7-year-olds in the COSI 2012/2013 study.\n\nIn Eastern Europe, stable behavior in secular obesity trends was observed for The Czech Republic, while the situation is not clear for Latvia and Lithuania.25 It is essential to highlight that, even though most Russian territory belongs to Asia, a significant proportion of its population lives in the European zone, as is the case of some ex-soviet republics such as Ukraine.26,27 In this regard, some studies have reported that Russia has a very particular milieu with a wide variety of risk factors predisposing childhood obesity development. For example, a recent study conducted by Bocharova et al. found a ten-year prevalence increase from 12.9% to 26.1% between 2008 and 2018; regrettably, access to better data in English is challenging, and this fact is an obstacle to in-deep and more comprehensive analysis.28 The last report from COSI took into account the data gathered between 2015 and 2017, reporting only in Moscow, a prevalence of overweight and obesity in boys of 27% and 10% respectively; meanwhile, girls exhibited 22% and 6% respectively.25\n\nContrary to the past years, countries from central Europe made an appearance in this report. For instance, France, Poland, and Austria show relatively low rates than the other nations. On the other hand, Slovenia had a notorious downturn compared to its previous records. Countries like The Netherlands, Switzerland, Iceland, The United Kingdom, and Germany did not participate in this initiative.29\n\nNotwithstanding, the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) aimed to long-term surveillance of Germany’s childhood overweight and obesity prevalence. In this program, children aged 3-6 and 7-10 exhibited a 9.1% and 15.4% overweight prevalence. On the other hand, obesity prevalence was 2.9% and 6.4% in the same age groups.29,30 As a result, KiGGS Wave 1 (2009-2012) pointed out that ultimately the rates reached a plateau when contrasted to KiGGS’ checkpoint of 2003-2006. Furthermore, the overweight and obesity prevalence rate in children aged between 4 and 10 and teenagers aged between 11 and 17 were slightly higher but not statistically significant.31 Lastly, the data gathered from the KiGGS Wave 2 (2014-2017) showed a prevalence of 15.4% and 5.9% for overweight and obesity, respectively, with no differences between sex. In summary, compared to the reference study, KiGGS (2003-2006), there was no increment in the prevalence of overweight or obesity in general.32\n\nThe Netherlands showed a similar behavior because, in 2009, about 14.8% of Dutch girls and 12.8% of boys were overweight, while 2.2% of girls and 1.8% of boys were obese. The aforementioned overweight prevalence is two to three times higher than the registered back in 1980 and nearly four to six times higher for obesity; notably, the most substantial increment of these rates was achieved in the last decades.33 However, a national study pointed out that the previous overweight prevalence trends had stalled in the country’s main cities like Amsterdam, Rotterdam, The Hague, and Utrecht, but neither rural nor smaller towns. Albeit the stalling trends denoted previously, overweight and obesity still have higher rates than in the eighties; thus, it is still considered a public health issue to be solved in The Netherlands.34\n\nAs mentioned above, Switzerland did not participate in the 2015-2017 COSI study.29 Moreover, the Health Promotion Switzerland (HPS) program identified that from 2010 to 2011 about 20.1% of children and teenagers were overweight or obese in large cities like Basel, Bern, and Zurich. Furthermore, during 2014-5 and 2015-16, students’ overweight and obesity prevalence was 16.4%. Interestingly, in the 2017-2018 school period, a 3% decrement in the overall prevalence was observed. Hence, the number of affected children has decreased slightly; however, researchers claimed that epidemiological surveillance remains essential despite these declining rates.29,35–37\n\nOther countries with independent epidemiological surveillance systems are Iceland and the United Kingdom.25 The latter holds an obesity monitoring system for those aged between 4 and 5 and 10 and 11 years, known as the National Child Measurement Programme (NCMP). For 2017-2018, overweight and obesity prevalence was higher for those aged between 10 and 11 (34.3%) compared to those aged between 4 and 5 years (22.6%).38,39 Additionally, obesity and overweight prevalence in England has increased among minor children, showing obesity numbers of 9.5% and 12.8% for overweight in those between 4 and 5 years old. In contrast, those aged between 10 and 11 years displayed a prevalence of 20.1% for obesity and 14.2% for overweight.40,41\n\nOn the other hand, the NCMP found that Wales exhibited higher prevalence rates than England. In the age group of 4 to 5 years, 11.9% of children were obese, and 14.6% were classified as overweight. Also, the data from Scotland indicated that 12% of the children had the risk of developing overweight, while 10% had become obese. On its part, due to the small sample size of North Ireland, it was not possible to perform significant comparisons between age groups over time; nevertheless, it was reported that about 8% of children aged between 2 and 10 years and 10% of children between 11 and 15 years old had obesity.40\n\nRegardless of a South-North pattern, some exceptions do not follow this behavior in Europe’s insular countries, as in Iceland. For example, the Organization for Economic Cooperation and Development (OECD) stated that by 2016, 30.9% of children aged between 5 and 9 years were overweight, and 12.6% had obesity, while 27% of those aged between 10 and 19 years were overweight and 8.5% had obesity. Likewise, a different behavior was found within the Nordic countries, given that Icelandic children appeared among the children with the highest rates of obesity in Europe.42\n\nInterestingly, a recent meta-analysis that included 28 European countries reported a stabilizing trend concerning excess weight in the child population, mainly in the continent’s north. However, despite these positive findings, Garrido et al.23 showed in their results that some Mediterranean countries failed to exhibit this pattern. Different authors have coined this phenomenon as the South-North Gradient,43–46 which supports the high prevalence rates found in the countries located in the South, highlighting the significant socioeconomic and lifestyle differences between the two regions.47\n\nAdditionally, it is crucial to take into account the impact of socioeconomic, as sudden socioeconomic changes could lead to increased childhood obesity in the most disadvantaged population groups.48–50 For example, a recent longitudinal study including 2,401 European children assessed metabolic alterations regardless of diet or physical activity. In this context, the study succeeded in showing (in contrast to children of families without such impairments) that certain indicators of socioeconomic disadvantages such as unemployed parents, low family income, and incomplete educational level, were correlated with a high metabolic risk in the children of these families.51 Therefore, the rise in childhood obesity prevalence in these underprivileged households may result from certain aspects, such as living a healthy lifestyle and not being a priority.51\n\nOn the other hand, weight disorders also interact with many factors ranging from genetic variations to environmental and dietetic influences.52,53 In this case, the number of Mediterranean countries that adhered to the ’70s ideal Mediterranean Diet has experienced a noticeable decrement54 due to socioeconomic factors that force them to abandon their usual healthy diet for one that is more westernized.55,56\n\nThere are certainly other risk factors for childhood obesity; for instance, the lower sizes found in southern countries.57,58 Also, geographical changes can lead to higher obesity rates.59 Besides, sleep duration, extended periods of watching television,60 and a sedentary lifestyle can heavily influence the prevalence rates of childhood obesity in those countries and contribute to higher obesity rates in this southern part of the continent.43,61\n\nThe Asian continent is considered to have severe public health issues regarding weight problems. In fact, for 2020, The United Nations International Children’s Emergency Fund (UNICEF), along with WHO and the World Bank Group (WBG), made a report concerning the levels and trends in childhood malnutrition globally (excluding Europe) due to the lack of epidemiologic evidence regarding this matter within some of its regions (Figure 2). This report rated Asia as the most heavily affected continent, given that it has 30.9% of the total global children under five years old with overweight, the equivalent to 17.2 million children. Furthermore, when segmented into sub-regions, Western Asia has the highest prevalence with 8.4% (2.3 million patients), followed by Southeastern Asia with 7.5% (4.2 million), Eastern Asia with 6.3% (5.7 million), Central Asia with 6.2% (0.5 million), and lastly South Asia with 2.5% (4.5 million).4 Notably, the obesity prevalence is more significant in higher socioeconomic strata and urban areas, contrary to the pattern found in other continents where the overweight is commonly found at lower socioeconomic levels.62\n\nSource: UNICEF, WHO, World Bank Group joint malnutrition estimates, Edition 2020.4 Note: *East Asia excluding Japan; ** Prevalence of Australia and New Zealand was estimated from data provided by Australia. Europe prevalence was not estimated because there is no data available covering all its regions.\n\nAlong these lines, a study published by Kim et al.63 reported a progressive increment in obesity rates in Korean children (aged 6 to 18 years) from 8.7% in 2007 to 15.0% in 2017. Moreover, Bahk and Khang64 performed a study to evaluate the trends in measures of childhood obesity among Korean children, using the data from five waves of the Korean National Health and Nutrition Examination Survey (KNHANES) including 18,174 children aged between 2 and 19. According to WHO charts, 31.2% of the boys were overweight, and 10.9% were obese, whereas overweight and obesity among girls were 21% and 4.6%, respectively (Table 2).\n\n* The systematic review by Farrag et al.72 included studies that used different criteria to determine childhood obesity.\n\nRegarding China, Zhang et al.65 reported overweight and obesity trends in children and teenagers aged between 7 and 18 years in the 2011-2015 period. It was evidenced that according to WHO, IOTF, and Working Group for Obesity in China (WGOC) criteria, overweight and obesity prevalence were 15.5% and 8.8%, 13.1% and 5.7%, 11.9%, and 8.8%, respectively. Moreover, 7-11 years old children displayed a 16% and 9.6% overweight and obesity prevalence, in contrast to the 14.6% and 7.4% in the 12-18 age group.\n\nSimilarly, according to a study carried out by the Global Burden of Disease (GBD) 2015 Obesity Collaborators, which addressed the prevalence of obesity in children and teenagers aged between 2 and 19 years in 195 countries, China obtained first place with an overall prevalence of 5.1%, followed by India with 3%. Notably, children aged between 2 and 4 years were the most affected in both sexes, reporting 2.7 million obese boys (5.2%) and 2.3 million obese girls (4.9%).66\n\nLikewise, obesity’s prevalence has turned into a concern for the Japanese Health Ministry.67 As a result, Nakano et al.68 executed a six-year longitudinal study that included 16,245 children; the aim was to assess overweight and obesity’s epidemiologic behavior for as long as they attended primary school. As a result, overweight and obesity prevalence was 15-23% and 4-7% in boys and 15-18% and 2-4% in girls, respectively. Moreover, it is worth mentioning that 60-80% and 35-70% of the boys with overweight and obesity in a primary school maintained the same pattern when reaching secondary school; conversely, the girls had lower rates, as 50-70% of them had overweight, and 30-60% had obesity when attending secondary school. Additionally, Morita et al.69 reported that out of 315 teenagers, 15.2% had obesity (48 students). Nonetheless, as the study found, most of them spent all their time in academic tutoring and showed better school performance than those assigned more time to physical activity.\n\nDespite childhood malnutrition has been the leading problem to be solved in the African continent, obesity and overweight prevalence have risen drastically over the past years. According to the UNICEF/WHO/World Bank Group report about child malnutrition trends, Africa represents the second geographic area with the highest prevalence of childhood overweight with 25% of the worldwide cases, the equivalent to 9.3 million children under five affected. Noteworthy, the overweight prevalence within the different African regions goes as follows: Southern Africa scored the highest with 12.7% overweight prevalence, followed by Northern Africa with 11.3%, Middle Africa with 5.1%, Eastern Africa with 3.7%, and lastly Western Africa with the lowest prevalence by 1.9%.4 Although South Africa has the lowest childhood overweight and obesity prevalence, the frequency of these conditions increased by 400% per decade between 1975 and 2016.57 It is also essential to address that the African continent suffers from other weight-related disorders such as growth stunting, affecting 151 million children under five years.4\n\nIn that matter, Farrag et al.70 carried out a systematic review that included studies from 2010 to 2015. This research intended to assess the obesity and overweight epidemiological behavior in children and teenagers between 2 and 19 years old who lived in regions of the Middle East and North Africa (MENA); consequently, reporting increasing numbers of obesity, especially in the gulf area in the recent years. Moreover, the top five countries with the highest numbers of overweight male children and teenagers were Egypt, Kuwait, Lebanon, Syria, and Saudi Arabia, with a prevalence ranging between 28.2% and 19.5%. On the other hand, the countries with the highest numbers of overweight female children and teenagers were Egypt, Libya, Kuwait, Saudi Arabia, and Syria, with a prevalence ranging between 28.2% and 20%. Likewise, Kuwait stood out as the leading country affected by obesity in children and teenagers, with a prevalence of 34.8% and 20.5% in boys and girls, respectively. Additionally, the same authors evidenced that physical inactivity degree, screen time, and family socioeconomic status are risk factors for childhood obesity.\n\nOn the other hand, Al Alwan et al.71 conducted a cross-sectional study to determine overweight and obesity prevalence in 1,243 Saudi children between 6 and 16 years old from Riyadh schools. Overweight prevalence rates were 21.1% and 12.7% for obesity. Similarly, a systematic review by Ng et al.21 that included 1,769 studies from 183 countries assessed the prevalence of overweight and obesity in individuals between 2 and 19 years old. The proportion of overweight and obesity in boys in African countries were, respectively, as follows: in Qatar 33.5% and 18.8%, in Iran 21.6% and 5.9%, in Iraq 19.5% and 8.2%, in Libya 32.5% and 14.5%, in Morocco 22.5% and 7.9%, in the Democratic Republic of the Congo 8.5% and 4.9%, in Syria 32.9% and 13.9%, and lastly in Turkey 20.4% and 7.1%. Furthermore, the prevalence of overweight and obesity in girls were, respectively, as follows: in Qatar 22.1% and 15.5%, in Iran 26.2% and 7.2%, in Iraq 25% and 8.2%, in Libya 41.7% y 22.1%, in Morocco 25.9% and 9.1%, in the Democratic Republic of the Congo 12.6% and 4.4%, in Syria 33.3% and 15.4%, and finally in Turkey 19.8% and 5.7%.\n\nLike other continents, overweight and obesity’s epidemiologic behavior represents a public health issue in Oceania.72 According to the report on child malnutrition assessed by UNICEF/OMS/WBG, 9.4% of children under five years old in Oceania were overweight, amounting to 100,000 children; conversely, Australia and New Zealand’s data were reported separately, possibly due to their population size and composition influence. However, Australia and New Zealand’s overweight prevalence reached 20.7%, equating to 0.4 million children. Remarkably, those countries’ sub-regional estimates are based only on Australian institutions’ data.4\n\nA 2017 Australian Government report confirmed a secular change in overweight and obesity prevalence over the last 30 years: Children between 2 and 5 years (born in 2010-2013) presented 8.8% overweight/obese prevalence, in contrast to those born in 1990-1993 exhibiting 4.2% overweight/obesity prevalence. Children aged 10-13 years and born between 2002 and 2005 were overweight/obese in 30.8%; in contrast, those born in 1982-1985 were only overweight/obese in 23.95 %. Finally, teenagers born between 1998 and 2001 were overweight/obese in 29.8% of the cases, but in those born in 1978-1981, only 18.7% had weight problems.73\n\nFurthermore, the New Zealand Ministry of Health’s latest report showed that 20.2% and 9.4% of children between 2 and 14 years old were overweight and obese. Apart from that, the research found that those children who belonged to the lowest socioeconomic status group had the highest prevalence of overweight and obesity compared to high socioeconomic status (26.8% vs 14% regarding overweight, and 6.9% vs 19.4% in the case of obesity). Additionally, when segmented by age groups, it was reported that 20.3% of children from 2 to 4 years old were overweight, and 4.3% were obese, making a total of cases of 24.6%. Also, children from 5 to 9 years old were overweight at 19.2%, and 10.3% were obese (Overall 29.5%), while overweight and obesity prevalence in children from 10 to 14 years old were 21% and 11.4%, respectively (Overall 32.5%). Moreover, overweight and obesity in Maori were 28.9% and 13.2%, respectively (Overall 42.1%), and overweight and obesity prevalence in pacific islanders’ children was 31% and 29.1%, respectively (both 60.1%). Contrarily, one study found that children of European and Asian ancestry had prevalence rates of 18.2% and 7.2% of overweight and obesity (both 25.4%), along with 15.7% and 3.4% of overweight and obesity (both 19.1%), respectively.74\n\nNotwithstanding, to estimate childhood obesity in other Oceanian islands, Pengpid et al.75 executed a study based on the Global School-Based Student Health Survey data, including 10,424 students aged 13-16 years from Fiji, Kiribati, Samoa, Solomon Islands, Tonga, and Vanuatu. These islands’ overweight and obesity prevalence rates were 18.2% and 6.1%, respectively. Mainly, Tonga had the highest prevalence rates (37.6% of overweight and 21.1% obesity), followed by Samoa (32.6% of overweight and 19.3 obesity), Kiribati (32.5% of overweight and 7.4% of obesity), Solomon Islands (19.8% of overweight and 2.7 obesity), Fiji (13.9% of overweight and 5.2% of obesity), and finally, Vanuatu (11.5% of overweight and 0.4% of obesity). This study concluded that soft drinks, sedentary behavior, smoking habits, and psychosocial factors (suicidal ideation, social and family support) were significantly related to overweight, obesity, or both. Contrarily, the authors evidenced that vegetable intake, alcohol consumption, physical activity, and other psychosocial factors such as discrimination, anxiety, and loneliness were not related to overweight or obesity.\n\nFor a long time, childhood overweight and obesity have increased in different regions of the American continent; thus, several research groups are currently studying this issue.76–79 According to the last UNICEF/WHO/WBG report on levels and trends of childhood malnutrition, America has 5.8 million children under the age of five years with overweight prevalence distributed as follows: North America has 8.9% overweight prevalence, followed by South America with 7.9%, the Caribbean Region with 7.0%, and Central America with 6.9%; thus, making this continent the 3rd one with the highest number of children affected by overweight.4\n\nIn the United States, according to the Centers for Disease Control and Prevention (CDC) and the U. S department of health and human services, childhood obesity prevalence has increased in the last years from 13.9% (1999-2000) to 18.5% (2015-2016), involving 13.7 million children and teenagers between 2 and 19 years. The preschool age group (2-5 years old) had a prevalence of 13.9%, followed by the age group between 6 and 11 years with 18.4% and the teenagers with 20.6%. Moreover, considering the ethnic groups, 22.0% of the young African Americans and 25.8% of the Hispanics were obese, numbers considerably higher than those found in young white non-Hispanics (14.1%) and non-Hispanic Asians (11%)80 (Table 3).\n\n* The prevalence rates proportionated by the Health Ministry of Colombia englobes both overweight and obesity (excessive weight).\n\nAdditionally, regarding the overweight and obesity epidemiologic behavior of American Natives in the USA, Zephier et al.81 analyzed the Aberdeen Area Indian Health Data that included 11,583 native Americans aged between 5 and 17 years from 18 tribes located in North Dakota, South Dakota, Iowa, and Nebraska. Consequently, 48.1% and 29.4% of the boys had overweight and obese, respectively, while the girls’ prevalence was 46.3% and 26.1%. Obesity prevalence varied by ethnicity with particular dietary habits playing a significant role. Native Americans, for example, tend to consume high amounts of fat, which contributes to their higher obesity rates.\n\nIn this vein, Skinner et al.82 analyzed the National Health and Nutrition Examination Survey (NHANES) 2015-2016 database, including all the children and teenagers aged between 2 and 19 years, reporting a 35.1% in overweight prevalence and 26.4% for obesity. When data were stratified according to age groups, the overweight and obesity prevalence was as follows: children aged 2 to 5 years was 26.0% and 15.7%, children aged between 6 and 8 years showed 32.8% and 25.3%, the group of 9 to 11 years had 35.6% and 24.8%, the group of 12 to 15 years had 38.7% and 30.3%, and the last group of 16 to 19 years had 41.5% and 34.5%. Thus, a growing trend for overweight and obesity was observed concerning age increment.\n\nLike the United States, Canada also exhibits worrying obesity statistics. Between 1978-1979 and 2004, this clinical entity increased from 6.3% to 12.7% (102% increase). In contrast, overweight augmented from 17% to 28%, increasing 29%.83 Likewise, according to the Canadian Health Measures Survey published in 2011, a third (31.5%) of the population between 5 and 17 years old had overweight (19.8%) and obesity (11.7%), equating to 1.6 million affected children and teenagers. When stratified by sex and age, it was observed that boys had a 15.1% prevalence and girls 8%. However, more significant differences were shown in the 5 to 11 years group because 19.5% of the boys and 6.3% of girls were obese.84 Moreover, in 2014, the Toronto Public Health Student Survey was executed, with a sample of 6,053 students aged between 12 and 17 years (currently studying 7th to 12th grade), showing an overweight prevalence of 20% and 9% for obesity (11% for boys and 6% for girls).85\n\nRegarding Latin America, childhood overweight and obesity are a public health concern coexisting with a critical sociopolitical background in some countries, behaving like a growing medium for a growing tendency to increase as children get older.86–88 In contrast, overweight augmented from 17% to 28%, increasing 29%.81–83 The Pan American Health Organization (PHO) reported that in Latin America and the Caribbean, about 7.2% of the children under five years old are overweight, which amounts to 3.9 million children, out of which 2.5 million live in South America, 1.1 million in Central America and 200.000 in the Caribbean.89\n\nFor that reason, Rivera et al.86 executed a study to expose a global perspective of the obesity problem in Latin America, reporting that Argentina had the highest prevalence of overweight children under the age of 5 years with a worrying 10.4%, followed by Mexico (9.8%), Chile (8.2%), Peru (6.9%) and Colombia (5.2%). Regarding those over the age of 5 years, Brazil showed an obesity prevalence of 11.8% in girls and 16.6% in boys, it was 11.8% for girls and 17.4% for boys in Mexico, whereas Chile showed 13.1% for both sexes and, lastly, Colombia showed 5.2% for both sexes. Concerning teenagers, Mexico exhibited a prevalence of 12.1% for girls and 14.6% for boys; Chile had 6.6% in both sexes, Brazil reported a 4% for girls and 5.8% for boys, and Colombia showed 3.4% for both boys and girls.\n\nFurthermore, Shamah-Levy et al.90 analyzed the Mexican Health and Nutrition Survey (ENSANUT) data from 7,758 children and teenagers. Those who are under the age of 5 years showed an obesity prevalence of 5.8% for females and 6.5% for boys. The highest frequencies were found in the school-age group, indicating that 11.2% of the girls and 18.3% of the boys were obese. This study found a 12.8% prevalence in girls and 15% in boys in teenagers. Likewise, the authors stated that the epidemiological behavior of overweight and obesity in Mexico does not follow a specific trend, making it highly heterogeneous in children and teenagers.\n\nIn South America, Chile has the highest overweight prevalence in children over the age of 5.91 By 2011, the Organization for Economic Cooperation and Development (OECD) published a report positioning Chile as the 6th country with the highest prevalence of childhood obesity worldwide.92 Moreover, according to the national health survey data (2016-2017), 27.6% of teenagers between 15 and 19 years old were overweight, and 12.2% were obese.93 Furthermore, Cañoles et al.94 studied a sample of 250 pre-school children in the Chilean public education system, reporting that 54.5% of them had a poor nutritional state (underweight, overweight, and obesity), out of which 27.7% of the children had overweight, and 19.1% had obesity.\n\nConcerning Ecuador, Ramos-Padilla et al.95 assessed the epidemiologic behavior of excessive weight in the urban population of Riobamba, registering an overweight prevalence of 17.8% and 6.3% for obesity. Nonetheless, Espinoza et al.92 carried out a study in children between 5 and 11 years old from a rural south American Indian native population reported an acute malnutrition prevalence of 21.5% and chronic malnutrition prevalence of 22.3%.\n\nIn Venezuela, according to the Dietary and Nutritional Surveillance System (SISVAN), by 2007, the prevalence of overweight/obesity among pre-school children was 12.7%, whereas the prevalence among scholars and teenagers raised to 19.3%.96 Furthermore, a study carried out by Herrera-Cuenca et al.97 assessed the anthropometric characteristics of 1,350 children aged between 7 and 12 years in 8 Venezuelan cities, reporting an overweight prevalence of 15.1% followed by an obesity prevalence of 26.4%. Additionally, according to the National Institute of Nutrition (NIN) papers regarding the current status of childhood overweight and obesity, it was reported that by the years 2008-2010, 17.5% and 9.8% of the children had overweight and obesity, respectively. For teenagers aged between 13 and 17 years, the overweight prevalence was 12%, and the obesity prevalence was 9.3%. According to the authors, excessive weight in Venezuela tends to decrease as individuals age.98\n\nOn the other hand, Araujo et al.99 assessed the presence of MS in 501 Venezuelan children and teenagers, reporting that, according to the International Diabetes Federation (IDF) criteria, the prevalence of MS was 2.9%, primarily seen in children with overweight and obesity, which had a prevalence of 14.7% and 16.3%, respectively. Nonetheless, Venezuela is not exempt from the coexistence of childhood obesity and malnutrition. Regrettably, the situation in Venezuela is complex, and it is not exempt from the coexistence of childhood obesity and malnutrition. What makes this situation even more concerning is the lack of up-to-date and comprehensive epidemiological data. The available information published by national health ministry is both scarce and outdated. This presents a significant challenge for policymakers, healthcare professionals, and researchers who rely on accurate and current statistics to address public health issues effectively. The absence of recent data hinders the ability to assess the true extent of the problem, identify trends, and develop targeted interventions. As a result, there is an urgent need for improved data collection and reporting mechanisms to monitor and combat the growing public health concerns related to childhood nutrition in Venezuela.\n\nWhat is the current state of Colombia?\n\nIn light of childhood malnutrition and obesity in Colombia, it has been suggested that this country faces a double malnutrition load; that is to say, the coexistence of a lacking and an excessive nutritional state as a consequence of an accelerated nutritional transition, a common phenomenon in developing countries.100,101 By 2011, the Organization for Economic Cooperation and Development (OECD) published a report positioning Chile as the 6th country with the highest prevalence of childhood obesity worldwide.92 Moreover, according to the national health survey data (2016-2017), 27.6% of teenagers between 15 and 19 years old were overweight, and 12.2% were obese.93 Furthermore, Cañoles et al.94 studied a sample of 250 pre-school children in the Chilean public education system, reporting that 54.5% of them had a poor nutritional state (underweight, overweight, and obesity), out of which 27.7% of the children had overweight, and 19.1% had obesity.\n\nIn this regard, Fajardo et al.102 carried out a study with a sample of 326 children aged between 7 and 11 years from Bogota, reporting an overweight and obesity prevalence of 22.4% and 15.3%, respectively. Concerning the children’s nutritional patterns (Obtained through the 24-hour reminder), it was observed that their diet was composed of 13% proteins, 35% fats, and 52% carbohydrates. Furthermore, the physical activity assessment revealed that 17% exercised 6 to 7 days a week for 20 minutes, being the boys more active than the girls (67.4% vs 44%; p=0.0002). Lastly, the authors evidenced that 67.8% of them dedicated 1 to 4 hours to watching TV during the midweek, increasing to 75.9% on weekends.\n\nSince 2005, the government and the Health Ministry of Colombia have applied a Nutritional State National Survey on children, teenagers, and adults every five years. The last report was published in 2015, stating that 6.3% of the children under five years old had overweight (7.5% boys and 5.1% girls), 25.6% played active games in the pre-scholar age, and 61.9% spent excessive time in front of a screen. Besides, 24.4% of the school-age children had excessive weight (overweight and obesity), 31.1% fulfilled the physical activity recommendations, and 67.6% spent too much time in front of a screen. Similarly, teenagers had an excessive weight prevalence of 17.9%, 13.4% achieved the physical activity recommendations, and 76.6% spent too much time in front of a screen. Moreover, this survey stated that the time in front of a screen increased in the highest socioeconomic levels.103\n\nConversely, it has been described that the place the children inhabit could potentially act as an important risk factor in the development of childhood obesity.100 In this regard, Briceño et al.104 executed a non-probabilistic study with a sample of 1055 scholars from rural and urban areas of the department of Boyaca, reporting a general overweight prevalence of 16.21% and 4.45% for obesity. Besides, after assessing this phenomenon in the urban area, it was observed that 18.85% and 5.64% of the children had overweight and obese, respectively; meanwhile, in the rural area, the overweight prevalence was 6.31%, and obesity was 0%. Similarly, another study executed by Medina et al.105 aimed to evaluate the nutritional state and BMI of 411 children and teenagers in 17 schools in Cundinamarca’s rural area, exhibiting 11.4% had overweight and 1.9% obesity. The rest of the 74.2% of the individuals had average weight (with 11.2% of them at risk of being underweight), and 1.2% had underweight. The authors concluded that 25.7% of the Mesa municipality population in Cundinamarca had some compromise in their nutritional state, confirming the coexistence of both nutritional disturbances in Colombia.\n\nAlso, a study carried out in the city of Medellin by Rodriguez Barrera et al.106 assessed the prevalence of obesity and the quality of life of 679 school-age children aged between 10 and 14 years, using the Kidsgreen-27 for the quality of life and the WHO’s software ANTRO-PLUS for the nutritional and anthropometric evaluation. It was reported that 19.9% of the sample had overweight, and 4.1% had obesity. Moreover, the authors concluded that school-age children’s quality of life with excessive weight was lower than their peers with normal weight. Besides, they presented a significant difficulty in executing physical activity and had more substantial health issues along with lower social compliance. Notwithstanding, these results can vary according to age, sex (an increased commitment was observed in boys than in girls), and specific cultural determinants such as self-perception and the definition of the corporal image.\n\nThe particular case of the North of Santander department\n\nNorth of Santander Department health report stated that childhood malnutrition represents one of the most relevant problems to tackle, and suggest performing epidemiological studies with appropriate and representative sample sizes.106 Although the last results from the National Nutritional Survey do not report specific data from North of Santander, the Eastern Region of Colombia (which includes the North of Santander) presented an overweight prevalence in children under five years of 6.7%.107\n\nIn Cúcuta, Reina et al.108 carried out a study to identify the risk factors related to overweight and obesity in 70 children of both sexes, reporting that 23% of the children were overweight, and 17% were obese; also, it was noticed that the highest prevalence of both entities belonged to the socioeconomic levels 2 and 3. Likewise, assessing children’s dietary habits lead to conclude that 30% of them did not perform any physical activity while 60% spent 1 to 2 daily hours of TV (out of which 23% had overweight); besides, they also spent 1 to 2 hours a day playing videogames.\n\nAlong these lines, Zambrano et al.109 executed another study in Cucuta with a sample of 382 children and teenagers from public schools, reporting that 55% had some nutritional impairment, with an overweight prevalence of 29% followed by obesity with 15%. Similarly, children between 10 and 13 years old showed an overweight prevalence of 32% and obesity of 17%, the boys being the most affected group. Conversely, the self-perception assessment of a student overweight revealed that 64% considered themselves thin, 24% thought they had a normal weight, and just 12% perceived themselves as overweight. This finding raises a question of whether their self-perception of normality was influenced by the assumption that obesity equates good health.\n\nIn 2020, a paper from the Nutritional Surveillance “WINSISVAN” regarding Northern Santander was published, which included 17,160 children and teenagers under 18 years old (53% were girls and 47% boys), out of which 92% were affiliated with a subsidized healthcare system, 28% lived in a rural area and 72% in an urban area. Based on the nutritional diagnosis, 15% of the children under the age of 5 were at risk of becoming overweight, 4% had it already, and 2% were obese. Moreover, the age group of 5-12 years showed that 12% had overweight, and 8% were obese. Lastly, concerning the age group of 13-17 years, 13% had overweight, and 8% were obese.110\n\nIt is mandatory to mention data concerning malnutrition and low length, given that the latter is a crucial diagnostic point when assessing children’s nutritional state because of its relationship with chronic malnutrition or long-term dietary deprivation.111–113 North of Santander Department health report stated that childhood malnutrition represents one of the most relevant problems to tackle, and suggest performing epidemiological studies with appropriate and representative sample sizes.\n\nIt was reported that the total prevalence of malnutrition among children under five years old was 4% and 4% for acute malnutrition; meanwhile, 9% were diagnosed with low length, and 21% were at risk of developing it. By assessing the same variables in children aged between 5 and 12 years, 7% had a low length for their age, and 21% were at risk of developing it. Additionally, 5% and 15% of the children aged between 5 and 12 years presented an underweight or underweight risk. Similarly, 7% of those aged between 13 and 17 years were underweighted, and 14% were at risk of becoming underweight.110 The latter results support the double nutritional load lying in this region.\n\n\nConclusions\n\nThis review’s findings suggest that despite the effort that has been put into investigating and addressing obesity, it remains a critical health problem worldwide. Notably, overweight and obesity are seen in the wealthiest nations and low and middle-income countries, posing a threat to any person or family member regardless of age, sex, race, and family obesity history. Furthermore, many researchers claim that the primary determinant in increasing obesity prevalence has been lifestyle modifications. Thus, physical activity patterns such as the decrement in outdoor activities increased exposure to entertainment technologies, and sedentarism are among the most critical risk factors for childhood obesity.62\n\nEven though each continent and the countries within each continent could exhibit a particular pattern regarding populational childhood weight behavior, the reality is that excess weight disorders are rising globally. Nevertheless, Europe′s childhood obesity prevalence shows an apparent stabilization; in North America, childhood obesity is a growing concern in parallel with the rise of adult obesity epidemics, and incredibly, South America is experiencing the double burden of obesity and malnutrition.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nDi Cesare M, Sorić M, Bovet P, et al.: The epidemiological burden of obesity in childhood: a worldwide epidemic requiring urgent action. BMC Med. 2019; 17(1): 212. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVazquez CE, Cubbin C: Socioeconomic Status and Childhood Obesity: a Review of Literature from the Past Decade to Inform Intervention Research. Curr Obes Rep. 2020; 9(4): 562–570. PubMed Abstract | Publisher Full Text\n\nGlobal Nutrition Report: 15:37:02.417090+00:00. Inequalities in the global burden of malnutrition.[cited 2020 Jul 18]. Reference Source\n\nWorld Health Organization: WHO|UNICEF-WHO-The World Bank: Joint child malnutrition estimates - Levels and trends. World Health Organization; 2020 [cited 2020 Jul 7]. Reference Source\n\nZobel EH, Hansen TW, Rossing P, et al.: Global Changes in Food Supply and the Obesity Epidemic. Curr Obes Rep. 2016; 5(4): 449–455. 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}
|
[
{
"id": "268623",
"date": "02 May 2024",
"name": "José Carlos Cabrera Linares",
"expertise": [
"Reviewer Expertise Sport 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\nCongratulations on your article. I consider that they have made a great effort and great job compiling all the data related to the current state of obesity and overweight. Despite this, the data included is not completely up to date and should be updated, since in recent years the trend has been increasing. In any case, the article is correct, written in simple and easy to understand language. In addition, numerous data are included that allow the reader to get an idea of the global problem such as overweight and obesity.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-177
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https://f1000research.com/articles/13-175/v1
|
11 Mar 24
|
{
"type": "Research Article",
"title": "A prospective study on health seeking behaviour and post exposure prophylaxis received by animal bite victims at the anti-rabies clinic in a tertiary care centre of urban Bangalore",
"authors": [
"Jithin Surendran",
"Ravish HS",
"Nitu Kumari",
"Ramya M Prasanth",
"Nidhi Fotedar",
"Ravish HS",
"Nitu Kumari",
"Ramya M Prasanth",
"Nidhi Fotedar"
],
"abstract": "Background Rabies is 100% preventable by administering early and complete post exposure prophylaxis (PEP). Animal bite victims must have the knowledge and attitude necessary to seek appropriate medical care at the earliest to receive the required PEP.\n\nObjectives The present study sought to ascertain the health-seeking behavior of animal bite victims, their knowledge and attitude regarding rabies prophylaxis, the PEP they received, and their level of compliance with the full course of anti-rabies vaccination.\n\nMethods The study included animal bite cases that presented to the anti-rabies clinic and matched the eligibility criteria. All the required details were recorded using an internally validated structured questionnaire. All participants were followed up for six months to ensure their health conditions and compliance with the vaccination schedule.\n\nResults Out of 1058 respondents, 57.9% were adults, with 46.6% belonging to middle socioeconomic class. 91.1% of them were informed biting animals as dogs. Before arriving at the anti-rabies clinic, 93.3% of the study subjects washed their wounds, and 62.4% visited to another health facility. Rabies knowledge was inadequate among the study participants, only 54.8% being mindful about the disease and its prevention. The compliance with the full course of antirabies vaccination was found to be 77.9%. All subjects were healthy, confirming that PEP is safe and effective.\n\nConclusion Regular social and behavioral change communication (SBCC) needs to be implemented with regard to health-seeking behavior.",
"keywords": [
"animal bite victims",
"compliance",
"efficacy",
"health seeking behaviour",
"post-exposure prophylaxis"
],
"content": "Introduction\n\nAnimal exposure among humans is a public health problem and poses a potential threat of rabies infection to over 3.3 billion people worldwide.1 These exposures occurs mainly in underserved populations, both in rural and urban areas, and has been documented for more than 4000 years.2 The magnitude and epidemiological pattern differ from country to country. According to data available, most cases occur in Africa and Asia, where children represent about 40% of population exposed to dog bites in those rabies endemic areas.3 A combination of large human and dog populations in congested habitable areas has led to more exposure in WHO’s South East Asia region than in any other part of the world.4\n\nIn the World Health Organization’s (WHO) South-East Asia (SEA) Region, which includes 11 nations, eight are rabies-endemic, and more than 1.4 billion people are at risk of contracting the disease. As a consequence, it remains a significant public health and economic challenge throughout the region.5 Each year, an estimated 12 million people in Asia seek treatment after being exposed to probable rabies-infected animals. Fear and anxiety following a dog bite result in a psychological consequence that is estimated to account for approximately 1,40,000 DALYs in Asia.6\n\nAn estimated 17.4 million animal bites occur in India each year, having a 1.7% incidence.7 In a rabies-endemic nation like India, where every animal bite is suspected of being a rabid exposure, exposed persons should engage in proper health-seeking behavior in order to get early and comprehensive post-exposure prophylaxis (PEP) for rabies antibodies.8 The knowledge and attitude regarding the disease prevention among the bite victims is important for their health seeking behaviour.9\n\nThe act of seeking medical assistance is “any action undertaken by individuals who perceive themselves to have a health problem or to be ill for the purpose of finding an appropriate remedy.” It is not an isolated event determined by individuals concentrating solely on their own self-interest; it is “part and parcel of individuals, families, or community’s identity, which involves a combination of social, personal, cultural, and experiential factors”. It is also part of the more general concept of health behavior, which includes behaviors carried out to preserve good health, refrain from illness, and cope with any deviation from a good state of health.\n\nAt the health care facility, whenever a patient comes for a health problem such as animal exposure; the post exposure prophylaxis should be provided depending upon the severity of the animal bite wounds/exposures as per the WHO/NCDC, India guidelines.10 The PEP consists of thorough wound washing with soap or detergent & water and application of virucidal agents to reduce the viral inoculum at the wound site; post exposure anti-rabies vaccination to induce antibodies which prevents the risk of virus entering peripheral nerves after a bite from a rabid animal and timely administration of rabies immunoglobulin (RIG)/rabies monoclonal antibodies (RMAb) in all category III exposures to neutralize the virus at the wound site.11\n\nTherefore, thorough wound washing with prompt administration of cell culture vaccine and simultaneous administration of RIG/RMAbs in all category III exposures is almost invariably effective in preventing rabies, even after high-risk exposure.12 It is also essential for animal bite victims to complete the full course of vaccination as recommended by the physician for full protection, as those who do not complete the full course of vaccines are still at risk of developing rabies.13 However, compliance with anti-rabies vaccination among bite victims is still a major issue, as it spans over a period of 28 days. Therefore, the health behaviors of animal bite victims are important for the completion of PEP.\n\n\nNeed for the study\n\nTo avail immediate and correct post exposure prophylaxis, animal bite victims should have the proper knowledge and attitude to seek proper health care services. Likewise, exposed individuals are supposed to complete the full course of anti-rabies vaccination for complete protection against the disease.\n\nThe present study was conducted to determine the health-seeking behavior of animal bite victims, along with their knowledge and attitude, the post exposure prophylaxis received by them, and their compliance with the full course of anti-rabies vaccination. The details regarding these important determinants are important to assemble new evidence for planning specific interventions to accomplish the task of eliminate rabies by 2030.14\n\n\nScope of the study\n\nThe study provided details regarding the health-seeking behavior of animal bite victims and assessed their knowledge and attitude toward rabies prophylaxis. It also provided details of the post exposure prophylaxis received by the patients and their compliance with the complete course of anti-rabies vaccination. This information is important for understanding the present situation and for the further implementation of specific strategies to eliminate rabies.\n\n\nAim & Objectives\n\nTo understand health-seeking behavior and post exposure prophylaxis received by animal bite victims.\n\n\n\n1. To determine the health-seeking behavior of animal bite victims attending an anti-rabies clinic.\n\n2. To assess the knowledge and attitude toward rabies prophylaxis and the perceived risk of disease transmission from different animals.\n\n3. To describe the post exposure prophylaxis provided at the anti-rabies clinic and determine the compliance of study subjects to complete the course of vaccination.\n\n4. To determine the clinical outcomes after receiving post exposure prophylaxis.\n\nMethods: The study was conducted at the anti-rabies clinic, Preventive Medicine Unit, Kempegowda Institute of Medical Sciences (KIMS) Hospital and Research Centre, Bangalore, after obtaining Institutional Ethics Committee approval.\n\nStudy subjects: Animal bite victims who reported to the anti-rabies clinic, KIMS Hospital, and Research Centre for availing post exposure prophylaxis services and gave written informed consent to participate in the study.\n\nSubjects were given information sheet in their understandable language to read and understand about the objectives of the study, methodology, possible side effects and benefits. Any queries raised by the study subjects were addressed by the investigator. Then, written informed consent from adults; informed consent from the guardian and informed assent was taken from adolescents and informed consent from the parents of children below 7 years who agreed to participate in the study were obtained (Annexure- I).\n\nStudy period: One and half years (January 2020 to June 2021).\n\nStudy design: A prospective longitudinal study.\n\nSampling method: Non probability type of purposive sampling technique.\n\nSample size: The sample size was calculated as per the compliance rate to complete course of anti-rabies vaccination, which is an important health behavior in post exposure prophylaxis; based on the published study as 77%15; with 95% confidence level; allowable error (d) = 5% and assuming 15% dropouts.\n\n1 – P = 0.23.\n\nd = desired relative precision (5% of 77% = 0.039).\n\nAssuming 15% of non-response rate 447 × 0.15 = 67\n\nSample size = 447 + 67 = 514 ≈ 525\n\nAs we included all patients who met the inclusion criteria during the study period, the net sample size was = 1058\n\n\n\n➢ Animal bite victims who gave written informed consent.\n\n➢ Study subjects who were available for follow-up.\n\n\n\n➢ Animal bite victims who had already started post exposure prophylaxis elsewhere and seeking further management.\n\n➢ Those with previous history of animal exposures and received post exposure prophylaxis or taken pre-exposure prophylaxis for preventing rabies.\n\n➢ Bite victims < 18 years without accompanying parents/guardians.\n\nThe Institutional ethical Committee of KIMS was discussed ethical issues and approved the following.\n\n• The study was conducted in compliance with the principles of the Declaration of Helsinki and following the ICH-GCP guidelines.\n\n• Signed informed consent was taken from the study subjects ≥ 18 years of age.\n\n• Written informed consent was obtained from parents or legal representatives for subjects of 2-17 years along with written informed assent from subjects aged 7-17 years.\n\n• All subjects were monitored for ADRs, if any, and treated free of cost.\n\n• Professional secrecy was maintained.\n\nThe Institutional Ethics Committee reviewed the proposed dissertation study entitled “A descriptive study on health seeking behaviour & post exposure prophylaxis received by animal bite victims at the anti-rabies clinic” by Dr Jithin Surendran, Post graduate student in the Department of Community Medicine under the Guidance of Dr Ravish HS, Professor of Community Medicine, Kempegowda Institute of Medical sciences, Bangalore, under Rajiv Gandhi University of Health Sciences, Karnataka during the meeting held on 27-10-2018. The members of the ethics committee were present at the meeting held on 27-10-2018 at 10:00 AM in Council Hall, Kempegowda Institute of Medical Sciences, Banashankari, Bangalore-560070. The approval reference number is KIMS/IEC/D106/2018, Dated 10-11-2018.\n\nCase Record Form: All information pertaining to the subjects who had come for post exposure prophylaxis during the study period was recorded in a separate case record form. The case record form included information on age, sex, address, phone number, education, occupation, relevant past and present medical history, weight, physical examination, history of any allergy, intake of any medication, history of any animal bites, and characteristics of exposure.\n\nLikewise, the details of health-seeking behavior and their knowledge and attitude toward rabies prophylaxis and perceived risk of disease transmission from different animals were also studied in detail.\n\nA detailed clinical examination, including a general physical examination and systemic examination, was performed to determine the health status of the animal bite victim. Similarly, all wounds present in the study subjects were examined in detail.\n\nThe bite wounds were classified according to WHO categorization as shown below.11\n\na If an apparently healthy dog or cat, in or from a low-risk area, is placed under observation, treatment may be delayed.\n\nb This observation period only applies to dogs and cats. Except for threatened or endangered species, other domestic and wild animals suspected of being rabid should be euthanized, and their tissues examined for the presence of rabies antigen by appropriate laboratory techniques.\n\nc Bites, especially on the head, neck, face, hands, and genitals, are category III exposures because of the rich innervation of these areas.\n\nParticipants in the study received post-exposure prophylaxis (PEP) at the anti-rabies clinic in accordance with guidelines set forth by the NCDC, India. The above included a thorough cleansing of the wound with soap and running water for ten to fifteen minutes, a full course of intramuscular anti-rabies vaccination according to the Essen regimen, which requires one dose of vaccine on Days 0, 3, 7, 14, and 28, and the simultaneous administration of either rabies immunoglobulin, such as human rabies immunoglobulin (HRIG)/equine rabies immunoglobulin (ERIG) or rabies monoclonal antibody (RMAb), to all category III exposures according to the calculated volume in accordance with weight on day “0.”\n\nHuman rabies immunoglobulin (HRIG) was calculated at a dose of 20 IU/kg body weight, equine rabies immunoglobulin (ERIG) at a dose of 40 IU/kg body weight, and human rabies monoclonal antibody (RMAb) at a dosage of 3.33 IU/kg body weight.\n\nAll wounds were infiltrated with RIG/RMAb to neutralize the virus locally at the wound site, as the virus may be present in any of the wounds. As much of the calculated dose of RIG/RMAb, as is anatomically feasible, was infiltrated into and around all wounds. If any, the remaining was administered deep intramuscularly at a site away from the anti-rabies vaccination. If there were multiple wounds, then the volume required for infiltration of each wound was determined, and the total volume for infiltration was determined by appropriate dilution of the passive immunization, and all wounds were infiltrated.\n\nAll subjects were observed for half an hour, to rule out any possible immediate adverse drug reactions, both local and systemic. Then, all study subjects were given a follow-up card indicating the date of the next dose of vaccination and contact details of the anti-rabbit clinic and the study personnel to contact any issues. Adverse drug reactions, if any, were recorded during subsequent visits of the subjects for vaccination on days 3, 7, 14, and 28. All adverse drug reactions were treated free of cost at an anti-rabies clinic.\n\nAll study participants were informed about the subsequent dates of vaccination and telephonic reminders on the day of vaccination. However, if there were any dropouts in the natural course of vaccination.\n\nAll animal bite victims who had completed the recommended course of anti-rabies vaccination were deemed compliant; however, those who has stopped at any point during the recommended course (apart from those who stopped after three doses, in which case the dog or cat continued to be healthy and alive for at least ten days following the exposure) were considered non-compliant or dropouts. All non-compliant cases were recorded, and the reasons for incomplete vaccination courses were determined by interviewing the non-compliant bite victims or their guardians via telephone.\n\nAll study subjects were followed up for 6 months to determine their health status and clinical efficacy of post exposure prophylaxis. The survival of the exposed persons after the completion of rabies PEP and beyond the usual incubation period of the disease (i.e., six months, is an indicator of the clinical efficacy of the treatment.\n\nThe final stage of the study was conducted during the COVID-19 pandemic period. The subjects were advised to follow appropriate COVID behavior and comply with the local authority guidelines. The recruitment strictly followed the necessary precautions to prevent the transmission of the disease. The patients were followed-up until the end of the study to rule out the development of COVID-19 and its complications.\n\nDuring the study period, the study was monitored by a guide and an institutional ethics committee.\n\nThe data collected in the study were statistically analyzed using MS Excel and IBM SPSS statistics software package version 25.0. The results were computed using frequencies and percentages. Logistic regression analysis was performed to determine the association between the study variables and health-seeking behavior of the study subjects.\n\n\nResults\n\nThe study included 1058 animal bite cases, who visited the anti-rabies clinic, Preventive Medicine Unit, Kempegowda Institute of Medical Sciences, Bengaluru, to receive post exposure prophylaxis. The details of the study participants are as follows.\n\nThe age range of 18–59 years comprised the majority of study participants, making up 57.9% of), followed by children under the age of 18 with 33.1%). The majority of the study participants were male (60.1%), and 84.4% of the respondents reported being literate. According to the Modified B.G. Prasad scale, 46.6% of the study subjects fell under medium socioeconomic class, and 35.6% of the population were employed.\n\nDogs accounted for the majority (92%) of the biting animals, among whom 65% of them were stray animals. More than 80% of the biting animals either lacked vaccinations or were uncertain about their vaccination status. A significant number of exposures occurred after unprovoked encounters, and for 41.3% of the respondents, the outcome of the animal that bit them was undetermined.\n\nOne of the primary predictors of post exposure prophylaxis is health-seeking behavior after exposure. Fortunately, 93.3% washed their wounds right away, and three-quarters of them used detergent soap to scrub the exposed area. The application of virucidal agents or antiseptics is an important component of PEP, and 56% of the study participants used it. A total of 62.4% of study individuals attended another health care institution before coming to the anti-rabies clinic, while 30.8% arrived at the study setting directly after exposure. 74.3% landed at the study sites within one day of exposure, implying that a significant number received the PEP within 24 h (Table 1).\n\nAn essential component for receiving early and appropriate PEP is knowledge and attitude towards rabies prophylaxis. Subjects’ general knowledge of rabies was satisfactory, as evidenced by the largest percentage of precise responses (88.8%) for ‘animals that transmit the disease’ and the lowest percentage (41%) for ‘disease severity’. Despite a maximum of 41.4% for the total number of ARVs to be given in PEP and a minimum of 17% for PrEP, the study subjects’ comprehension of PEP fell short of expectations.\n\nThe attitude responses were satisfactory among study subjects which have a maximum right response of 92.1% for ‘availability of ARV’ followed by ‘rabies as a preventable disease’ (88.6%) and ‘importance of wound wash after exposure’ (82.6%). The attitude regarding pre-exposure prophylaxis was directly related to their knowledge regarding same as only 31% replied that PrEP was equally important in preventing rabies (Table 2).\n\nThe perceived risk of disease transmission by the study subjects was assessed based on a 1 to 5 Likert scale, in which 1 is the lowest rating and 5 is the highest rating. The perceived risk of disease transmission by various animals among the study participants varied from person to person. The perception was poor for risk of disease transmission through other animals, apart from dogs, viz. disease transmission by cats, livestock, mongoose, monkey, and other wild animals was <25%. Rodents that were not considered potential transmitters of rabies were rated by the respondents (Table 3).\n\nPEP was provided to those with Category II (ARV) or III exposures. In most of the cases, PVRV was the type of ARV administered, and more than 61% of the patients with Category III exposures decided to receive rabies monoclonal antibody as passive immunization, followed by ERIG (38%). Prior to the administration of ERIG, the subjects underwent a skin sensitivity test; however 89% of them showed no reactions. Based on the anatomical feasibility, RIG/RMAB was infiltrated into and around the wound site. In 90% of the study subjects, it was infiltrated locally, while the remaining study subjects received the required amount both locally and by an intramuscular systemic injection.\n\nCompliance with the full course of the anti-rabies vaccine among the study participants showed a considerable drop off after each vaccination schedule. Out Of the 1058 subjects, 9.1% was the drop out for the 2nd dose of vaccination, which came down to 11.7%, 18.8%, and subsequently to the lowest of 22.1% for the last and final dose of ARV.\n\nA total of 234 dropouts and the reasons for dropout mentioned by the study subject after each telephonic interview were listed as long distance of travel, negligence, forgotten dates, interference with work timing, and school timings (Table 4).\n\nThe safety of post exposure prophylaxis was assessed in all study subjects up to day 28. The local adverse reactions included pain, erythema, itching, and swelling, and the systemic adverse events included body ache, fever, and malaise. All study subjects with adverse drug reactions were treated free of cost at the study center, and all subsided without any complications.\n\nAll study subjects were followed up for 6 months and were found to be healthy, showing that the post exposure prophylaxis provided at the anti-rabies clinic was effective in preventing the disease.\n\nTo assess the overall effect of the study variables on wound washing practiced as a health behavior, the multiple logistic regression model was applied to the variables that were statistically significant in the univariate logistic regression analysis. It was found that there was a significant association between the socioeconomic status of the animal bite victims, fate of biting animals, and type of wounds with their health behavior.\n\nA multiple logistic regression model was applied to the study variables that were statistically significant in the univariate logistic regression analysis with regard to the time interval for receiving post exposure prophylaxis. A significant association was found between the socioeconomic status of bite victims, vaccination status, and fate of biting animals.\n\nA multiple logistic regression model was applied to the study variables that were statistically significant in the univariate logistic regression analysis with regard to the association between the study variables and health care sought by bite victims. This showed that there was a significant association between the occupation of bite victims and vaccination status of the biting animals (Table 5).\n\n\nDiscussion\n\nThe present study provided details regarding the health-seeking behavior of animal bite victims and assessed their knowledge and attitude toward rabies prophylaxis and perceived risk of disease transmission. It also provided details of the post exposure prophylaxis received by the patients and their compliance with the complete course of the anti-rabies vaccine.\n\nThe health behavior in the present study showed that 93.3% of the subjects had washed their wounds, and 55.9% had applied local antiseptics. Similarly, a cross sectional study on epidemiology of animal bite cases attending the anti-rabies clinic of a rural tertiary care hospital of Haryana among 3897 animal bite victims revealed that only 54.1% animal exposed cases had washed their wound with either only water or with soap and water.16 Another descriptive study on epidemiological determinants of animal bite cases attending the anti-rabies clinic in Sassoon hospital, Pune including 3226 animal bite cases showed that only 33.7% had washed their wounds with soap and water after the bite.17\n\nThe present study also showed that 62.4% of the patients had visited other health care facility before coming to the anti-rabies clinic viz. corporation dispensaries, private hospitals, private clinics, etc.; 4.8% of them visited AYUSH doctors, and 2% consulted veterinarians. Likewise, 7.3% of them came to anti-rabies clinic for post exposure prophylaxis within an hour after exposure/bite and 67% of them came for treatment within 24 hours, whereas 25.7% came to anti-rabies clinic after 24 hours of exposure to seek post exposure prophylaxis. Similarly, a study from Kolkata of 257 people residing in rural areas showed that only 73.2% of the exposed individuals would like to go to allopathic doctors, whereas others would visit some local practitioners/religious practices.18\n\nThe present study also showed that there was a significant association between some of the characteristics such as occupation of the bite victims (OR = 1.7; 95% CI 1.1-2.7); socioeconomic status of bite victims (OR = 3.9; 95% CI 1.5-10.3), vaccination status of the biting animal (OR = 2.8; 95% CI 1.7-4.6), and fate of the biting animal (OR = 1.5 95% CI 1.1-1.7) and the wound characteristics such as site of wound (OR = 16.5; 95% CI 10.8-23.9) and type of wound (OR = 1.6; 95% CI 1.2-2.3) with their health seeking behavior. All these studies showed that the health-seeking behavior of the exposed was inadequate and must be addressed through continuous social and behavior change communication (SBCC) activities. Increased awareness engages communities and empowers people to save themselves by seeking proper health care, thereby helping to eliminate dog-mediated human rabies by 2030.\n\nThe present study showed that the knowledge regarding prevention of rabies was incomplete, as only 54.8% had heard about the disease, 41% new about the severity of the disease, 41.4% knew about the number of anti-rabies vaccination doses to be taken after the bite, 37.1% knew about the site of vaccination, 32.5% knew about the need for rabies immunoglobulin for severe exposures, and 17% knew about pre-exposure prophylaxis. Similarly, the attitude of the study subjects was not satisfactory with regard to type of exposures transmitting disease (67.8%), need for first aid measures after exposure (82.6%), 100% preventable disease (88.6%), need for post exposure prophylaxis (68.7%), place of anti-rabies vaccine availability (92.1%), correct system of medicine for prevention of rabies (74.9%), and need and dosage for pre-exposure prophylaxis (30.9%).\n\nSimilarly, other studies also showed that KAP for the prevention of rabies was not adequate. In Mandya, Karnataka, a survey on medical school students’ awareness of rabies prevention indicated that only 45.1% of the respondents knew the extent to which rabies is throughout India and only 36.3% of them was aware how to safeguard themselves from dog bites.19 A study of 220 schoolchildren found that their understanding of rabies transmission was only 33%, while their knowledge of animals transmitting the disease was 65%.20 Similarly a study conducted on Accredited social health activists in rural Karnataka region had a poor understanding of animals spreading rabies (23.8%), the proper amount of ARV (25.7%), and the site of vaccine administration (54.1%).21 These findings suggest that frequent health education sessions on rabies prevention at all levels are necessary to improve our understanding.\n\nIn the present study, a total of 97% of the study subjects received PVRV and remaining PCEC vaccine. Along with vaccine, 61% of the study participant preferred to receive RmAb and 38.2% of the study subjects received ERIG; among whom the skin sensitivity test was positive among 11% who developed mild hypersensitivity reactions. Patients with hypersensitivity were provided symptomatic treatment, and a full dose of RIG was administered.\n\nLikewise, another study conducted at the antirabies clinic in Bangalore among 65 subjects who had wild animal exposures showed that all of them had received complete post exposure prophylaxis according to WHO, which included thorough wound wash (100%) and infiltration of rabies immunoglobulin; equine in 93.8% and humans in 6.2% cases. All study subjects received anti- rabies vaccination via intramuscular route using various types of vaccines i.e.: PCECV (60%), PVRV (33.9%), PDEV (4.6%), and HDCV (1.5%).22\n\nA full course of anti-rabies vaccine and RIG/RMAb is an important component of PEP, which has to be provided at all health care centers to prevent rabies, even after high-risk exposure. In the present study, the compliance with full course of antirabies vaccination was 77.9%. The compliance for vaccination doses slowly reduced from 90.9% for the 2nd dose on day 3 to 88.3% for 3rd dose on day 7, 81.2% to 4th dose on day 14, and 77.9% for the last dose on day 28. The reasons for the dropout were long distance of travel to the anti-rabies clinic, interference with school timings, negligence, forgotten dates, and interference with work timings. None of them stopped the vaccination course after day 10, even though the biting dog/cat was alive and healthy, as they wanted to complete the course.\n\nSimilarly, a multicentric study conducted across the country among 529 animal bite victims, showed that majority (54.4%) of the animal bite victims had Category III exposures; the overall compliance to complete course of vaccination was 78.8%, namely 65.9% for intramuscular rabies vaccination (IMRV) and 85.1% for IDRV.9 Another cross-sectional study on compliance to anti-rabies vaccine among dog bite victims in an urban slum of Chennai showed that the compliance to complete course of vaccination was found to be 55.1%. The reasons for not completing the vaccination course were loss of wages, forgotten dates, and interference with school timing.23\n\nIn the present study, among the 1058 study subjects who received post exposure prophylaxis, 103 (9.9%) had adverse drug events. The local adverse reactions included pain, erythema, itching, and swelling, and the systemic adverse events included body ache, fever, and malaise. All adverse drug reactions were mild and subsided spontaneously or with symptomatic medications. Comparably, a study carried out in Bangalore on 550 victims of animal bites who were attending an anti-rabies clinic showed that an overall 7.1% of ADEs were reported by the study participants. The most common local adverse events were pain (8.5%), erythema (7.3%), and itching (5.8%); the most common systemic adverse reactions were fever, malaise, headache, and body ache.24 Likewise, a prospective, multicentric, post-marketing surveillance study on 168 subjects showed that immediate ADRs to ERIG administration were seen in 31.5%, including pain (30.4%), swelling (5.4%), pruritis (3.6%), induration (1.2%), itching, and erythema (0.6%).25\n\nEach of the studies showed that the adverse events to post-exposure prophylaxis (ADEs) were negligible and minor, and that they resolved on their own with symptomatic therapy without any further consequences. This indicates that PEP is safe for victims of animal bites. All subjects were followed up for six months and were found to be healthy, showing that the post exposure prophylaxis provided at the anti-rabies clinic was effective in preventing the disease.\n\n\nConclusion\n\nRabies is a preventable disease with timely and appropriate post exposure prophylaxis, which includes thorough wound washing, full course of anti-rabies vaccination, and infiltration of rabies immunoglobulin/rabies monoclonal antibodies into all category III wounds and exposures.\n\nIn the present study, the health-seeking behavior of the exposed individuals, their knowledge and attitude toward the prevention of rabies, and the perceived risk of disease transmission by various animals was inadequate and must be addressed appropriately.\n\nAdverse drug reactions for PEP were seen in a minimal number of study subjects, which were mild and subsided on their own or by symptomatic treatment, which showed that post exposure prophylaxis for all animal bite victims is safe and tolerable. Likewise, all study subjects were healthy and alive after a follow-up of six months, showing that the post exposure prophylaxis provided was effective in preventing the disease.\n\n\nRecommendations\n\n\n\n1. Knowledge and health-seeking behavior must be improved through continuous social and behavior change communication (SBCC) activities. This engages communities and empowers people to save themselves by seeking proper healthcare services.\n\n2. The compliance to full course of anti-rabies vaccination has to be assured in all animal bite victims, by proper health education, thereby motivating them and providing the dates of next vaccination in the treatment card/telephonic remainders.\n\n3. Post exposure prophylaxis services for all animal exposures must be provided free of cost by the government at all health centers throughout the year under the universal health coverage program.\n\n\nLimitations of the study\n\n\n\n1. Rabies virus neutralizing antibody (RVNA) analysis to assess the immunogenicity of the vaccine was not performed because of cost feasibility.\n\n2. The biting animals could not be followed up to confirm their health status owing to logistic reasons.",
"appendix": "Data availability\n\nFigshare: THESIS EXCEL DATA ENTRY.xlsx, https://doi.org/10.6084/m9.figshare.24709566.v1. 26\n\nFigshare: Extended data, https://doi.org/10.6084/m9.figshare.25151543.v1. 27\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nWorld Health Organization: Weekly epidemiological record. Rabies vaccines: WHO position paper. World Health Organ. Tech. Rep. Ser. 2018; 931: 201–220.\n\nTarantola A: Four thousand years of concepts relating to rabies in animals and humans, its prevention, and its cure. Trop. Med. Infect. Dis. 2017; 2(2): 5. Publisher Full Text\n\nWorld Health Organization: Weekly Epidemiological Record. Rabies vaccines: WHO position paper No. 32.2010; 85: 309–320.\n\nWilde H, Khawplod P, Khamoltham T, et al.: Rabies control in south and southeast Asia. Vaccine. 2005; 23(18): 2284–9. Publisher Full Text\n\nWHO South East Asia region: Strategic Framework for Elimination of Human Rabies Transmitted by Dogs in the South-East Asia Region. World Health Organization, Regional office for South East Asia; 2012.\n\nWHO fact sheet on rabies. accessed in May 2018.Reference Source\n\nSudarshan MK, Madhusudana SN, Mahendra BJ, et al.: Assessing the burden of human rabies in India: results of a national multi-center epidemiological survey. Int. J. Infect. Dis. 2007 Jan 1; 11(1): 29–35. PubMed Abstract | Publisher Full Text\n\nSudarshan MK, Mahendra BJ, Madhusudana SN, et al.: An epidemiological study of animal bites in India: results of a WHO sponsored national multicentric rabies survey. J. Commun. Dis. 2006 Mar 21; 38(1): 32–39. PubMed Abstract\n\nHaradanhalli RS, Anwith HS, Pradeep BS, et al.: Health-seeking behavior and compliance to post exposure prophylaxis among animal bite victims in India. Indian J. Public Health. 2019 Sep 1; 63(5): 20–25. Publisher Full Text\n\nNational Rabies Control Programme: National Guidelines for Rabies Prophylaxis, National Centre for Diseases Control. New Delhi: Government of India: Ministry of Health and Family Welfare; 2019.\n\nWHO Expert Consultation on Rabies prevention. Third report. Technical Report Series No. 1012. Geneva: World Health Organization; 2018.\n\nWorld Health Organization: New Global Strategic Plan to Eliminate Dog-mediated Rabies by 2030. World Health Organization; 2018.\n\nGongal G, Sampath G: Introduction of intradermal rabies vaccination–A paradigm shift in improving post exposure prophylaxis in Asia. Vaccine. 2019 Oct 3; 37: A94–A98. PubMed Abstract | Publisher Full Text\n\nVaccine Investment Strategy: Global Alliance for Vaccines and Immunization. Accessed on 30.09.2019. Reference Source\n\nShankaraiah RH, Rajashekar RA, Veena V, et al.: Compliance to anti-rabies vaccination in post exposure prophylaxis. Indian J. Public Health. 2015 Jan 1; 59(1): 58–60. PubMed Abstract | Publisher Full Text\n\nMajra JP, Verma R: Epidemiology of animal bite cases attending anti-rabies clinic of a rural tertiary care hospital of Haryana. APCRI J. 2016; 17(2): 27–30.\n\nShelke SC, Kamble MS, Niwal A: Epidemiological determinants of animal bite cases attending the anti-rabies immunization (ARV) OPD in Sassoon hospital, Pune. Int. J. Basic Appl. Sci. 2015; 5(2): 98–101.\n\nGhosal A, Naiya S, Roy T, et al.: Perception regarding animal bite: A community-based study in a rural area of Kolkata. APCRI J. 2016; 17: 18–22.\n\nVinay M, Sheethal MP, Mahendra BJ: Awareness regarding rabies and its prevention among first year medical students of Mandya. APCRI Journal. 2012; 13(2): 13–15.\n\nShwetha S, Vinay M, Harish BR: Effectiveness of child to child method of education regarding rabies and its prevention. APCRI J. 2018; 19: 28–29.\n\nRavish HS, Sharmila KN, Krishna C, et al.: Awareness on prophylaxis against rabies among ASHA workers. APCRI J. 2016; 18: 11–13.\n\nIswarya MR: A comparative study on rabies prophylaxis in anti-rabies clinic between a secondary and tertiary care hospital in Bengaluru city. J. Commun. Dis. 2017; 49: 1–5. Publisher Full Text\n\nShivasakthimani R, Vinoth GCD, Ravivarman G, et al.: Compliance of anti-rabies vaccine among dog bite victims in an urban slum of Chennai: a cross sectional study. Int. J. Commun. Med. Public Health. 2018; 5: 1487–1491.\n\nRavish HS, Kumari N, Ramya MP, et al.: Safety of rabies immunoglobulin (RIG)/rabies monoclonal antibody (RMAb) for post exposure prophylaxis in patients with potential rabies exposure. APCRI J. 2019; 21: 22–27.\n\nChawan VS, Tripathi RK, Sankhe L, et al.: Safety of equine rabies immunoglobulin in grade III bites. Indian J. Community Med. 2007 Jan 1; 32(1): 73–74. Publisher Full Text\n\nDr Surendran J : THESIS EXCEL DATA ENTRY.xlsx. Dataset. figshare. 2023. Publisher Full Text\n\nDr Surendran J : Extended data. figshare. Journal contribution. 2024. Publisher Full Text"
}
|
[
{
"id": "267093",
"date": "24 May 2024",
"name": "Dilceu Silveira Tolentino Júnior",
"expertise": [
"Reviewer Expertise Researcher in the field of human and animal rabies (neglected diseases)."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a very interesting study to seek to understand the health-seeking behavior of victims of animal bites, their knowledge and attitude towards anti-rabies prophylaxis, as well as evaluating the level of adherence to the complete cycle of anti-rabies vaccination. The study design is appropriate and the work is technically sound for the proposed objective. Statistical analysis and its interpretation are appropriate for the results obtained. I believe that all source data underlying the results is available to ensure full reproducibility and can support future studies. The conclusions are adequately supported and well represented by the results section. The work is well presented in a clear and precise way, but I suggest that the authors include some more current bibliographic references (from the last 5 years) to better contemporize the present work.\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": "11634",
"date": "28 Jun 2024",
"name": "DR JITHIN SURENDRAN",
"role": "Author Response",
"response": "Thank you very much for your thorough review and valuable feedback. I appreciate your positive evaluation of my study on health-seeking behaviour of animal bite victims and their knowledge and adherence to anti-rabies prophylaxis. I acknowledge your suggestion to include more recent bibliographic references from the last five years. I agree that incorporating these references will enhance the contemporary relevance of our work. Thank you once again for your constructive comments and insights."
}
]
},
{
"id": "256099",
"date": "15 Jul 2024",
"name": "Dr Harish B R",
"expertise": [
"Reviewer Expertise Prevention of Rabies"
],
"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\nBrief Description and relevance: This study focuses on the knowledge and attitude of animal bite victims in seeking post exposure prophylaxis and also on their compliance to the full course of post exposure prophylaxis. The study reveals compliance to be around 77.9% with various reasons for drop out being distance, negligence, forgetfulness and other commitments were and knowledge of rabies and its prevention among animal bites to be low at 54.8%. The study notes the need for sustained social and behavioral change communication (SBCC) to improve the health seeking behavior in animal bite victims and their knowledge of rabies prevention.\nGrammatical errors need to be rectified, otherwise, it is a pertinent study. It tries to answer the gap in knowledge and attitude of animal bite victims in seeking timely PEP. Aim and objectives are in line with the title and the study. Sampling method and sample size calculation is as required.\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/13-175
|
https://f1000research.com/articles/13-173/v1
|
11 Mar 24
|
{
"type": "Case Report",
"title": "Case Report: Burn injury on left hand ulceration and gangrene and debridement “Case report.”",
"authors": [
"Utkarsh Warghane",
"Ranjana Sharma",
"Ashish Warghane",
"Pritam Meshram",
"Ranjana Sharma",
"Ashish Warghane",
"Pritam Meshram"
],
"abstract": "Electricity constitutes a fundamental component of contemporary life, powering the majority of our appliances and devices, including indispensable once such as refrigerators. Nonetheless, it is of paramount importance to exercise the utmost caution when dealing with electricity, as even the slightest oversight or wiring hazard can precipitate tragic consequences, including loss of life. A 27-year-old male presented to the hospital with burns on his thighs and feet. He reported a history of an electrical burn on his right hand caused by an electrical socket at home while attempting to replace a light bulb. The wire from the socket came into contact with his thigh and foot. Initially, the family took him to a private hospital, but he was subsequently referred to a tertiary healthcare facility. The patient had a history of loss of consciousness at home and no reported chest discomfort, head trauma, or breathlessness. There was no family history of diabetes or hypertension. Initial, the family took him to a private hospital, but he was subsequently referred to tertiary healthcare facility. the patient had history of loss of consciousness at home and no reported chest discomfort, head trauma, or breathlessness. There was no family history of diabetes or hypertension. Initially investigating included a colour dropper study of the right hand and an x- rays. The patient underwent wound dressing using aseptic techniques and was admitted to the surgical intensive care unit for further management. An imperative aspect of education and awareness involves the proper instruction for safely handling electrical equipment, the use of appropriate clothing and protective gear while handling such equipment and the importance of switching off power supplies to reduce the incidence rate of such incidences.",
"keywords": [
"Burns",
"breathless",
"Radioactive sources",
"Electrical incidents."
],
"content": "Background\n\nElectricity constitutes a fundamental component of contemporary life, powering the majority of appliances and devices, including indispensable ones such as refrigerators. Nonetheless, it is of paramount importance to exercise utmost caution when dealing with electricity, as even the slightest oversight or wiring hazard can precipitate tragic consequences, including loss of life.\n\nA 27-year-old male presented to our hospital with burns on his thighs and feet. He reported a history of an electrical burn on his right hand caused by an electrical socket at home while attempting to replace the light bulb. The wire from the socket came into contact with the thighs and feet. Initially, the family took him to a private hospital, but he was subsequently referred to a tertiary healthcare facility. The patient had a history of loss of consciousness at home and had no reported chest discomfort, head trauma, or breathlessness. There had no family history of diabetes or hypertension. Initially, the family took him to a private hospital, but he was subsequently referred to a tertiary healthcare facility. The patient had a history of loss of consciousness at home and had no reported chest discomfort, head trauma, or breathlessness. There had no family history of diabetes or hypertension. Initially, we included a color dropper study of the right hand and radiographs. The patient underwent wound dressing using aseptic techniques, and was admitted to the surgical intensive care unit for further management. An imperative aspect of education and awareness involves proper instruction for safely handling electrical equipment, the use of appropriate clothing and protective gear while handling such equipment, and the importance of switching off power supplies to reduce the incidence rate of such incidents.\n\n\nIntroduction\n\nElectrical power is an indispensable necessity for the majority of us in the modern world. It powers a wide array of essential equipment including refrigerators. However, it is crucial to recognize that even the slightest lapse in electrical safety or hazardous wiring can lead to catastrophic consequences, including loss of life.1 Despite our profound dependence on electrical power, caution must be exercised in its utilization. The unsettling reality is that India, like many nations, has witnessed a distressing number of accidents resulting from electrical issues.2 According to the National Crime Record Bureau (NCRB), in 2015 alone, over 2,200 individuals lost their lives because of unintentional fires triggered by short circuits. It is worth nothing that these statistics grim as they may be, pale in compression with the staggering figures of the subsequent year, which saw over 11,000 electrical incidents across the nation, with approximately 4,800 proving fatal.3 The term “burn” encompasses injures incurred through direct exposure to a variety of sources, such as electricity, heat, chemical, or radiation. Human skin, the largest organ, comprises several layers, each with distinct characteristics. Burns are (superficial) burns affecting the epidermis, second-degree (partial thickness) burns impacting the epidermis and possibly some dermal layers, and third-degree (full thickness) burns penetrating deep into tissues, including muscle and bone. Precise assessment of burn depth is vital for effective treatment, and various methods such as the Palmer method, the Lund Browder strategy, and the rule of nine aid in this determination.4 Among all types of burn injuries, electrical burns are the most devastating.\n\nAlthough most thermal or electrical burns cannot be predicted by physical examination or by the size or severity of the burn, the heat produced by electric current causes tissue damage.5 Electric burn injuries are caused by the quantity of current that leaves the body upon contact as well as the source and timing of the contact. Heat is produced by electricity passing through nerves and blood vessels and along the outside of bones, which damages the adjusting tissue.6 In this compressive research, we delve into the intricate realm of electrical burn injuries, aiming to shed light on their multifaceted nature and the challenges they pose to medical professionals and patients. Exploring the various factors influencing the severity of electrical burns and examining the diverse and valuable resource resources for healthcare practitioners and researchers working in the field of burn injury management. Additionally, our study endeavors to increase awareness among the general population regarding the importance of electrical safety measures and the potential consequences of neglecting them. Through a thorough analysis of case studies, clinical insights, and the latest advancements in burn care, we aimed to contribute to the prevention and mitigation of electrical burn injuries, ultimately safeguarding lives and prompting safer practices in our technologically driven world.\n\n\nCase presentation\n\nA 27 years old male presented to our hospital with burn injuries affecting his thighs and feet. He reported a history of an electrical burn on his right hand sustained while attempting to fix a light bulb at home. During this incident, the electric socket wire contacted the thigh and foot. Initially, his family sought care at a private hospital where the initial management was provided. However, owing to the severity of his injuries, he was referred to our tertiary healthcare facility. The patient reported loss of consciousness at the time of the accident but denied experiencing any chest discomfort, head trauma, or breathlessness. In addition, there was no family history of diabetes mellitus (DM) or hypertension (HTN).\n\nUpon examination, physical findings revealed significant blackening of the skin and ulceration of the right arm, indicative of a third degree. Contractures were observed at the dorsal phalanges and proximal phalanges of the right hand, affecting the second, third, fourth, and fifth digits. Furthermore, the index finger exhibited a 4 × 4 cm area of the third-degree burn with black discoloration of the lateral aspect of the forearm, thigh, and foot displayed similar third-degree burns, accounting for the respective areas as per the Rule of nine (figure 1). A color Doppler study of the right hand demonstrated non-visualization of the distal radial and ulnar arteries in the raw wound area. An X-ray scan of the affected tissues yielded normal findings. An aseptic dressing was applied and the patient was admitted to the surgical intensive care unit with a diagnosis of third-degree burns, ulceration, and gangrene.\n\nThe attending physician recommended debridement of the patient’s right hand. Laboratory investigations revealed the following results: hemoglobin (Hb), 13%; total red blood cells 4 million/ul, total white blood cells, 11,300/μL; mean corpuscular hemoglobin concentration (MCHC) 93.3 g/dl, mean corpuscular hemoglobin (MCH), 32.5 pg; hematocrit (HCT), 37.5%; and total platelet count 5.79 lakh/ul. Blood coagulation profiles were as follows: activated partial thromboplastin time (APTT) 29.5 second (control 30.7 s), prothrombin time (PT) 11.9 seconds, and intentional normalized ratio (INR) 1.97. Urinalysis was negative for albumin, with 1-2 pus cells and 1-2 red blood cells. Biochemical blood profile indicated a urea level of 31 mg/dl, creatinine levels of 0.7 mg/dl, sodium level of 140 mEq/L, and potassium levels of 4.9 mEq/L. The patient’s Glasgow Coma Scale (GCS) score was normal, and neurological assessment revealed no abnormalities.\n\nThe patient was diagnosed with ulceration of the hand resulting from an electrical burn black skin discoloration. The general surgeon recommended wound debridement and amputation, if deemed necessary. Subsequently, the patient underwent serial wound debridement was performed. The extent of amputation was determined based on the vascularity and burn depth. Local neurodebridement was performed to address existing wounds bilaterally on the thighs. Additionally, the left upper limb was immobilized using a plaster cast. Wound culture analysis was recommended and the surgeon suggested a groin flap procedure to cover the exposed tendons. Daily debridement and dressing of the right hand were initiated, along with split skin grafting on the left thigh after debridement. A Vac dressing was applied to the right arm. The patient was advised to lie in the supine position and perform active-assisted toe movements on both sides (20 repetitions), active-assisted knee bending exercises, and static quadriceps exercises (10 repetitions each). Upper limb mobility exercises (10 repetitions) were performed by the physiotherapist.\n\nThe patient’s dietary intake was supervised by a dietitian, with recommendations to consume 2200 kcal/day with a high-protein, low-fat, and high-fiber diet. The treatment plan consisted of the following postoperative interventions. NBM (nil by mouth) status for 8 hours, intravenous fluid: Dextrose Normal Saline (DNS) at 100 mL/hr, Intravenous antibiotics Inj Ceftriaxone 1.5 mg, gastrointestinal protection: Inj Pantoprazole 40 mg, Analgesic: Inj paracetamol 100 mL and Inj. Tramadol SOS, limb elevation, intramuscular “diclofenac sodium (Dynapar)” SOS and oral antibiotic Cefixime 200 mg, “Vitamin C (Limci) 2”. SOS, Regular assessment of the wound healing progress, including monitoring for signs of infection, necrosis, or delayed wound healing, was advised. After a couple of weeks, the patient demonstrated remarkable resilience and cooperation with the treatment plan. Serial wound debridement sessions, coupled with meticulous dressing changes, led to gradual improvement in the condition of the right hand the groin procedure flap procedure successfully covered the exposed tendon, contributing to the overall healing process. The left thigh, which had undergone split-skin grafting, exhibited healthy granulation tissue formation, signalling a positive response to treatment. Throughout hospitalization, the patient’s vital signs remained stable, with no signs of infection or systemic complications. Laboratory parameters consistently showed values within the normal range, indicating a positive response to treatment. Meticulous care provided by the healthcare team, coupled with the patient’s determination, yielded a promising outcome. The patient was educated on the importance of post-discharge care, including wound healing care and physical therapy, to optimize long-term recovery.\n\n\nDiscussion\n\nRefrigerators are among the numerous modern appliances that rely on energy consumption for their operation. However, even the slightest negligence or wiring-related hazards can lead to catastrophic consequences. Our dependency on electricity necessitates a prudent approach for its use. The statistics of electrical accidents in India offer little solace, with the National Crime Record Bureau (NRCB) reporting nearly 2,200 fatalities resulting from unintentional fires caused by short circuits in 2015.7 It is worth noting that the subsequent year witnessed over 11,00 electrical mishaps nationwide, with 4,800 incidents resulting in fatalities. Burns, in this context, encompass injuries caused by direct contact with electrical, thermal, chemical, or radioactive sources.8\n\nClassification of burns involves several layers of the skin, with first-degree burns affecting the epidermis and potentially the dermis, second-degree burns affecting the epidermis and potentially portion of the dermis, third-degree burns encompassing damage to the epidermis, dermis, and occasionally subcutaneous tissue, and fourth-degree burns extending their harm to deep tissue, muscles, and even bone.9 Techniques such as the palmer method, Lund- Browder strategy, and rule of nine are commonly employed for assessing burn extension. Electrical burns are the most severe and intricate cause of burn injuries.10 The heat generated by the passage of electrical current is responsible for tissue damage, although the size and severity of thermal or electrical burns are often challenging to predict through physical examinations.6 Electric burn injuries are influenced by factors such as the amount of current exiting the body upon contact, source of electricity, and timing of contact. Heat is generated as electricity courses through blood vessels, nerves, and along the surface of bones, causing damage to the surrounding tissue.\n\nIllustrating the gravity of electrical burns, we present a case involving a 13-years-old boy who sustained severe burns while using a mobile phone in a bathtub. Upon hearing the child’s distress, the mother removed him from the bath and disconnected the charger, experiencing muscle spasms and momentary loss of consciousness. The boy was revived using a hard tap on his shoulder. Evaluation following the Advance Trauma Life Support guidelines revealed stable hemodynamic and respiratory conditions. Physical examination revealed two deep lesions: a circumscribed, oval-shaped lesion measuring approximately 1 × 1 cm on the palmar side of the hand between the thumb and index figure, displaying a central pallor, and a lacerated strip of skin measuring approximately 1 × 12 cm on the abdomen near the epigastric region. The total body surface area was less than 0.5%. Remarkably, the patient exhibited a significantly elevated blood creatinine kinase (CK) level of 1294 μ/L. Electrical heart scans yielded normal results. The patient was admitted to the pediatric ward for observation and a tertiary survey, during which his CK level increased slightly to 1400u/l. Myoglobinuria was detected in the urine, but no signs of rhabdomyolysis were observed. Given the absence of complaints or anomalies in the tertiary survey, the patient was discharged on post-burn day 2.11\n\nTo mitigate the risk of electrical burns, it is imperative that users exercise caution when using electrical equipment in bathroom settings. Electrical devices or cords should never be connected to a power source when in close proximity to water or when exposed to moisture.12\n\nA study conducted at Manipal shed light on the demographics of electrical burn victims, with the majority being male(99.0), aged between 18 and 40 (70.4%), and primarily consisting of unskilled laborers (56.8%), employed linemen or electricians (29.6), and farmers (11.1%).13\n\nIn another case, a 27-year-old male was admitted to our hospital with burns on his thighs and feet. He reported a history of electric burns on his right hand when a live wire from an electric socket made contact with his thigh and foot while he was fixing a light bulb at home. Initially, the family sought care at a private hospital before he was referred to our tertiary healthcare facility. Physical examination revealed skin blackening, ulceration, and third-degree burns on the right hand, with contractures affecting the dorsal and proximal phalanges, specifically the 2nd, 3rd, 4th, and 5th phalanges. Additionally, blackening of the forearm, thigh, and foot was observed, as per the rule of nine. A color Doppler study of the right hand indicated non-visualization of the distal radial and ulnar arteries due to the raw area, while X-ray findings were unremarkable. Aseptic dressing was performed and the patient was admitted to the surgical ICU with a diagnosis of third-degree burns, ulceration, and gangrene. The medical team recommended wound debridement and, if necessary, amputation of the right hand because of black discoloration of the skin. Local neurodebridement was performed for the exit wound in both thigh regions and limb elevation with plaster application was initiated in the left upper limb. Split skin grafting was performed on the left thigh after debridement, along with the application of a Vac dressing to the right arm. The patient was advised to remain in a supine position.14\n\n\nConclusion\n\nIn 2015, 2,200 lives were tragically lost due to unintended fires caused by short circuits, as reported by the National Crime Records Bureau (NCRB). The gravity of the statistic is further underscored by the subsequent year’s record, which revealed a staggering 11,00 electrical accidents nationwide, with a devastating 4,800 resulting in fatalities.\n\nIt is imperative to emphasize the significance of prompting safety practices in the use of electrical equipment. These include adhering to safety instructors, wearing appropriate clothing and protective gear, and diligently disconnecting power sources when not in use. It is also essential to address the specific risks associated with using home electrical equipment in bathrooms, ensuring strict adherence to safety regulations and standards.15\n\n\nConsent\n\nWritten informed consent was obtained from the patient for the publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of the journal.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nPatient education: Electrical burns (The Basics) - UpToDate. http\n\nCampbell RB, Dini DA: Occupational Injuries from Electrical Shock and Arc Flash Events. New York, NY: Springer New York; 2016. Publisher Full Text\n\n2,000 Annual Electrocution Deaths in India: 7 Safe Tips for Your Home. http\n\n(PDF) Treatment of burns in the first 24 hours: simple and practical guide by answering 10 questions in a step-by-step form. http\n\nCrumley I, Blom L, Laflamme L, et al.: What do emergency medicine and burns specialists from resource constrained settings expect from mHealth-based diagnostic support? A qualitative study examining the case of acute burn care. BMC Med. Inform. Decis. Mak. 2018 Dec; 18(1): 71. PubMed Abstract | Publisher Full Text | Free Full Text\n\ndeepak patel: Burn.Reference Source\n\nState-wise electrocution deaths: 2020. Reference Source\n\nWorkplace electrical safety with regard to power installer, repairer, and supervisor fatalities. http\n\nPage 120 - Handbook for Brunner and Suddarth’s Textbook of Medical-Surgical Nursing. http\n\nInterphalangeal joints of the hand - Wikipedia. Reference Source\n\nElsevier Enhanced Reader. Reference Source\n\nBae HS, Lee MY, Park JU: Intraoperative burn from a grounding pad of electrosurgical device during breast surgery.2018; 4.\n\nWorkplace Injury & Fatality Statistics - Electrical Safety Foundation International. Reference Source\n\nKumar S, Verma AK, Singh US: Electrocution-related mortality in northern India – A 5-year retrospective study. Egypt. J. Forensic Sci. 2014 Mar 1; 4(1): 1–6. Publisher Full Text\n\nDownload PDF|Electrical burns: Highlights from a 5-year retrospective analysis. http"
}
|
[
{
"id": "261227",
"date": "25 Apr 2024",
"name": "Andrea Mc Kittrick",
"expertise": [
"Reviewer Expertise Burns",
"outcomes",
"quality of life",
"research methodology"
],
"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\nPlease see the attached PDF file here with markup to support the feedback and review, to assist the authors.\n\nBackground: This case review has the potential to be very interesting for the reader. Unfortunately, there is a lack of information about the case - for example, all areas burnt, TBSA, hand dominance, time post injury.\n\nCase presentation: This is repetitive of the section before and the opportunity for more details have been missed. More detail would provide the reader with in-depth knowledge of the presentation. It would be beneficial to outline in detail the surgical interventions and timings. Each dressing used. All of the rehabilitation interventions and the rationale for these. When nutrition was provided and how this was measured.\n\nDiscussion: Unfortunately, this section repeats information from the case and discusses other cases which have similar mechanism of injury. In this section the authors should discuss their case with the wider literature pertaining to electrical burns.\n\nConclusion: Unfortunately, this section repeats information from the case. As no evidence was provided regarding outcome measures used this conclusion is not robust.\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": []
},
{
"id": "272476",
"date": "07 Jun 2024",
"name": "Jonathan Cubitt",
"expertise": [
"Reviewer Expertise I am a burns surgeon"
],
"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 case and can highlight problems related to electrical burns and complex wounds to the non burns community. However, it needs significant revision. There are multiple grammatical errors and repeated sentences. There are no obvious figures / pictures despite them being referred to. I would like to see a picture of the burns, the doppler images, the groin flap reconstruction and the eventual outcome. The additional 2 cases that are added into the discussion came as a surprise. If this is a case series then these should be presented in the beginning with photos etc as above. Then the discussion can reflect on the differences in management and outline the principles of electrical burn management including the cardiac issues, compartment syndrome, rhabdomyalysis etc. I don't think this should be indexed in the current state but would be happy to review again after a major revision.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? No\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-173
|
https://f1000research.com/articles/13-172/v1
|
11 Mar 24
|
{
"type": "Research Article",
"title": "Awareness of lung cancer risk factors and symptoms in Syria: an online cross-sectional study",
"authors": [
"Hidar Alibrahim",
"Haidara Bohsas",
"Sarya Swed",
"Yasmeen Abouainain",
"Mohammad Badr Almoshantaf",
"Mohamad Nour Nasif",
"Lazaward Kazan",
"Rawan Farid Alnadaf",
"Nadim Schkeif",
"Raghad Al Ali",
"Bisher Sawaf",
"Enas Swed",
"Sherihan fathey",
"Gowhar Rashid",
"Wael Hafez",
"Hidar Alibrahim",
"Haidara Bohsas",
"Sarya Swed",
"Yasmeen Abouainain",
"Mohamad Nour Nasif",
"Lazaward Kazan",
"Rawan Farid Alnadaf",
"Nadim Schkeif",
"Raghad Al Ali",
"Bisher Sawaf",
"Enas Swed",
"Sherihan fathey",
"Gowhar Rashid",
"Wael Hafez"
],
"abstract": "Background Globally, lung cancer is the leading cause of cancer fatalities and the second most frequent cancer. Population knowledge of the features of lung cancer is a crucial strategy for early diagnosis and decreasing the mortality rate of lung cancer patients. In this study, we aim to assess the Syrian population’s knowledge of lung cancer and its risk factors and to measure awareness of symptoms related to lung cancer.\n\nMethods This national cross-sectional study was conducted between October 12 to November 21, 2022, in Syria. We included Syrian people above 18 years from all Syrian governorates. The questionnaire consisted of three categories of questions: sociodemographic information, awareness of lung cancer symptoms, and awareness of lung cancer risk factors.\n\nResults Overall, 2251 participants were involved in this research; almost half of them (47.3%) were aged between 21-30 years, and 30.9% indicated they are smoking cigarettes. The overall mean score of knowledge regarding closed questions about risk factors of lung cancer was 4.29; however, the mean score of knowledge regarding open questions about symptoms of lung cancer was 1.52. About half of the study sample (51.3%) indicated that unexplained weight loss is a possible symptom of lung cancer. Our findings showed that cigarette smokers have a lower probability of having adequate knowledge toward lung cancer risk factors than a non-smoker (AOR=0.73, COR=0.68, P-value<0.05). We also defined that females have higher statistically significant odds (AOR=1.3, COR=1.38, P-value<0.05) for being knowledgeable about the symptoms of lung cancer compared to the male sample study.\n\nConclusion According to our findings, there is inadequate knowledge toward lung cancer risk factors and moderate knowledge of lung cancer symptoms. Along with educational programs to raise public knowledge of the dangers of smoking and other LC risk factors, effective tobacco control policy execution is crucial.",
"keywords": [
"Lung Cancer",
"Risk factors",
"Symptoms",
"Syria"
],
"content": "1. Background\n\nLung cancer is the most common cause of cancer-related deaths and the second most prevalent cancer worldwide (WHO, 2020). It is estimated that the incidence of lung cancer is 2.2 million globally. Also, there are 1.7 million death cases every year from lung cancer.1,2 It is classified histologically into two types: Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is more common, accounting for 85% of lung cancers, and includes three major subgroups: adenocarcinoma, large cell carcinoma, and squamous cell carcinoma.3 In 2018, the number of new lung cancer cases was evaluated as 79887 in the Middle East and North Africa region, and 2144 were from Syria. Although diagnosis and treatment of lung cancer have been improved, the 5-year survival rate in those regions remains at 8%. Among all countries in the region, Morocco and Tunisia had the highest number of lung cancer-related deaths.4 The most significant contributing risk factor to lung cancer is cigarette smoking. It is believed that there is a 5 to 10-fold increase in lung cancer risk among smokers. Also, the risk increases by 20% for nonsmokers exposed to passive smoking.5 Although more than 85% of the cases are caused by avoidable tobacco exposure, lung cancer remains the leading cause of cancer deaths worldwide.4,6 Other risk factors include family history, genetic tendency, occupational exposure (radon, ionizing radiation, diesel, and asbestos), chronic lung diseases and infections, lifestyle factors, and bad diet habits.6,7 Since lung cancer symptoms are non-specific, most patients are diagnosed at advanced stages, particularly stage IV.8 The most presenting symptoms are persistent cough, hemoptysis, chest pain, and dyspnea. Other metastatic symptoms can also occur, such as weight loss, fatigue, fever, and bone pain.8,9 It is confirmed that many genetic and epigenetic modifications are triggered by cigarette smoking.10 The knowledge of lung cancer-associated epigenetics helps us assess the risk, understand the process of carcinogenesis, diagnose the subtypes of cancer and predict the aggressiveness of the cancerous cells, response to treatment, prognosis, and metastasis. Therefore, we can make effective screening and treatment plans targeting those epigenetic alterations.10–12 An early lung cancer diagnosis is critical to decreasing mortality and enhancing prognosis. Screening people at high risk using low-dose computed tomography (LDCT) results in a 20% reduction in mortality rate, as proved by The National Lung Screening Trial (NLST). Annual screening of high-risk groups starting from age 50 is recommended in many current guidelines.13–15 It is recognized that late lung cancer diagnosis is due to the lack of understanding of the disease’s common symptoms. Therefore, raising public knowledge and awareness of lung cancer is crucial for early detection and treatment.16 It is believed that low-income countries and high tobacco consumption have less knowledge of symptoms and contributing factors of lung cancer, resulting in less effective treatment and a low survival rate.1,4 Therefore, our aim in this study is to assess the knowledge of lung cancer and its risk factors and to measure the awareness of lung cancer-related symptoms among the Syrian population.\n\n\n2. Methods\n\nAn online survey cross-sectional study was conducted between October 12 to November 21, 2022 in Syria. The inclusion criteria of study participants were adults (≥18 years old), Syrian nationals from all Syrian governorates. Participants who were non-Syrians, students or workers in healthcare facilities were excluded from the study. This survey was created in the light of a previous research that used modified, approved scales.17,18 Then, the questionnaire was translated into Arabic by healthcare professionals in order to be easily understood and answered for the participants, which the utilized questionnaire was uploaded as extended data (see data availability statement). Specific collaborators from many medical Syrian colleges (Data Collection Group) were responsible to collect the data by disrupting the online survey, which was generate at google form website, on social media platforms such as WhatsApp, Telegram, and Facebook. Regarding, the sample size calculation, it was estimated using Calculator.net tool (Population Size (The number of the individuals of the Syrian community in 2021 according to the world bank organization19 (PS) = 18,275,704. The proportion of the population who are aware toward the lung cancer (PP) = 50%, Confidence level (CL) = 95%, and the margin error (ME) = 5%, which the recommended sample size to represent overall findings at level of the Syrian population was 385.\n\nA modified version of the Lung Cancer Awareness Measure (LCAM) was utilized as an assessment tool. LCAM is a face-to-face questionnaire that was developed and approved by University College London and Cancer Research UK to measure the awareness of lung cancer.20 The questionnaire had three parts: The first one contained sociodemographic data of the participants. The second part focused on measuring the awareness of the — symptoms of lung cancer, and the last part analyzed the level of the knowledge toward the lung cancer risk factors. Although the awareness level was assessed in the original LCAM questions by using yes/no/unknown responses scale, in modified Arabic LCAM we used a 5-point Likert scale (1 = strongly disagree, 5 = strongly agree) to reduce the possibilities of random answers. Then, the resultant responses were converted into correct/incorrect responses as was done in the previous researches.21–25\n\n2.2.1 Sociodemographic variables\n\nIn this section, the sociodemographic data of the respondents were included. There were 10 questions covering the needed details about: 1) age. 2) Gender. 3) Marital status explained as single, married, divorced, or widowed. 4) Educational level as below secondary or post-secondary. 5) Occupational status as unemployed, student, employed, or retired. 6) Monthly income. 7) Suffering from a chronic disease. 8) Living place. 9) Knowing someone diagnosed with cancer. 10) History of cigarette/water pipe smoking expressed as never smoked, former, or current smoker.\n\n2.2.2 Awareness of lung cancer symptoms\n\nThis section was contained 14 questions with answers using 3- Likert scale (Yes, No, I don’t know) evaluating participants’ awareness level of symptoms lung cancer. Included symptoms were 1) unexplained weight loss. 2) Persistent chest infection ≥ 3 weeks. 3) Persistent cough for ≥ 2/3 weeks. 4) Persistent shortness of breath. 5) Persistent tiredness. 6) Persistent chest pain. 7) Persistent shoulder pain. 8) Coughing up blood. 9) Pain while breathing. 10) Loss of appetite. 11) Painful cough. 12) Changes in the shape of fingers and nails. 13) Developing an unexplained loud, high-pitched sound when breathing. 14) Worsening or change in an existing cough.\n\n2.2.3 Awareness of lung cancer risk factors\n\nThis part involved 9 questions with answers using 5 - Likert scale (1 = strongly disagree, 2 = disagree, 3 = not sure, 4 = agree, 5 = strongly agree) evaluating participants’ awareness level of risk factors lung cancer. Included risk factors were 1) Exposure to radon gas. 2) Exposure to near smoker. 3) Having a previous treatment of cancer. 4) Having a relative with lung cancer patient. 5) Exposure to chemicals such as asbestos. 6) Having a previous diagnosis of any cancer. 7) Air pollution. 8) Smoking. 9) Having a previous diagnosis with lung disease such as interstitial lung disease.\n\nTo ensure clarity and readability for respondents, we distributed the online survey among various Syrian individuals and incorporated their feedback to enhance the questionnaire. Although the initial questionnaire was adapted from a study conducted in an Arabic country (Palestine),21 we rigorously assessed its reliability and validity. Specifically, we computed Cronbach’s alpha for each scale, including knowledge of risk factors and symptoms of lung cancer, confirming consistency with previously published work.\n\nThe study was ethically reviewed and approved by Syrian Ethical Society for Scientific Research in Aleppo University (IRB: SA19/01). In compliance with ethical standards, a comprehensive statement about informed consent was provided to all participants on the first page of the online survey. At the first page of the online survey, all participants were informed about the study goal, research group’s identity, their right to pull out from the research, collected data privacy and protection, and the fact that only totally submitted information would be analyzed. Completing the whole survey takes from 5 to 10 minutes. For clarity, consent from participants was obtained, and this process was approved by the ethical review committee. Participants were presented with the necessary information to make an informed decision, and their consent was obtained written.\n\nThe IBM SPSS V. 28.0 package application was used to analyses the data (IBM Corporation, Armonk, NY, USA). a proprietary research instruments. It is confirmed that a valid copyright license for the use of SPSS v. 28.0 has been obtained. A P-value of 0.05 or less indicated statistical significance. A mean and standard deviation were provided for the quantitative data. In contrast, the categorical data was presented as frequency and percentage after the Shapiro-Wilk test confirmed that the distribution of the data was non-parametric. Kruskal–Wallis one-way analysis of variance and One-way analysis of variance tests were performed to determine the difference in the level of knowledge toward the risk factors and symptoms of the lung cancer between the subgroups. In order to determine the expected values of “Odds ratios” between the dependent variable (knowledge the risk factors and symptoms of the lung cancer) and independent factors (sociodemographic variables), we utilized a binary logistic regression, which we relied on the cut off points from the Palestinian research.17,18\n\n\n3. Results\n\nWe define that 2303 participants were invited to participate in this study, and 52 participants refused to complete the received online survey, so the final sample size of the study participants was 2251. Almost half of the respondents (n = 1041, 47.3%) aged between 21-30 years, and about two-thirds were females and were lived in the city (n = 1430, 63.5%), (n = 1475, 65.5%). Regarding the educational level, 72.6% of participants had a university (Bachelor’s\\Master) degree, and 35.1% (n = 791) of respondents were married. However, 1234 of the study participants (54.8%) reported moderate monthly income. The majority of participants (92.7%) were with no chronic disease. Finally, 30.9% of study participants indicated they were smokers (Table 1).\n\nThe mean score and standard deviation of knowledge regarding closed questions of risk factors of lung cancer (mean = 4.29, SD = 2.32); however, the mean score and stander deviation regarding the open questions were 8.63 and 3.07, respectively. Concerning the knowledge of lung cancer symptoms, the closed questions scored mean = 8.63, SD = 3.07, while open questions scored (mean = 1.52, SD = 1.25) (Table 2).\n\n3.2.1 Participants’ Awareness of Lung Cancer Symptoms\n\nConcerning the knowledge toward lung cancer symptoms, about half of the study respondents (1155, 51.3%) indicated that unexplained weight loss is a possible symptom. On the other hand, about 80% of participants believed that persistent (3 weeks or longer) chest infection might be a lung cancer symptom. Regarding the persistent shortness of breath (1904, 84.6%) of participants revealed it as one of the lung cancer symptoms. Nearly a quarter of participants didn’t identify loss of appetite as a possible symptom of lung cancer (543, 24.1%). Also, about a third of respondents didn’t recognize that lung cancer symptom include changes in the shape of fingers or nails. Finally, (n=518, 23.0%) didn’t know if worsening or change in an existing cough is one of the lung cancer symptoms (Table 3).\n\nRegarding the knowledge of lung cancer risk factors, 45.7% of study participants were unsure whether exposure to radon gas is one of the risk factors. As well, concerning cigarette smoke exposure, about half of the participants (n = 1065, 47.3%) agreed it is a lung cancer risk factor. Almost a quarter of respondents (546, 24.3%) didn’t agree that lung cancer risk factors included the presence of a close relative with lung cancer. In addition, 8.3% of participants strongly disagreed that exposure to chemicals, for example asbestos is one of the lung cancer risk factors, and just half of the study respondents indicated that smoking is a risk factor for developing lung cancer (Table 4).\n\nAs shown in Table 5, we noticed the mean score of knowledge (8.78, 4.38) toward symptoms and risk factors of lung cancer were higher in females than males. Regarding the education status, participants with University (Bachelor’s\\Master) and with a Ph.D. degree were more knowledgeable (mean = 8.77, 4.65) about lung cancer symptoms and risk factors, respectively. However, single participants had more knowledge (mean = 4.44) of risk factors of lung cancer than other marital status subgroups. Students had more averages of knowledge about symptoms and risk factors of lung cancer compared to other occupation status subgroups. Respondents who were smokers were less knowledgeable about identifying lung cancer symptoms and risk factors (mean = 8.36, 3.99). The participants said that persons aged 70 years old had a higher understanding regarding the symptoms and risk factors of lung cancer (Table 5).\n\nIn overall, good knowledge toward the risk factors of lung cancer was shown in females (34.8%, P-value < 0.05) more than in males (17.8%), and for the educational level, more knowledgeable persons were found in participants with university (Bachelor’s\\Master) degree group (40.4%, P-value < 0.01) compared to other educational sub-groups. Participants who were smokers and had an inadequate level of awareness regarding risk factors formed just 14.2%, and the participants who reported lung cancer not related to age and had good knowledge of risk factors of lung cancer were (34.8%) (Table 6).\n\nThere was a statistically significant difference between specific subgroups regarding the knowledge of symptoms of lung cancer, of which 37.7% and 25.8% of females have shown good and inadequate knowledge of risk factors of lung cancer, respectively. In addition, we define that there was a statistical difference between the educational subgroups regarding the level of knowledge of lung cancer risk factors, which the participants in the university educational category and those who had adequate knowledge (42.3%) were more than those who hadn’t (30.3%). In addition, less recognition toward lung cancer symptoms has been found among 29.1% of smokers, and 39.7% of respondents reported they taking an immediate appointment with a doctor with adequate knowledge toward lung cancer symptoms (Table 7).\n\nSeven out of twelve predictor factors were significantly linked with a good knowledge of lung cancer risk factors (P-value < 0.05). The university participants (Bachelor’s\\Master) educational category were more likelihood to recognize the lung cancer risk factors than other participants with primary degree (OR = 2.620, P-value < 0.05), and the respondents who were smokers were less likely to identify the adequate degree of the knowledge toward risk factors of lung cancer than who weren’t a smoker (OR = 0.773, P-value < 0.05). In addition, we showed that persons aged 70 years under the most risk of developing lung cancer in the next year had higher odds of understanding the risk factors 1.579 times than those who reported that lung cancer was not related to age (Table 8).\n\nFive out of twelve predictor variables were significantly associated with having an acceptable level of knowledge of the symptoms of lung cancer (P-value < 0.05), which females more likelihood to be knowledgeable about the lung cancer symptoms than males (OR = 1.301, P-value < 0.05), and the participants with a university (Bachelor’s\\Master) educational stage were more likely to recognize the lung cancer symptoms than other participants with primary degree (OR = 2.030, P-value). The participants who indicated that persons aged 50 years under the most risk of developing lung cancer in the next year had higher odds of understanding the symptoms of lung cancer 1.328 times than those who reported that the lung cancer was not related to age. However, respondents who didn’t know about taking an appointment with a doctor were less likely to identify an acceptable level of knowledge about lung cancer symptoms than those who reported they didn’t have symptoms (OR = .528, P-value < 0.05) (Table 9).\n\n\n4. Discussion\n\nLung cancer (LC) is the main cause of cancer-related fatalities and the second most diagnosed malignancy worldwide.26,27 Due to a lack of education about the disease and its symptoms, lung cancer is frequently identified late in low and middle-income countries (LMICs). If more people knew about lung cancer, it would be diagnosed and treated faster. Evidence shows that providing palliative care early on might increase a patient’s quality of life and possibly extend their lifespan.16 This research aims to assess how well-informed the Syrian public is about lung cancer and its avoidable risk factors, as well as how well-known the disease’s symptoms are. As per the results, participants’ knowledge levels were categorized as satisfactory and insufficient using two revised Bloom’s cutoff thresholds: 70% and 80% of the overall score. This classification was determined by the number of correct answers, with 24 and 27 correct responses out of a total of 34 questions, respectively. While the knowledge was higher among females, non-smokers, and people with a university degree or a doctorate, the knowledge was still rather low overall.\n\nThe most widely acknowledged respiratory symptom of lung cancer was identified as ’persistent shortness of breath,’ while the most recognized non-respiratory symptom was ‘unexplained weight loss.’ On the other hand, the least recognized respiratory symptom for lung cancer was ‘developing an unexplained loud, high-pitched sound when breathing,’ and the least acknowledged non-respiratory symptom was ‘changes in the shape of fingers/nails.’\n\nIt was found that having a strong knowledge of the symptoms of LC was connected with a shorter amount of time before seeking medical treatment, which can help with the early diagnosis of LC.28–31 As a result, determining the degree to which the general public is aware of the symptoms of LC is essential if one is to locate the knowledge gap that has to be filled by educational interventions. According to the findings of this research, there is potential for advancement in the level of public awareness of the symptoms of LC in Syria. It was discovered that Australia, Nigeria, and the United Kingdom all had less than desirable levels of understanding of LC symptoms.20,32,33 This may emphasize the vital need for standardized educational programs to enhance public awareness of LC symptoms by world health authorities. This is particularly important, considering LC substantially contributes to the global burden of cancer-related morbidity and mortality.27 The high rate of smoking prevalence in Syria, particularly among men, may contribute to increased awareness of the symptoms of LC.34 The general population is probably well aware that smoking is a risk factor for lung cancer; hence, there could be more curiosity among the general public to read more about lung cancer than other malignancies. This study showed that women had a better understanding of LC symptoms than men did, which is an interesting finding. Women, particularly those who do not smoke, have a greater risk of developing lung cancer than men.35 Syrian women may be aware of this fact, which may motivate them to increase their health literacy regarding LC. Additional research is required to evaluate people’s awareness of the risk factors associated with LC, as well as to investigate the disparities in awareness that exist between smokers and non-smokers, as well as between men and women. This study found that LC’s least recognized respiratory symptom was ‘developing an unexplained loud, high-pitched sound when breathing.’ The findings of another study carried out in the United Kingdom found that the least recognized respiratory symptom of LC was a ‘cough that does not go away for two or three weeks.32 It’s possible that people attributed their continuous coughing to something other than LC. This could have been due to participants mistaking the symptoms of LC for those of a less serious lung illness (like COPD) or to their own habits (like smoking).36,37 Conversely, ‘persistent shortness of In contrast to studies conducted in Australia, Nigeria, and Canada, where ‘coughing up blood’ was identified as one of the most recognized respiratory symptoms of lung cancer, the present findings highlight ‘persistent shortness of breath’ as a prominent respiratory symptom. Similarly, aligning with a study from the United Kingdom,32 the two least recognized non-respiratory symptoms in this study were ‘persistent shoulder pain’ and ‘changes in the shape of fingers or nails’ associated with lung cancer. In the future, educational activities should stress the fact that LC symptoms are not always respiratory.37 Consistent with previous research in Nigeria and the United Kingdom,32,33 we found that higher levels of education were related to a higher likelihood of demonstrating good awareness of LC. Participants with a greater level of education may be more likely to interact with others who share their expertise in health-related fields. Also consistent with previous research is the finding that having personal experience with cancer increases one’s awareness of LC symptoms.38,39 Female participants were more likely to show a high awareness of LC symptoms, a finding consistent with an Australian study.20 Assuming that the moderately high levels of awareness found in this study represent the population as a whole, it may be possible to achieve greater social justice by implementing standard educational interventions in Syria to increase public awareness of the symptoms of LC. Previous research has shown that educating the public about cancer symptoms increases consultations with medical professionals and leads to better early identification of LC.29,30 While cancer mortality in high-income nations is stable or decreasing, it is steadily rising in low- and middle-income countries like Syria and is expected to account for 75% of global cancer fatalities by 2030.39 Anti-smoking programs, better early detection, and more effective treatment are all factors in this drop.40 Since effective treatment modalities are often in short supply in low- and middle-income nations, early identification of cancer is crucial for better cancer management in these regions.16 Unfortunately, there is a lack of data on LC awareness or efforts to raise that awareness in poor and middle-income countries.16 Syrian health policymakers should prioritize identifying LC risk factors, developing educational programs, and implementing effective tobacco control laws to raise risk awareness, alter consumer behavior, and promote early diagnosis and presentation. Smokers aware of the higher risk of developing LC may quit early should they encounter any of the disease’s symptoms. Campaigns like this may also help dispel the misconception that smokers with respiratory difficulties have nothing else to worry about but their habits.20,41\n\nIn order to efficiently disseminate information through widely accessed channels targeting various demographic groups such as younger males or older age cohorts, it is imperative to conduct additional research on the information sources preferred by the general public. Understanding the sources from which different segments of the population obtain information can guide tailored communication strategies, ensuring that messages are effectively conveyed to specific audiences is required in Syria and the wider region. This research needs to focus on both Syria and the wider region. In addition, obstacles to health-seeking behavior need to be investigated to find solutions to these problems and enable early presentation at healthcare facilities.28,30 In addition, increasing investments in cancer prevention and control in low- and middle-income nations like Syria, where the disease is prevalent, but resources are limited, is essential but is sometimes neglected to owe to the expenses involved.40 Yet, programs that focus on LC awareness and prevention, such as anti-smoking campaigns and tobacco control regulations, are potentially low-cost and high-effect interventions that might have a favorable influence on the modification of risk factors and the early presentation of the disease.\n\nThis study has several strengths, the most notable of which are its high response rate and its recruitment of participants from various locations throughout Palestine. Using a cross-sectional questionnaire that was administered during an in-person interview helped reduce the likelihood that respondents relied on information obtained from other sources when responding to survey questions. There are a few limitations to this study. The use of convenience sampling does not assure that a representative sample will be generated and restricts the extent to which the findings may be generalized. On the other hand, this might have been somewhat compensated for by the high response rate and the fact that they were recruited from various geographical locations. For instance, females constituted 63.5% of the participants in this study, despite the fact that they account for around 50% of the population in Syria.42 Another potential restriction is that most of the people who participated in the research were young (less than 30 years old), and as a result, they were at a lesser risk of getting LC than older people. The fact that younger people make up the majority of Syria’s population.43 may explain why many younger people are participating in the demonstrations. Nevertheless, increasing awareness among young people may be an efficient technique for building a culture of early detection of LC symptoms and rapid medical care for any probable LC symptoms. This would be a civilization where early recognition of LC symptoms is a cultural norm.\n\n\n5. Conclusion\n\nThe knowledge of Syrian medical professionals on LC symptoms and risk factors was limited. Factors related to heightened awareness were female gender, postsecondary education, and nonsmoking status. The most recognized respiratory LC symptom was ‘persistent shortness of breath’, whereas the most recognized non-respiratory LC symptom was ‘unexplained weight loss. This research emphasizes the need for education and awareness efforts, especially in low and middle-income countries like Syria, where the prevalence of LC is significant yet often misdiagnosed due to a lack of knowledge about the disease.",
"appendix": "Data availability\n\nZenodo: Awareness of Lung Cancer Risk Factors and Symptoms in Syria: An Online Cross-Sectional Study, https://doi.org/10.5281/zenodo.10148451. 44\n\nThis project contains the following underlying data:\n\n• lung cancer.xlsx\n\nZenodo: Awareness of Lung Cancer Risk Factors and Symptoms in Syria: An Online Cross-Sectional Study, https://doi.org/10.5281/zenodo.10148451. 44\n\nThis project contains the following extended data:\n\n• S1 Table.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\nElshami M, Abukmail H, Aqel W, et al.: Awareness of Palestinians about lung cancer symptoms: a national cross-sectional study. BMC Pulm. Med. 2022; 22(1): 135. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWHO: Cancer. Reference SourceReference Source\n\nDuffy MJ, O’Byrne K: Tissue and Blood Biomarkers in Lung Cancer: A Review. Adv. Clin. Chem. 2018; 86: 1–21. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nDuruisseaux M, Esteller M: Lung cancer epigenetics: From knowledge to applications. Semin. Cancer Biol. 2018; 51: 116–128. PubMed Abstract | Publisher Full Text\n\nAnsari J, Shackelford RE, El-Osta H: Epigenetics in non-small cell lung cancer: from basics to therapeutics. Transl. Lung Cancer Res. 2016; 5(2): 155–171. PubMed Abstract | Publisher Full Text | Free Full Text\n\nToumazis I, Bastani M, Han SS, et al.: Risk-Based lung cancer screening: A systematic review. Lung Cancer. 2020; 147: 154–186. PubMed Abstract | Publisher Full Text\n\nNooreldeen R, Bach H: Current and Future Development in Lung Cancer Diagnosis. Int. J. Mol. Sci. 2021; 22(16). PubMed Abstract | Publisher Full Text | Free Full Text\n\nJones GS, Baldwin DR: Recent advances in the management of lung cancer. Clin. Med. (Lond.). 2018; 18(Suppl 2): s41–s46. Publisher Full Text\n\nNwagbara UI, Ginindza TG, Hlongwana KW: Lung cancer awareness and palliative care interventions implemented in low-and middle-income countries: a scoping review. BMC Public Health. 2020; 20(1): 1466. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElshami M, Abukmail H, Aqel W, et al.: Awareness of Palestinians about lung cancer symptoms: a national cross-sectional study. BMC Pulm. Med. 2022; 22(1): 135. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMansour AA, Elshami M, Al-Ser M, et al.: P2.11-01 Awareness of Lung Cancer Risk Factors in Palestine: Current Situation and Future Directions. J. Thorac. Oncol. 2022; 17(9, Supplement): S148. Publisher Full Text\n\nPopulation, total - Syrian Arab Republic. Reference Source\n\nCrane M, Scott N, O’Hara BJ, et al.: Knowledge of the signs and symptoms and risk factors of lung cancer in Australia: mixed methods study. BMC Public Health. 2016; 16: 508. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElshami M, Al-Slaibi I, Abukmail H, et al.: Knowledge of Palestinian women about cervical cancer warning signs: a national cross- sectional study. BMC Public Health. 2021; 21(1): 1779. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElshami M, Thalji M, Abukmail H, et al.: Knowledge of cervical cancer risk factors among Palestinian women: a national cross-sectional study. BMC Womens Health. 2021; 21(1): 385. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElshami M, Yaseen A, Alser M, et al.: Knowledge of ovarian cancer symptoms among women in Palestine: a national cross-sectional study. BMC Public Health. 2021; 21(1): 1992. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElshami M, Elshami A, Alshorbassi N, et al.: Knowledge level of cancer symptoms and risk factors in the Gaza Strip: a cross-sectional study. BMC Public Health. 2020; 20(1): 414. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElshami M, Bottcher B, Alkhatib M, et al.: Perceived barriers to seeking cancer care in the Gaza Strip: a cross-sectional study. BMC Health Serv. Res. 2021; 21(1): 28. PubMed Abstract | Publisher Full Text | Free Full Text\n\nInternational Agency for Research on Cancer: Lung Cancer Fact Sheet.2020. Accessed 1 November 2022. Reference Source\n\nSung H, Ferlay J, Siegel RL, et al.: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021; 71(3): 209–249. PubMed Abstract | Publisher Full Text\n\nMoffat J, Bentley A, Ironmonger L, et al.: The impact of national cancer awareness campaigns for bowel and lung cancer symptoms on sociodemographic inequalities in immediate key symptom awareness and GP attendances. Br. J. Cancer. 2015; 112 Suppl 1(Suppl 1): S14–S21. PubMed Abstract | Publisher Full Text\n\nIronmonger L, Ohuma E, Ormiston-Smith N, et al.: An evaluation of the impact of large-scale interventions to raise public awareness of a lung cancer symptom. Br. J. Cancer. 2015; 112(1): 207–216. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPower E, Wardle J: Change in public awareness of symptoms and perceived barriers to seeing a doctor following Be Clear on Cancer campaigns in England. Br. J. Cancer. 2015; 112(1): S22–S26. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSaab MM, Noonan B, Kilty C, et al.: Awareness and help-seeking for early signs and symptoms of lung cancer: A qualitative study with high-risk individuals. Eur. J. Oncol. Nurs. 2021; 50: 101880. PubMed Abstract | Publisher Full Text\n\nSimon AE, Juszczyk D, Smyth N, et al.: Knowledge of lung cancer symptoms and risk factors in the U.K.: development of a measure and results from a population-based survey. Thorax. 2012; 67(5): 426–432. PubMed Abstract | Publisher Full Text\n\nDesalu OO, Fawibe AE, Sanya EO, et al.: Lung cancer awareness and anticipated delay before seeking medical help in the middle-belt population of Nigeria. Int. J. Tuberc. Lung Dis. 2016; 20(4): 560–566. PubMed Abstract | Publisher Full Text\n\nWard KD, Eissenberg T, Rastam S, et al.: The tobacco epidemic in Syria. Tob. Control. 2006; 15 Suppl 1(Suppl 1): i24–i29. PubMed Abstract | Publisher Full Text\n\nRivera MP, Stover DE: Gender and lung cancer. Clin. Chest Med. 2004; 25(2): 391–400. Publisher Full Text\n\nCunningham Y, Wyke S, Blyth KG, et al.: Lung cancer symptom appraisal among people with chronic obstructive pulmonary disease: A qualitative interview study. Psychooncology. 2019; 28(4): 718–725. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWalter FM, Rubin G, Bankhead C, et al.: Symptoms and other factors associated with time to diagnosis and stage of lung cancer: a prospective cohort study. Br. J. Cancer. 2015; 112 Suppl 1(Suppl 1): S6–S13. PubMed Abstract | Publisher Full Text\n\nLubuzo B, Ginindza T, Hlongwana K: The barriers to initiating lung cancer care in low-and middle-income countries. Pan Afr. Med. J. 2020; 35: 38. Publisher Full Text\n\nFriedemann Smith C, Whitaker KL, Winstanley K, et al.: Smokers are less likely than non-smokers to seek help for a lung cancer ‘alarm’ symptom. Thorax. 2016; 71(7): 659–661. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShah SC, Kayamba V, Peek RM Jr, et al.: Cancer Control in Low- and Middle-Income Countries: Is It Time to Consider Screening? J. Glob. Oncol. 2019; 5: 1–8. PubMed Abstract | Publisher Full Text\n\nHaastrup PF, Jarbøl DE, Balasubramaniam K, et al.: Predictive values of lung cancer alarm symptoms in the general population: a nationwide cohort study. NPJ Prim. Care Respir. Med. 2020; 30(1): 15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSyria Population: Syria Population clock (live).Reference Source\n\nWorld Population Dashboard Syrian Arab Republic: Syrian Arab Republic - Overview.Reference Source\n\nAlmoshantaf MB: Awareness of Lung Cancer Risk Factors and Symptoms in Syria: An Online Cross-Sectional Study. [Data set]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "256618",
"date": "25 Apr 2024",
"name": "Mohamad Saab",
"expertise": [
"Reviewer Expertise lung cancer",
"cancer awareness",
"systematic reviews",
"cross-sectional research",
"testicular cancer."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for inviting me to review this manuscript which I have read with interest. Please see below my comments to improve this manuscript: GENERAL COMMENTS\n“lung cancer patients” replace with “patients with lung cancer” throughout the manuscript. Either run this paper by a native English speaker or use editing services since there are a number of errors in spelling, syntax, sentence structure etc. which distract from content. Some statements and conclusions made are not relevant to this study and read like they were written for a different study altogether.\nABSTRACT\n30.9% indicated they were smoking cigarettes (as opposed to are). “The overall mean score of knowledge regarding closed questions about risk factors of lung cancer was 4.29” you must indicate out of a possible maximum score of XXX, the overall mean score for knowledge… “Our findings showed that cigarette smokers have a lower probability of having adequate knowledge toward lung cancer risk factors than a non-smoker (AOR=0.73, COR=0.68, P-value<0.05)” rephrase: “We also found that cigarette smokers had a lower probability of having adequate knowledge toward lung cancer risk factors in comparison to non-smokers (AOR=0.73, COR=0.68, P-value<0.05)” “We also defined that females have higher statistically significant odds (AOR=1.3, COR=1.38, P-value<0.05) for being knowledgeable about the symptoms of lung cancer compared to the male sample study.” Do you mean we also found? The manuscript requires proofreading. “Knowledge toward” or “knowledge of”? choose one and use consistently throughout the paper.\nINTRODUCTION\nWritten as one long paragraph. This disrupts flow. Make sure to use new paragraphs to present new ideas. I can easily see 5 to 6 different paragraphs here. “Therefore, raising public knowledge and awareness of lung cancer is crucial for early detection and treatment.16 It is believed that low-income countries and high tobacco consumption have less knowledge of symptoms and contributing factors of lung cancer, resulting in less effective treatment and a low survival rate.1,4” add to this that population-based research aimed to promote lung cancer awareness, help-seeking and early detection is conducted predominantly in Western countries. Please cite this paper to back this up: (Saab MM, et al., 2021)[ Ref 1]\nMETHODS\n“Then, the questionnaire was translated into Arabic by healthcare professionals in order to be easily understood and answered for the participants, which the utilized questionnaire was uploaded as extended data (see data availability statement)” this sentence is structurally incorrect and does not make sense. Do you mean: “Then, the questionnaire was translated to Arabic by healthcare professionals to ensure that it is easily understood by participants. The questionnaire can be found in extended data.” “Which was generate at google form website” do you mean “which was generated using Google Forms?” Unfortunately, there are issues with English language throughout. I encourage you to either run this paper by a native English speaker or use editing services. These errors distract from the content. I will stop making these corrections at this point. “Specific collaborators from many medical Syrian colleges (Data Collection Group) were responsible to collect the data by disrupting the online survey, which was generate at google form website, on social media platforms such as WhatsApp, Telegram, and Facebook.” Do you mean distributing? Also, how was the questionnaire distributed on these platforms? Facebook groups? Sponsored ads? Who was targeted? As for WhatsApp, as this is a mobile phone messaging application, were participants’ phone numbers obtained? Pilot study: How many people filled the questionnaire during the pilot study? Were these responses included in the final analysis? Were any changes made to the instrument following the pilot study?\nRESULTS\n“We define that 2303 participants were invited to participate in this study, and 52 participants refused to complete the received online survey, so the final sample size of the study participants was 2251.” Not clear what is meant by “we define” also, how did you determine how many participants were invited to participate and how many refused if you sent the questionnaire online via social media? Usually, the reach of the survey and refusal cannot be determined in social media-based surveys. Again, a lot of spelling/English errors here. “3.2 Summary of participants’ knowledge scores on lung cancer risk factors and symptoms.” The section under this heading does not make sense.\nDISCUSSION\nOverall, well written. Again, the discussion must be broken down to several paragraphs to ensure better flow. An argument can be made that early help-seeking is not only the responsibility of the person at risk for LC. Healthcare professionals must also be equipped with the means to “pull” these people into the appropriate services. See these two papers: (Saab MM, et al., 2022)[ Ref 2] , (Saab MM, et al., 2022)[ Ref 3]\nSTRENGTHS AND LIMITATIONS\nDo you mean Syria? (as opposed to Palestine). You mention here that the survey was administered in person, yet in the methods above you say it was an online questionnaire. These discrepancies are concerning. The use of social media could have led to the younger age group participating in this study. “in the demonstrations” what demonstrations? The last sentence in this section reads like a recommendation and not a strength/limitation.\nCONCLUSION\nI refer to your exclusion criteria under section 2.1 earlier: “Participants who were non-Syrians, students or workers in healthcare facilities were excluded from the study” yet in your conclusion you state “The knowledge of Syrian medical professionals on LC symptoms and risk factors was limited” this reads like a conclusion for a different paper altogether. This is a major concern.\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?\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": []
},
{
"id": "274919",
"date": "14 May 2024",
"name": "Robert Smith",
"expertise": [
"Reviewer Expertise Epidemiology of cancer",
"Cancer Screening"
],
"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 conducted a survey to measure knowledge and awareness of symptoms of lung cancer.\n\nComments: In the abstract, a reader will not understand knowledge scores, so suggest the authors describe the knowledge levels instead of using scores. Please also adhere to IASLC language guidelines to describe people who currently or ever smoked. Specifically, avoid using the term \"smoker,\" since it results in stigma.\n\nI'm surprised at the high level of education in most of the survey respondents. Probably this warrants a comment.\nIn the discussion, the authors state that lung cancer is typically diagnosed late due to lack of education about the disease and symptoms. Probably it should be said that lack of knowledge is a factor in later stage at diagnosis, since most lung cancer symptoms do not appear until the disease is quite advanced. Too often, also, health care professionals dismiss symptoms as likely due to something less worrisome (not lung cancer) especially in people who don't smoke, or never smoked. The next statement claims greater knowledge would result in earlier diagnosis and faster initiation of treatment. Probably, but some citations would be useful to support this statement. Reference 8 provides some insights, but we have to infer that the presence of symptoms led to the detection--hence, the awareness.\n\nIn the 3rd paragraph, I'm not sure the 4 references (28-31) truly demonstrate that greater awareness of symptoms leads to those symptoms prompting the patient to seek medical care. I think you can infer that this likely would be the case, but I don't see a direct correlation. If I have missed something, suggest that the authors describe these findings more clearly. I do accept these observations, as well as just good sense, should lead to the goal of raising awareness with the hope that it will lead to earlier diagnosis.\n\nOne thing that warrants discussion is the importance of having health care professionals prepared to consider the possibility of lung cancer when patients present with symptoms. Delays in diagnosis are influenced by health care workers wishing to be reassuring that a common symptom (a cough) probably has a less worrisome cause than lung cancer.\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/13-172
|
https://f1000research.com/articles/13-171/v1
|
11 Mar 24
|
{
"type": "Research Article",
"title": "Content analysis of policy documents related to non-communicable diseases prevention and control in Sri Lanka: a developing country in the South-East Asia",
"authors": [
"Ishanka Talagala",
"Chrishantha Abeysena",
"Rajitha Wickremasinghe",
"Chrishantha Abeysena",
"Rajitha Wickremasinghe"
],
"abstract": "Background Health policies form the foundation for provisioning best level care and are important for all stakeholders including patients and healthcare providers. Health policy analysis and evaluation allows policy makers to improve an existing policy, terminate a non-effective policy and to successfully implement future policies. The objective was to assess the coherence between the two local policy documents on NCD prevention and control in Sri Lanka, the national NCD policy (NCD policy) and the multisectoral action plan (MSAP), and to assess the consistency of MSAP with the global action plan for NCDs.\n\nMethods The content analysis of the NCD policy and MSAP of Sri Lanka was conducted based on the modified criteria developed to the ‘Analysis of determinants of policy impact’ model, by two reviewers independently. Coherence between MSAP and the global NCD action plan were also assessed by two reviewers independently. Consensus for discrepancy was achieved through discussion.\n\nResults Accessibility was the strongest criteria for the NCD policy, while, resources and obligations were the weakest. Goals and monitoring and evaluation criteria were the strongest in the MSAP. Requirement for improvement were identified in policy background, goals, monitoring and evaluation, and public opportunities for the NCD policy. Accessibility, policy background, resources, public opportunities and obligations require further improvement in the MSAP. The MSAP is well coherent with the global road map for NCD prevention and control.\n\nConclusion Policy documents related to NCD prevention and control in Sri Lanka are coherent with the global action plan, while, there are areas within the local policy documents that need to be improved to enhance the coherence between the local documents. Lessons learnt by this activity need to be utilized by Sri Lanka and other countries to improve the uniformity between the NCD policy documents within the country as well as internationally.",
"keywords": [
"Non communicable diseases",
"policy",
"analysis",
"content",
"Sri Lanka",
"developing country",
"Asia",
"documents"
],
"content": "Introduction\n\nHealth policy is a plan, a statement of decisions, that is taken by those with responsibility to direct the investments and actions towards improving the health of the people, either by improving health care or by preventing diseases. It could manifest as a law, regulation, procedure, or guidelines (Buse, Mays, & Walt, 2005). Health policy makers therefore have an important role to play in the process of health policy formulation, as they have the responsibility of developing a logical pathway to address a particular health issue considering the demand of the people and limited resources at hand. This is of utmost relevance and importance in low resource countries like Sri Lanka.\n\nHealth policy evaluation and analysis therefore allows the policy makers to improve an existing policy, terminate a non-effective policy and to successfully implement future policies. Despite its importance, however, policy analysis and evaluation in lower- and middle-income countries like Sri Lanka is not a common practice. In Sri Lanka, the state (through the Ministry of Health) is both the main provider and the purchaser of health services, and is also involved in policy making, regulating, research and training along with its administrative functions. Therefore, one of the issues that the Ministry of Health faces is the information asymmetry, as usually the relevant information is available only within a particular unit or an institution. As in many other developing countries, Sri Lanka has weak regulations, issues with poor documentation, low human and other resources, low capacity to monitor and evaluate, short-term nature of funds for policy research and dependence on external donor funds (Walt et al., 2008).\n\nNevertheless, assessing the internal validity of the policy documents is one way of improving the effective implementation of a health policy. Here, internal validity refers to the clarity and comprehensiveness of the policy statements within all the relevant policy documents, in order to achieve the expected outcomes of a particular policy. Analysis of the relevant policy documents, therefore, is a straightforward method to assess how they influence the successful implementation of the policy. In addition to internal validity of the local policy documents, it is important that a country’s policy documents are in line with international policies and global action plans. This would allow all the countries across the globe to implement certain actions collectively to combat a public health issue, allow for comparisons among the countries and share knowledge and resources.\n\nNon communicable diseases (NCDs) account for 75% of all deaths while these diseases are among the top ten causes of deaths in Sri Lanka (Senaratne & Mendis, 2018). 54% of NCD-related deaths among males and 36% of NCD-related deaths among females in 2015 were below 70 years of age (Senaratne & Mendis, 2018). Pre-mature mortality and the chronic debilitating nature of these diseases requiring long term care and management, have major economic impacts on the individual, family and the country. In the Sri Lankan health system, where the bulk of the healthcare cost is borne by the state, this results in a major impact on the country’s economic development. Therefore, the development of effective NCD prevention policies and programmes is essential and worth investing in.\n\nThe national NCD prevention and control programme (administered by the ‘NCD unit’ and referred to hereafter in the document) was initiated in 2009; it was the first major attempt to address the spectrum of NCDs through documentation of the National policy and strategic framework for prevention and control of chronic non-communicable diseases (referred to as ‘NCD policy’ hereafter) (Ministry of Health Sri Lanka, 2010). This policy addresses the prevention and control of cardiovascular diseases including coronary heart diseases, cerebrovascular diseases and hypertension; diabetes mellitus; chronic respiratory diseases and chronic renal diseases while other NCDs including cancers and mental illnesses are addressed through separate policy documents (Ministry of Health Sri Lanka, 2010). The policy aims at addressing these diseases and their risk factors through primordial, primary, secondary and tertiary preventive strategies at different stages of the life cycle at different settings (Ministry of Health Sri Lanka, 2010). Considering the important roles played by different stakeholders in the prevention and control of the NCDs, the Ministry of Health documented the national multisectoral action plan for the prevention and control of non-communicable diseases (MSAP) (Ministry of Health Nutrition and Indigenous Medicine Sri Lanka, 2016), which iterates the responsibilities of, and activities for, each stakeholder to implement, to achieve the ultimate policy targets by the year 2025. Thus, the NCD unit of the Ministry of Health oversees the activities of stakeholders in order to achieve the NCD policy outcomes.\n\nBased on the Sri Lankan STEPS survey data of 2021 (Ministry of Health Sri Lanka, 2021), the overall current tobacco users has increased by 1.5%, with a 10.8% increase in current smokeless tobacco use, compared to 2015 (Ministry of Health Nutrition and Indigenous Medicine Sri Lanka, 2015). Further, current alcohol consumers have increased by 15.6%; the proportion with insufficient physical activity has increased by 14.5%; the proportion who are overweight has increased by 34.5%; the proportion who are obese has increased by 86.4%; the proportion of hypertensives has increased by 33.3%; the proportion with raised fasting blood glucose has increased by 97.3% and the proportion with high total cholesterol level has increased by 106.4%, by 2021 (Ministry of Health Sri Lanka, 2021) compared to 2015 (Ministry of Health Nutrition and Indigenous Medicine Sri Lanka, 2015). However, current smokers have reduced by 6%; the proportion who consumed less than five servings of fruits and/or vegetables per day has reduced by 6.5%; the proportion who always or often added salt or salty sauces to their food before they eat or as they are eating has reduced by 83.9%; and the proportion of those who always or often consumed processed food high in salt has reduced by 69.2% compared to that of 2015 (Ministry of Health Nutrition and Indigenous Medicine Sri Lanka, 2015).\n\nAlthough, these data were collected in 2021, amidst the COVID-19 pandemic, it is important to note that these results were observed following the effective period of the NCD policy and the MSAP. Hence, as the first step in evaluating the NCD policy implementation, it is imperative to evaluate the NCD policy documents for coherence internally as well as internationally. This study, therefore, evaluated the policy documents related to the prevention and control of NCDs in Sri Lanka for their internal validity. Since it is important that the country’s activities to combat NCDs are in line with the global actions, the MSAP was also compared with the WHO global action plan for the prevention and control of NCDs 2013-2020 (referred to as ‘global action plan’ hereafter) (World Health Organization, 2013), to assess its consistency with the global road map.\n\n\nMethods\n\nCheung et al. (2010) developed certain criteria to assess the alignment between policy statements and expected policy outcomes among policy documents related to the Australian chronic care programme. These criteria were based on the criteria validated by Rütten et al. (2003), which were initially based on von Wright’s concept of ‘logic of events’. This logic of events explains the factors that determine human action and the logic underlying the interaction between these factors. Thus, the model explains how the interaction between wants, abilities, duties and opportunities affect human behaviour, ultimately affecting the impact of a health policy. It explains that in certain circumstances with created opportunities for action through health policies, an individual would take actions based on their wants and duties, within their abilities. And all these actions would ultimately create new opportunities, resulting in further action (Rütten et al., 2003).\n\nTranslating this logic of events into policy level, Rütten et al. (2011) developed and validated the ‘Analysis of determinants of policy impact (ADEPT) model’. In the ADEPT model, ‘wants’ gets translated in to ‘goals’; ‘duties’ to ‘obligations’; ‘abilities’ to ‘resources’; and ‘opportunities’ refers to the institutional/organizational, political and public opportunities, that would ultimately affect the impact of a health policy (Rütten et al., 2011). This model has been utilized in several policy analyses and development projects worldwide (Rütten et al., 2011). The logic of events model and the ADEPT model consider the interaction between the determinants of human behaviour and appreciate the fact that these relationships change with the context. This is similar to the influencing factors in the policy formulation process, which are ever changing as well.\n\nCheung et al. (2010) modified the criteria in the ADEPT model by adding 16 new criteria. Criteria with strong relevance to analysis of the policy context were excluded as it was not possible to assess the context through analysing the documents. Further details of the changes made to the original ADEPT model and the reasons are published elsewhere (Cheung et al., 2010).\n\nThe NCD prevention and control activities implemented in Sri Lanka are mainly based on the key strategic areas identified by the NCD policy (Ministry of Health Sri Lanka, 2010). The implementation of these key strategies is through the activities identified in the MSAP (Ministry of Health Nutrition and Indigenous Medicine Sri Lanka, 2016). However, at the implementation stage, other health policies such as the national nutrition policy, the national health promotion policy and the national authority on tobacco and alcohol (NATA) act govern the implementation as well. Figure 1 shows the map of the main policy documents related to the NCD prevention programme of Sri Lanka. However, since the national NCD policy and the MSAP are the policy documents that are directly considered for the prevention and control of NCDs in Sri Lanka, the analysis of the current study was limited to these two documents.\n\nAnalysis of the policy documents related to the prevention and control of NCDs in Sri Lanka was based on the modified criteria developed by Cheung et al. (2010), which are given in Table 1.\n\n\n\n1. The policy document is accessible [hard copy and online].\n\n\n\n1. The scientific grounds of the policy are established.\n\n2. The goals are drawn from a conclusive review of literature.\n\n3. The source of the health policy is explicit.\n\ni. Authority [one or more persons, books scientific articles or sources of information].\n\nii. Quantitative or qualitative analysis.\n\niii. Deduction [premises that have been established from authority, observation, intuition, or all three].\n\n4. The policy encompasses some set of feasible alternatives.\n\n\n\n1. The goals are explicitly stated [the goals are officially spelled out].\n\n2. The goals are concrete enough [quantitative where possible and qualitative where not] to be evaluated later.\n\n3. The goal is clear in its intent and in the mechanism with which to achieve the desired goals, yet does not attempt to prescribe in detail what the change must be.\n\n4. The action centres on improving the health of the population.\n\n5. The policy is supported by evidence of external consistency in logically drawing a health outcome from the goals and policy outcome.\n\n6. The policy is supported by internal validity in logically drawing a health outcome from the goals and policy outcome.\n\n\n\n1. Financial resources are addressed [there are sufficient financial resources]\n\ni. The cost of condition to community has been mentioned.\n\nii. Estimated financial resources for implementation of the policy is given.\n\niii. Allocated financial resources for implementation of the policy are clear.\n\niv. There are reward/sanction for spending the allocated resources on other programmes.\n\n2. Human resources are addressed [there is enough personnel].\n\n3. Organizational capacity is addressed [my organization has the necessary capacities].\n\n\n\n1. The policy indicated monitoring and evaluation mechanisms.\n\n2. The policy nominated a committee or independent body to perform the evaluation.\n\n3. The outcome measures are identified for each of the explicit and implicit objectives.\n\n4. The data, for evaluation, collected before, during and after the introduction of the new policy.\n\n5. Follow up takes place after a sufficient period to allow the effects of policy change to become evident.\n\n6. Other factors that could have produced the change [other than policy] identified.\n\n7. Criteria for evaluation are adequate and clear.\n\n\n\n1. Co-operation between political levels involved [federal, state, area health] has either worsened or improved.**\n\n2. Support from other sectors [economy, science, justice] has either worsened or improved.**\n\n3. The political climate has either worsened or improved.**\n\n4. Cooperation between public and private organizations has either worsened improved.**\n\n5. The lobby for the action has either worsened or improved.**\n\n\n\n1. The media’s interest has either worsened or improved.**\n\n2. The population supports the action.**\n\n3. Multiple stakeholders are involved.\n\n4. Primary concerns of stakeholders recognised and acknowledged to obtain long term support.\n\n5. There is media’s interest.**\n\n\n\n1. The obligations of the various implementers are specified-who has to do what?\n\n2. The action is part of health professionals’ existing duties.**\n\n3. Scientific results are compelling for action.\n\n4. Health professional obliged to the population to act in this area.**\n\n** Excluded criteria from the current analysis as these items could not be directly assessed by assessing only the policy documents.\n\nCriteria A to H except criterion F, were considered as ‘fulfilled/strong’ if all the criteria were addressed within the policy document; if only some criteria were addressed, it was considered as ‘room for improvement’ and if none of the criteria were addressed, it was considered as ‘not fulfilled/weak’ (Cheung et al., 2010).\n\nTwo expert reviewers independently analysed the national NCD policy and the MSAP using the criteria given in Table 1, in 2020, prior to the COVID-19 pandemic in the country. Any discrepancy between the two reviewers for any of the criteria were further discussed to arrive at a consensus, and any further disagreement was resolved through an assessment by a third independent reviewer.\n\nFurthermore, the MSAP was compared with the global action plan for combating NCDs, for consistency between the two policy documents, by the two expert reviewers independently as well. Any discrepancy between the two reviewers for any of the criteria were further discussed to arrive at a consensus.\n\n\nResults\n\nTables 2a and 2b include review of the NCD policy and the MSAP based on the criteria given in Table 1.\n\nAccessibility: the two core policy documents for prevention and control for NCDs are currently accessible on the internet, the Ministry of Health website and the unit website. And the NCD unit web site is linked to the Ministry of Health website as well. Nevertheless, the accessibility and the availability of these documents to the field health staff, who are the implementers of the NCD policy and the action plan, is unclear and could not be assessed in this study.\n\nPolicy background: The NCD policy and the MSAP was written with authority, using statistics and deduction to provide the scientific background for the policy. The literature review included peer reviewed journal articles, reports of the World Health Organization, Ministry of Health Sri Lanka, World Bank, and information from the Registrar General’s Department.\n\nGoals: Goals in both the NCD policy and the MSAP were explicit, concrete and were qualitative. The actions are centred on improving the health of the population. The goal of the MSAP is more or less similar to the goal of the global action plan for the prevention and control of NCDs: 2013-2020 (World Health Organization, 2013) (Table 3), giving more emphasis to multisectoral collaboration while, the goal of the NCD policy is stated as “To reduce the burden due to chronic NCDs by promoting healthy lifestyles, reducing the prevalence of common risk factors, and providing integrated evidence-based treatment options for diagnosed NCD patients” (Ministry of Health Sri Lanka, 2010). The NCD policy objective states the quantitative policy goal of a 2% annual reduction of premature mortality due to NCDs through implementation of the key strategies to combat NCDs in the country (Ministry of Health Sri Lanka, 2010).\n\n\n\n1. A 25% relative reduction in premature mortality from cardiovascular disease, cancer, diabetes or chronic respiratory diseases\n\n2. At least 10% relative reduction in the harmful use of alcohol, as appropriate, within the national context\n\n3. A 10% relative reduction in prevalence of insufficient physical activity\n\n4. A 30% relative reduction in mean population intake of salt/sodium\n\n5. A 30% relative reduction in prevalence of current tobacco use in persons aged 15+ years\n\n6. A 25% relative reduction in prevalence of raised blood pressure and or contain the prevalence of raised blood pressure, according to national circumstances\n\n7. Halt the rise in diabetes and obesity\n\n8. At least 50% of eligible people receive drug therapy and counselling (including glycaemic control) to prevent heart attacks and strokes\n\n9. An 80% availability of the affordable basic technologies and essential medicines, including generics, required to treat major non-communicable diseases in both public and private facilities\n\n\n\n1. A 25% relative reduction in premature mortality from cardiovascular disease, cancer, diabetes or chronic respiratory diseases\n\n2. A 10% relative reduction in the use of alcohol\n\n3. A 10% relative reduction in prevalence of insufficient physical activity\n\n4. A 30% relative reduction in mean population intake of salt/sodium\n\n5. A 30% relative reduction in prevalence of current tobacco use in persons aged over 15 years\n\n6. A 25% relative reduction in prevalence of raised blood pressure and or contain the prevalence of raised blood pressure\n\n7. Halt the rise in obesity and diabetes\n\n8. A 50% of eligible people receive drug therapy and counselling (including glycaemic control) to prevent heart attacks and stroke\n\n9. An 80% availability of affordable basic technologies and essential medicines including generics, required to treat major non-communicable diseases in both public and private facilities\n\n\n\n• Establish A National NCD council and convene regular meetings bi annually\n\n• Develop advocacy packages on prevention and control of NCDs for politicians, each level in the health sector and non- health sectors at national, provincial and district levels\n\n• Advocacy meetings for the upper-level managers of the relevant ministries, authorities and departments at the national, provincial and district levels\n\n• Advocacy meeting for the political authorities\n\n• Design and launch a public education campaign on NCD\n\n\n\n• Integrate the prevention and control of NCDs in to national planning processes and broader development agendas\n\n• Share process indicators and global NCD targets with the national team working on Sustainable Development Goals\n\n\n\n• Conduct advocacy meetings with the officers in the Ministry of Finance and UN agencies for adequate funding\n\n• Initiate action to obtain the required human resources for NCD related work\n\n• Capacity building of relevant staff on NCD Prevention and Control\n\n\n\n• Conduct workshops at National, provincial and district levels to map stake holders and to design health promotion activities\n\n• Establish provincial and district level multi sectoral committees and monitor implementation of existing policies\n\n\n\n• Conduct advocacy meetings with the officers in the Ministry of Finance and UN agencies\n\n\n\n• Ensure activities relevant to different units of the MoH are coordinated to strengthen the linkages between different units of Ministry of Health for NCD prevention and control\n\n\n\n• Already available\n\n\n\n• Initiate action to obtain the required human resources for NCD related work\n\n• Capacity building of relevant staff on NCD Prevention and Control\n\n\n\n• Reduce affordability of tobacco products by increasing tobacco excise taxes\n\n• Create by law completely smoke-free environments in all indoor workplaces, public places and public transport\n\n• Warn people of the dangers of tobacco and tobacco smoke through effective health warnings and mass media campaigns\n\n• Ban all forms of tobacco advertising, promotion and sponsorship\n\n\n\n• Accelerate full implementation of FCTC\n\n• Bring about amendments to NATA Act 2006\n\n• Advocate to raise tobacco tax\n\n• Setup tobacco cessation services\n\n• Strengthen the services available for tobacco cessation\n\n• Improve community awareness on tobacco use including the use of smokeless tobacco\n\n• Conduct trade seminars in view of establishing tobacco free zones\n\n• Conduct awareness programmes for media personnel\n\n• Conduct tobacco research\n\n• Strengthen NATA\n\n• Train the health staff on tobacco (including smokeless) prevention and control\n\n\n\n• Implement the National Alcohol Policy\n\n\n\n• Monitor prevalence of alcohol among adults and harmful effects of alcohol in the country and share the findings\n\n• Reduce alcohol related violence and injuries\n\n\n\n• Establish treatment and rehabilitation services related to alcohol\n\n\n\n• Establish a mechanism to implement, monitor and evaluate alcohol policy at national and district levels\n\n\n\n• Implement the National Alcohol Policy\n\n• Establish a mechanism to implement, monitor and evaluate alcohol policy at national and district levels\n\n\n\n• Implement the National Alcohol Policy\n\n• Establish a mechanism to implement, monitor and evaluate alcohol policy at national and district levels\n\n\n\n• Implement the National Alcohol Policy\n\n• Establish a mechanism to implement, monitor and evaluate alcohol policy at national and district levels\n\n\n\n• Implement the National Alcohol Policy\n\n• Establish a mechanism to implement, monitor and evaluate alcohol policy at national and district levels\n\n\n\n• Reduce alcohol related violence and injuries\n\n• Monitor prevalence of alcohol among adults and harmful effects of alcohol in the country and share the findings\n\n\n\n• Reduce production and sale of illicit alcohol\n\n• Monitor prevalence of alcohol among adults and harmful effects of alcohol in the country and share the findings\n\n\n\n• Conduct STEP survey every 4-5yrs\n\n\n\n• Accelerate the implementation of the diet component of the Global Strategy on Diet, Physical Activity and Health\n\n\n\n• Increase availability of fruits and vegetables\n\n\n\n• Conduct advocacy meetings for town planners, politicians to improve environmental changes to promote physical activity\n\n• Establish/Strengthen the PA programmes in work places\n\n• Strengthen the PA programmes in the schools\n\n• Improve facilities for physical activity for the community\n\n• Develop physical activity guidelines for public\n\n\n\n• Introduce food labeling to indicate unhealthy foods\n\n• Increase availability of food based dietary guidelines\n\n• Make available data and initiate policies to increase intake of healthy foods\n\n\n\n• Promote maternal and child nutrition\n\n\n\n• Develop and implement a national salt reduction strategy\n\n\n\n• Take measures to reduce trans-fat in processed foods\n\n\n\n• Improve awareness of the public on cardio metabolic risk of consuming unhealthy foods through a mass media campaign\n\n• Conduct awareness programmes on healthy foods and food based dietary guidelines\n\n• capacity building of health workers on food based dietary guidelines\n\n\n\n• Increase tax for unhealthy food\n\n\n\n• Increase availability and access to NCD screening services\n\n• Improve NCD management at Primary Health Care level\n\n• Improve access to services to manage cardiovascular diseases\n\n• Improve access to services to manage Diabetes Mellitus\n\n• Improve access to services to screen Chronic Respiratory Diseases (CRD) - Asthma and chronic obstructive pulmonary disease (COPD)\n\n• Improve access to services to manage CRD\n\n• Improve Cancers screening services\n\n\n\n• Develop policies for sustainable health financing for NCD\n\n\n\n• Increase availability and access to NCD screening services\n\n• Publicize screening services through a mass media campaign\n\n\n\n• Capacity building of healthcare workers to manage NCDs\n\n• Establish a Council to produce clinical guidelines on NCDs\n\n\n\n• improve availability and access to essential NCD medicine and technologies\n\n• Improve the diagnostic and treatment facilities for cancer\n\n\n\n• Establish health promotion settings\n\n• Improve NCD management at Primary Health Care level\n\n\n\n• Improve availability and access to palliative care\n\n• Improve palliative care for cancer patients\n\n\n\n• Establish a national multi-disciplinary research committee\n\n• Prepare a national research agenda for NCD\n\n• Establish a forum/committee to translate research in to policy action\n\n\n\n• Capacity building of officers on research\n\n\n\n• Identify research questions to support the implementation, monitoring and evaluation of the NCD action plan\n\n• Conduct priority research\n\n\n\n• Conduct priority research\n\n• Capacity building of officers on research\n\n\n\n• Develop a monitoring framework to assess progress towards the goal\n\n• Conduct periodic NCD programme evaluation\n\n• Monitoring and evaluation framework for health system intervention\n\n\n\n• Improve staff and resources dedicated for data management in NCD\n\n\n\n• Improve staff and resources dedicated for data management in NCD\n\n\n\n• Integrate NCD monitoring into HMIS\n\n\n\n• Conduct national review meetings\n\n• Conduct district review meetings\n\nResources: Financial resources for the implementation of the NCD policy is included as a strategic objective in the NCD policy and is worded as “Ensure sustainable financing mechanisms that support cost-effective health interventions at both preventive and curative sectors” (Ministry of Health Sri Lanka, 2010), even though the allocated amount for the implementation of the policy, or the financial resources are not mentioned. The cost to the community due to NCDs is not explicitly mentioned either. Moreover, human resources for the implementation of the NCD policy is also addressed as a strategic objective within the policy as “Enhance human resource development to facilitate NCD prevention and care” (Ministry of Health Sri Lanka, 2010).\n\nThe estimated financial resources for the implementation of the MSAP has been estimated as LKR 15.2 billion (approximately USD 46,704,563 currently, based on the conversion rate of 1 USD = LKR 325.45 on 23rd October 2023) at its launch in 2016 (Ministry of Health Nutrition and Indigenous Medicine Sri Lanka, 2016). The MSAP identifies the sources of funding including a loan provided by the World Bank for health system improvement, and a proposed loan from JICA (Ministry of Health Nutrition and Indigenous Medicine Sri Lanka, 2016). As in the policy document, human resources and the organizational capacity were not addressed in the MSAP possibly due to specific activities not being identified to achieve the strategic objectives within the NCD policy.\n\nMonitoring and evaluation: In the NCD policy, the coordination mechanisms are clearly articulated with the onus being on the NCD unit under the Director NCD, the focal point in the Ministry of Health for policy implementation, monitoring and evaluation. The outcome measures, data required and criteria for evaluation, however, are not explicitly stated. A results-based monitoring and evaluation system was to be established to evaluate the implementation (Ministry of Health Sri Lanka, 2010). This gap is due to the lack of concrete goals and activities identified within the policy to achieve the ultimate policy objective. The policy does not mention about periodical follow up and monitoring to assess the effects of the policy.\n\nOn the other hand, the MSAP included a framework for monitoring progress in implementation based on inputs, processes and outcomes. Based on this framework, outcomes were to be assessed in the short-term (in 2018), the medium-term (in 2020) and in the long-term (in 2025). Although not explicitly stated, it appears that assessment of outcomes would be done by the NCD unit under the Director NCD of the Ministry of Health.\n\nPublic opportunities: The NCD policy and the National Health Council acknowledge stakeholder involvement and promote inter-sectoral and inter-ministerial collaboration. The National NCD steering committee has representation from Secretaries of relevant Ministries including that of Finance, Trade, Agriculture, Urban Planning, Education, Justice, Poverty Alleviation, and Social Welfare, and secretaries and directors of Provincial Health Ministries (Ministry of Health Sri Lanka, 2010). In the action plan, multiple stakeholders are engaged in preventive activities, and it is specified as who should do what and when. However, both the documents have failed to identify the primary concerns of the stakeholders.\n\nObligations: The obligations of the various implementers are clearly stated in the MSAP. However, granting of any rewards or penalties related to fulfilment of these obligations is unclear.\n\nThen, a comparison was made for congruence of the MSAP and the Global action plan for NCDs (Table 3).\n\nWhile the vision and goal of the MSAP were more or less similar to the global action plan (World Health Organization, 2013), the overarching principles, the nine voluntary global targets and the objectives of MSAP were the same as that of the global action plan (World Health Organization, 2013). The policy options iterated in the global action plan were then compared with the main activity areas identified in the national MSAP of Sri Lanka. All the policy options provided for countries in the WHO global action plan were found to be addressed via several activity areas in the MSAP of Sri Lanka (Table 3).\n\n\nDiscussion\n\nWe assessed the content and the comprehensiveness of the two main policy documents related to NCD prevention and control in Sri Lanka. These documents included the national policy and strategic framework for prevention and control of chronic non-communicable diseases - 2010 and the national multi-sectoral action plan for prevention and control of non-communicable diseases 2016-2020. Many of the evaluation criteria listed in Table 1 were met by the NCD policy and MSAP documents. Accessibility was the strongest for the NCD policy, while resources and obligations were the weakest. Goals and monitoring and evaluation criteria were the strongest in the MSAP. However, opportunities for improvement were identified in the policy background, goals, monitoring and evaluation, and public opportunities for the NCD policy. Accessibility, policy background, resources, public opportunities and obligations require further improvement in the MSAP. The comparison of the content of the MSAP and the WHO Global action plan for the prevention and control of non-communicable diseases 2013-2020 revealed that the vision, goal, overarching principles, the nine voluntary global targets and the objectives were more or less similar. Furthermore, there were similarities between the policy options identified in the global action plan and the various activities identified in the MSAP, indicating that the MSAP of Sri Lanka is in line with the global action plan as well.\n\nMapping of the policy documents related to NCD prevention and control enabled us to understand which documents are directly related with the NCD prevention and control and which are overlapping at the stage of implementation of the policy. The criteria developed by Cheung et al. (2010) enabled us to review and understand the comprehensiveness of the policy documents for NCD prevention and control in Sri Lanka. The criteria allowed a comprehensive content analysis of the policy documents and pinpoint the areas that require improvement. A comprehensive and clearly articulated policy document would increase the use of the policy document by the implementers as it clearly specifies the scientific background, and the different roles and responsibilities of stakeholders and implementers. This will directly increase the successful implementation of the policy as well.\n\nSince the national programmes are guided by the policy document and is implemented through the multi-sectoral action plan, it is essential that these documents are widely disseminated and easily accessible to all the stakeholders, especially to the programme implementers. It is also important that the dissemination mechanism be adapted to the facilities and ground realities of different countries. In Sri Lanka, while, the NCD policy has been effective from 2010-2020, it was reported that by 2012, only 24.2% in the country were computer literate, with only 20.6% having access to the internet (within and outside household) (Department of Census and Statistics Sri Lanka, 2012). Therefore, the availability and accessibility of policy documents by means other than through internet should have been promoted. However, these statistics have improved following the COVID-19 pandemic. Nevertheless, only 44.5% household population were using internet by the year 2021, with low usage in rural and estate sectors of the country (Department of Census and Statistics, 2021). Also, having the majority of health staff (perhaps doctors being the exception) and the population being technologically challenged with only 34.3% being computer literate and only 57.2% being digitally literate in the country in 2021 (again, with low computer and digital literacy in rural and estate sectors of the country) (Department of Census and Statistics, 2021), it is imperative that the policy documents be disseminated and made available and accessible through other mechanisms. However, given the background of limited printing due to unavailability of relevant resources in the current economic crises, it is essential that novel means need to be thought of in disseminating the policy documents.\n\nClear goal setting would strengthen a policy document as its use becomes easier for implementers, stakeholders and the public. Thus, setting clear goals to be achieved under each strategic objective of the NCD policy would increase the utilization of the policy and increase its successful implementation; in addition, it will make it easier for implementers, and internal and external evaluators to monitor and evaluate the implementation and the impacts of the policy.\n\nThe financial and non-financial resources required for implementation of the policy and the action plan should be explicitly stated in the documents. The estimated values and the action plan to obtain these resources along with a situational analysis on the currently available resources are important for the implementers of the policy. Documenting the current situation would allow easy evaluation of whether the required resources have been obtained or not during policy implementation. It would also allow policy implementers to prioritize activities, especially in low resource settings like in Sri Lanka. In addition, this will improve the understanding of the context within which the policy is implemented.\n\nDocumentation of the penalties for using allocated funds for any other activity would prevent disorganized use of funds based on personal or political opinion or influence, increasing the likelihood of successful implementation of the policy by ensuring the required flow of funds. This is important in low resource settings like Sri Lanka, with competing interests. Nevertheless, considering Sri Lanka, it is important to draw one’s attention towards the political and economic contexts within which the NCD policy and the MSAP have being effective. The country faced a separatist war till 2009, the global recession in 2009 largely affected developing countries like Sri Lanka and probably for many years to come (Koh & Yu, 2020), the slowing of the world economy since mid-2018 (Koh & Yu, 2020), the COVID-19 pandemic and the current economic crisis (Ahmed, 2023; World Bank, 2021) in the country resulted in diversion of funds and therefore has adversely affected the optimal implementation of the NCD policy. Hence, the impact of COVID-19 and the impact of the economic crises on the health system and other systems in the country need to be well considered in the future, when implementing and assessing public health policies including the NCD policy.\n\nDocumenting the monitoring and evaluation framework and the establishment of an independent body for evaluation is essential in all policy documents to ensure accountability of policy implementation and evaluation.\n\nChronic NCDs has now become a pandemic affecting all countries across the globe with a major impact on developing nations (World Health Organization, 2022). Therefore, WHO member countries collectively agreed upon the global action plan for the prevention and control of NCDs at the 66th World Health Assembly, provisioning a road map for the stakeholders in order to combat NCDs (World Health Organization, 2013). Therefore, while coherence between the local policy documents is essential for effective implementation of activities countrywide to combat NCDs, it is of important that the local policy documents are coherent with international policies and guidelines as well. Such consistency would allow easy international comparison of actions undertaken to combat NCDs between countries to understand the strategies that are effective in the global challenge to overcome NCDs.\n\n\nConclusion and recommendations\n\nWhile the policy documents related to NCD prevention and control in Sri Lanka are in coherence with the global action plan for the prevention and control of NCDs, there are many areas within these policy documents that need to be improved, to improve the coherence between the local documents. Lessons learned from this activity should be utilized to improve the future policy documentation in Sri Lanka. Further, lessons learnt from this activity may be utilized by other countries across the globe as well to improve the consistency between the NCD policy documents within the country as well as internationally.",
"appendix": "Data availability\n\nThe data for this article consists of bibliographic references, which are included in the References section.\n\n\nReferences\n\nAhmed N: Sri Lanka development update 2023.2023.\n\nBuse K, Mays N, Walt G: Making Health Policy. 1st ed.Glasgow, UK: 2005.\n\nCheung KK, Mirzaei M, Leeder S: Health policy analysis: a tool to evaluate in policy documents the alignment between policy statements and intended outcomes. Aust. Health Rev. 2010; 34(4): 405–413. PubMed Abstract | Publisher Full Text\n\nDepartment of Census and Statistics: Computer Literacy Statistics 2021: Annual Bulletin. Colombo, Sri Lanka: 2021.\n\nDepartment of Census and Statistics Sri Lanka: Census of Population and Housing - 2012. Colombo, Sri Lanka: 2012.\n\nKoh WC, Yu S; A Decade after the 2009 Global Recession Macroeconomic Developments.2020.\n\nMinistry of Health Nutrition and Indigenous Medicine Sri Lanka: National Multisectoral Action Plan for the Prevention and Control of Noncommunicable Diseases 2016-2020.2016.\n\nMinistry of Health Nutrition and Indigenous Medicine Sri Lanka: Non communicable diseases risk factor survey, Sri Lanka - 2015. Colombo, Sri Lanka: 2015.\n\nMinistry of Health Sri Lanka: The National Policy and Strategic Framework for Prevention and Control of Chronic Non-Communicable Diseases.2010.\n\nMinistry of Health Sri Lanka: Sri Lanka STEPS Survey 2021: Fact Sheet. Colombo, Sri Lanka: 2021.\n\nRütten A, Gelius P, Abu-Omar K: Policy development and implementation in health promotion-from theory to practice: the ADEPT model. Health Promot. Int. 2011; 26(3): 322–329. PubMed Abstract | Publisher Full Text\n\nRütten A, Lüschen G, von Lengerke T , et al.: Determinants of health policy impact: a theoretical framework for policy analysis. Soz. Praventivmed. 2003; 48(5): 293–300. Publisher Full Text\n\nSenaratne R, Mendis S: Prevention and Control of Noncommunicable Diseases Think Globally-Act Locally; Lessons from Sri Lanka. 1st ed.Colombo, Sri Lanka: Ministry of Health, Nutrition and Indigenous Medicine, Sri Lanka; 2018.\n\nWalt G, Shiffman J, Schneider H, et al.: “Doing” health policy analysis: methodological and conceptual reflections and challenges. Health Policy Plan. 2008; 23(5): 308–317. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Bank: Sri Lanka Development Update: 2021.2021.\n\nWorld Health Organization: Global action plan for the prevention and control of NCDs 2013–2020. Geneva, Switzerland: 2013.\n\nWorld Health Organization: Noncommunicable diseases.2022."
}
|
[
{
"id": "291931",
"date": "01 Aug 2024",
"name": "Emanuel Orozco-Núñez",
"expertise": [
"Reviewer Expertise Health policy and Systems research."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear authors,\nCongratulations for your well written paper. I found your arguments about the content of the NCD policy in Pakistan very clear and coherent. It is relevant the way in which you integrate your theoretical framework and your methods; these procedures provide consistency to your work. Nevertheless that you analyzed only two documents, the procedure is rigorous.\n\nOne situation that results problematic is to think NCD combat as a bunch of good intentions. In this sense, your paper provides evidence about the relevance of strengthening health systems and provide enough financing. It is noticeable that in LMICs some health improvement objectives look like wishful thinking without the sufficient financial support. Your paper provides arguments for questioning this practical situation.\nPerhaps your conclusions can be more strong if you specify what specific areas of the policy instruments should be improved; otherwise, argument looks vague. The same with the lessons learned, please specify what. With kind regards,\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? 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? Partly",
"responses": []
},
{
"id": "313917",
"date": "28 Aug 2024",
"name": "Kalpana Kosalram",
"expertise": [
"Reviewer Expertise Health Management",
"Public Health Monitoring and Evaluation",
"Project 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 Title and Abstract are detailed to make clear to the readers what the research is about. However, in the Abstract, the first line under ‘Results’ mentions the term \"Accessibility\" identified as the strongest criteria for the NCD policy, can mean accessibility of the policy itself, accessibility of healthcare services, or something else to the readers. Please expand to make this clearer.\nThe Introduction offers a well-justified explanation within the context of the available evidence. The discussion and concluding statements of the manuscript provide valuable pointers for uptake by other policymakers in low- and middle-income countries (LMICs) and could be further corroborated with information presented in the Introduction. The second paragraph of the Introduction briefly addresses the shortcomings in health policy evaluation and analysis in LMICs, with a more detailed focus on Sri Lanka. To strengthen the Introduction, it would be beneficial to include a few lines explaining why policy analysis is often overlooked in LMICs and how this gap negatively affects health outcomes.\nThe methodology applied is replicable. The strength of this research work is the use of the ADEPT model and the criteria developed by Cheung et al. (2010) to assess the internal validity of policy documents.\nAlthough the mapping and analysis was limited to the national NCD policy and the MSAP, the results section presents a thorough review of these two policy documents, highlighting areas of strength and weakness. Being a content analysis of policy documents, this study does not require explicit ethical considerations. However, addressing potential biases in document analysis or discussing the ethical implications of health policy decisions could have added depth to the analysis.\nThe discussion appropriately interprets the findings. The conclusion under Abstract and under Conclusion section mentions to \"enhance the coherence between the local documents.\" The authors could rephrase or include the word ‘internal coherence’ to make the opening statement appear slightly less contradictory.\n\nOverall, this study provides a valuable contribution to the field of health policy analysis, particularly in the context of NCD prevention and control in Sri Lanka. The Discussion and Conclusion section could expand offering more specific recommendations from the lessons learnt from this policy mapping activity, such as (i) incorporating other data sources for a more comprehensive understanding of the policy’s effectiveness like interviews or case studies (ii) proposing alternative dissemination methods (iii) proposing strategies for improving the internal coherence between local documents.\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/13-171
|
https://f1000research.com/articles/11-749/v1
|
06 Jul 22
|
{
"type": "Research Article",
"title": "Lower serum BDNF as a predictor of post-stroke cognitive impairment in acute ischemic stroke patients",
"authors": [
"Ismail Setyopranoto",
"Astuti Prodjohardjono",
"Sri Sutarni",
"Noor Alia Susianti",
"Muhammad Hardhantyo",
"Amelia Nur Vidyanti",
"Ismail Setyopranoto",
"Astuti Prodjohardjono",
"Sri Sutarni",
"Noor Alia Susianti",
"Muhammad Hardhantyo"
],
"abstract": "Background: Reduced level of serum BDNF in acute stroke patients is associated with poor outcomes. We aimed to identify the role of serum BDNF level as a predictor for post-stroke cognitive impairment (PSCI). Methods: This was a prospective study. We recruited acute ischemic stroke patients in Dr. Sardjito General Hospital Yogyakarta, Indonesia followed them up for 90 days (3 months). Serum BDNF was collected at day 5 and day 30 of stroke onset and measured by ELISA. Montreal Cognitive Assessment (MoCA) was used to measure the cognitive function at 90 days of follow up. ROC curve was conducted to measure the cut-off point of the BDNF level. Factors independently associated with PSCI were analyzed by using stepwise regression. Results: Among 89 patients recruited, 60 patients (67.41%) developed PSCI. The mean age of PSCI and non-PSCI patients was 62.7 ± 9.5 and 57.5 ± 8.7, respectively (p = 0.01). Patients with dyslipidemia were less likely to develop PSCI (OR 0.19, 95%CI 0.06–0.56, p < 0.05). In addition, patients with day 5-serum BDNF level < 23.29 ng/mL were five times more likely to develop PSCI compared with their counterparts (OR 5.02, 95%CI 1.67–15.04, p < 0.05). Conclusions: Among acute ischemic stroke patients, those with serum BDNF <23.29 ng/mL had a higher risk of developing PSCI, while those with dyslipidemia had a lower risk of PSCI. This study suggests that BDNF could be a predictor of PSCI, allowing for earlier detection and better preventive strategies.",
"keywords": [
"serum BDNF",
"predictor",
"post-stroke cognitive impairment",
"acute ischemic stroke"
],
"content": "Introduction\n\nAmong the stroke survivors, post stroke cognitive impairment (PSCI) is one of the common complications after stroke. Approximately, 53.4% post stroke patients suffered from PSCI which ranged from mild to severe cognitive impairment.1 The cognitive impairment will lead to severe disability and increase the cost of health care after stroke attacks.2,3 Nowadays, the investigations of biomarkers are developed to predict the long-term outcome and cognitive impairments after stroke. There are several growth factors that can affect the prognosis of patients with ischemic stroke in the long term, for example VEGF (vascular endothelial growth factor), BDNF (brain-derived neurotrophic factor), G-CSF (granulocyte-colony stimulating factor), Ang1 (angiopoietin 1), and SDF-1α (stromal-derived factor-1α).4–6\n\nThe most prevalent neurotrophin, Brain-derived Neurotrophic Factor (BDNF), is involved in neuronal survival, synaptic plasticity, angiogenesis, as well as neurite outgrowth in peripheral and central nervous systems.7,8 Both intravenous and intraventricular BDNF infusions reduced infarct size and showed neuroprotective benefits in experimental stroke model studies. Furthermore, there is evidence that BDNF is linked to various neuropsychiatric diseases.9\n\nAnother experimental study showed that local administration of BDNF ameliorates the functional motor recovery in ischemic stroke models.10 In human study, reduced level of serum BDNF has been found in acute ischemic stroke patients and is associated with poor functional outcome as well as more dependency.6,11–13 BDNF could improve brain plasticity and neuronal repair after stroke by promoting angiogenesis dan neurogenesis.14 Previous studies conducted among patients free of stroke revealed that higher BDNF was associated with better visual memory and global cognitive function.15,16 However, none of those previous studies investigated about the role of BDNF as a biomarker for predicting the development of PSCI among acute ischemic stroke patients.\n\nAssuming that the serum BDNF levels reflect brain levels, it seemed rational to think that measuring serum BDNF levels in the early stages of stroke would be effective for stroke outcome prediction. The present study aimed to identify the role of serum BDNF level in acute ischemic stroke patients in predicting PSCI. By understanding the important role of BDNF, the development of PSCI may be detected earlier thus early intervention can be applied leading to reduce the long-term disability, social, and economical burden caused by PSCI.\n\n\nMethods\n\nThis was a prospective study. The data was collected from June 2019 to May 2020. We recruited patients with acute ischemic stroke in Dr. Sardjito General Hospital Yogyakarta, Indonesia.\n\nWe included patients with: (1) first-ever stroke with the stroke onset within 5 days; and (2) aged >18-years old. We excluded those with: (1) recurrent stroke patients; (2) brain tumor, brain trauma, encephalitis, Parkinson’s disease, epilepsy, and dementia; and (3) depression or history of psychiatric diseases.\n\nDemographic, clinical, and laboratory data included serum BDNF were collected at day-5 of the stroke onset during hospitalization. In total, 89 eligible patients were selected during the study period.\n\nOutcome variable\n\nThe outcome variable was PSCI developed 3 months after stroke onset. We assessed the cognitive function at day 5, 30, and 90 after stroke onset by using Montreal Cognitive Assessment-Indonesian version (MoCA-INA) which has been validated for Indonesian population.17 PSCI group was defined if the total score of MoCA-INA at 90 days (3 months) after stroke was < 26.18 Meanwhile, a non-PSCI group was defined for those with MoCA-INA score ≥ 26.\n\nDemographic and clinical characteristics\n\nDemographic factors consisted of age (> 60 and ≤ 60 years old) and sex (male or female). Clinical characteristics consisted of body mass index (BMI) (obese or non-obese), hypertension (yes or no), systolic blood pressure (SBP), diastolic blood pressure (DBP), diabetes (yes or no), HbA1C, dyslipidemia (yes or no), lipid profile (the levels of triglycerides, HDL, LDL, and total cholesterol), as well as serum BDNF level at day 5 and 30 after stroke onset.\n\nWe classified the BMI based on WHO criteria for Asian population19,20 and further categorized the subjects into obese and non-obese (consisted of those with overweight and normal weight; there were no subjects with underweight). Systolic and diastolic blood pressure were measured by using sphygmomanometer performed at admission. We collected serum BDNF level at day 5 based on prior study which revealed that BDNF was reduced at acute stroke.21 We also collected serum BDNF at day 30 based on another study reported that BDNF level in acute stroke would be increased steadily and reached the highest level after 30 days.22\n\nMeasurement of serum BDNF level\n\nWe took the samples from patients’ serum on days 5 and 30 following the onset of the stroke. Between 7:00 and 9:00 a.m., a serum separator tube was filled with 5 mL venous whole blood from the patients. Patients were also told not to eat or drink anything for 10 hours before getting their blood drawn. Within 60 minutes of blood sampling, the venous whole blood was allowed to coagulate for 30 minutes at room temperature before being centrifuged at 1,000 × g for 15 minutes at 40°C to separate the serum and blood clot. The serum was extracted and stored at −20°C in a separate tube. The serum sample was transported to Prodia Laboratory Jakarta in a frozen state, sealed in a heat-insulated container with dry ice.\n\nWe measure the level of serum BDNF by an enzyme-linked immunosorbent assay (ELISA) using Human BDNF Immunoassay (Quantikine® R&D systems, Minneapolis, USA, Cat No: DBD00). The assay's minimal detection limit was 20 pg/ml, and its intra- and inter-assay coefficients of variation were both less than 10%. A monoclonal antibody specific for human BDNF was pre-coated in a 96 well polystyrene microplate (BDNF, R&D System, RD1S) at a concentration of 100L in a buffered protein base with preservative and then lyophilized. The test samples were applied in duplicate (50 L/well). In duplicate wells, a standard curve was created using BDNF (R&D systems, RD1S) at concentrations of 0, 62.5, 125, 250, 500, 1000, 2000, and 4000 pg/mL. In each well, a standard, control, or sample was added and incubated for 2 hours before adding the BDNF conjugate.\n\nAnother hour was spent incubating the mixture. Each well was aspired and washed once, then twice more for a total of three washes. Washing buffer (400 L) was used to wash each well with a squirt bottle, multi-channel pipette, manifold dispenser, or autowasher. Each well was filled with 200 mL of substrate solution and incubated at room temperature for 30 minutes, protected from light. Each well received 50 mL of Stop Solution. We lightly tapped the plate to ensure thorough mixing if the color change did not appear uniform. Using a microplate reader tuned to 450 nm, the optical density of each well was calculated in under 30 minutes.\n\nWe used the independent t-test, Mann-Whitney, and Chi-square test for analyzing the statistical differences between variables. We performed a receiver operating characteristics (ROC) curve analysis to determine the cut-off point of BDNF level. Bivariate analysis was conducted to analyze the relative risk of associated factors (including BDNF) between PSCI and non-PSCI group. We further performed multivariate analysis by using stepwise regression to measure factors independently associated with PSCI. All of the analyses were performed using the SPSS software version 25.0 (IBM Co. Ltd, NY, USA). A p value of < 0.05 indicated statistical significance.\n\nThis study has received ethical approval from the Medical and Health Research Ethics Committee of the Faculty of Medicine, Universitas Gadjah Mada, Indonesia (EC No. KE/FK/0682/EC/2020). All participants were provided the information regarding the study and signed the informed consent form.\n\n\nResults\n\nA total of 89 patients were included in this study, with 55.1% being within the age group of more than 60 years old. Most of the participants were male (61.8%), with 68.5% having hypertension. Serum BDNF was examined on day 5 and day 30 as a prognostic factor of PSCI in stroke patients. The mean BDNF levels at day 5 and 30 were 24.54 ± 6.42 ng/mL and 24.86 ± 8.51, respectively. As much of 67.41% of patients suffered from post-stroke cognitive impairment (PSCI) during the study period. The baseline characteristics of the study participants were presented in Table 1.\n\nFactors associated with PSCI were analyzed further as shown in Table 2. We found that age, dyslipidemia, and triglyceride levels showed a significant difference between the PSCI and non-PSCI groups (p < 0.05). Older patients had a higher risk to have PSCI compared with their younger counterparts (RR: 1.41, 95% CI: 1.03–1.94, p < 0.05). Patients with dyslipidemia were less likely to have PSCI compared with those without dyslipidemia. However, the PSCI group had a lower triglycerides level than the non-PSCI group (p < 0.05). In addition, the PSCI group had a lower MoCA-INA score than the counterpart group (p < 0.001) (Table 2).\n\n* p < 0.05.\n\n** p < 0.001.\n\nBased on the ROC curve (Supplementary Figure 1), the cut-off points of serum BDNF level at day 5 (BDNF I) was 23.29 ng/ml and at day 30 (BDNF II) was 28.79 ng/mL. These cut-off points were then included in the bivariate analysis, and we found that the mean serum BDNF level at day 5 in PSCI group was significantly lower than non-PSCI group (p < 0.001). However, there was no difference for BDNF level at day 30 in both groups. The patients with the BDNF level <23.29 ng/mL were more likely to develop PSCI (RR: 1.60, 95% CI: 1.19–2,15, p = 0.001) (Table 2).\n\nFor investigating factors that were independently associated with PSCI, we performed a multivariate analysis with stepwise regression. After adjusting by the covariates, we found that serum BDNF level at day 5 and dyslipidemia were significantly associated with PSCI. Patients with dyslipidemia were less likely to develop PSCI compared with the counterpart group (OR 0.19, 95%CI: 0.06–0.56, p < 0.05). Nevertheless, patients with day 5-BDNF level <23.29 pg/mL were five times more likely to develop PSCI compared with their counterparts (OR 5.02, 95%CI: 1.67–15.04, p < 0.05) (Table 3).\n\n* p < 0.05.\n\n\nDiscussion\n\nThe present study demonstrated that serum BDNF level at acute phase (day 5) and dyslipidemia were associated with PSCI in first-ever acute ischemic stroke patients. Patients with BDNF level <23.29 ng/mL had a higher risk of developing PSCI, while those with dyslipidemia had a lower risk of PSCI. To our knowledge, this is the first study that demonstrated that serum BDNF could be used as a predictor for post-stroke cognitive impairment 3 months after stroke.\n\nOur finding corroborates a prior cross-sectional study that reported that stroke survivors with cognitive impairment had a reduced level of serum BDNF and that the cognitive performance score was positively correlated with BDNF level.23 However, this study measured the level of BDNF during the post-acute phase with a median duration of illness was 10 months after stroke onset. Due to the nature of the cross-sectional study, this prior study could not suggest that BDNF can serve as a predictor for PSCI.\n\nThere are some proposed mechanisms for explaining why BDNF is associated with cognitive function in post-stroke patients. First, BDNF could increase angiogenesis, neurogenesis, and promote brain repair.24 In animal model of aging stroke, BDNF mediated facilitation of reversal learning/cognitive flexibility by inducing angiogenesis and neurogenesis which further improved the functional recovery of cognitive after stroke.24 Second, BDNF plays important roles in regulation and maintenance of synaptic plasticity. Synaptic plasticity is essential for maintaining normal cognition and attenuating brain’s resilience to recover from ischemic injury.14 BDNF involves in regulating the long-term potentiation (LTP) and long-term depression (LTD),25 as well as mediates learning and memory process in post-stroke rehabilitation.26–28\n\nIn the present study, we also found that patients with dyslipidemia had lower risk of developing PSCI. This finding is in accordance to prior study which reported that patients with dyslipidemia had a decreased risk of cognitive decline after stroke.29 The Framingham Heart Study also found similar result that high cholesterol level was associated with better cognitive function.30 However, contrary to the present study, a longitudinal study conducted in China found that increased total cholesterol and LDL were associated with cognitive impairment.31 The underlying mechanism of how dyslipidemia was associated with cognitive decline remains elusive. The interplay between dyslipidemia and cognitive function is very complex and may involve the distribution of fat mass and is influenced by age.20\n\nThe present study shows evidence that serum BDNF in acute stroke and dyslipidemia are associated with PSCI. This finding may help clinicians and researchers to predict PSCI earlier thus could prevent the worsening of cognitive function in post-stroke patients. Nevertheless, this study has some limitations. First, the sample size was small due to the participants only came from a tertiary hospital in Indonesia. Hence, the findings may not be generalized for the whole population. Second, the follow-up period was only 90 days (3 months) after stroke. Follow-up for a longer period of time will be beneficial to explore the potential role of BDNF as a solid biomarker. Moreover, we did not explore the molecular mechanisms of how reduced serum BDNF could impair cognitive function. More knowledge on this issue particularly related to the signaling pathway may be helpful in clinical and research settings.\n\n\nConclusions\n\nAcute ischemic stroke patients with lower serum BDNF (< 23.29 ng/mL) had a higher risk of developing PSCI, while those with dyslipidemia had a lower risk of PSCI. This study suggests that BDNF could be a predictor of PSCI, allowing for earlier detection and better preventive strategies.\n\n\nData availability statement\n\nUnderlying data is available on Zenodo: https://doi.org/10.5281/zenodo.6038470.\n\n\nAuthor contributions\n\nIS: conceptualization, methodology, validation, visualization, writing-original draft, writing-review & editing; AP: data curation, methodology, resources, supervision, funding acquisition; SS: methodology, validation, supervision; NAS: data curation, formal analysis, investigation, project administration, writing-review & editing; MH: methodology, formal analysis, software, validation, writing-review & editing; ANV: conceptualization, methodology, formal analysis, validation, visualization, writing-review & editing.",
"appendix": "Acknowledgements\n\nThe authors would like to thank all the patients who participated in this study and all data collectors for their genuine cooperation.\n\n\nReferences\n\nAam S, Einstad MS, Munthe-Kaas R, et al.: Post-stroke Cognitive Impairment—Impact of Follow-Up Time and Stroke Subtype on Severity and Cognitive Profile: The Nor-COAST Study. Front. Neurol. 2020; 11: 699. PubMed Abstract | Publisher Full Text\n\nClaesson L, Lindén T, Skoog I, et al.: Cognitive impairment after stroke–impact on activities of daily living and costs of care for elderly people. Cerebrovasc. Dis. 2005; 19: 102–109. PubMed Abstract | Publisher Full Text\n\nYang Y, Shi Y-Z, Zhang N, et al.: The disability rate of 5-year post-stroke and its correlation factors: a national survey in China. PLoS One. 2016; 11: e0165341. 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Stroke. 2013; 44: 2768–2775. PubMed Abstract | Publisher Full Text\n\nBélanger J-C, Bouchard V, Le Blanc J, et al.: Brain-Derived Neurotrophic Factor Mitigates the Association Between Platelet Dysfunction and Cognitive Impairment. Front. Cardiovasc. Med. 2021; 8: 1060. PubMed Abstract | Publisher Full Text\n\nHusein N, Lumempouw SF, Ramli Y: Montreal Cognitive Assessment Versi Indonesia MoCAIna untuk skrining gangguan fungsi kognitif. Neurona. 2010.\n\nNasreddine ZS, Phillips NA, Bédirian V, et al.: The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc. 2005; 53: 695–699. Publisher Full Text\n\nWHO: Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004; 363: 157–163. Publisher Full Text\n\nVidyanti AN, Hardhantyo M, Wiratama BS, et al.: Obesity is less frequently associated with cognitive impairment in elderly individuals: a cross-sectional study in Yogyakarta, Indonesia. Nutrients. 2020; 12: 367. PubMed Abstract | Publisher Full Text\n\nChaturvedi P, Singh AK, Tiwari V, et al.: Brain-derived neurotrophic factor levels in acute stroke and its clinical implications. Brain Circ. 2020; 6: 185–190. PubMed Abstract | Publisher Full Text\n\nHidayat A, Arief M, Wijaya A, et al.: Vascular Endothelial Growth Factor and Brain-Derived Neurotropic Factor Levels in Ischemic Stroke Subject. Indones. Biomed. J. 2016; 8: 115–118. Publisher Full Text\n\nHassan TM, Yarube IU: Peripheral brain-derived neurotrophic factor is reduced in stroke survivors with cognitive impairment. Pathophysiology. 2018; 25: 405–410. PubMed Abstract | Publisher Full Text\n\nHoulton J, Zhou LYY, Barwick D, et al.: Stroke Induces a BDNF-Dependent Improvement in Cognitive Flexibility in Aged Mice. Neural. Plast. 2019; 2019: 1460814–1460890. PubMed Abstract | Publisher Full Text\n\nWang G, Gilbert J, Man H-Y: AMPA receptor trafficking in homeostatic synaptic plasticity: functional molecules and signaling cascades. Neural. Plast. 2012; 2012: 825364–825364. 2012/05/13. PubMed Abstract | Publisher Full Text\n\nMizuno M, Yamada K, Olariu A, et al.: Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats. J. Neurosci. 2000; 20: 7116–7121. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHall J, Thomas KL, Everitt BJ: Rapid and selective induction of BDNF expression in the hippocampus during contextual learning. Nat. Neurosci. 2000; 3: 533–535. PubMed Abstract | Publisher Full Text\n\nMa Y, Wang H, Wu H, et al.: Brain-derived neurotrophic factor antisense oligonucleotide impairs memory retention and inhibits long-term potentiation in rats. Neuroscience. 1997; 82: 957–967. PubMed Abstract | Publisher Full Text\n\nSrithumsuk W, Kabayama M, Gondo Y, et al.: The importance of stroke as a risk factor of cognitive decline in community dwelling older and oldest peoples: the SONIC study. BMC Geriatr. 2020; 20: 24. PubMed Abstract | Publisher Full Text\n\nElias PK, Elias MF, D’agostino RB, et al.: Serum cholesterol and cognitive performance in the Framingham Heart Study. Psychosom. Med. 2005; 67: 24–30. PubMed Abstract | Publisher Full Text\n\nMa C, Yin Z, Zhu P, et al.: Blood cholesterol in late-life and cognitive decline: a longitudinal study of the Chinese elderly. Mol. Neurodegener. 2017; 12: 1–9."
}
|
[
{
"id": "146499",
"date": "10 Aug 2022",
"name": "Syahrul Syahrul",
"expertise": [
"Reviewer Expertise Stroke (Neurology)"
],
"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 article is presented according to accurate scientific research methods with appropriate and reliable literature sources. The research design is also in accordance with the research methodology and carried out with good technical method. The research methodology with statistical analysis that is available is quite good and allows for replication by other researchers. Interpretation Statistical analysis is carried out accordingly so that the implementation of the research results can be carried out. All data sources underlying the results are available to ensure full reproducibility. The conclusions in this article are supported by the results of the study.\nLow BDNF serum in patients with acute ischemic stroke as a predictor of impaired cognitive function must be confirmed by neurobehaviour examination and neuroimaging (MRI) examination of the head. The diagnosis of cognitive dysfunction in patients with acute ischemic stroke must be carried out comprehensively by taking into account the risk factors for stroke and other organ system disorders.\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": "176320",
"date": "20 Jul 2023",
"name": "Shubham Misra",
"expertise": [
"Reviewer Expertise Neurology",
"stroke",
"biomarker 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\nThe authors determine the role of serum BDNF as a biomarker of post-stroke cognitive impairment. Though an interesting topic, there are several inherent limitations in the article including small sample size, late biomarker measurement, less duration of follow up, that makes the article unsuitable for indexing.\nMy comments include:\nAbstract - Provide full form of BDNF, ELISA, ROC when used for the first time.\n\nBDNF level is being measured at day 5 in ischemic stroke patients. These are not acute patients. Please modify your terminology as it does not reflect acute stroke.\n\nThe main limitation of this study is the late measurement of biomarker at day 5 and small length of follow up. This is not clinically useful. An earlier detection is warranted. Why were BDNF levels measured at day 5 and not sooner, for e.g., within 24 hours? An earlier collection of blood sample in acute stroke patients would facilitate earlier detection of PSCI. Also, a longer follow-up is warranted to accurately identify cognitive impairment in stroke patients. Please elaborate on this in your discussion section.\n\nMethods: How was stroke diagnosis made in this study? Was it clinical or supplemented with neuroimaging? What was the definition of stroke. Please mention these details in the study design and participants section.\n\nMethods - More details regarding the inclusion and exclusion criteria is required. The provided information is insufficient. Did the authors include both stroke subtypes? What about pregnant females?\n\nStatistical analysis - Did the authors check the normality of the biomarker levels and other variables used in this study? If yes, then please mention the normality test used.\n\nStatistical analysis - The authors should refer to the TRIPOD guidelines for reporting the results of a prognostic biomarker study and should report their results in accordance with those guidelines.\n\nStatistical analysis - Please mention the measure of effect (Odds ratio or Risk ratio) that the authors used to synthesize their results.\n\nStatistical analysis - How did the authors calculate the cut-off value using the ROC curve? Was it manually done or using any index, for e.g., Youden Index?\n\nStatistical analysis - The authors should make two multivariable prediction models. One including biomarker and other predictors and the other without the biomarker. This will help identify if the addition of biomarker to the prediction model improved the predictive performance in predicting cognitive impairment after stroke.\n\nThe sample size of this study is too small to derive any meaningful conclusion. How did the authors derive this sample size? There is no sample size calculation provided in the manuscript. Please provide one.\n\nResults - Mention all the variables that were entered into the multivariable analysis.\n\nResults - Mention if there was any loss to follow-up in the study.\n\nHow was the follow-up conducted and by whom? Was it telephonic or face-to-face? There is no information regarding that.\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": "11189",
"date": "13 Apr 2024",
"name": "Amelia Nur Vidyanti",
"role": "Author Response",
"response": "My comments include: Abstract - Provide full form of BDNF, ELISA, ROC when used for the first time. Response: We have now provided the full form of BDNF, ELISA, and ROC in the abstract. Thank you for your suggestion. BDNF level is being measured at day 5 in ischemic stroke patients. These are not acute patients. Please modify your terminology as it does not reflect acute stroke. Response: Based on prior studies, the clinical staging of stroke (Cramer, 2008; Rehme et al., 2012; Zhao et al., 2014) is generally accepted as follows: the first 2 weeks are defined as the acute stage; 3–11 weeks post-stroke is termed the subacute stage in which most changes occur; 12–24 weeks post-stroke is the early chronic stage; and more than 24 weeks post-stroke is the chronic stage. BDNF in the present study was measured at day 5 after stroke onset in which it was still in the acute stage of stroke. The main limitation of this study is the late measurement of biomarker at day 5 and small length of follow up. This is not clinically useful. An earlier detection is warranted. Why were BDNF levels measured at day 5 and not sooner, for e.g., within 24 hours? An earlier collection of blood sample in acute stroke patients would facilitate earlier detection of PSCI. Also, a longer follow-up is warranted to accurately identify cognitive impairment in stroke patients. Please elaborate on this in your discussion section. Response: We thank the reviewer for the valuable comments and suggestions. The reason why we measured serum BDNF level at day 5 after stroke index is based on prior study. “Previous study showed that decrease BDNF level after 4 days from stroke index is associated with poor outcome in acute ischemic stroke patients. The cell death is completed in 5 days after stroke, and BDNF will lead to neuroplasticity during this time. Subsequently, lower serum BDNF will impair the neuroregeneration and may lead to poor outcome in acute ischemic stroke patients (Clarkson et al., 2011; Tuwar et al., 2023).” Regarding PSCI identification, we agree that longer follow-up is needed because cognitive functioning after stroke may have been fluctuated due to the change of cerebral hemodynamics. However, prior studies have demonstrated that the definition of PSCI is any severity of cognitive impairment, regardless of cause, noted after an overt stroke, and it occurs from 3-6 months after stroke (Sundar & Adwani, 2010; Garcia et al., 2015; He at al., 2023; Husseini et al., 2023). Therefore, in the present study we identified PSCI at 90 days (3 months) after stroke. We have elaborated on this issue in the method section of the revised paper. Methods: How was stroke diagnosis made in this study? Was it clinical or supplemented with neuroimaging? What was the definition of stroke. Please mention these details in the study design and participants section. Response: Thank you for your suggestions. We have now mentioned these details in the study design and participants’ section. “We included patients with: (1) first-ever acute ischemic stroke with <5 days after stroke onset, which is diagnosed based on clinical examination and head CT scan immediately after patients’ initial assessment in the emergency room; and (2) Age >18-years old. We excluded those with: (1) Recurrent stroke patients; (2) Brain tumor, brain trauma, encephalitis, Parkinson’s disease, epilepsy, pregnant females, and dementia; and (3) Depression or history of psychiatric diseases.” Methods - More details regarding the inclusion and exclusion criteria is required. The provided information is insufficient. Did the authors include both stroke subtypes? What about pregnant females? Response: We have now provided some details in the inclusion and exclusion criteria as below: “We included patients with: (1) first-ever acute ischemic stroke with <5 days after stroke onset, which is diagnosed based on clinical examination and head CT scan immediately after patients’ initial assessment in the emergency room; and (2) Age >18-years old. We excluded those with: (1) Recurrent stroke patients; (2) Brain tumor, brain trauma, encephalitis, Parkinson’s disease, epilepsy, pregnant females, and dementia; and (3) Depression or history of psychiatric diseases.” Statistical analysis - Did the authors check the normality of the biomarker levels and other variables used in this study? If yes, then please mention the normality test used. Response: We used Kolmogorov-Smirnov test to determine the normality of numerical data, the independent t-test, Mann-Whitney, and Chi-square test for analyzing the statistical differences between variables. Thank you for your suggestions. We have now provided this information in the revised paper. Statistical analysis - The authors should refer to the TRIPOD guidelines for reporting the results of a prognostic biomarker study and should report their results in accordance with those guidelines. Response: TRIPOD guidelines is attached in the resubmission along with the revised manuscript. Statistical analysis - Please mention the measure of effect (Odds ratio or Risk ratio) that the authors used to synthesize their results. Response: We have provided the information regarding OR in the statistical analysis and mentioned it in the result and discussion section. Statistical analysis - How did the authors calculate the cut-off value using the ROC curve? Was it manually done or using any index, for e.g., Youden Index? Response: We calculated the cut-off value by using Youden Index. We have now added this information in the Statistical analysis section. Statistical analysis - The authors should make two multivariable prediction models. One including biomarker and other predictors and the other without the biomarker. This will help identify if the addition of biomarker to the prediction model improved the predictive performance in predicting cognitive impairment after stroke. Response: We have now provided the multivariate analysis with some prediction models in the revised paper such as stated in the statistical analysis section and the result section (Table 3). Thank you for your valuable suggestion. The sample size of this study is too small to derive any meaningful conclusion. How did the authors derive this sample size? There is no sample size calculation provided in the manuscript. Please provide one. Response: We have now provided the sample size calculation in the revised paper as below: “We estimated the minimum sample size and found that it might be acceptable to represent the entire population. The sample size was calculated using the following for two population proportions (one-sided test) (Lwanga & Lemeshow, 1991): Equation 1 n= sample size P1= proportion of PSCI with lower serum BDNF P2 = proportion of PSCI with higher serum BDNF Based on previous study, the proportion of PSCI with lower serum BDNF is 88,7% (Prodjohardjono, 2020) and the proportion of PSCI with higher serum BDNF is 65,5% (Havlovska et al., 2023). With = 1.96 and = 0.84, the minimum sample size is as follows: Equation 2 n = 40 participants for each representing group With the 10% of dropout rate, the minimum sample size is 88 participants. Initially, we collected 99 participants. However, 10 participants were loss to follow up due to some reasons. In the end, there were only 89 participants who completed the study.” Results - Mention all the variables that were entered into the multivariable analysis. Response: We have reperformed the analysis and provided the multivariable analysis with 3 models in which all the variables were entered (Table 3). Thank you for your valuable suggestion. Results - Mention if there was any loss to follow-up in the study. Response: We have added this information in the sample size section accordingly. How was the follow-up conducted and by whom? Was it telephonic or face-to-face? There is no information regarding that. Response: We have now provided the information regarding the follow up in the study design section. Thank you for your valuable suggestions. “Demographic, clinical, and laboratory data were collected at day 5 of the stroke onset during hospitalization. Serum BDNF was collected at day 5 of the stroke onset during hospitalization and at day 30 during the home visit. Cognitive functioning was measured at day 5, 30, and 90. The follow-up was carried out by the study team through home visits.”"
}
]
}
] | 1
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https://f1000research.com/articles/11-749
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https://f1000research.com/articles/13-170/v1
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08 Mar 24
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{
"type": "Research Article",
"title": "Lecturers’ experiences of online learning communication in Indonesia during the COVID-19 pandemic: A phenomenological study",
"authors": [
"Anter Venus",
"Lukman Saleh Waluyo",
"Fitria Ayuningtyas",
"Kusumajanti Kusumajanti",
"Anter Venus",
"Fitria Ayuningtyas",
"Kusumajanti Kusumajanti"
],
"abstract": "Background Indonesia is currently implementing educational reforms to enhance university teaching and learning. The COVID-19 pandemic has significantly affected Indonesian universities, requiring lecturers to implement various changes. The phenomenon of online learning communication at various universities in Indonesia is critical considering today’s increasingly fierce competition due to digital disruption coupled with the impact of the pandemic. Therefore, lecturers must implement appropriate methods to conduct online learning communication effectively.\n\nMethods This qualitative phenomenological study was designed to explore lecturers’ understanding of the implementation of changes in online learning communication at Indonesian universities. In-depth interviews and field observations were conducted with lecturers who were efficient in online learning using a specific measurement standard. The research participants were identified using purposive sampling with a snowball approach. The study comprised 10 lecturers from UPN Veteran Jakarta who were experienced and efficiently delivered online lectures.\n\nResults The results provide a review of factors identified by the phenomenological and qualitative study that contribute to online learning communication, such as chemistry, lecturer preparation, and learning materials. The results of this study revealed several themes. Each section centers on the major themes that emerged from the datasets.\n\nConclusion Our findings aid in a better understanding of the benefits and constraints of using online learning communication in the classroom. These findings are crucial for university lecturers developing methods for enhancing the implementation of online learning communication. Moreover, the findings revealed that lecturers should engage in and create trusting interactions with their students. Providing technical support to keep both teachers and students engaged can be useful. More crucially, multimedia support and learning systems are essential for properly addressing lecturers’ tasks and learning materials. This study improves the understanding of online learning communications implemented by lecturers.",
"keywords": [
"online learning",
"communication",
"phenomenology",
"qualitative",
"Indonesia",
"lecturer",
"pandemic",
"digital"
],
"content": "Introduction\n\nThe expansion of online learning is rapidly transforming higher education, with an increasing number of colleges offering degree programs in online and remote learning modes worldwide. Traditional “correspondence” study has transitioned into online learning as a result of the digital communication breakthroughs of the 21st century, with many more universities, both urban and regional, providing programs that may entirely be pursued online.1\n\nThe COVID-19 pandemic has significantly impacted almost all aspects of our lives, including the Indonesian education sector. This has a significant effect on various learning activities. During the pandemic, the government-imposed restrictions on interactions and activities outside the home to limit the spread of the coronavirus infection, which hampered conventional learning methods.\n\nSeveral measures were implemented to ensure that educational activities continued despite the lack of face-to-face instruction. In particular, students and lecturers in higher education were unable to meet in the classroom; therefore, they adapted to changing circumstances, and devised new tactics such as implementing online learning.2\n\nCommunication, particularly in the educational sector, should be researched, because communication between instructors and students has the potential to promote learning and create a positive environment.3\n\nTechnology plays an important role in the continuity of learning through non-conventional media such as online media. Online learning is considered a solution that could connect teaching and learning activities during the pandemic. Most educational institutions have shifted their learning activities to the online mode. Therefore, online learning communication is an important aspect that must be investigated by stakeholders in the field of education including lecturers, students, schools, and universities. The current rapid development of technology and communication has had a significant impact on the changes that occur in society, including teaching and learning processes. Therefore, online learning communication by lecturers during the pandemic is an important research subject. The expected findings of this research reveal how the phenomenon of online learning communication in suitable public universities can encourage the development of science, technology, and social sciences.\n\nThe subject of online learning was selected because researchers believe that there were several new and unique aspects of online learning implemented during the COVID-19 pandemic that could not be conducted during face-to-face learning.\n\nOne of the policies implemented by the Indonesian government to prevent the spread of COVID-19 was the implementation of Large-Scale Social Restrictions (PSBB), one of which was to close schools. Over a period of almost three years since the outbreak of the pandemic, several changes have occurred in the world of education and have been experienced by students since the implementation of complete online learning. These changes are evident from various aspects of online learning activities, including the media used, interactions that occur, materials provided, and methods used. These changes have led to various communication experiences for students. Such a novel experience certainly has its own value or meaning for individuals who experience it first-hand. The more important the value of an experience, the more memorable it will be.\n\nHigher education is a more complex level of education than a school education. Higher education aims to develop graduates with high professional and academic abilities to develop or create science, technology, and arts to improve human welfare and national development. Therefore, scholars have focused on examining students’ online learning communication experiences during the COVID-19 pandemic.\n\nAs online learning is ongoing due to the COVID-19 pandemic, this topic is relevant and vital for publication. It is essential to evaluate the problems pertaining to online learning communication experiences and online learning policies set by the government to prevent or minimize the spread of COVID-19 in Indonesia. It is expected that the results can be used to improve the quality of online learning in Indonesia.\n\nRapid advances in science and technology have had a tremendous impact on social habits in recent years and have resulted in significant changes in the production, distribution, and communication of information. Consequently, the rate of knowledge expansion has accelerated, necessitating a constant update of current information. Simultaneously, the need for people to constantly analyze information and remain up to date with daily advancements is a top priority. Consequently, the use of information and communication technology (ICT) and the internet in education has increased, culminating in the proliferation of online environments.4\n\nIn online learning communication, from the students’ viewpoint, the lecturer needs to communicate with the students using informal channels (instant messaging, online chat groups, voice calls, and video calls) parallel alongside formal channels.3 Students and lecturers face several challenges in online learning communication, including a lack of technological proficiency, increased Internet expenses, and erratic communication and socialization between students.5\n\nEconomic situations, anxiety during online learning, the risk of user data security, finding suitable online learning media, and expectations are some of the problems students face while studying online.2\n\nOut of a broad range of learner characteristics, the factors that enable Generation Z students to succeed in dedicated online learning communication are the learners’ home institutions, which substantially impacted their preference for instructional delivery modality. According to students, the best aspects of a dedicated online course are a flexible timetable and quick access; however, they also want more real-time interactions with teachers and classmates, multimedia resources, and various applications (apps). According to students, metacognitive and thinking skills are essential for success in dedicated online courses.6\n\nThe ability to create a sense of presence for improving learning outcomes is an important aspect of online learning. Students should be provided with immediate feedback, meaningful learning experiences, and opportunities to form relationships with classmates and professors to improve their presence.7\n\nStudent happiness in online learning was significantly influenced by social presence, fueled by tool engagement. Moreover, in online learning, sex differences affect the links between tool interactions and social presence.8\n\nStudents revealed the various challenges they faced when using information technology (IT) platform applications for online learning. Work and information overload received from instructors via online learning platforms, technological hurdles connected to unaffordability of online learning support facilities, and mental health challenges related to stress and anxiety are examples of such obstacles faced by students.9\n\nOnline learning communication presents several technical, educational, and social challenges. Technical challenges are primarily related to the unreliability of internet connections and the lack of electronic equipment required by students. Pedagogical challenges include a lack of digital skills for teachers and learners, a lack of structured content, an abundance of online resources, learner interaction, lack of motivation, and teachers’ social and cognitive skills. Regarding the lack of presence, building content together creates meaning through continuous communication within the research community.\n\nSocial factors are mostly due to the lack of human engagement between instructors and learners, lack of private physical spaces at home for students to attend lessons, and lack of support from parents who simultaneously work remotely in the same spaces.10\n\nTime restrictions, low technological skills, inadequate infrastructure, a lack of institutional strategies and support, and negative attitudes of those engaged are some of the major challenges in the design and implementation of online learning communication in education. Improved educator skills, incentives, and rewards for the time spent developing and delivering online information, improved institutional strategies, support, and a positive attitude among all those involved in the development and delivery of online content are some of the solutions to these problems.11\n\nThe most significant component for both teachers and students in their online teaching and learning experiences was holding students to high standards of performance, academic honesty, and professional ethics. The faculty requires a well-designed online classroom with engaged students who complete their work on time, and students require an online instructor who is organized and communicative in the online classroom.12\n\nIn comparison with offline classrooms, student participation in online learning may be vague and difficult to understand. Without face-to-face interactions, instructors may be unable to measure student involvement accurately or adjust accordingly.13\n\nFace-to-face learning was rated higher than online learning in terms of social presence, social engagement, and satisfaction. However, no statistically significant differences in learning preferences were found among students. Some students preferred online learning because it provided them with opportunities to be creative using computer technology.14\n\nStudents’ engagement plays a key role in online learning. Student engagement is a four-dimensional construct with behavioral, cognitive, affective, and agentic components.15 Naji et al.16 recently conducted research on engineering students to determine the factors influencing their willingness to learn online during the COVID-19 pandemic. They discovered that four variables influenced students’ preparedness for online learning: 1) initial preparedness and motivation, 2) self-efficacious attitudes toward online learning, 3) self-directed online learning, and 4) support for online learning. Furthermore, social media platforms such as Facebook and Instagram can be used for online learning.17\n\nOnline learning is a new experience that allows students to study easily, without having to travel to campus. However, challenges persist in online learning. Due to the lack of effective network access, communication and directions in lectures are unclear. Student participation in online courses is hampered by the limited budget for Internet subscriptions. Student focus suffers as a result of excessive workload. The government should ensure that all regions have sufficiently stable Internet network connections and universities must provide students with subsidized Internet subscriptions to eliminate unaffordability. Consequently, lecture activities can proceed easily as planned.18\n\nUnderstanding and determining the factors of online learning communication from a lecturer’s viewpoint are essential for promoting successful online learning communication.\n\nAlthough studies assessing strategies to improve online learning communication have been conducted, none have been conducted from lecturers’ perspectives. Therefore, a review of the narrative and qualitative studies is required.\n\nWe reviewed observational and qualitative studies to identify the factors that lead to successful online learning communication from lecturers’ perspectives. Qualitative studies are necessary because of their methodology (the approach to answering questions about experience, meaning, and perspective), which is useful for addressing implementation issues.\n\nFurthermore, no studies have addressed this subject in Indonesian culture. Therefore, this qualitative study was conducted to explore the concept of online learning communication in Indonesian society.\n\nThis study explores lecturers’ experiences with online learning communication. Lecturers were asked to describe and discuss their perspectives regarding their experiences and views, the challenges they faced during online learning communication, and the types of support they required. The research questions that guided this study were as follows:\n\n1. What are lecturers’ experiences when implementing online learning communication?\n\n2. How do lecturers provide meaning to online learning communication?\n\n3. What are the challenges that lecturers face during online learning?\n\n\nMethods\n\nAll participants provided written informed consent before participation. Because they participated voluntarily, they were free to leave the interviews at any time. All the respondents provided informed consent. Subsequently, written consent was obtained to share the anonymized data. This research has been ethically approved on April 30th, 2021 by the research ethic commission of UPN Veteran Jakarta (No: 346/VIII/2023/KEPK).\n\nThis study employed a qualitative research method to analyze the data from the research results. This method allows holistic interpretation and explanation of a phenomenon regarding online learning communication experiences using words, without having to rely on quantitative data.\n\nQualitative research conducted aimed to determine and understand this phenomenon in depth. Data analysis was performed inductively. The processed data emphasized the depth (quality) of the data obtained more than the amount (quantity) of data.\n\nUsing qualitative research methods [1] allowed for the analysis of words or sentences uttered and the situation or conditions experienced by the informants in this study from their perspective. This approach focuses on using analyses and existing theories or concepts as supporting materials for creating a theory. The results of the study included interactions with the participants and observed behaviors. Data were collected from notes, memos, interview scripts, and other supporting documents.\n\nTo understand lecturers’ experiences in online learning communication, this study used a phenomenological [2] approach to reflect on and describe their experiences through interactions with the interviewer.19 The purpose was to accurately portray these lecturers to describe their observations and discover new meanings.\n\nThe phenomenological method used in this study was Heidegger’s hermeneutic phenomenology, which is oriented toward searching for the meaning of experience for the participants. Heidegger’s phenomenology is more flexible in identifying and validating research results. Heidegger developed a phenomenological method that allows for the inclusion of prior experience and presuppositions or preconceived knowledge from informants in research data. In this way, validation is no longer required because during the research process, participants and researchers are intensely involved in the process of sharing experiences.20\n\nThis research was conducted at a public university with approximately 10,000 students enrolled. This location was selected because it was possible to acquire access and cooperation between the administration and faculty members. Almost 500 lecturers from various backgrounds constituted university personnel. None of the lecturers were foreigners. The official language of instruction is Indonesian, and classroom contact hours are two hours and 30 minutes.\n\nAll university lecturers were invited to participate in the study (Table 1). Consequently, all participants were volunteers. The study sample comprised 10 lecturers from UPN Veteran Jakarta, who were experienced and considered excellent in delivering online lectures. The data were collected between June 2021 and April 2022. This study used nonprobability sampling with a snowball sampling technique. Snowball sampling was used to identify key informants who had significant information. Using this approach, several potential respondents were contacted and asked whether they knew others fitting the research criteria. The initial contact helped obtain recommendations from other respondents.\n\nThis study used in-depth interviews to obtain information and data by asking the informants several questions33 about the phenomenon of online learning communication. This strategy was selected for its adaptability and capacity to boost valuable intelligence among people while expanding the understanding of the concepts being studied.\n\nThe in-depth interviews aimed to explore participants’ in-depth experiences during online learning communication. The investigator informed the participants that they could withdraw at any time during the study and that they had the option to not respond to any of the questions.\n\nDuring the discussions, the participants were encouraged to express their opinions and experiences openly. Probing was used throughout the interviews to further develop lecturer responses and applicable samples. Each interview was audio recorded and converted into verbatim transcriptions to present the findings in narrative form. Moreover, handwritten notes were prepared to track valuable insights that could enrich the findings. To validate the results, each party was given an interview summary for a final review. The interviews took place at the university and required approximately 30 minutes to answer the research questions, and the participants answered five interview questions. The locations for group discussions were selected by the interviewees (e.g., workplace and online). At each meeting, the interviewer (the corresponding author) clarified the ponder’s goals. An audio recorder was used for data collection.\n\nQualitative data analysis was performed to develop the complex meanings that emerged from the raw data. Data analysis was performed by experts on the research team (dependability). The interviews were transcribed,31,32 and the data were analyzed through a phenomenological approach using survey questions as a guide. The study was designed using the following four levels: horizontalization, presentation of significant statements, analysis of themes (thematization), and phenomenological reduction (crystallization). The data analysis was performed both manually and using the software NVivo 14.\n\nIn the horizontal stage, the researcher describes and presents all data obtained from the informants, as they are placed and treated equally. Horizontalization is the stage of presenting data as a whole, where all data receive the same place and treatment.\n\nThe second stage involved presenting significant statements. During this stage, the researcher reduced the research data or sorted out the statements of the informants disclosed during the interview that were considered relevant to the research question. The researchers marked the relevant statements to distinguish them from irrelevant statements and flattened them (invariant ons/units of meaning of phenomena).\n\nThe third stage was a thematic analysis. In this case, themes were defined as a broad categorization of feelings, thoughts, and meanings that represented the essence of each participant’s experience. The theme in this context is important because it made it easier for researchers to map out the experiences of the participants and focus on examining the specific experiences of participants that have similarities with other participants.\n\nThe essence is the crystallization of several short and dense themes.21 In the essence of the experience stage, the researcher attempts to determine the essence of the research, which is the result of the crystallization of several short and concise themes, by rereading the identified themes, combining them, determining the most general statements of these themes, and covering all the themes that have been identified.\n\nAll the data required to explore these important themes were obtained from direct interviews as first-hand sources of information. Thus, the scientific conceptualization of the participant experience can be conducted validly without bias or distortion. In accordance with the process of analyzing Heidegger’s hermeneutic phenomenology, which emphasizes previous knowledge about the phenomenon under study, important categories or themes will first be presented and then juxtaposed with the themes that emerge from the interpretation process conducted by the research.22\n\nTracy’s23 eight-dimensional model for quality model was used to establish rigor in qualitative research: (a) worthy topic, (b) rich rigor, (c) sincerity, (d) credibility, (e) resonance, (f) major contributions, (g) ethics, and (h) meaningful coherence. In addition, researchers have used various tactics to improve the credibility, transferability, dependability, and confirmability of their results. Prior to data analysis, participants were permitted to double-check their responses through member checking.24 Following completion of the data analysis, each participant examined the interpreted findings for data validation and verification. Second, the researchers thoroughly described the data collection and analysis techniques, cross-checked emergent themes to eliminate repetition and data overlap before presenting them as narrative paragraphs and assessed the study protocol to allow for research replication.25 Finally, researchers aware of the research setting used journal logs to reflect on their views while completing the study to avoid bias. Consequently, they were able to eliminate subjectivity, retain objectivity, and maintain neutrality when collecting and analyzing data.\n\n\nResults\n\nThe results of this study revealed several themes. The first theme answers the first two interview questions and summarizes the lecturers’ experiences regarding the most challenging aspects of implementing online learning communication.\n\nThereafter, the remaining interview questions were addressed, and the superiority of digital learning was reported. Each section centers on the major themes that emerged from the datasets. Finally, the discussion addresses lecturers’ perceptions of the most significant requirements to implement successful online learning communication at universities and draws a connection between the findings of this study and extant studies.\n\nAccording to the participants, lecturers experienced several challenges in online learning communication. The most significant challenge for the lecturers is their lack of engagement in the learning process. In particular, the lack of interaction, chemistry, personal touch, and gestures were significant concerns for the lecturers.\n\nSeven lecturers reported interactions as a challenge in online learning communication. In support of this argument, a participant reported, “The ideal communication in online learning occurs when there is interaction between lecturers and students. If it occurs only in one direction, it is not effective, because if the student continuously focuses on the monitor without being allowed to interact, it could tire their eyes.”\n\nLecturers have experienced chemistry as a challenge in online communication. In support of this argument, a participant explained, “The most noticeable difference is in terms of chemistry and feedback from students. Even in online learning communications, one can receive direct feedback, however, in my opinion, receiving feedback is not similar to chemistry. Not speaking directly makes you feel less comfortable; therefore, you tend to get bored, and those you talk to also tend to get bored easily. This is because they speak in front of a laptop and do not directly interact with people; hence, there is a problem owing to the lack of human communication.”\n\nPersonal touch was a significant concern for the lecturers. Respondents argued that personal touch was a challenge when implementing online learning communication.\n\nFor example, a participant reported different experiences: “There is no conversation, there is no eye contact, or physical and mental contact. Although I can see their faces, my personal bonds are missing. Although the camera features are on, they are different from real classrooms.”\n\nThe lecturers experienced that understanding gestures in online learning communication that account for students’ learning styles was a challenging task.\n\nSpeaking about this issue, a participant mentioned, “I am unable to assess accurately during online learning; it means that I am not sure about the student’s understanding of the lecture. In the offline classes, this can be understood from their gestures. Although they turn on the camera, much delay occurs during the learning process; therefore, we cannot be sure whether they have understood the material taught and their experiences during the lecture.”\n\nIt is clear from lecturers’ experiences that various technical problems occur during online learning communication. In support of this argument, a participant stated, “While teaching online, some students have problems with cameras or microphones. It is difficult to ascertain whether it is simply a cry or whether there are defects in laptop devices. Therefore, I sometimes go back and forth to remind them to turn the camera on. The drawbacks are almost the same, perhaps network problems, because many of them do not come on camera when called; the reason is because the network is unstable. Furthermore, if they do not turn on the camera, we cannot determine the expression of the students at all or their interests during the lecture. Therefore, I prefer them to have cameras on them. Weather also affects they cannot be on camera. Regarding devices, several students do not have adequate laptops, computers, or any equipment at all and therefore use cell phones.”\n\nThe lecturers stated that online communication was ineffective. According to a participant, “I believe the effectiveness is lower than during face-to-face learning. The online medium can have several elements that hinder its effectiveness, for example, technical connections, device readiness, and existing features or facilities in the application.”\n\nSimilarly, a participant indicated, “Devices and technology that do not support, and cause internet network connection disturbances affect the mood of students as well as the mood of the lecturers. During a lecture, suddenly if the internet connection is interrupted, we forget what we are talking about. Restoring network connections is also time consuming. This affects the students’ moods and their ability to continue with the same interest.” These lecturers argued that they could not effectively implement online learning communication because of the noise. Speaking about the importance of noise free environment in online learning communication, a participant stated, “For example, during lectures, students often make presentations, and they are unable to mute their surroundings. This could disturb the class.” A participant further explained, “The more disturbing aspect is when they do not use a virtual background and family members can be seen going back and forth in the background. In one instance, the parent could be seen with towels in the background. This may be due to student negligence or ignorance. Additionally, sometimes when I ask a question, they turn on the microphone and the sound varies, possibly because they commute. The sound was noisy and disturbing; hence, I had to transfer the question to another student.” These experiences demonstrate their need for an environment where they feel secure in expressing themselves and have their voices heard in online learning communication. A participant commented, “Honestly I do not ask my students to turn on the camera, except in cases of direct interaction, as students say that turning on the camera consumes a large quota of internet.”\n\nSeveral respondents had different views on whether communication learning should be conducted online or face-to-face. However, 40% of the participants were of the opinion that the method of learning implementation must be adjusted according to the subject being taught.\n\nFor example, as conveyed by a participant, “In my opinion, students continue to prefer online learning because they are comfortable. However, certain courses are difficult to teach completely online. For example, courses on quantitative research method courses. These courses require full supervision from lecturers to ensure that students understand them thoroughly. If it is taught completely online, it will be somewhat difficult. However, complete online learning may not be problematic for other courses. Thus, it depends on the course and learning outcomes you aim. Therefore, we cannot equate one course with another, because each course has its own approach. Maybe several activities may be combined for online learning instead of being taught in a Zoom meeting or Google Meet. The courses can be conducted both online and offline, so that some activities can be conducted online, and the students can gather together for the offline activities.”\n\nA participant had the same view, “Perhaps there are some courses that must be attended offline. For example, courses are offered by the Faculty of Engineering, Faculty of Medicine, or Faculty of Health Sciences. However, some humanities courses can be conducted completely online. In some countries, the number of offline classrooms has decreased, therefore, those that can be conducted online are expected to continue. Online learning communication is beneficial for all parties, not only for lecturers but also for students who may be living far from campus; however, they can continue to study online. Moreover, they do not have to search for boarding houses or temporary accommodation while studying at the UPN.”\n\nA participant stated, “I believe in a more hybrid direction, hence, it is not 100% online or 100% offline. Although it is true that online learning communication benefits lecturers in terms of expenses such as saving transportation expenses, it also reduces teaching satisfaction because interactions with students are mediated. Online learning cannot replace offline learning completely. Some lessons should be conducted online, while others should be conducted offline. For example, general-knowledge classes can be conducted online. However, in the context of research or skill practicing a skill, it is more effective if conducted offline. Hence, I believe that the hybrid format is interesting to achieve the ideal format in learning for better education.”\n\nAccording to lecturers, several methods can be employed to maximize the efficiency of online learning communication. First, lecturers are willing to upgrade themselves to become acquainted with current online learning communication technology.\n\nA participant stated that, “Lecturers and students both have much knowledge of learning technologies, such as Zoom, Google Meet and other platforms. We have to become used to mastering the technology used to support online learning communication processes. Several types of platforms can be used; however, not all lecturers understand how to use them, hence, they must be trained. If a lecturer is aged 45 years or younger, it may be easy to adapt. However, if the age is above 45 years, it is difficult to train them as they need assistance, even in creating a conference link or sharing their screen. How do they aim to create learning innovations with the so many types of innovation provided on the Internet? Lecturers should apply this new development that must be applied in the future. Therefore, they are willing to learn and change. Commitment is the most important because as lecturers, we must adapt to changes to provide the best for our students.”\n\nSimilar views were shared by a participant. “Lecturers as educators must be able to follow the ongoing learning trends that are occurring worldwide. They must remain updated to ensure that they are not left behind. They have been provided complete information using videos and manual books and are also assisted by the e-learning team in each faculty so that they have no difficulty in using online learning communication.”\n\nMoreover, the delivery of learning materials is important. Lecturers believe that several methods may be used to maximize the deliverability of learning materials. A participant believes that “the point is how to engage students in the learning process. I attempt to make them more focused on the choice of words and intonation of the voice, which is firmer and heavier. This makes them more attentive to what I say than when I speak to them jokingly or casually and with normal intonation. I used diction that is firmer and straightforward because maybe they are studying while lying down or doing something else. We must be more dominant than in other activities. I stand even up when delivering the material is delivered. I believe that it is useful for me because it stimulates my brain. Moreover, for students, it offers more varied body and hand movements than when I teach while sitting. Additionally, while standing, I can stretch and draw attention.” The importance of diction was also stated by a participant, “The second step is to select words. Good diction will draw their attention. We teach verbally, with the help of PowerPoints, photographs, and words. This is more than simply reading the material.”\n\nParticipants differed in their views on the best duration for online and offline learning. According to a participant, based on my experience, if we use the same duration as offline learning, it will not be effective because the student will experience visual fatigue. If we speak normally, it is usually only effective for one hour, at the most. Therefore, our problem is how to use the two hours effectively and keep students engaged. Hence, I have adopted an approach in which I post all types of explanation materials first. I asked my students to read/watch it according to their convenience so that during class, their doubts and questions could be clarified. Later, we can assign them to a case study.” Other participants had similar views. A participant believes that it is important to provide breaks during the learning process. “I usually stop every 45 minutes because student focus is limited. If lectures are prolonged, students do not concentrate. Therefore, I provide a break of 10 min and then continue again.” Another participant stated, “In other universities, such as UNDIP (Diponegoro University), they rarely conduct synchronous learning. The maximum synchronous learning was only half of the course. However, the maximum duration should not be more than 30 min because students’ focus on online learning is limited. After 20 min, people typically lose interest. Moreover, students were happy that way as they did not have to be glued to Google Meet or Zoom all day. At least 20-30 minutes is sufficient to talk about issues that need to be discussed or explained further.”\n\nOnline learning communications provide features and facilities that cannot be found in offline learning such as video conferencing, animation, recorded videos, visual graphics, forums, quizzes, and attendance. Most lecturers have specific views on this topic. A participant believes that “in online learning communication, we can use many forms of media, such as video and animation.” Another participant believes that online learning communication that has been running at the UPN is useful because it not only provides learning material but also allows interaction through conferences or videos. Online learning is a model of futuristic learning. In the future, campuses may not require several rooms, because they can provide learning anytime and anywhere. Moreover, online learning videos can facilitate knowledge transfer from lecturers to students in a unique manner that may not be possible in offline classrooms.” A participant said, “I rarely conduct lectures during online classes.” In my experience, this method was not attractive to my students. Therefore, I usually assigned a video lesson to students and asked them to watch it before the next class. Thus, when the class begins, it is time for discussion, not for listening to my lectures.” According to a participant, “I told them that in my class I would not be lecturing on the material. I will record the learning materials and share the YouTube links. This recording is a significant effort, as my recordings are usually between seven and 10 minutes long. During class, we elaborated on this. Therefore, I do not expect that I will explain the material in class as it has been provided through video recordings, and I have uploaded all the references to the LMS.” Similarly, another participant stated, “Another option is to reduce the duration of lecture by providing video tutorials. Thus, we can provide interactive videos with sufficiently interesting graphics to keep the users absorbed.”\n\nLecturers have highlighted dyadic communication as an effective method of online learning. Therefore, methods that support two-way engagement such as presentations, experiments, quizzes, projects, case studies, and forums should be employed. As a participant stated in the interview, “We should not lecture anymore. Lecturers only facilitate students in the direction of their learning using a dialogue model and not one-way communication. Thus, we continue to have several challenges, as we are not directed there.”\n\nAnother participant supports similar methods of online learning communication. “We must provide incentive to students to encourage them to ask questions. I began my lecture with a quiz, as the video material had already been provided to them. There are several questions in the quiz, those who ask them are given a score, and they must be transparent. This process becomes easy with the use of learning apps. We created a discussion forum for those who asked questions. They were assessed and provided with feedback or a score.” A participant believes, “We can interact with students by providing them problems such as a case study. For example, I teach health service management and suggest, “You become a director at a hospital or the head of a puskesmas. How would you position yourself? What would you do?” Therefore, a discussion was initiated. However, it is difficult to identify relevant cases, as it requires practical experience.” Another participant stated that another method that can be used in online learning communication is to increase students’ activities at home, a type of pre- or post-activity before or after teaching. For example, provide them with a topic of discussion before lectures that can later be discussed in class. Alternatively, after lectures, they can be asked to read about or discuss a topic that they will bring up the following week. In online learning communication, everything is integrated into a single information system; thus, pre pre-activity or post-activity is integrated into the information system, making it easier for lecturers to manage.”\n\n\nDiscussion\n\nThis study identified student engagement as the most significant aspect of implementing online learning communication with respect to lecturers’ experiences of online learning communication in Indonesia during the COVID-19 pandemic. The lecturers discovered that student interaction primarily centered on the need to improve their online learning communication practices and that online engagement was highly valued by students for online learning communication. Students identified small-group interactions as the most important aspect of communication; however, non-participation by some members was cited as a major issue.26\n\nMore specifically, lecturers face challenges such as technical problems, duration, learning methods, and the use of multimedia. These findings align with previous research on lecturers in online learning communication.\n\nSome lecturers believe that using online learning communication to provide lecture material without having to meet in person is advantageous, although there are some technical problems, such as insufficient internet access.27,28 Lecturers highlighted the importance of using multimedia to implement online learning communication. This finding aligns with that of Palupi and Raharjo,29 who reported that, in online learning communication, one alternative is to combine two online learning tools, Zoom and Google Classroom. Zoom is a virtual conferencing platform used in online learning. However, it lacks facilities for sending assignments. Google Classroom has features that allow you to send and receive assignments as well as save quotes on the Internet. Both used together will complement each other to meet all the necessities of online learning.29 The lecturers in this study indicated the need to update themselves to learn about technology related to online learning communication. Shaharanee et al.30 found that university management must address several challenges in preparing lecturers for the transition from teaching and learning to online learning. Consequently, lecturers require additional training, particularly in technical and online learning. A reliable online learning platform is required for lecturers to embark on this new experience.30\n\n\nConclusions\n\nThe findings of this study can assist lecturers in understanding online learning communication in Indonesia. These findings are crucial for university lecturers developing methods for enhancing the implementation of online learning communication.\n\nLecturers are important in online learning communication and can aid or hinder change. Consequently, they must be aware of how online communication affects students at the personal level. Accordingly, the necessary support should be provided to help lecturers and students cope well with online learning communication.\n\nMoreover, the findings revealed that lecturers should engage in and create trusting interactions with their students. Providing technical support to keep lecturers and students engaged may be useful. More crucially, multimedia support and learning systems are essential for properly addressing lecturers’ tasks and learning materials.\n\nOnline learning communication is more successful when its duration is reduced. Moreover, lecturers benefit from hybrid learning methods because they can increase their self-efficacy when implementing online learning communication.\n\nOnline learning communication should not be the sole responsibility of lecturers. Students should also be a source of support. Thus, lecturers should cultivate an atmosphere that allows them and their students to enjoy online communication.\n\nThis study improves the understanding of online learning communications implemented by lecturers. As Indonesia continues to implement it, lecturers and students must respond to and actively engage in the process to ensure its success.\n\nThis study has a few limitations. First, it is a preliminary study that examines university lecturers’ experiences in online learning communication in Indonesia, and the challenges they face. Because this was an exploratory study, the results were inconclusive. The findings of this study can be used to build a research design or formulate a questionnaire to survey several people. Second, as some participants may have been afraid to express a negative opinion about their university, self-reported data may have lacked accuracy when examining a particular topic. Furthermore, the small number of participants (N=10) could be considered a limitation. Third, future research should explore student perspectives on online learning communication to verify these findings. This study may be replicated by integrating different research sites, sampling a larger population including students, and utilizing multiple data collection techniques. Furthermore, this study does not focus on the values, norms, and other elements of Indonesia’s sociocultural context, which may influence how lecturers view online learning communication. Instead, this research provides useful information about university lecturers’ experiences with online learning communication.",
"appendix": "Data availability\n\nFigshare: Transkrip Bahasa Indonesia New. https://doi.org/10.6084/m9.figshare.25139816. 31\n\nThe project contains the following underlying data:\n\n- transkrip bahasa indonesia new.docx (Transcripts of interviews)\n\nFigshare: English Transcript New. https://doi.org/10.6084/m9.figshare.25139813. 32\n\nThe project contains the following underlying data:\n\n- english transcript new.docx\n\nFigshare: Interview Guide. https://doi.org/10.6084/m9.figshare.24978213. 33\n\nThe project contains the following extended data:\n\n- interview guides.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\nStone C: Online learning in Australian higher education: Opportunities, challenges and transformations. Stud Success. 2019; 10(2): 1–11. Publisher Full Text\n\nSimamora RM: The Challenges of online learning during the COVID-19 pandemic: An essay analysis of performing arts education students. Stud Learn Teach. 2020; 1(2): 86–103. Publisher Full Text\n\nAlawamleh M, Al-Twait LM, et al.: The effect of online learning on communication between instructors and students during Covid-19 pandemic. Asian Educ Dev Stud. 2020.\n\nOrakcı Ş: The future of online learning and teaching in higher education. Global approaches to sustainability through learning and education. IGI Global; 2020; p. 28–45.\n\nSuryaman M, Cahyono Y, Muliansyah D, et al.: COVID-19 pandemic and home online learning system: Does it affect the quality of pharmacy school learning. Syst Rev Pharm. 2020; 11(8): 524–530.\n\nYu E: Student-inspired optimal design of online learning for generation. Z J Educ Online. 2020; 17(1): n1.\n\nSeckman C: Impact of interactive video communication versus text-based feedback on teaching, social, and cognitive presence in online learning communities. Nurse Educ. 2018; 43(1): 18–22. PubMed Abstract | Publisher Full Text\n\nPark C, Kim DG: Exploring the roles of social presence and gender difference in online learning. Decis Sci J Innov Educ. 2020; 18(2): 291–312. Publisher Full Text\n\nAl-Kumaim NH, Mohammed F, Gazem NA, et al.: Exploring the impact of transformation to fully online learning during COVID-19 on Malaysian university students’ academic life and performance. Int J Interact Mob Technol. 2021; 15(5). Publisher Full Text\n\nFerri F, Grifoni P, Guzzo T: Online learning and emergency remote teaching: Opportunities and challenges in emergency situations. Societies. 2020; 10(4): 86. Publisher Full Text\n\nO’Doherty D, Dromey M, Lougheed J, et al.: Barriers and solutions to online learning in medical education–an integrative review. BMC Med Educ. 2018; 18(1): 130. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTanis CJ: The seven principles of online learning: Feedback from faculty and alumni on its importance for teaching and learning. Res Learn Technol. 2020; 28: 28. Publisher Full Text\n\nCole AW, Lennon L, Weber NL: Student perceptions of online active learning practices and online learning climate predict online course engagement. Interact Learn Environ. 2021; 29(5): 866–880. Publisher Full Text\n\nBali S, Liu MC: Students’ perceptions toward online learning and face-to-face learning courses. J Phys Conf S. 2018, November; Vol. 1108(1): p. 012094. IOP Publishing. Publisher Full Text\n\nChiu TKF: Applying the self-determination theory (SDT) to explain student engagement in online learning during the COVID-19 pandemic. J Res Technol Educ. 2022; 54(sup1): S14–S30. Publisher Full Text\n\nNaji KK, Du X, Tarlochan F, et al.: Engineering Students’ Readiness to Transition to Emergency Online Learning in Response to COVID-19: Case of Qatar. Eurasia J Math Sci Technol Educ. 2020; 16(10). Publisher Full Text\n\nKumar V, Nanda P: Social media in higher education: A framework for continuous engagement. Int J Inf Commun Technol Educ. 2019; 15(1): 97–108. Publisher Full Text\n\nAlchamdani A, Fatmasari F, Rahmadani Anugrah E, et al.: The impact of Covid19 pandemic on online learning process in the college at southeast Sulawesi. J Kesehatan Lingkungan. 2020; 12(1si): 129–136. Publisher Full Text\n\nVan Manen M: Phenomenology in its original sense. Qual Health Res. 2017; 27(6): 810–825. Publisher Full Text\n\nBeck CT: Benefits of participating in Internet interviews: Women helping women. Qual Health Res. 2005; 15(3): 411–422. PubMed Abstract | Publisher Full Text\n\nLebowitz L, Newman E: The role of cognitive–affective themes in the assessment and treatment of trauma reactions. Clin Psychol Psychother. 1996; 3(3): 196–207. Publisher Full Text\n\nIdczak SE: I am a nurse: Nursing students learn the art and science of nursing. Nurs Educ Perspect. 2007; 28(2): 66–71.\n\nTracy SJ: Qualitative quality: Eight “big-tent” criteria for excellent qualitative research. Qual Inq. 2010; 16(10): 837–851. Publisher Full Text\n\nCreswell JW: Educational research. pearson; 2012.\n\nClark VLP, Creswell JW: Understanding research: A consumer’s guide, Pearson Higher, editor.2014.\n\nAnderson B, Simpson M: Group and class contexts for learning and support online: Learning and affective support online in small group and class contexts.2004.\n\nSimamora RM, de Fretes D , Purba ED, et al.: Practices, challenges, and prospects of online learning during Covid-19 pandemic in higher education: Lecturer perspectives. Stud Learn Teach. 2020; 1(3): 185–208. Publisher Full Text\n\nNasution AKP, Ahmad NQ: Student perceptions of online learning during the Covid-19 pandemic. J Salam. 2020; 4(2): 195–204.\n\nPalupi IR, Raharjo W: Zoom as a tool for online learning. Proceeding of LPPM UPN “Veteran” Yogyakarta CONFERENCE; SERIES 2020–POLITICAL AND SOCIAL SCIENCE SERIES. 2020; 1(1): 161–165.\n\nShaharanee M, Bakar M, Nordin H, et al.: Assessing lecturer’s readiness for online learning implementation during COVID-19 outbreak. Ilkogretim Online-elementary Education Online. 2020; 19(2): 79–84.\n\nWaluyo L: Transkrip Bahasa Indonesia New. [Dataset]. Figshare. 2024. Publisher Full Text\n\nWaluyo L: English Transcript New. [Dataset]. Figshare. 2024. Publisher Full Text\n\nWaluyo L: Interview Guide. [Dataset]. Figshare. 2024). Publisher Full Text\n\n\nFootnotes\n\n1 Further reading: Creswell JW. A concise introduction to mixed methods research. SAGE Publications; 2014.\n\n2 Further reading: Van Manen M. Phenomenology of practice: Meaning-giving methods in phenomenological research and writing. Routledge; 2016."
}
|
[
{
"id": "263313",
"date": "17 Apr 2024",
"name": "Sherwyn P Morreale",
"expertise": [
"Reviewer Expertise instructional communication",
"communication education",
"online education",
"communication competence",
"public speaking"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis qualitative phenomenological study represents a useful contribution to an area of inquiry that is contemporarily critical to any instructor or administrator with an interest in enhancing online education in higher education, locally or globally. The introduction and literature review point to a two-part rationale for the study’s research questions: (1) a gap in understanding online learning and communication from lecturers’ perspectives, and (2) the need to conduct such a study in the Indonesian culture. The interesting qualitative phenomenological method is carefully explained to ensure replicability, which could occur comparatively in other cultures. The data analysis section of the method is interesting and well described for the reader. Most important, the ten themes described in the results section are clearly described and illustrated by including direct quotations from the study’s participating lecturers. These strengths aside, this review now provides some recommendations intended to enhance the writing style and presentation of this study and its findings. Some of these recommendations are molar and relate to the overall writing while others are molecular and more specific. Molar Recommendations\nConsider clarifying terms that may be varyingly used by readers in various cultures and countries. Describe what is meant by “lecturers.” Are these full-time faculty, or part-time instructors/teachers, and are they fully responsible for teaching all aspects of a given course or courses? The term lecturer could mean a teacher who only speaks to students, which is lectures only, one-way communication. Also describe the types of online delivery of the courses presented by the ten lecturers in the study. Are the courses fully and solely delivered online, or are they hybrid, that is, part online and part in-seat/traditional delivery? Clarify these and any other essential terms that may be misunderstood, early in manuscript, perhaps toward the start of the methods section. Regarding writing style: Throughout the manuscript, sometimes only one sentence constitutes a paragraph. Instead, cluster ideas that clearly relate to one another in longer paragraphs that start with a lead-in line; for example, in the literature review: ” Research to date has provided insight into students ‘ viewpoints of their experiences with online teaching and learning.” Then describe the types of studies already included in the literature review about that topic. But don’t include in the literature review any opinions that are not supported by scholarly research, published or presented literature. Perhaps the discussion and conclusions sections could be somewhat more expansive. Two possible ways to be more expansive would be: in the discussion, harken back to and answer the study’s three research questions; answer each of the three with several sentences of discussion. Also, add Table 2 to the discussion. List the ten themes presented in the results and include a 1-2 sentence of each theme. That table could go at the end of the results.\n\nMolecular Recommendations\n\nThis sentence in the introduction may suggest that there is a dearth of research about communication education in online education. While there is a need for this and other such studies, considerable studies have been published in the U.S. and internationally (see for example 13 studies published in: Frontiers in Communication: Instructional Communication Competence and Instructor Social Presence. In the methods section, provide an explanatory sentence of Table1, perhaps phrased like this.\nTable 1 The ten participating lecturers included one lecturer from each of the following ten areas of study at the university.\n\nAt the end of the third paragraph of the data collection section, change the word ponder’ s to study’s. Be consistent with capitalization throughout, for example: Capitalize Internet when it’s used as a noun. Also proof section headings and subtitles for consistency of capitalization. In the third paragraph of the Results section, (Lack of Engagement), add a lecturer statement from the results so this theme is the same as the other themes. In the Results section:\nChange the subtitle from Hybrid learning based on the subject to: Variability in learning based on the subject Change the subtitle Maximizing Efficiency of Online Larning Communication to: Maximizing efficiency and effectiveness of online learning communication\n\nIn the Results section, subtitled Learning method, change A participant believes, to One lecturer believes…\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": []
},
{
"id": "263310",
"date": "02 May 2024",
"name": "Jude William Genilo",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn general, the study is important as it provides the experiences of lecturers regarding online courses during the pandemic era. The study was conducted satisfactorily. However, there are a few aspects that can be done to improve the research as follows:\nThe researcher can provide a more comprehensive discussion on the study’s context. For one, they can narrate the pandemic situation government actions to curb the pandemic, government actions (including support given like providing internet access, mobile phones, surveys, online platforms) on preventing the spread in schools and universities. Another, they can talk about internet access and social media use in the country during the study period. Also, they can give a brief introduction and description about UPN Veteran, including prior experience and training provided on hybrid or online learning, policies towards online learning, faculty number, policies during pandemic era regarding class attendance, etc.\n\nThe objectives can be made more specific. For example, what are the categories of experiences that they would like lecturers to share about – technology, pedagogy, adopting content, student performance, student interaction, co-learning experiences, etc.\n\nThere should be greater detail regarding the background of lecturers such as age, number of years teaching, training received on online learning, social media and internet use, class size, type of class taught whether theoretical, lab or field based, etc.\n\nRegarding related literature, there have been several studies written about teachers’ experiences during the pandemic – both quantitative and qualitative. More can be cited by the researchers. They can go to the open access HEED journal.\n\nRegarding the results, there should be a discussion about the typical online class experience of lecturers. How do they start classes? How do they prepare? Do they check attendance? What are their ground rules? How did they adjust their course outline to fit the new pedagogy? Did they change the ways they evaluate students? How did they take account about the students’ mental health situation? Did they collaborate with student affairs office? How was their reporting system to their chair or dean?\n\nThe researchers can also ask the lecturers about the lesson they learned during the pandemic and whether there are still some practices that they carry over to the post-pandemic situation.\n\nTo allow replication by others, the researchers may provide a description of the guide questions. Also, the researchers should state whether there were other artifacts that were looked into like PowerPoint presentations and class recordings of the sessions.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-170
|
https://f1000research.com/articles/13-169/v1
|
08 Mar 24
|
{
"type": "Data Note",
"title": "Translating nanoEHS data using EPA NaKnowBase and the resource description framework",
"authors": [
"Holly M. Mortensen",
"Bradley Beach",
"Weston Slaughter",
"Jonathan Senn",
"Antony Williams",
"William Boyes",
"Bradley Beach",
"Weston Slaughter",
"Jonathan Senn",
"Antony Williams",
"William Boyes"
],
"abstract": "Background The U.S. Federal Government has supported the generation of extensive amounts of nanomaterials and related nano Environmental Health and Safety (nanoEHS) data, there is a need to make these data available to stakeholders. With recent efforts, a need for improved interoperability, translation, and sustainability of Federal nanoEHS data in the United States has been realized. The NaKnowBase (NKB) is a relational database containing experimental results generated by the EPA Office of Research and Development (ORD) regarding the actions of engineered nanomaterials on environmental and biological systems. Through the interaction of the National Nanotechnology Initiative’s Nanotechnology Environmental Health Implications (NEHI) Working Group, and the Database and Informatics Interest Group (DIIG), a U.S. Federal nanoEHS Consortium has been formed.\n\nMethods The primary goal of this consortium is to establish a “common language” for nanoEHS data that aligns with FAIR data standards. A second goal is to overcome nomenclature issues inherent to nanomaterials data, ultimately allowing data sharing and interoperability across the diverse U.S. Federal nanoEHS data compendium, but also in keeping a level of consistency that will allow interoperability with U.S. and European partners. The most recent version of the EPA NaKnowBase (NKB) has been implemented for semantic integration. Computational code has been developed to use each NKB record as input, modify and filter table data, and subsequently output each modified record to a Research Description Framework (RDF). To improve the accuracy and efficiency of this process the EPA has created the OntoSearcher tool. This tool partially automates the ontology mapping process, thereby reducing onerous manual curation.\n\nConclusions Here we describe the efforts of the US EPA in promoting FAIR data standards for Federal nanoEHS data through semantic integration, as well as in the development of NAMs (computational tools) to facilitate these improvements for nanoEHS data at the Federal partner level.",
"keywords": [
"nanomaterial",
"database",
"ontology"
],
"content": "Introduction\n\nEngineered nanomaterials (ENM), usually defined as purpose-built materials with at least one dimension between approximately 1-100 nm, are a central component of the nanotechnology revolution and are increasingly used in a wide variety of industrial and commercial applications. The diverse applications of ENM include such widespread sectors as industrial catalysts and intermediates, electronics, health care, automotive materials, food containers, drugs, personal care products such as toothpaste and skin creams, sporting equipment, nano-enabled pesticides, and many more. The overall market size for nanotechnology is estimated to be $1.76 billion in 2020 and projected to exceed $33 billion by 2030 (Allied Market Research 2021).\n\nResponsible development of nanotechnology must include consideration of the potential implications for environmental health and safety (EHS). The widespread manufacture and application of ENM raises the potential for release of ENM at various points along the product life cycles ranging from initial synthesis and manufacture to product use, end-of-life and disposal. The release of ENM brings possible exposures to environmental species or humans (Boyes, Thornton et al. 2017). The US federal government includes numerous agencies responsible for assuring the safety of the public and/or the natural environment, according to applicable statutes, including any potential risks associated with applications of ENM. For example, federal agencies may consider potential exposures in the workplace (NIOSH and OSHA), via foods, drugs and cosmetics (FDA), consumer products (CPSC), in hazardous waste sites (ATSDR), and via air, water, pesticides or as regulated toxic substances (EPA). The efforts of federal agencies to support the advancement of nanotechnology is coordinated through the National Nanotechnology Initiative (NNI, https://www.nano.gov/), and the evaluation of Environmental Health and Safety (EHS), coordinated through the Subcommittee on Nanoscale Science, Engineering, and Technology, and the Nanomaterial Environmental Health Implications (NEHI) workgroup under the NNI.\n\nThe various agencies responsible for ENM EHS have complementary interests in assessing the potential hazards of ENM. Uniformly, these assessments are challenged by limitations of data regarding the actions of ENM across their life cycle. This is true despite a large and growing scientific literature on nanotoxicology. There is a need for coordination and integration of nano EHS data to facilitate safety and risk assessments, and to further nanomaterial science through “big-data” assessments such as meta-analyses and quantitative structure-activity relationships. Nanoinformatics, the compilation, integration, and assessment of nanoEHS data, is an important component of nanoEHS, and has been the focus of concerted international efforts (Haase 2018). The US-EU roadmap outlines a vision for data standards and organization that allows for computational re-use; however, all but a single contributed dataset at the time of writing is generated by EU initiatives.\n\nNanoinformatics efforts in the US have primarily been agency specific, whereby datasets are not interoperable and most often not accessible outside of any given agency. Efforts to coordinate data have been hindered by diversity of information, and format incongruities. The NEHI Database and Informatics Interest Group (DIIG) has recently formed a federal consortium to establish a standard protocol for the mapping of controlled vocabularies that is both consistent amongst the US Federal partner datasets, and between US and International efforts [NNI 2011 Research Strategy Update, 2023; Conference Proceedings, 2023]. The US EPA has contributed computational tools and training materials to further this effort.\n\nThe US EPA developed NaKnowBase (NKB), a database containing nanoEHS results published in peer-reviewed journals by EPA’s Office of Research and Development (ORD) (Boyes, Beach et al. 2022). The NKB is currently implemented as a relational database using the structured query language (SQL). Though SQL is a universal language, access to the data included in a database requires some knowledge of the language, and potentially further manipulation of the data that may be beyond the capabilities of some potential users. Short of creating a graphical user interface (GUI) and hosting individual datasets externally, which is not a cost- effective solution for any one dataset, it has become important to provide NKB information in a more accessible format. One way this has been accomplished by the US EPA is by providing NKB data to EPA’s CompTox Chemicals Dashboard (CCD) [Williams et al. 2017; Lowe and Williams, 2021], whereby NKB nanomaterials are linked to multiple points of information related to chemical toxicity.\n\nThe process of coordinating EPA NKB data with data from other US federal agencies, or other external databases, and CCD, requires consistency in nomenclature, and the ability to translate diverse terminology to common terms. This “Common Language” for nanoEHS parallels similar current efforts in the health sciences (NIEHS 2023) and, to our knowledge is the first effort in the “FAIRification” of nanoEHS data. The goals and expected outcome of this work and subsequent efforts are to enable improved assembly of nanoEHS data for computational use (e.g., modeling and discovery), improved consistency for data interpretation, sharing, and interoperability, increased findability and longevity of data, support for sharing and transfer of knowledge between US federal partners and further scientific communities. To address the need for a consistent nomenclature for nanomaterials, here we discuss the creation of a consistent naming convention for EPA tested nanomaterials, with a focus on data included in the EPA NKB. We discuss our work with ISA-TAB-Nano and how this relates/improves input/output and data sharing. Further, we discuss semantic mapping and the NKB Resource Description Framework (RDF), as well as our creation of the EPA OntoSearcher tool that allows for automated ontology mapping. We illustrate here, through NKB use case examples, how this work contributes to a common language for nanoEHS data, which can be applied to other nanomaterials datasets, and is in support of FAIR data standards.\n\n\nMethods\n\nWe have implemented an EPA-internal naming convention for nanomaterials using the Natural Language Processing (NLP) approach (Figure 1), which incorporates chemical, physical, and mercantile elements of each material. A prefix of “nano” denotes that this is a nanomaterial, followed by the core material and any shell or coating information. Given the unique qualities of nanomaterials are often due to their size, we include the diameter. Any information on the supplier ID for the material (product or lot numbers) are subsequent, followed by an incrementing designation to track the number of separate materials with the said parameter in our dataset. Figure 2 illustrates how the substance name maps onto a definition of the makeup of the chemical. We have mapped all chemical substances in the NKB to the EPA CCD (Figure 3).\n\nThese descriptions included physical, chemical, and commercial traits.\n\nWe have developed Python code (version 3; (Van Rossum 2009)) to automate formatting of ENM data into the standard and universally accepted ISO-TAB Nano format (Marchese Robinson, Cronin et al. 2015). We have written this code to both WRITE (export) NKB data in ISO-TAB Nano format, entitled NKBtoITN.py, as well as READ (input) external data already in the ISO-TAB Nano format for potential inclusion into NKB, entitled ITNtoNKB.py.\n\nWe have developed an application, entitled the EPA “OntoSearcher”. The OntoSearcher was developed in Python (version 3; (Van Rossum 2009)) and is compatible with all major operating systems. Two types of input files are required to run the application: one or more .owl files (a standard format for ontology files, typically provided by an ontology owner when disseminated) and the user’s dataset in.csv format. If the user’s data were originally in a.sql format, one.csv file should be provided per table. Each data field should be a column, and each set of entries should be a row. Ontosearcher requires the packages ‘rdflib’ (Boettiger 2018) to create and manage the graph, ‘rapidfuzz’ (Bachmann 2021) to handle fuzzy matching during searches, and ‘owlready2’ (Lamy 2017) to assign ontologies. OntoSearcher workflows for term matching and graph creation are provided in Figure 4 and Figure 5, respectively. Figures 6 illustrates the data tables resulting from the semantic mapping of NKB.\n\nThe user manually selects one or more ontologies, uses matcher() to see how well they cover the terms in the dataset, and is provided with suggestions for additional ontologies by bioportal_search(). This process continues until the user is satisfied with the coverage provided by the selected ontologies.\n\nThe user processes each table from their dataset individually. The table is converted to triples, and the results of the matcher() method are used to automatically convert as many terms as possible into their equivalents from the ontologies. The remaining unmapped terms are reported to the user for manual curation. Once the manual mappings are supplied to Ontosearcher, it finishes handling the replacements.\n\nThe second column lists the predicate. The third column lists the object of the triple, which is either a simple object or a “bag” of triples sharing a common theme. Bags are further extended to show their predicates and objects. Connections are made through a combination of DOIs and IDs, represented by the lines in the schema. Since all data in the NKB is sourced from a paper, all types of data draw their DOI from the Publication triples. The IDs are used for differentiation of mediums, materials, and assays within a DOI. Mediums are marked in orange, materials are in blue, and assays are in green. This schema trims each table in the interest of space.\n\nInteractive tutorials (S1, S2) have been developed using the Jupyter Notebook document format (Thomas Kluyver 2016). Use of OntoSearcher requires an Application Programming Interface (API) key to grant software access to a service and for the BioPortal web service (Whetzel, Noy et al. 2011). Input files are required in the.csv and.owl formats. An intermediate file is created in.json format. Output files are written in terse RDF triple language format or.ttl ((W3C team 2011); http://www.w3.org/TeamSubmission/turtle/), which is a text file format. The resulting.ttl file can be used directly by parties of interest, or alternatively, used to establish a SPARQL endpoint ((W3C team 2013); https://www.w3.org/TR/sparql11-overview/) for distribution and sharing of the RDF. Table 1 lists the publicly available ontologies and vocabularies used the in semantic mapping of NKB, each sources prefix in RDF and associated IRIs.\n\n\nResults\n\nThe NKB schema (Boyes, Beach et al. 2022) was designed to capture a material, the parameters of experiments performed upon it, and the results of those experiments. In order to improve the interoperability of NKB and other datasets, we implemented an EPA-internal naming convention for nanomaterials, depicted in Figure 1. This naming scheme was established using the Natural Language Processing (NLP) approach, which incorporates chemical, physical, and mercantile elements of each material. The utility of this approach is illustrated in Figure 2, whereby name of the substance maps onto a definition of the makeup of the chemical. While this naming convention is useful for EPA internal cases, such as connecting with the EPA CCD, it is not ideal for expanded comparisons because it may not contain enough information to remain distinguishable against other datasets (e.g., data that may not have particular parameters contained within NKB or CCD). Currently, we have 373 chemical structures mapped on the EPA CCD, available at https://comptox.epa.gov/dashboard/chemical_lists/NAKNOWBASE, and illustrated in Figure 3. This collaborative, cross EPA-ORD effort is updated as NKB ENMs are made available and added for curation.\n\nWe have implemented the spreadsheet-based format for nanomaterials sharing, ISA-Tab-Nano, which was inspired by the high-throughput genomics community (Thomas, Gaheen et al. 2013). Both pieces of code WRITE/OUTPUT (NKBtoITN.py), and READ/INPUT (ITNtoNKB.py) and corresponding documentation are made available to the public via EPA ORD and Data.gov and available for download (CSS_3.2.2.1_NKB_IsoTabNano.zip) at https://catalog.data.gov/dataset/css-3-2-2-1-naknowbase. Though this code is useful for specifically NKB to ISA-Tab-Nano conversion, we found that extending this code to other datasets was problematic; whereby, other data would have to be re-formatted to NKB format or code would need to be rewritten to accept alternate input formats.\n\nTo continue to improve NKB interoperability, we have developed an application, entitled “OntoSearcher”, that automates ontological term mapping for a given ENM dataset. We have developed this python code to read in ENM data from NKB, and generically for other data sources, map those data to ontological terms, and provide a corresponding diagnostic report on speed and accuracy of the mapping. The code and corresponding documentation for the tool and application, as well as training materials, are made available to the public via EPA ORD and Data.gov and available for download (OntoSearcher_Training_Materials.zip) at https://catalog.data.gov/dataset/naknowbase-interoperability-tools. Schematics of two OntoSearcher workflows, Phase 1 and Phase 2 are presented in Figure 4 and Figure 5, respectively. As illustrated in Figure 4, the Phase 1 OntoSearcher workflow illustrates the conversion of an existing dataset into an RDF. This process required two types of input files (i.e., .owl and.csv). The OntoSearcher ‘matcher’ method evaluates how well the supplied ontologies cover the dataset. In order to provide additional coverage of the dataset, ontologies are identified by bioportal search (Noy, Shah et al. 2009) in a ‘search’. The user iterates between ‘matcher’ and ‘search’ until their collection of ontologies covers a strong majority of their dataset. Lastly, when percentage of matches is achieved, the combined ontologies are output to file. In the second phase, shown in Figure 5, the dataset is added in table increments, to a graph. The ‘matcher’ method is used again, this time to determine which terms have been matched by the finalized ontologies and identify those terms that require manual curation. Terms are returned as either a matched group or an unmatched group, allowing the curator to review the automated matches. Term replacements are performed on the graph, whereby the natural language terms are swapped out from the raw data with the matching terms from the compiled ontologies. Next, the curator consults their ontologies to find matches for the unmatched terms. When the list of manual curations is complete, it is applied to the graph. In some cases, implied relationships between columns in the dataset will need to be explicitly stated by the curator by using the graph search method, such as a ‘nodebag’ method (e.g., ‘diameter value’ and ‘diameter units’ columns are both related to the concept of “diameter” to a human reader, but such relationships are not observed by the computer). Once the data have been matched to and replaced by the correct ontology terms, they are ready to be serialized into a.ttl file.\n\nFigure 6 illustrates the NKB RDF schema produced using the OntoSearcher tool and following the above procedures for semantic mapping of ten NKB tables that correspond to Boyes, et al. (Boyes, Beach et al. 2022) (i.e., Assay; Parameters; Result; Molecular Result; Material; Material FG; Contam; Publication; Medium; Additive). The NKB RDF has 10,261,162 triples, documenting 22,329 assays performed on a combined 373 materials from 128 publications. Table 1 lists each of the established and publicly available ontologies and vocabularies used in mapping, manual and automated, to terms in NKB tables illustrated in Figure 6.\n\nFigure 7 Illustrates a local (NKB) SPARQL use case query for publications included in NKB that contain data on ‘Titanium Dioxide core’, specifically. Results of this query are requested by publication DOI, and limited to 5 for illustration purposes. Figure 8 illustrates a federated SPARQL query across two EPA datasets, NKB (Boyes, Beach et al. 2022) and AOP-DB (Mortensen, Senn et al. 2021), where the user is inquiring as to which NKB nanomaterial is associated with the highest number of biological pathways in AOP-DB. Results are again limited to 5 for ease of illustration.\n\nThis query finds all materials in the NaKnowBase listed as having a Titanium Dioxide core, then groups the results by source publication and limits the display to the top 5.\n\nThis query calls to the AOPDB SPARQL endpoint for information on the relationships between materials (by CASRN), genes, and pathways. Then, locally, the results are used to query the NaKnowBase RDF and determine which NKB materials correspond to the results from the AOPDB. The results show the 5 material-gene combinations that impact the most pathways, as well as the DOI of the source paper for that material in the NKB. The materials are reported by link to the CompTox Chemicals Dashboard.\n\n\nDiscussion\n\nIn an effort to improve the EPA NKB from the relational database presented by Boyes et al. (2022), we have developed tools and applications which promote the development of a common language for ENMs and contribute to “FAIRification” of US Federal ENM data. The purpose of these tools are to enable improved assembly of nanoEHS data for computational use with minimized human curation, improved consistency of data format for interoperability, increased findability and longevity of nanoEHS data, and to enable support for sharing and transfer of knowledge between US Federal partners and further scientific communities.\n\nBecause manual curation for even a small dataset is not trivial, we created EPA OntoSearcher to semi-automate the process of mapping pre-defined ontological terms to individual datasets, and thereby minimizing manual input from the curator. We have developed code to read in ENM data from NKB and other data sources, and map those data to ontological terms, as well as providing a corresponding diagnostic report on speed and accuracy of the mapping. We walk the user through this process, as illustrated in the OntoSearcher workflows presented in Figures 4 and 5. We present our own use of the tool, with the EPA NKB semantic mapping illustrated in Figure 6, using the ontologies listed in Table 1. Multiple queries were performed on the NKB RDF using the locally stored.ttl file. Figure 7 contains a simple example, in which the.ttl file is queried for information on every instance of Titanium Dioxide in the dataset. Figure 8 contains a more advanced, federated query example, showing the benefits of the RDF format in traversing across datasets. Since the AOP-DB RDF is available through a SPARQL endpoint (Mortensen, Martens et al. 2022), we were able to perform a query directly on both datasets, listing any materials from the NKB that are involved in AOPs derived from the AOP-Wiki, and include information on which genes are relevant to the interaction.\n\nWith the RDF, formatting is reduced to an object, a relationship, and the target of that relationship (i.e., the “triple”). All data, however complex, can be reduced to some number of sets of these triples. The terms used as each part of a triple are drawn from rigidly-defined ontologies. Many ontologies already exist to provide structure to scientific vocabularies. Some of these ontologies, such as the Chemical Information Ontology (cheminf) ((Fu 2021); https://www.ebi.ac.uk/ols/ontologies/cheminf), are broad enough to be useful for reducing some aspects of nanomaterial data to triples (Hastings, Jeliazkova et al. 2015). However, unique disciplines require additional support for total coverage.\n\nWith the increase in study of nanomaterials over the last decades, we have seen an increase in nano-related databases, knowledgebases, web-based libraries, and registry repositories (Ayadi, Rose et al. 2021) for review). Further, the importance of nanomaterial-specific ontologies in relation to data-sharing has been recognized in many nano and nano-related subject areas (Thomas, Klaessig et al. 2011, Hastings, Jeliazkova et al. 2015, Jeliazkova, Chomenidis et al. 2015, Karcher, Willighagen et al. 2018, Ayadi 2020, Ayadi, Rose et al. 2021). Given the vast breadth of information, and format across these datasets, it becomes impractical and even untenable to carry out any data integration exercise that would allow a concerted observation, such as that necessary for regulatory decision-making. This observation prompts a dramatic need for a shift in thinking from recent nanoinformatics initiatives and efforts at nanomaterial data curation for specific purposes (National Science and Technology Council 2011, Hendren, Powers et al. 2015, Karcher, Willighagen et al. 2018, Yan, Sedykh et al. 2020). Further, given the current speed at which nanomaterials enter the marketplace, collecting and curating data on emerging nanomaterials is expected to become more difficult over time. Both the number of nanomaterials and the scope of characteristics to catalog are constantly increasing. Tools that assist and automate aspects of data processing, like EPA OntoSearcher, will become increasingly useful in our ability to maintain consistent curation standards, interpret, analyze and share data, while reducing risk of computer-introduced errors or biases. For example, automated tools can compare a term against thousands of definitions and synonym lists in the time it takes the human curator to compare against a single definition. Proper use of these tools reduces the curator’s workload to merely validating the matches made by the tool and handling whatever terms were absent from ontologies. Rapid integration of disparate data sources, enabled by these sorts of toolkits, will greatly affect nanoinformatics on all levels from the data customer, creator, and curator, to the analyst or assessor. Our ability to scrutinize multiple data sources consecutively allows for more efficient and timely understanding of emerging nanomaterials, while underlining the central role of data standardization, interoperability and FAIR practices in our ability to meet the incoming needs for interpretation of the effects of nanomaterials on the environment and public health.\n\n\nConclusions\n\nThe methods, tools and applications described here will be implemented for the inclusion, processing and FAIRification of novel EPA data related to nanomaterials. EPA and other Federal partners, as part of the NEHI DIIG, have proposed a federal nanoEHS consortium to create interoperable formats for federal nanoEHS data. The results of this effort are forthcoming.\n\n\nAuthor contributions\n\nHM: Conceived of, directed the study and analyses, and wrote and edited the manuscript; BB: revised the NKB RDF to version 2, improved the OntoSearcher tool, developed training documents, produced figures, wrote and edited the manuscript; WS: developed code for the initial version of OntoSearcher; JS: provided technical support and expertise for the first version of OntoSearcher and NKB RDF version 1; AW: Performed the NLP and mapping of NKB materials to DSSTox, assisted in creating the EPA nomenclature for NKB, created the NKB nanomaterial linkages in CCD and wrote and edited the manuscript; WB: wrote and edited the manuscript.\n\n\nEPA disclaimer\n\nThis manuscript has been reviewed by the Center for Public Health and Environmental Assessment, United States Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The authors declare no conflict of interest.\n\n\nORISE disclaimer\n\nThis research was supported in part by an appointment to the U.S. Environmental Protection Agency (EPA) Research Participation Program administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Environmental Protection Agency. ORISE is managed by ORAU under DOE contract number DE-SC0014664. All opinions expressed in this paper are the author’s and do not necessarily reflect the policies and views of US EPA, DOE, or ORAU/ORISE.",
"appendix": "Data availability\n\nThe U.S. EPA has made NaKnowBase data files, and all related code and training materials discussed here, publicly available through the EPA Office of Research’s Science Hub at: DOI: http://10.0.92.167/1523156, which feeds to Data.gov at https://catalog.data.gov/dataset/naknowbase-interoperability-tools.\n\nSource data for the entire NaKnowBase relational database (Boyes, Beach et al. 2022) is available at: https://catalog.data.gov/dataset/css-3-2-2-1-naknowbase, and at: https://gaftp.epa.gov/EPADataCommons/ORD/NaKnowBase/.\n\n\nAcknowledgements\n\nThe authors would like to acknowledge and thank Chris Grulke (previously affiliated with the US EPA/ORD) for his contribution to the early establishment of the EPA nomenclature for nanomaterials in NKB and those submitted to the CCD; Egon Willighagen and Amar Amar (University of Maastricht, BIGCAT) for their direction and comment on early versions of the OntoSearcher tool. We are also grateful for the internal EPA reviewers, Daniel Chang and Candice Lavelle, for their thoughtful review and critical comments on the manuscript.\n\n\nBibliography\n\nAllied Market Research: Nanotechnology Market By Type (Nanosensor and Nanodevice) and Application (Electronics, Energy, Chemical Manufacturing, Aerospace & Defense, Healthcare, and Others): Global Opportunity Analysis and Industry Forecast, 2021-2030.2021. Reference Source\n\nAyadi A, Auffan M, Rose J: Ontology-based NLP information extraction to enrich nanomaterial environmental exposure database. Procedia Comput. Sci. 2020; 176: 360–369. Publisher Full Text\n\nAyadi A, Rose J, de Garidel-Thoron C , et al.: MESOCOSM: A mesocosm database management system for environmental nanosafety. NanoImpact. 2021; 21: 100288. PubMed Abstract | Publisher Full Text\n\nBachmann M: RapidFuzz. Zenodo. 2021.\n\nBoettiger C: rdflib: A high level wrapper around the redland package for common rdf applications. Zenodo. 2018.\n\nBoyes WK, Beach B, Chan G, et al.: An EPA database on the effects of engineered nanomaterials-NaKnowBase. Sci. Data. 2022; 9(1): 12. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBoyes WK, Thornton BLM, Al-Abed SR, et al.: A comprehensive framework for evaluating the environmental health and safety implications of engineered nanomaterials. Crit. Rev. Toxicol. 2017; 47(9): 767–810. PubMed Abstract | Publisher Full Text\n\nFu G, Munteanu C, Davies M, et al.: cheminf.2021.\n\nHaase AKF e: EU US Roadmap Nanoinformatics 2030. EU Nanosafety Cluster; 2018.\n\nHastings J, Jeliazkova N, Owen G, et al.: eNanoMapper: harnessing ontologies to enable data integration for nanomaterial risk assessment. J. Biomed. Semantics. 2015; 6: 10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHendren CO, Powers CM, Hoover MD, et al.: The Nanomaterial Data Curation Initiative: A collaborative approach to assessing, evaluating, and advancing the state of the field. Beilstein J. Nanotechnol. 2015; 6: 1752–1762. Publisher Full Text\n\nJeliazkova N, Chomenidis C, Doganis P, et al.: The eNanoMapper database for nanomaterial safety information. Beilstein J. Nanotechnol. 2015; 6: 1609–1634. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKarcher S, Willighagen EL, Rumble J, et al.: Integration among databases and data sets to support productive nanotechnology: Challenges and recommendations. NanoImpact. 2018; 9: 85–101. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLamy JB: Owlready: Ontology-oriented programming in Python with automatic classification and high level constructs for biomedical ontologies. Artif. Intell. Med. 2017; 80: 11–28. PubMed Abstract | Publisher Full Text\n\nLowe CN, Williams AJ: Enabling High-Throughput Searches for Multiple Chemical Data Using the U.S.-EPA CompTox Chemicals Dashboard. J. Chem. Inf. Model. 2021; 61(2): 565–570. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMarchese Robinson RL, Cronin MT, Richarz AN, et al.: An ISA-TAB-Nano based data collection framework to support data-driven modelling of nanotoxicology. Beilstein J. Nanotechnol. 2015; 6: 1978–1999. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMortensen HM, Martens M, Senn J, et al.: The AOP-DB RDF: Applying FAIR Principles to the Semantic Integration of AOP Data Using the Research Description Framework. Front. Toxicol. 2022; 4: 803983. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMortensen HM, Senn J, Levey T, et al.: The 2021 update of the EPA’s adverse outcome pathway database. Sci. Data. 2021; 8(1): 169. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNational Science and Technology Council: Materials Genome Initiative for Global Competitiveness. National Science and Technology Council, Office of Science and Technology Policy; 2011.\n\nNIEHS: Environmental Health Language Collaborative.2023. Reference Source\n\nNoy NF, Shah NH, Whetzel PL, et al.: BioPortal: ontologies and integrated data resources at the click of a mouse. Nucleic Acids Res. 2009; 37(Web Server issue): W170–W173. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThomas DG, Gaheen S, Harper SL, et al.: ISA-TAB-Nano: a specification for sharing nanomaterial research data in spreadsheet-based format. BMC Biotechnol. 2013; 13: 2. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThomas DG, Klaessig F, Harper SL, et al.: Informatics and standards for nanomedicine technology. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2011; 3(5): 511–532. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThomas Kluyver BR-K, Pérez F, Granger B, et al.: Jupyter Notebooks-a publishing format for reproducible computational workflows. Loizides F, Schmidt B, editors. Positioning and Power in Academic Publishing: Players, Agents and Agendas; 2016; 87–90.\n\nVan Rossum GD, Fred L: Python 3 Reference Manual. Scotts Valley, CA: CreateSpace; 2009.\n\nW3C team: Turtle - Terse RDF Triple Language. Berners-Lee: D. Beckett and T; 2011.\n\nW3C team: SPARQL 1.1 Overview. T. W. C. S. W. Group; 2013.\n\nWhetzel PL, Noy NF, Shah NH, et al.: BioPortal: enhanced functionality via new Web services from the National Center for Biomedical Ontology to access and use ontologies in software applications. Nucleic Acids Res. 2011; 39(Web Server issue): W541–W545. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWilliams AJ, Grulke CM, Edwards J., et al.: The CompTox Chemistry Dashboard: a community data resource for environmental chemistry. J. Cheminform. 2017; 9(1): 61. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYan X, Sedykh A, Wang W, et al.: Construction of a web-based nanomaterial database by big data curation and modeling friendly nanostructure annotations. Nat. Commun. 2020; 11(1): 2519. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "263181",
"date": "08 May 2024",
"name": "Vladimir Lobaskin",
"expertise": [
"Reviewer Expertise Nanoinformatics",
"Materials science",
"Condensed Matter Physics"
],
"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 describes new tools facilitating the annotation and integration of nanomaterials data from EPA NaKnowBase. The motivation part outlines the current challenges in the NanoEHS area and proposes a solution following the FAIR principles and direction from the EU-US Nanoinformatics Roadmap. The developed methodology and software have obvious utility and are indispensable for current and future nanosafety research. The methodology is well justified and illustrated, and, most importantly, linked to the web resources. I am happy to recommend this paper with the following minor amendments.\n\nIt would be good to mention the paper on the latest major EU-US effort (Maier D, et al., 2023 [Ref 1]) Typos: Page 3: “Nanoinformatics, the compilation, integration, and assessment of nanoEHS data” - Generally, nanoinformatics entails more than this. It also includes data processing and management, annotation, ontologies, modelling tools, etc. I suggest rephrasing it as follows: “Nanoinformatics, the field concerning in particular the compilation, integration, and assessment of nanoEHS data” or add a more complete definition. Page 4: “agency specific” -> agency-specific Page 4: “and, to our knowledge is” -> and, to our knowledge, is Page 4,5: “ISO-TAB Nano” (3 instances) > ISA-TAB-Nano Page 5: “in.csv format. If the user’s data were originally in a.sql format, one.csv file should be provided per table.” - > in .csv format. If the user’s data were originally in a .sql format, one .csv file should be provided per table. Page 5: “Ontosearcher” -> OntoSearcher Page 5: “Figures 6 illustrates” -> Figure 6 illustrates Page 5: “the.csv and.owl” -> the .csv and .owl Page 5: “ in.json”, “resulting.ttl”, “or.ttl” -> in .json, resulting .ttl, or .ttl Page 6, Figures 4,5: redraw to remove the underlining of “bioportal_search()”, “.ttl” Page 6: “Natural Language Processing (NLP) approach (Figure 1), which incorporates chemical, physical, and mercantile elements of each material.” - repetition of a sentence from the Methods section. Page 7: “ISA-Tab-Nano” -> ISA-TAB-Nano. Page 8: “and.csv” -> and .csv Page 8: “when percentage of matches is achieved” – desired percentage or final percentage? It is better to be specific. Page 8: “The purpose of these tools are” -> The purpose of these tools is Page 8: “stored.ttl”, “the.ttl” - > stored .ttl, the .ttl Page 10: “registry repositories (Ayadi, Rose et al. 2021) for review).” -> registry repositories (see (Ayadi, Rose et al. 2021) for review). Page 11: “Haase AKF e” -> Haase A, Klaessig F\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and materials provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
},
{
"id": "269340",
"date": "25 May 2024",
"name": "Philip Doganis",
"expertise": [],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis work presents methods and tools to include, process and FAIRify NM data, whether new or not published in a machine-readable format with sufficient accompanying information. It provides an efficient and easy to use workflow that can lead to FAIR datasets. As with all automatic tools, the semantic integration OntoSearcher tool has some limitations inherent in the rationale structured into it, but if a tool can handle the straightforward terms and leave some ontology terms for the researcher that is great help in an otherwise daunting task. Perhaps an explanation of the parameterisation of the tool would be needed, so more experienced users can intervene. Overall, this is needed work that solves an existing problem.\nChange ISOTAB to ISATAB in linked documents, (i.e. in https://catalog.data. gov/dataset/css-3-2-2-1-naknowbase ) Brief mention of background and need for this and its interactions with existing work. interoperability with U.S. and European partners ? US-EU roadmap, is there a citation?\np.4 “Efforts to coordinate data have been hindered by diversity of information, and format incongruities. “ Also mention missing or partial description of protocols\nsince modelling is mentioned, are there scripts that enable easy extraction in a ready-to-model format?\np5. Define the connection to, or possible assignment of, DTXSIDs for the NMs. Will they be usable in the EPA tools (i.e. CCTE ?) Fig.6 provide in higher resolution or provide an external link where it is legible\np.8, 10 How does Ontosearcher handle multiple ontology results for a term? (does it choose the first?)\np.8 The phrase “(e.g., ‘diameter value’ and ‘diameter units’ columns are both related to the concept of “diameter” to a human reader, but such relationships are not observed by the computer)” should be rephrased for clarity. By refering “are not observed by the computer” does this refer to the processing of the data?\nFor example, there this entry: https://bioportal.bioontology.org/ontologies/OM?p=classes&conceptid=http%3A%2F%2Fwww.ontology-of-units-of-measure.org%2Fresource%2Fom-2%2FDiameter which is an example of the possibility to refer to diameter units of measure.\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and materials 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/13-169
|
https://f1000research.com/articles/13-167/v1
|
08 Mar 24
|
{
"type": "Research Article",
"title": "Cytogenetic profile and risk of transformation to acute myeloid leukemia (AML) in Indonesian patients with myelodysplastic syndrome (MDS): a pilot study",
"authors": [
"Noorwati Sutandyo",
"Agus Susanto Kosasih",
"Resti Mulya Sari",
"Lyana Setiawan",
"Ikhwan Rinaldi",
"Veronika Juanita Maskito",
"Yuniar Harris Prayitno",
"Agus Susanto Kosasih",
"Resti Mulya Sari",
"Lyana Setiawan",
"Ikhwan Rinaldi",
"Veronika Juanita Maskito",
"Yuniar Harris Prayitno"
],
"abstract": "Background Cytogenetics is a fundamental examination in the course and management of myelodysplastic syndrome (MDS) since it is widely used as a diagnostic and prognostic indicator for the disease. Some cytogenetic profiles are associated with a higher risk of acute myeloid leukemia (AML) transformation. This is the first study to evaluate the cytogenetic profile of Indonesian patients with MDS.\n\nMethods This prospective cohort study was conducted at the Cancer Center and several other referral hospitals. Patients with primary MDS aged >18 years were included in the study. Clinical examination, peripheral blood smear, and bone marrow aspiration were performed, followed by cytogenetic examination. The results were further categorized into revised international prognostic scoring system (IPSS-R) scores, and cytogenetic profiles were descriptively presented. Patients were followed up for one year to evaluate AML transformation.\n\nResults A total of 28 MDS patients, aged 66±12 years, were included in this study. The majority of the patients were male (n=17;60.7%), aged 65 years or above (n=19;67.9%), diagnosed with MDS-MLD (n=14;50%), and had an intermediate cytogenetic group (n=4;14.3%). The IPSS-R score was high in 6 (21.4%) patients and very high risk in 3 (10.7%) patients. During one-year follow-up, AML transformation occurred in 3 (10.7%) patients, and 10 (35.7%) patients ceased. Monosomy 7 was observed in 6 (21.4%) patients but in one metaphase each. Deletion of chromosome 5 (del(5)(q31)), del (16)(q21.1), and del (16)(q11.2) were found in a male patient with MDS-EB1.\n\nConclusions Monosomy 7 and deletion of chromosome 5 have been identified in Indonesian patients with MDS. MDS-EB has the highest risk of AML transformation.",
"keywords": [
"Myelodysplastic syndrome",
"Acute myeloid leukemia",
"cytogenetic profile",
"karyotyping"
],
"content": "Introduction\n\nMyelodysplastic syndrome (MDS) is a heterogeneous group of myeloid clonal disorders caused by ineffective hematopoiesis or failure of blood cell maturation, resulting in peripheral blood cytopenia and bone marrow failure.1 Patients with MDS have increased susceptibility to acute myeloid leukemia (AML).2 Most MDS cases are de novo or primary, while the remaining 10% are secondary, resulting from prior exposure to radiotherapy or chemotherapy for cancer.3\n\nThe reported incidence rate of MDS in the general population is 4.5 per 100,000 people per year, with a higher incidence in men than in women (6.2 vs. 3.3 per 100,000 people per year).4 In the United States alone, more than 10.000 new cases are reported annually. Studies have consistently shown that MDS is more commonly diagnosed in patients with advanced age.5 More than 80% of patients with MDS were first diagnosed at the age of 60 years, with a median age of 76 years, and only 6% of patients had disease onset under 50 years of age.6,7 Based on the Surveillance, Epidemiology, and End Results (SEER) Medicare database, the incidence of MDS is as high as 75 per 100,000 persons in the population older than 65.8 The incidence of MDS is expected to continue to increase because of the higher incidence of secondary MDS, improved awareness of the disease in the general population and clinicians, and more advanced clinical workups. MDS was more frequent in men than women.5 In Asian countries, the incidence of MDS was reported to be 2- to 4-fold lower, and the age of onset was ten years younger than that in Western countries.9\n\nMDS is considered a preleukemic condition, in which 30% of patients progress to AML.10 Age 65 years old and younger, bone marrow blast count >5%, and transfusion dependence were associated with AML transformation.11 Narayanan et al. reported that AML transformation occurred in 10% of MDS patients within six months.12 The pathophysiology of MDS and its progression to AML involves cytogenetic, genetic, and epigenetic factors.13\n\nCytogenetics plays a vital role in the disease course and management and serves as a diagnostic and prognostic indicator in MDS.14 Chromosomal karyotype is included in the Revised International Prognostic Scoring System (IPSS-R) as a fundamental factor for predicting the clinical progression of the disease and guiding the management plan.15 Through the IPSS-R risk group, a clinician can differentiate patients with higher risk, with the treatment goals of delaying AML transformation and improving overall survival.16 The current standard of management for high-risk patients includes hypomethylating agents, decitabine, azacitidine, and allogeneic stem cell transplants.17\n\nCytogenetic abnormalities were abnormal in >50% of the patients at diagnosis.18 Amplifications, deletions, and translocations were cytogenetic abnormalities found in 50% of primary MDS patients and 80% of secondary MDS patients.19\n\nCurrently, there are no published data regarding the cytogenetic profiles of MDS patients in Indonesia. This study aimed to provide a descriptive overview of patients’ demographic and cytogenetic profiles from the National Cancer Center in Indonesia.\n\n\nMethods\n\nThis prospective cohort study was conducted at the Cancer Center Hospital and the other 13 referral hospitals spread around the Jakarta metropolitan area, which sent bone marrow aspirates to the cancer center for leukemia phenotyping from December 2020 to December 2021. Subjects eligible for inclusion in the study were required to be at least 18 years old and exhibiting indications of primary MDS as determined through comprehensive assessments encompassing their medical history, physical examination, peripheral blood smear, and bone marrow cytomorphology. Patients with secondary MDS were excluded from this study.\n\nThe study’s sample size estimation employed the formula designed for determining the sample size in studies focusing on population proportions. The significance level (p) was established at 0.05, corresponding to a 95% confidence interval, resulting in the acquisition of the value ∝ = 1.96. The targeted research power was set at 90%, aligning with a value of Zβ = 1.282. The preferred level of absolute precision (d) was specified as 0.1. The proportion of MDS patients who carry cytogenetic abnormalities is 34%.\n\nDue to the decreasing number of visiting patients during the coronavirus disease (COVID-19) surge in 2020, a total sampling approach was adopted. All potential patients were approached by the hematologist in the respective hospital.\n\nThe diagnosis of MDS was established according to International Working Group (IWG) guidelines, which require that a patient must have at least two of the following prerequisites: 1) stable cytopenia for ≥6 months unless accompanied by a specific karyotype or bilineage dysplasia, in which case only two months of stable cytopenia are needed; and 2) the exclusion of other potential disorders as a primary reason for dysplasia, cytopenia, or both. Additionally, the diagnosis of MDS also requires ≥1 of 3 MDS-related (decisive) criteria: 1) dysplasia (≥10% in ≥1 of the three major bone marrow lineages), 2) a blast cell count of 5–19%, and 3) a specific MDS-associated karyotype [for example, del(5q), del(20q), +8, or -7/del(7q)].20\n\nDemographic and clinical data were collected, including age, sex, weight, height, body mass index (BMI), organomegaly (splenomegaly and/or hepatomegaly), lymphadenopathy, peripheral blood smear result, peripheral and medullary blast percentage, subtypes of MDS, cytogenetic group, and the Revised International Prognostic Scoring System (IPSS-R) score classification.\n\nThe IPSS-R score was calculated based on the following variables: cytogenetic subgroup, bone marrow blast percentage, hemoglobin level, platelet count, and Absolute Neutrophil Count (ANC), and the results were subsequently classified as very low, low, intermediate, high, or very high. MDS subtypes were established using the World Health Organization (WHO) 2016 classification, which includes MDS with multilineage dysplasia (MDS-MLD), single lineage dysplasia (MDS-SLD), ring sideroblasts (MDS-RS), excess blasts (MDS-EB -1 and 2), isolated del (5q), and unclassifiable (MDS-U).21\n\nTo mitigate the risk of potential bias, all bone marrow aspirate (BMA) samples were promptly transported to the clinical pathology laboratory of the Cancer Center Hospital within a four-hour window from the time of sample collection. A minimum of 10 mL of bone marrow aspirate (BMA) specimens was collected from each subject and separated into two tubes with different anticoagulants, that is, ethylenediaminetetraacetic acid (EDTA) for cytomorphology and heparin for cytogenetics. After short-term culture, the cells were harvested and placed on slides for conventional G-banding karyotyping. Karyotyping was subsequently analyzed using the Automated Cell Imaging System CytoVision® (Leica Biosystems, USA) and reported in accordance with the International Standard for Human Cytogenomic Nomenclature (ISCN 2016).\n\nPatients were then observed for one year through their routine appointments to determine whether they had transformed into AML by monitoring their periodic peripheral blood results. If any blast cells were found in the peripheral blood or the cytopenia deteriorated, a bone marrow puncture was performed to confirm whether there was an increase in the blast count to ≥20% of the total nucleated cells in the bone marrow.\n\nAll collected data were reported descriptively to provide clinical profiles and participants’ cytogenetics using IBM SPSS Statistics version 25 tabulation.\n\nThis study was approved by the ethical committee of the Cancer Center Hospital on September 14th, 2020 (No. 0123/KEPK/IX/2020). Written informed consent was taken from all participants subsequent to their agreement to participate in the study.\n\n\nResults\n\nA total of 28 patients with MDS were included in this study, with a mean age of 66±12 years old.41 We found that nine patients (32.1%) were below 65 years of age, with the youngest being 25 and the oldest being 85. The majority of the participants were male (n=17; 60.7%), and the sex ratio between men and women was 1.54. Six of the nine patients (66.7%) younger than 65 years of age were male. Two (7.14%) patients were aged < 50 years. The most prevalent MDS type in this study population was MDS-MLD (n=14/28; 50.0%), followed by MDS-SLD (n=7/28; 25.0%) and MDS-EB1 (n=5/28; 17.9%). The flow chart of the study population and additional demographic details are shown in Figure 1 and Table 1 respectively.\n\nCytogenetic analysis revealed metaphase in only 14 (50.0%) patients. Due to insufficient metaphase in the sample, cytogenetic grouping could only be done in nine patients (32.1%) (Table 2). There were 4 patients in the intermediate, 3 in the poor, and 2 in the very poor cytogenetic groups. Based on the IPSS-R category, five patients (17.8%) were at high risk, and three patients (10.7%) were categorized as very high risk, while the remaining 20 patients (71.4%) could not be categorized due to the absence of metaphase during cytogenetic analysis.\n\nThe cytogenetic profile showed monosomy 7 in six patients. However, it was only found in one metaphase in each patient, so it could not be interpreted as a clonal mutation. Deletion of chromosome 5 (del(5)(q31)), del (16)(q21.1), and del (16)(q11.2) was found in a male patient with MDS-EB1, considered a very poor cytogenetic group, who had AML transformation three months after the diagnosis. The patient died one month after the transformation to AML. In total, three patients developed AML during follow-up.\n\nThe 1-year overall survival rate in this study was 64.3%, with 10 of 28 patients deceased. The causes of death were AML (n=3; 30%), COVID-19 (n=3; 30%), bacterial pneumonia (n=2; 20%), cerebrovascular disease (n=1; 10%), and complications of diabetes mellitus (n=1;10%). In the deceased group, the median age of the patients was 69 (55-85) years, with a female-to-male ratio of 1 to 2.6, and the majority of them were MDS-EB1 (40%). The cytogenetic group, which was successfully identified in 9 patients, ranged from high to very high risk. In the surviving group, the median age of the patients was 69 (25-82) years, the female-to-male ratio was 1 to 1.125, and the majority of subjects had MDS-MLD (50.0%). Unfortunately, only three cytogenetic profiles were identified in this group, which indicated a high risk.\n\n\nDiscussion\n\nIn this study, more than half of the patients with MDS were male. This finding was in accordance with the epidemiology of MDS in the general population, which showed a global predominance in males globally.22,23 The sex ratio within our study is within the reported range, which is 1.24-2.125.9\n\nWe found that almost one-third of our study population was diagnosed under 65 years of age, younger than the general population of MDS patients. Based on the Dutch registry, the median age of the patients with MDS at the first diagnosis was 74.24 In Europe, the reported median age at diagnosis is 76 years.6 It has been highlighted that there was a difference in median age between Asian and Western countries, as reported by studies from China and Japan, ranging from 62 to 76 years old.25,26 The difference in age of onset between Asian and Western countries might be explained by differences in environmental exposure. Genetic factors may also have a significant effect. Less than 10% of the patients were diagnosed under 50 years of age, which was in accordance with a prior study.27\n\nOur data show that the MDS-MLD subtype has the highest frequency among other subtypes, constituting half of the study population. This finding is in accordance with a previous study showing that MDS-MLD was a subtype more represented in Asia, including Japan and China, with 43% and 41.2% of cases, respectively. In contrast, MDS unclassifiable (MDS-U) was ranked as the most prevalent type in Western countries, while the MDS-MLD had a much lower percentage (approximately 7.35%).9 Both Japanese and Chinese studies have reported that MDS-EB is the second most prevalent type of EB.28–30 However, this was not the case in our study population, in which MDS-SLD was the second most common, followed by MDS-EB-1.\n\nWe found that most MDS patients in our study sample had high and very high risks. This finding supports the notion that Asian patients have a higher risk of developing high-risk MDS. Two studies reported a higher frequency of intermediate risk and greater risk in Japanese patients than in more prevalent low-risk patients in Germany and Caucasians.30,31 Jiang et al. also confirmed a similar finding, compiling some Asian and Western studies. The study found that more Asian MDS patients had intermediate-, high-, and very high-risk, while in Western countries, very low- and low-risk patients had a higher distribution. The higher proportion of high-risk cytogenetic abnormalities in Asian patients might explain this finding.9\n\nThis study identified one subject with del(5q) and classified it as the MDS-MLD subtype. Del(5q) cytogenetics was associated with a good prognosis and was found to be twice as frequent in Asian patients, with a 4.63% prevalence than in Western countries (8.81%). The most common chromosomal abnormality in MDS is the deletion of the long arm of chromosome 5 (5q), which is found in up to 15% of diagnosed cases.32,33 del(5q) is more prevalent in Western patients with MDS than in Asian patients. Patients with isolated del(5q) are known to be lenalidomide-responsive, which results in a better prognosis. Anomaly of chromosome 7, either monosomy or deletion of 7q, is reported in approximately 10% of de novo MDS cases and up to 50% of therapy-related MDS cases. Monosomy 7 is correlated with worse prognosis and decreased overall survival in patients with MDS. In addition, there are hundreds of variants of cytogenetic abnormalities that have rarely been reported in MDS patients, such as -X, 3q abnormalities, +13/del(13q), i(17q), +21/-21. In a German study, rare chromosomal abnormalities occurred in less than 2% of patients with MDS. Additionally, we found del(20q) in one patient, although it was not a clonal mutation. Del(20q) is more prevalent in Asian patients than in Western patients, along with trisomy 8.\n\nThe underlying cytogenetic discrepancy between Asian and Western countries remains unknown, but it is thought to explain the severity of MDS in Asian patients. Although the incidence of MDS is lower in Asia, very high-risk, high-, and intermediate-risk groups, based on IPSS-R scores, are more prevalent than in Western countries, which reported more MDS patients in very low- and low-risk groups. The MDS-RS, MDS-del(5q), and MDS-U subtypes are more common in Western countries. In contrast, MDS-SLD, MDS-MLD, and MDS-EB are more common in Asian countries.\n\nSeveral comorbidities have been found to influence disease risk factors, such as congestive heart failure and chronic obstructive pulmonary disease, which are associated with shorter survival. Disease prognosis varies, ranging from indolent to progressive disease.34 The median overall survival in patients with MDS is only 5 years, which is considered to have a poor prognosis.\n\nOn average, 30% of patients with MDS develop transformation to AML during the course of the disease. In this study, the rate of AML transformation was 10.7% in one year. This finding is lower than that reported by Vamsi et al., who reported that AML transformation during a 1-year follow-up was 26.9% in higher-risk MDS patients, which were patients with intermediate IPSS-R prognostic risk or greater.16 Another study with eight years of follow-up reported AML transformation in 13.9% of MDS patients, with a median of 5 (1-23) months.35 It has been reported that approximately 10-35% of MDS cases evolve into acute leukemia during the disease course. The IPSS-R scoring system was used to estimate the risk of AML transformation five years after diagnosis.\n\nBased on the survival outcome, the overall survival rate in this study population was 64.3%; compared with other studies, the overall 3-year survival rate was 32%.36 Regarding MDS type, MDS-EB1 was reported as the most prevalent diagnosis in the ceased group. This finding supports previous studies reporting that MDS-EB has the worst prognosis among the other types, with a higher risk of AML transformation and shorter median survival, with 16 and 9 months for MDS-EB and MDS-EB2, respectively.37\n\nTo the best of our knowledge, this is the first cytogenetic profiling study conducted in Indonesia. In MDS patients, metaphase cytogenetics is used to identify chromosomal abnormalities in approximately 50% of patients.32 However, a limitation of our study is that most of the cytogenic samples had no metaphase, and the cytogenetic profile could only be found in suboptimal amounts (<10 metaphases) of patients (28.57%). It is recommended that when an abnormal result is obtained at diagnosis, at least 20 metaphases should be analyzed.38 Lower metaphase is related to a higher chance of missing small clones.39 Another issue is that we did not identify somatic mutations in the patients and thus could not evaluate the role of somatic mutations.\n\nConsidering that karyotyping in MDS therapeutic plans and prognosis has a significant influence, further evaluation is needed throughout the cytogenetic analysis process, from transportation and processing of samples, in which errors could occur at any point. A study from India reported that half of the culture failures occurred in samples processed for 24 hours and above. Technical errors include aged samples, low and high cell counts, the volume of the sample, and the culture technique.40 It should also be noted that cytogenetic testing is not routinely performed in Indonesia.\n\n\nConclusion\n\nMDS is heterogeneous in clinical manifestation and molecular etiology, with AML transformation as one of the final endpoints in the clinical course. Our study observed that MDS-EB was the subtype with the highest risk of AML transformation. Further studies with a larger sample size and modern cytogenetic methods, such as conventional FISH and spectral karyotyping, should be conducted to confirm the findings of this study.",
"appendix": "Data availability\n\nFigshare: MDS F1000. https://doi.org/10.6084/m9.figshare.25013561.v1. 41\n\nThis project contains the following underlying data:\n\n• Data MDS.xlsx\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 hospital and laboratory team members for their cooperative work and support.\n\n\nReferences\n\nHeibl S, Stauder R, Pfeilstöcker M: Is Myelodysplasia a Consequence of Normal Aging? Curr. Oncol. Rep. 2021; Vol. 23: 142. Springer. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlepin HD: Myelodysplastic Syndromes and Acute Myeloid Leukemia in the Elderly. Clinics in Geriatric Medicine. 2016; Vol. 32: pp. 155–173. W.B. Saunders. Publisher Full Text\n\nYarosh R, Roesler MA, Murray T, et al.: Risk factors for de novo and therapy-related myelodysplastic syndromes (MDS). Cancer Causes Control. 2021 Mar 1; 32(3): 241–250. Publisher Full Text\n\nPlatzbecker U, Kubasch AS, Homer-Bouthiette C, et al.: Current challenges and unmet medical needs in myelodysplastic syndromes. Leukemia. 2021; 35: 2182–2198. Springer Nature. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMa X: Epidemiology of myelodysplastic syndromes. Am. J. Med. 2012; 125(7 SUPPL): S2–S5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMa X, Does M, Raza A, et al.: Myelodysplastic syndromes: Incidence and survival in the United States. Cancer. 2007 Apr 15; 109(8): 1536–1542. Publisher Full Text\n\nSEER Cancer Statistics Review 1975-2009.2012. Reference Source\n\nCogle CR, Craig BM, Rollison DE, et al.: Incidence of the myelodysplastic syndromes using a novel claims-based algorithm: High number of uncaptured cases by cancer registries. Blood. 2011 Jun 30; 117(26): 7121–7125. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJiang Y, Eveillard JR, Couturier MA, et al.: Asian population is more prone to develop high-risk myelodysplastic syndrome, concordantly with their propensity to exhibit high-risk cytogenetic aberrations. Cancers (Basel). 2021 Feb 1; 13(3): 1–23. Publisher Full Text\n\nPorwit A, Saft L: The AML-MDS interface-leukemic transformation in myelodysplastic syndromes. J. Hematop. 2011; 4: 69–79. Publisher Full Text\n\nPrebet T, Toma A, Cluzeau T, et al.: Outcome of patients treated for myelodysplastic syndromes without deletion 5q after failure of lenalidomide therapy.2017; 8. Reference Source\n\nNarayanan S: Clinical, hematological, and cytogenetic profile of adult myelodysplastic syndrome in a tertiary care center. J. Blood Med. 2017 Feb 8; 8: 21–27. Publisher Full Text\n\nAdès L, Itzykson R, Fenaux P: Myelodysplastic syndromes. Lancet. 2014 Jun 28; 383(9936): 2239–2252. PubMed Abstract | Publisher Full Text\n\nSchanz J, Tüchler H, Solé F, et al.: New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J. Clin. Oncol. 2012 Mar 10; 30(8): 820–829. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSteensma DP: Myelodysplastic syndromes current treatment algorithm 2018. Blood. Cancer J. 2018 May 1; 8(5). Publisher Full Text\n\nKota V, Ogbonnaya A, Farrelly E, et al.: Clinical impact of transformation to acute myeloid leukemia in patients with higher-risk myelodysplastic syndromes. Future Oncol. 2022 Nov 1; 18(36): 4017–4029. PubMed Abstract | Publisher Full Text\n\nKoenig KL, Borate U: New inves ti ga tional com bi na tions for higher-risk MDS.Reference Source\n\nKawankar N, Vundinti BR: Cytogenetic abnormalities in myelodysplastic syndrome: An overview. Hematology. 2011 May; 16(3): 131–138. Publisher Full Text\n\nParidar M, Ghalesardi OK, Seghatoleslami M, et al.: Cytogenetic and molecular basis of BCR-ABL myelodysplastic syndrome: diagnosis and prognostic approach. J. Cancer Metastasis Treat. 2017 Feb 28; 3(2): 38. Publisher Full Text\n\nAl-Kali A, Barta SK; Fox Chase Cancer Center Þ et al.: Myelodysplastic Syndromes NCCN Guidelines® NCCN Myelodysplastic Syndromes Panel Members. J. Natl. Compr .Canc .Netw. 2017; 15.\n\nHong M, He G: The 2016 revision to the World Health Organization classification of myelodysplastic syndromes. J. Transl. Int. Med. 2017 Sep 30; 5(3): 139–143. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRollison DE, Howlader N, Smith MT, et al.: Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood. 2008 Jul 1; 112(1): 45–52. PubMed Abstract | Publisher Full Text\n\nWang F, Ni J, Wu L, et al.: Gender disparity in the survival of patients with primary myelodysplastic syndrome. J. Cancer. 2019; 10(5): 1325–1332. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDinmohamed AG, Visser O, Van Norden Y, et al.: Trends in incidence, initial treatment and survival of myelodysplastic syndromes: A population-based study of 5144 patients diagnosed in the Netherlands from 2001 to 2010. Eur. J. Cancer. 2014 Mar 1; 50(5): 1004–1012. PubMed Abstract | Publisher Full Text\n\nChihara D, Ito H, Katanoda K, et al.: Incidence of myelodysplastic syndrome in Japan. J. Epidemiol. 2014; 24(6): 469–473. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang W, Wang H, Wang XQ, et al.: First report of incidence of adult myelodysplastic syndrome in China. Ann. Hematol. 2012; 91: 1321–1322. PubMed Abstract | Publisher Full Text\n\nGerming U, Strupp C, Kündgen A, et al.: No increase in age-specific incidence of myelodysplastic syndromes. Haematologica. 2004 Aug; 89(8): 905–910. PubMed Abstract\n\nWang X, Liu W, Wang M, et al.: Cytogenetic characteristics of 665 patients with myelodysplastic syndrome in China: A single-center report. Oncol. Lett. 2021 Feb 1; 21(2). Publisher Full Text\n\nWang W, Wang H, Wang XQ, et al.: First report of incidence of adult myelodysplastic syndrome in China. Ann. Hematol. 2012; 91: 1321–1322. PubMed Abstract | Publisher Full Text\n\nMiyazaki Y, Tuechler H, Sanz G, et al.: Differing clinical features between Japanese and Caucasian patients with myelodysplastic syndromes: Analysis from the International Working Group for Prognosis of MDS. Leuk. Res. 2018 Oct 1; 73: 51–57. PubMed Abstract | Publisher Full Text\n\nKuendgen A, Matsuda A, Germing U: Differences in epidemiology of MDS between Western and Eastern countries: Ethnic differences or environmental influence? Leuk. Res. 2007 Jan; 31(1): 103–104. Publisher Full Text\n\nZahid MF, Malik A, Sohail M, et al.: Cytogenetic Abnormalities in Myelodysplastic Syndromes: An Overview. Int. J. Hematol. Oncol. Stem Cell Res. 2017; 11: 231–239. PubMed Abstract\n\nHaase D, Germing U, Schanz J, et al.: New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients.2007. Reference Source\n\nMalcovati L, Hellström E, Hellström-Lindberg H, et al.: Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet.2013; Reference Source\n\nShi J, Shao ZH, Liu H, et al.: Transformation of myelodysplastic syndromes into acute myeloid leukemias. Chin. Med. J. 2004 Jul; 117(7): 963–967. PubMed Abstract\n\nTriantafyllidis I, Ciobanu A, Stanca O, et al.: PROGNOSTIC FACTORS IN MYELODYSPLASTIC SYNDROMES. Maedica J. Clin. Med. 2012; 7: 296.\n\nGerming U, Strupp C, Kuendgen A, et al.: Refractory anaemia with excess of blasts (RAEB): Analysis of reclassification according to the WHO proposals. Br. J. Haematol. 2006 Jan; 132(2): 162–167. PubMed Abstract | Publisher Full Text\n\nRack KA, van den Berg E , Haferlach C, et al.: European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms. Leukemia. 2019; 33: pp. 1851–1867. Nature Publishing Group. PubMed Abstract | Publisher Full Text | Free Full Text\n\nde Swart L , Smith A, Haase D, et al.: Prognostic impact of a suboptimal number of analyzed metaphases in normal karyotype lower-risk MDS. Leuk. Res. 2018 Apr 1; 67: 21–26. PubMed Abstract | Publisher Full Text\n\nMartinovic S, Lalkota BP, Ghosh M, et al.: The Fundamentals to Minimize the Culture Failure in Hematological Malignancies. OAlib. 2020; 07(09): 1–6. Publisher Full Text\n\nSutandyo N, Susanto Kosasih A, Mulya Sari R, et al.: MDS F1000. [Dataset]. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "256195",
"date": "11 Sep 2024",
"name": "William Ying Khee Hwang",
"expertise": [
"Reviewer Expertise Haematologic malignancies"
],
"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 the first paper reporting the cytogenetic profile of patients with myelodysplastic syndromes in Indonesia. It correlates some of these with clinical outcomes with a one-year follow-up. The sample size is small, but the authors did try to determine the appropriate sample size. The article is written in a clear manner and the conclusions are sound, though the study should probably be expanded to include more patients later. Hopefully, this will encourage routine karyotyping for patients with MDS in Indonesia.\nThe authors appropriately cite another paper on the Asian population by Jiang Y et al. It might also be relevant to quote another paper coming out of Indonesia on this subject (albeit a meta-analysis) e.g. [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": []
},
{
"id": "335617",
"date": "25 Nov 2024",
"name": "Andree Kurniawan",
"expertise": [
"Reviewer Expertise Supportive care in cancer",
"head neck cancer",
"hematologic malignancies"
],
"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\nMy comments are 1. The authors have reported cytogenetic profile data in MDS in Indonesia population. This data has high novelty since there was no published data before. considering many difficulty of evaluating cytogenetic in Indonesian because not reimburse yet from national Indonesian Insurance. 2. This multi-center study also reported other than cytogenetic profile, potential factors contribute to mortality in MDS in COVID time. 3. In the discussion may add potential treatment in regard to finding in cytogenetic profiles. 4. The idea for Further research after this data should be added at the end of discussion. 5. The conclusion may be improve based on the cytogenetic profiles found.\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/13-167
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https://f1000research.com/articles/13-165/v1
|
08 Mar 24
|
{
"type": "Study Protocol",
"title": "Comparative evaluation of efficacy of a smartphone application for oral submucous fibrosis (OSMF) self-examination in follow-up of the patients compared to routine Outpatient Department-based follow-up: a clinical interventional study",
"authors": [
"Komal Vilas Dadgal",
"Swapnil C. Mohod",
"Vidya Lohe",
"Shraddha Patel",
"Vidya Lohe",
"Shraddha Patel"
],
"abstract": "Background: Sushruta (600 B.C.) described a condition called \"Vidari\" linked with progressive narrowing of mouth, depigmentation of the oral mucosa, and pain on taking food, oral submucous fibrosis (OSMF). In 1952, Schwartz called this illness, which affected five Indian women existing in Kenya, \"atrophica idiopathica mucosae oris.\" Pindborg and Sirsat coined the term \"oral submucous fibrosis\" in 1966, which is still in use today. With an overall Indian prevalence rate of between 0.2–0.5%, OSMF is primarily found in India and Southeast Asia, according to global estimations. Patients with OSMF need regular follow-ups and to maintain this follow-up it is not always possible for the patient to visit a dental clinic. Hence developing a smartphone-based application for the follow-up of OSMF will be of great value to the patients. The study aims to evaluate the effectiveness of a smartphone application on OSMF self-examination in the follow-up of patients. Methods: There will be three phases of the research. The first phase will be the development of a smartphone-based application for the follow-up of patients with OSMF. The second phase will be distribution and training the patients regarding the usage of the application and the third phase will be evaluating the effectiveness of the smartphone application in maintaining the follow-up of the patients. Expected results: The follow-up of patients with OSMF is expected to be better and feasible using a smartphone application as compared to regular Outpatient Department-based follow-up. Conclusions: Designing a mobile application for the ease of users presents difficulties since it must take accessibility into account, which influences how well the application is received by users. The goal of OSMF examination awareness facilitation and intervention is to raise public knowledge. Educational activities significantly contribute to the advancement of information, convictions, and OSMF screening practice. CTRI registration: CTRI/2023/06/054514 (registration pending)",
"keywords": [
"oral submucous fibrosis",
"self-examination",
"follow-up",
"smartphone applications",
"public awareness"
],
"content": "Introduction\n\nThe World Health Organization (WHO) described this condition as “a slowly progressing disease in which fibrous bands form in the oral mucosa, ultimately leading to the severe restriction of movement of the mouth including tongue” in 1978.1 In 2019, More and Rao described it as “a debilitating, progressive, irreversible collagen metabolic disorder induced by chronic chewing of areca nut and its commercial preparations; affecting the oral mucosa and occasionally the pharynx and esophagus; leading to mucosal stiffness and functional morbidity, and has a potential risk of malignant transformation”.2,3\n\nAccording to estimates, 7–30% of oral submucous fibrosis (OSMF) cases will develop into oral squamous cell carcinoma (OSCC).4 Due to the high malignant transformation rate of this illness (1.5–15%), death rates are high. OSMF incidence varies by area and ethnicity and is strongly correlated with culture, habits, and diet.5 Patients with OSMF are most predominant in South and South-East Asia. The high percentage of Indian immigrants in South Africa also contributes to the high prevalence of patients with OSMF there.6 Different South-East Asian nations have different oral submucous fibrosis (OSMF) prevalence rates. According to statistics, the prevalence is 0.9–4.7% in China, 0.6–6.42% in India, 0.15–14.6% in Vietnam, and 0.086–17.6% in Taiwan. According to statistics from WHO, more than five million individuals are living with OSMF worldwide.7 Patients with OMSF can range from 8 to 80 years old, and the mean age varies between studies.\n\nOSMF is closely linked with the use of betel nut/areca nut, which is classified as grade I hazard by WHO. The use of betelnut is very common in the Indian population being part of cultural events. The betelnut and its products are easily accessible.8 Various preparations of betel nut including smokeless tobacco, e.g., kharra, gutkha, and processed packed supari, are very common in this region, giving rise to the number of patients with OSMF.\n\nThe oral mucosa of patients with the condition has a leathery feel and perceptible vertical fibrous bands, which finally restricts mouth opening and makes the tongue hard. Early signs of the condition include a burning feeling when eating spicy food, losing normal pigmentation, and blanching of the mucosa. Ulcers, dry mouth, burning in the mouth, and restricted mouth opening are some of the clinical symptoms of OSMF.9 As the condition worsens, it could cause distress to the throat and esophagus, causing fibrosis of the upper digestive tract, while mouth-opening limitation is triggered by fibrosis of oral mucosa in the late phases of OSMF. Oral mucosa blanching is a significant clinical characteristic in the initial phases.7 Life quality is directly impacted by the characteristic manifestations and signs of OSMF patients who exhibit a constrained mouth opening.5 It should be noted that many patients with OSMF exhibit symptoms of anxiety, sadness, stress, and poor social interaction, and the incidence of these symptoms is contrarywise linked with the ailment’s severity.2\n\nA mobile application containing material that is specifically designed for end users, such as the general public, may increase the intervention’s acceptability and effectiveness. The creation of mobile applications that incorporate theory may emphasize and support behavior modification for health promotion in patients with OSMF.10 Public health promotion will be practiced by the built mobile application. Therefore, enhancing the mobile application’s visual appeal, usability, acceptance, and effectiveness is necessary.11\n\nPhase 1: Development of an evidence based self-assessment smartphone application:\n\na. To develop evidence based relevant content for the development of a user-friendly self-assessment smartphone application for patients with OSMF.\n\nPhase 2: Distribution of the smartphone application:\n\na. To train and counsel patients regarding the utilization of the smartphone application.\n\nb. To modify the application as per the requirement and suggestions of the user.\n\nPhase 3: To assess the outcome of the smartphone-based application on patient follow-up:\n\na. To assess the efficacy of smartphone self-assessment application in maintaining the follow-up of the patients.\n\n\nMethods\n\nEthical approval has been received from Datta Meghe Institute of Higher Education and Research, Sawangi, Wardha IEC reference number DMIHER (DU)/2023/568. Consent from the intervention group will be taken using electronic consent forms. For the routine outpatient department (OPD)-based follow-up, written consent form will be taken manually. This clinical trial study protocol adhered to the SPIRIT checklist.16\n\nAfter getting ethical approval from “The Institutional Ethics Committee (IEC)” of Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha, for this study, the patients will be selected as per the inclusions and exclusions given in the criteria. The study will be conducted at Sharad Pawar Dental College, Sawangi (Meghe), Wardha in the Dept. of Oral Medicine and Radiology.\n\nThe investigator will perform the intervention with the following inclusion and exclusion criteria.\n\nInclusion criteria\n\n1. Patients habitual to betelnut chewing (more than six months duration).\n\n2. Patients clinically diagnosed with OSMF.\n\n3. Patients having an acceptable literacy level (e.g., are able to read and write Hindi, Marathi, and English).\n\n4. Patients having access to smartphones.\n\n5. Patients who are able to provide electronic informed consent.\n\nExclusion criteria\n\n1. Patients who refuse to take part in the study will not be included.\n\n2. Patients having malignant lesions are also excluded from the study.\n\n3. Patients who are unable to read the application’s teaching materials on their smartphones.\n\nThe participants of the intervention group will be given access to smartphone application for the follow-up of the OSMF. Whereas the control group will not be given access to the application. The participants in the control group will be referred to the OPD for the follow-up of OSMF.\n\nThe intervention will be accustomed for seven months. The initial two months will be the training period for the participants for the usage and various features of the smartphone application. The smartphone application will also be surveyed for any modifications in the smartphone application.\n\nThe smartphone application will contain monthly and weekly follow-ups for the users and information regarding the disease and ill-effects of the use of betelnut and its products. After downloading the application, the user will have to fill the demographic details for the sign-in of the application. After the sign-in, the user will have access to follow-up section and the information available on the smartphone application. The user can follow the steps and answer the questions of the follow-up for the monthly and weekly follow-up.\n\nTo improve the adherence of the participants in the intervention group, the smartphone application will have a feature of notification reminder to adhere to the follow-up of OSMF on weekly and monthly basis.\n\nThe outcomes of the study will be regular follow-up of the patients who have OSMF or have the habit of betel-nut chewing. The participants can adhere to the follow-up more efficiently using the smartphone application for the follow-up and inspect for the improvement of the signs of OSMF on their own.\n\nAfter introducing the participants of the intervention group to the smartphone application, they will perform the weekly and monthly follow-ups for the period of 6 months.\n\n\n\n• Significance level Type I error rate, α = 0.05\n\n• Power (1-beta) = 0.8\n\n• Z alpha value = at 90% 1.645\n\n• Z beta value = at 80% 0.842\n\n• Ratio of sample size, Treatment/control =1\n\n• Allowable difference, d = μT− μC = 0.7\n\n• Expected population standard deviation, SD = 1.5\n\n• δ(>0), Margin = 1.1\n\n• Drop rate (%) = 10\n\nG power software analysis\n\nRatio var1/var0 = 1.5\n\nα err prob = 0.05\n\nPower (1-β err prob) = 0.95\n\nLower critical χ2 = 49.10\n\nUpper critical χ2 = 120.32\n\nDf = 80\n\nTotal sample size = 110\n\nActual power = 0.90\n\n\nResult\n\nThe total sample size will be 110 participants. Sample size depends on the true mean difference, d, standard deviations for the two groups, and a level of significance α (type|error), and the power. The total sample size n = n1 + n0 is minimized when r = σ1/σ0. With the aforementioned calculation, sample size determination with a 90% of confidence interval is 110, considering drop outs.\n\nAll the patients visiting the out-patient department (OPD) will be thoroughly inspected for the habit of betelnut chewing and will be introduced to the smartphone application which will be developed. They will be explained about the efficacy of the use of the application for the follow-up of the habit and OSMF which will also help the to cease the habit.\n\nSequence generation for both the groups will be done using simple randomization.\n\nAllocation concealment mechanism\n\nThe mechanism of implementing the allocation sequence is by sequential numbering.\n\nImplementation\n\nThe investigator will generate the allocation sequence, enroll the participants, and will assign the participants to intervention and the control group.\n\nThe participants belonging to both, intervention and control groups will be blinded.\n\nPhase 1: Development of the self-assessment smartphone application\n\nThe evidence-based informational materials on OSMF, cancer prevention, and self-examination will be taken from reliable sources such as articles published in indexed journal i.e scopus, pubmed and web of sciences.12 Following which, the contents will be modified, and animated educational videos will be created. Then, with the assistance of professionals in the creation of electronic content, the materials will be created with modifying rules and converting lessons to electronic formats, images, animations, also audio and video clips will be included.11\n\nThe resources will then be created using Android Studio, a software development environment for the Android platform, in the form of installable applications for mobile devices.\n\nThe application will be multilingual.\n\nThe OSMF application will consist of two components: the OSMF self-assessment and the OSMF educational resources.11\n\nThe participants’ smart electronic devices will have the application downloaded, and it can be utilized online. Patients will also be trained by the researcher for the handling of the application. It should be noted that an internet connection will be necessary for the application’s installation.\n\nPhase 2: Distribution of the application\n\nThe created application will be put on the smartphones of the participants in the following phase, and its functionality will be inspected. The patients will be trained to use the application along with motivation and counselling. After a month of testing, participants will be requested to get in touch with the researcher if they encounter any issues or have any concerns about using the application.11\n\nPhase 3: To assess the outcome of the smartphone-based application on patient follow-up\n\nThe data generated from application will be used to assess: i) Patient compliance; ii) modifications in symptoms; and iii) analysis of patient feedback will be done.\n\nThe study will be conducted in two groups: i) Group I: the control group, routine OPD-based follow-up (55) and ii) Group II: the smartphone application using group (55). The control group will be monitored by the conventional follow-up method of assessment in patients with OSMF and the latter group will be monitored through the self-assessment smartphone application. Depending on the findings of the two comparative groups, the efficacy of the application will be tested in maintaining the follow-up in the patients with OSMF.\n\nThe data will be collected from the patients for follow-up of OSMF visiting OPD for the control group. The data of the participants using the self-assessment smartphone application for OSMF follow-up who belongs to the intervention group will be stored in the application which can be accessed by the investigator. The data collected include demographic details such as age, address, contact details. Data will also be collected from the questionnaire of the self-assessment application for OSMF follow-up.\n\nRetention\n\nThe participants will get regular reminder notifications on their smartphone application which they will be using for the follow-up of OSMF which will improve participant retention. This will also ensure complete follow-up of the participants of the intervention group.\n\nFor the maintenance of the data quality, once the data is collected from the participants of the control and intervention group it will be cross-checked by all the investigators.\n\nDescriptive and frequency distribution will be used for demographic data. Chi-squared test and Pearson’s correlation analysis will be used to assess the impact of variables. A linear regression model will help to assess the relationship with demographic details.\n\nNot yet started.\n\n\nDiscussion\n\nThe follow-up of the OSMF patients is expected to be better using a smartphone application as compared to the regular OPD-based follow-up. Numerous studies on these applications have been carried out, and more than 40,000 mobile health applications are already accessible on several platforms. However, there isn’t enough research to prove that these mobile apps integrate theory and were created using a qualitative design process. However, as mobile health technologies advance, there is growing concerned about how mobile application performance is constrained by their usability, accuracy, and data privacy.11,13\n\nRêgo et al., 2022, undertook a study with the goal of creating and validating a tool for identifying oral cancer risk factors. To evaluate the probability of developing oral cancer, an application was created that included predictors of the disease.14 For 40 experts in oral diagnostics to evaluate the algorithm and test its usability and accessibility, simulated clinical scenarios were created. The oral cancer screening was efficient, had good sensitivity and usability, and may even help find early oral lesions.14\n\nChang et al., 2019 conducted a study to show the methodical development course and content of the oral self-care application. Behavioral diagnosis, intervention design, and oral self-care assessment are the three phases of the systematic development process for oral self-care assessment.15 Through skilled assessment of the beta and final versions of the application and serviceability testing of the final version by patients with periodontal disease, the produced oral self-care app was evaluated and found to have good usability. This study described a meticulous design procedure for creating a customized, evidence-based mobile application for oral self-care, which makes it a personalized application for enhancing oral health in individuals with periodontal disease.15\n\nThe OSMF self-examination awareness approach involves inspecting and palpating one’s oral mucosa or oral cavity periodically in order to become familiar with it and spot anomalies. The goal of OSMF examination awareness facilitation and intervention is to raise public knowledge. Educational activities significantly contribute to the advancement of information, convictions, and OSMF screening practice.13\n\nThe population that consumes betel nut and tobacco products is the main focus of the study. The consumption of betel nut and tobacco products is done by a vast number of the Indian population. It is not always feasible for the patients to visit a dental setup for maintaining the follow-up. The study will be helpful in the follow-up of OSMF patients more promptly.\n\nThe study will be published in PubMed, Scopus, and Web of Sciences journal.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nZenodo: SPIRIT checklist for ‘Comparative evaluation of efficacy of a smartphone application for oral submucous fibrosis (OSMF) self-examination in follow-up of the patients compared to routine Outpatient Department-based follow-up’. https://doi.org/10.5281/zenodo.7965059. 16\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nI would like to thank my institute and my colleagues.\n\n\nReferences\n\nGupta S, Jawanda MK: Oral submucous fibrosis: An overview of a challenging entity. Indian J. Dermatol. Venereol. Leprol. 2021 Oct 23; 87(6): 768–777. PubMed Abstract | Publisher Full Text\n\nSheshaprasad R, Pai A, Yaji A: Habit History in Oral Submucous Fibrosis: Have We Over Emphasized? Asian Pac. J. Cancer Prev. 2019; 20(2): 451–455. Publisher Full Text\n\nSharma SR, Chavan S, Karjodkar FR, et al.: Correlation of Clinical Features in Oral Submucous Fibrosis: A 9-Year Retrospective Study. Ethiop. J. Health Sci. 2022 Jan 1; 32(1).\n\nNiaz K, Maqbool F, Khan F, et al.: Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer. Epidemiology and health.\n\nShah G, Chaturvedi P, Vaishampayan S: Arecanut as an emerging etiology of oral cancers in India. Indian J. Med. Paediatr. Oncol. 2012 Apr; 33(02): 71–79. Publisher Full Text\n\nAli FM, Aher V, Prasant MC, et al.: Oral submucous fibrosis: Comparing clinical grading with duration and frequency of habit among areca nut and its products chewers. J. Cancer Res. Ther. 2013 Jul 1; 9(3): 471–476. PubMed Abstract | Publisher Full Text\n\nShivakumar GC, Sahana S, Saha S: Prevalence and site distribution of oral mucosal lesions in patients attending outpatient clinics of Oxford Dental College, Bangalore. J. Indian Assoc. Public Health Dent. 2010 Jan 1; 8(15): 69. Publisher Full Text\n\nMuthukrishnan A, Warnakulasuriya S: Oral health consequences of smokeless tobacco use. Indian J. Med. Res. 2018 Jul; 148(1): 35–40. PubMed Abstract | Publisher Full Text\n\nArakeri G, Thomas D, Aljabab AS, et al.: TFM classification and staging of oral submucous fibrosis: A new proposal. J. Oral Pathol. Med. 2018 Apr; 47(4): 403–409. PubMed Abstract | Publisher Full Text\n\nCheng AS, Liu X, Ng PH, et al.: Protocol: Breast cancer application protocol: a randomised controlled trial to evaluate a self-management app for breast cancer survivors. BMJ Open. 2020; 10(7): e034655. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShrivastava SR, Shrivastava PS, Ramasamy J: Self breast examination: A tool for early diagnosis of breast cancer. Am. J. Public Health Res. 2013 Jun 22; 1(6): 135–139. Publisher Full Text\n\nHeo J, Chun M, Lee KY, et al.: Effects of a smartphone application on breast self-examination: a feasibility study. Healthc. Inform. Res. 2013 Dec 31; 19(4): 250–260. Publisher Full Text\n\nNasution A, Yusuf A, Keng SL, et al.: Development of Mobile App for Breast Examination Awareness Using Health Belief Model: A Qualitative Study. Asian Pac. J. Cancer Prev. 2021 Oct; 22(10): 3151–3163. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRêgo TJ, Lemos JV, Matos AP, et al.: Development and professional validation of an App to support Oral Cancer Screening. Braz. Dent. J. 2022 Dec 5; 33: 44–55. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChang WJ, Lo SY, Kuo CL, et al.: Development of an intervention tool for precision oral self-care: Personalized and evidence-based practice for patients with periodontal disease. PLoS One. 2019 Nov 21; 14(11): e0225453. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDadgal K, Mohod S: Comparative evaluation of the efficacy of a smartphone application for oral submucous fibrosis (OSMF) self-examination in follow-up of the patients compared to routine Out Patient Department based (OPD) follow-up. [Dataset]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "255951",
"date": "30 May 2024",
"name": "Harshkant Gharote",
"expertise": [
"Reviewer Expertise As an Oral Physician I understand the epidemiology",
"clinical presentation and molecular pathogenesis of the disease studied in the present article."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 and elaborates materials and method.\nAuthors need to explain about follow up wherein only counselling and discontinuation of the habit will be included or any medical management will be employed? As chances of loss of follow up in conventional method will increase if no medical intervention is done.\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": "11811",
"date": "25 Jun 2024",
"name": "KOMAL DADGAL",
"role": "Author Response",
"response": "During the follow-up of the participants with OSMF, counseling, discontinuation of habit as well as medical intervention will be provided."
}
]
},
{
"id": "359598",
"date": "22 Jan 2025",
"name": "Prasad Nalabothu",
"expertise": [
"Reviewer Expertise smart phone technologies. digital dentistry applications"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe protocol raises several important concerns. One important issue is the lack of clarity about whether medical management or clinical interventions will be part of the follow-up process. This information is critical to assessing the effectiveness of the smartphone application for patients with OSMF. In addition, the protocol doesn't provide adequate information on how participants' privacy will be protected, particularly with regard to the protection of their personal health data. This is a critical issue in mobile health research. The study also lacks a clear definition of how the application will affect patient outcomes, leaving questions about its practical relevance unanswered. The sample size calculation is overly complicated and difficult to verify. The study also does not include a well-defined timeline or feasibility analysis for the phases of the study, in particular how the application will be modified based on user feedback. Without clear results, it is impossible to assess the effectiveness of the intervention being tested. I recommend not indexing of the study protocol due to significant gaps in methodology, ethical considerations and feasibility.\n\nIs the rationale for, and objectives of, the study clearly described? No\n\nIs the study design appropriate for the research question? No\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? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-165
|
https://f1000research.com/articles/12-982/v1
|
15 Aug 23
|
{
"type": "Opinion Article",
"title": "The importance of teaching climate-health literacy in psychotherapeutic training and continuing education",
"authors": [
"Paolo Raile"
],
"abstract": "Climate-health literacy is the ability to find, access, understand, interpret, evaluate, and communicate information about the impact of climate change on human health and to make decisions and act accordingly to that information. Climate change affects people's health in numerous ways, both directly and indirectly, e.g., by increasing the risks of cardiovascular disease, infections, depression, anxiety disorders, and trauma. It is important for health professionals to understand the complex interaction between climate change and health. A teaching concept is presented that incorporates the core elements of climate-health literacy.",
"keywords": [
"Climate-Health Literacy",
"Eco-Emotions",
"Eco-Anxiety",
"Climate Change",
"Mental Health"
],
"content": "Introduction\n\nWe live in a time of crises that affect our health in many ways. One of these is the climate crisis. Climate change affects health either directly in heat waves and other extreme weather conditions or indirectly through changes in natural systems, such as the increased release of allergens or more favorable conditions for disease-transmitting organisms. The extent to which climate change affects health can be assessed in conjunction with population dynamics, as well as in economic development and health care. According to a report on climate change and health by the Austrian Panel for Climate Change (APCC, 2018), a higher proportion of older or chronically ill people, poorer health care, and an increasing number of people with lower incomes lead to an increased societal susceptibility to climate change.\n\nIn February 2023, the research team of the “Kompetenzzentrum Klima und Gesundheit” (Competence Center for Climate and Health) wrote a research letter about health-related climate competence among health professions. The research team is part of the Gesundheit Österreich GmbH, which is the national research-and-planning institute for the health-care system, as well as the central agency for health promotion. The Republic of Austria represented by the Minister of Health is the sole shareholder of Gesundheit Österreich. In a letter about climate literacy among health-care professionals, they stated that physicians and nurses should have more literacy in dealing with climate-related health issues in their training programs (Brugger, 2023; Brugger and Horváth, 2023).\n\nAustrian research agencies have mentioned the psychological effects of climate change. The research letter is based on detailed reports by the APCC in 2018 and a long report and the study by Brugger in 2023. The psychological consequences are mentioned only once briefly or not at all in the report for politicians in the short forms of the APCC summary in 2018 and the research letter from Brugger and Horváth in 2023. This applies not only for Austria; the psychological consequences of climate change have a lower priority than physical ones worldwide. There are numerous studies on the effects of climate change on physical health, but few studies on its effects on mental health (Cianconi, Betrò, and Janiri, 2020).\n\nThe purpose of this paper is to make a scientifically based plea for greater consideration of the psychological impacts related to climate change in the education and training of health professionals. For reasons of limited publication space, only one health profession will be in the focus of this paper, namely psychotherapists. They work primarily with mental-health disorders and benefit most from climate-health literacy through learning about the effects of climate change on the human psyche and vice versa in education and training. The impact of climate change on mental health and the impact of mental health on physical health should also be included in the training and education of other health-care professionals.\n\n\nClimate-health literacy\n\nClimate-health literacy is a term recently used in scientific papers. It is more than a combination of climate literacy and health literacy. These two concepts are briefly defined below.\n\nSome authors use both climate literacy and climate-change literacy interchangeably, while others distinguish between them. Dupigny-Giroux (2017) suggests that climate literacy refers to knowledge about the climate and acting accordingly to this knowledge. Climate-change literacy is more specific and refers to the knowledge and actions evolving from knowledge about the anthropogenic climate change and its impacts. This paper uses the two terms synonymously and refers to knowledge about climate change, its impacts on the planet and humans, human impacts on the environment, and complex reciprocal influences. “In other words, a climate literate individual is an expert in the principles of climate science and can assess information and communicate about climate change clearly and take responsible action towards decreasing unsustainable practices that negatively affect the environment.” (Suhaimi and Mahmud, 2022, p. 2).\n\nA systematic review of health-literacy literature was published in 2012. The authors created a combined model based on 17 different definitions of health literacy. This model contains three health domains and four dimensions. In short, health literacy is the ability 1) to access information on clinical issues, risk factors for health, and health-promoting factors, 2) to understand medical information and information on factors risking and promoting health, 3) to interpret and evaluate this information, and 4) to make informed decisions based on the interpreted and evaluated information (Sørensen et al., 2012).\n\nBoth the fields of health and climate are very complex, as is concept of literacy. One reason is the difficulty of drawing a line between literacy and illiteracy. According to Suhaimi and Mahmud (2022), a climate literate is an expert on climate science. The question is, when is someone considered to be a climate-change expert, and what does this mean? The US Global Change Research Program wrote a guide on the essential principles of climate science to help individuals and communities gain climate literacy. They defined a climate-literate person as someone who “… understands the essential principles of Earth’s climate system, knows how to assess scientifically credible information about climate, communicates about climate and climate change in a meaningful way, and is able to make informed and responsible decisions with regard to actions that may affect climate.” (US Global Change Research Program, 2009, p. 4). The difference between the former and the latter definition may simply be wording, but the question is whether a climate-literate person must understand the principles of climate science or has to be an expert in the principles of climate science. Based on the (etymologic) original meaning of the term literacy, the ability to read and write, it is obvious that a literate person does not have to be a language expert but must have knowledge of the principles of reading and writing. Therefore, the definition of the US Global Change Research Program is briefly summarized below.\n\nHealth literacy is the ability to find, access, understand, interpret, evaluate, and communicate information about health, including clinical issues and both risky and protective health factors, and to make decisions and act accordingly to that information. Climate literacy is the ability to find, access, understand, interpret, evaluate, and communicate information about climate science, including the impact factors of climate change on living and non-living environments and vice versa (especially our impact on climate change), and to make decisions and act based on that information. Climate-health literacy is, therefore, the ability to find, access, understand, interpret, evaluate, and communicate information about the impact of climate change on human health and to make decisions and act accordingly to that information. The following definition of climate-health literacy based on a review of numerous studies and papers was published in 2020.\n\n“Based on our thematic analysis, we define climate and health literacy as the degree to which an individual understands the complex relationship between climate change and human health; a climate health–literate individual can recognize direct and indirect linkages between climate change and health, communicate risks, assess data, comprehend uncertainty, and make informed and responsible personal decisions or advocate for broader policies that protect health.” (Limaye et al., 2020, p. 2185; see also Grabow et al., 2023, p. 2).\n\nThe authors of this definition published seven climate health-literacy elements: 1) Root cause (what are the main causes of the anthropogenic climate crisis, which also affects our health), 2) Mechanism (how climate change affects human health), 3) Determinants (the strong bond between our environment and our health), 4) Implications (climate change worsens health disparities), 5) Interventions (How can the impact of climate change on our health be reduced?), 6) Evidence (Which evidence exists for climate-change impacts on our health and how do we get evidence?), and 7) Complexity (the enormous complexity of the connection between human health and climate change, which varies over space and time). The first two elements are so-called functional literacy, the next three elements are intermediate literacy, and the last two elements are advanced literacy (Limaye et al., 2020; Grabow et al., 2023).\n\nThe focus here lies on mental health. It can be useful to create a more specific definition of mental-health literacy concerning climate. The impact of psychological issues, like stress on physical health and the impact of a physical illness on our psyche, are evident. Psychosomatics is not just a modern word to describe the impacts of the mental state on physical health and vice versa, but a concept of a body-mind unity (Grassi et al., 2019; Lowen, 2012).1 A new concept “climate mental-health literacy” is not necessary because of the undividable nature of physis and psyche. This paper includes mental health in the term climate-health literacy.\n\n\nThe impact of climate change on the psyche and vice versa\n\nThere are numerous scientific publications on the interactions between climate change and mental health. The following list was compiled from many different articles and books but does not claim to be complete.\n\nExtreme weather events and natural disasters (droughts, fires, floods, storms)\n\nOver ten years ago, the IPCC report warned of an increase in extreme weather events and natural disasters due to climate change (IPCC, 2012). It is evident that such events can have a very negative effect on health if one is directly exposed to them. Floods and storms not only cause injuries and deaths, but also infectious diseases like cholera or food shortages, especially in countries with low adaptive capacities. Damage to the infrastructure can also hinder medical care and rescue operations (Codjoe et al., 2020; McMichael, 2015). Natural disasters can directly impact mental health. Traumatization and the post-traumatic stress disorder (PTSD), anxiety disorders, depression, and other mental illnesses can be a result of directly experiencing a natural disaster or losing loved ones or possessions in a natural disaster (Raile and Rieken, 2021). Heatwaves are also extreme weather events, but they have a different direct impact on human health.\n\nIncrease in the number of hot days and heatwaves\n\nClimate change is causing a rise in average temperatures and also an increase in their duration and intensity (Meehl and Tebaldi, 2004). Heatwaves lead to excess mortality, particularly among vulnerable groups, such as the elderly, the homeless, construction workers, pregnant women, and young children (Hajat, O’Connor, and Kosatsky, 2010; Xu et al., 2016). High temperatures and heatwaves also affect mental health. There is an increased risk of suicide and hospitalization, including admissions due to mental illness, during high temperatures. Heat can also worsen psychological symptoms and can cause stress affecting both the body and the mind (Thompson et al., 2018). Health professionals can help people better cope with heatwaves by educating them about the risks and prevention measures, performing summer check-ups including medication adjustments, scheduling early morning or evening appointments, and initiating active communication with high-risk individuals (Herrmann, 2023).\n\nThe unpredictable future\n\nAlmost no text addresses another direct impact of climate change on human health – the impact of its very existence as an unpredictable, lethal threat. The media reports about dystopian futures due to climate change, and billions of people worldwide are already experiencing changes in the climate and environment. The very fact that the climate crisis exists, and our future survival is uncertain creates anxiety and depression, especially if there is no hope of preventing the catastrophe (Raile and Rieken, 2021; Raile, 2023a).\n\nAir pollution and gases\n\nClimate change is closely connected with high CO2 emissions. Depending on the region, CO2 emissions come mainly from heating, cooking, transport, and electricity generation, especially from coal-fired power plants. The emission of CO2 is usually accompanied by air pollution and other factors that affect health in various ways, mainly due to respiratory and cardiovascular diseases (Lelieveld et al., 2015; Watts et al., 2018). Climate change increases ozone levels, which also have a negative impact on the respiratory and cardiovascular systems (Mücke, 2011; Watts et al., 2015). Air pollution also affects mental health. There is evidence that some air pollutants, like nitric oxides, are associated with the risk of a new onset of depressive symptoms or worsening of existing depressive symptoms (Buoli et al., 2018; Yang et al., 2021). Air pollution has a different influence on people with allergies.\n\nPollen and allergies\n\nDue to climate change, the duration of the allergy season, which is starting earlier and earlier, is increasing; the amount of pollen is increasing, and new allergens are appearing. The latter is a consequence of the increase in average temperatures, which is why heat-loving plants (and their pollen) spread to higher and cooler regions (Damialis, Traidl-Hoffmann, and Treudler, 2019; Ziello et al., 2012). Higher temperatures, increased CO2 concentrations and air pollutants, such as ground-level ozone, also increase the allergenicity of pollen (Beck et al., 2013). The health effects of allergies on the immune system, especially on respiratory health, including symptoms like allergic rhinitis or asthma, skin diseases, and life-threatening situations like anaphylactic shock, are well known. There is also evidence for a correlation between allergies and higher depression and suicide rates, increasing anxieties, and a general reduction in quality of life (Amritwar et al., 2017; Stadler et al., 2022).\n\nWater and food shortages\n\nAs a result of climatic changes, especially more extreme weather events like droughts, heavy rainfall, and sea acidification, the supply of food and drinking water is hardly maintainable, especially in less privileged countries (Kornhuber et al., 2023). Besides the direct health consequences of food and water shortages (starvation, dying of thirst), long-term deficiency symptoms can also arise due to zinc, protein, and iron deficiencies (Myers et al., 2014; Zhu et al., 2018). Food and water insecurity can lead to anxieties and other mental issues. Deficiencies of certain substances, such as iron, can also lead to developmental disorders which affect neurocognitive functions (McWilliams et al., 2022). General nutrient deficiencies are also correlated with severe depressive symptoms (Owczarek et al., 2022).\n\nInfectious diseases\n\nHigher temperatures accelerate the multiplication of pathogens (Cohen et al., 2020). Extreme weather events can cause water pollution (Boudou et al., 2020) increasing the risks of infectious diseases, especially in regions with lower hygienic standards for the water supply and a lack of sewage facilities (Cissé, 2019). Insects that spread infectious diseases, like ticks and mosquitoes, reproduce faster at high temperatures and spread further. Even in Central Europe, diseases such as dengue fever, chikungunya fever, zika disease, and leishmaniasis can occur more frequently (Thomas et al., 2018; Tidman, Abela-Ridder, and de Castañeda, 2021). Such diseases also have an impact on mental health when you consider how serious illnesses make you feel. Countless papers have been published over the past three years on the effects of one of these infections, namely coronavirus disease 2019 (COVID-19), as well as countermeasures, such as social distancing, on mental health (Panchal et al., 2023; Saqib et al., 2023; Witteveen et al., 2023). Not only do infections have an impact on mental health; the mental status also influences healing (Huremovic, 2019).\n\nBiodiversity loss\n\nBiodiversity is rapidly decreasing due to climate change and other human impacts, (Raven and Wagner, 2021). Biodiversity is an essential life-support system on which our existence depends. Human health is linked to biodiversity in at least four different ways: 1) Biodiversity provides food and medicine and reduces air and water pollution. Biodiversity, especially plants, also reduces exposure to extreme heat. 2) Experiencing the natural environment reduces stress and restores our ability to concentrate. 3) Physical activities in natural environments produce greater health benefits. Biodiverse neighborhoods support social interactions and social cohesion. The natural environment also provides places to bond with others and offers transcendental experiences. 4) The natural environment can also cause harm via exposure to microorganisms causing infections, harmful wildlife, allergens, sunstroke, etc. (Marselle et al., 2021). The loss of natural environments can cause stress, anxieties, depressions, solastalgia (the distress due to environmental change in the home environment) (Albrecht et al., 2007) and many other mental issues (Raile and Rieken, 2021).\n\nSocial factors (migration, wars, poverty)\n\nMany of the above-mentioned issues, the loss of the natural environment, the increase in extreme weather events, rising sea levels, and increasing water and food shortages impact society and cause an increase in poverty, migration, social unrest, and wars. In countries that are economically heavily dependent on agriculture and struggling with other socio-economic and political problems, climate change is also contributing to armed conflict (Koubi, 2019; Smirnov et al., 2022). The effects of migration on health can be diverse. Migrants tend to have a lower status in the host society, poorer access to the health system, and a higher risk of illness. There are many peri- and post-migration stressors which affect their mental health, like an increase in depressions, anxieties, etc. (Byrow et al., 2022; Spaas et al., 2022). Migration can also lead to fears and divisions in the host society (Metten and Bayerlein, 2023). Another social impact is climate activism. Due to the insufficient climate-protection activities of most governments, concerned people become climate activists and fight for climate protection. This can also affect mental health causing, e.g., activist burnout and depression (Latkin et al., 2022).\n\nPsychological factors (emotions, children)\n\nClimate change triggers a range of feelings that can be summarized as eco-emotions, like eco-anxiety, eco-worry, eco-fear, eco-despair, eco-anger, eco-guilt, eco-shame, and eco-grief. There are also positive emotions, like eco-hope (Raile, 2023a). Eco-anger can arise, for example, when people see that politicians or corporations do not act in the interest of climate protection, but against it. Such feelings, especially when they are strong, can affect (mental) health. When the feelings affect everyday life, they can cause sufferers to seek professional help. Another impact of climate change is the rise of concerns about having children. Besides the ecological footprint that a child leaves in their lifetime, many are tormented by the gloomy prospects that they would like to spare a child (Raile and Rieken, 2021).\n\nImpacts of (mental) health on climate change\n\nMental health can also impact climate change. We are all called upon to do our part to protect our environment and climate. If we struggle with our mental problems, such as depression, trauma, severe anxiety, and burnout, we cannot effectively protect the climate. We can only act in the interest of the community and the environment when we are doing well (Latkin et al., 2022; Raile, 2023a). Fortunately, there are numerous activities we can do to protect the climate AND our health. One example is cycling or walking instead of driving a car. Another example is eating less meat and fast food and switching to regional products (Herrmann, 2023). We have to take care of ourselves before we can take care of our environment and climate.\n\nThe effects of climate change on (mental) health listed here are far from complete and only give an idea of the high complexity of the interactions. A reasonably complete and sufficiently detailed review on the link between climate change and mental health would fill countless papers and books. Such literature exists (and has been cited here) and can and should be included in the education and training of health professionals, especially psychotherapists. The next section will briefly discuss psychotherapeutic education and training.\n\n\nPsychotherapeutic education in German-speaking countries with a focus on climate change\n\nThe practice of psychotherapy is not regulated by law in every country in the world. Where it is not, no law prescribes what training must be completed to work as a psychotherapist. In those countries where psychotherapy is regulated by law, there are usually training guidelines. These differ from one country to the next around the world (Pritz, 2002). The author of this paper has mainly studied psychotherapy training in German-speaking countries. The following paragraphs particularly apply to Germany, Austria, and Switzerland. The core statement can also be adopted for other countries.\n\nSince the new Psychotherapists Act in Germany from 2020, the path to psychotherapeutic licensure includes a polyvalent bachelor’s degree in psychology and a postgraduate master’s degree in psychotherapy, which is usually offered in combination with clinical psychology. After completing the master’s degree, one may work as a psychotherapist. Running one’s own practice is only permitted after further specialization over several years in a specific approach. The number of psychotherapeutic approaches that can be chosen is limited. Only cognitive behavioral therapy, psychodynamic psychotherapy, and systemic therapy are legally recognized in Germany. All other psychotherapeutic approaches, like gestalt therapy, can be practiced as an alternative practitioner, but not as a psychotherapist (Bundesrepublik Deutschland, 2020; Bundespsychotherapeutenkammer, 2021).\n\nOne must complete a master’s degree in psychology in Switzerland. Following this, several years of postgraduate training as a psychotherapist can be completed in a psychotherapeutic teaching organization. In total, 42 psychotherapeutic educational institutions are accredited in Switzerland covering various psychotherapeutic approaches, such as psychoanalysis, gestalt therapy, psychodrama, person-centered psychotherapy, systemic therapy, and many more (Schweizerische Eidgenossenschaft, 2016). Both Switzerland and Germany consider psychotherapy to be part of psychology and teach students experimental psychology right from the start. This is a view that the author has already opposed in several papers and books (Raile, 2023a, 2023b, 2023c) and will not be discussed further here.\n\nThe Psychotherapy Act of 1990 is still valid in Austria. It prescribes a two-part training schedule to become a psychotherapist. This consists of a general propaedeutic course and a specialized course in a specific approach. In Austria, 23 psychotherapeutic approaches are currently legally recognized, including psychosynthesis, individual psychology, gestalt therapy, and cognitive behavioral therapy. Unlike in Germany or Switzerland, it is not necessary to have a degree in psychology to complete psychotherapy training; it is even possible to become a psychotherapist without a degree in Austria (Bundesrepublik Österreich, 1990). This is expected to change in the next few years, as a new psychotherapy law is currently being prepared and is expected to be submitted for parliamentary review in the second half of 2023 (Datler et al., 2023).\n\nWhen the author of this paper published the first book on eco-anxiety three years ago (Raile and Rieken, 2021), there were no courses for psychotherapists that explicitly addressed the topic of climate change or the psychological effects of the climate crisis. There is still no dedicated course in the German-speaking world that teaches the complex interrelationships between climate change and (mental) health mentioned in the previous section in the necessary detail (Psychologists for Future, 2023, personal communication). Fortunately, there are at least individual training events:\n\n• In February 2023, the Forum Person-Centered Psychotherapy in Austria offered a seminar on climate change and the challenges for psychotherapy (Forum Personzentrierte Psychotherapie, 2023).\n\n• In March 2023, the Austrian Academy for Psychology offered a more specialized seminar on the Psychology of Climate Protection (ÖAP, 2023).\n\n• In May 2023, the Association for the Promotion of Clinical Behaviour Therapy offered a lecture by a psychotherapist from Psychologists for Future on the climate crisis and psychotherapy (VFKV, 2023). The same psychotherapist holds various lectures in different organizations and talks mostly about the climate crisis and psychotherapy (e.g., CIP-Akademie, 2021; Fortschritte Hamburg, 2022).\n\n• In June 2023, the Psychotherapy Association in Germany published an information webpage on climate protection and psychotherapy. They wrote about various aspects psychotherapists can do or should consider when treating patients. Besides clinical aspects, they wrote about health prevention and political engagement (DPtV, 2023).\n\n• In September 2023, the German Psychology Academy will offer a seminar on psychology, psychotherapy, and climate crisis. The lecture is intended to raise awareness among psychologists and psychotherapists about this important topic and to provide understanding of psychological mechanisms in connection with the climate crisis (Deutsche Psychologen Akademie, 2023).\n\nOrganizations like Psychologists for Future offer regular seminars on climate change and psychology/psychotherapy. The Sigmund-Freud University (SFU) in Vienna also offers seminars on climate change and psychotherapy for students and licensed psychotherapists. A Climate Study Group which organizes lectures and discussions on its own initiative has been formed by psychotherapy students at the SFU (SFU, 2023). A separate event was held in October 2022 titled “SFU Goes Climate”, where researchers from all faculties presented their contributions to researching and addressing the climate crisis (SFU, 2022). The Sigmund-Freud University has the first concept for a two-semester course on eco-emotions, which not only teaches the basics of climate change and its complex influences on (mental) health and vice versa, but also focuses on practical psychotherapeutic work (Raile, 2023d). Unfortunately, most German-speaking universities do not offer such training for psychotherapists, although the topic is highly relevant. The possible contents of such a training series are summarized and critically discussed in the next section.\n\n\nTeaching climate-health competency in psychotherapeutic education – an example\n\nWhen we think about creating a course for climate-health literacy, we must define our targeted audience. Are we talking to psychotherapists about the impact of climate change on mental health, or are we talking to other health professionals, like doctors and nurses, or are we talking to patients, or to the general public? Depending on the target group, the form of communication (use of technical vocabulary) or the content (assumption of prior knowledge) must be adapted. While the general population benefits more from learning about the mechanisms and effects of the climate crisis and individual coping strategies, psychotherapists benefit more from learning about the climate-specific aspects of mental health and how to adequately deal with those in practice. The following paragraphs present a concept of what such a training course could look like. The concept was developed by the author taking into account the theoretical foundations outlined in the previous section and in exchange with students (e.g., the Climate Study Group of Sigmund Freud University), psychotherapy colleagues (e.g., the co-author of the monograph on Eco-Anxiety) and experts (e.g., from Psychologists For Future). A modular and sequential three-level course is being considered with seminars for beginners, advanced professionals, and experts. The explanations below include the contents of the individual courses. The didactic, the way of conveying the contents, is not explicitly described, and can be freely chosen by the lecturers, whereby a mixture of frontal presentations and interactive elements is recommended.\n\nPhysical and climatologic basics\n\nFirst, it is important to make the physical and climatologic basics of climate change as understandable as possible to the participants. Not all people are aware of the basic mechanisms that lead to global warming, the increase in extreme weather events, and other impacts (Dupigny-Giroux, 2017; US Global Change Research Program, 2009). Since psychotherapists do not need any special expertise here, this part can be taught in a condensed form.\n\nDirect and indirect impacts of climate change on human health\n\nThis could be an overview seminar on the impacts of climate change on human health as explained in the chapter impact of climate change on the psyche and vice versa. The seminar should provide a broad but not necessarily profound knowledge about the connections between climate change and human health. Part of the lecture should contain explicit information about the impact of climate change on mental health since the targeted group consists of psychotherapists (Limaye et al., 2020; Grabow et al., 2023). Case studies from practice are useful.\n\nSelf-awareness and self-reflection\n\nFor psychotherapists, self-awareness and self-reflection are an essential part of their training, practice, and professional identity. The professional reflection of one’s own techniques and interventions in therapy, one’s own strengths and weaknesses and factors influencing the treatment accompanies them in their everyday professional life (Strauß and Taeger, 2021). It is particularly important for psychotherapists to reflect on their own role in the face of the climate crisis and to critically consider their actions and possibilities for action both within and outside the treatment setting. Such a seminar should be organized as a self-awareness group.\n\nClimate protection, psychological background of protective behavior, and professional ethics\n\nThis seminar is about climate protection and the psychological factors influencing protective behavior. Psychotherapists should not only know what everyone can do to protect the climate but should also have knowledge of important psychological inhibitors and enhancers of being actively protective, like established habits or fears. They also should think about and discuss their responsibilities, what they can do, what they should do, and what they must do to protect the climate and what are they not allowed to do because of their professional roles as psychotherapists (Raile, 2023a).\n\nThe direct and indirect impact of climate change on (mental) health\n\nWhile the beginners’ seminar on the same topic focuses on an overview of the many interactions between climate change and (mental) health, individual factors are dealt with in more detail in this course. The aim is to provide more in-depth knowledge (e.g., Codjoe et al., 2020; Kornhuber et al., 2023; Watts et al., 2018). Either a multi-part seminar or a weekend seminar could be offered and arranged so that individual influencing factors can be addressed in detail.\n\nEco-emotions: In the advanced seminar on eco-emotions, the wide range of emotions related to the climate crisis is extensively covered. Psychotherapists should not only gain knowledge about the triggers, but also learn about the characteristics that distinguish eco-emotions from other feelings (Raile, 2023a, 2023d). Depending on the scope of the seminar, individual eco-emotions like eco-anxiety can be discussed in more detail and case studies can be presented.\n\nCoping and resilience in the climate crisis\n\nPeople who suffer from such strong eco-emotions (like eco-anxiety) that they affect everyday life do not always come to psychotherapeutic practice. They find other coping strategies. These can be used by psychotherapists to offer their patients more comprehensive ways of dealing with their feelings (Raile and Rieken, 2021). The content can be connected meaningfully with resilience, the reason why some people suffer more from the psychological effects of the climate crisis than others.\n\nThe role of psychotherapists in the climate crisis\n\nBased on the seminars on self-awareness and ethics, psychotherapists should also become aware of their own role in the climate crisis (Orange, 2016). First, as role models regarding climate protection; second, as persons who can educate people about climate change and how to overcome factors inhibiting individual climate- protection measures; third, as mental-health experts who can implement preventive as well as curative measures.\n\nThe seminars in the experts’ section can be very different and adapted according to the target group. Different psychotherapeutic approaches and their treatment strategies for e.g., severe cases of eco-anxiety, eco-traumas, and activist burn out can be addressed as well as the psychosocial care system and regional support centers for those affected by direct or indirect impacts of the climate crisis. Content on the cooperation of different professional groups in the sense of improved prevention or education is also conceivable, as well as further expertise in climate protection and ethics.\n\n\nDiscussion\n\nThe concept presented here does not contain all the points dealt with in the previous section because not all of them are equally relevant for psychotherapists. A separate seminar for the impact of climate change induced infections on mental health may be more relevant for medical doctors but less relevant for psychotherapists due to their primary focus on mental health. However, it is important that mental-health professionals know about these connections and can communicate them. This makes the concept vulnerable to critical review, as other experts may see other contents as more important. Various seminar providers may also select contents according to specific interests to attract as many paying participants as possible. Other education and training providers may delete contents with reference to a limited budget or (in their view) a lack of relevance for psychotherapists. Regardless of the reasons for the deletions or the choice of contents, it is an important step forward if such topics are taught at all in psychotherapeutic education and training. In this regard, even a small step in this direction is a success in the fight against the advancing climate crisis and for people’s mental health in times of climate crisis.\n\nEspecially the teaching of contents like eco-emotions can be criticized by psychotherapists since dealing with emotions is part of psychotherapeutic training, anyway. This criticism can be countered in three ways: First, contents like crisis intervention or trauma therapy are also part of psychotherapeutic training, but not always sufficient to work in depth with severely traumatized people. Further training and specialization are never pointless, but relevant, for example, to get to know the specific characteristics of eco-emotions in depth. Second, pathological emotions, such as generalized anxiety disorder, are different from eco-anxiety, which can also display similar symptoms. The difference is that the threat, i.e., the climate crisis, is real, and the feelings of anxiety are basically adequate. Therefore, in addition to working on the feelings, we also must work on dealing with the causes. Contextual knowledge is of great importance here, which is why further training is important. Third, such training serves to sensitize psychotherapists to the climate crisis and its effects on the human psyche. This is not only important for psychotherapeutic work, but also for their own mental hygiene because psychotherapists can also experience eco-emotions, such as fear or anger (Raile, 2023d).\n\n\nConclusions and a plea for teaching climate-health literacy to health-care professionals\n\nClimate change is steadily progressing, and humanity does not presently seem able to stop it effectively. The consequences are severe and affect not only our planet and ecosystems, but also our health. For the sake of our health and because we can only effectively protect the climate if we protect our health, it is important that health-care professionals are informed about the effects of climate change. It is important that health-care professionals, presented here using the example of psychotherapists, have climate health literacy, i.e., knowledge of the complex mechanisms and interactions between climate change and health.\n\nAll psychotherapists and all institutions offering training and continuing education for psychotherapists and all other health-care professions are therefore recommended to include these contents in their curricula, to offer seminars, and to provide further information on these topics.",
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Publisher Full Text\n\nZhu C, Kobayashi K, Loladze I, et al.: Carbon dioxide levels this century will alter the protein, micronutrients, and vitamin content of rice grains with potential health consequences for the poorest rice-dependent countries. Sci. Adv. 2018; 4(5): eaaq1012. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZiello C, Sparks TH, Estrella N, et al.: Changes to airborne pollen counts across Europe. PLoS One. 2012; 7(4): e34076. Publisher Full Text\n\n\nFootnotes\n\n1 The question of body-mind duality vs. body-mind unity is a millennia-old philosophical question that has still not been clarified. The author of this paper adheres to the body-mind unity definition."
}
|
[
{
"id": "212179",
"date": "17 Oct 2023",
"name": "Melanie Boeckmann",
"expertise": [
"Reviewer Expertise Climate change education",
"climate change and health"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nContent-wise suggestions:\nFor sake of completeness, the line “Heatwaves lead to excess mortality, particularly among vulnerable groups, such as the elderly, the homeless, construction workers, pregnant women, and young children”, should also include people with pre-existing diseases.\nSome concepts could enhance the arguments made in certain sections. For example, in the “Social factors (migration, wars, poverty)” paragraph, including the concept of “climate migration” could enhance the arguments made.\nSimilarly, in the “Coping and resilience in the climate crisis”, it would be also important for climate vulnerability/ climate resilience to be added to the curricula. Psychotherapists should be aware that certain people due to socioeconomic, geographic, heath and demographic factors are more impacted by climate change than others. Consequently, this may also result in higher anxiety. The concept of “climate precarity” is rooted in the recognition of this inequality, which holds that class, social, labour and/or gender inequities amplify negative impacts from climate change. This concept could also enhance this paragraph. Additionally, from a community or systems level, namely the instrastructure and ecosystem resilience; social/economic resilience and climate adaptation measures also influence the level of resilience. Being aware of these dynamics and factors that impact the risk of a patient is quite important for psychotherapists as it gives them an understanding of what causes their eco-emotions and perhaps ways how these particular people can engage in protective behavior.\nAdditionally, some minor grammatical errors are noted below: Line to “…health either directly in heat…” Suggestion: “…directly through heat…”\nSentence: “People who suffer from such strong eco-emotions (like eco-anxiety) that they affect everyday life do not always come to psychotherapeutic practice.” Suggestion: “…that affect their everyday lives, do not…”\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "11197",
"date": "13 Apr 2024",
"name": "Paolo Raile",
"role": "Author Response",
"response": "Thank you very much for your valuable time, your comments, and your corrections. I implemented all of them into the new version of the manuscript and am very thankful for the improvements due to your suggestions."
}
]
},
{
"id": "229388",
"date": "26 Feb 2024",
"name": "James Irlam",
"expertise": [
"Reviewer Expertise Education for Sustainable Healthcare"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 generally well written, but it lacks even a brief description of the search strategy, and requires a discussion of its potentially limited applicability to psycho-education outside of German-speaking countries, and the implications for further research.\nPlease see my comments plus the language and grammar corrections in the attached PDF linked here.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": [
{
"c_id": "11198",
"date": "13 Apr 2024",
"name": "Paolo Raile",
"role": "Author Response",
"response": "Thank you very much for your valuable time, your comments, and your corrections. I implemented nearly all of them into the new version of the manuscript (but not \"the\" in Fridays for Future as you recommended) and am very thankful for the high improvements due to your suggestions. I enhanced the abstract, added the limitation in the last paragraph, and added a short paragraph on how I conducted the research/reviews. Thank you once again for your time!"
}
]
}
] | 1
|
https://f1000research.com/articles/12-982
|
https://f1000research.com/articles/13-163/v1
|
08 Mar 24
|
{
"type": "Opinion Article",
"title": "Freshwater systems in the Anthropocene: why we need to evaluate microplastics in the context of multiple stressors",
"authors": [
"Rachel K. Giles",
"Bonnie M. Hamilton",
"Rachel K. Giles"
],
"abstract": "Microplastics are a diverse contaminant with complex physical and chemical properties. While microplastics have varying effects, most studies to date have focused on evaluating microplastics as a single stressor under stable environmental conditions. In reality, organisms are exposed to more than microplastics, and thus, it will be increasingly important to evaluate the effects of microplastics in the context of multiple anthropogenic stressors. Here, we highlight the need to assess the physical and chemical effects of microplastics, as well as their interactions with other anthropogenic stressors, at multiple levels of biological organization (i.e., sub-organismal, individual, population, community, ecosystem). We also outline research priorities and recommendations that will facilitate ecotoxicological assessments to better encompass the multidimensionality of microplastics as environmental conditions continue to change. By taking a multi-stressor ecotoxicological approach, we can work toward a better understanding of microplastic and other stressor effects at multiple levels of biological organization to help inform robust, evidenced-based policy and management decisions.",
"keywords": [
"global change",
"multiple stressors",
"aquatic",
"emerging contaminants"
],
"content": "Introduction\n\nMicroplastics are a contaminant of emerging concern in freshwater ecosystems (Lambert and Wagner 2018; Rochman and Hoellein 2020). They can cause a range of adverse effects in freshwater biota at multiple levels of biological organization, due in part to their inherent complexity (e.g., size, polymer, morphology) (Rochman et al. 2019; Bucci et al. 2020). Studies that investigate microplastics as a single stressor (e.g., Li et al. 2024; Malinowski et al. 2023; Schür et al. 2023) have demonstrated that microplastics are impacting freshwater ecosystems. However, freshwater ecosystems are impacted by more than just microplastics, which current research often fails to incorporate.\n\nIn addition to microplastics, freshwater ecosystems are impacted by anthropogenic stressors including climate change (Carpenter et al. 1992; Perkins et al. 2010), pollutant loading (Amoatey and Baawain 2019; Peters et al. 2013), nutrient loading (Smith 2003) and invasive species (Gallardo et al. 2016; Dextrase and Mandrak 2006), which could be better incorporated into microplastic research (Figure 1). Each of these stressors individually impact freshwater ecosystems with effects ranging from loss of biodiversity (Habibullah et al. 2022; IPCC 2022), to degraded habitat (Paul and Meyer 2001) and altered ecosystem functioning (Everard and Moggridge 2012). Despite this, few microplastic studies incorporate the reality that freshwater ecosystems are impacted by not just microplastics, but rather many anthropogenic stressors.\n\nUsing a multi-stressor lens to understand the effects of microplastics in freshwater ecosystems is critical in understanding how these stressors may also impact other environments, e.g., terrestrial ecosystems. Freshwater ecosystems serve as the integral connection between terrestrial and aquatic environments; rivers in particular serve as the connection between terrestrial, freshwater, and marine ecosystems (Likens and Bormann 1974; Krause et al. 2019). Given this, and that freshwater ecosystems are viewed as sentinels (e.g., the canary in the coal mine) with respect to anthropogenic perturbations (Woodward et al. 2010; Perkins et al. 2010), it is an important environment to assess multiple stressor impacts.\n\nDespite the significant progress in our understanding of the sources, fate, and effects of microplastics in the last decade, knowledge gaps remain regarding how microplastics impact aquatic ecosystems in the context of multiple stressors, particularly at higher levels of biological organization, and how this data may be used to inform monitoring priorities and management decisions across aquatic and terrestrial ecosystems, alike. Here, we argue that researchers should (1) study microplastics as inherent multiple stressors by evaluating the physical and chemical effects; and (2) take an ecosystem level approach in investigating the effects of microplastics with other anthropogenic stressors present in the environment (e.g., metals, industrial chemicals) under varying environmental conditions (e.g., temperature, water chemistry). Last, we outline research priorities and recommendations to facilitate ecotoxicological assessments that will better encompass the multidimensionality of microplastics with other multiple stressors as environmental conditions (e.g., climate) continue to change. By taking a holistic approach and evaluating microplastics as a multi-stressor and in the presence of other anthropogenic stressors, we can move toward improved conservation and management policies and practices.\n\n\nMicroplastics as a physical and chemical stressor\n\nMicroplastics (<5 mm; Arthur et al. 2009) are inherently complex, varying in toxicity across physical and chemical characteristics (Rochman et al. 2019), whose nature and interactions remain misunderstood. While it has become clear that certain morphologies, sizes, polymer types, and additives may lead to varying effects (Zimmermann et al. 2020; Strungaru et al. 2019; Bucci et al. 2020; da Costa et al. 2023), most studies do not design experiments to evaluate these characteristics in combination; thus, failing to consider the inherent complexity of microplastics.\n\nThere has been significant progress in understanding the physical effects of microplastics, i.e., morphology and size. Previous research has established simpler morphologies like spheres, for example, are less toxic than complex morphologies like fibers and fragments (e.g., Ziajahromi et al. 2017; Qiao et al. 2019a; Cole et al. 2019; Danopoulos et al. 2022). Further, particle size influences toxicity (Thornton Hampton et al. 2022) as well as the toxicokinetics/dynamics in exposed organisms (Coffin et al. 2022; Thornton Hampton et al. 2022b). Understanding the mechanisms of toxicity and biological fate could be furthered by investigating mixtures of different morphologies and sizes.\n\nPolymer type is a chemical characteristic of microplastics that may influence toxicity due to its chemical constituents, e.g., monomers (Lithner et al. 2011), yet there is a lot we still don’t know about the effects of different polymer types. Some studies have experimentally tested hypotheses about how effects vary among different polymers types, and have found differences in observed effects (e.g., Zimmermann et al. 2020). Despite this, the majority of studies often focus on a few polymer types that are most easily accessible for research, namely polyethylene (PE) and polystyrene (PS; Thornton Hampton et al. 2022) and omit other polymer types with that are commonly found in the environment, such as polyvinyl chloride (PVC) and polyurethane (PU) (PlasticsEurope 2022; Zimmermann et al. 2020). While these studies have allowed us to understand the physiological and ecological impacts of specific microplastic polymers across different levels of biological organization, integration of other polymers and polymer mixtures will improve our understanding of the impacts of microplastics as a multi-stressors.\n\nAdditive chemicals are another chemical aspect of microplastics that should be considered more when assessing toxicity as they can illicit adverse effects (e.g., Tian et al. 2021; Chibwe et al. 2021; Zimmermann et al. 2019). Plastic additives provide specific properties such as flexibility, color, UV protection, and durability (Hahladakis et al. 2018; Hermabessiere et al. 2017), can account for nearly 60% of the total mass of the material (Net et al. 2015) and often are not bound to the polymeric matrix; thus, leaching into the environment (Hermabessiere et al. 2017). In the environment, these additives can be independently toxic (Catrouillet et al. 2021; Fauser et al. 2022, 2020; Tian et al. 2021). Biological effects may differ according to polymer type due to their varied chemical constituents (Groh et al. 2023; Hahladakis et al. 2018; Zimmermann et al. 2019). For example, styrenic compounds that are often found in polystyrene (PS) are known endocrine disruptors (Lithner et al. 2011), whereas additives such as flame retardants or UV-filters, which are found in a variety of polymer types, have been shown to have a range of toxicological effects, such as oxidative stress and cytotoxicity (Zimmermann et al. 2019). Given that additives are used commercially in microplastic production, they should be considered a co-contaminant when evaluating microplastic toxicity.\n\n\nEffects of microplastics with other environmental stressors\n\nWhile microplastics will impact ecosystems as a multiple stressor, they also interact with other anthropogenic stressors present in a system (e.g., climate change, increased salinity; Figure 1). The combined effects of these stressors may result in different ecological outcomes than when assessed in combination. Thus, in addition to being evaluated as a multi-stressor on its own, microplastics should be evaluated in relation to other ecological stressors present within the Anthropocene (e.g., climate change).\n\nMicroplastics co-occur with other emerging contaminants of concern such as pharmaceuticals, agricultural chemicals (e.g., pesticides; Bhagat et al. 2020), POPs (Rodrigues et al. 2019), and flame retardants (Lambert and Wagner 2018) whose combined effects to freshwater ecosystems should be considered (Figure 1). It is well established that these environmental contaminants have their own suite of toxic effects. For example, pharmaceuticals can lead to endocrine disruption in fish (e.g., estrogenic compounds from wastewater effluent, Kidd et al. 2007) while pyrethroid insecticides can lead to neurotoxicity in vertebrates (Vijverberg and van den Bercken 1990). In addition to co-occurring with microplastics, these anthropogenic contaminants may be transported by microplastic when they sorb to the surface of the plastic. While this is an important phenomenon that may contribute to the toxicity of microplastics and other stressors (see Lohmann (2017), Gouin (2021) and Koelmans (2022), a deep dive into this discussion is outside the scope of this paper. However, acknowledging the presence, potential transport, and toxicity of other chemical contaminants in an ecosystem, is important to disentangle the impacts of microplastics from those of other chemical contaminants in the environment (Campanale et al. 2020).\n\nClimate change is another aspect of the Anthropocene that is interacting with microplastics to modulate ecological effects in aquatic ecosystems. Some calls have been made to incorporate this reality in the microplastics field however, relatively few studies have experimentally tested this (e.g., Kolomijeca et al. 2020). Some studies have tested the multi-stressor effects of climate change and microplastics on a variety of organisms (e.g., Yang et al. 2020; O’Brien et al. 2022; Lins et al. 2022) shedding light on how aspects of climate change (e.g., CO2 and temperature) modulate biotic endpoints including individual growth (Yang et al. 2020), motility, survival (Lins et al. 2022), and species interactions (O’Brien et al. 2022). Given the urgency in understanding the impacts of climate change across a range of environments, studies should incorporate aspects of climate change when assessing ecological effects of microplastics.\n\nFinally, microplastic studies should seek to understand the effects of microplastics and other stressors at higher levels of biological organization. Experimental studies have shown that the effects of microplastics can span multiple levels of biological organization (Bucci et al. 2020), including at the community (e.g., biodiversity, species composition; Green et al., 2016; Redondo-Hasselerharm et al. 2020), population (e.g., abundance; Bosker et al. 2019), individual (e.g., survival, growth; Bucci et al. 2022; Silva et al. 2019), and sub-organismal (e.g., inflammation, oxidative stress; Qiao et al. 2019b) levels. However, studies tend to focus on individual, or population-level impacts, ignoring higher-level impacts. Clements and Rohr (2009) propose to treat contaminants as a predator, with direct and indirect impacts to individuals and trophic levels to elucidate effects at higher levels of biological organization; thus, improving community and ecosystem level effect assessments. This approach could be taken with microplastic studies to incorporate the complexity of microplastics themselves and their interactions with other stressors (e.g., chemicals, climate change, invasive species) to predict ecosystem-level effects.\n\n\nA need to apply novel approach methods to monitor microplastics in a multi-stressor world\n\nAddressing the multi-stressor impacts of microplastics with other stressors is no easy task but is nonetheless crucial to informing monitoring and management (Figure 2). To address this, new analytical, genomic, and design approaches are needed to better understand the toxicity of microplastics in the context of multiple stressors. Because most proposed monitoring programs focus on the physical characteristics of microplastics with only recent calls to include the chemical characteristics (Hamilton et al. 2022) researchers will need to re-imagine microplastic experiments in this multi-stressor view. Additionally, leveraging new technologies will facilitate better evaluation of the physical and chemical effects of microplastics through a multi-stressor lens, improving our understanding of the impacts at multiple biological levels of organization, ultimately improving monitoring and management decisions.\n\nTo facilitate multi-stressor assessments of microplastics with other anthropogenic stressors, experimental designs should be re-imagined. To assess the effects of multiple stressors, multiple experiment units are required to tease apart the effects of individual stressors. Logistically, including multiple experimental units can be challenging due to space, time, and human-power constraints. Ecotoxicologists should work together with other experts (e.g., engineers) to design instruments to facilitate multi-stressor work. For example, Nguyen et al. (2018) present a well-plate platform designed to test effects of climate change and other anthropogenic stressors on aquatic organisms. This platform was later used to investigate the multi-stressor effect of microplastics and climate change on algae (Yang et al. 2020; Guo et al. 2021), plants (O’Brien et al. 2022), and invertebrates (Lins et al. 2022). Technologies like these will help to facilitate multi-stressor testing of microplastics with other stressors.\n\nFurther, novel analytical approaches such as non-target screening, suspect screening, and effect-directed analysis, can be used to identify microplastics and other environmental contaminants, which will be critical to monitoring the effects of microplastics in nature. New developments in analytical chemistry involving high resolution mass spectrometers, (i.e., non-target and suspect screening) can enable the screening of a broad range of compounds in a sample (e.g., biota or plastics; Ballesteros-Gómez et al. 2016; Fries et al. 2022). These techniques often aim to identify contaminants rather than quantify them, but can also result in qualitatively identifying certain compounds (Schymanski et al. 2015; Fries et al. 2022). Regardless, non-target and suspect screening is an important first-step in identifying specific chemicals and microplastics in a complex mixture and matrix. Often combined with nontarget screening techniques, effect-directed analyses use toxicity assays to determine whether a sample with a stressor mixture exhibits a toxic effect. Here, the complexity of a sample is reduced and potential compounds that may illicit a toxic effect are identified. These approaches have been applied to plastics to a limited extent (Schönlau et al. 2019) and offer possibilities of addressing toxicity and chemical identification in a multi-stressor mixture.\n\nNew genomic tools can be used to determine contaminant burdens and effects at different levels of biological organization. For example, Zahaby et al. (2021) developed a toxicogenomics approach (ToxChip) to determine oil-related contaminant burdens in the livers of seabirds in the Canadian Arctic and successfully distinguished between the two distinct colonies of seabirds based on the expression of genes associated with trace element and polycyclic aromatic compound exposure (Zahaby et al. 2021). Furthermore, a recent study by Giroux et al. (2023) utilized eRNA/eDNA metabarcoding approaches to successfully detect community-level impacts of nanoplastics in benthic estuarine ecosystems. Here, Giroux et al. (2023) produced dose-response relationships of nanoplastics at a community level; thus, underscoring the importance of assessing and monitoring community-level effects. Additionally, RNA sequencing approaches can be used to understand the underlying mechanism of toxicity of microplastics and other stressors. RNAseq can be used to screen for differential expression of genes for organisms that have been exposed to varying stressors or stressor levels (e.g., Waller et al. 2019; Bertucci et al. 2017; Shaw et al. 2007). Through this analysis, candidate genes that are differentially expressed are identified and gene expression changes (up or downregulation) can be measured. Ultimately, by utilizing RNAseq, effects from one stressor can be disentangled from another, assuming that the gene response is specific to one stressor, and ultimately improve ecosystem level monitoring of multi-stressor effects.\n\nLast, to facilitate the multi-stressors assessment of microplastics with other anthropogenic stressors, engineering technologies can be used to reimagine toxicity experiments. To assess the effects of multiple stressors, multiple experiment units are required to tease apart the effects of individual stressors. Logistically, including multiple experimental units is challenging due to space, time, and human-power constraints. Ecotoxicologists should work together with engineers to design instruments to facilitate multi-stressor work. For example, Nguyen et al. (2018) present a well-plate platform designed to test effects of climate change and other anthropogenic stressors on aquatic organisms. This platform was later used to investigate the response of algae (Yang et al. 2020; Guo et al. 2021), plants (O’Brien et al. 2022), and invertebrates (Lins et al. 2022) to climate change with microplastics. Technologies like these will help to facilitate multi-stressor testing of microplastics with other stressors.\n\n\nConclusion\n\nTerrestrial and aquatic ecosystems are inextricably linked together, and are impacted by multiple stressors. Current ecotoxicology approaches must be adapted in order to incorporate the complexity of stressors that ecosystems are subject to in the Anthropocene. Here, we have argued that microplastics should be studied as multiple stressors; first on their own by incorporating physico-chemical aspects of microplastics into study designs and second, by considering their interactions with other anthropogenic stressors that may modulate effects at multiple levels of biological organization. Last, we highlight the need to embrace novel chemical, genomic, and other approaches to develop robust and consistent monitoring efforts across biological levels of organization. By implementing these changes, using these new techniques, and improving study design, monitoring and management of microplastics and other environmental stressors will be improved.\n\n\nAuthor contributions\n\nRKG and BMH contributed equally to the conception and production of this manuscript.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nWe would like to thank C. Rochman (University of Toronto, Department of Ecology and Evolutionary Biology) for her insight during the development and writing process.\n\n\nReferences\n\nAmoatey P, Baawain MS: Effects of pollution on freshwater aquatic organisms. Water Environ. Res. 2019; 91: 1272–1287. Publisher Full Text\n\nArthur C, Baker J, Bamford H: Proceedings of the International Research Workshop on the Occurrence, Effects, and Fate of Microplastic Marine Debris. NOAA Technical Memorandum NOS-OR&R-30. National Oceanic and Atmospheric Administration, Silver Spring, MD; 2009.\n\nBallesteros-Gómez A, Jonkers T, Covaci A, et al.: Screening of additives in plastics with high resolution time-of-flight mass spectrometry and different ionization sources: direct probe injection (DIP)-APCI, LC-APCI, and LC-ion booster ESI. Anal. Bioanal. Chem. 2016; 408: 2945–2953. 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}
|
[
{
"id": "256062",
"date": "23 Apr 2024",
"name": "Leah Thornton Hampton",
"expertise": [
"Reviewer Expertise aquatic toxicology",
"endocrine disruption",
"immunotoxicity",
"microplastics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 Comments:\nThe article entitled, “Freshwater systems in the Anthropocene: why we need to evaluate microplastics in the context of multiple stressors” highlights the need to evaluate the potential impacts of microplastics through a multi-stressor lens. The authors briefly summarize what is known about how specific microplastic characteristics (e.g., particle size, material type, and morphology) influence toxicological outcomes and provide a series of examples of creative approaches to microplastic toxicity testing, particularly for microplastic mixtures.\nOverall, the points made in the article are factually accurate, but there is a failure to acknowledge that there remains a significant amount of foundational toxicity testing to be done for microplastics (e.g., dose response, identification of effect mechanisms). In addition, there is also a lack of clarity and specificity on what actions the authors are recommending for the research community. If the first half of the article which summarizes previous knowledge is dramatically reduced, and the second half of the article was expanded in more detail to better support the arguments made, this piece could be much stronger. As it stands, this article generally repeats much of what has already been repeatedly suggested in the current body of literature (Provencher JF, et al., 2020 [Ref 1]), (Thornton Hampton L, et al., 2022 [Ref 2]), (Gouin T, et al., 2022 [Ref 3]), (Yin K, et al., 2021 [Ref 4]), (Connors KA, et al., 2017 [Ref 5), (Bucci K, et al., 2022 [Ref 6])\n\nI do strongly agree with the authors recommendation to collaborate across disciplines more broadly, but I also think this argument could be strengthened as well. I encourage the authors to expand on this concept. Finally, the title and abstract strongly imply a freshwater focus, but the points and argument made therein are also applicable to marine and terrestrial habitats which also must reckon with multiple anthropogenic stressors. I would recommend removing the freshwater angle as it is not needed.\nSpecific Comments:\nIn the introduction there is a focus on particle shape, size, polymer type, and chemical additives, but there are other physical and chemical particle features that may drive toxicity as well such as volume and surface area. Indeed, we know from decades of nanoparticle research that surface chemistry is critically important for toxicity. I would encourage the authors to describe those characteristics that are not focused upon as often within microplastics circles but are likely important based on previous knowledge from other contaminants and disciplines. There is an argument made to study impacts beyond the population level, but I found this argument to be somewhat weak given that effect mechanisms at lower levels of biological organization remain nebulous. It seems more pertinent to establish our understanding of toxicity at these lower levels before proceeding to complicated, costly studies at higher levels. It is also unclear how these types of studies would even be designed in the absence of a better understanding of microplastic toxicity overall. At several points, the environmental management community is cited as an important beneficiary of multidimensional microplastic toxicity studies. Yet, it is unclear as to how the results of these studies would be translated for use by the management community. I would suggest adding concrete hypothetical examples of what this may look like in reality. At the end of the article there is mention of emerging technologies for toxicity testing. While these tools may present new options for researchers, they need to make sense in terms of the questions being asked. In the examples provided, the studies focus on very specific scenarios, so it is unclear what the authors are advocating for in a broader sense.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": []
},
{
"id": "260577",
"date": "25 Apr 2024",
"name": "Maria Silvia Diaz-Cruz",
"expertise": [
"Reviewer Expertise Analytical Chemistry",
"environment",
"contaminants of emerging concern (microplastics",
"pharmaceuticals and personal care products",
"...)",
"wastewater treatment",
"and water reuse."
],
"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 opinion article describes the current approach to analyzing the presence, fate, and risk posed by microplastics in the environment, while also providing information to draw attention to the need to assess all of this considering different stressors (material characteristics, additives, adsorption of other compounds, temperature increase due to climate change, among others). Likewise, they argue that it is necessary to evaluate the impact at different levels of biological organization (ecosystem-community-population-individual-sub organismal). Only through this multifaceted approach will it be possible to have an accurate picture of the risks and develop appropriate use/disposal policies. The article is well-written and supported by current and appropriate literature. It concisely but descriptively reflects the current situation in the study of microplastics (MPs) in the environment and proposes a holistic vision that considers factors that have been little studied until now but that could lead to very different results from those currently available. Figure 2 could be made more fluid. This figure lacks numbers, which do appear in the figure caption.\nThe last paragraph before the conclusions, which begins \"Last, to facilitate the multi-stressor assessment....\" is a literal repetition of the first paragraph on the same page. Once these two issues are corrected, the paper can be ready for approval.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-163
|
https://f1000research.com/articles/12-16/v1
|
06 Jan 23
|
{
"type": "Study Protocol",
"title": "Study protocol for a systematic review of the social determinants of mental health and well-being of older migrants aged 50 years and above",
"authors": [
"Pankhuri Bhatia",
"Helen McLaren",
"Yunong Huang",
"Helen McLaren",
"Yunong Huang"
],
"abstract": "Background: Migration is a milestone event in a person’s life, bringing with it the challenges of settling down in an unfamiliar environment. The age at which migration takes place and the way migrants negotiate their old and new world significantly impacts their mental health. Thus, this systematic review seeks to analyse and summarize existing research detailing the contexts in which people migrate later in life and the associations between these contexts and social determinants of their mental health and well-being. Methods: Seven databases including PsycINFO, Web of Science, PubMed, Applied Social Sciences Index, Abstracts: ASSIA, Ageline, CINAHL, and Informit will be searched systematically for original journal articles published in English. In the first screening stage, the first reviewer (PB) will screen all titles and abstracts and mark all potentially eligible texts for full-text screening. The second reviewer (HM) will review the decisions made. Any potential conflicts will be resolved with discussion. Afterward, full texts of potentially eligible studies will be assessed for eligibility by two reviewers (PB and HM). The methodological quality (or risk of bias) of individual studies will be appraised using the Mixed Method Appraisal Tool. The thematic synthesis of the data will be performed using a hybrid approach incorporating deductive (framed against the social determinants of health using intersectionality as a lens) and inductive data-driven processes. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (Reg: CRD42022359881).",
"keywords": [
"migrants",
"immigrant",
"elderly",
"later-life",
"old age",
"mental health",
"well-being",
"systematic review protocol"
],
"content": "Introduction\n\nDemographic ageing is the defining feature of this century, associated with declines in fertility and increased life expectancy (Holecki et al., 2020). Adults above the age of 65 outnumber children below the age of 5, and by 2050, they are estimated to reach close to 2 billion, outnumbering adolescents as well (Segal, 2019). Additionally, the international migration of older adults has increased significantly. Globalisation processes and advances in communication technology not only accelerated the scale of international migration but also significantly altered the character of migration flows from permanent to more circular or temporary ones (Holecki et al., 2020; Zimmerman et al., 2011). The Internet, for example, has enabled visualizing a better life elsewhere and this can become a motivator for migration across age groups and regions. These changes necessitate a relook at the contexts in which people migrate and the implications for their mental health and well-being.\n\nThe largest migration trend is from less to more developed countries, with Europe and Oceania being the favourite migrant destinations (Melzer & Muffels, 2017). While migration takes place among all ages, the reason for international migration varies across age groups. The young tend to migrate for better education and improved employment prospects, and older people may follow their adult children for family reunification, or alternatively for accessing better healthcare, or lifestyle amenities (Scommegna, 2013).\n\nMigration, be it forced or voluntary, is a stressful phenomenon. It is more so for those migrating later in life because the intersections of migration and ageing make people susceptible to unique vulnerabilities (Litwin & Leshem, 2008). For example, older people’s adaptive capacities may be limited resulting in health, socioeconomic, and other support needs that are significantly different from younger age groups. Language barriers, limited employment opportunities, financial instability, and lack of entitlement benefits make them dependent on family members (Treas, 2008; Hadfield, 2014; Wu & Penning, 2015). This dependence is often accompanied by a loss of agency and control, significantly affecting their emotional health and well-being (Alvi & Zaidi, 2017). Existing evidence shows that older adults prefer to “age in place”, as a familiar environment with an existing support network that provides them with both independence and autonomy (Kennedy et al., 2015). Thus, it is important to look at the reasons that urge older people to leave their familiar environment and migrate.\n\nSo far, migration literature has been heavily skewed towards the working-age group i.e., the young, skilled migrants and international students (King et al. 2016; Coulter et al., 2016; Finney, 2011). Migration later in life (circular or permanent) requires specific attention as adapting to an unfamiliar environment can be particularly stressful for the elderly (Jang et al., 2020). Review studies considering the intersection of aging and migration are either country-specific, focused on the general ageing experiences, migration from developed to developing countries, or the social impact of late-life migration (Georgeou et al., 2021, Tang & Zolnikov, 2021; Maleku et al., 2021; Wang & Lai, 2020). The mental health impact of conflict-induced forced migration has also been studied extensively with a particular focus on refugees and asylum seekers (Virgincar et al., 2016). There have been some studies on the mental health and well-being of older adults otherwise at liberty to migrate. However, there is a lack of systematic review of such studies.\n\nThe 1998 United Nations Recommendations on Statistics of International Migration define ‘international migrant’ as a person who has changed their country of residence. Those migrating over the age of 65 are a significant number and would be close to 26 million worldwide (Zaiceva, 2014). In Australia, Canada, and New Zealand, the number of older retired migrants is close to the number of working migrants (Zaiceva, 2014). It is known that the likelihood of migration in later life reduces with age (Holecki et al., 2020), however, an initial scope showed that very few studies have focussed on the mental health and well-being of older migrants above 65 years. The age criterion for the proposed systematic review is expanded to older adults aged 50 years and above.\n\nThe main objective of the planned systematic review is to analyse and summarise existing research (both qualitative and quantitative) on the impact of international migration later in life on the mental health of older adults. The review of studies will specifically focus on answering the following research questions.\n\na) What are the individual, social and political contexts in which people decide to migrate later in life?\n\nb) What are the associations between later-life migration contexts and mental health and well-being?\n\n\nMethods\n\nThis study protocol is following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement (Moher et al., 2015).\n\nIt was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (Reg: CRD42022359881). Significant protocol amendments will be reported with the publication of the review.\n\nThe eligibility criteria for the included publications will be described based on the Population, Interest, context (PICo) framework (Lockwood et al., 2015).\n\nWe will include original studies on later-life migrants (≥ 50 years). Although the most accepted definition of old age is the age at which people start receiving a pension (i.e., above the age of 60, depending on country location), the socio-cultural definition of old age differs from country to country (WHO 2002; Zittoun & Baucal, 2021). For this review, later life would mean 50 years and above.\n\nThe migration experiences of different categories of migrants including refugees, asylum seekers, and displaced people vary a lot and thus can have a different impact on health outcomes. Thus, this review focuses exclusively on migrants and has excluded studies on refugees, asylum seekers, and other undocumented migrants. We will also exclude studies that are not specifically related to later-life migration. Navigating migration in older life is known to be particularly difficult. Liu et al., 2020). Research indicates older age at migration and limited years in the host country are significantly associated with negative mental health consequences which get moderated over time with increased cultural adaptation (Xiao et al., 2019). Negy et al., 2009 showed that retrospective memory of the migration experience declines after 5-years. The inclusion criteria for the length of stay of migrants in the destination country is thus set to ≤ 5 years. Studies in which the length of stay cannot be ascertained or is more than 5 years will be excluded.\n\nElderly migrants are more susceptible to mental health issues because of the loss of a familiar environment and difficulty making newer social connections (Wang et al., 2022). All studies looking at the positive or negative impact of migration on the mental health and well-being of elderly migrants will be included.\n\nAlthough internal migration can be equally challenging for older adults, for this review, studies focussing only on international migration/movement across international borders will be included. Studies related to intra-country/internal migration (rural to urban) will be excluded.\n\nWe will include all types of original studies that meet the above-mentioned inclusion criteria. Grey literature, reports of government and non-governmental organisations, editorial letters, conference papers, poster presentations, dissertations, expert opinions, letters to the editor, commentaries, and reviews will be excluded.\n\nNo restriction by the type of setting will be used.\n\nAll articles published from the date of origin of the database to 23rd May 2022 will be included.\n\nOriginal articles that are published in academic peer-reviewed journals will be included.\n\nStudies published only in English will be included.\n\nTo make the search comprehensive, a search of the current literature using seven electronic databases will be performed. These include (1) PsycINFO (via Ovid); (2) Web of Science (via Ebsco); (3) PubMed; (4) Applied Social Sciences Index and Abstracts: ASSIA; (5) Age line (via Ebsco); (6) CINAHL (via Ebsco); and (7) Informit Search. Hand-searching of potentially relevant studies will be done through the reference lists of all included studies and the reference lists of previously published related systematic reviews.\n\nThe search strategy will be developed using the PICo framework (Lockwood et al., 2015), combined with Medical Subject Headings (MESH) where applicable. Searches will be structured using a combination of keywords related to three main concepts; terms related to the study population such as “elderly”, “seniors”, (2) terms related to interest such as “mental health” or “mental issues”, and (3) terms related to context such as “migration”, “immigration”. The similarity of search terms will be ensured across databases to maintain consistency. The following are the search terms used in CINAHL VIA EBSCO without any limiters: (Grandparent OR grandparents OR grandmother OR grandmothers OR grandfathers OR grandfather OR geriatric* OR “senior citizens” OR “late-life” OR “later life” OR elderly OR “third age” OR “fourth age” OR retire* OR pensioners OR “Extended Family” OR “old aged” OR “older adults” OR “older adulthood”) AND (“mental health” OR “psychological health” OR “well being” OR wellbeing OR “Quality of life” OR “life satisfaction” OR coping OR resilience OR depression OR anxiety OR loneliness OR suicide OR suicidal) AND (migration OR immigration OR migrant? OR immigrant? OR “temporary visa” OR “temporary entrant” OR “documented migrants” OR “documented migrant” OR “documented immigrant?” OR “documented immigrants” OR “authorized immigrants” OR “authorized immigrant\")\n\nSearch results will be imported to Endnote, and then exported to Covidence systematic review software and duplicates will be auto-removed. While Endnote is a paid reference management software, free alternatives such as ReadCube Papers can likewise be used. Zotero is likewise a free alternative to Covidence for systematic screening of literature. In the first stage of screening using Covidence, the first reviewer (PB) will screen the titles and abstracts of each study against the inclusion criteria and the second reviewer (HM) will review the decisions made. Any disagreements will be mutually resolved through discussion. Potentially eligible records will be marked for full screening. Those titles and abstracts that provide insufficient information to determine relevance, will also be subjected to full screening. Afterward, full texts of potentially eligible studies will be retrieved for full-text review and assessed for eligibility by two review authors (PB and HM). Hand-searching of the references of selected articles will be conducted for identifying potentially relevant studies. During the entire process, the eligibility of the studies will be negotiated by consensus.\n\nA customised form will be used for data extraction. The following study characteristics will be extracted in a customised form:\n\no Details of authors\n\no Year of publication\n\no Country of study\n\n\n\no Aims/objectives/research questions\n\no Methodology\n\no Participant characteristics including the age of participants, country of origin, country to which they have migrated, and their context of migration.\n\no Key findings related to implications on mental health and wellbeing\n\nThe data extraction form will be developed through consultation. All the authors will contribute to data extraction. NVivo QSR will be used to assist in data extraction. A flow chart showing details of studies included and excluded at each stage of the study selection process will be provided.\n\nThe thematic synthesis of the data (both qualitative and quantitative) will be performed using a hybrid approach incorporating two contrasting philosophical methods of reasoning i.e., a top-down, deductive, theoretical process, and a bottom-up, inductive, data-driven process. For the deductive method, a table of priori codes will be created using an adaptation of the social determinants of health (SDH) framework with intersectionality as the lens. For effectively addressing mental health issues, causal pathways can best be understood with the SDH using an intersectional lens.\n\nOf all the frameworks used in health research – behavioural, cultural, structural, and social determinants of health – SDH is one of the most comprehensive frameworks as it takes into account a range of factors; social, economic, cultural, and political impinging upon the health of the person. WHO defines SDH as, “conditions in which people are born, grow, live, work, and age – conditions that together provide the freedom people need to live lives they value” (Commission on Social Determinants of Health, 2008, p. 26). SDH emphasizes the construction and impact of social structures and people’s relative positions in stratified hierarchies and power relationships and takes into consideration the interconnectedness of social, structural, and/or ecological factors that affect people’s health status (Castañeda et al., 2015). There has been growing interest in the social determinant of health framework in public health research and non-profit agencies, (Braveman et al., 2011), however, this framework has not been widely used in the field of immigration and health. An intersectional lens will be employed to understand the complexity and interconnectedness of various determinants.\n\nIndividual factors like age, gender, socioeconomic position, educational background, and financial stability which largely determine the welfare benefits one receives in the host country will be explored. An understanding of attitudes toward mental health, stigma, stereotypes, beliefs, and taboos related to mental illnesses is also important to understand the health-seeking behaviours of migrants in a new culture. This includes their relationship to the traditions and practices of the culture of origin.\n\nDespite the WHO’s emphasis on the ‘Health in all Policies’ approach, the influence of upstream SDH on migrants’ health largely goes unexplored in the migrant literature (WHO, 2014; Castañeda et al., 2015). For this review, attention would be given to the influence of upstream SDH including policies related to healthcare, welfare, insurance, and migration. Additionally, the economic policies of the host country, the differences in the socio-cultural context, and their impact on the mental health of migrants will also be explored.\n\nOlder migrants in most cases tend to stay with their adult children upon arriving in the host country (Liou & Shenk, 2016). Thus, family dynamics (conflict between intimate relationships), interactions with family members including spouse, children, grandchildren, and dependence on family members often lead to specific psychosocial stressors (Liou & Shenk, 2016). Specific attention will be given to the role of interpersonal relationships, formal and informal social networks, and social support systems in affecting the mental health and well-being of migrants. Migrants’ interactions with healthcare institutions, and other facilities like aged care, voluntary organizations working for migrants, and religious organisations will also be reported.\n\nThe priori set of codes will be supplemented with the codes emerging through the inductive analysis of the articles. To improve intercoder reliability, coding will be regularly reviewed by all three reviewers, and disparities and discrepancies (if any) will be addressed with consultation.\n\nA narrative synthesis will summarize and explain the characteristics and findings of the studies. Data will not be quantitatively synthesised. Quality appraisal of the included studies is a mandatory requirement of systematic reviews reported according to PRISMA guidelines. The methodological quality (or risk of bias) of individual studies will be appraised using the Mixed Method Appraisal Tool (MMAT) as it is highly useful in the appraisal of a range of study designs included in the mixed methods integrative systematic review (Hong et al., 2018; Pluye, 2015). To achieve consistency, the reviewers will develop a common understanding of the appraisal tool through discussions.\n\nOne of the main strengths of the protocol is its use of a comprehensive search strategy and a range of databases covering areas of migration, mental health, and ageing. No limitation has been applied in terms of the year of publication. It would be difficult to avoid publication bias because of the exclusion of grey literature and studies published in languages other than English. There is also a possibility of exclusion of some data of interest because of the exclusion of studies having a heterogenous population including undocumented migrants, refugees, asylum seekers, and displaced people, and studies not focussing specifically on later-life migration are also excluded.\n\n\nDiscussion\n\nIncreased migrations are reflective of widening global inequalities in terms of educational facilities, wages, healthcare facilities, and other resources. These increased migrations pose a challenge for global health equity movements as they put pressure on the health systems of the destination countries requiring arrangements for more healthcare workers, in line with development goals and for ensuring productive aging as international agreements entrust them with this responsibility.\n\nCountries so far have failed to acknowledge the difference between immigrants who aged in host countries and those who immigrated later in life (Ayalon et al., 2018). Additionally, voluntary migrants often get overlooked by policymakers as they aren’t viewed as deserving of social and health services (Castañeda et al., 2015). To our knowledge, this planned systematic review will be the first to examine the mental health implications for those willingly migrating later in life.\n\nThe findings of the review can serve in knowledge dissemination related to the factors that prompt the elderly to leave familiar environments and the identification of the congruence between the expectations of migrants and the initiatives taken by the host country for their successful integration and for achieving the goal of mental health for all. Issues related to access eligibility or barriers in the host country, and associations with older migrant health according to their migration contexts are also likely to be identified.\n\nThe results from the systematic review will be of interest to policymakers, health professionals, social workers, counselors, and non-governmental organizations. A lack of coordination in policies related to immigrants can prove to be inimical. The intersectionality approach will aid in better coordination of policies at different levels and the development of age-friendly migration and culturally informed health policies and enable the migrants to lead fulfilling lives by recognising them as valued, productive members of the host country.\n\nSearching and screening for relevant studies is expected to be completed in January 2023.\n\nAs systematic reviews use data from previously approved published studies, they are exempted from ethical approval. The results of this review study will be submitted for publication in a peer-reviewed journal.\n\nPB conceived and designed the study and is the guarantor. HM and YH supervised the entire process. PB and HM developed the search strategy, research questions, and study design. PB drafted the Protocol manuscript. HM and YH gave their inputs and revised the manuscript. All three authors approved the final draft of the protocol. All the reviewers will contribute to data extraction, synthesis, and the final draft of the review. All authors consent to abide by the protocol.",
"appendix": "Data availability\n\nNo underlying data are associated with this article.\n\nFigshare: CINAHL database search strategy for ‘Study protocol for a systematic review of the social determinants of mental health and well-being of older migrants aged 50 years and above. https://doi.org/10.6084/m9.figshare.21545673.v3 (Bhatia et al., 2022b)\n\nThis project contains the search strategy for CINAHL database.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAlvi S, Zaidi A: Invisible voices: An intersectional exploration of quality of life for elderly South Asian immigrant women in a Canadian sample. J. Cross Cult. Gerontol. 2017; 32(2): 147–170. Publisher Full Text\n\nBhatia P, Mclaren H, Huang Y: PRISMA-P Checklist. figshare. Dataset.2022a. Publisher Full Text\n\nBhatia P, Mclaren H, Huang Y: CINAHL Database Search Strategy.figshare. Dataset.2022b. 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}
|
[
{
"id": "177241",
"date": "19 Jul 2023",
"name": "Lucy P Jordan",
"expertise": [
"Reviewer Expertise Migration",
"mental health",
"policy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is an interesting topic. There are some serious issues with definitional terminology related to 'migrant' and 'elderly' which are further elaborated below. The authors should consider to refine these further before proceeding.\n\" exclusively on migrants\" needs better clarification. do you mean DOCUMENTED, LABOUR MIGRANTS, FAMILY REUNIFCATION? needs better specification\n\" ≤ 5 years. Studies in which the length of stay cannot be ascertained or is more than 5 years will be excluded.\" This is not clear. Why does the memory of migration matter for mental health? I could imagine it could matter as more transitory challenges could be captured before 5 years, thus, to exclude those with LESS than 5 years. However, I am not entirely clear what the specification is, nor the justification. Please clarify.\nSince you include those 50+ you cannot also call this population 'Elderly migrant'. Please be consistent and conscientious about the terminology used. 50s are really mid-life in current time with increase life expectancy. This influences the search strategy as well. There is a conflation of terminology and age inclusion which must be corrected. Someone who arrives in the early 50s may have very different eligibility criteria for benefits, for example, if they come to work.\n\n23rd May 2022? Why is the inclusion criteria set for over a year ago?\n\nAge in place; need further elaboration as there is significant literature about it as policy approach not only driven by personal preference.\n\n\" There have been some studies on the mental health and well-being of older adults otherwise at liberty to migrate\" needs citation support\n\"a) What are the individual, social and political contexts in which people decide to migrate later in life? b) What are the associations between later-life migration contexts and mental health and well-being?\" Both are very descriptive, could further critically analytical lens be adopted?\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? Not applicable",
"responses": [
{
"c_id": "11085",
"date": "13 Apr 2024",
"name": "Pankhuri Bhatia",
"role": "Author Response",
"response": "We thank the reviewer for their thorough review of the protocol and for providing us with valuable feedback. Their suggestions significantly enhanced the quality of the study. The reviewer’s suggestions have been incorporated in the revised version and point-by-point responses to their comments have been provided below We are pleased to inform you that the review has been accepted for publication - https://doi.org/10.1093/geront/gnae003 Comment 1: This is an interesting topic. There are some serious issues with definitional terminology related to 'migrant' and 'elderly' which are further elaborated below. The authors should consider to refine these further before proceeding.\" exclusively on migrants\" needs better clarification. do you mean DOCUMENTED, LABOUR MIGRANTS, FAMILY REUNIFICATION? needs better specification. RESPONSE: We thank the reviewer for their feedback and their interest in the topic. We have expanded on the definition of migrants used for this study and further clarified the inclusion and exclusion criteria. For this review, we will be focusing on “older unforced migrants.” Unforced migrants have been defined as those migrating for reasons other than an imminent danger to life due to situations such as war, conflict, persecution, or catastrophic natural disasters. These unforced migrants could be driven by several reasons including fiscal or social goals such as pursuing improved living conditions, healthcare, or an opportunity to reconnect with family members. Comment 2: \" ≤ 5 years. Studies in which the length of stay cannot be ascertained or is more than 5 years will be excluded.\" This is not clear. Why does the memory of migration matter for mental health? I could imagine it could matter as more transitory challenges could be captured before 5 years, thus, excluding those with less than 5 years. However, I am not entirely clear what the specification is, nor the justification. Please clarify. RESPONSE: The reviewer has rightly stated that by focusing on studies with the length of stay of migrants being less than or equal to 5 years, the researchers indeed aim to capture the potential transitory challenges that may arise during the early stages of relocation such as acculturation stress, cultural adaptation, and social integration, which can significantly impact mental health and wellbeing of these migrants. We have expanded on the rationale for the set criteria under the heading “Types of population.” Comment 3: Since you include those 50+ you cannot also call this population 'Elderly migrant'. Please be consistent and conscientious about the terminology used. 50s are really mid-life in current time with increased life expectancy. This influences the search strategy as well. There is a conflation of terminology and age inclusion which must be corrected. Someone who arrives in the early 50s may have very different eligibility criteria for benefits, for example, if they come to work. RESPONSE: Incorporating the reviewer’s suggestion, we have changed “elderly migrants” to “older migrants.” However, from a Western perspective, 50 years might be mid-life, but the sociocultural definitions that consider changes in social roles, family status, and physical characteristics of people could vary. For example: in many Asian countries retirement age for women who disproportionately bear the burden of caregiving responsibilities is set at 55 which is 5 years earlier than their male counterparts. Secondly, a preliminary search showed setting the cut-off age at 50 years or older would help achieve a decent sample size. Prior studies also suggest 50 and above as the age criteria for later-life migrations because this age represents nearly two-thirds of the average life expectancy and those relocating after 50 are significantly more likely to experience work history disruptions. Thus, this age range allows us to focus on a group of immigrants that represent a sizable proportion of the average life expectancy and have unique motivations and experiences, providing valuable insights into the late-life immigration process. This explanation has been added under the “types of the population.” COMMENT: 23rd May 2022? Why is the inclusion criteria set for over a year ago? RESPONSE: We have made relevant changes in the text. COMMENT: Age in place; needs further elaboration as there is significant literature about it as policy approach not only driven by personal preference. RESPONSE: We thank the reviewer for the feedback and we have added discussion about the same under the introduction section in the revised draft. Comment \" There have been some studies on the mental health and well-being of older adults otherwise at liberty to migrate\" needs citation support RESPONSE: We have added the citation for the same. Comment: \"a) What are the individual, social, and political contexts in which people decide to migrate later in life? b) What are the associations between later-life migration contexts and mental health and well-being?\" Both are very descriptive, could further critical analytical lens be adopted? RESPONSE: We thank the reviewer for their feedback. It is not feasible for us to change the objectives at this stage due to the progress already made in the study. However, analysing the current objectives through a customized SDOH framework has helped in gaining critical insights into understanding the motivators of migration for older unforced migrants and the factors impinging on their mental health and wellbeing."
}
]
},
{
"id": "226000",
"date": "23 Dec 2023",
"name": "Hong Liu",
"expertise": [
"Reviewer Expertise Work of Care",
"Social Policy",
"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 the protocol.\nThe systematic review protocol aims to explore the effects of migration on the mental health of older adults. It seeks to collate and analyze existing studies on the relationship between later-life migration and the social determinants of mental health and well-being. The protocol is well-organized and thorough, addressing a significant topic in migration and mental health research. Nonetheless, some improvements, particularly in terms of terminology and criteria justification, could enhance the protocol's clarity and effectiveness.\nHere are several points and recommendations for the authors:\n1. Definition of Migrant Types: The protocol would benefit from a more precise definition of 'migrant' for this study. Various migrant categories exist (e.g., labor migrants, family reunification migrants), and detailing which are included or excluded would improve research clarity.\n2. Age Range Justification: The choice of 50 years as the age threshold is logical, considering the study's global perspective. However, an explanation would aid international readers in understanding this decision. For instance, in some regions like China, the typical retirement age for women is 50 years, making them 'elders' in that context. Thus, acknowledging aging as a social construction and providing such clarifications is crucial.\n3. Rationale for Length of Stay Criterion: The decision to include migrants with a stay of ≤5 years needs more explanation. The protocol should discuss how this criterion aligns with the research questions, particularly in examining the social determinants of mental health and well-being in older migrants.\n4. Handling of Quantitative Data: The protocol contains inconsistent statements regarding quantitative data treatment. Initially, it mentions analyzing and summarizing both qualitative and quantitative studies (Objectives section, page 3). Yet, later, it suggests that quantitative data will not be synthesized numerically (Risk of Bias and Quality Assessment section, page 6). This contradiction could confuse readers about the role of quantitative data in the review. The protocol should clarify if quantitative data will be used descriptively or synthesized in some form, and how it will be integrated into the thematic synthesis.\n5. Additional Considerations:\nPolicy and Practice Implications: The protocol should elaborate on how the findings might inform specific policy changes or practical interventions to enhance the mental health of older migrants. Interdisciplinary Approach: Incorporating insights from disciplines such as sociology, anthropology, and gerontology could enrich the analysis, offering a more comprehensive understanding of the topic.\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? Not applicable",
"responses": [
{
"c_id": "11086",
"date": "13 Apr 2024",
"name": "Pankhuri Bhatia",
"role": "Author Response",
"response": "We are thankful to the reviewer for the thorough review of the protocol and for providing us with valuable feedback. Their suggestions significantly enhanced the quality of the study. All the reviewers' suggestions have been incorporated in the revised version and point-by-point responses to their comments have been provided below. We are pleased to inform you that the review has been accepted for publication - https://doi.org/10.1093/geront/gnae003 Comment: 1. Definition of Migrant Types: The protocol would benefit from a more precise definition of 'migrant' for this study. Various migrant categories exist (e.g., labor migrants, family reunification migrants), and detailing which are included or excluded would improve research clarity. RESPONSE: We thank the reviewer for their feedback and have provided a clear operational definition of ‘older unforced migrants’ used for the study. Comment2. Age Range Justification: The choice of 50 years as the age threshold is logical, considering the study's global perspective. However, an explanation would aid international readers in understanding this decision. For instance, in some regions like China, the typical retirement age for women is 50 years, making them 'elders' in that context. Thus, acknowledging aging as a social construction and providing such clarifications is crucial. RESPONSE: We agree with the reviewer’s feedback and their input. We have elaborated on the justification for the set criteria in the “types of population” section. Comment 3. Rationale for Length of Stay Criterion: The decision to include migrants with a stay of ≤5 years needs more explanation. The protocol should discuss how this criterion aligns with the research questions, particularly in examining the social determinants of mental health and well-being in older migrants. RESPONSE: We thank the reviewer for their feedback and have incorporated their suggestion under “types of population” by showing the probable links between the length of stay in the host country and its impact on the mental health and well-being of the migrants. Comment 4. Handling of Quantitative Data: The protocol contains inconsistent statements regarding quantitative data treatment. Initially, it mentions analyzing and summarizing both qualitative and quantitative studies (Objectives section, page 3). Yet, later, it suggests that quantitative data will not be synthesized numerically (Risk of Bias and Quality Assessment section, page 6). This contradiction could confuse readers about the role of quantitative data in the review. The protocol should clarify if quantitative data will be used descriptively or synthesized in some form, and how it will be integrated into the thematic synthesis. RESPONSE: We thank the reviewer for their insight and have incorporated their suggestion by clarifying the same (Risk of Bias and Quality Assessment section, page 6). Comment 5. Additional Considerations: Policy and Practice Implications: The protocol should elaborate on how the findings might inform specific policy changes or practical interventions to enhance the mental health of older migrants. RESPONSE: Incorporating the reviewer’s suggestion, we have added a paragraph on the same in the discussion section."
}
]
}
] | 1
|
https://f1000research.com/articles/12-16
|
https://f1000research.com/articles/12-1245/v1
|
28 Sep 23
|
{
"type": "Research Article",
"title": "The Investment Development Path theory: Evidence from developing countries’ agricultural sector",
"authors": [
"Justice Gameli Djokoto",
"Kofi Aaron A-O Agyei-Henaku",
"Charlotte Badu-Prah",
"Kofi Aaron A-O Agyei-Henaku",
"Charlotte Badu-Prah"
],
"abstract": "Background: We examined the investment development path (IDP) through the perspective of developing countries’ agricultural sector. Our analytical approach indirectly accounts for interactions among countries regarding cross-border resource transfers. Aside from providing knowledge on testing the IDP by inferential statistics, the information would be relevant for policymaking. Identifying the stage(s) in the IDP not only highlights the global appeal of agriculture but also guides firms seeking to expand beyond borders. This information is essential for developing an effective economic strategy. Methods: We employed data from 1991 to 2021 for 55 countries from the Food and Agriculture Organization Corporate Statistical Database (FAOSTAT) and applied a fixed effects estimator corrected for serial correlation and non-constant variances. Results and conclusions: We found that agriculture in developing countries is currently in stages I and II of the IDP. Broadly, agricultural production requires policies that would increase outward foreign direct investment and inward foreign direct investment. Domestic agricultural businesses in developing countries must develop capacity by learning from foreign multinationals. This would enable agricultural businesses to invest abroad. Such a move would lead to an increase in outward FDI. As this would have resulted from increased GDP per capita, it will lead to movement from the existing stage to higher ones.",
"keywords": [
"Agriculture",
"developing countries",
"IDP",
"internalisation advantage",
"inward foreign direct investment",
"investment development path",
"location advantage",
"ownership advantage",
"outward foreign direct investment"
],
"content": "Introduction\n\nThe net outward and direct investment situation of a country methodically correlates with its economic progress (Dunning, 1981a). Stages I, II, III, IV and V have been identified. These reflect the international attractiveness of the economy and firms’ cross-border expansion and give guiding steps for an appropriate economic strategy (Buckley and Castro, 1998; Djokoto and Pomeyie, 2021; Dunning, 1981a,b, 1986; Dunning and Narula, 1996; Gorynia et al., 2019).\n\nAs in the case of the total economy, the IDP could apply to the agriculture sector which continues to be important for many developing countries. The World Bank notes that developing agriculture is an extremely effective instrument to stop severe lack, promote collective wealth and feed an anticipated 9.7 billion persons by the year 2050. Compared to other sectors, the growth of the agricultural sector is two and four times more operative in boosting incomes amongst the most deprived (World Bank, 2022). Thus, developing countries have sought agricultural development through policies to entice foreign direct investment (FDI) into the agricultural sector (Djokoto, 2022; Ju et al., 2022; Tian, 2023; Wardhani and Haryanto, 2020). As a result of knowledge gained from foreign firms, agricultural multinationals (AM) have emerged in some developing countries (Chen and Guo, 2017). The outcome of the FDI policies and the progress of the AMs from developing countries have resulted in both inward and outward FDI into and out of developing countries (Chen and Guo, 2017; Ju et al., 2022; Tian, 2023; Wardhani and Haryanto, 2020). Indeed, from 2008 to 2019, $68.7 billion and $63.75 billion respectively were recorded as inward and outward FDI into agriculture. This is within the global investment need of $5 to $7 trillion per year (United Nations, 2014). How does the interaction between the inward and the outward FDI on one hand and agricultural development on the other explain the level of development in developing countries’ agriculture?\n\nSince the seminal work of John H. Dunning in 1979, many papers about the IDP have been published. Whilst some focused on individual countries (Bellak, 2001; Buckley and Castro 1998; Gorynia et al., 2009; Kosztowniak, 2018; Marton and McCarthy, 2007; Verma and Brennan 2011; Zhubikenov, 2022), others covered a collection of countries (Andreff, 2003; Barry, Görg and McDowell, 2003; Borowicz, 2021; Boudier-Bensebaa, 2008; Dai, 2021; Djokoto, 2021a; Djokoto and Pomeyie, 2021; Dunning & Narula, 1996; Dunning et al., 2001; Durán and Ubeda, 2001, 2005; Fonseca et al., 2016; Gorynia et al., 2010a, 2010b, 2012, 2019; Iacovoiu and Panait, 2014; Kuzel 2017; Ragoussis 2011; Satoglu, 2017; Trąpczyński et al., 2019, 2022; Zhubikenov, 2022). Sawitri and Brennan (2022) and Serafim (2011) published some reviews. These studies have two limitations. First, notwithstanding the origin of the IDP shown in Figure 1, some studies used regression analysis without accounting for other control variables, except Djokoto (2021a). Failure to incorporate relevant control variables raises issues about the robustness and the explanatory power of the model. Second, none of these studies addressed agriculture, a sector that is critical for the survival of mankind.\n\nNote: Not drawn to scale – For illustrative purposes only.\n\nOur study intended to fill these gaps by first, examining the agricultural sector of developing countries. Secondly, we considered other variables that explain net outward FDI other than the gross domestic product (GDP) per capita. Thirdly, we employed econometric estimations to support the trend line based on the scatter plot, which is the origin of the IDP. In our contribution, we found global agricultural production is in the IDP’s stages I and II. Broadly, agricultural production requires policies that would increase both outward and inward FDI. These include strong institutional support for FDI and improving the macroeconomic environment as these drive both inward and outward FDI. Promoting trade in agricultural commodities is essential in this regard.\n\nIn what follows, we review the IDP and present some empirical evidence on it. Next, we outline our empirical strategy and data. In the results and discussion section, we show the results of the selection of the appropriate model based on the information criteria, test for endogeneity and check the robustness of the IDP to estimators, charts, and control variables. The last section contains the conclusions and some policy recommendations.\n\n\nLiterature review\n\nAccording to Kumar and McLoed (1981), the theory of the IDP was propounded by John H. Dunning in 1979. This theory holds that the net outward direct investment situation of an economy is methodically correlated with its economic progress, vis-à-vis other countries. Revisions of the theory are contained in Dunning (1981a, 1986, 1988a, 1993), Narula (1993). Essentially, patterns of the relationship between GDPs per capita (GDPPC) and outward FDI less inward FDI define five idealised stages of development (Figure 1). The FDI pattern is in turn governed by the ownership, location, and internationalisation advantages of the indigenous and foreign firms (Dunning, 1988a, 1993, 1995, 1998).\n\nIn stage I, the place-specific merits of a country are inadequate to entice IFDI (Dunning, 1988a, 1993, 1995, 1998). Those attributable to non-artificial assets are, however, exempted. Limited local markets, unsuitable economic arrangements, or political management strategies are evidence of the lack of place-bound assets. These can reflect insufficient infrastructure and poor capacity of the labour force. The theory notes that in stage I, outward direct investment is less probable (Narula, 1993).\n\nThe continual little outward investment signal of a rise in inward direct investment is symptomatic of stage II (Dunning, 1988a, 1993, 1995, 1998). Foreign firms respond to the import restriction policies adopted in response to happenings in stage I. This is reflected in foreign firms investing in import substitution industries because of either an increase in the economy's size or the citizens' purchasing power. Foreign firms take advantage of the existing level of imperceptible resources including technology, registered marks, and management skills (Narula, 1993). The export sector would respond by increasing exports of largely non-artificial resources and prime products with some level of backward and forward linkage into labour-exhaustive little technical knowledge (Narula, 1993). By implication, a country should have some looked-for place features to entice IFDI, contingent on its development strategy, and preference for technical capacity development of local businesses.\n\nIn stage III, IFDI decelerates whilst outward foreign direct investment (OFDI) accelerates moving the negative net OFDI towards zero. Building on the capacity and lessons from stage II, in stage III, the technological capabilities of the country are more and more directed to the production of standardised goods (Narula, 1993). As the rise in incomes that started in stage II continues, citizens would clamour for superior attribute goods, inspired partly by the increasing keenness amid the delivering organisations (Narula, 1993). Dunning and Narula (1996) postulate the following: 1. Relative merits in labour-exhaustive undertakings will decline. 2. Local wages will increase. 3. OFDI will be sought more and more by countries at earlier stages of the IDP. 4. The initial possession recompenses of foreign businesses also start to get worn out, as local businesses obtain the modest merits and vie with them.\n\nIn stage III, firms' ownership merits influenced by control of trademarked assets will be as those of foreign firms in the country. As domestic firms develop capacity, the role of state-engendered ownership merits is probably less important. Stage III is typical of emerging economies (Frenken and Mbuvi, 2017).\n\nAs the OFDI continues to rise from stage III, the level rises to equal to or exceeds that of the IFDI (Dunning, 1988a, 1993, 1995, 1998). This is stage IV. In this stage, domestic firms can now effectively vie for market and resources with foreign-owned firms in the home country and can enter foreign markets as well (Narula, 1993). With increased human capital and technology, capital-intensive production techniques will be employed in the production of contemporary products. In the light of ownership, location and internationalisation paradigm, the location advantages will be built largely on created assets (Dunning, 1988a, 1993, 1995, 1998). In the view of Dunning (1993), the ownership merits will be more of a ‘transaction’ than an ‘asset’. OFDI will continue to grow relative to IFDI in stage IV.\n\nThe last stage, V, is described as a home for developed countries. This stage has some features (Dunning, 1988a, 1993, 1995, 1998). 1. There is a rising tendency for international business dealings to be internalised and become intra-multinationals rather than across borders. 2. No one country has complete domination of produced assets. 3. The multinationals’ ownership merits will depend less on their economy’s non-artificial assets’ endowment but increasingly on their capacity to obtain resources and on the capacity of businesses to form their merits competently and to feat the gains of international joint control. 4. Firms become globalised, and their countries of origin become indistinct. 5. The multinationals link geo-political gulfs and integration as such they no longer function with the interests of their countries of origin. They trade, acquire resources and process these in various countries, taking advantage of created and natural assets based on their lead best interest. 6. The ownership and geographical boundaries of the organisation become unclear as they get involved in a more and more interlocking network of trans-border supportive arrangements. 7. As the place-bound assets of countries increase in similarity, the inward and outward foreign direct investments are likely to match each other. The movements in the IFDI and OFDI would lead to unusable or fluctuating net OFDI. Essentially, the peaks and troughs of net OFDI become transient (Narula, 1993).\n\nIt is obvious from Figure 1 that a rise in GDPPC is connected to a rise in the position of the IDP. To some extent, this supports the common practice of using GDP per capita as an indicator of development (Abd Hakim et al., 2022; Macek, 2014; McNabb, 2018; Minh Ha et al., 2022; Neog and Gaur, 2020; Ranis, 2004; Radulović and Kostić, 2020; Santiago et al., 2020), measured as the human development index (HDI). Recently, Djokoto (2021b) found that the IDP explains human development (HD). Further, using the GDP per capita as an indicator for IDP, Djokoto (2022) showed that GDP per capita is positively related to human development. It is worth noting that although GDP per capita is an ingredient in the construction of the HDI, it is not the only ingredient.\n\nThe empirical literature is summarised in Table 1. Since the seminal paper of Dunning, the earliest empirical work was published in 1996 and the latest in 2022. The scope of the studies included single countries, regions, and development groups. The data structure varied from time series through cross-sectional to panel. Charts have been the main analytical tool. Others have been tables and regression analyses. There is evidence of all stages of the IDP. Whilst some empirical evidence confirmed the theoretical stages, others were inconsistent with the theory.\n\nSummary of the IDP literature.\n\nOne of our previous research projects studied the IDP of Small States and segregated Small States into both developed and developing countries (Djokoto, 2021a). The exchange rate influenced the net outward foreign direct investment per capita (NOFDIPC) for the developing, the developed and the combined sample. Inflation significantly influenced NOFDIPC for developing and developed Small States. Whilst the effect of the latter was negative, that of the former was positive. In the combined sample, the effect of inflation was neutral. Regarding human capital, the effect was significant for developing Small States and the combined sample but not for developed Small States. In the case of trade openness, the coefficient was negative and statistically significant for developed Small States but negative and statistically insignificant for developing Small States and the combined sample.\n\nIt can be observed from Table 1 that no IDP study focused on agriculture. Their assessments avoided higher-level statistical analysis. Our study goes beyond the diagrammatic illustration of the IDP to include econometric analysis with control variables. Our data covers developing countries’ agriculture.\n\n\nData, Models and Modelling\n\nThe quantitative research approach is employed by relying on secondary data. This has a cross-sectional dimension (countries) and a time dimension (years). Hence, panel data was used. The data were obtained from public sources.\n\nBefore the statistical analysis, we created charts of the IDP for agriculture. This involved a scatterplot of NOFDIPC on the vertical axis and GDPPC on the horizontal axis and fitted with a polynomial trend line. Although the origins of the IDP lie in the chart depiction of the nexus between NOFDIPC and GDPPC (Figure 1) (Dunning and Narula, 1996), statistical assessments tend to provide a more rigorous outcome (Dai, 2021; Djokoto, 2021a; Djokoto and Pomeyie, 2021; Fonseca et al., 2016; Satoglu, 2017).\n\nThe theory of IDP supposes the relationship between NOFDI and GDPPC (Boudier Bensebaa, 2008; Djokoto and Pomeyie, 2021; Dunning, 1981a, 1986; Durán and Ubeda, 2001, 2005; Frenken and Mbuvi, 2017; Gorynia et al., 2012, 2019; Iacovoiu and Panait, 2014), we specify model 1,\n\nNOFDIPC is the stock of OFDI less than the stock of IFDI divided by the total population (male and female) of a country for the corresponding year. The data on OFDI and IFDI for agriculture was reported as flows and not stocks. Consequently, the first observation for every country was considered the initial flow. The subsequent flows were added consecutively to build the stock. GDPPC is nominal GDP divided by the total population. We follow Dunning (1981a, 1986, 1988a, 1993) in this regard.\n\nHowever, other factors could explain NOFDIPC other than GDPPC (Andreff, 2003; Djokoto, 2021a; Durán and Ubeda, 2001, 2005; Frenken and Mbuvi, 2017). These can be discussed from two perspectives: the host country and the home country (Paul, 2014). We focus on the home country determinants based on the data employed. In a review of IDP studies, Sawitri and Brennan (2022) identified factors including international trade, exchange rate, human capital and inflation as other determinants of OFDI.\n\nHence,\n\nWhere the other variables are controls, namely trade openness (AGTO), the exchange rate (EXRATE), human capital (HC) and inflation (INFLA). AGTO is defined as the sum of exports and imports to the ratio of the gross domestic product for the agricultural sector. Both inward and outward FDI engenders trade. Accessing new markets by multinationals (MNEs) could start with exports of finished products to the to-be host country. Whilst in the host country, the AM could export intermediate finish products to the home country as well as other countries. Where resources are the attraction for the AM, trade could involve imports from the to-be host country. Thus, trade influences both outward FDI and inward FDI (Buckley et al., 2007; Djokoto, 2021a; Frenken and Mbuvi, 2017; Tolentino, 2008). EXRATE is the official exchange rate captured as the annual average of the local currency per US dollar. The increase in the value of the local currency will cause a decline in local currency resources to invest abroad (Buckley et al. 2007; Paul, 2014) which enhances the level of outward FDI. Also, the increase in value of the local currency, makes products and services more expensive. This decreases the attractiveness of exports relative to FDI; hence, positively influences FDI going out. Thus, the effect of the local currency’s value may harm FDI going out (Bhasin and Jain 2013; Djokoto, 2021a, Paul, 2014).\n\nHC was captured as the secondary school enrolment as a percentage of gross enrolment following Djokoto (2022). A skilled labour force is an ownership advantage that firms must possess to engage in outward FDI and to support inward FDI. Thus, human capital influences both outward and inward FDI (Djokoto, 2021a; Stoian, 2013; Tolentino, 2008).\n\nINFLA was defined as the annual growth rate of the consumer price index following Djokoto (2023), Amal and Tomio 2012; Djokoto, 2021a; Paul, 2014 and World Bank (2023a). In the presence of low macroeconomic stability, businesses will probably seek stable economic environments outside the home country. Proxying economic stability by inflation, a less volatile or more volatile inflation rate points to a positive business environment, that encourages a firm's outward relocation (Amal and Tomio 2012; Djokoto, 2021a; Paul, 2014). We specified equation 2, thus:\n\nEquation 3 was estimated for the appropriate powers of the GDPPC that were established econometrically.\n\nThe data consists of a panel of 55 developing countries in Table 2 from 1991 to 2021. The data include a total of 885 observations. Data to construct NOFDIPC and GDPPC were obtained from the Food and Agriculture Organization Corporate Statistical Database (FAOSTAT) (2023a, b) whilst data for EXRATE, HC and INFLA were obtained from the World Development Index of the World Bank (2023a, b). The countries included in the data were based on the availability of data from the sources. Further, to ensure consistency, all data was extracted from the United Nations data system.\n\nList of developing countries in the data.\n\nFirst, we established the polynomial order of the GDPPC using the information criteria (Akaike, 1974; Schwarz, 1978). Second, we expressly tested for the existence of endogeneity between our key variables, NOFDIPC and GDPPC. Thirdly, we estimated equation 3 using panel fixed effects (FE) and random effects (RE) estimators, selected the appropriate specification based on the Hausman test (Hausman, 1978) and tested for violations of the classical regression; serial correlation (Wooldridge, 2002) and heteroscedasticity using the modified Wald test for heteroskedasticity (Greene, 2000). The third step was applied to each model during the robustness check of the estimates of the GDPPC, GDPPC2 and GDPPC3 to the control variables.\n\n\nResults and discussions\n\nThe minimum NOFDIPC is -180.1437 (Uruguay, 2008) with a maximum of 32.5600 (Malaysia, 2011) (Table 3). The mean of -4.4210 is close to that of Mozambique in 2008. Based on the standard deviation of 17.2928, the variance is more than the mean suggesting overdispersion of the data. Similar overdispersion can be observed with GDPPC2. Except for GDPPC and HC for which the standard deviation is less than the respective means, for all other control variables, the standard deviation exceeds the mean.\n\nDescriptive statistics.\n\nAs the observation in Figure 2 is based on the scatter plot of NOFDIPC and GDPPC, it may well be that incorporating other control variables could change this. Thus, we estimated models 1 – 3 to test this. The AIC and BIC for model 3 are the lowest (Table 4). This suggests that model 3, with the cubic functional form, a polynomial of order 4 is appropriate for the curve based on the estimations. This conforms to the cubic curve shown as the trend line in Figure 2. This is in line with our specification of equation 3 to be modelled.\n\n*** p<0.01.\n\n** p<0.05.\n\n* p<0.1. 3.\n\nIn an earlier study with other colleagues, we found that agricultural FDI explained agricultural GDP (Djokoto et al., 2022). Other studies made similar findings ((Djokoto, 2013; Gunasekera et al., 2015) whilst the reverse is also true (Djokoto, 2012; Kassem and Awad, 2019; Lv et al., 2010), hence there can be an endogeneity problem. Rather than anticipate and model accordingly, we proceeded to test for endogeneity (Table 5). First, we modelled GDPPC as the dependent variable with all others as exogenous variables. We predicted the errors GDPPC_ue and did the same for GDPPC 2 and obtained GDPPC2_ue as well as GDPPC3 and obtained GDPPC3_ue. In Model 7, the predicted terms were introduced as additional explanatory variables. We then tested the significance of the GDPPC_ue, GDPPC2_ue and GDPPC2_ue with a chi-square test. Failing to reject the null hypothesis suggests that the error terms are not correlated with the NOFDIPC, hence the suspicion of endogeneity is not borne out by the data. Following the absence of endogeneity, equation 3 was estimated with FE and RE estimators. The Hausman test showed that the hull hypothesis that the differences between the matched coefficients are not systematic could not be rejected. Consequently, the RE estimation was preferred to fixed effects. The errors were found to be serially correlated and non-constant (heteroscedastic). We addressed this with robust standard errors. The serial correlation was resolved by introducing a first lag of NOFDIPC, d.NOFDIPC as appropriate.\n\n*** p<0.01.\n\n** p<0.05.\n\n* p<0.1. 3.\n\nThe estimates of GDPPC, GDPPC2 and GDPPC3 in 8 are consistent with those of models 9 – 13 (Table 6). The estimates of AGTO, EXRATE, HC and INFLA are also consistent across models 9 – 12 and model 13.\n\n* p<0.10.\n\n** p<0.05.\n\n*** p<0.01.\n\nWe focus on model 13 for discussions. The negative and statistically significant coefficient of GDDPC confirms the curve declines initially as in Figure 2. The statistically insignificant coefficients of GDPPC2 and GDPPC3 suggest points of inflexion. The positive and negative signs respectively show the rise and fall before and after the points of inflexion. The estimates correctly depict Figure 2 notwithstanding the introduction of the control variables. It is informative to note that notwithstanding the cubic function in Figure 2, confirmed by the model selection in Table 2 and estimates in Table 5, the curve remains below the GDPPC axis. Indeed, the curve does not show any significant rise after its first decline. Juxtaposing Figure 2 and Figure 1, developing agriculture is in stages I and II of the IDP. The stage I and II found is in line with the theory of the IDP proposed by Dunning (1981a, 1986, 1988a, 1993) and Narula (1993). This is consistent with the finding for the total economy studies for developing countries (Andreff, 2003; Satoglu, 2017) and other regions (Boudier-Bensebaa, 2008; Borowicz, 2021; Dai, 2021; Gorynia et al., 2009, 2010a,b, 2012; Zhubikenov, 2022). However, total economy studies of other regions found IDP stages other than I and II (Djokoto, 2021a; Iacovoiu and Panait, 2014; Kuzel, 2017; Trąpczyński et al., 2019).\n\nThe statistical significance of the GDPPC is in line with the evidence that the size of the economy determines FDI in agriculture (Djokoto, 2012; Djokoto, 2021c; Husmann and Kubik, 2019; Rashid and Razak, 2017). It also confirms the outcome of early studies of Dunning (1981a, 1986, 1988a, 1993) and Narula (1993). The statistical significance of the GDPPC also confirms the existence of the IDP. This should be viewed within the framework of the evidence that GDPPC, IDP and HD are positively correlated (Djokoto, 2021a,b,c, 2022; Djokoto and Pomeyie, 2021).\n\nThe continual low or negligible OFDI and rise in IFDI are observable. The outcome means that the location-specific advantages of developing countries are inadequate to attract IFDI. These can be attributable to inadequate infrastructure and poor capacity of the labour force. Foreign firms may be interested in investing in import substitution industries because of either an increase in the economy's size or the citizens' purchasing power. The weakness of the developing countries encourages foreign firms to take advantage of the existing level of imperceptible resources including know-how, registered marks, and managerial expertise. Foreign firms may also invest in export sectors increasing exports of largely non-artificial resources and prime commodities with some level of backward and forward linkage integration into labour- exhaustive low know-how.\n\nThe positive and statistically significant coefficient of AGTO implies that trade enhances NOFDI. Aside from accessing new markets with new products at the start of internationalisation, home, and foreign affiliates engage in the trade of raw materials and finished and semi-finished products. Where divestments occur, the markets could be filled with products from foreign affiliates of the home country. In all these, the constituents of trade openness, imports and exports take place, hence, this is a positive sign. Djokoto (2021a) found a negative sign of the estimates of trade that were statistically insignificant for both developing and the combined Small States except for developed Small States. Djokoto (2021a) did not provide reasons for the results on the trade variable.\n\nThe negative sign of the coefficient of EXRATE is consistent with that of Djokoto (2021a), there is a departure regarding the statistical significance. The coefficient of INFLA is also negative but statistically insignificant. Our finding is contrary to that of Djokoto (2021a) who found positive and statistically significant coefficients for developing Small States as well as the combined sample, but negative and statistically significant coefficients for developed Small States. As in the case of the other control variables, Djokoto (2021a) did not provide reasons for the significant coefficients.\n\nRegarding the control variables, in summary, agricultural trade openness enhances agricultural net foreign direct investment whilst the exchange rate has the opposite effect. Inflation does not affect agricultural net foreign direct investment.\n\n\nConclusions and recommendations\n\nWe employed data from 1991 to 2021 for 55 developing countries to empirically investigate the IDP for agriculture in developing countries. Our analytical approach indirectly accounts for interactions among countries regarding cross-border resource transfers. Aside from providing knowledge on testing the IDP by inferential statistics, the information would be relevant for policy. Further, the stage of the IDP reflects the cross-border attractiveness of agriculture and tortuously of agricultural businesses going abroad from the agricultural sector and gives guideposts for apt economic strategy.\n\nWe found agricultural production in developing countries in IDP’s stages I and II. Broadly, agricultural production requires policies that would increase both OFDI and IFDI. Agricultural multinationals in developing countries must develop capacity by learning from foreign multinationals. This would enable them to go abroad. Such a move would lead to an increase in OFDI. As this would have resulted from increased GDP per capita, it will lead to movement from the existing stage to higher ones. At the macroeconomic level, the government must support the building of strong institutions for FDI and improving the macroeconomic environment as these drive both OFDI and IFDI. Promoting trade in agricultural commodities is essential in this regard.\n\nOur study is limited to developing countries. Further studies can also explore the role of the IDP in transition and or developed countries.",
"appendix": "Data availability\n\nData for foreign direct investment and gross domestic product for agriculture were obtained from the Food and Agricultural Organisation of the United Nations dataset for various countries. These are available from the FAOSTAT (https://www.fao.org/faostat/en/#data/FDI). At the link select developing countries from the ‘COUNTRIES’ pane. Next, select Value US$ from the ‘ELEMENTS’ pane. In the ‘ITEMS’ pane, select FDI inflows to Agriculture, Forestry and Fishing and FDI inflows to Agriculture, Forestry and Fishing. In the ‘YEARS’ pane, select 1991 to 2021. Regarding agricultural GDP, at https://www.fao.org/faostat/en/#data/MK, follow the same steps for ‘COUNTRIES’ and ‘YEARS’. For the other panes, select Value US$ and Value added (Agriculture, Forestry and Fishing) for ‘ELEMENTS’ and ‘YEARS’ respectively. Regarding the other data, these are obtainable at the Databank of the World Bank (https://databank.worldbank.org/source/world-development-indicators). At the country tab at the link, select developing countries. Select the Official exchange rate (LCU per US$, period average), Inflation, consumer prices (annual %) and School enrolment, secondary (% gross) at the series tab. Finally, at the Time tab, select 1991, 1992, 1993 …. 2021. At the top right of the page click ‘download’. Please note that the FAOSTAT and the World Bank databases are publicly available.\n\n\nReferences\n\nAbd Hakim T, Karia AA, David J, et al.: Impact of direct and indirect taxes on economic development: A comparison between developed and developing countries. Cogent Economics & Finance. 2022; 10(1): 2141423. Publisher Full Text\n\nAkaike H: A new look at the statistical model identification. IEEE Trans. Autom. Control. 1974; 19(6): 716–723. Publisher Full Text\n\nAmal M, Tomio BT: Determinants of Brazilian Outward Foreign Direct Investment (OFDI): A Host Country Perspective. 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}
|
[
{
"id": "243485",
"date": "20 Feb 2024",
"name": "Jorge Fleta-Asín",
"expertise": [
"Reviewer Expertise Foreign Direct Investment",
"Public-Private Partnerships",
"Gender"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 document titled \"Impact of Agricultural Trade Openness on the Investment Development Path for Agriculture in Developing Countries\" explores the relationship between agricultural trade openness and the Investment Development Path (IDP) for agriculture in developing countries. The authors use data from 1991 to 2021 for 55 developing countries to empirically investigate the IDP, which indirectly considers interactions among countries regarding cross-border resource transfers. Through inferential statistics, the study aims to provide insights relevant for policymaking and economic strategy in the agricultural sector. The authors employ an analytical approach, incorporating random effects estimates and robustness checks with control variables to ascertain the impact of agricultural trade openness on agricultural net foreign direct investment (NOFDIPC). Their findings suggest that agricultural trade openness enhances NOFDIPC, while variables such as the exchange rate and GDP per capita exhibit opposite effects. Additionally, the study provides insights into the stages of the IDP, indicating that agricultural production in developing countries aligns with stages I and II of the IDP. Policy recommendations include fostering policies to increase both outward and inward foreign direct investment (OFDI and IFDI), developing institutional capacity for FDI, and promoting trade in agricultural commodities. We appreciate having been the reviewers of this article. We found the article interesting, it is well written, we have also learned and we believe there is room for improvement.\nBelow are a series of comments to improve the work:\n1. In the introduction it is said that there are works that analyze the IDP in a country (its path) or groups of countries, but they are not rigorous (they do not control for other variables) and do not focus on agriculture. This is not totally true because there are works where the PDI per se is analyzed or it is used with many control variables (in fact more and different than those used by the authors). An example here: Ref [1].\nFurthermore, I had not read that the IDP could explain isolated sectors, and I do not know to what extent it is a weakness of the work that we do not know if those countries with all the sectors would obtain the same results again (being in Stages I and II). We would have to be more cautious in the introduction, finding the gap.\n2. The IDP figure should indicate whether it is from the authors, they have taken it from another article, or it is based on “X” article.\n3. Regarding the methodology. While the authors employ rigorous statistical methods, enhancing transparency in the methodology section by providing more detailed explanations of the analytical approach, model specifications, and data sources would improve the reproducibility and credibility of the study. For example:\n- The NOFDIPC variable must be better justified. Why is it divided by the population? Why aren't logarithms applied?\n- Why are the control variables chosen and not others? And how do each of them influence each other specifically? Only a few are mentioned.\n- Doesn't the fact of introducing 3 variables that are combinations interacting with each other generate multicollinearity? The correlation table should appear, justifying its impact on the model (VIF), as well as considering the possibility of centering the interactions with respect to the means.\n- How are developing countries selected? Explain the criterion, because this can change and there are countries that over a period, if it is GDP/capita, can change their status. You should set the criteria and source. Are all the countries “developing” in such a long period of time according to one standard source?\n- Can you explain us how ((2021-1991)+1)* 55) countries makes you have around 800 observations?\n- The R2 of the models is very low, which may be a sign that many other things are not being considered in those models. Maybe it would be good to explain it and put in limitations.\n- When an investment attraction variable is estimated, its explanatory factors (generally location factors) are usually delayed by at least one period, given that it is understood that what motivates the decision precedes the subsequent result. The models do not mention that they are delayed, it does not appear in the t-1 subscripts, nor is it explained why it is not done. Either it is justified, or it is done, or it is put in limitations.\n- At the end of Table 4 a number 3 appears at the bottom, which we do not know what it is.\n- In the notes of the tables you mention “parenthesis”, should it be “parentheses” once they are two?\n4. About the contribution of the work and discussion/limitations.\nIn the end, the conclusion is that developing countries, specifically in the agriculture sector, are located in stages I and II of development, something that would explain the theory and would not be adding anything new. The authors should “sell” the implications or singularities of the work better.\nWhile the study acknowledges its focus on developing countries, further discussion on the limitations and generalizability of the findings would strengthen the article. Addressing potential confounding variables or factors not accounted for in the analysis could enhance the robustness of the conclusions.\n5. Future Research Directions. Including a section on future research directions could add value to the article by highlighting avenues for further exploration, such as examining the role of specific policy interventions or conducting comparative analyzes across different regions or country groups. Addressing these points would contribute to making the article scientifically sound and enhance its impact on both academic research and policymaking in the agricultural sector.\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": "11136",
"date": "13 Apr 2024",
"name": "Justice Djokoto",
"role": "Author Response",
"response": "Responses to Review by J. Fleta-Asin Comments: Background The document titled \"Impact of Agricultural Trade Openness on the Investment Development Path for Agriculture in Developing Countries\" explores the relationship between agricultural trade openness and the Investment Development Path (IDP) for agriculture in developing countries. The authors use data from 1991 to 2021 for 55 developing countries to empirically investigate the IDP, which indirectly considers interactions among countries regarding cross-border resource transfers. Through inferential statistics, the study aims to provide insights relevant to policymaking and economic strategy in the agricultural sector. The authors employ an analytical approach, incorporating random effects estimates and robustness checks with control variables to ascertain the impact of agricultural trade openness on agricultural net foreign direct investment (NOFDIPC). Their findings suggest that agricultural trade openness enhances NOFDIPC, while variables such as the exchange rate and GDP per capita exhibit opposite effects. Additionally, the study provides insights into the stages of the IDP, indicating that agricultural production in developing countries aligns with stages I and II of the IDP. Policy recommendations include fostering policies to increase both outward and inward foreign direct investment (OFDI and IFDI), developing institutional capacity for FDI, and promoting trade in agricultural commodities. We appreciate having been the reviewers of this article. We found the article interesting, it is well written, we have also learned and we believe there is room for improvement. Response We acknowledge your summary and general impressions of the paper. However, we note that the title of the paper is “The Investment Development Path Theory: Evidence from developing countries’ agricultural sector”. Below are a series of comments to improve the work: Specific Comments 1. In the introduction it is said that there are works that analyze the IDP in a country (its path) or groups of countries, but they are not rigorous (they do not control for other variables) and do not focus on agriculture. This is not totally true because there are works where the PDI per se is analyzed or it is used with many control variables (in fact more and different than those used by the authors). An example here: Ref [1]. Response The reference: Ramirez-Aleson, M., & Fleta-Asin, J. (2016). Is the importance of location factors different depending on the degree of development of the country? Journal of International Management, 22(1), 29-43, addressed the location factors of FDI. The dependent variable is FDI and not NOFDIPC as in our paper. Although the countries analysed were claimed by Ramirez-Aleson and Fleta-Asin to be based on the IDP, this was not the case. The authors used GDP per capita only to categorise countries into stages of development. This is at variance with the IDP methodology developed by JH Dunning, which employed the interaction of the net FDI (outward FDI – inward FDI) and GDP per capita. Therefore, Ramirez-Aleson and Fleta-Asin (2016) is not an IDP study in the true sense of the IDP methodology. Although many control variables were used, that is irrelevant to the study under review. Therefore, our failure to acknowledge Ramirez-Aleson and Fleta-Asin (2016) is in place. Hence, the assertions of the authors of the study under review, are ‘totally’ true. Comment Furthermore, I had not read that the IDP could explain isolated sectors, and I do not know to what extent it is a weakness of the work that we do not know if those countries with all the sectors would obtain the same results again (being in Stages I and II). We would have to be more cautious in the introduction, finding the gap. Response The application of IDP to sectors has been in the literature since 2009. See Gorynia, M., Nowak, J., & Wolniak, R. (2009). Poland's Investment Development Path: in search of a synthesis. International Journal of Economic Policy in Emerging Economies, 2(2), 153-174. See especially Figure 3, where the IDP chart of various sectors including manufacturing have been captured using charts and not rigorous econometric analysis. Moreover, as the IDP is dependent on the interaction of the net FDI and the GDP per capita, which can be different for industries in the same country and can differ between sectors and the total economy, differences in IDP between the sector and the total economy are plausible. We are thankful for this comment as it suggests readers could have the same concern. Thus, we have updated the second paragraph of the introduction to address this matter. Comment 2. The IDP figure should indicate whether it is from the authors, they have taken it from another article, or it is based on “X” article. Response The IDP figure is like others in some respects, but it is different from all others in its entirety. All figures are from the authors; thus, no specific acknowledgements were made. Comments 3. Regarding the methodology. While the authors employ rigorous statistical methods, enhancing transparency in the methodology section by providing more detailed explanations of the analytical approach, model specifications, and data sources would improve the reproducibility and credibility of the study. For example: Response Model specification is present, see for example equation 3. The data sources are outlined after equation 3. Additional information is provided to further enhance the paper. Comment - The NOFDIPC variable must be better justified. Why is it divided by the population? Why aren't logarithms applied? Response We have now explained that in the manuscript. We avoided logarithms as it would clear the nonlinearity that we seek to measure. Comment - Why are the control variables chosen and not others? And how do each of them influence each other specifically? Only a few are mentioned. Response We followed the literature in doing that (Andreff, 2003; Djokoto, 2021a; Durán and Ubeda, 2001, 2005; Frenken and Mbuvi, 2017). We focused less on the control variables are they are not the key variables. Comment - Doesn't the fact of introducing 3 variables that are combinations interacting with each other generate multicollinearity? The correlation table should appear, justifying its impact on the model (VIF), as well as considering the possibility of centering the interactions with respect to the means. Response We noted the VIF during our analysis. An important consequence of multicollinearity is the inflation of the standard errors leading to the invalidation of the hypothesis tests. Our hypothesis tests are not appreciably invalidated, moreover, the estimates are robust and consistent with theory, thus, we discounted the role of multicollinearity. Comments - How are developing countries selected? Explain the criterion, because this can change and there are countries that over a period, if it is GDP/capita, can change their status. You should set the criteria and source. Are all the countries “developing” in such a long period of time according to one standard source? Response The developing countries were chosen based on the United Nations classification in the statistical annexe of World Economic Situation and Prospects 2022 (https://www.un.org/development/desa/dpad/wp-content/uploads/sites/45/WESP2022_ANNEX.pdf). The classification has not changed throughout the study. This classification is not based on only GDP per capita, as in Ramirez-Aleson and Fleta-Asin (2016), but on other economic properties. All countries are developing according to the source, from 1991 to 2021. Comment - Can you explain us how ((2021-1991)+1)* 55) countries makes you have around 800 observations? Response Not every country had data over the period, hence we used an unbalanced panel. This is common with FDI data, especially, the outward FDI. Further, the lags resulted in some data attrition leading to differences in the number of observations listed in the model diagnostics section of some tables. Comment - The R2 of the models is very low, which may be a sign that many other things are not being considered in those models. Maybe it would be good to explain it and put in limitations. Comment In the econometric literature, low R2 are a concern if the model will be used for forecasting. However, as we used the model for hypothesis testing of the coefficients, the low R2 is not a limitation of the model. Comment - When an investment attraction variable is estimated, its explanatory factors (generally location factors) are usually delayed by at least one period, given that it is understood that what motivates the decision precedes the subsequent result. The models do not mention that they are delayed, it does not appear in the t-1 subscripts, nor is it explained why it is not done. Either it is justified, or it is done, or it is put in limitations. Response In IDP studies, the lag is not necessarily the case. Where GMM is used this takes account of the lags. Hence, we avoided the lags. Comment - At the end of Table 4 a number 3 appears at the bottom, which we do not know what it is. Response The ‘3’ was left after the footnote was edited. This is now deleted. Comment - In the notes of the tables you mention “parenthesis”, should it be “parentheses” once they are two? Responses Noted and correction is done. Comment 4. About the contribution of the work and discussion/limitations. In the end, the conclusion is that developing countries, specifically in the agriculture sector, are located in stages I and II of development, something that would explain the theory and would not be adding anything new. The authors should “sell” the implications or singularities of the work better. Response The primary goal of any IDP paper is to establish the stage of development based on the theory. That is our primary objective as well. After stating that, we noted the policy recommendations, as required in an applied economics paper. Comments While the study acknowledges its focus on developing countries, further discussion on the limitations and generalizability of the findings would strengthen the article. Addressing potential confounding variables or factors not accounted for in the analysis could enhance the robustness of the conclusions. Response We employed variables that have been used in IDP studies. Indeed, some did not use these at all. We have added a sentence (long one though) to account for this in the last paragraph of the paper. Comment 5. Future Research Directions. Including a section on future research directions could add value to the article by highlighting avenues for further exploration, such as examining the role of specific policy interventions or conducting comparative analyzes across different regions or country groups. Addressing these points would contribute to making the article scientifically sound and enhance its impact on both academic research and policymaking in the agricultural sector. Response Perhaps, as it was not designated as a section, you missed the content. The last paragraph of the paper presented the limitations and recommendations for further research. An additional sentence is now added to the paragraph to account for the need for generalisation and the findings to other sectors."
}
]
},
{
"id": "221936",
"date": "31 May 2024",
"name": "Emine Beyza Satoglu",
"expertise": [
"Reviewer Expertise FDI theories",
"global knowledge networks"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a well-written, well-organized paper and the empirical application is strong. The article focuses on the developing countries and argues the importance of foreign investment into the agriculture sector to further improve in the stages of IDP.\n\nDespite the fact that the paper properly applied IDP theory and provided a rich theoretical and empirical literature, in my opinion, the research question is not thought-provoking or original enough. I believe adding a deeper discussion on the nature of agricultural investment and its impact for the developing countries might improve the originality of the paper.\n\nSecondly, discussion/limitation part is very limited. IDP theory has its own flaws addressed by the literature (such as Dunning and Narula, 1996; Dunning, 2000;Duran and Ubeda, 2001). The authors should address these limitations (and more) and suggest some new directions to develop the research on FDI positions for agricultural sectors in developing countries.\n\nOn the other hand, I believe the paper is well-written, supported by its empirical basis and overall structure.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-1245
|
https://f1000research.com/articles/12-1510/v2
|
08 Mar 24
|
{
"type": "Study Protocol",
"title": "Comparative evaluation of marginal fit, internal fit and cement space of single unit lithium disilicate crown with shoulder finish line by two different methods of fabrication",
"authors": [
"Madhavi Selukar",
"Surekha Godbole Dubey.",
"Seema Sathe Kambla",
"Madhavi Selukar"
],
"abstract": "Background The coming era will be governed by technology. Computer aided designing (CAD) & computer aided manufacturing (CAM) dentistry is taking over the conventional dental practice establishing a benchmark in esthetics, quality and fit of the prosthesis. The fabrication of prosthesis by digital methods reduces the efforts in fabrication and time required for designing the prosthesis.\n\nAim This protocol aims at checking the marginal fit, internal fit and cement space of lithium disilicate crowns by comparing the two different methods of fabrication. To evaluate and compare marginal fit, internal fit and cement space of single unit “lithium disilicate crown” with shoulder finish line with two different methods of fabrication.\n\nMethods The current study is the experimental study conducted at Sharad Pawar dental college and Hospital. The protocol has been approved by the Ethical institutional committee with ref.no.DMIHER(DU)/IEC/2023/851. All the 54 participants who will visit the O.P.D of department of prosthodontics crown & bridge will be included in the study which will be conducted over a period of two years, the subjects will be informed about the research and written consent will be taken. The inclusion criteria for this study are patients aged 18-54 years in the need of full veneer maxillary incisors crown prosthesis. All the comparative results will be calculated with the help of stereomicroscope and descriptive statistics will be performed.\n\nExpected results The expected outcome or result proposed will be, the crown fabricated with CAD-CAM will give good fit compared to pressed method.\n\nConclusions Finding the accuracy in the fit and cement space of lithium disilicate crowns by conventional and digital method of fabrication will help the prosthodontist to deliver good results.",
"keywords": [
"Lithium disilicate",
"marginal fit",
"internal fit",
"cement space",
"fabrication method."
],
"content": "Introduction\n\nThe conventional crown fabrication method is a time-consuming and technique sensitive method, that requires meticulous fixation of the negative replica of the tooth by a stable means of registration, to minimize errors in manufacturing process of dental crowns. The transportation of impressions to the dental laboratory is governed by factors such as ambient temperature, transit time, distance from the laboratory, etc. These factors can affect impression accuracy.1 The time required to pour the cast, the physical properties of gypsum product also affect the impression quality causing minor distortions in the impression. The use of die hardener, die spacer and the entire casting process may be accompanied with some amount of error creating marginal discrepancy or any kind of discrepancy in dental prosthesis that may lead to periodontal problems and endodontic problems.\n\nComputer aided designing (CAD) & computer aided manufacturing (CAM) are currently growing and widely establishing technology. In the current scenario increased interest of dental surgeon and engineers in technology and artificial intelligence is taking over and developing a techno-societal approach towards dental problems. Both CAD and CAM are increasingly used in dental laboratory for fabrication of crown and bridge prosthesis. The use of this technology has reduced the efforts and time in fabrication of the prosthesis, making the treatment affordable both in terms of time & money compared to conventional methods.\n\nThe indirect restorations have long term success rate depending on “internal” and “marginal fit”. The poor fit will result in marginal dissolution, leading to secondary caries and failure of the prosthesis.2 Holmes et al. in his study, quoted marginal gap as perpendicular measurement from cervical margin of casting to preparation margin. He further defined absolute marginal discrepancy as angular combination of marginal gap & extension error (over and under extension).2 If the cement is exposed to saliva, it can be dissolved leading to weakened prosthesis, improper marginal gap on the other side.2 Marginal discrepancy will indicate marginal crown extension in relation to abutment margin and is of importance in overextension or under extension cases.\n\nThe “lithium disilicate crowns” are also widely used in dental practice in the current scenario. It is a glass ceramic material that is gaining popularity. This material is commonly used in dental laboratories according to pressing technology or manufacturing crowns. It has high fracture toughness, flexural strength and is very aesthetic. It is commonly known as “IPS e.max. Lithium disilicate (IPS e.max)” requires minimal invasive preparation that justifies the statement of Sir DeVan that “Perpetual preservation of what remains is more important than the meticulous replacement of what is missing.”\n\nIn this study we will be focusing on the properties of marginal fit, internal fit and cement space of lithium disilicate (IPS e.max) crowns fabricated by conventional and digital method respectively. The null hypothesis will state there is no difference in the internal fit, marginal fit and cement space of lithium disilicate crowns in the methods of fabrication.1\n\nThe replica technique is reliable, non-invasive and is a valid technique for calculating marginal fit and internal fit of crowns by an in vivo method. But, the disadvantage with this is that it is technique sensitive and there are chances of distortion of the replica impression.3\n\nRationale: The purpose of this study is to determine the “marginal fit”, “internal fit” and “cement space” of lithium disilicate crowns as these are important parameters for determining fit by two different methods of fabrication.\n\nAim: To evaluate and compare the “marginal fit”, “internal fit” and “cement space” of single unit lithium disilicate crown with shoulder finish line with two different methods of fabrication.\n\nObjective: To evaluate and compare,\n\n• Marginal fit of lithium disilicate (IPS e.max) crowns using different fabrication method.\n\n• Internal fit of lithium disilicate (IPS e.max) crowns using different fabrication method.\n\n• Cement space of single unit monolithic lithium disilicate (IPS e.max) crowns using different fabrication method.\n\n\nMaterial and method\n\nThe experimental study is being conducted in the department of prosthodontics and crown & bridge, Sharad Pawar Dental College and Hospital Sawangi(M).\n\nA total of 54 patients within the age group of 18-54 years, will be selected from patient coming to out-patient’s department (OPD) of prosthodontics and crown & bridge. The patients will be the residents of vidarbha region Maharashtra The members will be recruited from the outpatient department of prosthodontics and crown and bridge of Sharad Pawar Dental College. The sample population considered will be the residents of Vidarbha region Maharashtra. Further these 54 patients will be divided into two groups of 27 patients in each group randomly group A will consist of the subjects where lithium disilicate crowns are fabricated using CAD and CAM. Group B consisted of subject with whom lithium disilicate crowns will be fabricated using a pressed technique. Figure 1 represents the study design.\n\nTo compare 2 means, using mean and standard deviation.\n\nThe value of α = 0.05\n\nβ = 0.1\n\nThe mean in group 1, μ1 = 100\n\ngroup 2, μ2 = 63\n\nStandard deviation in group 1, σ1 = 54\n\ngroup 2, σ2 = 24\n\nRatio (group 2/group 1) = 1\n\nZ1-α/2 = 1.96\n\nZ1-β = 1.28\n\nAt 90% power\n\nSubstituting the values.\n\nMinimum sample size needed is 27 per group.\n\nTotal number of sample size needed 54.\n\nThe “marginal fit”, “internal fit” and “cement space” of “lithium disilicate crowns” will be calculated with the help of stereomicroscope. There will be 2 groups and 27 patients will be randomly distributed in each group.\n\nThe test used to perform statistical analysis will be unpaired t test.\n\n\n\n• Full veneer maxillary incisors in need of prosthetic restoration.\n\n• Patients in age group of 18-54 years.\n\nThe clinical implication is increased accuracy of the prosthesis.\n\n\n\n• Cantilever cases where a single crown is taken as an abutment to replace a missing tooth.\n\n• Mobile abutments.\n\n• Abutment tooth whose height is less than 4mm.\n\n• Patient allergic to other substances.\n\nArmamentarium\n\nBurs – TF11, SF-11, SF-41, EX11, EX12, WR13, end cutting bur.\n\nElastomeric impression material (light body & heavy body).\n\nAlginate impression material.\n\nEquipped CAD – CAM lab.\n\nEquipped Ceramic lab.\n\nLithium disilicate ingot.\n\nBurs for finishing & polishing ceramic\n\nDie stone.\n\nDental stone.\n\nDental plaster.\n\nStereomicroscope.\n\nTwo groups will be made group A & B. Group A will consist of the lithium disilicate crown fabricated by ano-digital method. Group B will consist of lithium disilicate crowns fabricated by a conventional method. All patients to be examined will be selected from patients coming to out-patient department (OPD) of prosthodontics and crown and bridge.\n\nEvery new patient coming to OPD will be checked for the inclusion and exclusion criteria.\n\nAccording to this criteria, selected patients will be allocated in group A and group B randomly. Informed consent will be taken from patients then only he/she will be included in the sample. Tooth preparation will be planned on the tooth of interest. Before starting preparation, a silicon putty will be adapted to the entire tooth and adjacent tooth on each side & an index of the silicon putty will be taken. A diagnostic wax up will be done if necessary. Incisal reduction will be done by marking depth orientation grooves. A no 171 bur of fine girt round end tapered diamond will be used to smooth the planes of occlusal reduction. Proximal reduction will be done with a diamond bur.\n\nThe lingual axial wall will be reduced with coarse grit tapered torpedo diamond & a shoulder finish line with subgingival margin will be prepared. After the completion of tooth preparation an impression will be taken with elastomeric impression material and a study cast and working cast with a die will be made. There are 2 methods of crown fabrication digital and conventional. The material used for the fabrication of the crown prosthesis is lithium disilicate ingot. Lithium disilicate will be used for crown fabrication with CAD-CAM and lithium disilicate ingot will be used to fabricate the crown by pressed method. The digital method is as follows. The cast will be scanned by the extra oral scanner in the CAD-CAM lab and the scans will be recorded and saved in stl/g-code format. The cast would be then articulated digitally with the help of virtual articulator using software and the designing of the prosthesis would be done. The material used for crown prosthesis is the lithium disilicate ingot, the crown will be fabricated by a subtractive method with 5 axis milling from an industrially fabricated block of lithium disilicate.1 With a few more subsequent steps, of sintering and finishing and polishing crown prosthesis is made using digital method.3\n\nAfter obtaining the cast a pattern will be fabricated. Investing and burn out procedures will be carried out. Ceramic ingots are then heat pressed in the mold cavity in a special ceramic press furnace, cooled and retrieved. Sub structure is obtained by pressing. As our inclusion criteria includes maxillary incisors staining and glazing procedures are made to get aesthetic result. Then the internal fit of the crown fabricated with digital and conventional method will be measured & the 2 groups will be compared.2\n\nFigures 2 & 3 gives a diagramatic representation of over and under extended crowns, marginal gap and internal gap.\n\nThe measurement of the internal fit, marginal fit and cement space will be done with the help of elastomeric impression material (light body and heavy body).4 The prepared crown prosthesis will be loaded with a light body elastomeric impression material and the impression of the prepared tooth will be taken with the processed crown.4 Then silicon putty will be used as a tray to retrieve the impression. Figure 4 is demonstrating the replica technique.\n\nThe impression is divided into 4 different parts mesial, distal, buccal, lingual, occlusal and the thickness of each segment is measured under a stereomicroscope to calculate the marginal fit, internal fit and cement space. Figure 5 determines the marginal and occlusal measuring points.\n\nThe expected outcome or result is that the crown fabricated with CAD-CAM will give good fit and result compared to pressed method. The key parameters of evaluation are marginal fit, internal fit and cement space. The error margin will be in between 0.12 mm to 0.15 mm.\n\nWill be published in indexed journal.\n\nNot yet started.\n\n\nDiscussion\n\nAn in vivo study was conducted by KW Boening et al. (2000) to assess the clinical fit and accuracy of ceramic crowns of anterior & posterior teeth. On evaluating the clinical fit of 80 anterior & posterior teeth, the author calculated the median marginal gap width of anterior and posterior teeth using an identical technique. Based on the computations made with the light microscope for each part, he concluded that anterior teeth had width of median marginal gap between 80 & 95 microns, while posterior teeth had median marginal gap widths between 90 and 145 microns. A median marginal gap width of 80–180 microns and 115–245 microns was observed respectively in anterior & posterior region.4\n\nIn the year 2014 Jonathan et al. studied comparison of marginal fit, internal fit, and cement space of crowns made by digital and conventional methods. The upper second premolar was prepared on a typodont for full ceramic crown. He scanned the typodont with a lab scanner & used a digital file to replicate maxillary arch from a monolithic block of yttria-stabilized zirconia that served as the master cast. He obtained a digital impression of the prepared upper right second premolar in his scanning unit. The scan file was exported & emailed to the dental lab. Digital articulation, digital waxing & final crown design. Fifteen crowns were fabricated by CAD technology designed with lithium disilicate glass-ceramic blocks & fifteen lithium disilicate glass-ceramic crowns were manufactured using laboratory and conventional techniques. The original zirconia die was removed from the zirconia master cast to assess the margins of crown. Circumferential edge gap measurements were taken at eight locations. Vertical component determined the measurements. An entire measure of 240 images (2 groups, 15 crowns per group, 8 sites per group) were done.1\n\nNecla et al. in 2014 assessed marginal gaps & two finish line design shoulder and chamfer of all ceramic crowns with absolute marginal discrepancy, using micro-CT pre and post cementation, they divided 60 extracted maxillary premolar teeth into two groups, and extended grouping was done based on the crowns they received. The results of this study concluded that the all-ceramic system exhibited clinically acceptable margins. The Feldspar-Cerec-Inlab ceramic system showed the least variance, except for MG values in the coronal mesial region. The MG and MD values of all ceramics increased significantly after cementation, except for the MG shoulder-prepared design and the MD chamfer-prepared design. The conclusion of Necla et al. In the studies conducted, all-ceramic crowns had a clinically acceptable marginal fit. The fieldpathic cerac inlab system showed minimal variance compared to other ceramics.5\n\nStefanie Anke Rau et al in 2018 analysed the clinical fit of monolithic zirconia single crowns in a prospective cohort study. A total of 30 molars were restored with monolithic zirconia single crowns. Silicone impressions were made to measure clinical fit using a stereomicroscope. Measurements were taken at 17 points per crown on the marginal and occlusal surfaces. The average clinical fit was 0.104 mm at the coronal margin and 0.101 mm at the occlusal surface. The conclusion of the study was that zirconia monolithic single crowns have shown acceptable clinical fit.6\n\nJi-Eun Ryu et al. in the year 2020 evaluated marginal and internal fit of 3D printed provisional crowns according to assembled directions using silicon replica technique. In this technique they scanned the prepared resin tooth and single crown was designed using computer aided design (CAD) software. Provisional 10 crowns were printed using a DLP based 3D printer at 6 directions (120 degree, 135 degree, 150 degree, 180 degree, 210 degree, 225 degree) respectively with. In total 60 crowns were printed to measure marginal and internal fit. A duplicate silicon model was fabricated and thickness was measured using a digital microscope. Sixteen reference points were set and divided into 4 groups marginal gap, cervical gap, axial gap and occlusal gap. Measurements were analyzed using one-way ANOVA and Dunnet T3. The conclusion of the study was that the 3D printed provisional crowns varied in the marginal and internal fit depending upon the assembled angle and best fit was achieved with assembled angles of 150 and 180 degrees.7\n\nRecently in year 2021 Maria Rizonaki et al. evaluated marginal and internal fit of CAD-CAM ceramic crowns made from lithium disilicate based on 3 different finish lines (rounded shoulder, chamfer, feather-edge). Thirty anterior lithum disilicate crown (n = 10 per finish line group) were fabricated with the help of TRIOS intraoral scanner. An attempt was made by the author to cement the crowns on the respective prepared typhodont teeth with fabricated duplicate dies the absolute marginal discrepancy, marginal gap & internal gap was evaluated by using microcomputed tomography. Values obtained from each specimen from sagittal and trans axial section were 66 and a rendering software program was used to calculate the volume of cement gap for each specimen by means of 3D region growing. Marginal discrepancy & gap values were statistically significant between group. The differences in cement space between groups were not statistically significant.2\n\nThe proposed study is approved by ethical committee with the ethical committee ref.no DMIHER (DU)/IEC/2023/851.",
"appendix": "Data availability\n\nNo data is associated with this article.\n\nThis is version 1 of protocol.\n\nRepository name: Zenodo. Comparative evaluation of marginal fit, internal fit and cement space of single unit lithium disilicate crown with shoulder finish line by two different methods of fabrication. DOI: 10.5281/zenodo.7926172\n\nThis file contains the following data:\n\n• SPIRIT_checklist.docx (Spirit Guideline 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\nNg J, Ruse D, Wyatt C: A comparison of the marginal fit of crowns fabricated with digital and conventional methods. J. Prosthet. Dent. 2014 Sep; 112(3): 555–560. PubMed Abstract | Publisher Full Text\n\nRizonaki M, Jacquet W, Bottenberg P, et al.: Evaluation of marginal and internal fit of lithium disilicate CAD-CAM crowns with different finish lines by using a micro-CT technique. J. Prosthet. Dent. 2022 Jun; 127(6): 890–898. PubMed Abstract | Publisher Full Text\n\nShillingburg HT, Hobo S, Whitsett LD, et al.: Fundamentals of fixed prosthodontics. Chicago, IL, USA: Quintessence Publishing Company; 1997 Jan.\n\nBoening KW, Wolf BH, Schmidt AE, et al.: Clinical fit of Procera AllCeram crowns. J. Prosthet. Dent. 2000 Oct; 84(4): 419–424. PubMed Abstract | Publisher Full Text\n\nDemir N, Ozturk AN, Malkoc MA: Evaluation of the marginal fit of full ceramic crowns by the microcomputed tomography (micro-CT) technique. Eur. J. Dent. 2014 Oct; 08(04): 437–444. Publisher Full Text\n\nRau S, Raedel M, Mikeli A, et al.: Clinical Fit of Monolithic Zirconia Single Crowns. Int. J. Prosthodont. 2018 Sep; 31(5): 443–445. Publisher Full Text\n\nRyu JE, Kim YL, Kong HJ, et al.: Marginal and internal fit of 3D printed provisional crowns according to build directions. J. Adv. Prosthodont. 2020; 12(4): 225–232. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "311743",
"date": "27 Aug 2024",
"name": "Tariq Abuhaimed",
"expertise": [
"Reviewer Expertise Dentistry",
"Dental materials",
"bioengineering",
"endodontics",
"restorative dentistry"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReport on study protocol.\nThe study will evaluate internal gap and marginal gap in two types of full crown fabrication methods, CAD/CAM and pressing. Although, previous literature is available, but the study has the advantage of being performed on patients. The rational of the study is acceptable. However, the methodology of the study lacks details as follows:\nThe aims of the study include evaluation of cement space, which is basically the same as internal gap. The included teeth are maxillary incisors. However, the proposal should be amended regarding the measuring points. As indicated, the inclusion criteria were changed but the measuring points were not. (see point 3). There are some discrepancies in measuring points protocol. “The impression is divided into 4 different parts mesial, distal, buccal, lingual, occlusal” and Fig 5 says the replica will be cut into 6 parts while the Figure shows 9 parts. It is vital to explain how light buddy impression of the prepared tooth is performed in terms of the force applied and duration. This will significantly affect the gap space. Statistical analysis should be revised. English language should be revised. References of the literature discussed are missing.\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? No\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
},
{
"id": "260656",
"date": "11 Sep 2024",
"name": "Christian Höhne",
"expertise": [
"Reviewer Expertise DentistryProsthodonticsOral Surgery & MedicineEducation & Educational ResearchBiochemistry & Molecular BiologyScience & TechnologyMaterials ResearchChemistryBiomechanicsMetal-free RestorationsCeramic DenturesImplantologyImplant ProstheticsCAD/CAM3D printingAdditive ManufacturingDevelopment of Standardized Testing MethodsEstablishment of New Teaching ConceptsVirtual and Augmented RealityDevelopment of Modular Training Models"
],
"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, No results or pretesting’s of the protocol is available so far. The use of a microscope is outdated and the described method for analyzing the different gaps is not understandable and clearly described. Analyzing the fabrication differences by today quality standards is no longer possible with a microscope. Analyzing differences by hand is not reproducible. The assumed error margin 0.12-0.15 is far away from what is needed here. You should start all over with a new concept based on a proper approach by reading the literature.\nSome details in the manuscript Abstract: Background:\n“The coming era will be governed by technology. Computer aided design (CAD) & computer aided manufacturing (CAM) dentistry is taking over the….” CAD/CAM is already used widely in dentistry and not the coming era.\nAbstract: Methods:\n“… 18-54 years in the need of full veneer maxillary incisors crown prosthesis. …” I think you mean “full coverage crowns”?\nNo specific manufacturer of the material for the crowns was mentioned in the abstract. Far too less references discussed here. No results or pretesting available.\n\nIs the rationale for, and objectives of, the study clearly described? No\n\nIs the study design appropriate for the research question? No\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? No",
"responses": []
}
] | 2
|
https://f1000research.com/articles/12-1510
|
https://f1000research.com/articles/13-162/v1
|
08 Mar 24
|
{
"type": "Research Article",
"title": "Rural household resilience to food insecurity in Majang Zone, Southwestern Ethiopia",
"authors": [
"Shibru Zerihun",
"Mesay Mulugeta",
"Meskerem Abi",
"Mesay Mulugeta",
"Meskerem Abi"
],
"abstract": "Background Due to shocks and stressors brought on by both natural and man-made events, households that depend on subsistence agriculture frequently experience uncertainty about guaranteeing their food security. The modern strategy for achieving food security in the face of shocks depends on identifying the variables that affect resilience and working to increase rural households’ capacity to withstand shocks related to food insufficiency. The goal of this study was to evaluate how resilient households were to food insecurity and its determinants.\n\nMethods From primary and secondary sources, cross-sectional data of both quantitative and qualitative types were gathered. The data acquired through surveys from 320 households was analyzed using a multivariate analytical method that included principal component analysis (PCA) and OLS regression. To bolster the findings, data from focus group discussions (FGDs) and key informant interviews (KIIs) was substantially utilized.\n\nResults According to the findings of the analysis, 40% and 60% of households, respectively, become resilient and non-resilient. All but the stability parameter significantly impacted resilience. Resilience to food insecurity is significantly increased by an increase of 2.128, 1.697, 0.648, 0.363, and 0.158 units in the adoption of agricultural technology, asset ownership, access to essential services, and adaptive capacity, respectively. On the other hand, the stability dimension negatively impacts resilience, with each additional unit lowering households’ capacity for resilience by 0.155 units.\n\nConclusions The study suggests that to reduce both short-term and long-term shocks and stresses of food insecurity and to increase the capacity for resilience, the government’s policies and programs and those of other development partners must focus on building the main components of resilience.",
"keywords": [
"Households",
"Food insecurity",
"Resilience",
"PCA",
"OLS",
"Econometrics"
],
"content": "Introduction\n\nFor all living things to survive, food is a basic necessity. Humans rely on outside sources that are controlled by numerous natural and artificial elements to secure their food. From a conceptual standpoint, food security “exists when all people, at all times, have physical and economic access to sufficient, safe, and nutritious food that meets their dietary needs and food preferences for an active and healthy life” (Clay, 2002). Despite ongoing efforts, it is still difficult to meet the world’s food needs because farm households in developing nations frequently experience a variety of recurrent and unexpected shocks that expose them to food and nutrition insecurities (Ansah et al., 2019), which are caused by both climate-related and non-climate-related disasters (Upton et al., 2022; Mbow et al., 2019). According to Denning & Fanzo (2016) and Eneyew and Bekele (2012), the key factors affecting food and nutritional security are land policies and management practices that degrade natural resources. The frequency and intensity of risk exposure among vulnerable people have also increased as a result of unfavorable economic and social pressures (FAO, 2016b). Population pressure (Habtegebriel, 2016; Rockefeller Foundation, 2015); unemployment; violence; and climatic shocks (FAO et al., 2019); COVID-19; desert locusts; displacement; and high food costs (IPC, 2020; FAO, 2020; Abebe, 2017) were mentioned as some of the other major causes of food insecurity.\n\nAccording to the joint FAO and WFP report (2021), severe food insecurity has increased, affecting 193 million people in 53 countries and up to 49 million people in 46 countries, including Ethiopia. The nation is currently in danger of experiencing famine or famine-like conditions. More than 250 million of the almost 690 million hungry people live in Africa, and an additional 83 to 132 million people are undernourished due to the COVID-19 pandemic, according to (FAO et al., 2020). Because of inadequate logistical, institutional, and infrastructure conditions, structural food insecurity issues are also widespread.\n\nTo achieve food and nutrition security, it is essential to create a productive, sustainable, and resilient food system as well as households that can handle shocks and pressures. In the face of disruptions, resilient and strong agri-food systems can open doors for innovation and new development paths (Thompson et al., 2007). With global poverty and food insecurity continuing to exist, the idea of development resilience began to gain favor (Upton et al., 2022). The majority of studies in the area of food security concentrated on estimating the likelihood of a future loss of sufficient food (Alinovi et al., 2010a). Resilience, according to USAID (2012), is “the capacity of individuals, families, communities, governments, and systems to buffer against, adapt to, and recover from shocks and pressures in a way that lowers chronic vulnerability and facilitates inclusive growth”. As a longer-term development strategy, resilience offers a fresh perspective on how to effectively plan for and analyze the effects of shocks and stressors in line with food security (Jones, 2019; Alfani et al., 2015; Constas et al., 2014), as well as designing and evaluating programs to build resilience (Kasie, 2017). In areas where there is a risk of food insecurity and susceptibility to recurring shocks, strengthening resilience as a program is essential for sustained social and economic progress (Frankenberger et al., 2012).\n\nResilience capability varies among the communities studied, according to studies done at various scales (D’Errico & Smith, 2020; Frankenberger and Nelson, 2013; Alinovi et al., 2010a) and levels (Frankenberger et al., 2014). Answering issues like “resilience of what and to whom,” “what livelihood practices are responsible,” and “how the shock environment dictates the capacity of resilience in a household” is therefore often significant (D’Errico & Smith, 2020). In their study on household resilience to seasonal food insecurity, Guyu and Muluneh (2015) found that there were, respectively, 65.25 and 34.75% of less resilient and resilient households in the study area. In addition, socioeconomic and institutional factors including farm size, intensification, asset ownership, income diversification, credit, production of cash crops, and membership in savings and credit societies and labor-sharing groups have a big impact on building resilience capacity (Tefera et al., 2017). In addition, it is claimed that having access to agricultural resources, particularly land, is essential for a household’s ability to withstand food insecurity (Ciani & Romano, 2014). Similar studies in Niger revealed that regions with irrigation capability and low reliance on agriculture dependent on rainfall are more robust. According to the same study, female households have lower adaptive capacities and fewer resources than male household leaders, making them less robust. The prevalence of food insecurity is 10% greater among women than among men (FAO et al., 2021) due to gender-related inequities that have been demonstrated. Participation in social safety nets also makes it possible to develop strong resilience. According to Boukary et al. (2016), households’ ability to cope with food insecurity is negatively impacted by long-term average rainfall. Ansah et al. (2019) similarly concluded that investments in programs and policies aimed at strengthening households’ capacity for resilience can help lower childhood malnutrition and guarantee long-term food security.\n\nUndiversified, subsistent rain-fed agricultural and livestock production in the research region frequently keeps households non-resilient and exposes them to seasonal food insecurity. Most districts had food shortages for 3-6 months on average, and the majority of people (84%) exhibited insufficient resilience during this time. Additionally, more than 40% of the households were unable to raise Birr 500 in a week, and one-third of the households were unable to recoup from their disaster losses (DRMFSS, 2015). According to MoFED (2012), the major causes include highly increased deforestation, migration, underdeveloped institutions and infrastructure, fragmented holdings, rapid population expansion, limited access to modern agricultural technologies, and illiteracy. Land grabbing and commercialization were claimed by Girma & Muluneh (2021) as being extremely important issues. Food insecurity was primarily caused by a combination of inadequate off-farm income, diseases, poor market and credit access, poor access to drinking water and sanitation, policy gaps, and price inflations (DRMFSS, 2015; Seyoum, 2015; MELCA-Ethiopia, 2013). Guyalo et al. (2022) identified such difficulties as corrupted, unresponsive, non-transparent, and non-participatory land and project governance structures or policies.\n\nFew studies on resilience have been undertaken concerning food security in Ethiopia, both in terms of quantity and location (Debessa, 2018), which calls for additional multidisciplinary study. According to Frankenberger et al. (2012), a comprehensive resilience assessment must identify the causal causes that resilience programming must address. Furthermore, the limited number of studies on how to quantify resilience to poverty and food insecurity leaves little room for improvement (Constas et al., 2014). Similarly, there aren’t many studies on the resilience concept in Ethiopia, and those that do tend to focus on a small number of specific livelihood arrangements and methodological foundations. In broader geographic contexts, fewer empirical studies concentrate on how households respond to food insecurity shocks and their resilience to future food insecurity (Debessa, 2018). A portion of the research employs panel data sets to analyze data at the national level (Befikadu, 2019). On the level of household resilience in the study area, one barely obtains research outcome evidence. This leads to a vacuum in the ability to identify the factors that influence households’ dynamic food security, resilience, and coping mechanisms, as well as plan for and develop intervention strategies.\n\nAccording to this study, the conventional methods of responding to crises are insufficient and unsustainable unless they are intended for short-term emergency response due to the high prevalence of food insecurity and the unknown level of household resilience. To determine how many households fall into the resilient or non-resilient category and what underlying natural, social, economic, and environmental variables contribute to the issue, it is necessary to tackle the problem of food security using the resilience concept. Additionally, it can serve as a starting point for the creation of effective working policies, programs, and strategies by development partners and policymakers. According to Choularton et al. (2015), the resilience idea is currently regarded as a unifying policy instrument. As a result, the study’s goal is to evaluate how resilient rural households are to food insecurity in the study area. Specifically, the objectives are:\n\n• To examine the resilience status of rural households to food insecurity in the study area\n\n• To identify the level of influence of the resilience dimensions on the resilience capacity of households\n\n\nMethods\n\nThe study was conducted in the Majang zone, Gambella People’s Regional State, southwestern Ethiopia. Approximately 620 kilometers separate Addis Abeba and the zonal capital of Meti. There are two Districts in the area: Godere and Mangeshi, with an agroecology that is considerably wider and elevations that range from 800 m to 2100 m above sea level. The region is situated between latitudes 7° 4′ 2.41″ and 7° 46′ 47.79″N and 35° 38′ 48.00″E to 34° 36′ 30.54″E. According to Mathewos & Bewuketu (2018), the zone has a total land area of 2252.79 km2. The zone is bordered by the Oromia Regional State in the north, the Southern Western Regional State in the east and south, Abobo in the northwest, and Gog and Jor in the west. The Zone has a total population of 89033, with 46119 men and 42914 women, as of the CSA’s (2013) projection for the 2022 census. Each of the 32 Villages administered by Godere and Mangeshi Districts is habituated with projected populations of 61079 and 27954, respectively. With an average of 5.3 people per household, 88% of the population lives in rural areas, and more than 60% of that population is under 20 years old.\n\nThe Majang zone is one of Ethiopia’s few areas endowed with abundant natural resources. The Majang Forest Biosphere Reserve is the name given to the forest and its resources, which serve as the community’s primary source of income, by the United Nations Organization for Science, Culture, and Education (UNESCO). Commercial farming (coffee), agriculture, honey production, fishing, hunting, foraging for fruits and spices in the forest, small and petty trades, and commercial farming are the main sources of subsistence in the study region. NTFPs, wood products, and traditional forest honey production provide for almost 87% of all households’ income. Raising livestock is another prevalent habit; however, it is not a significant source of income.\n\nWhile the Godere district is dominated by other ethnic groups, including the Sheka, Kafa, Oromo, Amhara, Sheko, and Tigre, who are frequently referred to as the “highlanders” by native Majang populations, Mengeshi district is a Majang community-dominated woreda and is located in the lowland agro-climatic zone. Part of Godere district’s agro-climatic conditions are in the lowlands, but the majority are found in the mid- and high-altitude regions. The region has a hot, humid environment, and according to Ethiopia’s rainfall maps, it is the wettest place in the nation. Around 2100 mm and 20–33 °C are believed to be the mean annual temperature and rainfall, respectively. A flat to gentle slope, occasional rocky steep slopes, and deep valleys on the hills and along important streams define the environment. The majority of the streams are perennial and have relatively significant water discharges, but rural populations worry that deforestation is reducing the amount of water flow. The soils in the region are mostly dystric nitrate and range in color from red-brown to dark brown. Agriculture, grazing land, woodland, habitation, wetland, infrastructure, and wasteland are the main land cover types. Forestry and agriculture both cover the majority of the zone’s land.\n\nThe study was conducted in the Gambella People’s Regional State’s Majang Zone. Since combining qualitative and quantitative household data in a single research project enables a thorough and holistic understanding of the issue of interest, a mixed-methods design was utilized for the study (Degefa, 2006). Furthermore, Ciani & Romano (2014) asserted that the pragmatic approach, which combines quantitative and qualitative approaches, is becoming increasingly popular in studies of resilience to food poverty. The Food and Agriculture Agency (FAO) was the first agency to use the idea in food security contexts and has extensive experience evaluating resilience using both quantitative and qualitative methodologies (FAO, 2016a). The embedded design was picked for the study out of the six mixed designs that Creswell (2012) suggested. The embedded design allows for the simultaneous or sequential collection of both qualitative and quantitative data, but the quantitative method is employed most often, and the results from the qualitative data are used to support the findings of the quantitative analysis. Cross-sectional data types are best associated with embedded design.\n\nThe study households were chosen using a multistage selection technique. First off, since there are only two districts in the zone and they all have comparable livelihoods and administrative boundaries, Mengeshi and Godere were chosen on purpose. Second, out of the 32 villages, 10 villages—four in Godere and six in Mengeshi—were chosen systematically by random sampling under the premise that a high sampling ratio (about 30%) was thought to be adequate for small populations (1000). The sample villages were chosen based on the presumption that they were subsistence farmers, that the Majang community dominated, and that they were attached to a life reliant on the forest. To compute the respondent households from each village based on the proportion share of the total households, the 2022 estimated population (households) of each villages was used. The 10 Villages’ total population and households totaled 15826 and 3557, respectively. Finally, respondents were chosen at random using Cochran’s (1977) processes for large populations using the probability proportional to size technique.\n\nZ2 is the normal curve’s abscissa, which eliminates a region at the tails (1-α equals the appropriate confidence level), where no is the sample size. e is the desired level of precision, p (0.6) is the estimated proportion of an attribute or all forms of food-insecure households that are present in the zone’s population, and q is 1-p, as has been highlighted in the reports of Hailemariam (2011) and DRMFSS (2015). The 95% confidence interval is assumed for this research, and the Z table value equals 1.96. 369 households make up the sample size according to the formula.\n\nThe final sample size is calculated using Cochran’s (1977) formula for the sample size adjustment for sample sizes greater than 5% of the population.\n\nSince the sample size is greater than 5% of the population, the ultimate sample size is n1, and N is the size of the population. The ultimate sample size is therefore [369/1+ (369/3557)] = 334. Data from a few families was omitted due to the incompleteness of some household data, and 320 sample households served as the sampling unit for the final analysis.\n\nPrior to conducting the data collection work an official letter written by Addis Ababa University, the research hosting institution, was submitted to bureaus and offices, and briefings were held to create understanding on the overall objective of the study. A cross-sectional household data from primary and secondary sources was used in the study. The data was collected using questionnaires, FGDs, KIIs, and desk review from secondary sources. All methods adopted in the data collection were given consent of approval from institutional review board (IRB) of college of development studies, Addis Ababa University.\n\nThere are both closed-ended and open-ended questions in the survey data collection tool, with the closed-ended questions having ratings on ordinal, ratio, or categorical scales. The open-ended questions were designed to elicit more information for some of the closed-ended and description-needed questions. The questionnaire types are those developed by the authors and an institutionally approved one, and standardized questionnaires of the Food Consumption Score (FCS) and the Household Food Insecurity Access Scale (HFIAS). The data was sourced from 320 randomly chosen rural household respondents from 10 villages in the two districts. The questionnaires were administered to the household respondents guided by trained enumerators. The data gathered by this method is purely primary type. The data was collected using tablets and mobile apparatuses in which the questions in the questionnaires are filled into KoboToolbox data collection application.\n\nThe goal of the focus group discussion sessions was to gather primary data, which included descriptions of the top priority questions derived from the survey, assessments carried out in the research field, and literature consultation. The in-person discussion was framed with a comprehensive set of terms of reference questions that served as lead questions. Before starting the debate, the authors briefed the discussants about their goal of minimizing bias and establishing a shared understanding. Together with four hired data enumerators, the corresponding author—who is presently pursuing his PhD—collected the data. The corresponding author has worked as a postgraduate research advisor and has experience conducting and publishing research publications. The four male data collectors have all earned BSc degrees and have been employed by Ethiopia’s Central Statistics Authority (CSA) as contractual data collectors. A group of seven to ten individuals of both sexes was selected from the previously sampled household respondents, elderly persons, women, and youth groups at the village level for each of the ten FGDs that were held, one in each of the ten villages.\n\nSimilar to the other data-gathering methods, a clear understanding of the aim and merits of the research was made before interviews were conducted. To gather primary information relevant to the specified key explanatory questions, KIIs were done by interviewing people with varying levels of authority and responsibility, such as experts, officials, extension agents, and NGO staff. The primary data sources were specialists from the bureau and offices of development agents at the village level, agriculture, health, water, education, cooperatives, environment and climate, and disaster risk management. Within each purposively selected office, there were two individuals: a lead specialist and the office head as interviewees. The research’s corresponding author carried out the KIIs. This session has also included the implementation of the necessary procedural fulfillments and descriptions discussed in the FGDs.\n\nThe secondary data was gathered from the internet and desk review of paper works. Information on related literature reviews was gathered from published journal articles, books, chapters, reports of accredited sources, and from databases of recognized portals. Office paper works of organized plans, accomplished tasks and assessment reports, published bulletins, and brushers were used as secondary data sources of both numeric and narrative types. Access to documented data was requested by an official letter. The secondary data were collected to supplement and justify the data from the primary sources.\n\nThis study was granted ethical approval consent from the Institutional Review Board (IRB) of College of Development Studies (CoDS) of Addis Ababa University on 24/08/2023 and with Reference Number of spe/e/c/28/07/2023. The IRB letter is accessible at https://doi.org/10.20372/aau_rdm/EAOGKA (Zerihun et al., 2023). Further detail on the letter can be requested from the IRB board via the email: cods.irb@aau.edu.et.\n\nInformed consent was obtained from all subjects involved in the study. The household respondents and focus group participants were told the objectives and purpose of the study, that participation was voluntary, and were requested to all the questions. They were informed they were free to refuse to respond to any questions and withdraw at any time. The key informants were also briefed about the objective of the research and its merits towards contributing to the community, policy makers, researchers, and assured of nonexistence of any political or legal concerns. These participants were provided with mobile numbers and emails of immediate supervisors of the research lest they communicate for any inconveniency they encounter during the interview. Official letters of cooperation have been written to the concerned bureaus and offices to inform them of the objectives and intentions of the research.\n\nIn this study, the resilience of households to food insecurity was not measured as a capacity but rather as an indicator of food security, such that higher resilience scores are assumed to be indicative of better food security status. Both quantitative and qualitative analytical methods were used based on the characteristics of the variables investigated. Descriptive and inferential statistics were deployed using STATA software version 13 (https://www.stata.com). The descriptive results project percentages, means, and standard deviations, and the inferential statistics employ an econometric method applying the specified model.\n\nThe data collected using the survey method was first cured in Microsoft excel and then coded after importing into STATA software. To check the data normality, homogeneity and multicollinearity tests were conducted. Next, the data were subjected to their specific models for analysis and interpretation. Likewise, the qualitative data were analyzed such that the information gathered via FDGs and KIIs were transcribed into a written format, major themes were identified and the data were organized. Finally, the organized data were interpreted contextually to validate and substantiate the results from the quantitative analysis. The secondary data types were read, information extracted, and integrated into the study as supplementary information and reviews to justify the research objectives, methods, results.\n\nThe results of the descriptive statistics were utilized to determine the degree to which determinant components’ resilience affected the ability of families to withstand food insecurity as well as to shed light on various socioeconomic traits of the households. The drivers of resilience’s impact on food insecurity and their causal connections were examined using econometric analyses. Following the models described along the principal components, an ordinary least squares (OLS) regression model was used for the econometric study to look into the correlates of resilience status. The following mathematical illustration (Equation 3) provides an estimation of the expected value of the dependent variable Y.\n\nWhere: Yij = Dependent variable “Resilience to food insecurity”\n\nβ0 = Constant,\n\nβ1, β2 … βi = Coefficients of variables,\n\nX1, X2 … Xi = explanatory variables\n\nεi = Error term\n\nFitting the resilience components into the model, the working equation takes the following form.\n\nWhere RI is household resilience; a is a constant; b1–7 are the coefficients of each variable (the component indices developed during the PCA analysis); and e is an error term.\n\nIn many food security-centered resilience analysis frameworks, like those developed by Alinovi et al. (2010a), the quantitative analysis of resilience identified seven or eight key dimensions of resilience that integrated capital and capacity approaches, including income and food access, access to essential services, assets, adaptive capacity, stability, adoption of agricultural technology, social capital, and/or social safety nets. To account for the study’s environment, the components that determined resilience capacity were stated as recommended by FAO (2016a) and (Alinovi et al., 2010a). PSNP is substituted by its anonymous counterpart, Social Capital (SC), as there are no rural social safety net programs deployed in the zone and only urban safety net is just starting in the zone’s capital, Metti town. Guyu and Muluneh (2015) substituted the traditional SSNs that are inherent and used by the community in the study area for the SSNs as a way to help build social capital in places where the formal program is not implemented. The inclusion of observable factors under each component was made based on refined evidence from the literature and the researchers’ prior experience of the study area. The PCA creates uncorrelated indices or components from an initial set of n correlated variables (x1, x2, x3, …, xn), and each component is a linearly weighted combination of the initial variables. The mathematical equation takes the following form (Equation 5):\n\nWhere Yi is the household’s component score on the ith PCA, ain represents the weighted value for the ith principal component and the nth variable.\n\nSince the pillars are latent and cannot be directly quantified to indicate resilience at the household level, the resilience status of the households to food insecurity was examined using a two-stage analytical model. Each of the pillars can also be measured using socioeconomic and institutional characteristics that have been observed. Multivariate techniques are frequently used in research to quantify outcomes, and cross-sectional data from national demographic and household surveys, as well as individually designed and self-administered surveys, were employed for measuring the level of household resilience to food security (Ansah et al., 2019; Beyene, 2016; Alinovi et al., 2010a). First, principal component analysis is used to estimate an index for each component individually across a collection of observable variables. The resilience index is then derived using a factor analysis on the interacting components estimated in the first stage, where the weights are the percentages of variance explained by each factor and the resilience index is a weighted sum of the factors created using Bartlett’s scoring method. According to Beyene (2016), who cited DiStefano et al. (2009), the Bartlett technique typically yields latent variable ratings that are univocal and unbiased.\n\nTo determine whether principal component analysis (PCA) is appropriate, model fitness and sample adequacy tests are computed. A KMO value of 0.5 in a decent model is required to pass the Kaiser-Meyer-Olkin (KMO) measure of sampling adequacy test. Bartlett’s test of sphericity was run concurrently to demonstrate the lack of multicollinearity or singularity issues. By examining the determinant of the R-matrix, which should be larger than 0.00001 as stated in Field (2009), multicollinearity or singularity concerns can be identified. Since it is analytically impossible to use these variables for factor analysis, or PCA, the best scaling technique was used to estimate the latent components that are related to the dummy or categorical variables by changing the observed variables. All variables in transformation are assumed to have a normal distribution with a mean of zero and a unit variance. Each observed variable is multiplied by a negative one to make it compatible with the meaning of the hidden variable when some of the seen variables are negative indicators of the latent variable.\n\nVarimax, or orthogonal factor rotation, is used to separate the loadings amongst variables after PCA factor extraction. Varimax rotation is regarded as a good general strategy that makes factor interpretation simpler since it aims to maximize the dispersion of loadings within factors by heavily loading fewer variables onto each factor, leading to more interpretable clusters of factors. Field (2009) claimed that loadings with an absolute value of more than 0.3 were generally regarded as being important. However, he recommended that significant consideration be given to taking critical values of factor loadings of 0.722 for a sample size of 50 and that these values should be greater than 0.512, 0.364, 0.298, 0.21, and 0.162 for sample sizes of 100, 200, 300, 600, and 1000, respectively. The following equation represents the development of the household resilience index.\n\nWhere Ri = estimated resilience index for household i, WC = the weight (factor score coefficient) for the Xth indicator of resilience in the PCA, Xi = the ith household’s value for the Xth variable (indicator) (Note: the Xth’s in the current study’s context are the variables denoted by AP, ATA, ABS, S, SC, AC and IFA in equation 1 above) Xj = the mean of Xth variable for overall households. Si = standard deviation of the Xth variable for overall households.\n\nThe households combined index for each latent component (covariate of the overall resilience) is computed according to equation 5 below, as has been applied in a variety of research works (Tekalign, 2022; Dhraief et al., 2019; Debessa, 2018; Beyene, 2016; Guyu & Muluneh, 2015).\n\nWhere RIn is the resilience index of the nth household, ∂n is the variance explained by each factor, factors 1, 2, 3 … n are the respective factors generated by the factor analysis representing each latent dimension.\n\nThe next step is to assess each household’s overall resilience to food insecurity status after calculating the index for each latent variable for that particular household. The factor technique and principal component analysis are used to obtain the overall resilience index (RI) for each family. As a result, the households were divided into the four resilience categories that had been arbitrarily proposed (Beyene et al., 2023). These groups were said non-resilient if the overall resilience index is (RI<0.00), moderately resilient (0.00≤RI<0.5), resilient (0.5≤RI <1.0), and highly resilient (1.0<RI). The categories for resilience were coded 1 through 4 in increasing order, with 1 being designated as susceptible and 4 being highly resilient.\n\n\nResults and discussion\n\nA total of 320 rural households participated in this study, and the majority (90%) depend on agriculture to meet their dietary needs. The majority of households (79%) have a male head of family and are married (88%). 89.7% of households have agriculture as their sole source of income, 9.7% have agriculture plus trade, and 0.6% have income from other sources. The average household size is five family members, which is in line with the national average. The average age of the household is roughly 40 years, with the minimum and maximum ages being 18 and 75 years, respectively. The households had a mean total land holding of 2.63 ha, which is three times greater than the national and regional averages stated by CSA (2021) but less than 0.5 ha when the net land use is restricted to the production of food crops. According to calculations, the households’ average annual farm and non-farm earnings were 20273 and 495 birr, respectively. When expressed as a mean per capita yearly income, the figures for on- and off-farm incomes are 4054 and 100, respectively. In the research area, the average household dependency ratio was found to be greater (87.65%), with the highest dependency ratio approaching 400%.\n\nAccording to the results of the descriptive statistics, 42.19% of the respondents had at least completed elementary school, while 57.81% had not attended any formal schooling. Additionally, almost three-quarters of the respondents stated that they were not receiving the services and technologies they needed to promote the expansion and productivity of their subsistence agriculture. Only 39% of them receive agricultural extension service contacts as a result, although FTCs are built in their Villages (60.62%), improved seeds are provided to them (25.62%), traditional irrigation systems are used to supplement crop production (12.81%), they are members of cooperatives and participate in cooperative activities (16.87%), they can obtain veterinary services for their livestock (20%), they can prepare and apply fertilizer (13.44%), they can use oxen to plow their agricultural land, and they are able to purchase and apply chemical pesticides (32.50%).\n\nThe analysis outputs of the observable variables explained their respective latent components at varying magnitudes and significance levels. The resilience dimensions used to estimate the resilience status of households include income and access to food, access to basic services, assets, adaptive capacity, stability, agricultural technology adoption, and social capital. The number and expected contribution of independent variables towards resilience to food insecurity under each pillar, the components retained, and the indices produced accordingly are portrayed below.\n\nThe income and food access (IFA) pillar is closely related to households’ ability to absorb shocks with what they have on hand and other food access options, which is why it has a positive link with resilience to food insecure circumstances. Income limits a household’s access to food by determining how much it can spend on food and how much food it can consume. The Household Food Insecurity Access Score (HFIAS) and the Food Consumption Score (FCS) of the households, both of which are proxy tools for measuring food access, were used to construct the index for IFA along with the household’s farm income, off-farm income, number of income sources, and amount of credit received. Except for the HFIAS, all the variables show a positive correlation because those scores rise when food security increases.\n\nThe findings of the main component analysis demonstrate that the variables being investigated are sufficient to explain the IFA because the model adequacy test, measured by the KMO measure of sampling adequacy (0.615), is significantly higher than the cutoff established by Kaiser’s rule (0.50). Chi2 = 538.113, df = 6, and p<0.01 values for Bartlett’s Test of Sphericity showed that there was no singularity or multicollinearity among the variables. The correlation results show a perfect connection between the converted data and the IFA latent variable, with an R-matrix value of 0.183. All six continuous-scale factors were loaded onto a single component with an eigenvalue of 2.31 and a total variance of 57.88%. Except for off-farm income, which loaded below the minimum and was eliminated from the analysis following the orthogonal rotation matrix factor loading retention requirement, all five variables sufficiently scored loadings above the minimum. The component loadings of the variables utilized in the model are shown in Table 1. Since each of the three variables is measured on a continuous scale, PCA is applied directly to them.\n\n\n\nAssets are the capital that enables households to withstand challenges and shocks. When a household has varied assets on hand, they feel safe and protected from unforeseen events that may otherwise throw their life off balance. The two most important assets for rural households are land and livestock. Both productive and nonproductive assets act as buffer stocks under difficult circumstances as a short- and long-term way to avoid shocks and be robust. The household’s jewelry, telephone, television, plow, bike, table, and radio were all considered assets in some areas, although the definition of an asset depends on the context (Boukary et al., 2016). Estimates of the agricultural asset components of resilience were based on land holding size, cattle ownership (TLU), beehive ownership, and possession of jewelry, radios, jewelry, televisions, satellite dishes, mobile phones, tables, sofas, beds with sponge mattresses, bicycles, and motorbikes. TLU was transformed using the conversion equivalents table for Sub-Saharan Africa published by Njuki et al. (2011). Presumably, each factor will increase the likelihood of resilience to food insecurity.\n\nBefore doing the PCA, the dummy variables underwent optimal scaling adjustment to be suitable for PCA. The variables’ suitability and model fitness for the principal component analysis were assessed after analysis, and the test result demonstrates that the variables are eligible with a KMO test value of 0.79. With χ2 = 916.335 and df = 55, the factor test was also significant (p<0.01), and the correlation matrix value of 0.054 showed that there were no collinearity issues among the variables. Using Kaiser’s formula to estimate the latent variable AP, four components were kept that together account for 64.34% of the overall variability. Five, two, three, and two-component loadings of more than 0.3 values, respectively, were applied to components 1, 2, 3, and 4 (Table 2).\n\n\n\nThe third crucial component of resilience, adaptive capacity, describes how well a household can adjust to and respond to shocks. According to Dhraief et al. (2019), the phrase refers to the circumstances that make it possible for individuals to foresee and react to changes, minimize, cope with, and recover from the effects of change, as well as seize new possibilities. The latent pillar AC was established using the indicators of educational average, diverse sources of income, and household dependency ratio (Baye, 2017). The adaptability or coping capability of households experiencing food insecurity difficulties is also influenced by the age, size, and marital status of the household. These observable factors, such as sex, age, marital status, family size, education, diversity of income sources, and the dependency ratio of households, were used to explain this pillar. Except for the dependency ratio, all of the variables used to index AC were thought to positively affect resilience to food insecurity. The marital status of household variables and the sex of the head of the household were transformed using optimal scaling statistics. The sample variables used to determine the AC pillar were found to be sufficient (KMO = 0.616), and the correlation matrix’s determinant of 0.096 verifies the model’s fitness in all necessary conditions for PCA to be performed without any concerns about multicollinearity or singularity. A Chi square value of 740.363 and a degree of freedom of 21 led to a significant (p<0.01) result for the Bartlett test of sphericity.\n\nThe results of the principal component analysis showed that every variable had a significant absolute value greater than 0.3, which indicated that it was important in explaining the AC pillar of resilience. Retained were two components with eigenvalues of 2.25 and 2.11, which together accounted for 32.31% and 30.12% of the overall variance (62.40%). The first component is heavily weighted with the factors of household size, age, and dependence ratio, while the second component is heavily weighted with the variables of household sex, marriage status, and years of education. The dependency ratio’s inverse relationship with adaptive capacity, which results in a household’s adaptive capacity eroding as a result of the considerably more non-working yet consuming household members, is what accounts for the dependency ratio’s negative loading value on component one (Table 3).\n\nThe equation estimating the AC latent variable is:\n\nInfrastructure and institutions that offer services are essential to improving the resilience of rural households. Public service delivery is typically capital-intensive and exogenous to households’ dependence on governmental and non-governmental supporting organizations. To increase the effectiveness of a household’s access to assets, access to public services is essential (Alinovi et al., 2010b). Infrastructures like roads, markets, water points, irrigation systems, and other services like farmers’ development agents, electricity, educational facilities, telecommunications, health facilities, credit institutions, and transportation all play crucial roles in supporting the effort to remain resilient. The distance to a source of drinkable water, the distance to the nearest highway, the distance to a school, and the distance to a medical facility are all used to calculate the latent variable ABS. In this analysis, accessibility and distance to public services are negatively correlated; thus, each has been multiplied in reverse to change the direction of influence. In addition to the variables, access to telephone services, electric service, and rural credit services were measured on a categorical scale and needed to be transformed into a ratio scale using the best possible scaling technique.\n\nFollowing the execution of all statistical tests for PCA, it was discovered that the model is suitable and competent for significantly expressing ABS. The samples were sufficient to support factor analysis, as demonstrated by both the individual and aggregate (0.786) KMO tests. The R-matrix value of 0.058 is over the stipulated minimum cutoff level (0.00001), suggesting the absence of multicollinearity or singularity problems among variables. The factories or Bartlett’s Test of Sphericity result was significant (χ2 =898.787, df = 28, and p<0.01). Ten explanatory variables were used to determine ABS, but two of them—distance to health facilities and distance to a primary school—were removed due to their minimal loading or inadequate ability to explain the latent variable. The PCA identified three components that explained variances of 37.26%, 19.36%, and 14.56%, respectively, with eigenvalues of 2.981, 1.549, and 1.165 in ascending order. The total variance was explained by four factors loaded on Component 1, two loaded on Component 2, and two loaded on Component 3 (Table 4).\n\nIn least-developed countries, practically all rural households depend heavily on agriculture. Given that the agricultural sector is supported by enhanced agricultural inputs and technology that can increase crop and livestock production and productivity, food security, and therefore resilience to shocks and stresses, To measure the ATA latent component, sixteen variables were taken into account, including methods and tools for increasing agricultural and livestock output. Crop rotation, intercropping, improved seed, chemical pesticides, synthetic fertilizer, organic fertilizer application, oxen plowing, constructed crop storehouse or gotera, coffee drying on the bed, mulch application, irrigation, use of modern beehives, veterinary service, artificial insemination, and keeping livestock in separate homes are all examples of crop diversification practices. All the variables were transformed using optimal scaling approaches and run in PCA because they were all dummy variables. Four variables—use of synthetic fertilizer, usage of contemporary beehives, crop rotation, and coffee drying bed—were omitted from the analysis because they had singularity problems for the first two, to which the response was “no,” and because they had low factor loading for the latter two. The utilization of modern beehives and the total absence of chemical fertilizer use by the studied families gave rise to the singularity case.\n\nTherefore, the PCA was performed using 12 indicator variables (Table 5) to forecast how the ATA will affect households’ levels of resilience to food insecurity. To test the variables for variable correlation and collinearity and to make them suitable for PCA, an optimal scaling procedure was applied to them. The results that were subsequently produced showed that the variables are a linear combination of predicted factors to quantify the pillar for resilience measurement. The KMO statistics score of 0.843 indicates that the sample is adequate, and at the same time, Bartlett’s test rejects the null hypothesis that the original correlation matrix is not an identity matrix (p< 0.01, Ch2 = 1306.477, and df = 66). The correlation matrix’s determinant was found to be significantly over the minimum significance threshold of (0.016) in the test for the presence of multicollinearity or singularity. Variables with score loadings of 0.3 and components with eigenvalues larger than or equal to one were allowed to be retained by the factor analysis. Overall, three components (the first loaded with five variables, the second and third with four variables each) with eigenvalues of 2.946, 2.173, and 1.995 each explain variances of 24.55%, 18.11%, and 16.63%, respectively (Table 5).\n\n\n\nThe sixth element of resilience is stability, which typically refers to a household’s options and ability to resist various socioeconomic and ecological circumstances that could impair a household’s ability to provide for its members. Since they are linked to shock and stress, the factors that are utilized to estimate this pillar typically have adverse effects. Most similar studies use variables like crop shocks, livestock shocks, human health shocks, climate-induced shocks, economic shocks, and so on to denote pillar S, showing how it has an inverse relationship to food insecurity resilience. Each observed variable for the relevant scenario was multiplied by -1 to make it comply with the stability pillar’s definition. Theoretically, stable households are thought to be more resilient to food insecurity. To calculate S, this study takes into account human health issues like serious illness, frequent medical visits, and having a family member with a disability; pre- and post-harvest crop shocks that are defined by disease and insect damage, weeds, wind and frost attack, and flood; climatic shocks like rainfall pattern or variability; socio-economic variations like frequency of DAs’ visits and support, commodity price variability, and latrine use; and lives. One of these observable variables, shown in Table 6, was employed in the study; the others were left out due to concerns about the variables’ multicollinearity and sample adequacy for PCA.\n\nSince each of the five variables has a ratio scale, PCA is possible. The outcome of the factor analysis demonstrated that the variables are sufficient and that multicollinearity or singularity are not issues. At χ2 = 97.712, df = 10, the Kaiser-Meyer-Olkin Measure of Sampling Adequacy was found to be adequate (0.63), and the Bartlett test of sphericity was significant (p<0.001). The model is appropriate, as indicated by the correlation matrix’s (R-matrix) determinant of 0.734. According to Kaiser’s criterion, two components were kept, with their respective eigenvalues of 1.56 and 1.21 explaining variances of 31.15% and 24.13% for the two PCA measurement indicators. In addition, two variables associated with agricultural output were placed on the second factor, whereas the three variables related to human health were grouped under the first component and shared a significantly higher variance. Additionally, according to the component loadings (Table 6), animal shocks are the most important factor in enhancing the study households’ ability to withstand food insecurity.\n\n\n\nSocial capital networks are intra- or inter-social group ties that are based on a sense of community or belonging and actively support the resilience of both individuals and groups. They are governed by conventions, ideologies, and institutions developed locally to further common goals and interests. In communities, social capital is crucial because it offers support and backups that increase a household’s or a group’s resilience, especially in times of stress and shock. In more advanced situations, these platforms can be turned into chances for business ownership and wage employment, as well as official and informal loans, cash advances, inputs on credit, talents, and shared resources for production and marketing. Idir, members of religious organizations, Iqub, Debo, and people’s readiness to help are a few of the most popular ones.\n\nThe willingness of people to help one another out in difficult circumstances, Idir membership, and religious group participation were used to represent the SC component for this study (Table 7). The variables underwent an optimum scaling adjustment before PCA because they are categorical in nature. The samples were found to be suitable in the subsequent PCA analysis, scoring a KMO value of 0.664, and the model was found to be appropriate and fit (R-matrix = 0.201) according to the significant Bartlett test of sphericity (p<0.01, χ2 = 506.984, df = 15). Since all six variables have component loading values greater than the criterion of 0.298, they are all statistically significant. The two components that were kept explained 63.33% of the total variance, with eigenvalues of 2.22 and 1.58.\n\n\n\nThe latent component indices from the principal component analysis of the latent components computed earlier in stage one are used to create the overall resilience index (RI) of the households. The indices of the seven pillars, ATA, IFA, ABS, AP, AC, SC, and S, were subjected to PCA at stage two of the resilience analysis under the assumption that all the blocs are normally distributed with mean zero and unit variance. At the second stage of the analysis, factor analysis using the principal component factor approach may have been used in several research articles (Eze et al., 2021) that focused on resilience-centered topics. These variables’ suitability and appropriateness for the model were examined, and all necessary measures were determined to be met. Accordingly, the KMO measure of 0.859 indicated that the samples were enough, and the value of the correlation matrix’s determinant, which is 0.045, indicates that multicollinearity or singularity concerns are not present, becoming significant (p< 0.01) with a Chi square value of 977.339 and a degree of freedom of 21.\n\nAccording to Kaiser’s criteria, one component explaining 53.07% of the total variance and having an eigenvalue greater than one (3.715) is kept. All variables had acceptable factor loadings except the variables measuring adaptability and social capital. The largest factor loadings were found for income and food access, followed by the adoption of agricultural technology, asset ownership, access to basic public services, and stability in that order, showing the relative contributions made by each block in helping households in the study area become resilient to food insecurity. The stability component, on the other hand, is loaded with a negative value (Table 8). Observed variables are, in fact, an indicator of instability because of the nature of the variables used to evaluate stability, which requires that there be a negative association with resilience to food insecurity.\n\nHence the overall resilience index is generated as in equation 15 below:\n\nBased on two analytical outputs, the determination of families’ food insecurity resilience statuses was carried out. In the first, the total resilience index of households was used to identify the categories or resilience status of households. The importance of the pillars in determining the household resilience capacity was covered in the second analysis, which was econometric.\n\nTable 9 below lists the groups of households in the research area that are resilient to food insecurity. The findings showed that the population’s level of resilience is only moderately stable, with roughly 47.5% of families vulnerable and an additional 12.19% uncertain, bringing the percentage of weak resilience to almost 60%. The findings are in line with studies of nearly identical cont, respectively, with 23.13% and 17.19% each (Table 9).\n\nAdditionally, as in the works of Debessa (2018), Ciani & Romano (2014), Alinovi et al. (2010a) and Alinovi et al. (2010b), the relative importance of the covariates in indicating the resilience capacity of households was done via the size of loadings of the components (pillars) as an alternative path to detect the substantive importance of each. According to Field (2009), the factor loadings in a particular analysis can take the form of either correlation coefficients or regression coefficients, providing two different avenues for analytical comparison. As a result, the factor loadings of the pillar components used to explain the combined resilience index (Figure 2) showed diverse magnitudes and directions of effect, suggesting that one contributes considerably to building resilience but not significantly more so than the other. In light of this, ABS, AC, and SC played relatively few roles despite having a positive correlation, whereas IFA, ATA, and AP significantly and positively contributed to families’ resilience ability. In terms of relative relevance, it was determined that the IFA pillar contributed more than the ATA and AP pillars. The study area is heavily dominated by commercial crop production, such as coffee and apiary operations, and these considerably contribute to the well-being of the households. As a result, the income and food availability dimensions were shown to be crucial in the resilience-building process. The stability pillar of the resilience component showed a negative correlation with the outcome index, indicating that the research area had seen a high occurrence of food security shocks. Animal and crop-related biotic and abiotic problems account for the majority of the shocks, in particular. Both the key informants and the focus group participants saw how large crop shocks such as heavy rain, snow, strong wind, insect pest attacks, weeds, and illnesses have limited the amount of potential food that could have been produced from crops. Notable are also the shocks that have been identified as contributing to the decreased productivity of livestock output, including diseases such as trypanosomiasis, foot-and-mouth disease, and a lack of fodder and veterinary services. During discussion sessions the households claimed that they have to travel long distances to purchase medicines and medical equipment for their livestock without prescriptions but these aided their common understandings.\n\nIdentification of the relative significance of each pillar in establishing the resilience category for the families is equally important to understanding the status of the resilience of the households. The overall index was used as the dependent variable in the Ordinary Least Squares (OLS) regression analysis, while the indices of each pillar were used as the independent variables. To determine how much these pillars affected households’ resilience to food insecurity in the research area, they were regressed against a predetermined cutoff value of the overall resilience index (RCI). The outcomes of the OLS regression study are discussed below.\n\nThe OLS regression analysis result showed that all seven factors, except social capital, had considerably and highly affected the resilience status of households to food insecurity (Table 10). The results of the econometric analysis, in contrast to the component loading-based conclusions, showed that adoption of agricultural technologies and asset ownership came in second and third place in terms of relevance. The findings show that, with all other variables maintained constant, a unit increase in agricultural technology availability increases households’ ability to withstand food insecurity by more than double (2.13 units), on average. The capacity for resilience will also improve by 1.697 units for every additional unit of assets owned by households. Similarly, a better intervention to foster access to services, building adaptive capacity and income and food access dimensions positively contributes to lifting of the resilience capacity by 0.648, 0.363 and 0.158 respectively. The social capital dimension remained insignificant, according to the group discussions result, social capital variables such as idir, equb, debo, and dado that could have positive contribution in building resilience have been little exercised particularly in the Majang community.\n\n* Significant.\n\n** Highly Significant.\n\n*** Very Highly Significant.\n\nns Non-Significant.\n\n\nConclusion and recommendations\n\nThis study looks at how resilient households are to food insecurity and how much of an impact determinant factors have on that resilience. Contrary to the well-known short-term food security research and treatments, resilience in food security studies enables us to efficiently plan for and assess the consequences of shocks and stressors in a longer-term development strategic approach.\n\nIn the study area, it is argued that households’ resilience to food insecurity is unstable. Families who have access to food and income, build wealth, use agricultural inputs and technology, and have superior adaptive capacity are more likely to withstand the shocks and pressures of food insecurity. Those who have access to public services are also more likely to do so. To decrease the number of vulnerable households and increase the abilities of those who are resilient, it is crucial to enhance these characteristics. Agricultural technology use, asset ownership, and access to essential services have all helped people become more resilient, whereas social capital has made a negligible difference in this regard. On the other hand, a household’s level of resilience to food insecurity was negatively impacted by stability or sensitivity.\n\nThe study suggests that to bring about long-lasting change and improve the good aspects of the resilience-building components, it is also advisable to focus on the following livelihood capital segments: A major policy objective is the implementation of local land use plans and the certification of rural land for both sustainable use of forest products (NTFPs) and trust-building by assuring farmer households. It was acknowledged that the rush of people into the area had increased pressure and competition for natural resources, which in turn had an impact on individuals whose livelihoods depended on forest products, such as apiary activities.\n\n• Developing methods that aim to ensure production and nutritional sensitivity and remain resistant to frequent and unforeseen shocks in the agricultural sector, including the livestock and crop sub-sectors, in particular, it is necessary to identify and work on mitigation techniques to lessen the impact of typical crop and livestock-related shock and stress as well as unexpected onsets of damage.\n\n• Installing early warning systems that automatically launch adaptable response mechanisms at the necessary scale through the development of coordination and links among institutions engaged in food and nutrition security analysis, early warning, and response; offering technical backups to raise awareness; and starting vulnerable targeted life-supporting programs, such as rural safety nets, are necessary in this regard.\n\n• It is thought that bolstering local institutions and public services like research facilities, cooperatives, credit and saving institutions, veterinary services, input suppliers, farm loan providers (banks), crop insurance provisions, and comparable others will significantly help to raise household resilience over the long term.\n\n• Given that this study’s social capital dimension of resilience revealed a poor relationship among households, it is worthwhile to build social cohesiveness as a long-term strategy. Technical and political participation with adequate attention is necessary at the right moment to create chances for activities that diversify revenue.\n\nThe study generally advises that any efforts by the government and other development actors to implement policies and programs should prioritize and build on the critical aspects of food security resilience so that households can successfully avoid short-term shocks and stresses and strengthen their long-term development plans and their implementation success.\n\n\nAuthor contributions\n\nThe research conceptualization, methodological refining, analytical software choice, data curation, analysis, investigation, and writing were handled by Mr. Shibru Zerihun; and visualization, reviewing, and supervision were carried out by Dr. Mesay Mulugeta and Dr. Meskerem Abi. All authors have read and agreed to the published version of the manuscript. Authorship must be limited to those who have contributed substantially to the work reported.",
"appendix": "Data availability\n\nDataverse: ‘Rural Household Resilience to Food Insecurity in Majang Zone, Southwestern Ethiopia’, https://doi.org/10.20372/aau_rdm/EAOGKA (Zerihun et al., 2023).\n\nThis project contains the following underlying data:\n\nFourteen data files, seven in excel and seven in STATA DTA formats, on each of the seven resilience components and the overall resilience index. The data files AC, ABS, IFA, S, SC, ATA and AP refer to data of adaptive capacity, access to basic services, income and food access, sensitivity, social capital, agricultural technology adoption and asset possession components respectively. Additionally, a word data file containing transcripts from FGDs and KIIs, and a PDF data file of informed consent from Institutional Review Board (IRB) of Addis Ababa University College of Development Studies have been stored.\n\nThis project contains the following extended data: Interview guides for FGDs and KIIs, questionnaire and signed IRB letter.\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 would like to thank Gambella and Addis Ababa Universities for helping to partially sponsor the study. I offer heartfelt gratitude to the administrations and sector offices of the Majang Zone and District facilitating easy data access at all levels and providing available information throughout data gathering. 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}
|
[
{
"id": "276358",
"date": "28 May 2024",
"name": "Shishay Kahsay weldearegay",
"expertise": [
"Reviewer Expertise Food security",
"socio-economic",
"poverty",
"impact 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, resilience should be defined and underpinned with a strong theoretical foundation. from the point of view of the document, it does not show resilience is a problem in the study area. some empirical studies are outdated try to use the latest articles and be consistent in the use of &, and, and. In addition, I did not see a strong justification for the linkage between food insecurity and resilience in the introduction. Methods 1. if possible try to add agricultural productivity to the area 2. first off, is an informal word use other formal words in the sample size determination line one 3. I do not agree, with the sampling of villages, the number of the target population may increase in Mengeshi however the number of sites should be similar with Godere. 4. clearly show us your unit of analysis 5. from which do you take 0.6 for p values, who reported 60% of the population is food insecure 6. how representative your sample is? because you omitted 14 respondents why don't you add others who fulfill the inclusion criteria? 7. what is your justification for using FCS and HFIAS, why not others? and why not use one food security measurement? 8. why don't you form the FGD separately female and male? because females may fear expressing their opinions in front of males. 9. secondary data should be from reputable journals not published journals 10. your output variable is not continuous rather it is scale/truncated, so how do you test normality 11. where is your qualitative data, I have not seen any, please incorporate your qualitative data or omit it from the methods section.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? 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": "276355",
"date": "04 Jul 2024",
"name": "Fentahun Tesafa",
"expertise": [
"Reviewer Expertise Food and nutrition security",
"household resilience to food insecurity shocks",
"livelihood and poverty",
"value chain and market analysis",
"impact evaluation and adoption studies",
"agriculture and food system transformation",
"production economics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper provides empirical evidence on household’s resilience to food insecurity shocks and stressors in the context of rural settings. The manuscript addresses an important world issue that contributes to the current literature and policy debate in food and nutrition security as shock exposures of societies are continuously increasing nowadays. However, authors lack to show unequivocally the conceptual (analytical) framework used in the current study may limit the repeatability, besides their findings might be delimited to certain variables while ignoring important one(s). The results of your study may need to be further triangulated with findings of previous studies on the similar topic and a bit detailed in the discussion section.\nMinor comments: Slight edition may be required to use appropriate punctuation somewhere in the text, avoid repetition of similar statements in different places, and maintain coherence of ideas between paragraphs.\n\nAbstract\nThe abstract seems well articulated that reflects all pictures of the manuscript. The term “an increase of” found after “increased by….” along the first line on p.2 in the abstract seems a repetition to delete. Is there also a place in the keywords to consider other key variable(s) of interest like Ethiopia … instead of OLS and Econometrics?\nIntroduction In “Introduction” section authors tried to highlight the conceptual links between household resilience and food insecurity shocks, while limited empirical evidence to show gap(s) in extant literature that your study is expected to address concerning determinants and interdependencies. (1) I suggest a literature review following a briefer introduction that focuses on your findings in the result section and in discussion before the conclusion that ties back to these findings in relation to the literature. Minor comments: (2) The reference (FAO, 2006b) cited in the first paragraph along line 4 from the bottom needs to be (FAO, 2006a) as this author is cited here at the first time. (3) Along the line just below this citation, the semicolons separating unemployment; violence; and climatic shocks seem inappropriate, instead comma to use, and the same holds to others even along same line after COVID-19, …. (4) Citing authors at the initial of their statement can be stated as according to author (year), but this might not be if authors were cited at the end, unlike the one in paragraph 2 at the bottom, according to (FAO et al., 2020) needs to cancel “according to”. (5) Paragraphs 1 & 2 in the introduction part may be articulated as one, as the same idea is taken. Major comments (6) Could you include the conceptual (analytical) framework of your study somewhere appropriate to put may be between the Introduction and Method sections? Doing so may allow replication by others, besides clear and attractive for readers.\nMethods\nIn the Description of the study area, NTFPs found in paragraph 2 on p4 along line 3 from the bottom is an abbreviation to be extended here as seen at the first time. In the Design section, the term “Agency” end of The Food and Agriculture Agency (FAO) along line 5 of paragraph 1 on p.5 needs to be replaced by Organization. Others may require rephrasing for the flow of ideas clear to be readers. For e.g., in the Sample size determination section, the statement “To compute the respondent households … each villages was used” in paragraph 1 on p5 may need to rephrase as “To determine the number of sample households to be drawn from each village proportional to share of total population, we used the estimated population size of households in the year 2022”. Instead of the respondent households, it seems the number of households that could be computed. In the same sentence, unless 2022 is qualified with year, may not be clear whether this represents year or number of households. Following statement “The 10 Villages’ total population and households totaled 15826 and 3557, respectively” also requires little revised as “The population size of the 10 villages totaled 15826 people and 3557 households”. Figures, Tables and Equations shall also be cited in the main text. For instance, Equations (1) and (2) on p.5 were not cited anywhere in the text. In FGDs section, some statements may not be important to include like “The corresponding author has worked as a postgraduate research advisor and has experience conducting and publishing research publications. The four male data collectors have all earned BSc degrees and have been employed by Ethiopia’s Central Statistics Authority (CSA) as contractual data collectors” once authors stated “experienced data collectors with BSc degree were employed to facilitate the discussion and data collection process”. Major comments To this end, may you summarize the data collection methods (surveys, FGDs, KIIs and desk review) in one paragraph in a way to articulate which method is appropriate for what, instead of each discussed separately? Moreover, the FGDs and KIIs as qualitative approaches can be applied in two ways: (1) as means to verify the data collection instruments (questionnaires) that will be used for quantitative research in the main survey, that is, often adopted in exploratory sequential, mixed methods research design; and (2) once the main survey and quantitative analysis carried out, the qualitative approaches will then be applied onto certain households selected based on the key findings of the main survey aiming to verify the results qualitatively, which is common in explanatory mixed methods research design. This suggests the data collection section could be little detailed in the way to address this issue.\n\nData analysis\nAs understood from the beginning Data analysis section on p.6, why resilience was used in this study as an indicator of food security but not as household’s capacity to food insecurity needs a bit detailed. This may however be captured in your conceptual framework that supposed to prepare. Equation (3) needs a bit clarified, as some parameters seem inappropriately merged. Need to modify Equation 5 into Equation 7 that found on p.9 along line 4 in paragraph 2.\nResult and discussion\nMoving along last line of paragraph 1 in the “Result and discussion” section, we found … highest dependency ratio (DR) approaching 400%, may be confusing for readers how it could be above 100%, suggests a bit detailed how DR is operationally defined/used in your study. May be good if your descriptive results on socioeconomic characteristics of households are supported with tabular (or graphical) presentation.\nResults obtained from principal component analysis On p10 in paragraph 2 along the last 5 lines, it is clear that among six continuous-scale factors used to estimate IFA index, you found only off-farm income excluded based on minimum retention criterion. If so, it would be five variables seen in Table 1 instead of being four; even this was also stated as three in another statement at the end …. since each of the three …. This three needs to be modified as five instead. However, from the eigebvalue of 2.31, it seems only four variables treated in the final estimation of IFA index. So, may be two variables excluded in the equation. Some of the results discussed in this paragraph were not presented in Table 1, e.g. correlation of each transformed variable with IFA latent construct.\n\nOnce Equation 9 on p11 represents the weighted average used to estimate AP pillar, why it was divided by 4 (i.e. by the number components retained) needs little detailed. The same comment holds for other equations that retained above one component. Figure 2 on p17 needs to be modified as legends and some points within the figure seem dismantled and what Serial 1 repeatedly written in the figure represent are not clear.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? 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/13-162
|
https://f1000research.com/articles/11-1050/v1
|
14 Sep 22
|
{
"type": "Systematic Review",
"title": "Quality assessment of systematic literature on uterine fibroids: a systematic review",
"authors": [
"Mary Okesola",
"Julius Okesola",
"Olubanke Ogunlana",
"Israel Afolabi",
"Julius Okesola",
"Olubanke Ogunlana",
"Israel Afolabi"
],
"abstract": "Background: A systematic literature review (SLR) is a research methodology that examines data and findings of other authors relative to specified research questions (RQ), collects multiple research studies, and summarises them to answer a research question using rigorous methods. Many SLRs have been published on uterine fibroids (UFs) in the last two decades but there is a dearth of knowledge on assessment of the quality to determine the reliability of results. Methods: This study employed the SLR method to identify available SLRs published on UFs. Dybå and Dingsøyr quality standards and dichotomous grading scales were employed to determine the quality of primary studies. On February 3rd, 2022, an auto search was conducted twice over Citeseer, EBSCO, ACM, Springer Link, IEE Computer society digital library, and Scopus using 17 search strings. Two teams independently screened papers and compared notes with the inclusion/exclusion criteria. 11 criterial were adapted to evaluate the quality of the SLR’s. Results: 33 SLRs were subjected to data extraction after inclusion/exclusion criteria. Answers to our primary research question was positive as the aims and contexts of the SLRs are generally clear and the methodologies employed are all inclusive. The research outputs of the primary studies are valid and justifiable as their research statements were clear and findings unambiguous. Although some studies failed some quality criteria, answers to all RQs were affirmative as the percentage scores of the studies on each of the quality conditions is favourably high. Conclusions: The auto search may be incomplete because some qualified SLRs may have been missed as the choice of search strings was limited and may have omitted terminologies. Notwithstanding, with average quality scores of 83% in reporting, 81.2% in rigour, and 79% in credibility, this study concludes that majority of the meta-analysis published so far on UF are valid and reliable.",
"keywords": [
"Medicine",
"meta-analysis",
"Past Studies",
"Quality Condition",
"Quality Assessment",
"Structured Review",
"Systematic Literature Review",
"Uterine Fibroids."
],
"content": "Introduction\n\nEvidenced-based studies started in medicine and became generally accepted as expert opinions based on results obtained from scientific experiments appears more reliable than those obtained from medical advice.1 Evidence here refers to a combination of best quality scientific works on a topic or research question. A systematic literature review (SLR) is a main method of this synthesis. It is a methodologically rigorous review of research results aimed not just at aggregating all existing evidence on a research question but also targeted at supporting the development of evidence-based guidelines for practitioners.1 Its use in software engineering and computer sciences subject areas, and its application has been increasing since 20041 as it considers findings from varying sources to form a position. Notwithstanding this popularity, the quality of the SLRs’ results should be assessed to determine both the level of confidence to be placed on them as well as the required recommendations to offer.2\n\nAs an instance, we have two schools of thought regarding gynaecological conditions in pregnancy. Myomectomy during ceserean section (CS) was condemned for severe bleeding and potential hysterectomy. Whereas, there are advocates for myomectomy at sittings of surgery three to six months after delivery to promote uterus involution, myomas shrinkage, and reduce operative time and blood loss.3,4 Nowadays, gynaecologists are advocating for the removal of myoma due to its minimal operative time, mild (or no) complications to call for a second surgery, and gross reduction in the total cost of myomas surgery. Systematic literatures have reviewed the perioperative complications of caesarean myomectomy (CM) and found increased operative time and drop in haemoglobin in cases of caesarean myomectomy.3 in their Evidenced-based reviews, Arowolo et al.,5 also argued that Uterine artery embolization advantages over surgery is short-term and that the benefits were similar on the mid- and long-term. However, the qualities of these studies have not been evaluated to raise the confidence in their findings and reduce bias in their review process for better interpretation of results.\n\nPrimary studies assessment can actually be complicated since there is no specific definition for “quality”.2,6 However, some notable researchers such as Jadadet et al.,7 Dybå and Dingsøyr,8 Kitchenham et al.,,9 and Sjoberg et al.,10 have successfully developed guidelines and tools specifically meant for the purpose, but much more concerned about what the results are, their validity, and whether or not they will be locally useful.6,11 Since the “quality of a study is closely linked to the research methods used and the validity of the findings generated by the study”,10 this study comprehensively reviewed the quality of the past available related studies published by evaluating various methods used by primary studies of each of the selected SLRs to clearly established the validity of their results. Hence, the authors did not place a date or year bound/limit on the search engine in other to have a sizeable number of primary studies to work with having realized that not much SLRs has been done on leiomyomas or myomas to date – February 3rd, 2022.\n\n\nPast related works\n\nQuality is regarded as “an extent to which systematic errors or bias may be prevented through the review and analysis of primary studies”.12 Yet, researchers are less interested in quality assurance and assessment as only very small numbers of SLRs aimed at the quality assessment of their primary studies.\n\nOrlando et al.,13 employed the National Institutes of Health Study Quality Assessment tools to perform quality assessment of SLR towards identifying the identifying best practices for non-hysteroscopic myomectomy for women with myomas but still desire future fertility. Their initial searches on selected databases returned 2,163 studies out of which only 51 met their inclusion criteria. The authors noted that the route of non-hysteroscopy myomectomy and intraoperative uterine artery occlusion did not significantly affect pregnancy rates or outcomes. Giving a clear insight into patient selection and intraoperative techniques for non-hysteroscopy myomectomy, the study recommended further research with well-designed clinical trials to highlight the relationships between myoma characteristics and reproductive outcomes.\n\nNotwithstanding its high prevalence, the fibroids psychosocial impact was yet to be compared with other chronic conditions and evaluated across the quality-of-life indicators. Hence, Go, Virginia et al.,14 thoroughly appraised the available evidence against the UF psychosocial burden in premenopausal women and contrasted the quality of life validated and symptom scores before and after treatment. The authors engaged three independent reviewers to screen various abstracts and tiles of selected SLRs towards obtaining full text studies from notable databases for further assessment. They observed that quality-of-life scores in UF patients were usually low at baseline compared to after treatment and that, there are therapeutic success and improvement of both physical and emotional symptoms after treatment.\n\nTranoulis, Anastasios15 auto-searched some digital libraries and broad indexes to produce the first meta-analysis that could provide a convincing overview of efficacy and safety of laparoscopic uterine artery occlusion (LUAO). Comparing the long and short-terms morbidity of laparoscopic myomectomy (even without LUAO), the study modified the Jadad score to assess the quality of Randomized controlled trials (RCTs) but employed methodologic index for nonrandomized studies to evaluate the quality of observational studies (OSs).\n\nsymptomatic uterine myomas, two independent researchers in Liu, Lu16 carried out data selection to perform a comparative study of the clinical outcomes of uterine artery embolization and those of high-intensity focused ultrasound (HIFU) ablation in women with myomas. The study quality was assessed using the “Cochrane Handbook for Systematic Reviews” while the pooled mean difference and relative risks were both calculated at 95% confidence interval for the respective continuous data and dichotomous data. Although, the authors could not ascertain that HIFU is far better for desired pregnancy considering the confounding factors, they postulated that uterine artery embolization (UAE) lowers both postoperative re-intervention rate and pregnancy rate for women with uterine myomas and provide more significant alleviation of symptoms and improvement in quality of life.\n\n\nMethods\n\nResearchers have built several guidelines and checklist good enough for quality assessment in SLR. While majority of these tools rally round the validity of the research outcomes, a few others look more at the methodological characteristics of the study. Jadad et al.,7 and CASP17 are popular tools and commonly adapted in Sociology and Software Engineering18 but their scales are not directly applicable to Medicine. Hence, following the raising of the study questions and review of past related studies, Dybå and Dingsøyr8 11 criterial were adapted in this study to evaluate the quality of the SLR’s primary studies. In which case, each of these criteria, graded with a dichotomous scale (Yes=1; No=0), is categorized into the following four main issues for ease of quality assessments.\n\n• Reporting: Criteria (1, 2, and 3) are about the quality of the report of research aims, rationale, and context.\n\n• Rigor: Criteria (4, 5, 6, 7, and 8) have to do with the objectivity of the research methods used to establish the validity of data collection tools and the analysis methods, and hence the trustworthiness of the findings.\n\n• Credibility: Criteria (9 and 10) are connected directly to assess the credibility of the research methods to ensure the validity of the findings.\n\n• Relevance: Criterion 11 is concerned with the relevance of the study to the research community.at large.\n\nThe primary research question (RQ) is “How reliable are the meta-analysis in the Uterine Fibroids”?\n\nThis question is broken down into the following secondary questions to address the study objectives\n\n• RQ1: Are the SLRs studies centred on clear aims and description of context?\n\n• RQ2: How inclusive are the methodologies employed in the primary studies?\n\n• RQ3: Are the study output valid?\n\nWe conducted three independent searches on February 3rd and 4th 2022, and all were without publication date restriction. Our initial auto searches of five notable digital libraries and broad indexes for relevant SLRs (Citeseer, EBSCO, ACM,Springer Link, IEE Computer society digital library) did not return much related studies. Our second Search was over Scopus and returned 153 studies fleshed SLRs but PowerPoint templates or lecture notes. This search was complicated as it was done 17 times using the underlisted set of search strings (SS) since Scopus does not allow very simple construction of complex searches:\n\n1. “Fibroid OR leiomyomas OR myomas” AND “review of studies”\n\n2. “Fibroid OR leiomyomas OR myomas” AND “structured review”\n\n3. “Fibroid OR leiomyomas OR myomas” AND “systematic review”\n\n4. “Fibroid OR leiomyomas OR myomas” AND “literature review”\n\n5. “Fibroid OR leiomyomas OR myomas” AND “literature analysis”\n\n6. “Fibroid OR leiomyomas OR myomas” AND “in-depth survey”\n\n7. “Fibroid OR leiomyomas OR myomas” AND “literature survey”\n\n8. “Fibroid OR leiomyomas OR myomas” AND “meta-analysis”\n\n9. “Fibroid OR leiomyomas OR myomas” AND “past studies”\n\n10. “Fibroid OR leiomyomas OR myomas” AND “subject matter expert”\n\n11. “Fibroid OR leiomyomas OR myomas” AND “Analysis of research”\n\n12. “Fibroid OR leiomyomas OR myomas” AND “empirical body of knowledge”\n\n13. “Fibroid OR leiomyomas OR myomas” AND “overview of existing knowledge”\n\n14. “Fibroid OR leiomyomas OR myomas” AND “body of published research ”\n\n15. “Fibroid OR leiomyomas OR myomas” AND “review”\n\n16. “Fibroid OR leiomyomas OR myomas” AND “literature analysis”\n\n17. “Fibroid OR leiomyomas OR myomas” AND “literature listing”\n\nHowever, our third search, which was limited to the source - “Science Direct” only, was simple and straightforward as the underlisted complex searches were applied only once using the independent search strings SS1 and SS2 in isolation:\n\nSS1 Title, abstract or author-specified keywords\n\n(leiomyomas OR myomas) AND (“literature review” OR “systematic review” OR “structured review” OR “review of study” OR “literature analysis” OR “in-depth survey” OR “literature survey”)\n\nSS2 Title, abstract or author-specified keywords\n\n(leiomyomas OR myomas) AND (“meta-analysis” OR “past studies” OR “subject matter expert” OR “Analysis of research” OR “empirical body of knowledge” OR “overview of existing knowledge” OR “body of published research”)\n\nHaving noted that not many SLRs are available on Fibroid studies, all searches were conducted without publication date restrictions. However, the searches were limited to document title and keywords, which usually carry the research subjects. To avoid human error, two researchers were engaged to independently conduct the literature search, and their results were compared for completeness. Searches over Scopus are mainly not fully fleshed out but they are still relevant to this study as their output helps to validate our search process when compared with papers found in our last search. Since 96 of 98 fully fleshed SLRs found therein were part of the total SLRs found in the third search, we adjudge our search process and procedure to be okay and accurate.\n\nThe results of the three searches were integrated together to have 169 papers in total which we eventually subjected to initial screening over their title, abstract, and keywords. Sorting on the document title, the total papers was reduced to 65 having removed 104 articles including the 98 SLRs found in Scopus to avoid duplication since they are also found in Science Direct (our third search). We assume that the abstract or title of any quality papers should contain at least one of the search strings. Hence, searching over both the title and abstract columns to exclude papers that have no abstract19 or those that exclude literature review or any of the search strings (SS), another 12 articles were removed and the total SLRs were further reduced to 53, all of which were subsequently subjected to a more detailed assessment:\n\nThese 53 SLRs were electronically downloaded and two teams of two members each were formed to screen the papers for possible exclusion or inclusion. Consequently, the teams compared their notes to prevent false acceptance or false rejection, and differences were addressed following the underlisted exclusion criteria:\n\n• The SLR is not fully fleshed but a mere research or lesson note.\n\n• The topic is medicine or surgery and not related to Fibroid nor discusses systematic/literature reviews.\n\n• The SLR followed a vague search process.\n\nThree papers6,20,21 were rejected in this process for not being full-fleshed research publications, but a mere research/lesson note or PowerPoint template. 15 SLRs were excluded based on unrelated topics or failure to discuss systematic literature but dissimilar domains like surgery or Microbiology. Similarly, two other papers22,23 did not follow a defined search process and were dropped to have just 33 SLRs subjected to data extraction (Figure 1).\n\nA similar procedure to data selection was followed to extract data and identified the SRSs presented on Table 1. As a quality assurance measure, the following parameters were identified for each of the selected papers:\n\n• The publication date/year (to show how current the SLRs)\n\n• The type of the document (journal, workshop, book chapter, conference).\n\n• The number of primary studies in the SLR (as stated by the author).\n\n• The aspects of UF studied\n\nThis study employed the Dybå and Dingsøyr7 criteria to evaluate the quality of the selected SLRs.24,25 The choice of this set of criteria was because it contains 11 criteria checklists (as against others with fewer criteria) and covers all the main aspects of any research quality – reporting, credibility, relevance, and rigor. Adapted to this work, the selected SLRs are therefore independently assessed with the following criteria:\n\nQ1 Does the study answer the research questions defined or presents the results in a clear way?\n\nQ2: Is the research aim clearly stated?\n\nQ3: Is the context where the study was conducted adequately described?\n\nQ4: Was the study appropriately designed to address its aims and objectives?\n\nQ5: Was the recruitment strategy to drive the research aim appropriate?\n\nQ6: Were there control group(s) to compare with the treatments?\n\nQ7: Was the data collection method good enough to address research issues?\n\nQ8: Was the data analysis necessarily difficult?\n\nQ9: Has the relationship between researcher and participants been adequately considered?\n\nQ10: Is the statement of findings clearly stated?\n\nQ11: Is the research valuable to practice or research interest?\n\nA dichotomous scale was used to score and grade the questions. In which case:\n\nOur quality assessment procedure is like the one used for data selection (Figure 1) where:\n\n1. Two teams of two researchers each are formed and all the SLRs were individually assessed by each team.\n\n2. Each team member independent treated each study by answering the quality questions, giving adequate justification.\n\n3. The pair researchers compared their notes and agreed on terms to finalize their team results.\n\n4. To avoid human error, two teams of researchers were engaged to independently conduct the literature search. They placed their findings side-by-side to compare their results, settle disputes (if any), and produce a quality output as presented on Table 1.\n\n\nResults\n\nOur research questions are addressed on this section to ensure that they have all been answered and the SLRs’ qualities have been established. The results of the SLRs’ quality assessment are summarised on Table 2. The pass mark is fixed at 50%.\n\nThe answer to the RQ1 is positive as evidenced on Table 2 where the average score of Q1, Q2, and Q3 which particularly address RQ1 is 83% affirmative. Although five studies failed on Q2 and six failed on both Q1 and Q3 each, the percentage Scores of each on the quality condition (reporting) is favourably high. The failure on Q1 is traced to the five articles that properly addressed their research questions but failed to make their results/findings clear enough. Other failures were due to the articles that did not have clear research goals and those with obscure research contexts. Majority of the study representing 83% of the total samples, subjectively elucidated the (research) participants actions and made use of qualitative approaches, which is the most appropriate to address their study goals.\n\nYes, Most of the primary studies employed complete and all-encompassing research methodologies going by their QC score of 81% in “Rigour” on Table 2. This answer to RQ2 is determined by the status of “rigour”, which is an absolute function of the average scores of Q4, Q5, Q6, and Q8.\n\nAlthough 10 of the 33 primary studies did not employ appropriate recruitment strategies for their studies, and the research objectives of 11 are inappropriately designed. Exactly 10 are also silent on the control group(s) required to compare their research methods. However, all of them gave extensive description of their analysis processes and present sufficient data to support their findings (Q7 and Q8); they were simple in data collection and detailed in sample analysis.\n\nYes, the research outputs of the primary studies are valid and justifiable considering the 79% QC score on the research “credibility” even though, some of them truly failed on Q10 as their research statements were unclear and finding ambiguous. Some researchers did not actually consider their influence in their research questions formulation, sample collection and even their choice of location (Q9), but this is limited to only five primary studies where the researchers disclosed their possibilities of being biased. Hence, adequate recognition was given to the relationship between the researcher and the participants\n\nWe may have missed some qualified studies that used other terminologies to describe their literature review. Notwithstanding, this cannot be major as our search strings did not leave out any related terminologies found in every literature reviewed except “research aggregation” and “study/research synthesis” which we stumbled on at the tail end of this study Future researchers should take notes of these terminologies to avoid omission of qualified SLRs for review.\n\n\nConclusion\n\nAll the SLRs passed all the quality questions (Table 2) with the lowest in Q4. They also met and greatly surpassed all the quality conditions (QC) to clearly confirm that the primary studies are valid and of good quality. Therefore, answer to our primary (RQ) raised is affirmative; the meta-analysis in the Uterine Fibroids are very reliable. However, the SLRs needed to appropriately design their studies to be specific on their goals and objectives. They should also be explicit on the control groups with which their treatments and research methods are compared.\n\nIt is important for auto search to be complete and error free for reliable outputs and valid findings. When planning future studies therefore, the researchers should extend their search strings to include other terminologies that may have been missed in this study.\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\nReporting guidelines\n\nFigshare: PRISMA checklist for ‘Quality assessment of systematic literatures on uterine fibroids: a systematic review’, https://doi.org/10.6084/m9.figshare.20654010.v1.55\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "Acknowledgment\n\nThis study was supported by Covenant University, Ota, Nigeria in paying the APC for this study.\n\n\nReferences\n\nKitchenham B, Pearl Brereton O, Budgen D, et al.: Systematic literature reviews in software engineering - A systematic literature review. Inf. Softw. Technol. 2009; 51(1): 7–15. Publisher Full Text\n\nOkesola JO, Okokpujie KO, Adebiyi AA, et al.: QUALITATIVE ASSESSMENT OF SYSTEMATIC LITERATURES IN SOFTWARE ENGINEERING. J. Theor. Appl. Inf. Technol. 2018; 96(18): 6018–6027.\n\nBaby HA, et al.: Myomectomy during caesarean section: Safety and feasibility of the procedure. Bangladesh J. Obstet. Gynecol. 2015; 30(1): 10–14. Publisher Full Text\n\nSparić R, Guido M, Tinelli A: Miomektomia podczas cieogonekcia cesarskiego i mozliwe czynniki ryzyka przyjeeogonekcia do oddziału intensywnej terapii-badanie retrospektywne. Ginekol. Pol. 2015; 86(10): 731–736. 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Publisher Full Text\n\nPritts EA, Parker WH, Brown J, et al.: Outcome of occult uterine leiomyosarcoma after surgery for presumed uterine fibroids: A systematic review. J. Minim. Invasive Gynecol. 2015; 22(1): 26–33. PubMed Abstract | Publisher Full Text\n\nMourgues J, Villot A, Thubert T, et al.: Uterine myomas and lower urinary tract dysfunctions: A literature review. J. Gynecol. Obstet. Hum. Reprod. 2019; 48(9): 771–774. PubMed Abstract | Publisher Full Text\n\nLewis EI, Chason RJ, Decherney AH, et al.: Novel hormone treatment of benign metastasizing leiomyoma: An analysis of five cases and literature review. Fertil. Steril. 2013; 99(7): 2017–2024. PubMed Abstract | Publisher Full Text\n\nKoo YJ, et al.: Pregnancy Outcomes and Risk Factors for Uterine Rupture After Laparoscopic Myomectomy: A Single-Center Experience and Literature Review. J. Minim. Invasive Gynecol. 2015; 22(6): 1022–1028. Publisher Full Text\n\nMaheux-Lacroix S, Li F, Laberge PY, et al.: A Systematic Review of Imaging for Polyps and Leiomyomas in Women with Abnormal Uterine Bleeding. J. Minim. Invasive Gynecol. 2017; 24(7): S60–S61. Publisher Full Text\n\nLete I, González J, Ugarte L, et al.: Parasitic leiomyomas: A systematic review. Eur. J. Obstet. Gynecol. Reprod. Biol. 2016; 203: 250–259. PubMed Abstract | Publisher Full Text\n\nLee D, Lee JR, Suh CS, et al.: A systematic review and meta-analysis comparing single port laparoscopic myomectomy with conventional laparoscopic myomectomy. Eur. J. Obstet. Gynecol. Reprod. Biol. 2019; 239: 52–59. PubMed Abstract | Publisher Full Text\n\nKrungkraipetch K: Laparoscopic myomectomy with simultaneous uterine artery ligation: A literature review of prospective studies. J. Reprod. Heal. Med. 2016; 2(2): 67–73. Publisher Full Text\n\nGoyal M, et al.: Cesarean myomectomy in the last ten years; A true shift from contraindication to indication: A systematic review and meta-analysis. Eur. J. Obstet. Gynecol. Reprod. Biol. 2021; 256: 145–157. PubMed Abstract | Publisher Full Text\n\nNair S, Gill AJ, Dhupar N, et al.: 38. Fumarate hydratase-deficient uterine leiomyoma – Case report and literature review. Pathology. 2019; 51: S159–S160. Publisher Full Text\n\nA. AdvancingM. InvasiveG. Worldwide: AAGL Practice Report: Practice Guidelines for the Diagnosis and Management of Submucous Leiomyomas. J. Minim. Invasive Gynecol. 2012; 19(2): 152–171. PubMed Abstract | Publisher Full Text\n\nZhang Y, Ma D, Li X, et al.: Role of Barbed Sutures in Repairing Uterine Wall Defects in Laparoscopic Myomectomy: A Systemic Review and Meta-Analysis. J. Minim. Invasive Gynecol. 2016; 23(5): 684–691. PubMed Abstract | Publisher Full Text\n\nRusso M, Suen M, Bedaiwy M, et al.: Prevalence of Uterine Myomas Among Women with 2 or More Recurrent Pregnancy Losses: A Systematic Review. J. Minim. Invasive Gynecol. 2016; 23(5): 702–706. Publisher Full Text\n\nSanders AP, Chan WV, Tang J, et al.: Surgical outcomes after uterine artery occlusion at the time of myomectomy: systematic review and meta-analysis. Fertil. Steril. 2019; 111(4): 816–827.e4. Publisher Full Text\n\nVerpalen IM, et al.: Magnetic resonance-high intensity focused ultrasound (MR-HIFU) therapy of symptomatic uterine fibroids with unrestrictive treatment protocols: A systematic review and meta-analysis. Eur. J. Radiol. 2019; 120: 108700. PubMed Abstract | Publisher Full Text\n\nSizzi O, et al.: Assessing the risk of laparoscopic morcellation of occult uterine sarcomas during hysterectomy and myomectomy: Literature review and the ISGE recommendations. Eur. J. Obstet. Gynecol. Reprod. Biol. 2018; 220: 30–38. PubMed Abstract | Publisher Full Text\n\nShazly SAM, et al.: Hysteroscopic Morcellation Versus Resection for the Treatment of Uterine Cavitary Lesions: A Systematic Review and Meta-analysis. J. Minim. Invasive Gynecol. 2016; 23(6): 867–877. PubMed Abstract | Publisher Full Text\n\nQin H, Lin Z, Vásquez E, et al.: High soy isoflavone or soy-based food intake during infancy and in adulthood is associated with an increased risk of uterine fibroids in premenopausal women: a meta-analysis. Nutr. Res. 2019; 71: 30–42. Publisher Full Text\n\nVan Der Kooij SM, Bipat S, Hehenkamp WJK, et al.: Uterine artery embolization versus surgery in the treatment of symptomatic fibroids: A systematic review and metaanalysis. Am. J. Obstet. Gynecol. 2011; 205(4): 317.e1–317.e18. Publisher Full Text\n\nOkesola J, Okesola M, Ogunlana O, et al.: PRISMA_2020_checklist.docx. figshare. Journal Contribution. 2022. Publisher Full Text"
}
|
[
{
"id": "165452",
"date": "31 Mar 2023",
"name": "Mary Ann Lumsden",
"expertise": [
"Reviewer Expertise I am retired from active research but undertook several RCTs involving treatment of uterine fibroids."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nA systematic review of systematic reviews is an interesting concept and should be helpful.\nHowever, it is always important to remember that all systematic reviews are only as good as the studies included in them and the methodologies used.\nThe authors state that they give more account to the results and their plausibility than the methodology and I feel this is rather a pity as it misses an opportunity to do something really meaningful.\n\nIt was done very quickly which surprised me and I do not generally use these databases for a search such as this. However, the use of the 11 criteria is certainly valid but I would like to have had more detail on this and how it was assessed.\nI do not think it true that all SLRs do not assess quality, particularly those in the better journals. I also wondered about the use of the examples of choosing non-hysteroscopic myomectomy which I would rate well and the 2nd on pychosocial burden.\nAssessment of non-randomised studies is fraught with problems and are unlikely to be high quality studies by definition. Thus drawing conclusions from an SLR is unlikely to be useful. In addition there is an incorrect reference (No 16 which I think should perhaps be 26.\nRQ2 worried me considerably: 'Although 10 of the 33 primary studies did not employ appropriate recruitment strategies for their studies, and the research objectives of 11 are inappropriately designed. Exactly 10 are also silent on the control group(s) required to compare their research methods. However, all of them gave extensive description of their analysis processes and present sufficient data to support their findings (Q7 and Q8); they were simple in data collection and detailed in sample analysis.' I can't help feeling that any conclusions drawn here would be meaningless.\nOverall this is a methodology worth developing further but I think I think must include consideration of methods use and not just results to be meaningful.\nI look forward to hearing more about the ideas in this article.\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",
"responses": [
{
"c_id": "11099",
"date": "13 Apr 2024",
"name": "Julius Okesola",
"role": "Author Response",
"response": "… In addition, there is an incorrect reference (No 16 which I think should perhaps be 26. Now corrected Overall this is a methodology worth developing further but I think it must include consideration of methods use and not just results... Consideration of Methods have been addressed in the first paragraph of the ‘Method’ section where Dybå and Dingsøyr 8 criterial which are popularly considered suitable in Medicine were adapted in this study."
}
]
},
{
"id": "215409",
"date": "18 Oct 2023",
"name": "Andrea Etrusco",
"expertise": [
"Reviewer Expertise Obstetrics and Gynecology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 with great interest the Manuscript titled “Quality assessment of systematic literature on uterine fibroids: a systematic review”, which falls within the aim of this Journal.\n\nIn my honest opinion, the topic is interesting enough to attract the readers’ attention. Nevertheless, authors should clarify some point and improve the discussion citing relevant and novel key articles about the topic.\nAuthors should consider the following recommendations:\nManuscript should be further revised by an English language editor;\n\nFIGO has recently updated the classification of uterine leiomyomas, giving to FIGO type 3 myoma a different importance which can open up new therapeutic scenarios. The study does not cite the only meta-analysis present in the literature (PMID: 37183601), and the only systematic review present in the literature (PMID: 37568356) in this regard. Your article should be expanded with these two revisions.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": [
{
"c_id": "11098",
"date": "13 Apr 2024",
"name": "Julius Okesola",
"role": "Author Response",
"response": "Manuscript should be further revised by an English language editor: The article is now being reviewed by an English Language Editor. Your article should be expanded with these two revisions of FIGO publications - PMID: 37183601 and PMID: 37568356. It is practically impossible for our study to be expanded with these two studies as both were published years after our auto search was conducted. The first was published on May 15 2023 while the other was published on July 27, 2023. Whereas, our auto search was conducted on February 3rd and 4th, 2022 – almost one and half years earlier."
}
]
}
] | 1
|
https://f1000research.com/articles/11-1050
|
https://f1000research.com/articles/12-1504/v1
|
27 Nov 23
|
{
"type": "Research Article",
"title": "Strategic palmar trimming before conventional shoeing shows potential for managing underrun heels in horses",
"authors": [
"Chanoknun Poochipakorn",
"Kanokpan Sanigavatee",
"Thita Wonghanchao",
"Onjira Huangsaksri",
"Metha Chanda",
"Chanoknun Poochipakorn",
"Kanokpan Sanigavatee",
"Thita Wonghanchao",
"Onjira Huangsaksri"
],
"abstract": "Background: This study aimed to investigate the potential of strategic palmar trimming before conventional shoeing for managing hoof malconformation in horses with underrun heels. Methods: Eleven affected horses were divided into control (5 horses with 14 defective hooves) and experimental (6 horses with 16 defective hooves) groups. The experimental group underwent strategic palmar trimming before conventional shoeing, while the control horses received regular trimming before traditional shoeing. Dorsal hoof wall angle (DHWA)/heel angle (HA) ratios, heel-bulb distance, and six parallel lines indicating solar surface dimension were determined before, and after 5, 10, 15, 20, 25, and 30 weeks of the different farriery protocols. Palmar trimming distance was only measured in experimental horses. Results: A group-by-time interaction was observed for DHWA/HA ratios and solar surface dimension. Separate effects for group and time were observed in the heel–bulb distance. A modification in hoof conformation was detected at 25-30 weeks only in horses in the experimental group, including decreases in DHWA/HA ratio, heel–bulb distance, and palmar trimming distance, coinciding with an increase in palmar width of trimmed hooves. Conclusions: Different trimming protocols produced a different effect on hoof conformation. Therefore, tactical remedial trimming can potentially control poor hoof conformation in horses with underrun heels.",
"keywords": [
"heel angle",
"horse",
"strategic palmar trimming",
"shoeing",
"solar surface",
"underrun heels"
],
"content": "Introduction\n\nUnderrun heels, also known as collapsed heels or long toe–low heel conformation, are among the most common hoof distortions causing poor performance in horses (Bigham and Tabatabaei 2007). The condition is characterised by a palmar angle that is more than 5° smaller than the hoof angle (Dabareiner and Carter 2003, Hunt 2012, Sigafoos 1990). The hoof wall grows distally from the coronet with a uniform slope from toe to heel (O’Grady 2008). The dorsal hoof wall angle (DHWA) and heel angle (HA) should thus theoretically be the same. However, the HA is generally smaller than the DHWA. A higher likelihood of wear at the heel than at the toe region during locomotion might contribute to angle disparity (Barrey 1990, Moleman et al. 2006).\n\nIn principle, the palmar hoof region has an important role in shock absorption and management of the mechanical force applied to the hoof structure (Eliashar 2007, Hood et al. 2001, O’Grady 2012). Repetitive disproportionate loading on the palmar area during movement is thought to result in underrun heels in horses (Hunt 2012). In a severely distorted hoof, the horn tubules in the heel region are bent forward and run parallel to the ground surface (Dabareiner and Carter 2003). As a result, this forward shift of the weight-bearing surface causes mechanical overloading of the palmar region and may generate bruising and chronic palmar pain (Hunt 2012). Moreover, repetitive overloading, concomitant with a low heel and interphalangeal joint dorsiflexion, creates a negative angle between the distal phalanx’s solar surface and the ground (Floyd 2010, O’Grady 2006). This negative angle may induce tissue injuries in the palmar region, thereby reducing its ability to dissipate the descending mechanical force during locomotion (Floyd 2010, Hunt 2012). Overloading also applies abnormal forces to the navicular bone and related apparatus. This induces degenerative changes in the navicular bone, leading to navicular syndrome (McGuigan and Wilson 2001, Wilson et al. 2001).\n\nThe management goal in horses with underrun heels is to establish a normal hoof capsule and increase the palmar angle, which will restore hoof function and exercise performance (Hunt 2012, O’Grady et al. 2018). Appropriate hoof trimming procedures have been shown to correct a negative palmar angle accompanied by a long toe–low heel conformation (Floyd 2010). After basic trimming, heart bar shoes, straight bar shoes, or shoeing with heel plates or wide-webbed heel shoes have been utilised to support regrowth and repair; however, the shape of these shoes make them unsuitable for long-term use in competition horses (Hunt 2012). Elevating the heel using a shoe with a built-in wedge pad to produce a normal hoof angle has also been used to correct this defect (Dabareiner and Carter 2003, Hunt 2012); however, this method may induce progressive overloading and lead to perpetually curved horn tubules (Hunt 2012).\n\nThe outcomes of underrun heel correction by various corrective shoeing approaches have been inconsistent. In this study, we proposed an alternative farriery protocol for managing underrun heels: strategic palmar trimming before conventional shoeing. The objectives of the present study were as follows: first, to evaluate the potential of the alternative farriery protocol to improve hoof conformation and palmar angle, and second, to investigate the estimated time required for this proposed method to improve hoof conformation variables in horses with underrun heels.\n\n\nMethods\n\nThe Ethics Committee for Animal Experiments of Kasetsart University approved all procedures included in this study (ACKU64-VET-040) on June 4, 2021. Since the study was conducted as routine shoeing practice in horses under veterinary supervision. Moreover, no invasive operation was performed in this study. There was, therefore, the most negligible probability of suffering during shoeing protocol throughout the study. The owners of the animals have signed an informed consent to use their animals in this study. This article is reported inline wih Animal Research: Reporting of in vivo Experiments (ARRIVE) guidelines (Sanigavatee 2023a).\n\nEleven client-owned horses (6 geldings and 5 mares, aged 13–19 years and weighing 420–480 kg) suffering from underrun heels were studied. These horses had underrun heels as determined by a difference of at least 5° between the toe and heel angles (Hunt 2012), which was the inclusion criterion for this study (Supplemental File 1; Table S1). They were excluded from this study if the injury or lameness occurred, causing severe lameness during the study period. Horses were recruited from equestrian riding clubs, including the Horse Lovers’ Club (13.995917138209828, 100.68551338185088), Checkmate Horse Club (13.976257409277178, 100.70805959728767), House of Horse riding club (13.812821261748075, 100.78691136835704), and Bang Phli riding school (13.597609837219945, 100.6835924548628). Affected horses were randomly divided into control (5 horses, 14 defective hooves) and experimental (6 horses, 16 defective hooves) groups. The number of horses was based on clinical cases that showed underrun heel conditions. In this study, four horses suffering from underrun heels in four hooves, six horses with underrun heels in both front hooves and a horse showing underrun heels in both real hooves (Extended data, Supplementary File 1; Table S1; Sanigavatee 2023b). To categorise into control and experiment groups, four horses that showed underrun heels in four hooves were distributed evenly to the control and experiment groups. Seven horses with underrun heels on either front or rear hooves were randomly selected by drawing from a hat as a lottery method. Thus the sample size (number of underrun-heeled hooves) in the control and experiment groups was 14 and 16, respectively. There were no differences in mean DHWA/HA between groups in this study (15.09 ± 1.28 (control) vs 16.69 ± 1.43 (experiment), p = 0.42). Before the trial, they were conventionally shod at four- to six-week intervals and usually performed aerobic exercise during 20–50 min on 2–4 days per week. The horses were kept in their usual environment. They were housed in individual stables (4 × 4 × 6 m3). Commercial pellets and Pangola hay were provided three times a day, and clean water was freely accessible. There were no therapeutic interventions before the start of the study. The horses were allowed to perform light exercise during the study if lameness was reduced to uneven gait or no foot pain.\n\nLameness examinations\n\nAll horses underwent a full lameness examination before the beginning of the study. Lameness was evaluated by three equine practitioners and scored from 0 to 5 according to the scale outlined by the American Association of Equine Practitioners (AAEP) (Kester 1991), in which 0 denotes no lameness and 5 indicates non-weight-bearing lameness. In brief, the horses trotted on a hard surface over a total distance of 60 m. An additional lameness evaluation was performed on all defective hooves by hoof tester compression on the solar surface area. The joint flexion test, flexor tendon palpation, and extension test were performed sequentially. Palmar digital anaesthesia using 2% lidocaine hydrochloride (L.B.S. Laboratory Ltd., Bangkok, Thailand) was performed uniaxially to localise the area of the foot pain in case lameness was present in the horse. Gait analysis was also performed before each farriery session.\n\nRadiographic examination\n\nBefore the first farriery session and at 15 weeks and 30 weeks, the 30 affected hooves were radiographed in dorsopalmar, lateromedial, and 65° dorsopalmar projection to assess bone defects and internal hoof configuration. The distal phalanx/ground surface angle was also assessed radiographically (Poskom PXM-20 BT, Diagnostic Imaging Systems, Inc., SD, USA) in the affected limbs, as described previously (Kummer et al. 2006).\n\nStrategic palmar trimming and shoeing adjustments\n\nEach horse underwent hot-shoeing performed by experienced farriers under veterinary supervision every 5 weeks during the 30 weeks of the experiment. Of note, one horse with four defective hooves and two horses with defective front hooves were excluded from the control group due to the injury, regardless of the shoeing protocol, after 10 and 25 weeks, respectively. The strategic hoof trimming protocol in the experimental group was intended to eliminate the collapsed palmar tubules and prevent the palmar region from bearing weight. Before each farriery session, the injured hooves were measured from the toe to the heel bulb to calculate three equal areas using a Measure King™digital tool (ONTEL, Fairfield, New Jersey, USA). Each hoof was cut at the dorsal one-third and rasped to provide a ground contact surface of approximately the dorsal two-thirds of the hoof (Figure 1a and b). The hoof was then pressed onto Play-Doh to obtain a surface model to determine the solar surface dimensions. The rasped hoof was repeatedly measured to establish the three equal regions. The palmar third of the hoof was trimmed horizontally until the angle of the sole was visualised (Figure 1c). Finally, all horses were shod with metal shoes (Mustadfors Bruks, Dal Langed, Sweden) on the affected and healthy hooves, according to the standard method described elsewhere (Karle et al. 2010, Leśniak et al. 2017, Weishaupt et al. 2013). All shoeing protocols in this study were performed closely with one experienced equine practitioner to standardise the hoof trimming method and farrier practice.\n\nThe length was initially measured (yellow line) and cut at the dorsal one-third (white double-headed arrow) (a). The horn was then rasped to allow ground surface contact for approximately the dorsal two-thirds of the hoof (b). After the second measurement, the palmar third was horizontally trimmed until the sole angle was visualised (black-headed arrows). The trimming was intended to create a space between the affected palmar region and the metal shoe (c).\n\nHoof conformation\n\nBefore and after each sequential shoeing session, lateral view images of affected hooves were captured at a distance of 40 cm using a Canon EOS 500D Digital SLR Camera (Canon Inc., Tokyo, Japan) (Figure 2a and b). The DHWA, HA, and distance of the heel bulb to the caudal ground contact of the hoof were evaluated before each shoeing session. The palmar trimming distance was estimated after each shoeing session. The data were calculated using the ImageJ program (version 1.52a) (LOCI, University of Wisconsin, Madison, WI, USA) and expressed as DHWA/HA ratio, absolute heel-bulb distance, and palmar trimming distance.\n\nThe lateral views were captured before (a) and immediately after (b) shoeing. Measurements of the DHWA (1), hoof height (2), HA (3), heel height (4), palmar trimming distance (5), and heel-to-bulb distance (6) allowed for evaluation of the DHWA/HA ratio and the average heel–bulb and palmar trimming distances. A Play-Doh hoof model was constructed after basic trimming (c) and then divided by six parallel lines perpendicular to the central line for solar surface determination (d).\n\nHoof surface dimension measurements\n\nThe hoof surface dimensions were determined according to a method described previously (Chanda et al. 2020). Briefly, Play-Doh solar surface images were captured at a constant distance of 70 cm using a Canon EOS 500D digital SLR camera (Canon Inc., Tokyo, Japan) (Figure 2c). The circumference of the hoof ground surface was calculated using the GoodNotes 5 application (Time Base Technology Limited, Kowloon, Hong Kong). The surface was then divided by six parallel lines perpendicular to the central line of the solar surface using the AutoCAD software program (version O.49.0.0) (Autodesk Inc., San Rafael, California, USA) (Figure 2d). Each parallel line was measured (in mm) from the medial to the lateral side using the ImageJ program (version 1.52a) (LOCI, University of Wisconsin, USA) to determine changes in the solar surface dimension.\n\nStatistical analyses were performed using GraphPad Prism version 9.5.1 (GraphPad Software, San Diego, CA, USA). Due to missing data in the repeated measurements, a mixed-effects model (Restricted Maximum Likelihood: REML) was used to analyse the change in the DHWA/HA ratio, absolute heel–bulb distance, and length of the six parallel lines on the solar surface in horses in the control and experimental group. Tukey’s multiple comparisons test was used to compare results within the group. Šídák’s multiple comparisons test was applied to compare parameters between the groups at given times. Palmar trimming distances were analysed by the Friedman test with a Dunn multiple comparisons test because this parameter showed a non-normal distribution following the Kolmogorov-Smirnov test. Data were expressed as the mean ± SEM. Statistical significance was set at p < 0.05.\n\n\nResults\n\nThe results of the lameness examination of horses in the control and experimental groups are shown in Tables 1 and 2, respectively (Sanigavatee 2023a). Approximately half the horses exhibited mild lameness on the front legs. Furthermore, all affected horses demonstrated sensitivity to compression by the hoof tester on the sole, particularly in the palmar region. Most horses in the control group were positive for the fetlock flexion test. In contrast, only a few horses in the experimental group were positive for the fetlock flexion test. All lame horses responded to palmar digital nerve desensitisation, showing a dramatic decrease in lameness following the regional anaesthesia protocol. The radiographic images demonstrated bone defects, including synovial invagination, irregular shape of the navicular bone’s distal border, and negative palmar angle of the hoof in some horses in this study (Extended data, Supplementary File 2; Sanigavatee 2023b).\n\nCompared to the hooves’ palmar trimming length in the early sessions (Figure 3a), the trimming length of the defective hooves was shorter in later shoeing sessions (Figure 3b). A considerable shortening in palmar trimming length was detected at 25 weeks (37.51 ± 1.97 vs 27.85 ± 1.10 mm; p < 0.05) and 30 weeks (37.51 ± 1.97 vs 26.33 ± 1.04 mm; p < 0.01) (Figure 3c).\n\nThe images of the front hooves of horse 2 demonstrate the palmar trimming length at the 25-week shoeing session (yellow double arrows) (a) and the 30-week shoeing session (red double arrows) (b). The line chart illustrates the quantitative change in palmar trimming distance at each shoeing session (c). **p < 0.01 when compared to the values at the first shoeing session (0 wk) in horses with the strategic palmar trimming protocol.\n\nAlthough there was no group-by-time interaction (p = 0.6248), separate effects of group (p = 0.0045) and time (p = 0.0182) were observed for the change in the heel–bulb distance. The heel–bulb distance was unchanged in horses in the control group throughout the study period. However, in horses in the experimental group, it was significantly shorter at 25 weeks (25.50 ± 1.35 vs 20.51 ± 0.70 mm; p < 0.01) and 30 weeks (25.50 ± 1.35 vs 20.57 ± 1.15 mm; p < 0.05) (Figure 4).\n\n*p < 0.05 and **p < 0.01 when compared to the values at the first shoeing session (0 wk) in horses with strategic palmar trimming.\n\nThere was a group-by-time interaction (p = 0.0101) for change in DHWA/HA ratios in the present study, but no separate effects of group (p = 0.1208) and time (p = 0.0685) were found. There was no change in DHWA/HA ratio in horses in the control group (Extended data, Supplementary File 3; Figure S2a-c; Sanigavatee 2023b), but the ratio changed in the experimental group (Exteded data, Supplementary File 4; Figure S3a-c; Sanigavatee 2023b).\n\nA decrease in DHWA/HA ratio in experimental horses was initially detected at 25 weeks (1.60 ± 0.08 vs 1.33 ± 0.06; p < 0.05) and remained at 30 weeks (1.60 ± 0.08 vs 1.34 ± 0.05; p < 0.05) (Figure 5). The radiographic images also showed an improved hoof angle after 30 weeks compared to the negative hoof angle at the initial farriery session in the experimental horses (Extended data, Supplementary File 5; Sanigavatee 2023b).\n\n*p < 0.05 when compared to the values at the first shoeing session (0 wk) in horses with strategic palmar trimming.\n\nTable 3 shows the modification of the solar surface, indicated by a change in the length of the six parallel lines. There was a group-by-time interaction for change in the length of all measured parallel lines (line 1; p = 0.0127, line 2; p = 0.0003, and lines 3-6; p < 0.0001). Time on its own interacted with a change in the length of lines 1 (p = 0.0113), 3 (p = 0.0202), 4 (p = 0.0047), and 5 (p = 0.0381), but not of lines 2 (p = 0.0565) and 6 (p = 0.4566). There was no separate group effect for the modification of any of the parallel lines in this study.\n\n*and ‡indicate the effects of group-by-time interaction and time on change in given parallel lines in response to palmar trimming before conventional shoeing.\n\nThe solar surface dimension was unchanged in horses in the control group throughout the study period (Extended data, Supplementary File 3; Figure S2d-f; Sanigavatee 2023b). In contrast, the solar surface of the hooves in the experimental group changed over time (Extended data, Supplementary File 4; Figure S3d-f; Sanigavatee 2023b). Even though a fluctuation in length was observed in lines 3 and 4 at 10, 20, and 30 weeks of the shoeing protocol (10 vs 20 weeks; p < 0.01 in both lines and 20 vs 30 weeks; p < 0.05 in both lines), the length of the six parallel lines after 30 weeks did not differ from the length before the first session in horses in the control group. Similarly, there was a marked fluctuation in the length of line 1 at 25 and 30 weeks (p < 0.05) and line 2 at 10 and 30 weeks of the shoeing protocol (p < 0.05) in horses in the experimental group. Nonetheless, the length of lines 1-4 at 30 weeks was not different from the value before remedial farriery.\n\nThere was a difference between groups in the length of lines 5 and 6 at the start of the trial (p < 0.01 in both). A change in lines 5 and 6 was observed in the experimental group over time. The length of line 5 was increased at 25 and 30 weeks compared to the start of the trial (p < 0.05 at both time points). An increase in the length of line 6 was detected earlier, at 10 weeks, until the end of the study at 30 weeks compared to before remedial farriery (p < 0.01 at 10 and 15 weeks, p < 0.05 at 20 weeks and p < 0.001 at 25 and 30 weeks).\n\n\nDiscussion\n\nThe present study investigated the effect of conventional shoeing combined with strategic palmar trimming on hoof conformation and recovery time in horses with underrun heels. The significant findings of the experiment include: 1) there was a farriery protocol-by-time interaction for changes in DHWA/HA ratio and solar surface dimension, indicating a distinct impact of the farriery protocol on hoof conformation; 2) hoof angle, heel angle, and solar surface dimension changed simultaneously in response to remedial farriery using strategic palmar trimming before conventional shoeing; 3) an increase in heel angle as a result of a decrease in DHWA/HA ratio was initially noted at 25 weeks; 4) a reduction in heel–bulb distance and palmar trimming length was detected at 25-30 weeks in response to remedial farriery; 5) hoof ground contact, particularly in the palmar region, improved markedly from week 25 of corrective shoeing onwards. Therefore, strategic palmar trimming followed by conventional shoeing showed potential to control underrun heels in horses. The farriery protocol should be followed for at least 25 weeks to improve hoof conformation and heel angle in horses with underrun heels.\n\nSeveral pathological lesions, including palmar bruising and abscesses, sheared heels, hoof wall separation, subcapsular soft tissue damage, and osteoarthritis of the interphalangeal joints, have been reported to accompany underrun heel conformation (Dabareiner and Carter 2003, Hunt 2012, Turner 2010, Turner 1988). Furthermore, hoof conformation defects in conjunction with the bone lesions of the navicular syndrome may be detected in horses with underrun heels (Dabareiner and Carter 2003). This conformation defect does not always result in lameness despite repetitive abnormal loading leading to underrun heels in horses (Hunt 2012). Moreover, the underrun heel conformation may persist without evidence of navicular syndrome (Wright 1993). Our results support this idea, as the horses in the present study showed unilateral lameness on the front legs, even though they showed underrun heel conformation in the other limbs (Extended data, Supplementary File 1; Tables S2 and S3; Sanigavatee, 2023b). Although evidence of degeneration, such as synovial invagination and irregular navicular bone shape, was not associated with lameness in the horses in this study, the mechanical force acting on the navicular bone in horses with underrun heels is still of concern (Hunt 2012). In addition, excessive compression of the navicular bone, exerted by the tensile force of the deep digital flexor tendon, was also reported to be caused by underrun heel conformation (Turner 1989). Hence, navicular syndrome secondary to underrun heels should still be considered.\n\nThe interval between consecutive shoeing sessions has been found to influence hoof conformation (Leśniak et al. 2017, O’Grady and Poupard 2003, Van Heel et al. 2005). Shoeing at 8-week intervals has been reported to increase dorsal hoof wall length and decrease DHWA, which puts the distal interphalangeal joint under certain stress (Moleman, et al. 2006). A 4–6-week shoeing interval could optimise the prevention of excessive loading on the palmar region, thereby lowering the risk of long-term injuries (Leśniak et al. 2017). For this reason, shoeing in our recent study was carried out at five-week intervals to reap the maximum benefits of remedial farriery. Lameness in experimental horses was markedly reduced at 20–30 weeks (Extended data, Supplementary File 1; Table S4; Sanigavatee 2023b), while there was almost no change in gait abnormality in the control group.\n\nIn the present study, a change in DHWA/HA ratio and heel–bulb distance was detected in horses with strategic palmar trimming before conventional shoeing, while it was unchanged in horses with regular trimming and traditional shoeing. It has been reported that appropriate trimming to restore the normal hoof angle is possibly more crucial than applying additional devices (O’Grady 2006, O’Grady and Poupard 2001). It has been proven that hoof trimming has a significant effect on hoof conformation (Kummer et al. 2006). Theoretically, hoof trimming and shoeing in a horse with foot pain should re-establish balance and correct hoof problems. Trimming and shoeing are expected to diminish the biomechanical forces exerted on the palmar hoof area (Dabareiner and Carter 2003). Trimming and shoeing have been used to modify the external hoof capsule and the internal structures (O’Grady 2008). Therefore, hoof trimming and shoeing are crucial in distorted hoof management (Hunt 2012). The general concept of managing underrun heels incorporates three principles: first, toe trimming to reduce the overgrown toe, thereby facilitating breakover and restoring the proper axis and position; second, multiple rounds of palmar trimming to eliminate the curved horn tubules, creating healthy horn that can withstand palmar loading; third, proper trimming and shoeing management to reduce palmar loading on the affected hooves (Hunt 2012). In the anatomy of the foot, the distal phalanx should reside in the dorsal two-thirds of the hoof capsule, while the soft tissues should occupy the palmar third of the hoof capsule (O’Grady 2012). In practical terms, underrun heels may still be present even though the hoof angle has been anatomically corrected with basic hoof trimming. The palmar tubules may still be in contact with the ground, producing a fulcrum at this point when loading. This may lead to the continuous forward growth of the distorted palmar tubules, resulting in curling horn in the palmar region. The strategic palmar trimming described in the present study was designed to adhere to these three principles and enable the hooves to bear the natural descending forces. The purpose of the cut at the dorsal one-third of the hoof capsule was to shorten the toe and raise the hoof-pastern axis position. After tactical rasping, the ground contact surface extended to the dorsal two-thirds of the capsule and this was believed to be sufficient to withstand natural loading on the distal phalanx. Strategic trimming of the palmar third was designed to eliminate the curling heel and the tubules’ contact with the ground in the palmar region before shoeing. Thus, as the heels did not bear weight, the palmar horn tubules were allowed to grow distally, improving the heel angle. Moreover, this trimming protocol has considerable potential to improve the position of the axis to dissipate loading on the palmar region and promote heel growth, as demonstrated by the hoof-pastern axis improvement seen in the radiographs (Extended data, Supplementary File 6; Sanigavatee 2023b). In addition, following the strategic farriery protocol, the trimming length became shorter in the palmar third while retaining an appropriate ground contact length in the dorsal two-thirds of the hoof capsule (Extended data, Supplementary File 7; Sanigavatee 2023b). Lighter loading was likely experienced in the palmar region due to the strategic hoof trimming protocol. The progressive shortening of both heel–bulb length and palmar trimming distance may indicate, at least in part, that the palmar horn tubules grew more distally when this tactical shoeing protocol was applied. Therefore, the present study provided objective evidence for the importance of strategic palmar trimming in correcting underrun heels in horses.\n\nThe solar surface dimension remained constant in shod horses without strategic palmar trimming, whereas it changed over time in horses with tactical remedial trimming. The length of lines 1-4 was unchanged in horses in the present study, as the toe and quarter portions are less elastic than the heel region (Chanda et al. 2020). The expansion of the palmar area, illustrated by the increased length of lines 5 and 6, was marked at 25 and 30 weeks of remedial farriery. Although the length of lines 5 and 6 was different between the two groups before the start of the trial, there was no difference between groups in the length of both lines at the end of the study: the palmar size in horses with remedial farriery increased, while it remained constant in shod horses without the strategic trimming. A decrease in heel–bulb distance and palmar trimming length, coinciding with an improvement in heel angle and other aspects of hoof conformation at 25-30 weeks of remedial farriery, suggest that this is the minimum time required to improve hoof conformation in horses with underrun heels. Nevertheless, this period may vary depending on the severity of hoof distortion, the level of experience of the farrier, the shoeing interval, and environmental factors such as riding ground surface, nutrition, and type of activity.\n\nThe small number of affected horses in each group was the main limitation of this study. Further validation of this alternative farriery protocol with a larger sample size is required. In addition, hoof radiography could not be performed at every farriery session due to lack of machine availability, so the onset of the improvement in negative palmar angle could not be documented.\n\n\nConclusions\n\nStrategic hoof trimming accompanied by conventional shoeing can considerably improve hoof conformation by increasing the heel angle and expanding the hooves’ palmar region in horses with underrun heels. Remedial farriery should be continued for at least 25 weeks to achieve an improvement in the affected feet. A close collaboration between a specialised veterinarian and an experienced farrier is paramount to obtain a positive outcome from strategic shoeing management in horses with underrun heels.",
"appendix": "Data availability\n\nFigshare: Data availability in horse with and without strategic palmar trimming. https://www.doi.org/10.6084/m9.figshare.23269382.v3 (Sanigavatee 2023a).\n\nFigshare: Supplementary file: horse with and without strategic palmar trimming. https://www.doi.org/10.6084/m9.figshare.23290178.v4 (Sanigavatee 2023b).\n\nFigshare: Completed ARRIVE checklist for ‘Strategic palmar trimming before conventional shoeing shows potential for managing underrun heels in horses’. https://www.doi.org/10.6084/m9.figshare.23269382.v3 (Sanigavatee 2023a).\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nThe authors would like to thank Vaewratt Kamonkon, director of the Horse Lover’s Riding Club, Chalermcharn Yotwiriyapanit, director of the House of Horse Riding Club, Ploypailin Pattanakul from Checkmate Horse Club and Supote Ruchirasak from Bang Phli riding school for allowing us to include their horses in the study. The assistance in data collection by Naphassakorn Siviroj, Raktiphorn Khamtae, and Kanok Akkayamas is highly appreciated. We are grateful to SM1 Apichai Pongaree and SM1 Chetrat Treesoon and SM1 Somchai Tanoorat for the professional remedial farriery.\n\n\nReferences\n\nBarrey E: Investigation of the vertical hoof force distribution in the equine forelimb with an instrumented horseboot. Equine Vet. J. 1990; 22: 35–38. Publisher Full Text\n\nBigham A, Tabatabaei A: Field study of hoof wall problems in unshod working horses. Bulg. J. Vet. Med. 2007; 10: 179–183.\n\nChanda M, Puangthong C, Sanigavatee K, et al.: The effect of the z-bar shoeing method on surface dimension of the hoof wall and time required for therapeutic shoeing in three horses with a sheared heel. J. Appl. Anim. Res. 2020; 48: 406–412. Publisher Full Text\n\nDabareiner RM, Carter GK: Diagnosis, treatment, and farriery for horses with chronic heel pain. Vet. Clin. North Am. Equine Pract. 2003; 19: 417–441. PubMed Abstract | Publisher Full Text\n\nEliashar E: An evidence-based assessment of the biomechanical effects of the common shoeing and farriery techniques. Vet. Clin. N. Am. Equine Pract. 2007; 23: 425–442. PubMed Abstract | Publisher Full Text\n\nFloyd AE: Use of a grading system to facilitate treatment and prognosis in horses with negative palmar angle syndrome (heel collapse): 107 cases. J. Equine Vet. 2010; 30: 666–675. Publisher Full Text\n\nHood DM, Taylor D, Wagner IP: Effects of ground surface deformability, trimming, and shoeing on quasistatic hoof loading patterns in horses. Am. J. Vet. Res. 2001; 62: 895–900. PubMed Abstract | Publisher Full Text\n\nHunt RJ: Farriery for the hoof with low or underrun heels. Vet. Clin. N. Am. Equine Pract. 2012; 28: 351–364. PubMed Abstract | Publisher Full Text\n\nKarle A, Tank P, Vedpathak H, et al.: Horseshoeing: an overview. Vet. World. 2010; 3: 148.\n\nKester W: Definition and classification of lameness. Guide for Veterinary Service and Judging of Equestrian Events.1991. 4 ed.\n\nKummer M, Geyer H, Imboden I, et al.: The effect of hoof trimming on radiographic measurements of the front feet of normal Warmblood horses. Vet. J. 2006; 172: 58–66. PubMed Abstract | Publisher Full Text\n\nLeśniak K, Williams J, Kuznik K, et al.: Does a 4–6 Week Shoeing Interval Promote Optimal Foot Balance in the Working Equine? Animals. 2017; 7: 29. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcGuigan M, Wilson A: The effect of bilateral palmar digital nerve analgesia on the compressive force experienced by the navicular bone in horses with navicular disease. Equine Vet. J. 2001; 33: 166–171. PubMed Abstract | Publisher Full Text\n\nMoleman M, Van Heel M, Van Weeren P, et al.: Hoof growth between two shoeing sessions leads to a substantial increase of the moment about the distal, but not the proximal, interphalangeal joint. Equine Vet. J. 2006; 38: 170–174. PubMed Abstract | Publisher Full Text\n\nO’Grady SE: Strategies for shoeing the horse with palmar foot pain. Proceedings of the 52nd Annual Convention of the American Association of Equine Practitioners. 2006.\n\nO’Grady SE: Basic farriery for the performance horse. Vet. Clin. N. Am. Equine Pract. 2008; 24: 203–218. PubMed Abstract | Publisher Full Text\n\nO’Grady SE: Farriery for the Hoof with a Sheared Heel. Vet. Clin. N. Am. Equine Pract. 2012; 28: 381–392. PubMed Abstract | Publisher Full Text\n\nO’Grady SE, Poupard DA: Proper physiologic horseshoeing. Vet. Clin. North Am. Equine Pract. 2003; 19: 333–351. Publisher Full Text\n\nO’Grady SE, Poupard D: Physiological horseshoeing: an overview. Equine Vet. Educ. 2001; 13: 330–334.\n\nO’Grady SE, Turner TA, Ridley JT: How to Apply the Appropriate Farriery Principles to the Horse with Low Heels in the Hind Feet. Proceedings of the proceedings of 64th American Association Equine Practitioners Symposium, San Francisco, California. 2018.\n\nSanigavatee K: Data availability in horse with and without strategic palmar trimming. [Dataset]. figshare. 2023a. Publisher Full Text\n\nSanigavatee K: Supplementary file:horse with and without strategic palmar trimming. [Dataset]. figshare. 2023b. Publisher Full Text\n\nSigafoos R: Morphology, management, and composite reconstruction of the underrun heel. Am. Farriers J. 1990; 16: 26–37.\n\nTurner T: Shoeing strategies for palmar foot pain. Proceedings of the 16th Congress of Italian Association of Equine Veterinarians Carrara (Italy).2010.\n\nTurner TA: Diagnosis and treatment of the navicular syndrome in horses. Vet. Clin. N. Am. Equine Pract. 1989; 5: 131–144. Publisher Full Text\n\nTurner TASC: Hoof abnormalities and their relation to lameness. Proceedings of the 34th Annual Convention of the American Association of Equine Practitioners. 1988.\n\nVan Heel M, Moleman M, Barneveld A, et al.: Changes in location of centre of pressure and hoof-unrollment pattern in relation to an 8-week shoeing interval in the horse. Equine Vet. J. 2005; 37: 536–540. Publisher Full Text\n\nWeishaupt MA, Waldern NM, Amport C, et al.: Effects of shoeing on intra-and inter-limb coordination and movement consistency in Icelandic horses at walk, tölt and trot. Vet. J. 2013; 198: e109–e113. Publisher Full Text\n\nWilson A, McGuigan M, Fouracre L, et al.: The force and contact stress on the navicular bone during trot locomotion in sound horses and horses with navicular disease. Equine Vet. J. 2001; 33: 159–165. PubMed Abstract | Publisher Full Text\n\nWright I: A study of 118 cases of navicular disease: clinical features. Equine Vet. J. 1993; 25: 488–492. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "229996",
"date": "02 Jan 2024",
"name": "Anderson Fernando de Souza",
"expertise": [
"Reviewer Expertise Equine lameness",
"hoof balance",
"biomechanics",
"fracture repair",
"large animal 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\nThis article describes a method for correcting the hooves of horses with underrun heels, by making specific trimming in the palmar/plantar region of the hoof associated with the use of horseshoes. Basically, the authors relieved the load applied to the caudal portion of the hoof in order to allow the tubules in this region to grow more vertically. There were interesting results that may support a benefit over the control group. Generally, the article is methodologically appropriate and relevant, despite the small number of animals evaluated. In this reviewer's view, the proposed method could make sense in a rigid structure, but in the horny tissue of the hoof, which is flexible, the floating effect of the heels probably lasts for a short time after hoof trimming. This may be due to deformation of the wall, loosening of the nails, and/or bending of the horseshoe, causing the part of the hoof wall that has been relieved to become load-bearing again. I would like the authors to include information and discussions about the issue of the horseshoe in relation to the hoof before re-shoeing.\nBelow is a list of suggestions for the authors to consider:\nAbstract - Include some background or change the sub-item to \"Objectives\". - Perhaps the term \"imbalance\" would be more appropriate than \"malconformation\".\nIntroduction\n- Include the study's hypothesis; - In the objectives, the authors refer to an \"alternative farriery protocol\", but in this case, the term \"trimming\" would be more appropriate, as this was the only difference between the groups.\nMethods\n- Use the terms \"fore and hind limbs\", and \"fore and hind hooves\" to refer to the limbs throughout the text. - \"Real hooves\"? did you mean \"hind hooves\"? - The authors included lame animals in the study and indicated that some of them improved over the course of the study. How do the authors differentiate the improvement in hoof balance from the proposed treatment and not from the simple return of the hoof load to the lame limbs? - The manuscript indicates that several farriers perform hoof management, but with a small number of animals, this can be an important source of variation. Ideally, only one farrier should have performed the management. Please indicate how many farriers took part in the study and whether the authors considered this a source of variation in their data analysis. - Three animals were removed from the control group, does this mean that only 3 animals finished the study? This reflects an important limitation for the analysis, as you probably cannot identify differences for this group. I suggest that the authors revise their statements to support their conclusions for the moments when all the animals were present in the study and only make assumptions for later moments.\nResults\n- The term \"uneven gait\" seems very subjective to me, what do the authors mean by this? - In the text there is a call for figures 3a, 3b and 3c, but there is only one figure 3. Check this. - Include the exact probability values throughout the text. - Figure 3: in the caption, there is mention of hoof images, but there is nothing of this in the figure, check this. - Figure 4: place the figure after the caption in the text. - Table 3: what do the superscript letters mean?\nDiscussion\n- In the first paragraph the authors need to be clear in their statements about which groups were better in which aspects analyzed, just saying that \"changes\" happened is too general.\n- \"Remedial farriery\", \"corrective shoeing\"... avoid using so many terms to refer to the same subject, as it creates confusion in understanding.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-1504
|
https://f1000research.com/articles/13-161/v1
|
07 Mar 24
|
{
"type": "Research Article",
"title": "High throughput biological sequence analysis using machine learning-based integrative pipeline for extracting functional annotation and visualization",
"authors": [
"Md Al Amin",
"Feroza Naznin",
"Most Nilufa Yeasmin",
"Md Sumon Sarkar",
"Md Misor Mia",
"Abdullahi Chowdhury",
"Md Zahidul Islam",
"Md Al Amin",
"Feroza Naznin",
"Most Nilufa Yeasmin",
"Md Sumon Sarkar",
"Md Misor Mia"
],
"abstract": "The Differential Gene Expression (DGE) approach to find out the expressed genes relies on measures such as log-fold change and adjusted p-values. Although fold change is commonly employed in gene expression studies, especially in microarray and RNA sequencing experiments to quantify alterations in a gene’s expression level, a limitation and potential hazard of relying on fold change in this context is its inherent bias. As a consequence, it might incorrectly categorize genes that have significant differences but minor ratios, resulting in poor detection of mutations in genes with high expression levels. In contrast, machine learning offers a more comprehensive view, adept at capturing the non-linear complexities of gene expression data and providing robustness against noise that inspired us to utilize machine learning models to explore differential gene expression based on feature importance in Type 2 Diabetes (T2D), a significant global health concern, in this study. Moreover, we validated biomarkers based on our findings expressed genes with previous studies to ensure the effectiveness of our ML models in this work which led us to go through to analysis pathways, gene ontologies, protein-protein interactions, transcription factors, miRNAs, and drug predictions to deal with T2D. This study aims to consider the machine learning technique as a good way to know about expressed genes profoundly not relying on the DGE approach, and to control or reduce the risk of T2D patients by helping drug developer researchers.",
"keywords": [
"Bioinformatics",
"Machine Learning",
"Type-2 Diabetes",
"Proteins",
"Pathways",
"Gene Ontology",
"RNA-Sequence",
"Drug"
],
"content": "1. Introduction\n\nDifferential Gene Expression (DGE) analysis usually based on the DESeq2 package1 is a traditional and common bioinformatics technique that helps to identify expressed genes under different conditions offering insights into genes that exhibit varying expression levels.2 In RNA sequence data, fold change in gene expression studies can be biased, potentially misclassifying genes with large absolute differences but small relative ratios.3 However, the advent of Machine Learning (ML) has brought about a significant change in bioinformatics, and it is now widely acknowledged as a powerful tool that can provide detailed and useful explanations of complex data that were once difficult to understand.4 And with the passage of time, in the medical sector, ML techniques are getting popularity, being effective for decision-making.5,6 Using different kinds of ML algorithms is noticeable in RNA sequence data for different types of detection and to find out the correlation of sequences,7 as well as for showing the effectiveness of machine learning algorithms in detecting splice variants from RNA sequence data.8 Such as: To identify and classify cancers early on, different computer algorithms have been used on microarray data sets. These include support vector machines, random forest, and neural networks.9 On the other hand, this study uses a neural network to analyze RNA sequence-expressed genes from different datasets to predict a patient’s health status.10 And in this paper, the primary objective is to classify or identify different types of cancers based on the patterns found in the gene expression data. By doing so, the research aims to enhance the accuracy and efficiency of cancer diagnosis, potentially leading to more targeted and effective treatments11 that inspired us to apply ML models in the bioinformatics field, especially in the RNA sequence count data.\n\nType 2 Diabetes (T2D), sometimes referred to simply as diabetes, is a long-term illness that affects the metabolic process.12 According to IDF, around 6.7 million people were dead in 2021, which is one of the major ten reasons for death in the universe, and around 541 million adults are affected by T2D.13 It was also projected in 2021 that by 2030, 643 million people would have diabetes, and by 2045, 783 million people will have the disease.14 However, the risk of serious complications from T2D is greatly reduced if it can be diagnosed in its early stages.15 Moreover, pioneers of improved biotechnology invented several bioinformatics tools that assisted the course of study about T2D.16 Yet, other groups of researchers have relied on machine learning (ML)-based aid systems for forecasting chronic illnesses.17–19 Researchers have suggested utilizing machine learning-based classification models to estimate the prevalence of T2D depending on its risk factors.20–23 So, this information encouraged us to be involved with T2D.\n\nIn our research on individuals with T2D, we utilized a feature importance method using XGBoost to identify highly expressed genes from RNA sequencing count data detecting T2D and not T2D individuals based on count data. This approach was used instead of relying solely on adjusted p-values and log fold Change values to determine significant genes. By training various algorithms on RNA sequence count data, we achieved notable prediction accuracies, with XGBoost emerging as a standout, and this approach not only enhances gene detection accuracy but also challenges traditional bioinformatics metrics, suggesting a richer machine learning-driven perspective on the genetic prospect of diseases like T2D. Moreover, on our detected expressed genes or significant features, we went through several bioinformatics analyses such as pathways, gene ontologies, protein-protein interactions, transcription factors, miRNAs, and drug predictions to deal with T2D. More importantly, we validated our findings with past studies to show the effectiveness of our models. So, in the future, this study will help researchers to gain knowledge more about mutated genes through machine learning, and to think about the prevention of T2D based on bioinformatics analysis like drug prediction discussed in this paper.\n\n\n2. Methods\n\nWe initiated our study by selecting the RNA-Sequence count dataset (GSE81608)24 from GEO.25 This dataset was chosen for its reliability, especially in the context of biological data. The specifics of this dataset are detailed in Table 1. For ease of access and analysis, we downloaded the raw-count data from GREIN.26 Afterward, the data underwent a pre-processing through Utilizing the “pandas” library27 step to prepare this data for machine learning training.\n\nOn the preprocessed data, we trained six distinct ML models: Random Forest, AdaBoost, Gradient Boosting, Logistic Regression, Decision Tree, and XGBoost on the 80% of our dataset where 20% was for test. These models were trained on two classes: diabetes and non-diabetes. Our primary objective was to identify significant features28 which in our study were considered as differentially expressed genes.29 The entire machine learning process on this dataset is depicted in Figure 2. Additionally, for a more intuitive understanding, we visualized the RNA sequencing data and DGE in 4.\n\nOn our findings (significant features), we delved deeper into the data using a set of bioinformatics techniques. This comprehensive approach covered protein-protein interaction network analysis, gene ontology and pathway analysis, transcription factors and miRNAs analysis, hub gene extraction, and protein-drug interactions. To ensure the robustness and validity of our methods, we validated our results with existing literature. For a more intuitive understanding of our analytical approach, we have visually represented our methodology in Figure 1. For our gene ontology and pathway analysis, we turned to EnrichR.30 This tool provided insights into various sights of gene ontology, including biological processes, cellular components, and molecular functions. To further enrich our pathway analysis, we involved with information from trusted databases such as KEGG,31 Reactome,32 WikiPathways,33 Elsevier, and BioCarta.34 Throughout this process, we maintained an adjusted p-value of less than 0.05 as our benchmark for deciding significant pathways. On the other hand, our exploration into protein-protein interactions was simplified by the STRING online tool.35 Following this, we embarked on the creation of a hub-protein network, using the Cytoscape application with the cytohubba plugin.36 For insights into transcription factors, we recommended the JASPAR37 and ChEA38 databases. This allowed us to identify graphically plausible transcription factors that might connect with our differentially expressed genes (DEGs). This exploration was further enhanced using the NetworkAnalyst tool. Additionally, the TarBase39 and miRTarBase40 databases were instrumental in shedding light on miRNA-DEG interactions. NetworkAnalyst41 was the center of our analysis of TFs–gene and miRNAs–gene interaction networks. Moreover, for our exploration into drug-protein interactions, we relied on DrugBank,42 a comprehensive online resource of medicines and their associated drug targets.\n\n\n3. Results\n\nThe evaluation of machine learning models is crucial across all domains but regardless of data related to biology is inescapable.79 While accuracy is a commonly used metric to evaluate a model’s performance, it alone may not provide a comprehensive assessment, especially in the context of biological or health-related datasets. Therefore, to achieve a clear understanding of a model’s efficacy, we incorporated a range of metrics including Precision,43 Recall,44 F1-Score,45 and Specificity,46 RocAuc, True Positive Rate, and False Positive Rate. These metrics collectively offer a perspective on the model’s performance, capturing various aspects of its predictive capabilities. The confusion matrix serves as a foundational tool in this context, covering the various measures employed to evaluate the efficiency of a classification model. However, To diagnose T2D from RNA sequence data, we used five unsupervised models Gradient Boosting, XGBoost, Logistic Regression, Random Forest, and AdaBoost. The XGBoost model performed well, with the highest prediction accuracy at 0.941% and the second lowest Log-Loss at 0.282%, showing values of confusion matrix for Precision 0.943, Recall 0.958, RocAuc 0.937, Specificity 0.915, F1-Score 0.950, TPR 0.958 and TFR 0.085%. Besides, the Gradient Boosting model showed the second highest prediction accuracy at 0.941% and the lowest Log-Loss at 0.280%, representing values of confusion matrix for Precision 0.948, Recall 0.943, RocAuc 0.937, Specificity 0.915, F1-Score 0.950, TPR 0.958 and TFR 0.085%. On the other hand, AdaBoost is the worst model in this accuracy, with the lowest accuracy of 0.744%. In addition, the accuracy is 0.884% in the third and 0.772% in the fourth positions for Logistic Regression and Random Forest, respectively. All the values have been shown in the Table 2, and the Figure 3 visualize the performance of the models based on the Accuracy and Log-Los.\n\nAlthough we trained 5 different models to get our significant features (expressed genes), we selected the top 100 important genes based on our best-performed model, XGBoost with 0.941% accuracy, among them because this one has been trained well and showed the best performance (shown in Figure 3). In addition, we included our predicted expressed genes in the Extended data supplementary file-1). However, by the way of using this method, we ignored the conventional method, Differential Gene Expressions (DEGs). For the XGBoost model, the parameters we used have been provided in Table 3.\n\nUtilizing the computational tool EnrichR, we conducted a gene set enrichment approach to determine pathways and took into account five pathways databases to conduct experiments utilizing DEGs of T2D. The 20 leading terms of signaling Pathways are presented in Figure 5. The top 10 terms in biological processes, molecular operations, and cellular components are included in Table 4. The adj. p-value, mostly less than 0.05, filters both the GO and the Pathways, which are then ordered ascendingly.\n\nWe used STRING to analyze the PPI network and a Cytoscape representation to predict the adherence pathways and recurrent interactions between DEGs. Utilizing topological metrics, such as a degree higher than 15°, extremely communicating proteins were defined via PPI interpretation. The most prominent DEGs include 75 nodes in this PPI network (shown in Figure 6) and 226 edges between them. Hub genes have a strong association in potential units and top 10% interconnectivity. Due to these interconnections, hub genes typically play a crucial role in biological systems. To find the top 18 DEGs (hub genes), we used Cytoscape’s Cytohubba plugin. Figure 7 illustrates the hub genes notably: TP53, INS, KDM1A, SNAI1, RCOR1, CTBP1, RPA1, RAD52, SQLE, CYP51A1, CFTR, CPE, C3, PRMT1, NFYB, CD38, CFP and CASP10. These identified hub proteins could be useful as therapeutic targets, yet their roles still need to be explored. T2D-related differentially expressed genes (DEGs) and their hub genes are summarized in Table 5.\n\nThe circular nodes in the diagram symbolize differentially expressed protein genes, while the edges depict the communication between nodes. The PPI consists of 75 nodes connected by 226 edges. The PPI network was generated utilizing STRING and visualized via Cytoscape.\n\nThe most up-to-date MCC and BottleNeck techniques available in the Cytohubba plugin were used to obtain hub genes. The top 14 hub genes from each approach are highlighted below, along with the links between them and other compounds. BottleNeck contains 58 nodes and 100 edges, but the MCC network has only 48 nodes and 90 edges.\n\nWe used a network-based strategy to parse the governing TFs and miRNAs to locate substantial transcriptional changes and learn more about the hub protein’s signaling molecules. Transcription factors are proteins that govern gene activity and transcription over all life forms.47 Tiny RNA molecules called miRNAs have a role in post-transcriptional expression regulation. We investigated the interaction between DEGs and TFs, as shown in Figure 8, and DEGs and miRNAs, as shown in Figure 9. Major promoters of the TFs of differentially expressed genes were ELK4, FOXC1, FOXL1, GATA2, JUN, MEF2A, NFIC, NFKB1, POU2F2, PPARG, RELA, TEAD1, USF2, YY1, PRRX2, STAT3, TP53, E2F1, CREB1, NANOG, CREM, RUNX1, TP63, AR, HNF4A, POU5F1, SOX2, MITF, SPI1, MYC, FLI1, SUZ12, and EGR1. Mir-6883-5p, mir-6785-5p, mir-149-3p, mir-4728-5p, mir-17-5p, mir-210-3p, mir-374a-5p, mir-21-3p, mir-129-2-3p, mir-7-5p, mir-16-5p, mir-1-3p, mir-124-3p, mir-155-5p, mir-27a-3p, mir-34a-5p, let-7b-5p, and mir-107 were specified so that a concise overview of the DEGs operating at post-transcriptional regulators could be established. This Table 6 summarizes both transcriptional and post-transcriptional regulatory factors of type 2 diabetes-related differentially expressed genes.\n\nThe circular cyan nodes represent transcription factors, while the circular red nodes represent gene icons that connect with transcription factors.\n\nHere, the square node represents miRNAs, while the circular-shaped gene symbols connect with miRNAs.\n\nTo understand the structural features implicated in signal transduction, conducting a protein-drug interaction analysis48 is necessary. We listed 18 potential treatment drugs for frequent DEGs as possible pharmacological candidates in T2D employing NetworkAnalyst techniques dependent on drug-protein connections from the DrugBank library. Figure 10 shows 14 well-known therapeutic agents, including Insulin Human, Dalteparin, Lovastatin, Atorvastatin, Insulin glargine, Myristic acid, M-cresol, Insulin peglispro, L-lysine, L-ornithine, Ivacaftor, Glyburide, Bumetanide, and Lumacaftor that were found in the Protein Drug Interactions of DEGs of T2D. The potential uses of the remaining four chemical compounds in healthcare are still being investigated.\n\nHere, the rectangular node symbolizes drugs, whereas the circular gene symbols are linked to drugs.\n\n\n4. Discussion\n\nIn the modern era, over time, as artificial intelligence is improving rapidly, Machine Learning is performing as an essential part in the bioinformatics sector analyzing data profoundly.49 Although we can use ML techniques on most of the RNA sequence data, in this research, we have analyzed T2D data because it is a chronic illness that can have severe and life-threatening complications.15 In this study, we presented a count-based classification pipeline to identify expressed genes applying the feature importance technique, as well as to detect the patient based on count data. Moreover, the approaches used here enable us to process large amounts of transcriptome data and draw reliable conclusions regarding T2D proteins involving various bioinformatics techniques, allowing us to comprehensively understand T2D and identify associated biomarkers.\n\nIn our comprehensive investigation of Type 2 Diabetes (T2D), we employed several supervised machine learning algorithms, including Random Forest, AdaBoost, Gradient Boosting, Logistic Regression, Decision Tree, and XGBoost. Their performance metrics, accuracies, and losses are visually represented in Figure 3 and detailed in Tab-2. From a bioinformatics perspective, we conducted Pathway enrichment analysis (Figure 5), Gene Ontology assessments (Table 4), Protein-Protein Interaction studies (Figure 6), and explored Hub-Protein interactions (Figure 7), Transcriptional Factor interactions (Figure 8), miRNA interactions (Figure 9), and drug-protein interactions (Figure 10). Each hub gene was meticulously detailed with its features in Table 5. Furthermore, we provided an in-depth overview of both transcriptional and post-transcriptional regulatory differentially expressed genes in Table 6. Our machine learning models’ efficacy in identifying significant genes from RNA sequence data sourced from NCBI for T2D is illustrated in Figure 4. For a holistic understanding of our research approach, we’ve outlined the entire methodology in Figure 1. Our dataset is comprehensively presented in Table 1, and the parameters of our top-performing model, XGBoost, are shown in Table 3.\n\nIn terms of our best model XGBoost, XGBoost’s superior performance on our dataset can be attributed to several factors. Its ability to model complex non-linear relationships, combined with built-in L1 and L2 regularization, makes it adept at handling high-dimensional data. Unique features such as internal handling of missing values, tree pruning, and efficient column block computation further enhance its efficiency. The model’s adaptability in hyperparameter tuning, resilience to outliers, and capability to capture feature interactions likely contributed to its edge. Additionally, the inherent nature of some datasets might align better with gradient-boosted trees, suggesting that our data’s underlying patterns were particularly suited for XGBoost. The mathematical equation of the aim and process of the XGBoost model is shown below:\n\nGiven a dataset with n samples and m features, the prediction of the model for the ith instance at the tth iteration is denoted as ŷit. The objective function to be optimized in XGBoost at each iteration is:\n\nHere, T is the number of leaves in the tree and wj is the score assigned to the jth leaf.\n\nThe optimal structure of the tree is found by minimizing:\n\nGene Ontology (GO) and pathway enrichment analysis is a widely used statistical method in bioinformatics that helps researchers to gain insights into the biological relevance of extensive gene sets. In T2D, persistent exposure to high glucose levels and free fatty acids induces beta-cell dysfunction and may initiate beta-cell apoptosis.50 Sterol regulatory element binding proteins (SREBPs) regulate lipid production and adipogenesis. SREBPs expression was considerably reduced in individuals with type 2 diabetes.51 Neutrophil degranulation is related to an aberrant echocardiographic patterning T2D.52 The expression of the FAS signaling pathway (CD95) was connected to systemic and skeletal muscle insulin resistance.53 IFN-gamma or TNF-alpha Mediated Cell Proliferation is associated with T2D. Interferon-gamma is crucial for the ruination of cells and the onset of T2D.54 Tumor necrosis factor (TNF)-alpha, a cytokine derived primarily from macrophages and adipocytes, can encourage insulin resistance (IR) and inevitably aid the advancement of T2D (T2D).55 The innate immune system plays a crucial part in T2D by contributing to low-grade inflammation and insulin resistance, which are key factors in the development and progression of the disease.56 Several MHC class I alleles, such as HLA-B and MHC class II alleles(including HLA-DRB1 and HLA-DQB1) were associated with T2D risk.57,58\n\nWe identified hub proteins that are expressed highly or poorly in T2D patients. Patients with T2D had significantly greater serum TP53 levels than healthy non-diabetic controls.59 The decreased level of CTBP1-AS2 was linked with diabetes in the Iranian population.60 The presence of complement factor 3 (C3) is linked to insulin resistance.61 ROS- and RAS-mediated diabetic retinopathy involves PRMT-1 and DDAHs-induced ADMA upregulation.62 In a sizeable portion (9–15%) of patients with Type 2 or persistent Type 1 diabetes, CD38 autoantibodies have been discovered. Most of these autoantibodies (about 60%) exhibit agonistic characteristics, such as Ca2+ mobilization in lymphocytic cell lines and in pancreatic islets, indicating that they are biologically active. CD38 autoantibodies promote glucose-mediated insulin secretion in human pancreatic islets.63 The hypomethylation of CASP10 may result from T2D and severe and long-lasting hyperglycemia.64 In humans, CFTR deficiency causes intrinsic abnormalities in insulin secretion inside the islets.65\n\nOur discovered TFs are associated with T2D. The adult human pancreas has been found to express the Sox2 gene. It seems improbable that Sox2 will have a genetic influence on the development of T2D.66 In the human intestine, MYC transcription factor expression is correlated with either glycaemic management (HbA1c level) or body mass index (BMI).67 In the skeletal muscle of T2D patients, STAT3 is constitutively phosphorylated, and increased STAT3 signaling plays a role in the etiology of T2D and insulin resistance.68 Much research has been conducted on the peroxisome proliferator-activated receptor gamma (PPARG), whose ligands have become effective insulin sensitizers in type 2 diabetes.69 YY1 plays an important role in T2DM and it might be useful as a new therapeutic target in the fight against the disease.70\n\nOur identified miRNAs are also linked to T2D. Targeting the SOCS1-mediated NF-B Pathway, miR-210-3p Increases Insulin Resistance and Obesity-Induced Adipose Tissue Inflammation. MiR-374a-5p appears to be associated with the downregulation of pro-inflammatory biomarkers that are connected to insulin resistance and is elevated in metabolically healthy obese persons as compared to metabolically abnormal obese patients.71 A possible biomarker for the early diagnosis of diabetic nephropathy is miR-21-3p, whose expression is downregulated in association with the onset of diabetic nephropathy.72 MiR-7-5p targeting may be a likely therapeutic approach to metabolic illnesses brought on by insulin dysfunction.73 Patients with diabetic neuropathy have dysregulated long non-coding miR-1-3p axis.74 Compared to healthy individuals, peripheral blood mononuclear cells (PBMCs) obtained from T2D patients exhibited low miR-155 expression.75\n\nOur identified potential drug molecules can be effective for T2D patients. Insulin Human N (medium-acting) and Insulin Human R (short-acting) both are used in diabetes mellitus to lower blood glucose levels. Insulin glargine modulates carbohydrate, protein, and lipid metabolism by suppressing hepatic glucose synthesis and lipolysis and improving peripheral glucose clearance. Long-acting insulin, or insulin peglispro, is used to treat both T1D and T2D.76 Glyburide belongs to the class of medications known as sulfonylureas, which stimulate the pancreas to produce insulin and reduce blood sugar levels.77 T2D and its associated illnesses may be prevented and treated using myristic acid.78 There is some uncertainty on how Dalteparin, Lovastatin, Atorvastatin, Myristic acid, M-cresol, L-lysine, L-ornithine, Ivacaftor, Bumetanide, and Lumacaftor interact with T2D. So, more studies as well as preclinical and clinical trials are required.\n\n\n5. Conclusions\n\nAs our research aims to provide the machine learning approach to identify significant genes through feature importance technique and to address the global burden of T2D and enhance the lives of individuals, affected by this chronic disease, based on bioinformatics methods, we went through machine learning approach and common bioinformatics methods.\n\nIn terms of the machine learning approach, our research represents a remarkable advancement in bioinformatics and (T2D) research. Combining machine learning algorithms, statistical analysis, and bioinformatics techniques, we have gained valuable insights into the molecular mechanisms underlying T2D. It would help us to identify expressed genes not solely being dependable on the conventional bioinformatics approach, Differentially Expressed Genes (DEGs). As well as, for a large number of features, a machine learning approach would be an effective and more reliable approach to predict expressed genes. We have successfully processed and analyzed vast amounts of information by utilizing large volumes of transcriptomic data. Our XGBoost model could be an example that showed a noticeable performance with 94.1% accuracy. This achievement demonstrates the potential of machine learning as a powerful tool for precise and efficient T2D diagnosis, which also can significantly impact clinical practice by enabling early intervention and personalized treatment approaches based on count data.\n\nOn the other hand, in our comprehensive molecular biomarker study on T2D, we analyzed a diverse set of molecular entities, including 20 pathways, 30 gene ontologies, 51 transcriptional factors, 18 hub-genes, 18 miRNAs, and 18 potential drugs where we were able to validate a subset among them. So, according to our validation, key pathways such as SREBPs, neutrophil degranulation, FAS signaling, IFNgamma/TNFalpha-mediated cell proliferation, and the innate immune system were highlighted as central to T2D’s development. Hub proteins, notably TP53, CTBP1-AS2, C3, PRMT-1, DDAHs, CD38 autoantibodies, CASP10, and CFTR, present promising avenues for disease research and treatment. Similarly, transcriptional factors like Sox2, MYC, STAT3, PPARG, and YY1, coupled with miRNAs such as miR-210-3p, miR-374a-5p, miR-21-3p, miR-7-5p, and miR-155, shed light on the regulatory dynamics underpinning T2D. Furthermore, our research identified potential drug molecules, including insulin analogs, sulfonylureas, myristic acid, and other compounds, that hold promise for therapeutic intervention. While further preclinical and clinical trials are necessary to validate their efficacy and safety profiles, these findings offer potential avenues for revolutionizing T2D treatment strategies and improving patient outcomes.\n\nOverall, this study represents a significant advancement in using machine learning to identify expressed genes from RNA sequence count data, and by integrating key bioinformatics methods on T2D and validating our findings against prior research, we offer a robust approach to understanding and addressing T2D at the molecular level.\n\nOne of the limitations of our study is the accuracy of our models, which needs further improvement. While our current approach provided insights, the application of deep learning models in future studies could enhance the precision of our findings. Additionally, there remains a set of biomarkers that we have yet to validate with existing literature. A thorough validation of these biomarkers is essential, as it would offer researchers a more detailed understanding of expressed genes, ultimately aiding in more accurate analyses and better strategies to address T2D.\n\n\nAuthor contributions\n\nMd Al Amin: Took the lead in conceptualization and design of the work; primary role in data curation and analysis; led the writing of the original draft of the manuscript; major contributor in review and editing; gave final approval of the version to be published; agreed to be accountable for all aspects of the work.\n\nFeroza Naznin: Played a significant role in the formal analysis of the data; contributed to the investigation; involved in writing, review, and editing of the manuscript; gave final approval and agreed to be accountable for all aspects of the work.\n\nMost Nilufa Yeasmin: Led the acquisition of resources; involved in data curation; gave final approval and agreed to be accountable for all aspects of the work.\n\nMd Sumon Sarkar: Took the lead in software development; contributed to the validation of the results; gave final approval and agreed to be accountable for all aspects of the work.\n\nMd Misor Mia: Led the visualization process; supported the investigation; gave final approval and agreed to be accountable for all aspects of the work.\n\nAbdullahi Chowdhury: Contributed to the methodology; supported the writing, review, and editing of the manuscript; gave final approval and agreed to be accountable for all aspects of the work.\n\nMd Zahidul Islam: Acted as the primary supervisor and administrator of the project; took a leading role in writing, reviewing, and editing the manuscript; gave final approval and agreed.",
"appendix": "Data availability\n\nZenodo: Data from Analysis on Type-2 Diabetes RNA-Sequence Data, https://doi.org/10.5281/zenodo.10603991. 79\n\nThis project contains the following underlying data:\n\n- Data from analysis.zip (protein-protein interaction network analysis, gene ontology and pathway analysis, transcription factor and miRNA analysis, hub gene extraction, and protein-drug interactions).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nZenodo: Top 100 proteins, https://doi.org/10.5281/zenodo.10603257. 80\n\nThis project contains the following extended data:\n\n- Top-100-proteins.txt (supplementary file-1).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nData repository: Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI). Title: RNA Sequencing of Single Human Islet Cells Reveals Type 2 Diabetes Genes. The persistent identifier: GSE81608. Archived source code at time of publication: http://dx.doi.org/10.1016/j.cmet.2016.08.018 Link of dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE81608 and http://www.ilincs.org/apps/grein/?gse=GSE81608\n\nDescription of this dataset: Gene Expression Omnibus (GEO) at the National Center for Biotechnology. (Pancreatic islet cells are critical for maintaining normal blood glucose levels and their malfunction underlies diabetes development and progression. They used single-cell RNA sequencing to determine the transcriptomes of 1,492 human pancreatic α -, β -, δ - and PP cells from non-diabetic and type 2 diabetes organ donors. They identified cell type specific genes and pathways as well as 245 genes with disturbed expression in type 2 diabetes. Importantly, 92% of the genes have not previously been associated with islet cell function or growth. Comparison of gene profiles in mouse and human α - and β -cells revealed species-specific expression. All data are available for online browsing and download and will hopefully serve as a resource for the islet research community.)\n\nLicense: Data is available under the terms of the Open Database License. GEO is an open-access database, meaning the data stored within it is freely available for anyone to access, download, and reuse.\n\nFor the citation of this dataset: “Xin, Y., Kim, J., Okamoto, H., Ni, M., Wei, Y., Adler, C., Murphy, A.J., Yancopoulos, G.D., Lin, C. and Gromada, J., 2016. RNA sequencing of single human islet cells reveals type 2 diabetes genes. Cell metabolism, 24(4), pp. 608-615.”\n\n\nReferences\n\nLove M, Anders S, Huber W: Differential analysis of count data–the deseq2 package. Genome Biol. 2014; 15(550): 10–1186. 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Biol. 2014; 8(4): 1–7.\n\nKhan A, Fornes O, Stigliani A, et al.: Jaspar 2018: update of the open-access database of transcription factor binding profiles and its web framework. Nucleic Acids Res. 2018; 46(D1): D260–D266. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLachmann A, Xu H, Krishnan J, et al.: Chea: transcription factor regulation inferred from integrating genome-wide chip-x experiments. Bioinformatics. 2010; 26(19): 2438–2444. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSethupathy P, Corda B, Hatzigeorgiou AG: Tarbase: A comprehensive database of experimentally supported animal microrna targets. RNA. 2006; 12(2): 192–197. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuang H-Y, Lin Y-C-D, Li J, et al.: mirtarbase 2020: updates to the experimentally validated microrna–target interaction database. Nucleic Acids Res. 2020; 48(D1): D148–D154. PubMed Abstract | Publisher Full Text\n\nZhou G, Soufan O, Ewald J, et al.: Networkanalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Res. 2019; 47(W1): W234–W241. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWishart DS, Feunang YD, Guo AC, et al.: Drugbank 5.0: a major update to the drugbank database for 2018. Nucleic Acids Res. 2018; 46(D1): D1074–D1082. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFawcett T: An introduction to roc analysis. Pattern Recogn. Lett. 2006; 27(8): 861–874. Publisher Full Text\n\nSofaer HR, Hoeting JA, Jarnevich CS: The area under the precision-recall curve as a performance metric for rare binary events. Methods Ecol. Evol. 2019; 10(4): 565–577. Publisher Full Text\n\nLever J, Krzywinski M, Altman N: Points of significance: model selection and overfitting. Nat. Methods. 2016; 13(9): 703–704. Publisher Full Text\n\nLange RT, Lippa SM: Sensitivity and specificity should never be interpreted in isolation without consideration of other clinical utility metrics. Clin. Neuropsychol. 2017; 31(6-7): 1015–1028. PubMed Abstract | Publisher Full Text\n\nCheng C, Alexander R, Min R, et al.: Understanding transcriptional regulation by integrative analysis of transcription factor binding data. Genome Res. 2012; 22(9): 1658–1667. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLahti JL, Tang GW, Capriotti E, et al.: Bioinformatics and variability in drug response: a protein structural perspective. J. R. Soc. Interface. 2012; 9(72): 1409–1437. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaldi P, Brunak S: Bioinformatics: the machine learning approach. MIT Press; 2001.\n\nCnop M, Welsh N, Jonas J-C, et al.: Mechanisms of pancreatic β-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes. 2005; 54(suppl_2): S97–S107.\n\nLaudes M, Barroso I, Luan J, et al.: Genetic variants in human sterol regulatory element binding protein-1c in syndromes of severe insulin resistance and type 2 diabetes. Diabetes. 2004; 53(3): 842–846. PubMed Abstract | Publisher Full Text\n\nMinistrini S, Andreozzi F, Montecucco F, et al.: Neutrophil degranulation biomarkers characterize restrictive echocardiographic pattern with diastolic dysfunction in patients with diabetes. Eur. J. Clin. Investig. 2021; 51(12): e13640. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWueest S, Mueller R, Blüher M, et al.: Fas (cd 95) expression in myeloid cells promotes obesity-induced muscle insulin resistance. EMBO Mol. Med. 2014; 6(1): 43–56. PubMed Abstract | Publisher Full Text | Free Full Text\n\nvon Herrath MG , Oldstone MB: Interferon-γ is essential for destruction of β cells and development of insulin-dependent diabetes mellitus. J. Exp. Med. 1997; 185(3): 531–540.\n\nTilg H, Moschen AR: Inflammatory mechanisms in the regulation of insulin resistance. Mol. Med. 2008; 14: 222–231. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBerbudi A, Rahmadika N, Tjahjadi AI, et al.: Type 2 diabetes and its impact on the immune system. Curr. Diabetes Rev. 2020; 16(5): 442–449. PubMed Abstract | Publisher Full Text\n\nMarzban A, Kiani J, Hajilooi M, et al.: Hla class ii alleles and risk for peripheral neuropathy in type 2 diabetes patients. Neural Regen. Res. 2016; 11(11): 1839–1844. PubMed Abstract | Publisher Full Text\n\nFrydrych LM, Bian G, O’Lone DE, et al.: Obesity and type 2 diabetes mellitus drive immune dysfunction, infection development, and sepsis mortality. J. Leukoc. Biol. 2018; 104(3): 525–534. PubMed Abstract | Publisher Full Text\n\nSliwinska A, Kasznicki J, Kosmalski M, et al.: Tumour protein 53 is linked with type 2 diabetes mellitus. Indian J. Med. Res. 2017; 146(2): 237–243. PubMed Abstract | Publisher Full Text | Free Full Text\n\nErfanian Omidvar M, Ghaedi H, Kazerouni F, et al.: Clinical significance of long noncoding rna vim-as1 and ctbp1-as2 expression in type 2 diabetes. J. Cell. Biochem. 2019; 120(6): 9315–9323. PubMed Abstract | Publisher Full Text\n\nWlazlo N, Van Greevenbroek MM, Ferreira I, et al.: Complement factor 3 is associated with insulin resistance and with incident type 2 diabetes over a 7-year follow-up period: the codam study. Diabetes Care. 2014; 37(7): 1900–1909. PubMed Abstract | Publisher Full Text\n\nChen Y, Xu X, Sheng M, et al.: Prmt-1 and ddahs-induced adma upregulation is involved in ros-and ras-mediated diabetic retinopathy. Exp. Eye Res. 2009; 89(6): 1028–1034. PubMed Abstract | Publisher Full Text\n\nAntonelli A, Ferrannini E: Cd38 autoimmunity: recent advances and relevance to human diabetes. J. Endocrinol. Investig. 2004; 27: 695–707. PubMed Abstract | Publisher Full Text\n\nVolkmar M, Dedeurwaerder S, Cunha DA, et al.: Dna methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. EMBO J. 2012; 31(6): 1405–1426. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKoivula FNM, McClenaghan NH, Harper AG, et al.: Islet-intrinsic effects of cftr mutation. Diabetologia. 2016; 59: 1350–1355. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGu HF, Gu T, Östenson C-G, et al.: Evaluation of sox2 genetic effect on the development of type 2 diabetes. Gene. 2011; 486(1-2): 94–96. PubMed Abstract | Publisher Full Text\n\nEllegaard A-M, Knop FK: Myc mrna expression throughout the intestine is not associated with body mass index or type 2 diabetes, Endocrinology. Diabetes Metab. 2022; 5(2): e00327. Publisher Full Text\n\nMashili F, Chibalin AV, Krook A, et al.: Constitutive stat3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. Diabetes. 2013; 62(2): 457–465. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJanani C, Kumari BR: Ppar gamma gene–a review. Diabetes Metab. Syndr. Clin. Res. Rev. 2015; 9(1): 46–50. PubMed Abstract | Publisher Full Text\n\nKosasih FR, Bonavida B: Yy1-mediated regulation of type 2 diabetes via insulin, YY1 in the Control of the Pathogenesis and Drug Resistance of Cancer.2021; 271–287.\n\nDoumatey AP, He WJ, Gaye A, et al.: Circulating mir-374a-5p is a potential modulator of the inflammatory process in obesity. Sci. Rep. 2018; 8(1): 7680. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAkpınar K, Aslan D, Fenkçi SM, et al.: mir-21-3p and mir-192-5p in patients with type 2 diabetic nephropathy. Diagnosis. 2022; 9(4): 499–507. PubMed Abstract | Publisher Full Text\n\nSaeidi L, Shahrokhi SZ, Sadatamini M, et al.: Can circulating mir-7-1-5p, and mir-33a-5p be used as markers of t2d patients? Arch. Physiol. Biochem. 2021; 129: 771–777. Publisher Full Text\n\nAshjari D, Karamali N, Rajabinejad M, et al.: The axis of long non-coding rna malat1/mir-1-3p/cxcr4 is dysregulated in patients with diabetic neuropathy. Heliyon. 2022; 8(3): e09178. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJankauskas SS, Gambardella J, Sardu C, et al.: Functional role of mir-155 in the pathogenesis of diabetes mellitus and its complications. Non-coding RNA. 2021; 7(3): 39. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJacober S, Prince M, Beals J, et al.: Basal insulin peglispro: overview of a novel long-acting insulin with reduced peripheral effect resulting in a hepato-preferential action. Diabetes. Obes. Metab. 2016; 18: 3–16. Publisher Full Text\n\nLanger O, Yogev Y, Xenakis EM, et al.: Insulin and glyburide therapy: dosage, severity level of gestational diabetes, and pregnancy outcome. Am. J. Obstet. Gynecol. 2005; 192(1): 134–139. 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}
|
[
{
"id": "303201",
"date": "22 Jul 2024",
"name": "Farizky Martriano Humardani",
"expertise": [
"Reviewer Expertise in silico and endocrine"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study presents comprehensive and well - organized data on markers for T2DM and associated drugs. However, I have several feedback points for improvement:\n1. Points 3.3, 3.4, and 3.5 do not show any correlation or new data analysis. If these points are correlated or are a continuation of previous results, please state this in the first sentence. This will help clarify whether the data is new or part of a continuous analysis, preventing potential confusion for readers.\n2. Point 3.6 also needs clarification. It's unclear whether the medications listed are considered based on previous results or other factors. Additionally, the reason why these medications are labeled as \"potential\" is not evident. Please provide the rationale for this classification.\n3. The paragraph stating, \"We identified hub proteins that are expressed highly or poorly in T2D patients. Patients with T2D had significantly greater serum TP53 levels than healthy non-diabetic controls,\" should list the genes with reduced or increased expression before specifying individual genes. For example, \"The decreased level of CTBP1-AS2....\" should precede specific gene mentions. This issue is also found in other paragraphs and needs revision.\n4. The findings in the discussion should be elaborated. I suggest integrating the results, such as TF, gene expression, and other findings, into a comprehensive mechanism of T2DM. This would enhance the discussion beyond merely mentioning results, such as \"MiR-7-5p targeting may be a likely therapeutic approach to metabolic illnesses brought on by insulin dysfunction. Patients with diabetic neuropathy have a dysregulated long non-coding miR-1-3p axis. Compared to healthy individuals, peripheral blood mononuclear cells (PBMCs) obtained from T2D patients exhibited low miR-155 expression.\"\n5. The conclusion is too lengthy and should be streamlined. For instance, the following passage should be discussed in the results or discussion section: \"On the other hand, in our comprehensive molecular biomarker study on T2D, we analyzed a diverse set of molecular entities, including 20 pathways, 30 gene ontologies, 51 transcriptional factors, 18 hub-genes, 18 miRNAs, and 18 potential drugs where we were able to validate a subset among them. So, according to our validation, key pathways such as SREBPs, neutrophil degranulation, FAS signaling, IFNgamma/TNFalpha-mediated cell proliferation, and the innate immune system were highlighted as central to T2D’s development. Hub proteins, notably TP53, CTBP1-AS2, C3, PRMT-1, DDAHs, CD38 autoantibodies, CASP10, and CFTR, present promising avenues for disease research and treatment. Similarly, transcriptional factors like Sox2, MYC, STAT3, PPARG, and YY1, coupled with miRNAs such as miR-210-3p, miR-374a-5p, miR-21-3p, miR-7-5p, and miR-155, shed light on the regulatory dynamics underpinning T2D. Furthermore, our research identified potential drug molecules, including insulin analogs, sulfonylureas, myristic acid, and other compounds, that hold promise for therapeutic intervention. While further preclinical and clinical trials are necessary to validate their efficacy and safety profiles, these findings offer potential avenues for revolutionizing T2D treatment strategies and improving patient outcomes.\" Any redundant statements or those already discussed should be revised.\n6. Overall, this study is good and comprehensive but requires revisions to enhance the quality of the manuscript. Good job, authors!\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "317925",
"date": "01 Oct 2024",
"name": "Hemant Kulkarni",
"expertise": [
"Reviewer Expertise T2D",
"machine learning / deep 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\nThe authors take a machine learning approach to identification of DEGs in the context of type 2 diabetes. The dataset is from real-life, the sample size is adequate, the methods are well described and the results appropriately stated.\nAll the machine learning models are well established and several studies exist that make a similar assessment of the potential use of ML in prediction of the disease state. Indeed, prediction of the disease state is (or should be) less of a concern for this type of study, what matters is a reliable identification of the DEGs. The article uses traditional methods for assessment of the relevance of the identified DEGs but still it neither obviates nor circumvents the real question - is the DEG identified by the ML model more reliable or dependable than those identified by the traditional methods. I don't think this study addresses that question convincingly. The study also doesn't provide any explanation of how the model identifies a specific DEG other than importance as quantified by gain.\nIn short, the study doesn't provide any mechanistic insights through ML modeling - it only offers an alternative approach to DEG identification. Whether this approach is scientifically more rigorous is neither addressed by this study nor clearly evident.\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/13-161
|
https://f1000research.com/articles/12-144/v1
|
08 Feb 23
|
{
"type": "Research Article",
"title": "The transparency of quantitative empirical legal research published in highly ranked law journals (2018–2020): an observational study",
"authors": [
"Jason Chin",
"Kathryn Zeiler",
"Natali Dilevski",
"Alex O Holcombe",
"Rosemary Gatfield-Jeffries",
"Ruby Bishop",
"Simine Vazire",
"Sarah Schiavone",
"Kathryn Zeiler",
"Natali Dilevski",
"Alex O Holcombe",
"Rosemary Gatfield-Jeffries",
"Ruby Bishop",
"Simine Vazire",
"Sarah Schiavone"
],
"abstract": "Background: Scientists are increasingly concerned with making their work easy to verify and build upon. Associated practices include sharing data, materials, and analytic scripts, and preregistering protocols. This shift towards increased transparency and rigor has been referred to as a “credibility revolution.” The credibility of empirical legal research has been questioned in the past due to its distinctive peer review system and because the legal background of its researchers means that many often are not trained in study design or statistics. Still, there has been no systematic study of transparency and credibility-related characteristics of published empirical legal research. Methods: To fill this gap and provide an estimate of current practices that can be tracked as the field evolves, we assessed 300 empirical articles from highly ranked law journals including both faculty-edited journals and student-edited journals. Results: We found high levels of article accessibility, especially among student-edited journals. Few articles stated that a study’s data are available. Preregistration and availability of analytic scripts were very uncommon. Conclusion: We suggest that empirical legal researchers and the journals that publish their work cultivate norms and practices to encourage research credibility. Our estimates may be revisited to track the field’s progress in the coming years.",
"keywords": [
"metaresearch",
"open science",
"transparency",
"credibility",
"empirical legal research"
],
"content": "Introduction\n\nIncreasing the transparency of research is a key component of the ongoing credibility revolution1 occurring in many fields.2 This movement seeks to improve research credibility by ensuring that claims can be tested and critiqued by other researchers. Further benefits of the credibility revolution are efficiency, in that transparent research is reusable by other researchers to explore new questions,3 and that transparent research enhances public trust in science, comporting with lay expectations about how science ought to be conducted.4 Despite its work being cited by courts and policymakers,5 the field of empirical legal research has so far largely refrained from engaging in significant reforms.6 In this article, we measure the transparency and other related characteristics of 300 empirical legal studies published between 2018 and 2020 in law journals rated highly by traditional metrics. For the purposes of this article, we define empirical research as research that performs analysis on quantitative data.7\n\nThe “credibility revolution”8 responded, in part, to a “crisis”9 reported in many fields, in which researchers were unable to replicate the findings of published studies.10 Failures to replicate and other controversies were well-publicized and documented in psychology.11 However, other fields that run adjacent to legal research have not been immune, such as economics12 and criminology.13 Recently, for instance, economists have described and documented reproducibility failures in studies employing secondary data.14\n\nThe credibility revolution involves a host of changes to the research process, such as improved transparency, higher standards of evidence, and more replication research.15 Transparency-focused reforms make the data and process underlying results more accessible, making it easier for other researchers to verify, correct, and build upon existing research.16 Transparency can also be advanced through preregistration (or prospective trial registration and a pre-analysis plan as it is called in medical research and economics respectively), which is a time-stamped statement of the research protocols and hypotheses that is posted prior to data collection.17 Preregistration is designed to address publication bias and questionable research practices (known in some fields as researcher degrees of freedom, p-hacking, and specification searching). Similarly, registered reports, which are research reports that are peer-reviewed and usually preregistered prior to data collection, aim to promote transparency and decrease incentives to engage in questionable research practices.18 Early research suggests results from registered reports contain a more realistic proportion of null results.19\n\nFuller reporting in the form of data sharing, as well as providing more details of methods and statistical analyses performed, allows other researchers to better scrutinize findings and detect errors in research.20 For instance, researchers recently discovered a case of data fraud in a study purporting to find that signing one’s name before versus after providing information in a document reduces dishonesty.21 This study has been cited often for its legal and policy consequences,22 including by the UK Behavioural Insights Team (i.e., Nudge Unit).23 Beyond availability of the raw data, which helped other researchers to uncover the fraud, replication also played a role. Failures to replicate other studies in the paper led to increased scrutiny of the entire set of results, which eventually led researchers to take a closer look at the data. One of the authors of the problematic paper, who had worked on the non-fraudulent studies reported within the same article, wrote in response to the discovery of the fraud:24\n\nThough very painful, this experience has reinforced my strong commitment to the Open Science movement. As it clearly shows, posting data publicly, pre-registering studies, and conducting replications of prior research is key to scientific progress.\n\nTransparency can also make research more efficient because other researchers can leverage open data and materials to test new questions, and to synthesize existing data in meta-analyses.25 Conversely, research efforts can be wasted in the absence of open data in the sense that those data cannot be obtained by subsequent researchers seeking to reuse them. This is because researchers change emails and institutions or leave academic research behind altogether, making them unavailable to share data upon request.26 Moreover, many researchers who are reachable, decline to share data and materials when they are contacted, or promise to deliver the data but never follow through.27\n\nSeveral metascientific studies, across a variety of fields, have conducted “state-of-the-science” audits, in which recent published studies are randomly sampled and coded for various transparency and credibility-related features.28 These metascientific studies have generally found very low levels of transparency. One study examined psychology articles published from 2014-2017.29 Only about 2% of the studies sampled had available data, approximately 17% had available materials, and 3% were preregistered.30 Note, however, that studies published during this timeframe were conducted in the early days of the reported crisis in psychology.31\n\nWhile these findings are worrisome, recent reforms in other fields may have led to an increase in transparency related practices in recent years. For instance, journals that implemented open data policies (e.g., requiring open data under some circumstances) show substantial increases in the proportion of studies with open data, albeit with imperfect compliance.32\n\nMoreover, a survey across many fields directly asking researchers about when they first engaged in a transparency-related practice (open data, open materials, open code, and preregistration) found that uptake has increased in recent years, suggesting that recent reforms and initiatives are moving the needle.33\n\nNumerous researchers have questioned the credibility of empirical legal research. In a relatively early critique, Epstein and King reviewed all law journal articles published over a ten-year period that contain the word “empirical” in the title.34 They found numerous errors, generally centering around poor transparency and reproducibility. For instance, many authors had not fully described how they gathered data and then reasoned from that data to their conclusion. Similar critiques have been levied since then, such as reports that empirical legal studies misinterpret statistical results (e.g., p-values), misapply statistical methods, and fail to verify that the assumptions underlying their methods were met.35 Furthermore, author eminence likely plays a biasing role in empirical legal research because student editors may be especially vulnerable to accepting articles based on the status of the author. Even outside of the student context, author status has been shown to affect peer review decisions.36 Most recently, Huber and colleagues found that an article submitted with a Nobel Laureate as corresponding author received over 40% fewer reject recommendations as compared to the same manuscript with a PhD student as corresponding author.37\n\nMatthews and Rantanen conducted the most recent metaresearch on empirical legal research, measuring data availability.38 They sampled from the top 20 journals in the Washington & Lee rankings from 2010-2019, as well the Northwestern Law Review and the Journal of Empirical Legal Studies. They added the latter two because they provided a contrast with the other journals in the sample in terms of peer review. The Northwestern Law Review is one of the rare student-edited journals to routinely seek peer reviews for empirical work, and the Journal of Empirical Legal Studies is fully faculty-edited and peer reviewed. Matthews and Rantanen found low levels of data availability across the 614 articles in their sample, with only 12% making data available without contacting the author. Moreover – and despite its specialization on empirical works and policy encouraging authors to make their data available – the Journal of Empirical Legal Studies underperformed the other journals with only 6% data availability.\n\nLimited data availability is especially troubling given several other aspects of empirical legal research that sets it apart from cognate fields. For instance, as individuals formally trained in the law rather than in empirical science, many authors of empirical legal work have less methodological expertise than researchers in other sciences. This lack of training may contribute to errors and unfamiliarity with methodological safeguards. The field’s lack of expertise also limits the usefulness of peer review (for journals that do use it).\n\nThese factors suggest that transparency is especially important for empirical legal research. For instance, accessible data and analytic scripts and preregistration can assist with error and bias detection. And, other aspects of transparency, such as articles that are openly available and declare funding sources and conflict of interests, help others assign credibility to reported results. Still, outside of the low data availability at elite journals, there is little current knowledge about transparency of empirical legal research. The last large study that assessed a broad array of transparency indicia was conducted 20 years ago. It included only articles with “empirical” in the title39 and the results were not quantified in a way that makes them easy to update and revisit. This study seeks to fill these gaps.\n\n\nMethods\n\nTo estimate the transparency of credibility-related features of recent empirical legal research, we examined a sample of 300 law journal articles published between 2018 and 2020. We chose this sample size because it is consistent with many previous transparency studies.40 Based on those authors’ reports41 of how long it took them to extract the relevant features of each article, we judged that coding 300 articles was a practical target given our available resources. To provide a comparison between the student-edited journals (that tend to not use peer review, but rather the judgment of student editors to make acceptance decisions) and faculty-edited journals (that tend to rely on peer review), we chose 150 articles from each. We classified articles as empirical if they included original analyses using descriptive or inferential statistics of original or pre-existing quantitative data (e.g., survey studies, content analyses of judicial decisions, meta-analyses).\n\nAs described below, we coded features such as statements about the availability of data, preregistration, and declarations of conflicts of interest. This is the first study of its kind in empirical legal research, and we are not testing hypotheses; thus, the results should be considered descriptive and exploratory. This study is preregistered and provides open data, code, and materials.79\n\nWe deviated from previous studies measuring transparency in two main ways. First, previous studies using this type of protocol focused on fields whose journals contain a high proportion of empirical research (e.g., psychology, organizational behavior research, otolaryngology, addiction medicine),42 so they randomly sampled studies without screening out studies that did not use empirical methods. This approach would have been inappropriate for the current study because it would have led us to include a large number of non-empirical studies (~90% of published work, according to a prior estimate).43 As a result, we developed an approach for early screening of non-empirical research (see literature search string below). We also deviated from some previous studies by sampling only from highly ranked journals. This may have biased our results towards finding higher research transparency than the field generally has, because higher rank typically translates to greater selectivity, and thus should in principle enable higher standards. Note also that given the perceived importance of the journals in our sample, low levels of transparency would be especially concerning.\n\nTo develop a search string to more efficiently identify and sample articles that met our specifications, we conducted a preliminary examination of the literature. We coded 2019-2020 articles from 10 law journals that Washington and Lee ranks in the top 25 (1,024 total articles).44 Through reading those articles, we identified 92 (or 9% of the sample) meeting our definition of empirical within this dataset.45\n\nUsing the knowledge from that preliminary examination, we first considered two different ways of more quickly identifying empirical articles without reviewing the full text. First, we considered selecting only articles with the word “empirical” in the title as Epstein and King had done in their landmark study. However, only 10% of the empirical articles in the preliminary examination sample had the word “empirical” in their title. This strategy, therefore, would miss a great deal of empirical work, raising concerns about the representativeness of the sample and making it more difficult to find our target of 300 recent empirical studies. We also considered selecting only articles with “empirical” in their abstract; however, that strategy would have missed approximately 50% of the articles identified by the more intensive method used in our preliminary examination.\n\nUltimately, we decided to use the words in the abstracts of the 92 empirical articles we identified in our preliminary examination, and to write a search string based on those words. That search string is:\n\nABS (“content analysis” OR data* OR behavioral OR behavioural OR empirical OR experiment OR meta-ana* OR multidimensional OR multivariate OR quantitative OR statistical OR study OR studies OR survey OR systematic)\n\nOne limitation of this strategy is that, in our preliminary examination, about 8% of the empirical articles we identified did not have an abstract. As a result, any search strategy that uses abstract searches is bound to miss a small proportion of empirical articles, such as commentaries with a trivial empirical component. This may bias our findings towards including more instances of systematic data analysis that would be adverted to in an abstract. Despite this limitation, the search method is efficient (i.e., full text searches would have yielded too many false positives for our team to review) and reproducible (i.e., the full search string and results are provided, as are all exclusions and reasons for exclusion).\n\nSample\n\nFigure 1 details our sampling process and exclusions. We used the search string described above to search Scopus for articles published between 1st January 2018, and the date of our search, 29th January 2021. We populated our overall sample of 300 articles with 150 articles from the top 25 student-edited journals from the Washington and Lee rankings (W&L) (based on its “combined score” in 2019) and 150 faculty-edited journals from the 25 journals (by impact 2019 factor) in the Web of Science’s “law” database.46 That is, we applied our search string to both of those journal lists. The Washington and Lee search returned 596 articles and the Web of Science search returned 859 articles (see Extended data).80\n\nArticles were first identified through the Scopus search string described in the methods. They were then screened for eligibility in random order until the samples were complete. The excluded articles and the reasons for their exclusion are available in the Extended data, “W&L screened out” and \"Web of Science screened out”.\n\nBecause searches returned several of what we classified as non-empirical articles (e.g., the abstract contained the word “data” to describe data regulation laws), one author (JC) randomly sorted both lists and then screened out articles that did not meet our inclusion criterion (i.e., the study includes an analysis of quantitative data) until we reached the pre-specified sample of 150 articles for each group (Figure 1). Of the 596 articles in the W&L sample, we needed to review 510 to obtain our sample of 150 (i.e., 31% of those reviewed were selected, the rest were excluded). For the Web of Science sample, we needed to review 383 to find 150 empirical articles (i.e., 40.1% of those reviewed were selected, the rest were excluded).\n\nThe relatively high rate of exclusions suggests that our search string was overly inclusive, adding more work for us but reducing the chance that we missed a large proportion of empirical articles. The articles screened out and the reasons for their exclusion are described in our Extended data (“W&L screened out” and “Web of Science screened out”).80. After we initiated coding of these articles with the protocol below, we found that 8 were incorrectly categorized as empirical, so we selected the next 8 from the list as replacements. These are the numbers that are reflected in Figure 1 and above.\n\nArticles were coded using the structured form developed by Hardwicke and colleagues.47 Following the Hardwicke et al., protocol (as well as other transparency coding projects for systematic reviews, see O’Dea et al.),48 each article was coded by two of the authors, with disagreements resolved through discussion between those coders and a third author if the coders could not agree (see Extended data).80 The coders were all trained on five articles and did not begin coding the target sample of articles until they reached consensus on the five training articles. As we discuss below, two items were difficult to code, and so we discontinued coding them and do not present the result for them. For multiple-study articles (we defined studies as distinct data collection activities), we coded only the first-reported study. Coding one article in the student-edited sample took about 30-45 minutes. Coding an article in the faculty-edited sample took about 10-20 minutes. This reflects the longer length of the articles in the student-edited sample and that their methods and data were frequently difficult to locate due to the lack of a standard article format. We coded articles from February to September 2021.\n\nThe features of the articles that we coded are detailed in the coding sheet and in Table 1 (and further detailed in our preregistration). Some of these features are relevant background information on the studies, such as the statistics used by the researchers, the nature of the data, and data sources. Others are relevant to the transparency and credibility of the research, such as whether authors stated that data and analysis scripts were available, whether the study was preregistered, and whether it was a replication (replications have helped uncover spurious results in prior studies).\n\nThe full set of variables can be found in the full structured coding form.\n\n\n\n• Was the article available through the journal’s website (without university library access, i.e., gold open access)?\n\n\n\n• Was the article available through another service (e.g., ResearchGate, SSRN)?\n\n\n\n• Does the article state whether or not data are available?\n\n\n\n• How does the statement indicate the data are available?\n\n\n\n• Can you access, download, and open the data files (without contacting the author)?\n\n\n\n• Does the article state whether or not analysis scripts are available?\n\n\n\n• How does the statement indicate the analysis scripts are available?\n\n\n\n• Can you access, download, and open the analysis files (without contacting the author)?\n\n\n\n• Does the article state whether or not materials are available?\n\n\n\n• How does the statement indicate the materials are available?\n\n\n\n• Can you access, download, and open the materials files (without contacting the author)?\n\n\n\n• Does the article state whether or not the study (or some aspect of the study) was preregistered?\n\n\n\n• Where does the article indicate the preregistration is located?\n\n\n\n• Can you access and open the preregistration?\n\nWith respect to data availability, Hardwicke et al. attempted to code whether authors provided a clear reference to where the data could be found (“source of data provided but no explicit availability statement”).49 Due to difficulty coding this item, they did not report this and instead collapsed these types of data references into “no – there was no data availability statement”. Because we expected the current study to include several cases of authors analyzing pre-existing data and datasets, we initially attempted to preserve this as a distinct item in our coding form. However, our coders also encountered difficulty with it (e.g., sometimes articles would provide a vague reference to another article, and, when we accessed that article, it referenced yet other articles). So, our results also collapse these types of data references into the “no data availability statements” category (as we note below, our data availability results are closely in line with Matthews and Rantanen, lending confidence in our data availability conclusions). We did, however, include a separate item for secondary data studies (Table 1) in which we coded whether authors provided an index of the secondary data items (e.g., references to the judicial decisions included).50\n\nWe report 95% confidence intervals calculated using the Sison-Glaz method for multinomial proportions.51\n\nOur study deviated from our preregistration in two ways. First, we originally planned to code sample size but did not complete this coding because studies did not provide a single sample size. Second, as noted above, we originally planned to code whether the authors provided the source of the data, but we did not complete this because it was impractical for reasons noted in the previous paragraph.\n\n\nResults\n\nOverall, we found a low level of transparency on the characteristics we measured. Only 19% of articles stated that their data are available, and we were able to access that data in only about half of those cases.52 Preregistration and availability of analytic scripts were also very uncommon, and, in fact, almost nonexistent in the empirical legal research examined here. However, we found several positive aspects of the literature to build on. For instance, about 50% of studies employing original data stated that at least some materials were available. In addition, article accessibility was high among the empirical legal research examined here, especially among articles in student-edited journals (100% of those articles were available without library access). These findings are detailed below.\n\nGeneral characteristics of our sample are reported in Table 2, specifically the proportion of articles that: analyzed original or secondary data; used human participants; reported an experiment; were a synthesis (which we operationalized as studies that self-identified as a systematic review or meta-analysis); and reported descriptive or descriptive and inferential statistics. Secondary data analysis was more common (65% of studies, 95% CI = [59%, 70%]) than analysis of original data. Secondary data were also more frequently employed in the student-edited journals (79%, 95% CI = [73%, 85%]) than in the faculty-edited journals (51%, 95% CI = [43%, 59%]). Furthermore, 40% (95% CI = [35%, 46%]) of studies relied on human participants. This figure was 21% (95% CI = [15%, 27%]) among the student-edited journals and 60% (95% CI = [53%, 69%]) among the faculty-edited journals.\n\nThe variables are: original or secondary data, whether there were human subjects, whether the study was an experiment, whether it was a synthesis (i.e., systematic review or meta-analysis), and whether it used descriptive statistics or descriptive statistics along with inferential statistics.\n\nTurning to methodology, our sample contained fewer experiments (which require random assignment according to our definition) relative to secondary data analyses (18% of studies, 95% CI = [14%, 22%]). Syntheses were very uncommon, with only six in the sample (all six in the faculty-edited sample). Most articles (68% (95% CI = [62%, 73%])) contained descriptive and inferential statistics (the remaining 32% reported only descriptive statistics). 78% (95% CI = [72%, 85%]) of the faculty-edited articles used inferential statistics versus 57% (95% CI = [49%, 65%]) in the student-edited sample.\n\nAmong the 194 articles that used secondary data, 53 or 27% (95% CI = [21%, 35%]) of articles analyzed judicial decisions, 11 (6% (95% CI = [0%, 13%])) analyzed company documents, and a further 11 analyzed statutes or legislation (see “table 2secondary” in Extended data).80 Human participants were recruited from a variety of groups, with 12 of the 121 articles (10% (95% CI = [2%, 19%])) sampling from university students, 35 (29% (95% CI = [21%, 38%])) sampling from the general population, and 74 (61% (95% CI = [53%, 70%])) sampling from special populations. Those special populations53 included difficult-to-reach groups such as judges, young offenders, and government employees (see “table 2 special” in Extended data).80\n\nThe articles in our sample were generally easy to access as compared to estimates from previous metascientific studies in criminology and psychology (Table 3, Figure 2).54 86% (95% CI = [82%, 90%]) of articles had publicly available versions – 100% of the student-edited journal articles and 71% (95% CI = [65%, 79%]) of the faculty-edited group. 70% of articles (95% CI = [65%, 76%]) were gold open access, meaning they were accessible on journals’ websites. This was the case for 100% of the articles in student-edited journals, whereas 41% (95% CI = [33%, 49%]) of the faculty-edited articles were gold open access. Empirical legal researchers also regularly use pre- and post-print services to provide open access versions of their work. 42% (95% CI = [36%, 48%]) of articles in the overall sample were downloadable on SSRN and 22% (95% CI = [18%, 27%]) were downloadable on ResearchGate.\n\nThe variables are: article accessibility, the presence and content (if applicable) of statements about funding, conflicts of interest, data availability, materials availability, and analysis script availability. We further coded whether there was a statement that the study was preregistered and whether the authors described the study as a replication. The figures for materials availability include only the articles that collected original data. Note that this figure reflects availability statements. As discussed in text, actual accessibility was considerably lower.\n\nThe left column includes articles from the student-edited sample and the right column is from the faculty-edited sample. Numbers within bars refer to the number of articles that meet the given standard.\n\nTurning to conflicts of interest and funding statements, we found that most articles did not provide any such declaration. In fact, only 11% (95% CI = [8%, 15%]) of articles include a conflicts of interest statement. Conflicts of interest statements were more common in the faculty-edited journals with only one article in the student-edited sample containing such a statement. As to statements of funding sources, 40% (95% CI = [35%, 46%]) of articles contained a statement. Again, such statements appear to be rarer in the student-edited sample (see Table 3).\n\nThe availability of the data, analysis scripts, and materials in our sample was generally low (Table 3, Figure 3). Just 19% (95% CI = [15%, 23%]) of articles provided a statement that data are available. Of articles with data availability statements, the most common means for sharing data were via a third-party repository (39%, 95% CI = [26%, 53%]), by contacting the author (28%, 95% CI = [16%, 42%], and via a personal or institutional website (21%, 95% CI = [9%, 35%]) (see “tabledatahow” in Extended data).80 We checked whether the data referenced in the statements were readily available (i.e., whether we could access them without further steps, such as contacting the author). Only about half (53%, 95% CI = [40%, 66%]) were readily available, making the effective data availability rate about 10%. This figure closely corresponds to Matthews and Rantanen’s 12% estimate of data availability (also without contacting authors) at predominantly student-edited journals published from 2010 to 2019.55\n\nThe student-edited sample is reported in the left column and the right column is the faculty-edited sample. Numbers within bars refer to the number of articles that meet the given standard. Data availability, analysis script availability, and preregistration bars include the full sample (150 per group), whereas the bars for materials availability include only the articles that collected original data. Note that this figure reflects availability statements, whereas, discussed in text, actual accessibility was considerably lower.\n\nIn the social sciences, much of the move towards providing data availability statements has occurred in the context of psychological research, where original data are often collected. As a result, it may be useful to drill down on articles reporting on original data. Limiting our analysis to these articles (N = 106), we found 29% (95% CI = [22%, 39%]) included a data availability statement, whereas only 13% (95% CI = [9%, 18%]) of articles reporting on secondary data did so (N = 194).\n\nFor secondary data, as noted above, we coded the steps authors took to provide information about the dataset. In most cases, authors did not provide any details about the dataset (see “table_secondarySteps” in Extended data).80 In 26 of the 194 (13%, 95% CI = [8%, 20%]) articles reporting on secondary data, the authors provided an index of the secondary data (e.g., a list of judicial decisions relied on). Several others linked to sources, such as external websites, that were no longer accessible.\n\nVery few studies included a statement about the availability of their analysis scripts (6%, 95% CI = [4%, 9%]). Providing analysis code is especially important when reporting inferential statistics (e.g., to determine the exact statistical test and assumptions the authors used), but of the 203 studies that relied on inferential statistics, only 8% (95% CI = [5%, 12%]) made their code available. Even these figures are somewhat inflated, however, because only for approximately half of the articles with script availability statements could we access the scripts without taking further steps (again, due to dead links and statements indicating that the scripts were available on request).\n\nThe materials availability results presented in Table 3 and Figure 3 are limited to studies with original data. We presented them this way because sharing of study materials (e.g., survey instruments, vignettes) is arguably less applicable to analysis of existing data. However, some studies analyzing secondary data do involve useful materials that could be shared, such as the coding sheets used by researchers who tally different sorts of judicial decisions. Of studies that reported on original data, about 44% (95% CI = [35%, 54%]) stated that materials were available. Recall that this figure does not mean that all materials were made available, but rather that authors stated that at least some materials were available. Moreover, we were able to access materials for only 39 of the 47 (83%, 95% CI = [74%, 94%]) studies that stated that materials were available, making the effective material available rate about 37% among studies that report on original data.\n\nAlmost no studies reported being preregistered (3%, 95% CI = [1%, 5%]). Of the 8 preregistered studies, we could not access the preregistrations of 2. The purported locations of the 8 preregistrations were: the Open Science Framework (5 studies), the AsPredicted.org registry (1 study), the PROSPERO registry (for syntheses; 1 study), and the Evidence in Governance and Politics (EGAP) registry (which is hosted by the Open Science Framework; 1 study).\n\nVery few studies stated that they were reporting the results of a replication (4%, 95% CI = [2%, 6%]).\n\n\nDiscussion\n\nOur results suggest that there is ample room to improve empirical legal research transparency. Our hope is that our results encourage researchers in the field of quantitative empirical legal research to move forward in making their work verifiable and reusable. Articles in our sample generally had low levels of transparency and credibility-related characteristics that we measured. These results are not much different than many other fields (Table 4).56 On a more positive note, with respect to article accessibility, empirical legal research performs very well, especially for articles published in student-edited journals. Of course, accessibility without fuller transparency risks readers relying on unverifiable results. Ideally, research should be fully transparent and accessible.\n\nCulina et al. (2020) and Hardwicke et al. (2018a) focused on journals that had recently implemented transparency guidelines (Culina et al. studied such journals in Ecology; Hardwicke et al. focused on the journal, Cognition). A fuller description of the methodological differences between these studies and an expanded table is available (Extended data, “Table 4 - online supplement”).\n\nComparing student-edited and faculty-edited journals on other transparency and credibility-related characteristics, we generally did not find large differences. However, student-edited journals did seem to have a smaller proportion of articles with conflicts of interest and funding statements. Deficiencies in reporting funding may be due to law professors relying largely on internal funding that they do not see as important to report. While such funding might raise fewer concerns than that from external sources, it is impossible for the reader to know – without a statement – whether a study received funding and from what source. The best practice, one we saw among some articles in our sample, would be to explicitly declare funding sources and conflicts or the lack thereof, and law journals should require these declarations. Moreover, many legal researchers may have affiliations that should be disclosed, such as governmental appointments, affiliations with think tanks, and company directorships or board memberships.\n\nWhile we urge caution in comparing our results to those from transparency studies of other fields, such a comparison may be instructive in some ways (see Table 4). In particular, we did not observe large differences (other than in materials availability, see below) between empirical legal research and other fields. However, the two comparison studies in Table 4 (sampling from social science generally and otolaryngology) did not restrict their samples based on journal ranking,57 whereas our study sampled only from what many would describe as the top journals in the field. It arguably would be reasonable to expect that these journals should be leading the field in producing verifiable and reusable work. Moreover, the other studies focus on articles published in the mid-2010s, and so we might expect stronger adoption of transparency and credibility reforms in our sample. In other words, the results of our study likely provide an optimistic comparison with other fields of research.\n\nRegarding the effects of reforms, Table 4 also contains two comparisons with studies that have sampled only from journals that have implemented transparency and openness guidelines. In particular, Culina and colleagues sampled only from ecology journals that had implemented data and analysis script availability policies (both mandatory guidelines and encouragements).58 In addition, Hardwicke et al., examined data availability of studies published by the journal Cognition, which had implemented a mandatory data availability policy.59 As can be seen in Table 4, recent articles in those journals show markedly higher levels of data and script availability than our study found in empirical legal research. We cannot say what caused the relatively high levels of data and script availability in these journals, but these results suggest journal guidelines may play an important role in reform efforts. However, seeing as Matthews and Rantanen found that the Journal of Empirical Legal Studies underperformed student-edited law journals despite having a policy that encourages data sharing, it seems unlikely that mere encouragements are sufficient.\n\nOur results might be limited in other respects. First, empirical legal research is a multi-disciplinary field, which uses a panoply of methods from several research traditions.60 As a result, some forms of transparency may be less applicable for some methods than for others. We attempted to take this into account by reporting results for some of these practices separately for different types of studies (e.g., reporting materials transparency for studies reporting on original data; reporting analysis script transparency for studies reporting inferential statistics). In this respect, our results may overestimate transparency levels by restricting analyses to only one subset of studies, when in fact the practice would be beneficial for a broader range of studies. For example, many studies reporting on secondary data would nevertheless be more reproducible if they shared materials such as coding sheets used by research assistants who coded legislation or judicial decisions.61\n\nSecond, we did not contact authors to determine whether statements that data, materials, or analysis scripts were available upon request would be honored or whether authors of studies that do not mention availability would disclose information upon request. As noted above, however, multiple studies have found that most authors do not provide their data when requested, even when their paper includes a statement indicating that data are available upon request.62 Most recently, Gabelica and colleagues found that authors provided just 7% of 1,792 requested datasets despite the authors indicating that the data were available.63 While some authors may have responded to our requests, relying on author responses is problematic in the long run because researchers retire or otherwise leave academia, leading to a “rapid” decrease of research data availability over time.64 In addition, this method of transparency presents a significant obstacle for third parties who wish to access these artifacts for purposes that the authors may view as not in the authors’ interests (e.g., because the requesters suspect an error in the original article). The importance of posting data, as opposed to promising to make it available upon request, has been recognized by government funders, some of whom require authors of funded studies to post data upon publication.65\n\nThird, we did not attempt to take into account data sharing limits such as privacy and proprietary datasets.66 However, we did code whether any statement was made about data availability, which would have included statements about barriers to sharing data, and we did not find any studies that explained their lack of data sharing in such terms, so this may not have been prevalent. Alternatively, authors simply might not have reported their inability to share the data. Moreover, we attempted to code other means of transparency for secondary data analysis (e.g., indexes of cases relied on) and found that few papers took up any such options. Future metaresearch projects may wish to take a more focused approach, targeting specific empirical legal research methods to better understand their norms and limits related to transparent research and reporting.67\n\nFourth, our coding is only current as of September 2021. If, for example, articles have since been edited to indicate data availability, our results will not reflect that. While that is unlikely, it is perhaps more probable that some articles were temporarily open access because they had just been released, but have now moved behind paywalls. As a result, our results may overestimate open access, especially among the faculty-edited journals published by commercial publishers.\n\nFifth, using the impact factor metric for Web of Science to identify faculty-edited law journals may have included journals that some in the empirical legal research community would disagree about as important journals in the field. For instance, the impact factor for the Journal of Empirical Legal Studies resulted in it not being included, despite it being the journal produced by one of the main societies in the field. However, including journals based on our subjective judgment would have introduced bias into the findings. And, our results for data availability closely matched that of Matthews and Rantanen, who did study the Journal of Empirical Legal Studies.\n\nWe also highlight that the mere presence of data, analysis scripts, and preregistration does not mean that associated findings will be reproducible. Systematic research has found that data is often not well documented, making it difficult to reproduce findings.68 Future projects should consider focusing on a smaller number of studies for which some data are available to determine if the results are fully reproducible.69 Similarly, other aspects of research quality, such as whether preregistrations were actually followed, are an important avenue for future research.\n\nWhere do we go from here? As we reviewed above, transparency has proven vital in uncovering flaws, limitations, and fraud in published work. We call on journals to adopt policies to increase the transparency of published studies.70 This may be especially important for journals that are not commonly peer reviewed, such as student-edited journals, because peer review detects some flaws and errors.71 Even then, however, studies have found that peer reviewers detect just a minority of errors deliberately added to the reviewed studies.72 Only with a high level of transparency can we hope that errors in important studies are likely to be caught, as transparency enables post-publication peer review.\n\nThe fact that at least some datasets employed in empirical legal research studies are proprietary and cannot be made publicly available should not cause the field to shy away from general data availability requirements. For example, in psychology it is common for privacy issues to preclude data sharing. Journal guidelines in this field sometimes balance privacy and other ethical constraints on data sharing with data availability by asking authors to explain any restrictions in the manuscript and requiring data sharing if such an explanation cannot be provided.73 An example of such a statement is: “The conditions of our ethics approval do not permit public archiving of anonymized study data. Readers seeking access to the data should contact the lead author X or the local ethics committee at the Department of Y, University of Z. Access will be granted to named individuals in accordance with ethical procedures governing the reuse of sensitive data. Specifically, requestors must meet the following conditions to obtain the data [insert any conditions, e.g., completion of a formal data sharing agreement, or state explicitly if there are no conditions].”74 This policy is consistent with TOP guidelines for data transparency (Level II), which require data to be posted to a trusted repository and any exceptions to be explained in the article.75 Editors might also consider requiring authors who use proprietary data to include explicit statements related to limitations that arise from the inability to verify claims derived from such data. Specifically, readers should be explicitly warned about relying on unverifiable results.\n\nFinally, empirical legal research can take advantage of the larger movement in the social sciences, medicine, and many other fields, by leveraging the technology, training, and ideas flowing from those credibility revolutions. Free technologies like the Open Science Framework provide a place not just to store data, but to collaborate, establish version control, preregister, and store video stimuli. Other examples include tools like Github (a data and code repository), AsPredicted (a general study registry), Declare Design (a tool for creating a preregistration), and the American Economic Association’s registry for randomized controlled trials. Straightforward guides to data staring, preregistering, and many other transparency and credibility-related activities are now available.76 At least one guide specific to some empirical legal research methodologies is also available, and we hope more are on the way.77 With these tools at their fingertips – and as a field whose data and results are often of great public importance – there is little reason researchers in the field of empirical legal research should not become leaders in the move towards transparency and credibility.",
"appendix": "Data availability\n\nOSF: Transparency and reproducibility-related practices in empirical legal research https://osf.io/msjqf/. 78\n\nThis project contains the following underlying data:\n\n• Raw data 1 (https://osf.io/ktpcd)\n\n• Raw data 2 (https://osf.io/jx7fe)\n\nOSF: Transparency and reproducibility-related practices in empirical legal research https://osf.io/msjqf/. 79\n\nThis project contains the following extended data:\n\n• W&L screened out (https://osf.io/qf7sc)\n\n• Web of Science screened out (https://osf.io/vbu63)\n\n• Disagreements (https://osf.io/7q32m)\n\n• table 2secondary (https://osf.io/usfy4)\n\n• table 2special (https://osf.io/m589c)\n\n• tabledatahow (https://osf.io/67t9y)\n\n• table_secondarySteps (https://osf.io/xczpy)\n\n• Table 4 - online supplement (https://osf.io/z6tx3)\n\n\nAcknowledgements\n\nThanks to those who commented on presentations of earlier versions at Hebrew University, University of Washington in St. Louis School of Law, 2022 AALS Annual Meeting, 2021 Conference on Empirical Legal Studies at the University of Toronto School of Law, USC School of Law. 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PLoS ONE. 2011; 6(11): 1. Publisher Full Text\n\nZeiler K: The Future of Empirical Legal Scholarship: Where Might We Go from Here? J. Legal Educ. 2016; 66: 78.\n\n\nFootnotes\n\n1 Marcus R. Munafò et al., A manifesto for reproducible science, 1 Nat. Hum. Behav. 1 (2017) at 4-5.\n\n2 Id.; Joshua D. Angrist and Jörn-Steffen Pischke, The credibility revolution in empirical economics: How better research design is taking the con out of econometrics, 24(2) J. Econ. Perspect. 3 (2010); Simine Vazire, Implications of the credibility revolution for productivity, creativity, and progress, 13(4) PERSPECT. PSYCHOL. SCI. 411 (2018); Garret Christensen et al., Open Science Practices are on the Rise: The State of Social Science (3S) Survey, MetaArXiv, https://osf.io/preprints/metaarxiv/5rksu (accessed 2022).\n\n3 Munafò et al., supra note 1 at 2-3.\n\n4 Cary Funk et al., Trust and Mistrust in Americans’ Views of Scientific Experts, Pew Research Center (2019) 24; Justin T. Pickett and Sean Patrick Roche, Questionable, Objectionable or Criminal? Public Opinion on Data Fraud and Selective Reporting in Science, 24 Sci. Eng. Ethics 151 (2018).\n\n5 Kathryn Zeiler, The Future of Empirical Legal Scholarship: Where Might We Go from Here? 66 J. Legal Educ. 78 (2016); Jason M. Chin, Malgorzata Lagisz and Shinichi Nakagawa, Where is the evidence in evidence-based law reform? 45(3) U.N.S.W.L.J. 1124 (2021); Abigail Matthews and Jason Rantanen, Legal Research as a Collective Enterprise: An Examination of Data Availability in Empirical Legal Scholarship, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4057663 (accessed 2022) at 4.\n\n6 Zeiler, id.; Jason M. Chin and Kathryn Zeiler, Replicability in Empirical Legal Research, 17 Annu. Rev. Law Soc. Sci. 239 (2021).\n\n7 This generally tracks the definition provided in Michael Heise, The past, present, and future of empirical legal scholarship: judicial decision making and the new empiricism, Univ. Ill. Law Rev. 819 (2002); we acknowledge that many definitions of empirical legal research have been offered, see Shari Seidman Diamond and Pam Mueller, Empirical Legal Scholarship in Law Reviews, 6 Annu. Rev. Law Soc. Sci. 581 (2010) at 582-583. As we detail below, our definition is useful for the present study, which measures transparent practices.\n\n8 Vazire, supra note 2; Munafò, supra note 1.\n\n9 Monya Baker, 1,500 scientists lift the lid on reproducibility, 533 Nat. 452 (2016).\n\n10 Open Science Collaboration (OSC), Estimating the Reproducibility of Psychological Science, 349 Science 3451 (2015); Richard A. Klein et al., Investigating variation in replicability: A ‘many labs’ replication project, 45(3) Soc. Psychol. 142 (2014); Richard A. Klein et al., Many Labs 2: Investigating Variation in Replicability Across Samples and Settings, 1 Adv. Meth. & Pract. Psychol. Sci. 443 (2018); Charles Ebersole et al., Many Labs 3: Evaluating participant pool quality across the academic semester via replication, 67 J. Exp. Soc. Psychol. 68 (2016); Richard A. Klein et al., Many Labs 4: Failure to Replicate Mortality Salience Effect With and Without Original Author Involvement, https://psyarxiv.com/vef2c (accessed 2022); Colin F. Camerer et al., Evaluating replicability of laboratory experiments in economics, 351 Science 1433 (2016); Colin F. Camerer et al., Evaluating the replicability of social science experiments in Nature and Science between 2010 and 2015, 2 Nat. Hum. Behav. 637 (2018).\n\n11 See Leif D. Nelson, Joseph Simmons, Uri Simonsohn, Psychology’s Renaissance, 69 Annu. Rev. Psychol. 511 (2018); Leslie K. John et al., Measuring the Prevalence of Questionable Research Practices With Incentives for Truth Telling, 23(5) Psychol. Sci. 524 (2012).\n\n12 Angrist and Pischke, supra note 2; Sarah Necker, Scientific misbehavior in economics, 43 Res. Pol. 1747 (2014).\n\n13 Jason M. Chin et al., Questionable Research Practices and Open Science in Quantitative Criminology, J. Quant. Crim. (2021).\n\n14 See e.g., Garret Christensen and Edward Miguel, Transparency, Reproducibility, and the Credibility of Economics Research, 56 J. Econ. Lit. 920 (2018); Andrew C. Chang and Phillip Li, Is Economics Research Replicable? Sixty Published Papers from Thirteen Journals Say “Often Not,” 11 Crit. Fin. Rev. 185 (2022) (finding the lack of replicability is due mainly to lack of data availability). In economics, secondary data is referred to as “observational data.”\n\n15 Vazire, supra note 2; E. Miguel, et al., Promoting Transparency in Social Science Research, 343 Science 30 (2014).\n\n16 Brian A. Nosek et al., Promoting an open research culture, 348 Science 1422 (2015).\n\n17 Brian A. Nosek et al., The Preregistration Revolution, 115(11) PNAS 2600 (2018).\n\n18 Christopher D. Chambers and Loukia Tzavella, The past, present and future of Registered Reports, 6 Nat. Hum. Behav. 29 (2021).\n\n19 Anne M. Scheel, Mitchell Schijen and Daniël Lakens, An excess of positive results: Comparing the standard Psychology literature with Registered Reports, 4(2) AMPPS (2021).\n\n20 Simine Vazire and Alex O. Holcombe, Where are the Self-Correcting Mechanisms in Science?, 26(2) Rev. Gen. Psychol. (2022).\n\n21 Uri Simonsohn, Joseph Simmons and Leif D. Nelson, [98] Evidence of Fraud in an Influential Field Experiment About Dishonesty, http://datacolada.org/98 (accessed 2022).\n\n22 See: Brigitte C. Madrian, Applying Insights from Behavioral Economics to Policy Design, 6 Annu. Rev. Econom. 663 (2014).\n\n23 Cabinet Office Behavioural Insights Team, Applying behavioural insights to reduce fraud, error and debt (2012), https://vng.nl/sites/default/files/knowledge_base_compliance/Rapport_201608_Applying_behavioural_insights.pdf (accessed 2022)\n\n24 Francesca Gino, Gino-memo-data-colada-August16.pdf, http://datacolada.org/storage_strong/Gino-memo-data-colada-August16.pdf (accessed 2022) [emphasis added].\n\n25 Iain Chalmers and Paul Glasziou, Avoidable waste in the production and reporting of research evidence, 374 Lancet 86 (2009).\n\n26 Timothy H. Vines et al., The Availability of Research Data Declines Rapidly with Article Age, 24 Curr. Biol. 94 (2014); Jelte M. Wicherts et al., Willingness to Share Research Data is Related to the Strength of the Evidence and the Quality of Reporting of Statistical Results, 6(11) 1 PLoS ONE (2011).\n\n27 Id.\n\n28 Tom E. Hardwicke et al., An empirical assessment of transparency and reproducibility-related research practices in the social sciences (2014–2017), 7(2) R. Soc. Open sci. 190806 (2020); Tom E. Hardwicke et al., Estimating the Prevalence of Transparency and Reproducibility-Related Research Practices in Psychology (2014–2017), Perspect. Psychol. Sci. (2021); Austin L. Johnson et al., An assessment of transparency and reproducibility-related research practices in otolaryngology, 130(8) The Laryngoscope 1894 (2020); Mopileola Tomi Adewumi et al., An evaluation of the practice of transparency and reproducibility in addiction medicine literature, 112 Addictive Behaviors 106560 (2021); Elizabeth R. Tenney et al., Open Science and Reform Practices in Organizational Behavior Research over Time (2011 to 2019), https://psyarxiv.com/vr7f9/ (accessed 2022).\n\n29 Hardwicke et al., 2021, Id.\n\n30 Id.\n\n31 Nelson et al., supra note 11.\n\n32 Tom E. Hardwicke et al., Data availability, reusability, and analytic reproducibility: evaluating the impact of a mandatory open data policy at the journal Cognition, 5 R. Soc. Open sci. 180448 (2018a); Anisa Rowhani-Farid and Adrian G. Barnett, Has open data arrived at the British Medical Journal (BMJ)? An observational study, 6 BMJ Open e011784 (2016); Antica Culina et al., Low availability of code in ecology: A call for urgent action, 18(7) PLoS Biol. e3000763 (2020).\n\n33 Christensen et al., supra note 2.\n\n34 Lee Epstein and Gary King, The Rules of Inference, 69 U. Chi. L. Rev. 1 (2002).\n\n35 Shari Seidman Diamond, Empirical Legal Scholarship: Observations on Moving Forward,\n\n113 Nw. U. L. Rev. 1229 (2019).; Zeiler, supra note 5; Gregory Mitchell, Empirical legal scholarship as scientific dialogue, 83 N.C. L. Rev. 167 (2004). In other metaresearch in empirical legal research, Diamond and Mueller (supra note 7) tracked the amount of quantitative and qualitative empirical research in law journals, finding that only about 10% of articles in highly ranked U.S. law journals contained original empirical work; see also Michael Heise, An Empirical Analysis of Empirical Legal Scholarship Production, 1990-2009, 2011 U. Ill. L. Rev. 1739 (2011). And Hall and Wright examined trends in the use of one particular empirical legal research methodology—systematic analysis of judicial decisions. They found that papers in this area rarely cited methodological articles and seemed to reinvent the wheel, methodologically, in each iteration: Mark A. Hall and Ronald F. Wright, Systematic Content Analysis of Judicial Opinions, 96 Calif. L. Rev. 63 (2008).\n\n36 Kanu Okike et al., Single-blind vs Double-blind Peer Review in the Setting of Author Prestige, 316 JAMA 1315 (2016); Huber, Jürgen et al, Nobel and novice: Author prominence affects peer review, 119(41) PNAS e2205779119 (2022); Simine Vazire, Our obsession with eminence warps research, 547 Nat. 7 (2019).\n\n37 Huber et al, id.\n\n38 Matthews and Rantanen, supra note 5.\n\n39 Epstein and King, supra note 34 at 15-16.\n\n40 N = 250 in Hardwicke et al., 2020, supra note 28; N = 250 in Hardwicke et al., 2021, supra note 28; N = 286 in Johnson et al., supra note 28; N = 244 in Adewumi et al., supra note 28; N = 2234 in Tenney et al., supra note 28; N = 300 also provides a margin of sampling error of about 6%, although we did not include this in our a priori justification: American Association for Public Opinion Research, Margin of Sampling Error/Credibility Interval, https://www.aapor.org/Education-Resources/Election-Polling-Resources/Margin-of-Sampling-Error-Credibility-Interval.aspx (accessed 2022).\n\n41 E-mail from Tom E. Hardwicke to Jason M. Chin (Jan. 26, 2020).\n\n42 See the sources at supra note 28.\n\n43 Diamond and Mueller, supra note 7.\n\n44 We used the 2019 list, which was the latest available when we started coding. To get a broad range of journals, we chose the top 5 on the list (Yale Law Journal, Harvard Law Review, Stanford Law Review, Columbia Law Review, and University of Pennsylvania Law Review) and the bottom 5 (Fordham Law Review, Boston College Law Review, Boston University Law Review, Cornell Law Review, and Northwestern University Law Review). We began coding in January 2021, so any issues released after that date are not included (sometimes, a year’s issue is not released until the following year); see Washington & Lee Law, W&L Journal Rankings, https://managementtools4.wlu.edu/LawJournals/ (accessed 2022).\n\n45 See https://osf.io/hyk8c/ for our coded data. See https://osf.io/9q47g/ for the analytical code we used to produce the descriptive results.\n\n46 Using the same method of selecting student-edited and faculty-edited journals as Chin and Zeiler, supra note 6.\n\n47 Hardwicke et al., 2021, supra note 28.\n\n48 Rose E. O’Dea et al., Preferred reporting items for systematic reviews and meta-analyses in ecology and evolutionary biology: a PRISMA extension, 96 Biol. Rev. 1695 (2021).\n\n49 Hardwicke et al., 2021, supra note 28.\n\n50 For an example of this approach, see Bijal Shah, Executive (Agency) Administration, 72 Stanford Law Rev. 641 (2020). Although, raw data can be provided in many cases. For instance, see Oona A. Hathaway, Curtis A. Bradley and Jack L. Goldsmith, The Failed Transparency Regime for Executive Agreements: An Empirical and Normative Analysis, 134(2) Harv. L. Rev. 629 (2020) in which the authors digitized the data they relied on and made them available on Harvard Dataverse.\n\n51 Cristina P. Sison and Joseph Glaz, Simultaneous confidence intervals and sample size determination for multinomial proportions, 90(429) J. Am. Stat Assoc. 366 (1995).\n\n52 Recall that some of the variables we measured are on the level of the article (i.e., article accessibility and if the article is accessible, where it is accessible; conflict of interest statement; funding statement) with all others pertaining to the first reported study within an article. For simplicity, we will refer to the units described below as “articles.” We acknowledge that there may be some bias in coding only the first reported study in that first reported studies may be different in some ways than subsequent studies in an article. However, we judged it to be unlikely that the variables we were interested in (e.g., data availability statements, preregistrations) would differ in any meaningful way across studies, and we would expect authors to adopt the same transparency approach across all studies within a single article.\n\n53 We were interested in special populations because law, as an applied field, has a special interest in certain groups and stakeholders.\n\n54 Matthew P. J. Ashby, The Open-Access Availability of Criminological Research to Practitioners and Policy Makers, 32(1) J. Crim. Jus. Educ. 1 (2021); Hardwicke et al., 2021, supra note 28 at 5: “Among the 237 English-language articles, we obtained a publicly available version for 154 (65%, 95% CI = [59%, 71%]”.\n\n55 Matthews and Rantanen, supra note 5.\n\n56 See the sources at supra note 28.\n\n57 See the sources at supra note 28.\n\n58 Culina et al., supra note 32.\n\n59 Hardwicke et al., supra note 32.\n\n60 Hall and Wright, supra note 35 at 63. Future studies may wish to develop a way (a priori) of studying the law & (economics, political science, psychology, etc.) discipline an article comes from (e.g., by reference to the journal or education background of authors) to determine if that is associated with transparency of the article’s methods.\n\n61 PLOS might represent the cutting edge when it comes to disclosure of transcripts compiled in qualitative data studies (“Guidelines for qualitative data: For studies analyzing data collected as part of qualitative research, authors should make excerpts of the transcripts relevant to the study available in an appropriate data repository, within the paper, or upon request if they cannot be shared publicly. If even sharing excerpts would violate the agreement to which the participants consented, authors should explain this restriction and what data they are able to share in their Data Availability Statement. See the Qualitative Data Repository for more information about managing and depositing qualitative data.”: PLOS ONE, Data Availability, https://journals.plos.org/plosone/s/data-availability (accessed 2022); for best practices in data sharing, see Michelle N. Meyer, Practical Tips for Ethical Data Sharing, 1(1) Adv. Meth. & Pract. Psychol. Sci. 131 (2018).\n\n62 Vines et al., supra note 26 (reporting that, after a request, Vines et al. received data for only 19% of a sample of 561 studies published between 1991 and 2011 and that the percentage received decreased over time mostly due to authors reporting that the data were lost or stored on inaccessible media); Wicherts et al., supra note 26 (reporting that, after a request, Wicherts et al. received data from 43% of 49 corresponding authors of papers published in 2004 by top psychology journals and that those who did not send data by six years after the initial request, which was followed by two reminders, were more likely to have reported suspect results); Tom E. Hardwicke and John P. A. Ioannidis, Populating the Data Ark: An attempt to retrieve, preserve, and liberate data from the most highly cited psychology and psychiatry articles, 13(8) PLOS ONE e0201856 (2018) (reporting receipt, within six months of initial request, of 32% of 111 datasets used to produce results published in highly cited psychology and psychiatry studies from 2006-2016); Wolf Vanpaemel et al., Are We Wasting a Good Crisis? The Availability of Psychological Research Data after the Storm, 1(1) Collabra: Psychology 1 (2015) (reporting receipt, after initial request and reminders, of 38% of 394 datasets used to produce results published in four American Psychological Association journals in 2012); Michal Krawczyk and Ernesto Reuben, (Un)Available upon Request: Field Experiment on Researchers' Willingness to Share Supplementary Materials, 19(3) Account. Res. 175 (2012) (reporting receipt of information that the authors indicated was available upon request from 44% of 200 emailed authors of studies published in 2009 by business and economics journals). In the face of such results, journals have published articles that proceed as we do, merely reporting the rate of mentions of data availability without reaching out to authors to request data. See e.g., Joshua D. Wallach, Kevin W. Boyack and John A. Ioannidis, Reproducible research practices, transparency, and open access data in the biomedical literature, 2015-1017, 16(11) PLoS Biol. E2006930 (2018); Hardwicke et al., supra note 28.\n\n63 Mirko Gabelica, Ružica Bojčić and Livia Puljak, Many Researchers Were Not Compliant with Their Published Data Sharing Statement: Mixed-Methods Study, J. Clinical Epidemiology (2022) https://doi.org/10.1016/j.jclinepi.2022.05.019 (reporting receipt of 7% of 1,792 datasets used to produce results published during January 2019 by BioMed Central in open access journals, in which all authors promised to provide the data upon request).\n\n64 Vines et al., supra note 26.\n\n65 See U.S. Department of Education, Institute of Education Sciences. 2020. Policy Statement on Public Access to Data Resulting from IES Funded Grants. Available at https://sparcopen.org/wp-content/uploads/2021/01/DoEd-Policy-on-Public-Access-to-Data_IES-Funded-Grants.pdf (accessed 2022).\n\n66 Meyer, supra note 61.\n\n67 As discussed above, we saw approaches to more transparent handling of secondary data ranging from providing a detailed index of the secondary data (Shah, supra note 50) to digitizing the data and making it publicly available (Hathaway, Bradley and Goldsmith, supra note 50). Best practices documents ought to be created that explain the scenarios in which such methods are possible and desirable. See e.g., Weston, Sara J. et al. Recommendations for Increasing the Transparency of Analysis of Preexisting Data Sets, 2 Adv. Meth. & Pract. Psychol. Sci. 214 (2019). Given that users of secondary data usually modify publicly available datasets before producing results (e.g., to “clean” the data), pointing readers to the publicly available dataset is insufficient for purposes of transparency.\n\n68 Tom E. Hardwicke et al., Analytic reproducibility in articles receiving open data badges at the journal Psychological Science: an observational study, 8 R. Soc. Open sci. 201494 (2018b); Riana Minocher et al., Estimating the reproducibility of social learning research published between 1955 and 2018, 8 R. Soc. Open sci. 210450 (2018); Hardwicke et al., 2018, supra note 28.\n\n69 Id.\n\n70 Model guidelines can be found at Center for Open Science, The TOP Guidelines were created by journals, funders, and societies to align scientific ideals with practices, https://www.cos.io/initiatives/top-guidelines (accessed 2022). See also PLOS ONE, supra note 61.\n\n71 Sara Schroter, et al., What errors do peer reviewers detect, and does training improve their ability to detect them? 101(10) J. R. Soc. Med. 507 (2008).\n\n72 Id.\n\n73 Cortex, Transparency and Openness Promotion (TOP) guidelines, https://www.elsevier.com/__data/promis_misc/Cortex-TOP-author-guidelines.pdf (accessed 2022).\n\n74 Id. PLOS, an open-access journal publishing primarily in science and medicine, will not publish studies reporting conclusions that depend solely on the analysis of proprietary data (“If proprietary data are used and cannot be accessed by others in the same manner by which the authors obtained them, the manuscript must include an analysis of publicly available data that validates the study’s conclusions so that others can reproduce the analysis and build on the study’s findings.”) See PLOS ONE, supra note 61. The American Economic Review requires authors to provide non-disclosable data to its data editor and/or a third-party replicator. Available at https://www.aeaweb.org/journals/data/data-code-policy (accessed 2022). On the methods front, researchers have developed new methods for disclosing data in ways that do not violate non-disclosure agreements. See Trivellore E. Raghunathan, Synthetic Data, 8 Annu. Rev. Stat. Appl. 129 (2021) (reviewing various approaches for generating and analyzing synthetic data sets that are generated to protect confidentiality).\n\n75 Center for Open Science, supra note 70.\n\n76 Olivier Klein et al., A Practical Guide for Transparency in Psychological Science, 4 Collabra: Psychology 4 (2018) 20; (2019). Sophia Crüwell et al., Seven easy steps to open science: An annotated reading list, 227 Zeitschrift für Psychologie, 237 (2019).\n\n77 Jason M. Chin et al., Improving the Credibility of Empirical Legal Research: Practical Suggestions for Researchers, Journals and Law Schools, 3(1) Law, Technology and Humans (2021).\n\n78 Jason M Chin et al, “The transparency of quantitative empirical legal research published in highly ranked law journals (2018–2020): An observational study – Underlying data” https://osf.io/msjqf/.\n\n79 Jason M Chin et al, “The transparency of quantitative empirical legal research published in highly ranked law journals (2018–2020): An observational study – Extended data” https://osf.io/msjqf/."
}
|
[
{
"id": "162735",
"date": "27 Feb 2023",
"name": "Antica Culina",
"expertise": [
"Reviewer Expertise meta research",
"evolutionary ecology"
],
"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 MS uses articles published in the field of empirical legal research to study the occurrence of several practices related to transparent research and credibility revolution – such as preregistration, open data and protocols, or open access to publication. These appear to be very low in empirical legal research. As the first that looked into how common these practices are in the field, this paper can serve as a benchmark for any further improvements in the field. Further, it can serve as a encouragement to improve upon the situation.\nThe study is well presented, easy to follow, and applies the transparent practices in its design, reporting and conduct. With this it can also be a great example of how studies in the field of empirical legal research can be done. I really enjoyed reading this work.\nMy suggestion involve:\nIn the intro, I suggest to first present the benefits of open practices that are not connected with e.g. spotting errors and similar (these usually go less well with researchers). E.g. first emphasize the benefits to research/public as data and codes or methods are available so other can use them for different type of research, evidence synthesis etc, which all bring much higher gain from conducted research. And then I would always mention error checking and similar after these more `positive` outcomes. I am unclear as of how well the general readership of the journal will be familiar with some of the terms, e.g. replication failure. If readership is unlikely to know about these, maybe provide some more background on the transparent practices in the intro, or provide a table with the definitions (e.g. open data, open materials, open code, preregistration…) Have high impact journals been chosen so there is a higher likelihood of detecting existence of some of the transparent practices? This is not clear from what is currently represented in the MS. Before the method section, or at its beginning, the reader needs to know what exactly is this MS after? What exact practices are examined. Up to that point this is vague – rather, only some parts of what will be considered are mentioned (e.g. transparent practices) but it is not clear what this exactly entails. I remain unclear on how the search string was derived to. Some of the terms seem quite random. E.g. content analysis? Is the sting truly providing an unbiased set of studies in the field? (apart from not finding studies without an abstract). Introduction does not say much about general state of journal and funders policies on transparency in the field. Is it something that is becoming required? Do they follow some other, maybe more progressive fields? Table 4 – why were these examples selected? Table 4 – for Culina et al, 79% articles had available data, so 21% did not have data available. Also, note that Culina et al did not look into Data or Analysis Codes Availability statements, but rather whether data/analysis were available somewhere, regardless of whether they were mentioned as such. Can ` Where do we go from here? ` paragraph be separated as a subsection if journal allows? I think this section is vary important, as the current MS sets the stage by providing the evidence that the field is not transparent. In the call for change in practices, I would add a few points\n\nInclude funders: they also set standards for the work they fund, e.g. by setting data sharing policy for funded research. Funders (and institutions) should also help researchers when researchers want to apply transparent practices (e.g. by providing data stewards). Rewards and assessment system must also change. E.g. DORA declaration is a great example of rewarding practices other than publishing in high impact journals. If more research / academic institutions and funders would apply an altered assessment system, open practices would likely become more common A step further for journals is once they have a policy, that they engage data editors, who check if the material submitted are indeed contain the information they state they contain.\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": "10708",
"date": "17 Jan 2024",
"name": "Jason Chin",
"role": "Author Response",
"response": "Thanks so much Antica - we were waiting for the final review to begin revisions. We expect to post them in mid-January 2024. - Jason et al"
}
]
},
{
"id": "185632",
"date": "17 Aug 2023",
"name": "Stefanie Mueller",
"expertise": [
"Reviewer Expertise Experimental Psychology",
"Meta-Science"
],
"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 describes the adoption of transparency practices for studies in the field of legal research. The studies were published in either faculty-edited journals or in student-edited journals. Student-edited journals were selected based on their Washington & Lee ranking (which I assume is a well-known source in the legal community); faculty-edited journals were selected based on their impact factor as reported in the Web of Science”law” database. Within these journals, the authors’ goal was to select studies that analyzed quantitative data. To this end, articles were pre-selected using a pilot-tested search string, then the resulting lists of articles were randomized and manually screened by one of the authors until the pre-specified sample size of 150 for each list was reached. A pre-existing coding scheme was used to assess the study characteristics, with a focus on features of transparency (e.g. data availability). The authors report the results descriptively using absolute numbers and percentages. They also report confidence intervals calculated using a method appropriate for their data. They find generally low transparency for most features except for article accessibility.\n\nThe manuscript is very well written and models the standards of transparency that the authors (and I) would like to see in (quantitative) research. The background, procedure, and results were easy to follow while explained in detail. The methods seem appropriate to me. All in all, I have only a few and very minor suggestions for improvement.\n\nTypo on page 7, under “sample”: “150 faculty-edited journals from the 25 journals” → “150 faculty-edited articles from the 25 journals”.\n\nFig 1: I suggest using a sans serif font for better readability.\n\nTable 2: I suggest using the same darker background color for the row “Studies in student-edited journals” and “Studies in faculty-edited journals” as for all as it helps the reader to classify the main categories\n\nFig 2 and 3: The figures are redundant to the data presented in the table and currently do not add value (in my honest opinion). I’d suggest either dropping them completely or re-organizing them a bit so that they become clearer. (e.g. increase distance between the bar graph and the heading of the next panel below, use the same bar width for Fig 2 as for Fig 3; alternatively: re-organize the plot by placing all the bar graphs in the right column and the label student-/faculty-edited in the rows, that would aid the visual comparison between student-/faculty-edited and allows you to reduce the legends; then, arrange the bar graphs in pairs according to the dimensions displayed, i.e., smaller distance between members of one pair, larger distance to the next pair).\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": "10709",
"date": "17 Jan 2024",
"name": "Jason Chin",
"role": "Author Response",
"response": "Thank you Stefanie for these helpful comments. We were waiting for the final review to begin revisions. We expect to post them in mid-January 2024. - Jason et al"
}
]
},
{
"id": "185631",
"date": "12 Oct 2023",
"name": "Rob Heirene",
"expertise": [
"Reviewer Expertise Psychology",
"Addiction",
"Scientific reform"
],
"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\nMany thanks for the invite to review this interesting manuscript.\nArticle summary: The article reports a meta-scientific review of 300 empirical articles published in the legal field in 2019-2020). The authors aimed to determine the level of engagement with transparent/open research practices in the field and found low levels, save the accessibility of publications. The methods used are consistent with that of a systematic review; the review was preregistered; and all data, code, and materials are shared online.\nPlease see my comments on each of the article sections below.\nAbstract: I’m not sure whether there are any restrictions on the word count for the abstract that would preclude this, but it would be helpful to include some numerical figures in the results section (e.g., the percentage of preregistered articles) so that the readers can get a better understanding of what the authors mean by “very uncommon” etc.\nIntroduction: This section is well written, provides good coverage of literature related to the credibility revolution and its importance, and clearly outlines the need for the present review of empirical legal studies\nThe practical benefits of engaging with transparent research practices outlined on page 4 are excellent and provide a cogent argument for data sharing etc. for researchers who may be unsure of the benefits. I only have one concern. On page 3, the authors state: “Preregistration is designed to address publication bias and questionable research practices (known in some fields as researcher degrees of freedom, p-hacking, and specification searching).”\nI’m not familiar with the term “specification searching”, but I don’t believe researcher degrees of freedom, p-hacking, and questionable research practices are all equivalent in meaning. Researcher degrees of freedom is not inherently “bad” or indicative of QRPs, it’s just something that exists and can be exploited (the exploitation being the QRP). Similarly, while p-hacking is a type of QRP, there may be QRPs which are not a form of p-hacking. For example, a recent survey of QRPs among researchers in the Netherlands includes the following as QRPs: Making conclusions that are not sufficiently substantiated by the data, improper referencing of sources, inadequate notetaking of the research process, not submitting negative studies for publication (i.e. publication bias). While some of these may be classified as research misconduct, it is clear that many others view QRPs as more than just p-hacking.\nGopalakrishna et al. (20221).\n\nThe researchers could rectify this issue by providing more specific definition of publication bias and questionable research practices and/or further elaborating on each of the terms included in the parentheses. I think it’s important to provide clarity here as the authors suggest that the field of interest has not engaged well with the credibility reform and may therefore be less familiar with the terms than researchers in other fields (e.g., psychology).\nMethods: On page 6 the authors link directly to their preregistration, but don’t link to their openly available data, code, and materials described in the same sentence. For consistency and the benefit of readers, I would advise directly linking to all of these resources here.\nThe article search process is clearly described and its good to see the authors acknowledge the (entirely reasonable) limitations of their approach.\nIt’s not entirely clear to me why the authors selected the two different samples to look at and why looking at the high-impact journals was important? Please can the authors clarify.\nResults: This section is clearly presented and I have no concerns other than the minor issues below.\nHow many of the reviewed studies were published in each year? Apologies if this is included somewhere and I’ve missed it.\nFigure 2: It’s very difficult to see the numbers at the far right-hand side of the C1 and C2 panels as the boxes are so small. I actually couldn’t make out what the numbers were and was unsure whether they were obscured by the border of the boxes. I know the figures are also in the table above, but I’d recommend the authors adjust the plot to put these numbers outside of the boxes and then include an arrow to point to the relevant box. When I was reproducing the authors’ analyses, I edited their script to achieve this. I have included all of the edited code relating to this figure at the end of this peer-reviewed report that the authors can use, if they wish, to achieve this. Note that I increased the size of the text labels in my edited code, since making them fit inside of the smaller boxes was no longer a concern.\nDiscussion: The authors provide a clear summary of their findings and how they relate to previous research in the legal field and other disciplines. A number of useful suggestions/ recommendations are provided for improving transparency and reporting practices within the field, including ways to overcome common barriers (e.g., the data access statement when privacy concerns preclude open sharing). I have no concerns or recommendations regarding this section.\nTransparency & Reproducibility: I have extensively reviewed the study preregistration and the prespecified methods all appear consistent with those presented in the article, other than deviations explicitly acknowledged by the authors.\nI have also downloaded the analysis scripts and datasets from OSF and reproduced both the coding results/checks and formal analysis, including all figures and tables in the manuscript. I don’t have any concerns about the authors analysis process, but I do have a couple of suggestions for the authors to improve the reproducibility and presentation of the analyses (apologies if any of my suggestions are already well-known to the authors):\nFirst of all, I commend the authors for providing their analysis scripts in a clear and intelligible format. Including a rendered R markdown document with the ability to download the underlying source code is an excellent way of sharing analysis code.\n\nI ran into quite a few issues with deprecated functions in the coding checks script. I would recommend the use of a package like {groundhog} (https://groundhogr.com/) so that anyone who tries to reproduce your code will be using the same package versions as you were when you first produced the script.\n\nRelatedly, I would set the date at the top of the page to automatically be set as the date it was last rendered for full transparency (you can use this code in the YAML header of markdown and Quarto docs: date: \"r format(Sys.time(), '%d %B, %Y')\")\n\nI would also suggest the authors include their session info at the end of the analysis document using the sessionInfo() function from the {utils} package. This will further assist with ensuring reproducibility of the script years down the line.\n\nGiven the benefits of using R markdown over simply sharing and R script, I would have liked to have seen the authors provide more of text description around code chunks, and break the code chunks up more so that each printed output comes from one code chunk. This would make it a lot easier to read and follow for coders and non-coders alike. The authors have done a great job of commenting the code to explain what they did, but the code is hidden and only outputs are shown – I think this is great but further necessitates the use of explanatory text before and after code chunks.\n\nThis may not have been possible at the time of analysis, but I would recommend using Quarto to present analysis documents in the future over RMarkdown. The syntax is practically identical and it is very similar to working with markdown, but I find the published HTML documents tend to appear neater and easier to follow, including tidier code folding options. It’s also very easy to publish the rendered document to QuartoPub (https://quartopub.com/) so you don’t have to include a html file that has to be downloaded to be viewed on OSF (you can just include a link to a published page which is likely to be more accessible for those less familiar with coding).\nTo reiterate, the above are just suggestions that the authors can choose to adopt or ignore. I highly commend the authors for sharing their data files and analysis scripts in a way that allows their findings to be independently reproduced, as I have done here. This is how research should be done, but it takes time and effort and this should be recognised.\nOverall comments:\nI hope the authors find my comments useful in revising their manuscript.\nKind regards,\nDr Rob Heirene (I sign my reviews)\nCode (please let me know if this hasn't rendered well in the review report and I will be happy to share this via another method): # set up some colour palettes blue_palette <- brewer.pal(9, \"Blues\")[1:10] div_palette <- brewer.pal(6, \"Set3\")[c(1,3,4,6)] barPlot <- function(data, palette, title, legendTitle){ d <- data plt <- ggplot(data=d, aes(x=NA, y=prop, fill = var, label = label)) + geom_bar(colour = 'black', stat=\"identity\", width = 0.25) + scale_x_discrete(breaks = NULL, expand = c(0,0)) + scale_fill_manual(values = palette, guide = guide_legend(reverse=T)) + scale_y_continuous(labels = scales::percent) + theme_minimal(base_size = 12) + theme(legend.position = \"top\", legend.justification='left', legend.direction='horizontal', legend.key.size = unit(1,\"line\"), axis.title.y=element_blank(), axis.text.y=element_blank(), axis.ticks.y=element_blank(), axis.title.x=element_blank()) + guides(fill = guide_legend(title.position = \"top\", nrow = 1, reverse = T)) + geom_text(data=subset(d,label != 0), size = 4, position = position_stack(vjust = 0.5)) + labs(fill=legendTitle) + ggtitle(sprintf(\" %s\", title)) + coord_flip(clip = 'off') + geom_text( x = 1.2, y = 1, inherit.aes = FALSE, label = sprintf(\"N = %i\", sum(d$n)), check_overlap = TRUE, hjust = 1, size = 3 ) return(plt) } # build all the individual plots plt_articleAccess_student <- barPlot(d_openAccess_student, blue_palette[c(2,6)], \"Article availability - Student-edited\", \"Status:\") plt_articleAccess_peer <- barPlot(d_openAccess_peer, blue_palette[c(2,6)], \"Article availability - Peer-reviewed\", \"Status:\") plt_funding_student <- barPlot(d_funding_student, c(div_palette[c(1,4,3)], blue_palette[c(10,6)]), \"Funding - Student-edited\", \"Statement reports:\") plt_funding_peer <- barPlot(d_funding_peer, c(div_palette[c(1,4,3)], blue_palette[c(10,6)]), \"Funding - Peer-reviewed\", \"Statement reports:\") plt_dataOpen_student <- barPlot(d_dataOpen_student, blue_palette[c(2,4,6)], \"Data availability - Student-edited\", \"Statement reports:\") plt_dataOpen_peer <- barPlot(d_dataOpen_peer, blue_palette[c(2,4,6)], \"Data availability - Peer-reviewed\", \"Statement reports:\") plt_analysisOpen_student <- barPlot(d_analysisOpen_student, blue_palette[c(2,6)], \"Analysis script availability - Student-edited\", \"Statement reports:\") plt_analysisOpen_peer <- barPlot(d_analysisOpen_peer, blue_palette[c(2,6)], \"Analysis script availability - Peer-reviewed\", \"Statement reports:\") plt_materialsOpen_student <- barPlot(d_materialsOpen_student, blue_palette[c(2,6)], \"Materials availability - Student-edited\", \"Statement reports:\") plt_materialsOpen_peer <- barPlot(d_materialsOpen_peer, blue_palette[c(2,6)], \"Materials availability - Peer-reviewed\", \"Statement reports:\") plt_preregOpen_student <- barPlot(d_preregOpen_student, blue_palette[c(2,6)], \"Preregistration - Student-edited\", \"Statement reports:\") plt_preregOpen_peer <- barPlot(d_preregOpen_peer, blue_palette[c(2,6)], \"Preregistration - Peer-reviewed\", \"Statement reports:\") selected_palette <- blue_palette[c(2,4,6)] # Updated conflicts of interest plot for student edited journals: plt_conflict_student <- ggplot(data=d_conflict_student, aes(x=NA, y=prop, fill = var, label = label)) + geom_bar(colour = 'black', stat=\"identity\", width = 0.25) + scale_x_discrete(breaks = NULL, expand = c(0,0)) + scale_fill_manual(values = selected_palette, guide = guide_legend(reverse=T)) + scale_y_continuous(labels = scales::percent) + theme_minimal(base_size = 12) + theme(legend.position = \"top\", legend.justification='left', legend.direction='horizontal', legend.key.size = unit(1,\"line\"), axis.title.y=element_blank(), axis.text.y=element_blank(), axis.ticks.y=element_blank(), axis.title.x=element_blank()) + guides(fill = guide_legend(title.position = \"top\", nrow = 1, reverse = T)) + geom_text(data=subset(d_conflict_student,label != 0 & prop > 0.05), size = 4, position = position_stack(vjust = 0.5)) + geom_text(data=subset(d_conflict_student,label != 0 & prop < 0.1), size = 4, position = position_stack(vjust = 155)) + # add label outside of graph labs(fill=\"Statement reports:\") + ggtitle(sprintf(\" %s\", \"Conflicts of interest - Student-edited\")) + coord_flip(clip = 'off') + geom_text( x = 1.2, y = 1, inherit.aes = FALSE, label = sprintf(\"N = %i\", sum(d$n)), check_overlap = TRUE, hjust = 1, size = 3 ) + # Add arrow geom_segment(aes(x = 1, y = 1.03, xend = 1, yend = 1.001), arrow = arrow(length = unit(0.03, \"npc\")), size = 1.1) # Updated conflicts of interest plot for peer reviewed journals: plt_conflict_peer <- ggplot(data=d_conflict_peer, aes(x=NA, y=prop, fill = var, label = label)) + geom_bar(colour = 'black', stat=\"identity\", width = 0.25) + scale_x_discrete(breaks = NULL, expand = c(0,0)) + scale_fill_manual(values = selected_palette, guide = guide_legend(reverse=T)) + scale_y_continuous(labels = scales::percent) + theme_minimal(base_size = 12) + theme(legend.position = \"top\", legend.justification='left', legend.direction='horizontal', legend.key.size = unit(1,\"line\"), axis.title.y=element_blank(), axis.text.y=element_blank(), axis.ticks.y=element_blank(), axis.title.x=element_blank()) + guides(fill = guide_legend(title.position = \"top\", nrow = 1, reverse = T)) + geom_text(data=subset(d_conflict_peer,label != 0 & prop > 0.05), size = 4, position = position_stack(vjust = 0.5)) + geom_text(data=subset(d_conflict_peer,label != 0 & prop < 0.1), size = 4, position = position_stack(vjust = 155)) + # add label outside of graph labs(fill=\"Statement reports:\") + ggtitle(sprintf(\" %s\", \"Conflicts of interest - Student-edited\")) + coord_flip(clip = 'off') + geom_text( x = 1.2, y = 1, inherit.aes = FALSE, label = sprintf(\"N = %i\", sum(d$n)), check_overlap = TRUE, hjust = 1, size = 3 ) + # Add arrow geom_segment(aes(x = 1, y = 1.03, xend = 1, yend = 1.002), arrow = arrow(length = unit(0.03, \"npc\")), size = 1.1) Figure 2\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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": "10710",
"date": "17 Jan 2024",
"name": "Jason Chin",
"role": "Author Response",
"response": "Thank you Rob for the feedback and helpful code! We were waiting for the final review to begin revisions. We expect to post them in mid-January 2024. - Jason et al"
}
]
}
] | 1
|
https://f1000research.com/articles/12-144
|
https://f1000research.com/articles/13-159/v1
|
07 Mar 24
|
{
"type": "Research Article",
"title": "Development of competencies in secondary education through the motivational style of autonomy support",
"authors": [
"Miguel Llorca-Cano",
"Juan Antonio Moreno-Murcia",
"Julio Barrachina-Peris",
"Elisa Huéscar",
"Juan Antonio Moreno-Murcia",
"Julio Barrachina-Peris",
"Elisa Huéscar"
],
"abstract": "Background The aim of the study was to test the effect of a meta-disciplinary intervention based on the motivational style of autonomy support on the development of competencies in secondary school students. It was carried out by means of a quasi-experimental design and lasted for three months.\n\nMethods A total of 62 students between the ages of 12 and 16 (M = 13.61; SD = 1.16) participated, with 33 in the experimental group and 29 in the control group, along with 12 teachers (7 in the intervention group and 5 in the control group). The study measured teaching motivational style, satisfaction of basic psychological needs, motivation, and key competencies.\n\nResults The results demonstrate improvements in the autonomy-supportive motivational style, satisfaction of the basic psychological need for autonomy, autonomous motivation, and competencies in the experimental group, while the control group exhibited an increase in the chaos style.\n\nConclusions These findings reveal the positive impact of the supportive motivational style on the development of key competencies establishing it as an active, valid, and reliable methodology to motivate secondary school students.",
"keywords": [
"motivation",
"basic psychological needs",
"active methodologies",
"learning",
"commitment."
],
"content": "Introduction\n\nThe data and figures published by the Ministry of Education and Vocational Training on educational outcomes (MEFP, 2021) position Spain with the highest repetition rate in Compulsory Secondary Education (ESO) in the European Union and with an early school dropout rate (not concluding ESO) only surpassed by Malta. The PISA Report (2018) revealed that students with strong attachment to their school received greater emotional support from their families and were less likely to be absent from school.\n\nThe analysis of school climate found that most students considers very positive to help their peers, and more than a third said that Spanish teachers waited a long time for classmates to calm down. Students scored higher in reading when they perceived their teachers to be enthusiastic, to show interest in the subject and to enjoying teaching. These data suggest that creating a learning climate in which students feel motivated to complete academic tasks is now a priority for teachers.\n\nRecent studies show the relationship between the autonomy-supportive motivational style and a learning climate that fosters student involvement through its impact on mediators, regardless of the content addressed (Cheon, Reeve and Vansteenkiste, 2020; Gómez Rijo et al., 2023; Niemiec and Ryan, 2009; Reeve and Cheon, 2021; Reeve and Shin, 2020; Ryan and Deci, 2020). Thus, the use of a positive communicative style in class, (e.g. autonomy support), which extols the value of the student’s personal progress and is accompanied by explanations, has been shown to positively predict academic performance and task engagement, as these messages satisfy basic psychological needs (Santana-Monagas et al., 2021, 2022a, 2022b).\n\nCurrent research on classroom climate is adopting a new perspective supported by a multidimensional or circumplex approach (Aelterman et al. 2019; Escriva-Boulley et al., 2021; Cohen et al., 2022; Moé et al., 2022; Vermote et al., 2020, 2022), with the aim of interpreting more accurately the relationships between oscillations in student-perceived motivational climate and changes in teacher motivational style.\n\nIn summary, the circumplex model (Aelterman et al. 2019) adopts a multidimensional structure based on the degree of support or frustration of basic psychological needs and the greater or lesser directivity of the teaching intervention, integrating four major styles. Two of them are on the axis of basic psychological needs (Control and Chaos vs Autonomy Support and Structure) and the other two on the directivity axis (Control and Structure vs Chaos and Autonomy Support). These styles are concretized around eight subdimensions and associated in pairs to the styles: autonomy support (participative and attuned) and structure (guiding and clarifying) on the basic psychological-needs axis, and chaos (waiting and abandoning) and control (demanding and demanding) on the directivity axis (Figure 1).\n\nThe model has been implemented through the Situations-in-School (SIS) questionnaire (Aelterman et al., 2019), enabling the simultaneous analysis of the effect of the four styles and their adjacencies in different contexts (Burgueño et al., 2023; Cohen et al. 2022; Delrue et al. 2019; Escriva-Boulley et al., 2021; Franco et al., 2023; Van Doren et al., 2023). It also provides evidence that when teacher intervention during instruction is adaptive, learning demands are more effectively met and quality motivation develops (Van Doren et al., 2023).\n\nIn this sense, given the affinities between the demands of competency learning and the strategies presented by an adaptive motivational style (Autonomy Support and Structure) (Hamodi, Moreno-Murcia, and Barba, 2018; Moreno-Murcia, Llorca-Cano, and Huéscar, 2020; Moreno-Murcia, Ruiz, and Vera, 2015), it is expected that this approach can help boost the development of students’ competencies, as postulated in the educational system (LOMLOE, 2020). The literature has shown that adequate student functioning in class is related to the optimization of their autonomy, through the support of student autonomy (Pérez-González et al., 2019; Van Doren et al. 2023) and that such functioning requires satisfying the mediators (autonomy, competence, and relationship with others), bringing numerous benefits at all levels (cognitive, behavioural and emotional) (Ryan and Deci, 2020; Tian and Shen, 2023).\n\nCompetency-based learning (Bolívar, 2010; Valle and Manso, 2013) emphasizes student involvement in terms of performance or performance requirements, giving relevance to autonomy, reflection, and responsibility. It also emphasizes the importance of the teacher as a mediator or facilitator in the process of acquisition and development of the competencies established in the exit profile (Royal Decree, 217/2022). Thus, since the development of competencies requires the activation of adaptive behavioural patterns, in terms of performances with progressive autonomy, the teacher’s intervention should be adjusted to the demands posed by the process. This involves supporting the student’s autonomy, clarifying, and guiding their learning, empathizing, and providing emotional support (Zang, 2022) to generate a positive classroom climate that stimulates their involvement and, therefore, motivates them to continue learning.\n\nIn this direction, Gómez Rijo et al. (2023) conclude that strategies such as the promotion of student participation in the evaluation and the establishment of standards, peer learning, or the design and co-direction of tasks are methodological alternatives that encourage the support of student autonomy in the classroom, as previously demonstrated by other studies (Cheon, Reeve and Vansteenkiste, 2020; Cents-Boonstra et al., 2022; Reeve and Shin, 2020). These findings demonstrate that employing learner-centered methodologies predicts autonomous motivation and improves learner engagement in class (Leo et al. 2020; Tian and Shen, 2023).\n\nHowever, despite the existing synergies between the autonomy-supportive motivational style and the development of competencies, there are hardly any studies that provide evidence of the impact of an intervention based on the autonomy-supportive motivational style on the development of competencies (Barrachina, 2017; Barrachina-Peris et al., in press). Considering the importance acquired by competencies in the educational profile of 21st-century students (European Commission, 2018; Royal Decree, 2017/2022) and the relevance given to teachers in this process, the present study is proposed. Its main purpose was to test the effect of the motivational style of autonomy support on the development of competencies, Basic Psychological Needs satisfaction and autonomous motivation.\n\nDeci Ryan’s (2000, 2002) Self-Determination Theory (SDT) aims to explain human behaviour through various motivational styles, contextual influences, and interpersonal perceptions. According to SDT, there are three basic psychological needs directly linked to motivation and personal well-being: autonomy, which refers to the level of independence and control that a person experiences over his or her decisions (feeling an active part); competence, related to the ability to feel capable of successfully developing a task (perception of self-efficacy); and relatedness to others, associated with the establishment of socio-affective bonds with peers (developing a group identity) (Ryan and Deci, 2017).\n\nMotivation, according to Ryan and Deci (2017), can manifest itself in different gradients that fluctuate based on the degree of self-determination (intrinsic motivation, extrinsic motivation, and demotivation).\n\nIn this sense, if a teacher can provide a context that encourages active involvement in decision-making among students, focuses on the process rather than the outcome and acts as a facilitator, students will develop a more self-determined motivational orientation towards the content presented in class (Moreno-Murcia et al., 2012). For this reason, interventions that guide teachers towards improving their interpersonal style are considered fundamental.\n\nThe motivational teaching style can influence the motivation of students during their classes and can be situated along a spectrum ranging from a controlling style to the support of student autonomy (Tessier et al., 2010). Regarding the latter, the aim is to satisfy the three basic psychological needs and consequently, achieve self-determined motivation. On the contrary, extreme control, which relies on pressuring students without their active participation in the process, may lead them to act from a more extrinsic perspective (Cheon and Reeve, 2015; Escriva-Boulley et al., 2018; Fin et al., 2019; Haerens et al., 2015; Reeve, 2010; Yew and Wang, 2016).\n\nThere is evidence that using an autonomy-supportive interpersonal teaching style can be an effective trigger for the development of intrinsic motivation, which is the most valuable for learning as it elicits student engagement based on interest, enjoyment, and willingness to learn (Chang et al., 2016; Moreno-Murcia et al., 2012; Ntoumanis and Standage 2009). A teacher’s ability to foster self-determined motivation in their students is crucial for achieving goals set (Taylor et al., 2010). As demonstrated by Reeve (2016), the use of an autonomy-supportive interpersonal style by the teacher promotes a classroom climate in which students become more proactive, d increase their commitment to the task, and take more responsibility in the learning process as they have a more prominent role (Hamodi et al., 2018; Moreno-Murcia et al., 2020).\n\nToday, a versatile educational paradigm is emerging, structured around key and life-long competencies (OECD, 2005). A competency is demonstrated when an action results from reflection and the appropriate application of practical skills, knowledge, motivation, values and attitudes required by the task itself (OECD, 2002, 2005). Bolívar (2010) states that the competency-based approach represents a paradigm shift compared to previous models that were based on the fragmentation, accumulation and reproduction of knowledge. Itgives importance to the mobilization of knowledge in a specific context and the autonomy of students to manage their own learning. In this approach, according to Royal Decree 217/2022 of March 19, the role of the teacher is fundamental in the transfer process, as they act as a facilitators of learning by using active, contextualized methodologies, and maintaining levels of motivation in students. Such approach promotes meaningful and functional learning prioritizes the applicability of knowledge, its transfer to different contexts and emphasizes a globalizing and transversal approach (order ECD/65/2015; Bolivar, 2010; OECD, 2005). Even though it has become an entrenched model (LOE, 2006; LOMCE, 2013; LOMLOE, 2020), difficulties are still encountered in its practical implementation (Pérez-Pueyo et al., 2013; Barrachina and Blasco, 2012; Zapatero-Ayuso et al., 2017). In this context of change, there is a need for successful initiatives aimed at the development of key competencies in students. Principles such as self-regulation, autonomy and interaction underlie the competency-based approach and have been widely addressed in the Self-Determination Theory (SDT) (Deci and Ryan, 2000). Supported by this theory, different studies have described the positive relationship between the interpersonal style of autonomy support and student involvement, interest, and enjoyment in their classes, as well as the development of a favorable classroom climate and more meaningful and functional learning (Moreno-Murcia and Sánchez-Latorre, 2016; Fin et al., 2019; Jang et al., 2016). Research has shown that the nature of teacher optimization on student motivational factors is a crucial factor in improving educational quality and student success (De Jong et al., 2022; Monarca and Rappoport, 2013; Schuster et al., 2021; Hargreaves, 2019).\n\nSo far, there have been limited studies that have evaluated the impact of collaborative interventions on key competencies. Additionally, it is also challenging to find studies that analyse the relationship of these competencies with other variables that can predict active and self-determined learning such as the motivational teaching style (Barrachina-Peris, 2017; Moreno-Murcia et al., 2020).\n\n\nMethod\n\nThe sample consisted of 62 Spanish students from compulsory secondary education with ages between 12 and 16 years old (M = 13.61; SD = 1.16). The female to male ratio was 50/50:, female (n = 31) and male (n = 31). They were divided into an intervention group (n = 33), of which 18 were boys and 15 girls, and a control group (n = 29), composed of 13 boys and 16 girls. On the other hand, 12 teachers between 28 and 57 years of age (M = 40.66; SD = 10.50) participated, 58% of whom were male (n = 7) and 42% female (n = 5). The participating teachers were divided into two groups, experimental (n = 7) and control (n = 5).\n\nAutonomy support. The Situations-in-School (SIS) questionnaire (Aelterman et al., 2019), validated in the Spanish context by Moreno-Murcia et al. (2023) and composed of a total of 60 items, was used. This questionnaire determines the interpersonal style used by the teacher, looking at how the teacher acts in 15 possible situations or scenarios that occur during the sessions and, in turn, 4 ways of acting are presented for each of these situations (one for each teaching style: autonomy support, structure, control and chaos). Therefore, there would be 15 situations with 4 ways of resolution, totalling 60 answers when completing the questionnaire (e.g. for autonomy “When presenting the rules in class, the teacher invites us students to give our opinions about the rules, so that they help us feel comfortable in class”; for control “the teacher tells us students that we must follow them all as he says, even warning us that there will be sanctions if we do not comply”; for structure “the teacher announces his expectations to start cooperating with us”; for chaos “the teacher does not care at all about the rules or our opinions”). It was measured through a Likert-type scale ranging from 1 (does not describe me at all) to 7 (describes me extremely well). Cronbach’s Alpha for the pre-test and post-test of the different dimensions that make up the questionnaire were as follows: autonomy (.89 and .90), structure (.85 and .88), control (.83 and .88) and chaos (.87 and .90).\n\nBasic psychological needs in the academic environment. The Spanish translation of the Échelle de Satisfacción des Besoins Psychologiques in the educational context (León et al., 2011) by Gillet et al. (2008) was used. This scale consists of 15 items to measure three dimensions: perception of autonomy (e.g. “I have a say in the development of the programs of my subjects.”), perception of competence (e.g. “I often feel that I can do well.”) and perception of relatedness (e.g. “I feel at ease with others.”). Responses are rated on a Likert-type scale from 1 (strongly disagree) to 5 (strongly agree) points. The Crombach’s Alpha of the different dimensions in the pre-test and post-test of the intervention were in: Autonomy (.75 and .76), competence (.77 and .77), and relatedness (.80 and .79).\n\nAcademic motivation. The Spanish version of the Échelle de Motivation en Éducation, Escala de Motivación Académica (EMA) by Núñez, Martín-Albo and Navarro (2005) was used. The EMA is composed of 28 items distributed in seven subscales of four items each: demotivation (e.g. “I don’t know why I go to high school and, honestly, I don’t care.”), external regulation (e.g. “Because I want to live well once I finish my studies.”), introjected regulation (e.g. “Because it will help me make a better decision regarding my career direction.”), identified regulation (e.g. “Because when I do well in class I feel important.”), intrinsic knowledge motivation (e. g. “Because my studies allow me to continue learning many things that interest me.”), intrinsic achievement motivation (e.g. “Because of the satisfaction I feel when I overcome difficult academic activities.”) and intrinsic motivation to stimulating experiences (e.g. “Because for me, high school is fun.”). They were preceded by the pre-question “Why do you study this subject?”, and were measured using a Likert-type scale ranging from 1 (Does not correspond at all) to 7 (corresponds completely). The consistency of each dimension was for: autonomous motivation (.94 in the pre-test and .93 in the post-test) and for controlling motivation (.78 in the pre-test and .75 in the post-test). Intrinsic motivation to knowledge (.82 at pre-test and .79 at post-test), intrinsic motivation to achievement (.82 at pre-test and .87 at post-test), intrinsic motivation to stimulating experiences (.82 at pre-test and .76 at post-test), identified regulation (.80 at pre-test and .75 at post-test), introjected regulation (.78 at pre-test and .75 at post-test), external regulation (.85 at pre-test and .85 at post-test), and demotivation (.90 at pre-test and .90 at post-test).\n\nStudent competences. The “Key Competences Perception Scale” (ECC) developed by Moreno-Murcia et al. (2015) was used, which is composed of 9 items that measure the students’ perception of the acquisition of the different key competences. These items (e.g. “Expressing my ideas and respecting those of others”) are preceded by the previous sentence “What my teacher is teaching me allows me to be able to…”. Responses were rated by means of a Likert scale ranging from 1 (Strongly disagree) to 7 (Strongly agree). The internal consistency of this dimension was .88 in the pre-test and .84 post-test.\n\nThe project was approved by the Project Evaluation Body of the Miguel Hernández University (2017.06.259.E.OEP). This study was developed according to the principles expressed in the Declaration of Helsinki; First, the school administration was contacted to explain the objective of the study, and participation was approved through the school council. The parents/guardians of the students were asked for written authorization to participate and the treatment of the data was guaranteed in accordance with the institutional ethical guidelines regarding consent, confidentiality and anonymity. Questionnaires were completed at the beginning and end of the intervention.\n\nA quasi-experimental design was used for sample selection, given that the participants could not be randomly selected because they were previously divided into groups. The sample was distributed into 13 groups, of which 7 had a teacher who followed an intervention model with a motivational style of autonomy support and the remaining 6 did not follow differentiated methodological guidelines.\n\nBefore starting the intervention, the teachers of the experimental group were asked to film themselves teaching to evaluate the initial individual motivational style. Subsequently, they received training in an Autonomy Support Intervention Program (PIAA) (Moreno-Murcia et al., 2019a; Huéscar et al., 2022) for 40 hours, which included several face-to-face sessions aimed at understanding the motivational style of autonomy support and being able to transfer it to the context of their classes effectively. The training took place in two phases from October to December and combined face-to-face and virtual teaching. In the former, theoretical seminars were held, interspersed with practical workshops, in which the models and strategies shown in the literature to implement more autonomous styles and differentiate them from controllers were analysed (Niemiec and Ryan, 2009; Reeve 2009, 2016; Reeve and Halusic 2009; Reeve and Jang, 2006; Reeve and Cheon, 2015). Videos in which teachers applied strategies were shown and analysed. The aim was to identify the key points of the strategies presented and to establish consensus on their implementation. Group discussion was used to increase the degree of reliability and validity of the measure among participants. This phase was complemented with synchronous and asynchronous virtual training.\n\nIn the second phase, based on the proposal of Moreno-Murcia et al. (2021) and Huéscar et al. (2022), the autonomy support strategies were applied in a graded manner through practical workshops. Thus, the week prior to the implementation of each strategy, the teachers of the experimental group analysed them and wrote examples for their subject, which were reviewed and approved by the group of experts. For training in the autonomy-supportive motivational style, the Measuring Interpersonal Teaching Style (MEID) scale was used (Barrachina-Peris et al. 2022). The same scale was used during the intervention to analyse the motivational style displayed by the participating teachers (control and experimental). Three moments were recorded throughout the intervention: at the beginning, during its development and at the end. According to the literature (Sarrazin et al., 2006; Aelterman et al., 2014; Haerens et al., 2013; Reeve and Jang, 2006), the use of a given motivational style was determined when the teacher oriented a minimum of 80% of his/her classroom interactions to its application. Thus, in the experimental group, 80% of the interactions had to be directed to the autonomy-supportive motivational style (implementing the strategies by giving autonomy) while in the control group, this percentage had to represent the controlling teaching intervention (applying the strategies by encouraging control).\n\nThe indicators obtained by each group in the study are show in Table 1.\n\nFirst, to test the homogeneity of the two groups before the intervention, a one-factor analysis of variance was performed. Cronbach’s alpha coefficient was used to verify the internal consistency of each factor. To ensure the homogeneity of all dependent variables, a Levene’s test was performed on the pre-test and post-test. The effect of the intervention was assessed through a 2×2 (group × time) repeated measures analysis (ANOVA). To answer the research questions, a repeated measures ANOVA was conducted with all dependent variables (autonomy supportive style, structure style, controlling style and chaos style; psychological need for autonomy, psychological need for competence, psychological need for relatedness; autonomous motivation and controlling motivation and competencies). Cohen’s d was calculated to estimate the effect size. Data analysis was performed with the SPSS 52.0 statistical package.\n\n\nResults\n\nTo test the homogeneity of the two groups before the intervention, a one-factor analysis of variance was performed, considering as dependent variables (autonomy support style, structure style, controlling style and chaos style; psychological need for autonomy, psychological need for competence, psychological need for relationship; self-determined motivation, controlling motivation and competence) and as a fixed factor (the group), finding significant differences in the controlling motivation variable (p < .05).\n\nThe repeated measures analysis (Table 2) revealed significant differences in the variable support for teacher autonomy in the intervention group, improving in the post-test with respect to the pre-test (p < .05). Autonomous motivation significantly improved in the experimental group (p < .05) in the post-test, as did the basic psychological need for autonomy (p < .05) and relationship (p < .05). In relation to the competencies, the final measure showed a significant improvement in the experimental group (p < .05) with respect to the initial measurement, decreasing its value in the control group. In the control group, significant differences were only obtained in the teaching motivational style variable Chaos (p < .05).\n\n* p < .05.\n\n\nDiscussion\n\nThe aim of the study was to test the effect of the motivational style of autonomy support on psychological needs, motivation and competence development in secondary school students. The intervention was carried out for three months and included previous teacher training in autonomy support (PIAA). After analysing the data, a generalized positive effect was observed in the experimental group, which supports the initial hypothesis. Thus, students who received their classes through the autonomy-supportive motivational style presented better indicatorss in the satisfaction of basic psychological needs and self-determined motivation, the results being aligned with previous studies (Reeve, 2011; Chang et al., 2016; Conesa et al., 2022; Reeve and Cheon, 2021; Hosseini et al., 2022; Aelterman et al., 2014; Cheon and Reeve, 2015; Trigueros, et al., 2019; Fin et al., 2019; Moreno-Murcia and Sánchez-Latorre, 2016; Yew and Wang, 2016; Barkoukis et al. 2020).\n\nRegarding basic psychological needs, a significant improvement is observed in the autonomy variable, which is important since, according to De Muynck et al. (2017) and Cheon et al. (2020), it acts independently on well-being factors (Baten et al., 2020) and is positively associated with agentic commitment, active participation and persistence in their own learning, producing improvement in the student’s academic performance (Reeve and Shin, 2020) and well-being (Santana-Monagas et al. 2022a). In this sense, the study reveals the importance of adopting a teaching perspective that contemplates the student’s interests and gives them responsibility so that they feel an active part of the development of the tasks, as already pointed out by some recent studies (Cuevas et al., 2018; Cook-Sather et al., 2021; Jiang and Zang, 2021; Reeve and Shin, 2020) reaffirming existing contributions in the literature (Niemiec and Ryan, 2009; Reeve, 2006, 2011, 2016). Although significant improvements on competence and relationship needs were expected in the experimental group, the results obtained could be explained around several factors. Firstly, due to the duration of the intervention and its effects on the teaching behavioural pattern, which could have been insufficient for the teacher to reach a self-regulated mastery of the style (Huéscar et al. 2022), revealing some discrepancies between the perception of the application of the style and reality, as previous studies (Reeve and Jang 2006; Aguado-Gómez et al. 2016) pointed out. In this sense, the studies conducted show the existence of a wide variability around the duration and contents for training in the motivational teaching style (Su and Reeve 2011; Pérez-González et al. 2019) with disparate results in the application of the style. Taking into account the time availability of the intervention and with the aim of facilitating its more effective practical application, the PIAA model was followed (Moreno-Murcia et al., 2021; Huéscar et al., 2022) since it presents a proposal structured in phases that facilitates its application in practice that has demonstrated its validity in the educational context (Moreno-Murcia et al., 2019a). Another factor could be related to the degree of group and social cohesion of the experimental groups and the management performed by the teacher in class through his motivational style. It has been shown that group cohesion is positively related to the satisfaction of basic needs, autonomous motivation and involvement in class (Bosselut et al., 2018) and for this purpose the establishment of task climate and the use of interpersonal styles of support for basic psychological needs are of utmost importance (Leo et al., 2020), since good cohesion has shown its importance in confidence for the resolution of group tasks and collective efficacy, being key in motivational processes (Leo et al., 2021). The factors described above may have influenced the results obtained with respect to the structure and relationship mediators and coincide with the findings of Waterschoot et al. (2019), which highlights the importance of lesson planning so that students feel an active part and are involved in the teaching and learning process.\n\nIn relation to the development of competencies, an improvement was observed in the intervention group with respect to the control group. These results coincide with previous studies that showed that active styles improve motivation and the development of competencies (Moreno-Murcia et al. 2020) and that the autonomy-supportive style positively predicts competencies in adolescent students (Barrachina-Peris, 2017; Moreno-Murcia et al., 2015). Therefore, the autonomy-supportive motivational style can become a facilitator of active learning (Reeve, 2006; Reeve and Cheon, 2021), basis on which competency learning is built (Order ECD/65/2015) and competencies are developed (Bolivar, 2010; Royal Decree 217/2022; EU, 2018). The study shows a positive relationship between the autonomy-supportive motivational style and self-determined motivation, which is consistent with the results of other works (Abula et al., 2020; Barkoukis et al., 2020; Fin et al., 2019 and Sánchez-Oliva et al., 2017) that support the transfer of the benefits obtained in class to other personal and social contexts of the student, such application process being a determining factor for the development of competencies (Bolívar, 2010; European Union, 2018).\n\nFramed in SDT (Deci and Ryan, 2000; Ryan and Deci, 2000) the study follows the line of works showing that autonomously motivated students present a greater willingness to put more effort into different tasks and a higher perceived competence (Feng et al., 2019; Mouratidis et al., 2011; Ryan and Frederick, 1997; Vansteenkiste et al., 2018), helping to extrapolate it to different tasks of daily life (Komarraju and Nadler, 2013; Jiang et al., 2019). In this line, Johansen et al. (2023) indicate that an autonomously motivated student is more likely to show emotional engagement that leads them to participate in a more active way in various situations where they have to solve tasks due to involvement and enthusiasm and when a context that supports autonomy is posed, people become actively involved (Ryan and Deci, 2000; Skinner and Pitzer, 2016).\n\nIn terms of pedagogical contributions, this study suggests that providing autonomy support in the classroom is fundamental for fostering students’ competencies, thus expanding the practical implications of autonomy support and its relationships with correlates of motivation. Affirming the validity and usefulness of implementing strategies to support autonomy already validated (Huéscar et al., 2022) such as: giving students a choice of content among different possibilities, offering level options within the tasks themselves, favouring participation and cooperative work, promoting a positive climate in class, guiding the student towards the search for answers without facilitating the solution to the problems posed or the use of non-controlling language, etc. When students perceive that their autonomy is supported through an optimal learning climate, they are more likely to mobilize their internal motivational resources and decide to engage voluntarily in the different tasks, thus facilitating their perception of competence (Moreno-Murcia and Barrachina Peris, 2022).\n\nThe study has promoted teacher collaboration, revealing it to be a key factor in improving the quality of education in schools. Based on these findings, if similar studies are proposed in the future, the variable teacher collaboration could be further regulated and the impact exerted on the teaching and learning process could be analysed, as pointed out by studies that confirm the positive effect on student academic performance (Hargreaves, 2019; Reeves et al., 2017; Moolenaar et al., 2012; Main and Bryer, 2005; Goddard et al., 2007; Westheimer, 2008), on teacher motivation and satisfaction and the development of innovative practices (Kolleck, 2019; Vangrieken et al., 2015; Vangrieken et al., 2017; Donmoyer et al., 2012).\n\nThe study has several limitations. On the one hand, the sample size. Despite having 12 groups and 62 students, an increase in the sample would allow comparison of the results at the trans-contextual level. Another limitation is associated with the duration of the intervention. To improve the reliability of the data, longitudinal studies covering longer periods (one or more school years) are proposed in order to analyse the long-term effect, especially on the development of competencies at the end of the basic education stage (6-16 years). Another limiting factor would be associated with the specific context of the application process of the autonomy support strategies and their supervision, which could have minimized the effect that other factors may have had on the results (time of the course, group cohesion, among others), factors that we suggest should be considered in future studies that delve deeper in this direction.\n\nIn conclusion, this study supports the results obtained in previous works and opens lines of future work aimed at applying the motivational style of autonomy support using specific training programs (PIAA). The work has shown that, if teachers are trained collaboratively, the quality of teaching is increased and improvements are produced in the development of competencies in secondary education, satisfying basic psychological needs, improving self-determined motivation. This study is the first to investigate how the implementation of autonomy support in an educational context of adolescent students is related to the different competencies through the promotion of autonomous motivation, making it necessary for researchers to highlight the importance of building optimal learning environments that support student autonomy.",
"appendix": "Data availability\n\nFigshare: Dates of PIIE, https://doi.org/10.6084/m9.figshare.24542071.v1 (Moreno-Murcia, 2023).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nThis work is part of the call for “Projects of innovation and research in education” of the Conselleria d’educació de la Generalitat valenciana. (DOCV 7823/07.07.2016).\n\n\nReferences\n\nAbula K, Beckmann J, He Z, et al.: Autonomy support in physical education promotes autonomous motivation towards leisure-time physical activity: Evidence from a sample of Chinese college students. Health Promot. Int. 2020; 35(1): e1–e10. PubMed Abstract | Publisher Full Text\n\nAelterman N, Vaanstenkiste M, Soenens B, et al.: Towards an integrative fine-grained insight in motivating and demotivating teaching styles: The merits of a Circumplex approach. J. Educ. Psychol. 2019; 111: 497–521. 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{
"id": "261430",
"date": "07 May 2024",
"name": "Estelio H. M. Dantas",
"expertise": [
"Reviewer Expertise Gerontology",
"Fitness"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis review provides an evaluation of the research article titled ‘Development of competencies in secondary education through the motivational style of autonomy support’. The article presents a significant contribution to the field of educational psychology, particularly in understanding the role of teaching styles in fostering student motivation and competency development. Strengths:\nRigorous Methodology: The study employs a quasi-experimental design and includes a significant sample of students and teachers, which strengthens the validity of the results. Evidence-Based Intervention: The meta-disciplinary intervention based on the autonomy-supportive motivational style is well-grounded in self-determination theory, a recommended practice in educational literature.\nArea for Improvement:\nIntervention Detailing: It would be beneficial to provide more details about the specific activities carried out during the intervention to allow for replication in future studies.\nOverall, this is a valuable contribution to the field of educational psychology, providing insights into the role of teaching styles in fostering student motivation and competency development. However, further research is needed to fully understand the long-term impacts of such interventions.\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": "261426",
"date": "30 Aug 2024",
"name": "Pedro Saenz-Lopez Bunuel",
"expertise": [
"Reviewer Expertise Teaching training"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n-An approval status which summarizes your views on the article and helps directly determine whether an article will complete peer review. The manuscript has the structure is right, the sample is good enough, the analysis is adequate, the references are updated. -A peer review report which supports your answers and approval status, with more detail where necessary. Please also include one or two sentences to summarize the article. The objective of this article is to measure the effect of an intervention in secondary school students. The design is a quasi-experimental study in which the experimental group develop a motivational style of autonomy support. The tested variables have been satisfaction of basic psychological needs, motivation, and key competencies. the findings demonstrate a positive impact of the supportive motivational style on the satisfaction of the basic psychological need for autonomy, autonomous motivation, and competencies. In the study some limitations are shown such as the sample size or the duration of the intervention. They suggest this and other aspects to be considered in future studies. Some details to improve the manuscript: - INTRODUCTION -Competency-based education and motivation 1st paragraph. Erratum: It gives (It gives) -REFERENCES Add doi link and references (if it is possible). For example: [1] -INTRODUCTION AND DISCUSSION The aim is very clear in the abstract. I suggest including more clearly in the text (at the end of the introduction and at the end of the discussion to conclude answering it). - INTRODUCTION 2ND Paragraph. It seems that positive climate depends on emotional aspects (emotional, support, calm down, enthusiastic). After this shows up this sentence: “These data suggest that creating a learning climate in which students feel motivated to complete academic tasks is now a priority for teachers”. It would be necessary to explain the relation between emotional and motivational climate.\nIs the work clearly and accurately presented and does it cite the current literature?\nYes, the manuscript is very clear, and the structure and the information has been presented accurately. Most of the references has been published in the last 6 years\nIs the study design appropriate and does the work have academic merit?\nYes, the aim of the research was to measure the effect of an intervention. Thus, the cuasi-experimental design is appropriate to achieve it.\nAre sufficient details of methods and analysis provided to allow replication by others?\nI think so, because the methodology explain the procedure and through some cited references, other researchers could replicate the study.\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes, firstly they have tested the homogeneity of the two groups, then they have verified the internal consistency of each factor and the homogeneity of all variables. Secondly, they have assessed the effect of the intervention and estimate the effect size. Everything through adequate analysis.\nAre all the source data underlying the results available to ensure full reproducibility?\nYes, on the one hand the explanation is clear to reliquiae. On the other hand the data are available through a link\nAre the conclusions drawn adequately supported by the results?\nYes, the findings are clearly shown and the discussion is developed adequately supported by the results of this study and others research's looking for useful conclusions.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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": "273445",
"date": "06 Sep 2024",
"name": "Gavin R. Slemp",
"expertise": [
"Reviewer Expertise SDT",
"motivation",
"psychology",
"wellbeing"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 completed this review with the with a PhD student. We reviewed the article separately, and I include my comments first and their comments after mine:\nMy comments: The aim of the present study was to examine the effect of an intervention based on motivating styles and SDT to see if it yielded beneficial outcomes in secondary school students, using a quasi-experimental design. Results suggested some improvements in autonomy support, autonomy, autonomous motivation, whereas these were generally not observed in the control group. Authors conclude that they found a positive effect of their intervention.\nOverall, there are some things to like about this paper. It is good we are seeing more interventions like the current study and the intervention seems to be based on solid foundations covered in the SDT literature. That said, I do have some concerns that temper my enthusiasm, which I also outline below.\n\n- The introduction gives a lot of background information about SDT and related concepts, such as the circumplex model and motivation subtypes, but it does little to problematize the need for the study. I think you could do more here as there is only a few lines of text at the end of the introduction to say a few interventions exist. Why do we need more interventions? What will they contribute to knowledge? I think more could be done to elaborate on these points.\n- After reading the method, it was not clear to me how participants were allocated to conditions, and only several pages later did we learn it was a quasi-experimental trial. Please make this important point more salient early in the paper.\n- Not much information is really provided about the intervention. Can you please be clearer about what participants experienced? How many sessions were involved and for how long? What was the focus of each session? Why was the intervention design in the way it was? etc. There is some information provided here but it could be considerably more substantial to give complete information.\n\n- Please include a consort diagram that shows the flow of participants from screening all the way through to last measurement. It is useful for readers to understand the extent and effect of attrition.\n\n- In preliminary analyses and results sections, the first 2 sentences of each section are verbatim. I would suggest rephrasing given each section should be incorporating different information, which would allow you to better distinguish the preliminary analyses from the actual results presented later.\n- Refer to measurements as time 1, time 2, and time 3, rather than moments, which is the current language used to describe them. Also, frequency should be N? It is not really clear whether table 1 includes N, which makes it very confusing. Please also ensure to report means, SDs, N for each time point for each group for each variable.\n- Report the actual p-values, rather than thresholds as they are presented in the section \"Intervention Effect\". Please also give more information, such as the means of both groups and an effect size that compares/quantifies the group by time interactions, which will allow readers to better understand how strong these effects are. Also, a problem with the results section, as well as the paper overall, is that it is generally unclear who the intervention group is. Is it the group who received the training? Or is it the group who studied under those who received the training? I think it would be beneficial to provide two sets of metrics to capture the different layers/cohorts for your intervention effects.\n\n- A clear limitation that has not been mentioned is the fact that this study was a quasi-experiment rather than a randomized controlled trial, limiting inferences about causality.\nPhD student:\nThe 5th paragraph (pg. 3), when discussing the circumplex model, has a typo. It says, “demanding and demanding”, when this should say “domineering and demanding” Definition of autonomy on pg. 4 is not accurate. Autonomy is different from independence. Suggest correcting this. Suggest also using the correct term “amotivation” rather than “demotivation” (pg. 4) The justification for the current study (pg. 5) was fairly short and abrupt. It was unclear what this study offers that previous autonomy-supportive school-based programs have not already investigated. I would suggest giving some extra information regarding this. The use of a clear hypothesis would help clarify the aims of the study. It’s a bit unclear why this is a quasi-experimental design. Why were students and teachers not randomly assigned into control/experimental groups? The participant section simply states that they were divided into groups. This doesn’t seem to preclude randomisation. Authors should clarify. At the bottom of page six it states that “The sample was distributed into 13 groups, of which 7 had a teacher who followed an intervention model with a motivational style of autonomy support and the remaining 6 did not follow differentiated methodological guidelines”. Should this say 5 not 6 teachers, given in the methods section, only 5 were in the control group. I commend the authors on the use of the MEID to measure the autonomy and controlling styles of teachers during the PIAA training. Was this process done blinded or by the researchers who knew which condition the teachers were in? If not blinded, this may lead to bias in rating the experimental group teachers as more autonomy supportive. I would recommend clarifying how this was done and any biases that might affect the rating of teachers motivational style. Under Intervention Effect it states: “In relation to the competencies, the final measure showed a significant improvement in the experimental group (p < .05) with respect to the initial measurement, decreasing its value in the control group.” I suggest changing wording around ‘decreasing its value in the control group’ as this sounds as though competences decreased significantly in the control group, when according to table 2 they did not. Given the large number of dependent variables that may be related, would it be advised to perform a MANOVA to see if any significant omnibus effects are present before exploring each individual variable Limitations of the present study should also mention the lack of randomisation and need for true RCT in the future.\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? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-159
|
https://f1000research.com/articles/12-1113/v1
|
07 Sep 23
|
{
"type": "Research Article",
"title": "Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS)",
"authors": [
"Mariam Kekenadze",
"Clarissa Rocca",
"Valentina Turchetti",
"Sara Nagy",
"Nana Kvirkvelia",
"Shorena Vashadze",
"Eka Kvaratskhelia",
"Maia Beridze",
"Rauan Kaiyrzhanov",
"Henry Houlden",
"Clarissa Rocca",
"Valentina Turchetti",
"Sara Nagy",
"Nana Kvirkvelia",
"Shorena Vashadze",
"Eka Kvaratskhelia",
"Maia Beridze",
"Rauan Kaiyrzhanov"
],
"abstract": "Background: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder that affects the upper and lower motor neurons. Several genetic risk factors have been identified in the past decade with a hexanucleotide repeat expansion in the C9orf72 gene being the most significant. However, the presence of C9orf72 repeat expansion has not been examined in the Transcaucasian region, therefore we aimed to analyze its frequency in Georgian patients with ALS. Methods: We included 64 self-reported Georgian patients with ALS from different parts of the country, fulfilling the Gold Coast criteria. To investigate the presence of an expanded GGGGCC hexanucleotide repeat in the non-coding region of the C9orf72 gene, we performed Repeat-Primed PCR (RP-PCR).\n\nResults: In total, 64 sporadic and two familial ALS cases were identified. Patients were aged 26 to 84 years with a mean age of 58.3 years at disease onset. Bulbar onset was observed in 21.88%, upper limb onset in 34.38%, and lower limb onset in 43.75% of the patients. Frontotemporal dementia (FTD) fulfilling the Strong criteria was diagnosed in seven patients (10.94%). C9orf72 repeat expansion was detected in only one case using RP-PCR; the patient had a family history of dementia. Conclusions: Our results indicate that C9orf72\n\nhexanucleotide expansion does not belong to the major genetic risk factor of ALS in Georgian patients. Further genetic studies in a bigger study population are needed to reveal the genetic causes of ALS in the Transcaucasian population.",
"keywords": [
"ALS",
"MND",
"Gene",
"C9orf72",
"Georgia",
"DNA",
"Genetics",
"Genomics"
],
"content": "Introduction\n\n“Does it take place through simple propagation, extending gradually across the neuroglia?”.1 This is what French neurologist J. M Charcot questioned regarding the disease development of amyotrophic lateral sclerosis (ALS) almost 150 years ago. Although the pathogenesis of ALS is still unknown, extensive studies have revealed important genetic risk factors in the past decade. C9orf72 (#MIM 105550), SOD1 (#MIM105400), TARDBP (#MIM612069, #MIM612069), and FUS (#MIM608030) are the most frequently mutated genes that have been shown in ALS,2,3 with the hexanucleotide repeat expansion in C9orf72 being the most significant and accounting for 30–50% of familial and 7% of sporadic ALS cases in the European population.2,3 However, the genetic basis of ALS has not been investigated in the Transcaucasian region. Therefore, we aimed to determine the frequency of C9orf72 repeat expansion in Georgian patients with ALS.\n\n\nMethods\n\nIn total, 64 self-reported ethnically Georgian patients with ALS have been included in the study. There was no prior dataset of ALS patients in Georgia, nor epidemiological data about the disease, despite considering small size of Georgian population and rarity of the disease worldwide, we estimated that at least 50 participants would be scientifically significant number for this research. Ethical approval was obtained from Tbilisi State Medical University (TSMU) ethics committee (Date: 8th June 2020, approval no. N3-2020/80) and University College London (UCL) institutional board (Short Title:IGC, CI:Prof H Houlden, Sponsor EDGE ID:146653,IRAS Approval Number:310045, Protocol V1.12 22.06.2019). Before the study, written informed consent was obtained from all subjects or their legal representatives in cases where participants were unable to write and sign the form.\n\nPatients were recruited via phone during the years of 2019-2023 and the database of the First University Clinic of TSMU as well as of collaborative clinics were utilized for the study. Participants were contacted first of all to get information if they were still alive or not, and ask if they would agree on genetic testing in the future. No information was collected at that point, nor blood samples, before ethical approval was granted and consent taken from participants.\n\nDiagnosis of ALS was based on the new Gold Coast criteria, incorporating progressive motor impairment documented by history or repeated clinical assessment, preceded by normal motor function, and the presence of upper and lower motor neuron dysfunction in at least one body region, or lower motor neuron dysfunction in at least two body regions, most importantly excluding other diseases.4 Patients were reevaluated according to the Gold Coast criteria, however prior diagnosis and assessments were done by involved clinics. Patients diagnosed with conditions such as spinal muscular atrophy, Kennedy disease, monomelic amyotrophy, Hirayama syndrome, or multifocal motor neuropathy were excluded from the study, there were no other exclusion criteria. Also, clinical symptom studies were conducted using the Mayo Clinic Laboratory Neurological Questionnaire. Patients were distributed into clinical subtypes of ALS: typical, progressive muscular atrophy, primary lateral sclerosis, and progressive bulbar palsy. Furthermore, based on site of onset they were divided into three groups: bulbar onset, lower limb onset, upper limb onset. Cognitive changes were assessed using Addenbrooke’s Cognitive Examination Scale (ACE III) and the Frontal Behavioral Questionnaire, Frontotemporal dementia (FTD) was diagnosed according to the Strong critiera,5 and the patient’s quality of life was assessed by ALSFRS-R.\n\nVenous blood samples were collected in Georgia by MK, 5 ml venous blood samples were taken from the median vein of the forearm, EDTA k2 Vacutainers were used for storage and transferred to UCL Queen Square Institute of Neurology, Neurogenetics Laboratory for further research. The genomic DNA of the included subjects was extracted from whole blood using the Promega ReliaPrep™ Blood gDNA Miniprep System using manufacturers instructions.\n\nTo investigate the presence of an expanded GGGGCC hexanucleotide repeat in the non-coding region of the C9orf72 gene, we performed Repeat-Primed PCR (RP-PCR) in all patients and in three positive controls. The primers and thermocycling conditions used for the assay have been previously described.6 RP-PCR is able to determine whether an expanded allele is present in an individual, in which case a characteristic stutter pattern is seen7 (Figure 1).\n\nThis figure is an original figure produced by the authors for this article. RP-PCR, Repeat-Primed PCR.\n\nAll primers were used with the same molar concentrations. A PCR Mastermix was prepared by mixing 12.5 μl of Amplitaq Gold 360 Master Mix (ThermoFisher), 9.5 μl of 5M Betaine (ThermoFisher), 1 μl of 10 pmol/μl FAM labelled Forward primer (5′-TGTAAAACGACGGCCAGTCAAGGAGGGAAACAACCGCAGCC-3′), 1 μl of 10 pmol/μl Reverse primer (5′-CAGGAAACAGCTATGACC-3′), 1 μl of 10 pmol/μl repeat specific reverse primer (5′-CAGGAAACAGCTATGACCGGGCCCGCCCCGACCACGCCCCGGCCCCGGCCCCGG-3′) and 1 μl of 100 ng/μl DNA. Samples were amplified with an initial heat denaturation of 95°C for 10 minutes, followed by 10 cycles of 95°C for 30 seconds, 58°C for 2 minutes, 72°C for 2 minutes, and then 25 cycles of 95°C for 10 minutes, followed by 10 cycles of 95°C for 30 seconds, 58°C for 2 minutes, 72°C for 2 minutes with a 20 seconds increase per cycle. The final extension step was 72°C for 7 minutes. The PCR was run on a 9700 Block, at ramp speed 9600. After PCR, 1 μl of the reaction product was added to a mix with 9.2 μl of Formamide (Roche) and 0.1 μl of GeneScan 500 LIZ Size Standard (ThermoFisher). After a denaturation step at 95°C for 5 minutes, samples were analyzed using the ABI 3739 Genetic Analyser. Data were analyzed with the GeneMapper (RRID:SCR_014290) software (v. 4.0, Applied Biosystems).\n\n\nResults\n\nPatients with ALS were aged 26 to 84 years with a mean age of 58.3 years at disease onset. In total, 63.8% of the patients were 50–69 years old. A total of 51% of the patients were male, 49% were female with a male-to-female ratio of 1:1.\n\nAfter initial examination of 70 patients for eligibility, two patients were not confirmed to be eligible in the first stage, due to misdiagnosis of ALS, one of them had myasthenia gravis (MG) with anti-MUSK antibodies and the second patient had SMA (Spinal muscular atrophy) type 4. Four patients were not included in the study after being confirmed eligible, due to geographical conditions researchers were not able to get samples, and patients were not mobile, thus it was impossible for them to be transferred to the hospital (Figure 2).\n\nThis figure is an original figure produced by the authors for this article.\n\nBulbar onset ALS was observed in 21.3%, upper limb onset (UL-ALS) in 38.3%, and lower limb onset (LL-ALS) in- 40.4% of the patients (Table 1). FTD fulfilling the Strong criteria was diagnosed in seven patients (10.94%). Two patients (3.13%) have been identified to have familial ALS (FALS) based on family history.8\n\nWe screened all patients for GGGGCC hexanucleotide expansions between two 5′ non-coding exons of the C9orf72 locus using RP-PCR. We used a reliable assay that confidently differentiates between positive and negative cases by detecting up to 40 repeats, thus categorizing them as pathogenic expansions. An accurate number of repeats in each allele can be detected in the negative cases. The repeat size in the general population has been observed to vary between two to 30 for healthy individuals, while affected people present at least one expanded allele with repeats ranging between 30 to several hundred hexanucleotides,6,7 please see Figure N1 for comparison After performing RP-PCR, GGGGCC expansion was observed in only one patient. Most of our cases presented a homozygous two-repeats expansion. The mean expansion in our cohort was 2+3.11 repeats (Allele1 2-2, Allele2 2-12).9\n\n\nDiscussion\n\nA pathogenic repeat expansion in the non-coding region of the C9orf72 gene has been described to be the most common risk to develop familial ALS. However, most studies have been performed in European study populations10–13 and little is known from non-European countries. Based on these, a significant variation in c9orf-ALS frequency and distribution throughout Eurasia can be observed, with east Asian populations experiencing lesser cases, and India and Taiwan being exceptions (Figure 3).\n\nThe bottom part shows the list of c9orf72 sALS and fALS cases in Eurasian countries reported before.10,12–25 This figure is an original figure produced by the authors for this article. ALS, Amyotrophic lateral sclerosis; sALS, sporadic ALS; fALS, familial ALS.\n\nIn our study, we aimed to investigate the frequency of c9orf-ALS in Georgian patients. However, from our 64 patients only one tested positive for pathogenic GGGGCC repeat expansion, and the patient demonstrated bulbar onset ALS, with a history of severe dementia. Our results possibly indicate a different genetic background and the presence of distinct risk factors for ALS in this ethnic group. The Georgian geography with its isolation and small population size, particularly in the highlands, might have led to the bottleneck effect and enhanced genetic differentiation seen in our data.\n\nHowever, our results are limited due to the small cohort size. Further, the rare existence of the pathogenic repeat expansion could also be due to a previous single founder mutation. Smith et al. (2013) identified a haplotype that proves this point, that all massive GGGGCC hexanucleotide repeat expansion mutations—identified within intron 1 of C9orf72—carriers arose from a single common founder.13The most sensible explanation would therefore be that the expansion mutation arose on just one occasion in the European population. The results could further be explained by a close link between Georgian and Asian genetic pools, however, researchers reported that Caucasian groups were much closer to European than to West Asian groups with respect to mtDNA, opposite to be true for the Y chromosome, indicating a predominantly West Asian influence.26\n\n\nConclusions\n\nFurther genetic studies in a larger cohort are needed to confirm our results and to reveal genetic risks for ALS in the Transcaucasian population.\n\n\nEthics approval and consent to participate\n\nEthical approval was obtained from Tbilisi State Medical University (TSMU) ethics committee and University College London (UCL) institutional board. All experiments were performed in accordance with WMA declaration of Helsinki – Ethical principles for medical research involving human subjects. Informed consent was obtained from all participants. All participants consented in written form to participate in the study. All authors attest that the participants were aware of the study’s purpose, risks, and benefits.",
"appendix": "Data availability\n\nFigshare: ALS Patients GEORGIA, https://doi.org/10.6084/m9.figshare.23731674. 8\n\nThis project contains the following underlying data:\n\n- The spreadsheet data for all participants and outcomes underlying the Results section of the paper and Table 1.\n\nFigshare: RP-PCR Traces, https://doi.org/10.5522/04/23661813. 9\n\nThis project contains the following underlying data:\n\n- The raw data of the genetic testing (RP-PCR Traces).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nResearch was conducted as part of the Queen Square Genomics group at the University College London, supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. We are also grateful to Queen Square genomics at the Institute of Neurology University College London, supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre, for the bioinformatics support. For the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.\n\n\nReferences\n\nCharcot J, Sigerson G: Lectures on the Diseases of the Nervous System. Philadelphia: Lea; 1879.\n\nMasrori P, Van Damme P: Amyotrophic lateral sclerosis: a clinical review. Eur. J. Neurol. 2020; 27(10): 1918–1929. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZou ZY, Zhou ZR, Che CH, et al.: Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry. 2017; 88(7): 540–549. PubMed Abstract | Publisher Full Text\n\nShefner JM, Al-Chalabi A, Baker MR, et al.: A proposal for new diagnostic criteria for ALS. Clin. Neurophysiol. 2020; 131(8): 1975–1978. PubMed Abstract | Publisher Full Text\n\nStrong MJ, Grace GM, Freedman M, et al.: Consensus criteria for the diagnosis of frontotemporal cognitive and behavioural syndromes in amyotrophic lateral sclerosis [published correction appears in Amyotroph Lateral Scler. 2009 Aug;10(4):252]. Amyotroph. Lateral Scler. 2009; 10(3): 131–146. PubMed Abstract | Publisher Full Text\n\nvan der Ende EL , Jackson JL, White A, et al.: Unravelling the clinical spectrum and the role of repeat length in C9ORF72 repeat expansions. J. Neurol. Neurosurg. Psychiatry. 2021; 92: 502–509. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRenton AE, Majounie E, Waite A, et al.: A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011; 72(2): 257–268. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKekenadze M, Rocca C, Kaiyrzhanov R, et al.: ALS Patients GEORGIA. [Dataset]. figshare. 2023. Publisher Full Text\n\nRocca C, Kekenadze M, Turchetti V, et al.: RP-PCR Traces. University College London. [Dataset]. 2023. Publisher Full Text\n\nDeJesus-Hernandez M, et al.: Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron. 2011; 72(2): 245–256. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLogroscino G, Traynor BJ, Hardiman O, et al.: Incidence of amyotrophic lateral sclerosis in Europe. J. Neurol. Neurosurg. Psychiatry. 2010; 81(4): 385–390. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDorst J, Chen L, Rosenbohm A, et al.: Prognostic factors in ALS: a comparison between Germany and China. J. Neurol. 2019; 266(6): 1516–1525. PubMed Abstract | Publisher Full Text\n\nSmith BN, Newhouse S, Shatunov A, et al.: The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder. Eur. J. Hum. Genet. 2013; 21(1): 102–108. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOgaki K, Li Y, Atsuta N, et al.: Analysis of C9orf72 repeat expansion in 563 Japanese patients with amyotrophic lateral sclerosis. Neurobiol. Aging. 2012; 33(10): 2527.e11–2527.e16. Publisher Full Text\n\nÖzoğuz A, Uyan Ö, Birdal G, et al.: The distinct genetic pattern of ALS in Turkey and novel mutations. Neurobiol. Aging. 2015; 36(4): 1764.e9–1764.e18. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLysogorskaia EV, Abramycheva NY, Zakharova MN, et al.: Genetic studies of Russian patients with amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Frontotemporal Degener. 2016; 17(1-2): 135–141. PubMed Abstract | Publisher Full Text\n\nMok KY, Koutsis G, Schottlaender LV, et al.: High frequency of the expanded C9ORF72 hexanucleotide repeat in familial and sporadic Greek ALS patients. Neurobiol. Aging. 2012; 33(8): 1851.e1–1851.e5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlavi A, Nafissi S, Rohani M, et al.: Repeat expansion in C9ORF72 is not a major cause of amyotrophic lateral sclerosis among Iranian patients. Neurobiol. Aging. 2014; 35(1): 267.e1–267.e7. Publisher Full Text\n\nZou ZY, Li XG, Liu MS, et al.: Screening for C9orf72 repeat expansions in Chinese amyotrophic lateral sclerosis patients. Neurobiol. Aging. 2013; 34(6): 1710.e5–1710.e6. Publisher Full Text\n\nJang JH, Kwon MJ, Choi WJ, et al.: Analysis of the C9orf72 hexanucleotide repeat expansion in Korean patients with familial and sporadic amyotrophic lateral sclerosis. Neurobiol. Aging. 2013; 34(4): 1311.e7–1311.e9. PubMed Abstract | Publisher Full Text\n\nEdgar S, Ellis M, Abdul-Aziz NA, et al.: Mutation analysis of SOD1, C9orf72, TARDBP and FUS genes in ethnically-diverse Malaysian patients with amyotrophic lateral sclerosis (ALS). Neurobiol. Aging. 2021; 108: 200–206. Publisher Full Text\n\nTsai CP, Soong BW, Tu PH, et al.: A hexanucleotide repeat expansion in C9ORF72 causes familial and sporadic ALS in Taiwan. Neurobiol. Aging. 2012; 33(9): 2232.e11–2232.e18. PubMed Abstract | Publisher Full Text\n\nNarain P, Gomes J, Bhatia R, et al.: C9orf72 hexanucleotide repeat expansions and Ataxin 2 intermediate length repeat expansions in Indian patients with amyotrophic lateral sclerosis. Neurobiol. Aging. 2017; 56: 211.e9–211.e14. PubMed Abstract | Publisher Full Text\n\nHe J, Tang L, Benyamin B, et al.: C9orf72 hexanucleotide repeat expansions in Chinese sporadic amyotrophic lateral sclerosis. Neurobiol. Aging. 2015; 36(9): 2660.e1–2660.e8. PubMed Abstract | Publisher Full Text\n\nYilmaz R, Grehl T, Eckrich L, et al.: Frequency of C9orf72 and SOD1 mutations in 302 sporadic ALS patients from three German ALS centers. Amyotroph. Lateral Scler. Frontotemporal Degener. 2023; 24: 414–419. PubMed Abstract | Publisher Full Text\n\nNasidze I, Ling EY, Quinque D, et al.: Mitochondrial DNA and Y-chromosome variation in the Caucasus. Ann. Hum. Genet. 2004; 68(Pt 3): 205–221. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "218006",
"date": "07 Nov 2023",
"name": "Karri Kaivola",
"expertise": [
"Reviewer Expertise Neurogenetics"
],
"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 their manuscript titled ”Analysis of C9orf72 repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS)”, Kekenadze et al. assess using repeat-primed PCR the C9orf72 hexanucleotide repeat expansion frequency in 64 ALS patients from Georgia. The C9orf72 hexanucleotide repeat expansion is the most common genetic risk factor in populations of European descent, but not in other populations.\nEven though the study population is small, it is enough to rule out C9orf72 expansion as a common cause of ALS in Georgia as only one patient carried the mutation. The knowledge gained from this study is pretty much covered in the previous sentence, but the study is methodologically acceptable. There are minor things to address:\nThe introduction is very short and sweet. I was hoping more background on the C9orf72 expansion prevalence in nearby regions and what is known about ALS genetics prior to this study in Georgia. These questions were partly covered at the start of the Methods and Figure 3, I would bring some of that information to Introduction.\n\nAlso would be useful to know, is the Georgian population homogenous and does the study cohort represent the whole population or just some part of it?\n\nIn Methods the authors write “we estimated that at least 50 participants would be scientifically significant number for this research.” Estimated how and what does scientifically significant number mean? Is this based on e.g. C9orf72 expansion frequencies in neighboring countries?\n\nIn Results after listing excluded cases, the authors could repeat the final sample number, even though it is in Figure 2.\n\n1st sentence of 2nd paragraph in Discussion: “c9orf-ALS” is a bit colloquial, I would use the full gene name c9orf72.\n\nThere is a stray citation number 13 in discussion in sentence “identified within intron 1 of C9orf72—carriers arose from a single common founder.13”\n\nThe C9orf72 prevalence in Figure 3 seems unbelievably high in Belgium and Sweden (63-84% of fALS cases). I would urge the authors to reassess the evidence for these numbers, as all the numbers I have seen from robust reports have been considerably smaller.\n\nIn Figshare: ALS Patients GEORGIA table, the full dates of births of the patients are visible. Given the rarity of the disease, this makes the patients very identifiable, and I strongly urge the authors to remove such personally identifiable information and replace them with e.g. age. They could also add the C9orf72 allele lengths to the table.\n\nThe single founder hypothesis of C9orf72 expansion is very contested1, I would refrain from making statements about a single founder.\nIn conclusion, this is a small study that fills a small gap in knowledge, but the study is generally well made and presented.\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": "10569",
"date": "16 Nov 2023",
"name": "Mariam Kekenadze",
"role": "Author Response",
"response": "Dear reviewer, Many thanks for your immense effort in reviewing our article, all the comments are much appreciated and looked at in detail. We would like to respond to some of them. 1. Georgia is located in the Caucasus, neighboring countries are Armenia, Azerbaijan, Turkey, and Russia. After a thorough search of the literature using various languages, we were not able to find any relevant information about c9orf72 expansion prevalence in Armenia and Azerbaijan, however, there are some data available from Turkey and Russia, demonstrating low incidence in later countries, we depicted following in Eurasia map, Figure 3. Furthermore, there have not been any studies, including genetics, in the ALS population prior to this one in Georgia, indicating the significance of this research. 2. There is sparse information regarding the genetic architecture of the Georgian population, therefore it is difficult to conclude the homogeneity of the population. The study indeed represents the whole Georgian population, samples were gathered from different parts of Georgia, and results are published in different article: https://pubmed.ncbi.nlm.nih.gov/37166887/ 3. We concluded that scientifically significant results would represent identifying a similar number of ALS patients in the Georgian population size according to worldwide incidence/prevalence of the disease. Unfortunately, there is no data available regarding c9orf72 gene expansion prevalence in ALS patients in neighboring countries. 4. We agree with the reviewer. 5. C9orf72 positive cases in familial ALS in Belgium and Sweden, we used the following article: Smith BN, Newhouse S, Shatunov A, et al.: The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder. Eur. J. Hum. Genet. 2013; 21(1): 102–108, who reported these findings. 6. Thank you for pointing out the issue with privacy in Figshare, we will fix it."
}
]
},
{
"id": "238668",
"date": "19 Jan 2024",
"name": "Naoki Suzuki",
"expertise": [
"Reviewer Expertise Neurology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 report focuses on investigating the frequency of C9ORF72 mutations in ALS cases in Georgia, an area that has not been previously studied. This report holds considerable significance.\nAbstract: In the abstract, it is mentioned that there are 64 self-reported patients; however, in the Results section, it is specified as 64 sporadic and 2 familial cases. To avoid confusion, please correct the total count to 66.\nMethods: In the Methods section, it is stated as \"ethnically Georgian.\" Is it acceptable to assume that there are no individuals with mixed ethnic backgrounds, such as half or quarter Georgian? Additionally, basic demographic information about Georgia's population would be appreciated.\nResults: For cases with C9ORF72 expansion, one instance with a family history of dementia is noted. It would be beneficial to provide details on the type of dementia and its progression.\nParticipants: The statement indicating that scientifically significant interpretations can be made with 50 or more participants is made. Could you please provide the basis for this claim?\nTable 1: In Table 1, PBP (Progressive Bulbar Palsy) is listed as zero, while Bulbar onset ALS includes 14 cases. Please clarify the definition of PBP and how Typical ALS is defined.\nFigure 3: Concerns are raised about the data from the Nordic region in Figure 3, as the percentages appear unusually high. Please verify the accuracy of the literature sources.\nTypo：a single common founder. 37Themost sensible\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "11068",
"date": "13 Apr 2024",
"name": "Mariam Kekenadze",
"role": "Author Response",
"response": "Thank you for your effort and review it is much appreciated! 1. Indeed 64 self-reported patients were involved in the study, among them 62 sporadic and 2 familial cases. This has to be addressed. 2. Ethnically Georgian patients were only from Georgian background, with no mixture of other ethnicities. It was unchallenging to find purely Georgian patients because Georgians are the predominant ethnic group in Georgia (almost 90% of the population) and they tend to marry within their own ethnic group. 3. The patient who had pathological c9orf72 repeat expansion had a positive history of dementia in the family, in particular, her brother suffered from FTD, and her mother was diagnosed with dementia as well, however, the type was not specified in reports. FTD was suspected. 4. A scientifically significant number would be 50, considering the low incidence of the disease and the population number of Georgians (around 3-3,5 million) 5. PBP is marked by progressive weakness of the muscles innervated by cranial nerves of the lower brain stem. Clinical manifestations include dysarthria, dysphagia, facial weakness, tongue weakness, and fasciculations of the tongue and facial muscles. Bulbar onset ALS - starts with the degeneration of lower motor cranial nerves and involves later motor neurons throughout the neuroaxis. 6. The data was utilized from this article, the European Journal of Human Genetics. Smith BN, Newhouse S, Shatunov A, et al.: The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder. Eur. J. Hum. Genet. 2013; 21(1): 102–108 7. The typo should be addressed."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1113
|
https://f1000research.com/articles/12-1253/v1
|
02 Oct 23
|
{
"type": "Research Article",
"title": "Psychometric properties of the Maslach Burnout Inventory in healthcare professionals, Ancash Region, Peru",
"authors": [
"Rosario Margarita Yslado Méndez",
"Junior Sánchez-Broncano",
"Carlos De La Cruz-Valdiviano",
"Ivette Quiñones-Anaya",
"Enaidy Reynosa Navarro",
"Rosario Margarita Yslado Méndez",
"Junior Sánchez-Broncano",
"Carlos De La Cruz-Valdiviano",
"Ivette Quiñones-Anaya"
],
"abstract": "Background: Burnout syndrome (BS) among healthcare professionals in Peru demands immediate attention. Consequently, there is a need for a validated and standardized instrument to measure and address it effectively. This study aimed to determine the psychometric properties of the Maslach Burnout Inventory (MBI) among healthcare professionals in the Ancash region of Peru. Methods: Using an instrumental design, this study included 303 subjects of both sexes (77.56% women), ranging in age from 22 to 68 years (M = 44.46, SD = 12.25), selected via purposive non-probability sampling. Appropriate content validity, internal structure validity, and item internal consistency were achieved through confirmatory factor analysis, and discriminant validity for the three dimensions was obtained. Evidence of convergent validity was found for the Emotional Exhaustion (EE) and Personal Accomplishment (PA) dimensions, with reliability values (ω > .75). Results: The EE and PA dimensions exhibited acceptable levels of reliability (ω and α > .80). However, the Depersonalization (DP) dimension demonstrated significantly lower reliability (α < .60 and ω < .50). Conclusions: A correlated three-factor model was confirmed, with most items presenting satisfactory factor loadings and inter-item correlations. Nonetheless, convergent validity was not confirmed for the DP dimension.",
"keywords": [
"Burnout",
"Psychometrics",
"Validity",
"Reliability",
"Healthcare Professionals"
],
"content": "Introduction\n\nBurnout Syndrome (BS) represents a global concern in public health, as it affects health professionals with increasing frequency and intensity. BS is a disease associated with occupational risk that impacts quality of life, physical and mental health, well-being, and can even endanger life (through suicidal behaviors) of those affected by it.1,2 As a result of BS, the provision of optimal patient care is hindered, as it affects job performance and productivity; the degree of satisfaction of health professionals and patients;3 and it exposes healthcare facilities to economic losses and deficiencies in achieving goals.4 Therefore, it's essential to periodically evaluate BS levels in healthcare staff for timely detection, treatment, and prevention of this mental and occupational health issue. This will ensure that patients receive reliable and competent clinical care.\n\nBS emerges as a reaction to prolonged occupational stress, often surfacing when healthcare workers' stress coping mechanisms prove inadequate to handle their job-related stressors.5 The Maslach Burnout Inventory (MBI)6 is utilized to gauge BS, capturing three distinct dimensions: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). EE signifies the sense of emotional oversaturation and fatigue from work; DP represents an impersonal and indifferent response towards patients; whereas PA indicates feelings of competency and success within the professional sphere.7 An individual is diagnosed with BS when they exhibit elevated levels in the domains of EE and DP, but a diminished sense of PA.\n\nThere are multiple tools to measure BS; however, in Peru, the most commonly used instrument to assess BS levels in health professionals is the MBI. The MBI has several versions, such as the MBI-HSS,8,9 the MBI-HSS (MP),7 and the MBI “Burnout” Inventory by Maslach - Burnout Syndrome due to Care-related Occupational Stress,6 which is a Spanish adaptation of the MBI. This adaptation is based on a three-factor structure composed of 22 items. These items are evaluated using a Likert scale ranging from 0 (never) to 6 (daily). The items are organized into three dimensions: Emotional Exhaustion (EE - 9 items), Depersonalization (DP - 5 items), and Personal Accomplishment (PA - 8 items). Subsequently, scores are categorized into BS levels: mild, moderate, and severe.\n\nPast investigations into the psychometric characteristics of the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) utilizing healthcare professional samples have yet to achieve consensus regarding the instrument's solid psychometric attributes.10 Some studies confirm the 22-item three-factor structure, validity, and reliability of the MBI-HSS11,12; other studies corroborate the three-factor model, but with elimination of some items.13–17 Other studies have found a four-factor model18 and a five-factor model.19\n\nIn Peru, the three-factor structure of the MBI-HSS was confirmed in Peruvian physicians with the elimination of three items. Additionally, a three-factor model was found in Peruvian nurses with the elimination of five items.20 However, there are no reports on the psychometric properties and standardization of Maslach and Jackson's MBI in its 1997 version, despite its frequent use in studies conducted in Peru.21–23\n\n\nLiterature review\n\nResearch pursuits have been launched worldwide, using a diverse set of statistical procedures, to scrutinize the psychometric characteristics of the MBI. These investigations have concentrated on deciphering the intrinsic structure of this measurement tool. In the context of the 22-item versions, structures ranging from one-factor, two-factor, three-factor models,24 to four-factor structures25 have been discerned. Some studies have advised the exclusion of certain items to augment the model fit indices. As such, one study discovered a two-factor model comprised of only 7 items26; other studies recognized a three-factor model with 20 items,14 19 items,27 18 items,28 or 15 items29; while others detected five-factor models containing 19 items.30 Lately, several authors have suggested that the bifactor model offers superior fit, enabling the entire set of indicators to load directly on a general factor, that is, the global BS and individual factors.\n\nIn 2022, González-Rodríguez et al. conducted a study in Spain with the goal of evaluating the psychometric properties of the MBI-HSS tool. They aimed to validate its accuracy by confirming the original factor structure and its convergent validity, as well as assessing reliability through internal consistency. The results revealed a strong internal consistency (α = 0.882). The four factors demonstrated direct and moderate interrelations, with correlation coefficients ranging between 0.328 and 0.534.31\n\nIn the context of Vietnam, Thai and colleagues carried out a cross-sectional quantitative study with a sample of 1162 medical professionals, including doctors and nurses from fifteen hospitals. Their findings indicated that the 22-item version of the MBI-HSS provided a better fit to the data, effectively capturing the three interconnected facets of Burnout Syndrome, specifically Emotional Exhaustion (EE), Depersonalization (DP), and Personal Accomplishment (PA). The study also confirmed the measurement invariance of the MBI-HSS across different sexes and job roles. However, the data did not fit well for the group predisposed to common mental disorders. The conclusion drawn was that the Vietnamese version of the MBI-HSS operates as a valid measurement tool among Vietnamese professionals not at risk of mental health issues.12\n\nAlso, in Iran Lin and colleagues in 2022 conducted a cross-sectional quantitative study using a sample of 306 healthcare professionals, which included 106 doctors and 200 nurses. The findings from this study indicated that the MBI-HSS-MP exhibits strong psychometric properties among healthcare professionals across all three dimensions that were examined.32 Similarly, in 2021, a quantitative, exploratory, descriptive, and analytical study was carried out by Pereira and colleagues, involving a participant pool of 282 health professionals. The study confirmed the three-factor structure of the MBI. However, items 9, 12, 15, and 16 demonstrated a factor load below the suitable cut-off and were consequently omitted from the model. The results of the study validate that the MBI serves as a reliable and factorially valid instrument for evaluating burnout among healthcare professionals in Brazil.33\n\nMukherjee et al., in 2022, conducted research in the United Kingdom to determine the psychometric properties of the MBI-HSS in pediatric oncology staff, analyze its factorial structure, assess its internal reliability, and evaluate whether it met the requirements of the Rasch model. They employed a quantitative approach in a sample of 203 health workers from seven major treatment centers and a charity dedicated to child cancer in the UK (comprising 115 nurses, 40 doctors, 29 social workers, and 18 play specialists) who completed the MBI-HSS. The results from the factor analysis did not support the traditional three-factor structure of the MBI-HSS. Instead, they suggested the presence of seven distinct factors. Assessments using Coefficient Alpha and Rasch modeling showed that while the Emotional Exhaustion (EE) and Personal Accomplishment (PA) subscales met the standards for interval-level measurements in group-level diagnoses, the Depersonalization (DP) subscale did not meet these benchmarks. Further investigation revealed a “floor effect” in several DP items.34\n\nAlso, in 2020, a research investigation was conducted by Slabšinskienė and her team in Lithuania. Their findings confirmed that women tend to experience higher levels of emotional exhaustion compared to their male counterparts. Furthermore, it was found that dentists with more advanced specializations were significantly less prone to Burnout Syndrome than those engaged in general practice. These results not only affirm the factorial validity of the MBI but also underscore its stable structure and the differences in Burnout Syndrome dimensions across various demographic and workload sectors.35\n\nIn 2020, Calderón-De la Cruz and Merino-Soto conducted a research study, the results of which revealed a three-factor internal structure within the MBI-HSS after excluding three items. The reliability was considered adequate, with scores ranging between 0.845 and 0.918. However, this dropped significantly when correlated errors were taken into account, with scores between 0.335 and 0.517. In conclusion, the suitability of the proposed 19-item structure was confirmed, validating the internal structure of the MBI-HSS among Peruvian physicians. Furthermore, the 22-item version was deemed irrelevant for the assessment of Peruvian physicians, and thus was dismissed.20\n\nIn addition, in 2020 Calderón-De la Cruz and colleagues conducted a research study, the results of which identified three distinct factors. However, after excluding seven items, they produced a condensed 15-item version which exhibited satisfactory reliability, with omega coefficient values ranging between 0.797 and 0.837. This brought into question the validity of the original MBI-HSS when applied to nurses, leading them to propose this 15-item version as an alternative. In conclusion, the need to tailor the MBI-HSS to the specific needs of Peruvian nursing professionals was confirmed, as the original version was found to be unsuitable for this group. Nevertheless, a satisfactory alternative was offered in the form of a 15-item version, which demonstrated both an adequate internal structure and reliability.36\n\nSeveral studies have pinpointed factors related to the mental health outcomes experienced by healthcare professionals, underscoring the significant influence of workplace stressors and the importance of effective coping strategies.37,38 These include: 1) insufficient hospital resources, 2) increased occupational risk due to potential virus exposure, 3) prolonged working hours, 4) irregular sleep patterns, 5) challenges in maintaining a work-life balance, 6) neglect of personal and family needs due to increased workload, and 7) inadequate communication and a lack of up-to-date information. Each of these factors has been recognized as a significant contributor to increased physical and mental fatigue, anxiety, stress, and burnout.39–41\n\nIn recent years, BS has emerged as a recognized psychosocial issue stemming from prolonged occupational stress, positioning it as a critical area of focus in fields like occupational health psychology and organizational/work psychology. The ramifications of burnout include both physiological and psychological complications in employees, significantly impacting their job performance. One particular study reported a general prevalence of BS among physicians amounting to 67%, coupled with high instances of EE, DP, and diminished feelings of PA. These figures underscore the importance of ongoing research and effective interventions to manage and prevent BS among healthcare professionals and in other high-stress occupations.42\n\nIn Peru, it was found that 6.9% of physicians in Arequipa presented severe levels of BS.43 Likewise, a frequency of BS was found for medical interns in Lima hospitals of 33% and 35% in the years 2017 and 2018, respectively.44 The occurrence of symptoms related to BS, including anxiety, depression, diminished satisfaction and quality of care, as well as post-traumatic stress and higher suicide rates, are notable concerns.45 Amidst the coronavirus disease 2019 (COVID-19) pandemic, there's an intensified need to address these issues as healthcare professionals are operating within increasingly stressful environments, often encountering traumatic situations and heavy workloads. This demands a comprehensive understanding of these professionals' mental health, which is fundamental to developing effective interventions. Regular assessments, mental health support programs, coping strategies, and initiatives promoting work-life balance can all serve as crucial elements in preserving the psychological wellbeing of healthcare workers. The ultimate goal is to ensure that those who provide care are also receiving it, a consideration that has never been more critical than in the challenging context of the COVID-19 pandemic.\n\nBS has been recognized as a health concern since it was first documented in the late 1960s.46 The subsequent five decades of research, albeit uncoordinated, have produced various definitions and measures of BS worldwide, leading to some inconsistencies. The principal tool for gauging BS is the MBI,9 utilized across a range of populations, including the general clinical population,11 healthcare professionals with versions such as the MBI–HSS,31,47 the MBI–Medical Personnel (MBI–MP), and the MBI–General Survey (MBI–GS). The original questionnaire appraises three dimensions through a total of 22 items: EE (representing feelings of being emotionally overextended by one's work), DP (a disengaged and impersonal reaction towards patients), and PA (emotions of competence and successful achievement in one's profession).\n\nMaslach and Jackson (1981) proposed the three-dimensional model of the MBI, which includes three dimensions that together explain BS in any worker who is directly related to other people or clients.8 These dimensions include: EE, which involves a feeling of being emotionally overextended and exhausted due to constant interactions with those under one's care; DP, characterized by the development of negative, detached, and cold attitudes or responses towards others; and PA, which reflects how workers evaluate themselves in relation to their work environment and professional growth. Generally, low levels of PA correspond with a perception of the work environment as being negative and failing to meet their expectations.\n\nIn terms of BS dimensions, EE often arises as a response to stress when individuals feel overwhelmed by their job requirements but lack the emotional or physical resources to cope with these demands. DP embodies the interpersonal context of work, reflecting negative or excessively detached responses towards various aspects of the job. Personal PA, on the other hand, relates to feelings of competency, efficiency, and job satisfaction.48 These three dimensions have shown consistent score reliability in over 80 studies published to date. They have been further validated for human service professions, encompassing healthcare professionals.11,31,47\n\nTo evaluate the psychometric properties of the MBI, researchers often use the Classical Test Theory (CTT). Within this framework, two critical concepts, reliability and validity, are fundamental for assessing the quality of a measurement tool. The understanding of validity has evolved substantially over time. According to the 1985 Standards for Educational and Psychological Testing and Manuals, it is emphasized that validity is a singular entity, where the validity of an assessment is determined by its construct validity.49 The 2014 Standards argue that the term “test validity” is improper, therefore, the notion of different types of validity is considered irrelevant. Instead, these standards advocate for the provision of multifaceted information relevant to the specific purpose behind the development of the test or measurement tool.50 It's important to reiterate that the validation process doesn't apply to the test itself, but rather to the interpretations drawn from individuals' scores for a specified objective.\n\nFrom this perspective, the responsibility for a test's validity doesn't solely rest on the test creator, but also extends to the person administering the test.51 Similarly, the validity of a test isn't definitively established, but rather involves an ongoing process of gathering evidence.50 From a scientific perspective, construct validity is the only form of validity that is deemed acceptable. Therefore, the rationale and methods employed for its determination typically align with the scientific method. Evidence for construct validity is derived from multiple sources and presupposes a precise definition of the construct, along with its dimensions or facets if necessary.52\n\nSimilarly, it's important to recognize that no single study validates or proves an entire theory; it only does so in relation to certain deductions that can be drawn from it.50 Concerning the constructs, if the results are negative, they can be interpreted in three ways: the test may fail to measure the construct, the theoretical framework might be flawed, leading to potentially incorrect inferences, or the design of the study may not be conducive to an effective test of the hypotheses.53 These interpretations suggest a deficiency in both psychometric and theoretical research knowledge, which could lead to ambiguous interpretation of negative results. Lastly, it's crucial to remember that unexpected relationships, just as much as anticipated ones, form part of the construct's nomological network and contribute to the understanding of the scores.52\n\nAlternatively, reliability is associated with the degree of consistency across multiple instances of a measurement procedure for a given group's test scores, from which the reliability and consistency of an individual's score can be inferred.50 This definition implies that identical test scores should be obtained under the same administration and scoring conditions at different times.53 It is also inferred that reliability refers to the precision of the measurement, independent of what the test measures. Moreover, the reliability of scores is not absolute but rather is relative to the characteristics of the group in which it is being assessed.54\n\nThis study contributes to the expanding knowledge concerning the validity and reliability of scores from Maslach and Jackson's (1997) MBI for measuring burnout among healthcare professionals in Peru.6 The variability in this instrument's internal structure suggests that its psychometric properties should be periodically assessed, especially when it's applied to a population where it hasn't been adapted or standardized. The practical significance of this study lies in providing a valid and reliable instrument for diagnostic assessment, clinical practice, and research, with the objective of designing prevention and intervention programs. Additionally, this study carries social relevance as it enables diagnosis of the real situation of burnout in the context of a pandemic. This helps control negative consequences and improve the mental and occupational health of healthcare professionals.\n\nThe overarching question guiding this research is: What evidence of reliability and validity does the MBI present in healthcare professionals from the Ancash region, Peru? Specific objectives are proposed:\n\n1. To establish the validity of the MBI in healthcare professionals from the Ancash region, Peru, using criteria from expert judges and confirmatory factor analysis (CFA).\n\n2. To gauge the reliability of the MBI in healthcare professionals from the Ancash region, Peru, using Cronbach's alpha coefficient.\n\n3. To assess the validity of the MBI in healthcare professionals from the Ancash region, Peru, through structural equation modeling (SEM), including both discriminant and convergent evidence.\n\n4. To compute MBI scores to obtain interpretative norms (reference values) for the instrument in healthcare professionals from the Ancash region, Peru, using ROC curves.\n\n5. The prevailing hypothesis suggests that the MBI exhibits satisfactory psychometric properties in terms of reliability and validity, and provides standardized scores for healthcare professionals from the Ancash region in Peru.\n\n\nMethods\n\nApplied research, which seeks to provide innovative solutions to problems that affect an individual, group, or society.55 This study focused on measuring burnout in healthcare professionals from the Ancash Region, Peru. It corresponds to an instrumental design research,56 as the psychometric properties of a measurement instrument will be analyzed, specifically the MBI. In this way, reliability and validity evidence will be provided for the mentioned test, as well as the establishment of interpretative norms for scores (standardization). Appendix A and B shows the first three items of this instrument.\n\nThe study population included 1,844 healthcare professionals from three level II hospitals in the Ancash Region of Peru. These professionals were actively working as healthcare personnel during the COVID-19 pandemic.57 The sample was collected through non-probabilistic convenience sampling. 366 participants responded to the survey, but 63 surveys were discarded due to the detection of atypical values.58 Therefore, the final sample consisted of 303 participants, which allowed for a better estimation in the statistical analyses performed. The data was collected online during the months of September and October 2021. Regarding the sample size, it was estimated that, to validate this instrument, the sample should consist of at least 300 participants, as suggested by Comrey and Lee (1992).59\n\nThe inclusion criteria for the study stipulated that participants must be healthcare professionals aged between 25 and 68 years,60 have a minimum of one month's work experience,61 and have agreed to participate in the study via informed consent. The study excluded healthcare professionals who were undergoing any psychological or psychiatric treatment,62 as well as those who were on leave or had ceased their work activities during the administration of the instruments.\n\nBefore administering the survey, permission was sought from each director of the hospitals under investigation. Subsequently, the survey was made available only to participants who were informed and accepted the informed consent. Health professionals were invited to participate in the study via WhatsApp and emails. To avoid bias, incomplete surveys were discarded during data cleaning. The study employed an online survey method and utilized the following tools: 1) A sociodemographic form that gathered data on the following variables: age, sex, marital status, employment status, occupation, work area, type of job, care for COVID-19 patients, diagnosis with COVID-19, years of service, and hours of patient contact. 2) The Maslach Burnout Inventory (MBI) (Maslach & Jackson, 1997), which is a 22-question Likert-type questionnaire that measures feelings related to work.9\n\nThe comprehensive statistical evaluation was conducted in four phases. The first phase comprised the calculation of descriptive statistics for the items, encompassing mean, standard deviation, skewness, and kurtosis. The last two coefficients represent the extent of deviation from a normal distribution, with desirable values ranging between -2 and 2.63 Furthermore, the research inspected the floor and ceiling effects of the items, concentrating on the proportion of participants who selected the lowest and highest response options, respectively. Items that noted percentages equal to or less than 15% were considered devoid of these effects.64 In addition, the discrimination power of the items was estimated through the item-rest corrected correlation, considering values greater than.20 as acceptable.65\n\nIn the second phase, validation evidence founded on the test's internal structure was gathered via confirmatory factor analysis (CFA). The employed estimation technique was the Weighted Least Squares Mean and Variance Adjusted (WLSMV) with robust standard errors and a scaling correction (SS) statistical test, which was applied to the polychoric correlation matrix of the items. Pertaining to the goodness-of-fit indices employed to evaluate the estimated models, the ratio of chi-square to degrees of freedom (SSχ2/df) was leveraged, considering values below 2 as satisfactory.66 The Comparative Fit Index (CFI) and Tucker-Lewis Index (TLI) were utilized, with values greater than .95 considered satisfactory.67 The Root Mean Square Error of Approximation (RMSEA) and Standardized Root Mean Square Residual (SRMR) were also taken into account, viewing values less than.08 as acceptable.68 The Weighted Root Mean Square Residual (WRMR) was included in the assessment, with values under 1 deemed satisfactory. Additionally, factor loadings that exceeded.50 were considered to be acceptable.66\n\nIn the third phase, evidence of validity based on correlations with other variables was gathered. This involved evaluating both convergent and discriminant validity evidence. The assessment of convergent validity evidence was performed via the average variance extracted (AVE) for each factor, with acceptable minimum values determined according to the guidelines suggested by,69 taking into account factor loadings, Cronbach's alpha reliability coefficient, and the quantity of items in the evaluated factor. Conversely, evidence of discriminant validity was derived using two methodologies. The heterotrait-monotrait ratio (HTMT) was utilized, with values below 0.85 regarded as suitable.70 The Fornell-Larcker criterion was also implemented, which necessitates the comparison of the square root of the AVE for each factor with its correlations to other factors. To consider evidence of discriminant validity, the square root of the AVE for a factor should exceed its correlation with other factors.71\n\nFinally, in the fourth stage of the analysis, the dependability of test scores was evaluated using internal consistency methods. This procedure incorporated the use of the Cronbach's alpha coefficient, calculated on the basis of the covariance among the items.72 This coefficient ranges from 0 to 1, with a value of.70 or higher deemed acceptable.73 In addition, MBI scores were standardized utilizing ROC curves to derive interpretive norms for the instrument.\n\nThe data analysis was carried out using R software, version 4.1.2.74 A variety of packages were employed for specific functions: the tidyverse package version 1.3.0 for data manipulation, the NANIAR package version 0.6.0 for detecting missing values, the Test Data Imputation package version 1.1 for imputing missing values, the MissMech package version 1.0.2 for checking the missing completely at random (MCAR) assumption, the psych package version 2.0.8 for item analysis, the lavaan package version 0.6-7 for CFA, and the semTools package version 0.5-3 for estimating reliability, AVE, and HTMT.\n\nIn the current study, meticulous steps were undertaken to counteract and mitigate possible biases. Prior to the survey's distribution, approval was secured from the leadership of the involved hospitals. Participation was restricted to those healthcare professionals who provided their informed consent. To ensure a neutral selection process, invitations were disseminated to potential participants via WhatsApp and email. Furthermore, any incomplete responses were eliminated during the data refinement phase, safeguarding the integrity and accuracy of the concluding data.\n\nThe General Health Law No. 26842 of Peru,75 updated until the year 2022, up to date until 2022, underscores the significance of fostering scientific and health-related technological research, while also safeguarding health service providers. This study was designed to ensure no risks for the participants since it did not entail any physiological, psychological, or psychiatric alterations or interventions. Prior to the application of the study tool, informed consent was secured from the participants. The Ethics Committee of the Universidad Nacional Santiago Antúnez de Mayolo in Huaraz, Peru gave their approval for the study via REPORT No. 0010-2022-UNASAM-DII/CEI/M, on July 17, 2021.\n\n\nResults\n\nBefore conducting the statistical analysis, the initial data were thoroughly reviewed to identify missing data and outliers. In this regard, no missing values were found, but 26 univariate outliers were detected (7 in DP and 19 in PA) using the absolute deviation from the median. Additionally, 37 multivariate outliers were observed through a robust version of Mahalanobis distance.58 Therefore, 63 cases were removed to obtain a final database consisting of 303 participants, which allowed for a better estimation in the conducted statistical analyses.88 It's crucial to mention that the sample size achieved in this study surpasses the suggested minimum of 300 cases for studies utilizing factor analysis.76\n\nTable 1 provides a detailed overview of the demographic data of the sample population. The healthcare professionals participating in the study had ages ranging from 22 to 68 years, with an average age of 44.46 and a standard deviation of 12.25. The sample was largely made up of females, representing 77.56% of the total. In terms of marital status, those who are married constituted the largest proportion, at 43.23%. The majority of participants were employed in permanent positions (62.71%). Regarding occupation, the majority were nurses (38.94%) and belonged to various areas such as gynecology-obstetrics (15.84%), Covid-19 (13.86%), and emergency (13.53%). Additionally, most participants worked in on-site settings (88.45%). Regarding questions related to Covid-19, the majority of healthcare professionals did not have direct contact with confirmed Covid-19 patients (55.12%) and were not diagnosed with a Covid-19 infection themselves (66.34%). Finally, the majority of the sample had a tenure of 1 to 5 years (37.29%) and had more than 7 hours of patient contact per day (70.96%).\n\nTable 2 presents the descriptive and discrimination analysis of the items. Regarding the central tendency of the items, item BS_19 obtained the highest average score (M = 5.43), while the lowest mean was found in item BS_22 (M = 0.68). In terms of item dispersion, item BS_06 had the highest variability (SD = 1.92), while the lowest variability was observed in item BS_19 (SD = 0.93). Regarding the item shape measures, the skewness and kurtosis values indicated that items BS_04, BS_09, BS_12, BS_19, and BS_22 had issues in both indicators (outside the range of -2 and 2). Additionally, items BS_05, BS_07, BS_13, BS_17, and BS_18 showed excessive kurtosis (values greater than 2). These results suggest that, in the mentioned items, the distributions do not follow a normal curve. Furthermore, most of the items exhibited floor and ceiling effects, except for items BS_01 and BS_02. Finally, the corrected item-test correlation indicated that the majority of the items had good discriminative ability, as they obtained values greater than.20, except for items BS_05, BS_10, BS_15, and BS_22, which belong to the dimension of DP.\n\nTable 3 exhibits how validity evidence, predicated on the content of the MBI, recognized as one of the five key sources of validity evidence50 was gathered during this study. This evidence was assembled via the assessment performed by six specialists versed in areas such as quantitative methodology, psychometrics, instrument design, and mental health metrics. These experts appraised the relevance, representativeness, and lucidity of the items using a five-point scale (1 = not at all to 5 = entirely), as well as their essentiality for assessing burnout in healthcare professionals. A majority of these expert evaluators were clinical psychologists with over eight years of professional service, and their ages ranged between 35 to 60 years.\n\n* A = Average.\n\n** V = V de Aiken.\n\n*** CVI = Lawshe's Content Validity Index.\n\nThe Aiken's V coefficient, which spans from 0 to 1, was employed to acquire a quantitative measurement of the judges' evaluation of the items' relevance, representativeness, and clarity, with a value nearing 1 suggesting a more favorable evaluation of the item. In the context of this study, values greater than.70 were deemed sufficient.77 In order to quantitatively encapsulate the assessment of whether the items were indispensable for measuring BS or not, the Content Validity Ratio (CVR) was used, adopting the method suggested by.78 An item was regarded as essential if it had a CVR of 1.00, contingent on the quantity of judges.79\n\nRegarding the results of the 22 items in the instrument (Table 3), all of them had Aiken's V values above.70 in the evaluation of item content. This indicates that the items are relevant, representative, and clear for measuring the target variable.77 In terms of the assessment of whether the items are essential or not, most of them showed critical values equal to 1.00, except for items BS_05 and BS_22, which had values of.67 and.33, respectively. Therefore, the six judges evaluated items BS_05 and BS_22 as non-essential for measuring burnout in healthcare professionals. Both items belong to the dimension of DP.\n\nTable 4 shows the validity tests in terms of internal structure by confirmatory factor analysis. Four models, as identified in previous literature, were scrutinized: an oblique three-factor model, a hierarchical three-factor model inclusive of a general factor, a unifactorial model featuring a solitary general factor, and a bifactorial model that concurrently tests both a three-factor unrelated model and a unifactorial model. The first two models showed good fit indices (SSχ2/gl < 3, RMSEA < .80, CFI > .90, TLI > .90, SRMR < .80, and WRMR close to 1). However, the unifactorial model had inadequate fit indices (Table 4), and the bifactorial model did not converge, so both models were discarded.\n\nBoth the oblique and hierarchical models displayed comparable values in their goodness-of-fit indices. Therefore, to discern which model was superior, the reliability of the score values was examined across both models. In the hierarchical model, the reliability of the general factor was very low (ω = .483), so this model was discarded from the study.\n\nConsequently, the correlated three-factor model was analyzed, as shown in Table 5. Most items in this model possessed factor loadings greater than.40, with the exception of item BS_15, which had a factor loading of.287 (also seen in Table 5). Regarding the interrelation among the factors, significant and moderate correlation values were noted. The correlation between EE and DP stood at.626, between EE and PA was -.657, whereas the correlation between DP and PA was -.468, as depicted in Figure 1.\n\nAs shown in Table 6, the reliability of MBI scores was assessed via the internal consistency of the items, employing alpha (α) and omega (ω) coefficients, given that the measurement model was tau-equivalent, as verified through confirmatory factor analysis (χ2 = 628.190, df = 225, χ2/df = 2.79, SRMR = .093, RMSEA = .077 [95% CI.070, .084], CFI = .920, TLI = .918). The results inferred that the dimensions of EE and PA exhibited satisfactory levels of reliability (with ω and α values greater than.80). However, in the dimension of DP, reliability was very low (α < .60 and ω < .50). Furthermore, the strength of correlations between items within each dimension was scrutinized. The analysis revealed that within the dimensions of EE and PA accomplishment, the average inter-item correlation surpassed.40. However, within the DP dimension, the items exhibited a weaker correlation to each other, yielding an average inter-item correlation of just.21.\n\nConcerning the evidence of convergent validity, assessed via the Average Variance Extracted (AVE), an acceptable level was detected for the dimensions of emotional exhaustion and personal accomplishment, this being substantiated by their reliability values (with ω values exceeding.75), number of items (between 7 and 9), and magnitudes of the factor loadings of their items, which were above.50.69 However, in the dimension of DP, the AVE was lower than.25, indicating that this dimension lacks evidence of convergent validity or variance attributable to the specified measurement model.\n\nPertaining to the evidence of discriminant validity, all three dimensions demonstrated suitable values for the HTMT2 ratio (below.85), recording values of.686 (emotional exhaustion), .306 (depersonalization), and.678 (personal accomplishment). However, the Fornell and Larcker criterion was solely satisfied by the EE dimension, as its square root of the AVE (.699) surpassed the correlations with the other two factors.71\n\nTable 7 presents percentile norms for the three dimensions of the MBI, with three categories (low, medium, and high) corresponding to the 25th, 50th, and 75th quartiles, respectively.80 For the dimension of EE, scores between 0 and 9 indicate a low level, between 10 and 24 indicate a medium level, and scores between 25 and 54 indicate a high level. In the dimension of DP, scores between 0 and 1 indicate a low level, between 2 and 7 indicate a medium level, and scores between 8 and 30 indicate a high level. For the dimension of PA, scores between 0 and 39 correspond to a low level, between 40 and 45 indicate a medium level, and scores between 46 and 48 indicate a high level. Considering these factors, elevated scores in EE and DP, coupled with low scores in personal accomplishment, are deemed suggestive of BS issues.\n\n\nDiscussion\n\nThe results indicated that most items of the MBI showed good discriminative ability within their respective dimensions, except for four items in the DP dimension, indicating low discrimination. Regarding the validity of the instrument, evidence based on content showed that the items were relevant, representative, and clear for measuring burnout, although two DP items were assessed as non-essential. In addition, the confirmatory factor analysis revealed a good fit for the three-factor correlated model. Convergent evidence was found within the dimensions of PA and EE, while discriminant evidence was present across all three dimensions. Finally, percentile norms were created for interpreting scores. It was determined that the EE and PA dimensions displayed satisfactory internal consistency, whereas the DP dimension demonstrated relatively low reliability.\n\nDescriptive item analysis mainly indicated kurtosis problems, meaning that a high percentage of participants chose only one response option, resulting in floor or ceiling effects. In some cases, these effects were excessive, such as in items BS_13, BS_05, BS_10, BS_15, and BS_22, where more than 50% of respondents chose the lowest alternative (floor effect), with the latter four items belonging to the DP dimension, suggesting a general tendency to have low scores in that dimension. On the other hand, the most notable ceiling effect was observed in items BS_04, BS_07, BS_09, BS_12, BS_18, and BS_19 (all related to PA), as more than 50% of the sample selected the highest response option, indicating that the majority of participants had a tendency to obtain high scores in that dimension.\n\nRegarding the discrimination of items within each dimension, assessed through corrected item-test correlations, it was found that most items exceeded the criterion of .20, indicating good discriminative ability. However, four items in the DP dimension (BS_05, BS_10, BS_15, and BS_22) showed low values, ranging from.052 to.186, suggesting a weak association of each item with the overall score in that specific dimension. Additionally, the remaining DP item (BS_11) slightly surpassed the threshold of.20 (ritc = .209). As a result, the DP items demonstrated poor discriminative ability.\n\nThese results differ from the study by,81 where all items showed a corrected item-test correlation greater than.20, as well as from the study by González-Rodríguez et al. (2022), where only item BS_04 had a value below the indicated criterion (ritc = .114), and from the research by Oh and Lee (2009), where item BS_14 was the only one that exhibited low discrimination (ritc = .030).31 The difference in results could be attributed to the sample used, as the mentioned studies worked with participants who were not healthcare professionals (e.g., university teachers). Additionally, there are also differences in the calculation of the corrected item-test correlation, as81 y31 correlated the items with the total MBI score, while in the present study, the analysis was conducted within each dimension, similar to what82 did.\n\nRegarding the validity analysis, three sources of evidence were collected: content-based evidence, internal structure evidence, and evidence of relationships with other variables. Evidence for content-based validity was gathered from the assessments made by six expert judges who evaluated the relevance, representativeness, clarity, and essentiality of the items for measuring burnout. The assessments made by the judges were positive in regard to relevance, representativeness, and clarity for all items. The Aiken's V coefficient was employed to compile their responses, resulting in values above.70 (with a range from .83 to 1.00). These findings complement the results of,81 who also assessed general aspects of the MBI based on the judgment of eight experts, with Aiken's V coefficients ranging from.88 to 1.00. On the other hand, the judges indicated that almost all items were essential, except for BS_05 and BS_22, which were considered non-essential for measuring BS, with Lawshe's validity index values of.67 and.33, respectively. Both items belong to the DP dimension.\n\nConcerning the evidence for validity based on the internal structure, four models were evaluated using confirmatory factor analysis. Both the unidimensional model and the bifactor model didn't produce satisfactory results. The unidimensional model showed insufficient goodness-of-fit indices, and the bifactor model failed to achieve computational convergence, possibly due to the complexity of the bifactor model coupled with the sample size. The last two models, the three-factor correlated model (comprising EE, DP, and PA) and the hierarchical model (which includes the three aforementioned factors and an overarching general factor - BS - underlying them), both obtained adequate and equivalent fit indices.\n\nIn the hierarchical model, despite having good fit indices (SSχ2/gl < 3, RMSEA < .80, CFI > .90, TLI > .90, SRMR < .80, and WRMR close to 1), the general factor of burnout showed low internal consistency (ω = .483), indicating low reliability of the scores. Therefore, the hierarchical model was discarded, and only the three-factor correlated model was interpreted. This model aligns with the findings of Loera et al. (2014) in a group of Italian nurses, although in that study, items BS_12 and BS_16 were excluded from the model. It also aligns with the study by28 in Finnish nurses, although items BS_6, BS_13, BS_16, and BS_22, as well as the correlation between the errors of items BS_17 and BS_18, were excluded. Additionally,83 found the same structure in Peruvian nurses, both with the full 22-item version of the MBI and with a reduced 15-item version. Similar findings were also found by83 in a sample of nursing staff from public health institutions in Peru, using the general 16-item version (MBI-GS).\n\nSeveral studies have echoed the findings of the current research, identifying the same three-factor correlated structure, although these studies have been conducted in domains beyond healthcare. For instance, a study in South Korea identified the same three dimensions within a cohort of child protection service workers, however, a condensed 15-item variant displayed superior goodness-of-fit indices during the confirmatory factor analysis.82 Nonetheless, there are also studies that present varying and contradictory structures. For example, consulted studies highlight discovered a four-factor model in a sample of Spanish social workers, where the fourth factor was designated as interpersonal psychological strain.31 This result, however, was achieved through a principal component analysis, selecting the quantity of factors according to Kaiser's rule of eigenvalues exceeding 1, and employing Varimax rotation. These practices are currently dissuaded as they may yield incorrect and biased estimations.76,84\n\nRegarding evidence of validity based on correlation with other variables, both the EE and PA displayed both convergent and discriminant validity. Conversely, the DP dimension solely exhibited evidence of discriminant validity. Convergent validity evidence was obtained via the Average Variance Extracted (AVE), which encompassed an exhaustive analysis of this indicator in conjunction with other elements such as reliability, factor loadings, and the count of items.69 The dimension of depersonalization exhibited an unacceptable level (AVE = .237) and thus did not meet this validity criterion.\n\nFurthermore, two methods were employed to assess discriminant validity: the HTMT2 ratio and the criterion by.71 The results were consistent for the dimension of EE, indicating that it possesses discriminant validity evidence. However, for the other two dimensions, while the HTMT2 ratio was adequate, the results differed according to the.71 This discrepancy arose as the square root of the AVE for both dimensions was lower than their correlations with another factor.\n\nDespite the criterion by71 not being acceptable for DP and PA, it was decided to give greater importance to the results of the HTMT2, as this criterion is better suited for discriminant validity evidence within the framework of structural equation models.70 In light of this, all three dimensions showcase discriminant evidence, signifying that EE, DP, and PA are distinct from each other in their measurement of BS. In simpler terms, they encapsulate different facets of BS in the manner this variable is quantified using the MBI.\n\nRegarding the reliability of scores in the correlated three-factor model, both EE and PA exhibited acceptable levels of internal consistency (ω and α > .80). These findings are consistent with what has been reported in other studies, where a ω value above .70 was found24,36,81,85,86 and a value of α above.7028,29,36,81,85 for these dimensions.\n\nHowever, the dimension of DP displayed low levels of internal consistency (α = .574 and ω = .492). These reliability results for this dimension have also been found in previous studies.20,29,81 Therefore, the DP scores demonstrate low reliability. This is consistent with the previous results presented for this dimension, as four items exhibited low discriminant ability, two items were considered non-essential by expert judges, one item had the lowest factor loading in the confirmatory factor analysis (less than.40), the items had lower inter-item relationships, with an average inter-item correlation of.21. Additionally, it was the only factor that did not have evidence of convergent validity.\n\nLastly, percentile norms were established for interpreting scores on the MBI among healthcare professionals in the Ancash Region. Three categories were delineated in this regard: low, moderate, and high, corresponding to the first quartile (25%), second quartile (50%), and third quartile (75%) respectively.80 However, it was suggested to apply the interpretational meaning for the dimensions of EE and PA, but not for the DP dimension, due to its observed low level of reliability and other unsatisfactory indicators discussed in this section. Additionally, the calculation of a total BS score was not feasible based on the study's findings, as the general factor observed in the hierarchical model also showed weak internal consistency. Thus, based on the aforementioned, it was inferred that an individual is likely to experience burnout problems if they present a high score in EE and a low score in PA.\n\nOne of the study's limitations was the size of the sample utilized. Initially, there were 366 participants, but after removing univariate and multivariate outliers, the final sample was reduced to 303 cases, limiting the ability to perform further statistical analyses such as factorial invariance or item differential functioning analysis. However, the sample size was still larger than the recommended minimum of 300 cases for psychometric studies when the number of items is not very large.54,76 Moreover, the study examined convergent and discriminant validity evidence based on the factors of the MBI, without incorporating any external variables beyond BS (for instance, using additional instruments). Nonetheless, the study did utilize indicators that are currently recommended for such an analysis, like AVE (Average Variance Extracted) and the HTMT2 ratio.69,70\n\nThe main contribution of this study is that it goes beyond psychometric properties by establishing percentile standards for the MBI dimensions and their respective low, medium, and high categories. This facilitates the interpretation of the test scores (these standards will enable the interpretation of results in future applications). The direct scores obtained by a participant in the test, on their own, are meaningless; to interpret them, it's essential to refer to established standards. Therefore, the instrument can be used in clinical, organizational, and research areas for the design of public policies aimed at the prevention and intervention of BS. Furthermore, Ancash is a region in Peru where healthcare professionals working in its 12 hospitals exhibit higher levels of BS compared to healthcare staff from other regions.21–23,87 As such, this at-risk group should be evaluated semi-annually or annually with an objective, valid, and reliable instrument, one that offers quick and practical scoring, like the one presented in this study.\n\nFirstly, while the sample size used exceeded the minimum recommendation of 300 cases for psychometric studies,54,56,76 it restricted our ability to conduct further statistical analyses, such as factorial invariance or differential item functioning analysis. Secondly, the study's focus on convergent and discriminant validity was solely based on MBI factors, without introducing any external variables beyond BS. For instance, no additional instruments were utilized. Nonetheless, the study employed currently recommended indicators for such analyses, like AVE (Average Variance Extracted) and the HTMT2 ratio.69,70 Lastly, while a non-probabilistic convenience sampling was theoretically justified and used, caution is advised when replicating this study in different settings or in follow-up research. Additionally, it is suggested that future studies be conducted on larger probabilistic samples and include other types of validity and reliability to enhance and standardize the instrument.\n\n\nConclusions\n\nThe MBI proves to be an effective tool for assessing burnout in healthcare professionals, particularly in terms of its dimensions of EE and PA. It demonstrates evidence of content validity, internal structure (confirming a correlated three-factor model), and relationships with other variables (both convergent and discriminant evidence). Additionally, it showcases its reliability through the internal consistency of scores. However, the use of DP scores is not recommended due to their low reliability, with item BS_15 exhibiting a low factor loading (.287). Therefore, this psychometric instrument can be utilized to measure BS in research studies where this variable is involved, whether it is to describe its prevalence in a specific group, compare scores across different groups, or understand its relationship with other variables that are part of its nomological network.",
"appendix": "Data availability\n\nZenodo: Psychometric Properties of the MBI in Healthcare Professionals, Ancash Region, Peru. https://doi.org/10.5281/zenodo.8048477. 88\n\nThis project contains the following underlying data:\n\n- Database (Statistical results after the application of the Maslach Burnout Inventory).xlsx\n\n- Final results (PDF).docx\n\nZenodo: Psychometric Properties of the MBI in Healthcare Professionals, Ancash Region, Peru. https://doi.org/10.5281/zenodo.8048477. 88\n\nThis project contains the following extended data:\n\n- Data key for the instrument.pdf\n\n- The Aiken's V.xlsx\n\n- The Lawshe's CVR.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\nArayago R, González Á, Limongi M, et al.: Burnout syndrome in residents and anesthesiologists. Salus. 2016 [cited 2023 May 10]; 20(1): 13–21. 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Publisher Full Text Reference Source\n\nYslado R, Atoche R, Quispe M, et al.: Factores sociodemograficos intra y extra organizativos relacionados con sindrome de quemarse por el trabajo en profesionales de salud de hospitales. Ancash. Peru. 2011. Rev. Investig en Psicol. 2011 Dec 30 [cited 2023 May 2]; 14(2): 55–69. Publisher Full Text Reference Source\n\nYslado R, Atoche R, Cermeño B, et al.: Síndrome de Burnout y factores sociodemográficos-organizativos en profesionales de salud. Hospitales del callejón de Conchucos, Ancash, Perú - 2012. Rev Investig en Psicol. 2013 Jul 15 [cited 2023 May 2]; 16(1): 191–209. Publisher Full Text Reference Source\n\nPoghosyan L, Aiken LH, Sloane DM: Factor structure of the Maslach burnout inventory: An analysis of data from large scale cross-sectional surveys of nurses from eight countries. Int. J. Nurs. Stud. 2009 Jul 1; 46(7): 894–902. PubMed Abstract | Publisher Full Text\n\nChao SF, Mccallion P, Nickle T: Factorial validity and consistency of the Maslach Burnout Inventory among staff working with persons with intellectual disability and dementia. J. Intellect. Disabil. Res. 2011 May 1 [cited 2023 May 2]; 55(5): 529–536. PubMed Abstract | Publisher Full Text\n\nKalliath TJ, O’Driscoll MP, Gillespie DF, et al.: A test of the Maslach Burnout Inventory in three samples of healthcare professionals. Work Stress. 2010 [cited 2023 May 2]; 14(1): 35–50. Publisher Full Text\n\nGómez R, Alonso M, Llamazares M: Factorial Validity of the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) in a Sample of Spanish Social Workers. J. Soc. Serv. Res. 2018 Mar 15 [cited 2023 May 2]; 45(2): 207–219. Publisher Full Text\n\nKanste O, Miettunen J, Kyngäs H: Factor structure of the Maslach Burnout Inventory among Finnish nursing staff. Nurs. Health Sci. 2006 Dec 1 [cited 2023 May 2]; 8(4): 201–207. PubMed Abstract | Publisher Full Text\n\nOh SH, Lee M: Examining the psychometric properties of the Maslach Burnout Inventory with a sample of child protective service workers in Korea. Child Youth Serv. Rev. 2009 Feb 1 [cited 2023 May 2]; 31(2): 206–210. Publisher Full Text\n\nDensten IL: Re-thinking burnout. J. Organ. Behav. 2001 Dec 1 [cited 2023 May 2]; 22(8): 833–847. Publisher Full Text\n\nGonzález-Rodríguez R, Domínguez J, Verde-Diego C, et al.: Psychometric properties of the Maslach Burnout Inventory - Human Services in Social Work professionals in Spain. Health Soc. Care Community. 2022 May 1 [cited 2023 May 2]; 30(3): 949–956. Publisher Full Text\n\nLin CY, Alimoradi Z, Griffiths MD, et al.: Psychometric properties of the Maslach Burnout Inventory for Medical Personnel (MBI-HSS-MP). Heliyon. 2022 Feb 1 [cited 2023 May 2]; 8(2): e08868. Publisher Full Text Reference Source\n\nPereira S d S, Fornés-Vives J, Unda-Rojas SG, et al.: Confirmatory factorial analysis of the Maslach Burnout Inventory – Human Services Survey in health professionals in emergency services. Rev. Lat. Am. Enfermagem. 2021 Jan 8 [cited 2023 Feb 6]; 29: e3386. Reference Source\n\nMukherjee S, Tennant A, Beresford B: Measuring Burnout in Pediatric Oncology Staff: Should We Be Using the Maslach Burnout Inventory? J. Pediatr. Oncol. Nurs. 2020 Jan 1 [cited 2023 May 2]; 37(1): 55–64. PubMed Abstract | Publisher Full Text\n\nSlabšinskienė E, Gorelik A, Vasiliauskienė I, et al.: Factorial Validity and Variance of the Maslach Burnout Inventory between Demographic and Workload Groups among Dentists of Lithuania. Int. J. Environ. Res. Public Health. 2020 Dec 8 [cited 2023 May 2]; 17(24): 9154. Reference Source\n\nCalderón-De la Cruz GA, Merino-Soto C, Juárez-García A, et al.: Is the factorial structure of the Maslach Burnout Inventory Human Service Survey (MBI-HSS) replicable in the nursing profession in Peru? A national study. Enfermería Clínica (English Ed.). 2020 Sep 1 [cited 2023 May 2]; 30(5): 340–348. Publisher Full Text\n\nVizheh M, Qorbani M, Arzaghi SM, et al.: The mental health of healthcare workers in the COVID-19 pandemic: A systematic review. J. Diabetes Metab. Disord. 2020 Dec 1 [cited 2023 May 8]; 19(2): 1967–1978. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMuller AE, Hafstad EV, Himmels JPW, et al.: The mental health impact of the covid-19 pandemic on healthcare workers, and interventions to help them: A rapid systematic review. Psychiatry Res. 2020 Nov 1 [cited 2023 May 8]; 293: 113441. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWoo T, Ho R, Tang A, et al.: Global prevalence of burnout symptoms among nurses: A systematic review and meta-analysis. J. Psychiatr. Res. 2020 Apr 1 [cited 2023 May 8]; 123: 9–20. PubMed Abstract | Publisher Full Text\n\nVera San Juan N, Aceituno D, Djellouli N, et al.: Mental health and well-being of healthcare workers during the COVID-19 pandemic in the UK: contrasting guidelines with experiences in practice. BJPsych open. 2020 Jan [cited 2023 May 8]; 7(1). Publisher Full Text Reference Source\n\nLai J, Ma S, Wang Y, et al.: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019. JAMA Netw. Open. 2020 Mar 2 [cited 2023 May 8]; 3(3): e203976–e203976. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nRotenstein LS, Torre M, Ramos MA, et al.: Prevalence of Burnout Among Physicians: A Systematic Review. JAMA. 2018 Sep 18 [cited 2023 May 8]; 320(11): 1131–1150. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nMuñoz-del-Carpio A, Arias WL, Caycho-Rodríguez T: Burnout syndrome in medicine men from Arequipa city (Peru). Rev. Chil. Neuropsiquiatr. 2019 [cited 2023 May 8]; 57(2): 139–148. Publisher Full Text Reference Source\n\nCecilia K, Linares C, Felipe L, et al.: Persistencia del síndrome burnout en internos de medicina en hospitales de Lima, Perú (año 2018). Investig en Educ médica. 2019 Oct 17 [cited 2023 Feb 6]; 8(32): 9–15. Publisher Full Text Reference Source\n\nMacía-Rodríguez C, Martín Iglesias D, Moreno Diaz J, et al.: Síndrome de burnout en especialistas de medicina interna y factores asociados a su desarrollo. Rev Clínica Española. 2020 Aug 1 [cited 2021 Dec 26]; 220(6): 331–338. PubMed Abstract | Publisher Full Text Reference Source\n\nBradley HB: Community-based Treatment for Young Adult Offenders.1969 Jul 1 [cited 2023 May 8]; 15(3): 359–370.\n\nDoherty AS, Mallett J, Leiter MP, et al.: Measuring Burnout in Social Work.2020 Mar 13 [cited 2023 May 8]; 37(1): 6–14. Publisher Full Text\n\nSchaufeli W, Maslach C, Marek T: Professional burnout: recent developments in theory and research. Routledge; 2018 [cited 2023 May 8]; 299. Reference Source\n\nSireci S, Padilla J-L: Validating assessments: introduction to the special section. Psicothema. 2014 [cited 2023 May 8]; 26(1): 97–99. PubMed Abstract | Publisher Full Text Reference Source\n\nAmerican Educational Research Association: American Psychological Association, Education.NC on M, editor. The Standards for Educational and Psychological Testing. AERA Publications Sales; 2014 [cited 2023 May 2]. Reference Source\n\nHughes DJ: Psychometric Validity. Wiley Handb Psychom Test A Multidiscip Ref Surv Scale Test Dev. 2017 Jun 21 [cited 2023 May 8]; 2–2: 751–779. Publisher Full Text\n\nSireci S: On the validity of useless tests.2015 Apr 2 [cited 2023 May 8]; 23(2): 226–235. Publisher Full Text\n\nPeeters MJ, Harpe SE: Updating conceptions of validity and reliability. Res. Soc. Adm. Pharm. 2020 Aug 1 [cited 2023 May 8]; 16(8): 1127–1130. PubMed Abstract | Publisher Full Text\n\nCook DA, Beckman TJ: Current concepts in validity and reliability for psychometric instruments: Theory and application. Am. J. Med. 2006 Feb 1 [cited 2023 May 8]; 119(2): 166.e7–166.e16. Publisher Full Text Reference Source\n\nHernández-Sampieri R, Mendoza CP: Metodología de la investigación: las rutas cuantitativa, cualitativa y mixta. Ciudad de México: McGraw-Hill; 2018 [cited 2023 Sep 10]. Reference Source\n\nAto M, López JJ, Benavente A: Un sistema de clasificación de los diseños de investigación en psicología. An Psicol/Ann Psychol. 2013 Sep 20 [cited 2023 May 8]; 29(3): 1038–1059. Publisher Full Text Reference Source\n\nDirección Regional de Salud Ancash: Dirección Regional de Salud Ancash.2022 [cited 2023 Jun 10]. Reference Source\n\nLeys C, Klein O, Dominicy Y, et al.: Detecting multivariate outliers: Use a robust variant of the Mahalanobis distance. J. Exp. Soc. Psychol. 2018 Jan 1; 74: 150–156. Publisher Full Text\n\nComrey AL, Lee HB: A First Course in Factor Analysis. New York: Psychology Press; 2nd ed2013 [cited 2023 Jun 10]; 1–442. Publisher Full Text\n\nAkl A, Mohiyaldeen I, Alshatti R, et al.: The Prevalence of Burnout and Its Associated Factors Among Surgical Specialists in Kuwait Ministry of Health Hospitals. Front. Public Health. 2022 Jan 31 [cited 2023 Jun 10]; 10: 679834. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmerican Psychiatric Association: Guía de consulta de los criterios diagnósticos del DSM-5. Cuad Med Forense. 2015 [cited 2023 May 10]; 21(3–4): 198–199. Reference Source\n\nBartone PT, McDonald K, Hansma BJ: Hardiness and Burnout in Adult U.S. Workers. J. Occup. Environ. Med. 2022 May 1 [cited 2023 May 10]; 64(5): 397–402. Publisher Full Text\n\nTabachnick BG, Fidell LS: Using Multivariate Statistics. 7th ed.Pearson; 2019.\n\nMcHorney CA, Tarlov AR: Individual-patient monitoring in clinical practice: are available health status surveys adequate? Qual. Life Res. 1995 Aug [cited 2023 May 8]; 4(4): 293–307. Publisher Full Text\n\nKerlinger FN, Lee HB: Foundations of Behavioral Research. 4th ed.College Publishers; 2000.\n\nKeith TZ: Multiple Regression and Beyond: An Introduction to Multiple Regression and Structural Equation Modeling. 3rd ed. Routledge; 2019.\n\nPerry JL, Nicholls AR, Clough PJ, et al.: Assessing Model Fit: Caveats and Recommendations for Confirmatory Factor Analysis and Exploratory Structural Equation Modeling.2015 Jan 2 [cited 2023 Feb 6]; 19(1): 12–21. Publisher Full Text\n\nHu LT, Bentler PM: Cutoff criteria for fit indexes in covariance structure analysis: Conventional criteria versus new alternatives.2009 [cited 2023 Feb 6]; 6(1): 1–55. Publisher Full Text\n\nMoral de la Rubia J: Revisión de los criterios para validez convergente estimada a través de la Varianza Media Extraída. Psychol Av la Discip. 2019 Nov 20 [cited 2023 May 2]; 13(2): 25–41. Publisher Full Text Reference Source\n\nHenseler J, Ringle CM, Sarstedt M: A new criterion for assessing discriminant validity in variance-based structural equation modeling. J. Acad. Mark. Sci. 2015 Jan 1 [cited 2023 Feb 6]; 43(1): 115–135. Publisher Full Text\n\nFornell C, Larcker DF: Evaluating Structural Equation Models with Unobservable Variables and Measurement Error. J. Mark. Res. 1981 Feb; 18(1): 39–50. Publisher Full Text\n\nCronbach LJ: Coefficient alpha and the internal structure of tests. Psychometrika. 1951 Sep [cited 2023 May 8]; 16(3): 297–334. Publisher Full Text\n\nTaber KS: The Use of Cronbach’s Alpha When Developing and Reporting Research Instruments in Science Education. Res. Sci. Educ. 2018 Dec 1 [cited 2023 May 8]; 48(6): 1273–1296. Publisher Full Text\n\nTeam TRDC: R: A Language and Environment for Statistical Computing. The R Development Core Team; 2022 [cited 2023 Feb 6]; 1–2673. 1st ed.Reference Source\n\nLey N.° 26842. Ley N° 26842. Ley General de Salud.1997. Reference Source\n\nLloret-Segura S, Ferreres-Traver A, Hernández-Baeza A, et al.: El análisis factorial exploratorio de los ítems: una guía práctica, revisada y actualizada. An Psicol/Ann Psychol. 2014 Aug 12 [cited 2023 May 10]; 30(3): 1151–1169. Publisher Full Text Reference Source\n\nVentura-León J, Caycho-Rodríguez T, Sánchez-Villena AR, et al.: Academic Inspiration: Development and validation of an instrument in higher education. Electron. J. Res. Educ. Psychol. 2022 Dec 1 [cited 2023 May 10]; 20(58): 635–660. Publisher Full Text Reference Source\n\nLawshe CH: A quantitative approach to content validity. Pers. Psychol. 1975 [cited 2023 May 10]; 28(4): 563–575. Publisher Full Text\n\nAyre C, Scally AJ: Critical Values for Lawshe’s Content Validity Ratio: Revisiting the Original Methods of Calculation. Assoc Assess Res Couns. 2013 Dec 13 [cited 2023 May 10]; 47(1): 79–86. Publisher Full Text\n\nAbad FJ, Olea J, Ponsoda V, et al.: Medición en ciencias sociales y de la salud. Madrid: Síntesis; 2011 [cited 2023 May 10]. Reference Source\n\nYslado R, Ramirez EH, García-Figueroa ME, et al.: Clima laboral y burnout en profesores universitarios. Rev Electrónica Interuniv Form del Profr. 2021 Aug 20 [cited 2023 May 10]; 24(3). Publisher Full Text Reference Source\n\nOh SH, Lee M: Examining the psychometric properties of the Maslach Burnout Inventory with a sample of child protective service workers in Korea. Child Youth Serv. Rev. 2009 Feb 1; 31(2): 206–210. Publisher Full Text\n\nCalderón-de la Cruz GA, Merino-Soto C, Juárez-García A, et al.: Is the factorial structure of the Maslach Burnout Inventory Human Service Survey (MBI-HSS) replicable in the nursing profession in Peru? A national study. Enfermería Clínica (English Ed.). 2020 Sep 1; 30(5): 340–348. Publisher Full Text\n\nFerrando PJ, Lorenzo-Seva U, Hernández-Dorado A, et al.: Decalogue for the Factor Analysis of Test Items. Psicothema. 2022 Feb 1 [cited 2023 May 12]; 34(1): 7–17. PubMed Abstract | Publisher Full Text\n\nOrnelas JRB, Contreras MO, García PJJ, et al.: Composición factorial del Inventario de Burnout de Maslach para Estudiantes en universitarios mexicanos. Acta Univ. 2020 Sep 16 [cited 2023 May 10]; 30: 1–13. Publisher Full Text Reference Source\n\nCastillo R, Paredes M: Estructura factorial del Inventario de Burnout de Maslach (MBI-GS) en personal de enfermería de instituciones públicas de salud peruanas. Interacciones. 2020 Mar 15 [cited 2023 May 9]; 6(1): e220–e220. Publisher Full Text Reference Source\n\nYslado RM, Norabuena RP, Sánchez JD, et al.: Programa de intervención breve para reducir el burnout de profesionales de la salud, Perú. Rev Univ y Soc. 2020 [cited 2022 Jul 27]; 12(5): 289–289. Reference Source\n\nYslado RM, Sánchez-Broncano J, De la Cruz-Valdiviano C, et al.: Psychometric Properties of the Maslach Burnout Inventory in Healthcare Professionals, Ancash Region, Peru. Zenodo. 2023 Jun 16 [cited 2023 Jun 16]. Reference Source"
}
|
[
{
"id": "221619",
"date": "08 Dec 2023",
"name": "Arnold Alejandro Tafur Mendoza",
"expertise": [
"Reviewer Expertise psychometrics",
"measurement",
"assessment",
"quantitative methodology",
"factor analysis."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article presents the evaluation of the psychometric properties of one of the most widely used scales for the measurement of burnout syndrome, the Maslach Burnout Inventory (MBI), in a relevant sample such as health professionals who, according to the existing literature, is the main group that suffers the negative consequences of burnout (stress, anxiety, etc.). The article is well structured and reports the results of analyses relevant to the functioning of the MBI, exploring various sources of validity evidence (based on content, internal structure and relationship with other variables), as well as the consideration of the omega coefficient for the analysis of the reliability of the scores. Furthermore, the results obtained are adequately discussed in contrast with the relevant and updated literature, pointing out the limitations and contribution of the research.\nIn order to improve the reporting of the research conducted, I would recommend the following minor corrections to clarify some of the terms used in the article.\nRemove Table 5 or Figure 1 from the text, as both elements contain the same information and are therefore redundant. In particular, I would remove Table 5, as the visualisation of the results of the confirmatory factor analysis (the correlation between the factors, the factor loadings and the error variances) could be clearer for the reader.\n\nIn Table 2, replace DE, As and Cu by SD, Sk and Ku, as the former are used because they are in Spanish and the latter correspond to their English version. The article is in English. The same happens in Table 7, where \"Asymmetry\" should be replaced by \"Skewness\", which is the correct statistical term in English. In Table 3, instead of \"Average\" there should be \"Mean\". In Table 4, instead of \"IC\" there should be \"CI\", which corresponds to the confidence interval. Finally, in Table 6 there are again problems with some of the statistics mentioned above. It would be important to review the entire article again to verify that there is no other error with the English language.\n\nOn page 3, in the study by González-Rodríguez et al. (2022), it is necessary to indicate how they evaluated the evidence of convergent validity and what results they obtained. Also, indicate which structure they evaluated, since they indicate that it was the original model (I understand the three-factor model), but then they indicate that they found four factors. Clarify the reporting of these results.\n\nOn page 6, clarify the wording of the objectives. In objective 1, it is incorrect to say that validity is established, what is done is to provide evidence of validity, where appropriate, based on the content of the test through the criteria of expert judges and based on the internal structure through confirmatory factor analysis. In objective 2, a more appropriate term is \"Estimate reliability\" and if appropriate also add that they used the omega coefficient. In objective 3, it is better to indicate that they sought to provide evidence of validity based on the relationship with other variables and to indicate the methods they used for convergent (AVE) and discriminant (HTMT2 ratio and Fornell and Larcker) evidence, as stated on page 7. In objective 4 (and on page 7), there is an error, as they did not use ROC curves for interpretive norms, but percentile scores. Remove objective 5, as it looks more like a hypothesis and is not relevant for this type of psychometric study.\n\nOn page 7, it should be added that the omega coefficient was also estimated for the assessment of internal consistency reliability.\n\nDelete the last paragraph on page 7, as it is redundant with what is already mentioned at the top of the page. End this section only by pointing out everything related to the software used.\nWith these minor corrections, the article would be clearer for the interested reader. Success in the process of reviewing the comments.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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": "11113",
"date": "13 Apr 2024",
"name": "Enaidy Reynosa Navarro",
"role": "Author Response",
"response": "Observation 1: The suggestion was added, and Table 5 was deleted. Observation 2: The indicated corrections were made and the full text was checked for any other English language errors. The indicated corrections were made and the full text was checked for any other English language errors. Observation 3: The suggestion was added: “Results indicated an acceptable fit for the four-factor correlated model (Emotional Exhaustion, Depersonalization, Personal Realization, and Interpersonal Psychological Stress). Cronbach's alpha coefficients indicated acceptable reliability for all four factors, with values between .718 and .911 (31).” Observation 4: The objectives were modified as suggested: 1. Provide valid evidence of the MBI in healthcare professionals from the Ancash region, Peru, based on the content of the test through the criteria of expert judges and based on the internal structure through confirmatory factor analysis (CFA). 2. Estimate the reliability of the MBI in healthcare professionals from the Ancash region, Peru, using Cronbach's alpha and omega coefficient. 3. Provide evidence of validity based on the relationship with other variables through convergent (average variance extracted, AVE) and discriminant evidence (HTMT2 ratio and the Fornell and Larcker criterion). 4. To compute MBI scores to obtain interpretative norms (reference values) for the instrument in healthcare professionals from the Ancash region, Peru, using percentile scores. Observation 5: The suggestion was added to the manuscript: “…and omega coefficient. These coefficients range from 0 to 1…” Observation 6: The paragraph was deleted: “In the current study, meticulous steps were undertaken to counteract and mitigate possible biases. Before the survey's distribution, approval was secured from the leadership of the involved hospitals. Participation was restricted to those healthcare professionals who provided their informed consent. To ensure a neutral selection process, invitations were disseminated to potential participants via WhatsApp and email. Furthermore, any incomplete responses were eliminated during the data refinement phase, safeguarding the integrity and accuracy of the concluding data.”"
}
]
},
{
"id": "211342",
"date": "30 Jan 2024",
"name": "Brian Norman Peña Calero",
"expertise": [
"Reviewer Expertise Specialist in data and psychometric analysis",
"research development and research and analysis consultancy."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 the psychometric results of the instrument are good, it would be convenient to add the revision of an additional model without item 15 and any other item that impairs the estimation of its reliability. Additionally, if a second-order model is suspected, it would be convenient to include the assessment of a bifactor model. The article appropriately evaluates the psychometric behavior of the Maslach Burnout Inventory (MBI), highlighting the participant selection and the psychometric analysis plan to achieve research objectives. To improve the communication of the results, the following suggestions are made:\nIn Table 5, where a low factorial load for item 15 is indicated, it could be added that this item also had inadequate performance in the descriptive analysis (Table 2). In the discussion section, it is recommended to detail more about the poor performance of item 15, its content, and possible reasons for its inadequacy in the model. If deciding to keep item 15 in the model, despite its significant difference in factorial loads, explaining the reason would be advisable. Otherwise, evaluating the depersonalization factor without this item could be considered. Regarding the bifactor model, it would be useful to mention if its convergence was evaluated with subsequent modifications, such as the removal of items.\nWith these minor modifications, the article will be able to provide significant insight into the psychometric behavior of the instrument of interest.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "11114",
"date": "13 Apr 2024",
"name": "Enaidy Reynosa Navarro",
"role": "Author Response",
"response": "Observation 1: The suggestion was added to the manuscript: “This same item also performed poorly at the descriptive level with the lowest discrimination (ritc = .052) and the highest floor effect (68.65%) compared to the other items.” Observation 2: The suggestion was added to the manuscript: “Within the CFA, as well as in the descriptive analyses, item BS_15 was the most problematic item with the lowest factor loading (λ = .287). The content of the item \"I don't care about what happens to some of my patients\" refers to the lack of concern on the part of healthcare staff about the health of their patients. In the pandemic context where the study was conducted, COVID-19 was a collective problem, so, naturally, there is a direct or indirect concern for patients. This could be one of the reasons why the item did not work well in the model and why it did in pre-pandemic studies. One reason from a methodological point of view is that it is the only item in the whole PD dimension, and the whole test, that contains an explicit negation (not), which may have given problems in the comprehension of the item when it was answered.” Observation 3: The suggestion was added to the manuscript: “Despite the above, it was decided to keep the item, as its content is not interchangeable with any other item in the PD dimension, and removing it would imply an under-representation of content in the dimension. Moreover, it would limit the possibility of directly comparing the results obtained here with previous studies.” Observation 4: The suggestion was added to the manuscript: “In the bifactor model, convergence with subsequent modifications (e.g. deletion of items) was not assessed to avoid capitalization of chance and possible under-representation of dimension content.”"
}
]
}
] | 1
|
https://f1000research.com/articles/12-1253
|
https://f1000research.com/articles/12-1309/v1
|
11 Oct 23
|
{
"type": "Opinion Article",
"title": "Corneal blindness in the developing world: The role of prevention strategies",
"authors": [
"Anahita Kate",
"Sayan Basu",
"Anahita Kate"
],
"abstract": "Corneal blindness is an important contributor to the burden of global blindness and has a greater prevalence in low-income countries of the developing world where resources and infrastructure are limited. The causes of corneal blindness too are different from high-income countries and include infectious keratitis, ocular trauma, and xerophthalmia. Persons with these indications tend to have unfavourable outcomes after corneal transplantation, limiting their chances of benefitting from this sight-saving procedure. However, most causes of corneal blindness in the developing world are preventable. This highlights the importance of understanding the unique challenges in these regions and the need for targeted interventions. This article discusses various prevention strategies, including primordial, primary, and secondary prevention, aimed at reducing the burden of corneal blindness in low-income countries. These include capacity building, training, and awareness campaigns to reduce the risk factors of ocular trauma, infectious keratitis, and improve access to first aid. It is also important to promote safe eye practices and tackle nutritional deficiencies through public health interventions and policy changes. Providing the required training to general ophthalmologists in the management of basic corneal surgeries and diseases and enhancing the accessibility of eye care services in rural areas will ensure early treatment and prevent sequelae. Current treatment modalities belong to the tertiary level of prevention and are largely limited to corneal transplantation. In developing nations, there is a scarcity of donor corneal tissue necessitating an urgent expansion of eye banking services. Alternative approaches to corneal transplantation such as 3D printed corneas, cultured stem cells, and biomaterials should also be explored to meet this demand. Thus, there is a need for collaborative efforts between healthcare professionals, policymakers, and communities to implement effective prevention strategies and reduce the prevalence of corneal blindness in the developing world.",
"keywords": [
"corneal blindness",
"corneal transplantation",
"keratoplasty",
"eye banking",
"prevention of blindness"
],
"content": "Introduction\n\nThe faculty of sight is one of our most essential senses and is necessary for basic survival. This is reflected not only in the abundance of published literature on vision compared to other senses but also in the perception of sight as the most valued sense by the general public.1,2 The plethora of policies and programmes targeted at reducing the burden of blindness and its associated morbidity also stem from this idea. The causes of blindness targeted within these schemes are identified through various epidemiological studies or population based surveys and include etiologies such as cataract, uncorrected refractive error, glaucoma and age related macular degeneration.3,4 Interventions such as dispensing glasses, improving access to cataract surgeries and glaucoma/retina screening camps go a long way in decreasing the disease burden. Although this approach is practical on a global scale, it may inadvertently overlook certain diseases which are important causes of visual impairment in certain populations.\n\nBlindness secondary to corneal pathologies is one such category that affects nearly 5.5 million individuals bilaterally and another 6 million people unilaterally.5(p198) A variety of causes including poor nutrition at birth, infected ocular abrasions from agricultural work, or workplace injuries due to lack of protective glasses lead to corneal blindness. The majority of these cases are concentrated in developing countries where limited resources and inadequate infrastructure pose significant obstacles to addressing this problem effectively. Corneal blindness presents unique challenges as its treatment modalities are not as straightforward or universally effective as cataract surgery. This article will discuss the unique nature of the causes of corneal blindness in developing countries and explore various strategies that can be implemented to reduce the burden and impact of this condition.\n\n\nBlindness and the relative contribution of corneal blindness\n\nThe global crude prevalence of vision loss is 14% of which moderate-severe vision impairment has a prevalence of 3.7%, while blindness is 0.5%.6 There is a disparity within the distribution of these cases which is highlighted by the Global Vision Database (GVD) and its regional classification system that classifies regions based on geographic and epidemiological similarity. The age-adjusted prevalence of vision loss is 4.6% in the “high-income region” which increases to 18.2% in “Sub-Saharan Africa” and is the highest in “South Asia” (22.2%).6 A similar trend is seen in the age-adjusted prevalence of blindness with values of 0.2%, 1% and 0.9% in the high-income region, Sub-Saharan Africa, and South Asia respectively.6 This difference is present not only in the magnitude of visual morbidity but also the causative pathologies. The major diseases responsible for blindness as per the Global Burden of Disease Study in the “high income region” are glaucoma (28.2%) and age-related macular degeneration (ARMD) (21.6%).3,6 However, these diseases contribute lesser to the overall cases of blindness in “South Asia” with 6.4% and 3% of blindness being secondary to glaucoma and ARMD respectively.4 Cataract is the most common cause of blindness in this region (63.1%). Interestingly, the second highest pathology in South Asia (16.8%) is a broad category of “residual causes”, and this is where corneal blindness resides. Individual studies from countries in this region will help understand the proportion of blindness due to corneal pathologies and together, these cases account for a majority of the global burden of corneal blindness.7–11 This difference pertains not only to the absolute numbers of individuals affected by corneal blindness, but also extends to the age distribution of the affected population.5 The incidence of childhood corneal vision loss in developing countries is nearly 20 times greater than that of developed ones.12 The associated effect on the quality of life will be greater in this subset of the population and will directly impact their socio-economic productivity. The causes of corneal blindness (see below) and its etiology may vary between low- and high-income settings. Therefore, national programmes in developing countries that focus on cataract or refractive errors may be inadequate to tackle other conditions that cause visual morbidity. A full-fledged programme will need focused, population-based studies to identify the full range of conditions contributing to severe vision loss and blindness. The availability of robust data around corneal blindness in particular, will enable the development of comprehensive programs designed to address its challenges at both regional and nationwide scales.\n\n\nCauses of corneal blindness\n\nEstablishing the true incidence and prevalence of corneal blindness is a challenge because most of the existing literature reports hospital-based rates or uses surrogate measures such as indications for transplantation. The latter may not be representative as there are several eyes with corneal blindness which may not be amenable to corneal transplantation. Furthermore, lack of access to transplantation in developing countries may result in underestimation of the prevalence of the indications in these areas. Within the developed countries, keratoplasties are most commonly carried out for keratoconus, pseudophakic or aphakic bullous keratopathy and re-grafts.7,13–15 This is in contrast to developing countries where corneal scars, ocular trauma, and infectious keratitis are the most common indications for a corneal graft.7,13,16,17\n\nThe importance of this difference in indications is reflected in the stark difference in the survival rates of grafts with the latter group having a poorer prognosis.13,18–20 This occurs because of factors such as host bed vascularization, prior perforation, peripheral anterior synechiae and other chamber abnormalities that ensues during the course of the contributory disease. Another important difference in the pattern of indications is that a large proportion of the diseases in the developing countries are preventable. More than 80% of this visual morbidity is avoidable and this has to be considered in the context of the fact that these cases account for that of more than half of the world’s corneal blindness cases.9,16 A similar pattern is observed in pediatric corneal blindness, where vitamin A deficiency, a preventable condition, emerges as the leading cause.21,22 Furthermore, greater than 45% of the affected children reside in South Asian countries which highlights the need to reduce this prevalence and address the issue effectively.21,23,24\n\n\nMeasures to decrease the burden of corneal blindness\n\nCorneal blindness has an adverse impact on daily functioning, social well-being and the overall quality of life. Thus, it is imperative to reduce its prevalence. Classifying these measures based on the level of prevention achieved will help understand where the lacunae lie, which can then be addressed. Briefly, these levels include primordial, primary, secondary, and tertiary prevention (Figure 1).25,26 Primordial prevention aims at preventing the emergence of risk factors in the general population for the disease being targeted.26,27 Decreasing the incidence of a disease in a cohort with risk factors for the same is known as primary prevention, while screening and early detection of the established disease is secondary prevention.25–27 Tertiary prevention is carried out to reduce the sequelae and to treat the complications that ensue from a given disease.25–27\n\nThe lower two levels are broad indicating the widely available care provided, ensuring accessibility across different areas. The upper two levels are taller emphasizing the comprehensive nature and extensive range of services provided at those levels.\n\nCorneal transplantation, which is the mainstay of treatment of corneal blindness, falls under tertiary prevention of corneal blindness. While eye banking and corneal transplantation are indispensable tools for any corneal surgeon, relying solely on these interventions are insufficient to eradicate the problem of corneal blindness in the developing countries. This is because the indications differ significantly in these regions, resulting in grafts in developing countries having an unfavourable prognosis. Moreover, the majority of the corneal blindness in these regions arise from preventable causes. This is an important distinction to acknowledge because currently there is a dearth of eye banking services and infrastructure, and several agencies and policies are aimed at eliminating this deficiency. While ramping up this sector is crucial, an equal effort needs to be directed at the other end of the spectrum to reduce the incidence of corneal blindness itself by preventing the emergence of these diseases. Additionally, it will also reduce the socioeconomic burden on both the patients and healthcare systems. The subsequent section will discuss the various strategies at different levels of prevention in the context of some of the diseases that are commonly implicated in corneal blindness in developing countries. This includes infectious keratitis, ocular trauma including chemical injuries, pseudophakic bullous keratopathy, dystrophies, and vitamin A deficiency.28,29 Examples of what different levels of prevention would look like in two case examples of ocular burns and corneal scar due to ocular trauma have been presented in Figures 2 and 3.\n\nEnhancing ocular protection and hygiene:\n\nPromoting eye safety practices such as wearing protective eyewear when engaging in activities that pose a risk of eye injury, such as sports and construction work, can prevent corneal injuries that may lead to blindness. Encouraging good hygiene practices such as regular handwashing, avoiding touching the eyes with dirty hands, and ensuring safe contact lens hygiene can help reduce the incidence of corneal infections. Social media platforms can effectively disseminate the message and reach a wide audience, amplifying the awareness and impact of these initiatives.\n\nDietary and nutritional aid:\n\nEnsuring a well-balanced diet rich in essential nutrients, particularly vitamin A, can reduce the burden of vitamin A deficiency related corneal pathologies in children and young adults. This can be tackled by increasing awareness amongst healthcare workers who are in direct contact with preschool children and young women. These individuals can sensitize caregivers regarding the importance of a nutritious diet in preventing xerophthalmia. Additionally the use of fortified food can add to the daily intake of vitamin A.30\n\nGenetic screening:\n\nGenetic screening for hereditary corneal dystrophies can identify individuals carrying recessive genes and help in premarital counselling. This will not only facilitate reducing the incidence of corneal blindness but also help identifying “at risk” groups who will benefit from screening of these diseases.\n\nEpidemiological research:\n\nEpidemiological research is one of the most significant gaps that requires immediate attention since this data will help improve our understanding of the risk factors, at-risk groups, and potential strategies to prevent corneal blindness. This is especially true with respect to establishing the true incidence and prevalence of corneal blindness which is currently calculated using surrogate measures such as indications of keratoplasty and hospital-based registries which are prone to their inherent biases. Identifying the most important factors responsible for these preventable causes of corneal blindness will allow concentrating efforts and resources on mitigating the same.\n\nPolicies and legislations:\n\nWith the data from large population-based studies, ophthalmic societies can propose and advocate legislations that promote eye safety and health. Examples include better packaging of edible lime which is an important cause of severe ocular burns in South Asia and ensuring standardised, appropriate protective eyewear for workers in factories and agrarian settings.31 Implementing these policies and regulations at the national or community level can have a significant impact on primordial prevention.\n\nImproving health education and public awareness:\n\nPromoting programs that educate people on lifestyle modifications and health practices can decrease the risk of corneal diseases. This starts with increasing awareness of diseases such as infectious keratitis, vitamin A deficiency and ocular burns in the context of their consequences and measures of prevention. This can also involve engaging communities such as school employees and factory workers in these promotion activities and creating opportunities for active participation which can foster a sense of ownership and responsibility for eye health. Improving health care seeking practice in the event of any ocular trauma or suspicion of infection should be advocated. Additionally, procuring over the counter medications and usage of traditional remedies should be discouraged.\n\nPromoting eye safety practices:\n\nPromoting eye safety practices include wearing protective eyewear by workers in industries with a high-risk for ocular trauma, burns, and infections. Training should be provided to the workers to administer basic first aid at the work site. While there is some understanding of these predisposing factors and the individuals at risk, extensive research is required to comprehensively identify the exact risk factors associated with each condition and determine the populations most susceptible to it. This will also help advocate the necessary policy changes.\n\nCurriculum based residency programs:\n\nThe implementation of well-defined guidelines for surgical training of residents and trainees will facilitate the evaluation of their performance and provide support whenever necessary. Adequate supervision and assistance based on each phase of the learning curve will help improve the outcomes of cataract surgery and decrease the prevalence of pseudophakic/aphakic bullous keratopathy.\n\nNutritional support and vaccinations:\n\nNutritional support and vaccinations that specifically target young children and pregnant women can help reduce the incidence of xerophthalmia related blindness which is an important and preventable cause of corneal blindness in low income countries. Current guidelines dictate that vitamin A prophylaxis is to be administered only to at-risk individuals. These doses are administered as per recommended protocols to pregnant women and children less than six years of age residing in areas which are endemic to vitamin A deficiency.22 Similarly ensuring children are appropriately vaccinated against measles can help reduce the incidence of xerophthalmia.32\n\nHealth education:\n\nSince the secondary prevention level is targeted at screening and early detection of the disease with prompt institution of treatment, specific measures will be unique to each disease. Furthermore, all measures will necessitate the presence of both trained personnel and ease of access to the same. The outcomes of ocular trauma, whether it be penetrating injuries or ocular burns, are significantly influenced by the promptness and effectiveness of the initial first aid/surgical interventions provided. Increased public awareness of these interventions will improve care seeking practice and permit setting up of first aid centres that can be manned by non-ophthalmic individuals.\n\nScreening and early detection:\n\nScreening programmes that target high-risk populations such as schools for vitamin A deficiency and predisposed groups for genetic corneal pathologies will help early detection of these diseases and enable timely interventions. Similarly setting up smaller units in villages with trained ophthalmic personnel can help screen and treat corneal epithelial defects and abrasions before they fulminate into infectious keratitis.33,34\n\nMedical and surgical therapy:\n\nEnsuring the availability of medications targeting the microorganisms commonly involved in infectious keratitis in specific geographic regions is essential. Similarly setting up reliable and efficient labs that can detect these pathogens are also paramount to ensure an accurate microbiological diagnosis is being made.35 Use of innovative techniques such as trypan blue for fungal filaments, that provide simple, rapid and reliable methods of examination will also enable early diagnosis of infectious keratitis.36 Educating general ophthalmologists in triaging severity of infections and ocular trauma will enable appropriate and timely referrals to higher centres for the necessary care. Providing surgical training for fundamental procedures like corneal tear repairs, corneal foreign body removals, amniotic membrane grafts, and tarsorrhaphies, can not only ensure timely execution of these procedures but also alleviate the workload on advanced centres, thus, allowing them to concentrate on more complex cases.\n\nThis tier focuses on addressing the sequelae of different corneal pathologies and ensuring visual rehabilitation to improve the quality of life. The majority of the clinical care currently provided falls within this level, and this section will discuss existing approaches and propose methods to improve upon them.\n\nCorneal transplantation:\n\nThis is the main modality of treatment for several corneal pathologies and aims to replace the diseased cornea with a healthy one. However, there are several issues that prevent optimal implementation of this procedure in developing countries.\n\nThe demand for donor corneas is not met by the supply and this needs to be addressed by improving the infrastructure and human resources. Estimates show that nearly 13 million individuals currently await a corneal transplantation globally and one million new cases get added every year.12,37 This discrepancy between the demand and supply is exacerbated in developing countries. For example, In India, 100,000 transplantations per year are necessary to reduce the burden of corneal blindness. However, the procurement rate is less than 25% of this burden--and only half the harvested corneas are utilized.38–40 Hence, to meet the needs of corneal transplantation, nearly 200,000 corneas need to be harvested. Ensuring these numbers requires a multipronged approach which targets the donor tissue availability as well as its storage and preservation. A multitiered system with eye banks that cater to a predefined target population can effectively expand their reach and secure an ample supply of donor corneas. This infrastructure should support not only traditional corneal transplantation but also the newer lamellar techniques. Increased public awareness of eye donation programmes and the need for donor corneas will help close the supply gap. The establishment of centralized registries, documenting patient lists and prioritizing their needs, can facilitate the allocation of this valuable resource to individuals in greatest need on a priority basis.\n\nCapacity building plays a crucial role in facilitating the optimal utilization of corneal tissues. This includes not only the training of corneal surgeons in the fundamental aspects of keratoplasty but also paraclinical staff to ensure the accurate collection of viable donor corneas. Eye bank technicians need to be trained in preparing lamellar endothelial grafts. Ensuring the presence of trained corneal surgeons in rural areas will not only enhance access to keratoplasty facilities but also facilitate improved adherence to postoperative follow-up and care.41 Providing training to corneal surgeons in lamellar keratoplasties and other emerging surgical modalities will aid in their widespread adoption and implementation. This will not only result in improved outcomes but also enable the utilization of multiple grafts from a single donor tissue, maximizing the potential benefits of each donated cornea.42 Finally, corneal surgeons should be versed not only in surgical skills but also in judicious case selection which will go a long way in optimizing the utilization of this scarce resource and improving the outcomes of these grafts.\n\nThe limitations of corneal transplantation have been discussed in the previous section which highlight how relying solely on keratoplasties is not a viable option for developing countries. Even for cases which have a good prognosis such as keratoconus or corneal opacifications without vascularization/anterior segment abnormalities, the postoperative course is subject to several issues which can affect the final visual outcome. This includes post-keratoplasty astigmatism, suture-related complications, graft infiltrates, and secondary glaucoma.43–45 Moreover, the postoperative care demands rigorous adherence and relies heavily on the patient's diligent compliance, as well as the presence of a supportive socio-economic system. However, establishing such a system can often pose challenges, especially in developing countries. Hence, alternatives to keratoplasties that circumvent these issues and provide long-term effective and reliable outcomes are the need of the hour.\n\nContact lenses (CL):\n\nAlthough CL have been around for several decades, it is with the advent of better lens materials and large scleral lenses with fluid reservoirs that they became game changers for corneal specialists.46–48 They are indicated in a vast number of diseases that range from corneal scars and keratoconus to severe ocular surface diseases.49–52 They not only improve the visual function by correcting the irregular astigmatism but also improve the overall health of the ocular surface. Enhancing awareness regarding the indications and benefits of these lenses will play a crucial role in promoting CL use. Training ophthalmologists and optometrists in dispensing these lenses will contribute to their broader distribution.\n\nOcular surface reconstruction and artificial corneas:\n\nVery often patients with seemingly opaque corneas can experience complete visual rehabilitation through procedures such as limbal stem cell transplantation. Surgeries such as simple limbal epithelial transplantation can not only address the deficient limbal epithelial stem cells but also modulate the underlying corneal scar and decrease its density.53–56 These procedures have stable long-term outcomes with good visual function, thus eliminating the need for keratoplasty in cases where corneal transplantation would not yield favourable outcomes.55,57,58 Providing training to corneal surgeons in the indications, perioperative management, and surgical techniques related to these procedures will equip them with the necessary skills to effectively handle such cases. Dissemination of information on basic and complex ocular surface reconstruction procedures will allow continued medical education to occur.59–63 Conducting periodic workshops will also help refresh these skills. Research endeavours are crucial to developing similar techniques that can circumvent the necessity for corneal grafting in these patients.\n\nThe use of prosthetic devices to replace the diseased cornea has been explored for several decades and recent advances have offered options that have good visual outcomes.64–66 Furthermore, they do not require high grade corneal tissue, and thus help improve utilization rates. However, the retention and long-term efficacy of these devices remains a limitation.64–66 With the advent of completely synthetic devices such as the CorNeat, corneal replacements can be carried out independent of donor corneal tissues.67,68\n\nMolecular therapy:\n\nThis is another appealing option that modulates scar formation during the process of corneal wound healing thus preventing the formation of the scar itself. Several interventions are being explored with respect to this and include bioactive molecules, exosomes, nanomedicine, recombinant viral vectors, and microRNAs.69,70 However, these are still in the experimental phase and will require clinical validation prior to their adoption in routine clinical practice.\n\nBioengineered cornea:\n\nSubstitutes for the cornea are an attractive option aimed at addressing the issue of deficient donor tissue. These substitutes can be cell-based, which recreate individual layers of the epithelium, stroma and endothelium.71 The other approach to tissue engineering is the scaffold-based models which are primarily for stromal regeneration. These models can be natural or synthetic. The former has a better capacity for integrating with the surrounding host tissue, while the latter can be modulated to the desired requirements.72,73 Natural polymers can also be obtained from human donor corneas which are deemed unsuitable for transplantation. As a result, this approach enables optimal utilization of tissue resources and allows for the acquisition of multiple grafts from a single tissue source.72 The use of 3D-printing technology to print an artificial cornea with raw materials such as collagen, alginate, and decellularized extracellular matrix is a promising solution to the problem of deficient donor corneas.74\n\nOther advances such as cultured endothelial cells which can be directly injected into the anterior chamber can not only be used as the primary treatment modality in pseudophakic bullous keratopathies but also for failed grafts.75,76 This can provide a minimally invasive option to revive otherwise failed transplants. Other options include targeted gene therapy and anti-sense oligonucleotides.76 Simple procedures such as removal of the diseased endothelium to pave the way for the surrounding endothelial cells in partial endothelial failure are also being explored.76 These techniques that do not rely on donor tissue or specialized equipment are urgent requirements.\n\nSupportive care and rehabilitation:\n\nPersons with corneal blindness may suffer from a range of problems including but not limited to depression, economic and personal dependence, and mobility issues. Providing supportive care services and rehabilitation programs to these individuals to help them cope with the physical, emotional, and social aspects of their condition is a crucial aspect of tertiary care. This may involve physical therapy, occupational therapy, counselling, or support groups and helps them reintegrate into society. These services not only help maintain household independence but also financial independence to the greatest extent possible.\n\nUniversal eye health care:\n\nThe current standard of care can effectively treat a significant proportion of the causes of corneal blindness. However, there exist several barriers that prevent individuals afflicted with these diseases from accessing this care. In order to address these barriers, a comprehensive and collaborative approach is essential, involving various stakeholders including healthcare providers, policymakers, and both public and private financial aid organizations.77 Incorporation of eye health into universal healthcare policies is imperative to ensure holistic care and this requires the necessary financial and human resource planning. By including eye care in these key areas, we can effectively address the diverse needs of individuals and communities and ensure accessible quality eye care services.\n\n\nConclusion\n\nThe global distribution of corneal blindness exhibits significant disparities, predominantly affecting mid to low-income countries. Current treatment approaches primarily focus on the tertiary level of prevention but are often unable to guarantee long-term visual rehabilitation. Novel therapeutic options that are not only effective but also inexpensive and accessible are the need of the hour. Additionally, a substantial portion of corneal blindness cases stem from preventable causes. Redirecting efforts and allocating resources towards primordial and primary prevention would effectively alleviate the burden of corneal blindness. A collaborative and concerted effort from healthcare professionals and government entities, facilitated by effective policies, can succcessfully channel resources and focus on the prevention of corneal blindness. By preventing the disease itself, the resultant burden on the healthcare system will also reduce and the elimination of this form of blindness can lead to substantial positive economic outcomes. The societal benefits of improved quality of life and increased social integration will further contribute to building a world where everyone can live to their full potential.",
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PubMed Abstract | Publisher Full Text\n\nArundhati A, Chew MC, Lim L, et al.: Comparative Study of Long-term Graft Survival Between Penetrating Keratoplasty and Deep Anterior Lamellar Keratoplasty. Am J. Ophthalmol. 2021; 224: 207–216. PubMed Abstract | Publisher Full Text\n\nChristo CG, van Rooij J , Geerards AJ, et al.: Suture-related complications following keratoplasty: a 5-year retrospective study. Cornea. 2001; 20: 816–819. Publisher Full Text\n\nWagoner MD, Ba-Abbad R, Al-Mohaimeed M, et al.: Postoperative complications after primary adult optical penetrating keratoplasty: prevalence and impact on graft survival. Cornea. 2009; 28: 385–394. PubMed Abstract | Publisher Full Text\n\nHarthan JS, Shorter E: Therapeutic uses of scleral contact lenses for ocular surface disease: patient selection and special considerations. OPTO. 2018; 10: 65–74. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchornack MM: Limbal stem cell disease: management with scleral lenses. Clin. Exp. Optom. 2011; 94: 592–594. PubMed Abstract | Publisher Full Text\n\nParra AS, Roth BM, Nguyen TM, et al.: Assessment of the Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) scleral lens on visual acuity for corneal irregularity and ocular surface disease. Ocul. Surf. 2018; 16: 254–258. Publisher Full Text\n\nKreps EO, Pesudovs K, Claerhout I, et al.: Mini-Scleral Lenses Improve Vision-Related Quality of Life in Keratoconus. Cornea. 2021; 40: 859–864. PubMed Abstract | Publisher Full Text\n\nLim L, Lim EWL: Current perspectives in the management of keratoconus with contact lenses. Eye (Lond.). 2020; 34: 2175–2196. Publisher Full Text\n\nChaudhary S, Kate A, Chappidi K, et al.: Safety and Efficacy of Contact Lenses in Eyes After Simple Limbal Epithelial Transplantation. Cornea. January 2023. Publish Ahead of Print. Publisher Full Text\n\nKate A, Singh S, Das AV, et al.: Dry eye disease and risk factors for corneal complications in chronic ocular graft-versus-host disease. Indian J. Ophthalmol. 2023; 71: 1538–1544. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBasu S, Sureka SP, Shanbhag SS, et al.: Simple Limbal Epithelial Transplantation: Long-Term Clinical Outcomes in 125 Cases of Unilateral Chronic Ocular Surface Burns. Ophthalmology. 2016; 123: 1000–1010. Publisher Full Text\n\nKate A, Mudgil T, Basu S: Longitudinal Changes in Corneal Epithelial Thickness and Reflectivity following Simple Limbal Epithelial Transplantation: An Optical Coherence Tomography-Based Study. Curr. Eye Res. October 2021; 47: 336–342. PubMed Abstract | Publisher Full Text\n\nShanbhag SS, Nikpoor N, Rao Donthineni P, et al.: Autologous limbal stem cell transplantation: a systematic review of clinical outcomes with different surgical techniques. Br. J. Ophthalmol. 2020; 104: 247–253. Publisher Full Text\n\nBasu S, Hertsenberg AJ, Funderburgh ML, et al.: Human limbal biopsy–derived stromal stem cells prevent corneal scarring. Sci. Transl. Med. 2014; 6: 266ra172. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBasu S, Fernandez MM, Das S, et al.: Clinical outcomes of xeno-free allogeneic cultivated limbal epithelial transplantation for bilateral limbal stem cell deficiency. Br. J. Ophthalmol. 2012; 96: 1504–1509. PubMed Abstract | Publisher Full Text\n\nSejpal K, Ali MH, Maddileti S, et al.: Cultivated limbal epithelial transplantation in children with ocular surface burns. JAMA ophthalmology. 2013; 131: 731. Publisher Full Text\n\nShanbhag SS, Patel CN, Goyal R, et al.: Simple limbal epithelial transplantation (SLET): Review of indications, surgical technique, mechanism, outcomes, limitations, and impact. Indian J. Ophthalmol. 2019; 67: 1265–1277. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKate A, Deshmukh R, Donthineni PR, et al.: Management of corneal perforations in dry eye disease: Preferred practice pattern guidelines. Indian J. Ophthalmol. 2023; 71: 1373–1381. Publisher Full Text\n\nKate A, Vyas S, Bafna RK, et al.: Tenon’s Patch Graft: A Review of Indications, Surgical Technique, Outcomes and Complications. Semin. Ophthalmol. 2022; 37: 462–470. PubMed Abstract | Publisher Full Text\n\nSharma S, Kate A, Donthineni PR, et al.: The role of Tenonplasty in the management of limbal and scleral ischemia due to acute ocular chemical burns. Indian J. Ophthalmol. 2022; 70: 3203–3212. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShanbhag SS, Singh S, Koshy PG, et al.: A beginner’s guide to mucous membrane grafting for lid margin keratinization: Review of indications, surgical technique and clinical outcomes. Indian J. Ophthalmol. 2021; 69: 794–805. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBasu S, Sureka S, Shukla R, et al.: Boston type 1 based keratoprosthesis (Auro Kpro) and its modification (LVP Kpro) in chronic Stevens Johnson syndrome. BMJ Case Rep. 2014; 2014: bcr2013202756. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBasu S, Serna-Ojeda JC, Senthil S, et al.: The Aurolab Keratoprosthesis (KPro) versus the Boston Type I Kpro: 5-year Clinical Outcomes in 134 Cases of Bilateral Corneal Blindness. Am J. Ophthalmol. 2019; 205: 175–183. PubMed Abstract | Publisher Full Text\n\nShanbhag SS, Senthil S, Mohamed A, et al.: Outcomes of the Boston type 1 and the Aurolab keratoprosthesis in eyes with limbal stem cell deficiency. Br. J. Ophthalmol. 2021; 105: 473–478. Publisher Full Text\n\nLitvin G, Klein I, Litvin Y, et al.: CorNeat KPro: Ocular Implantation Study in Rabbits. Cornea. 2021; 40: 1165–1174. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKate A, Basu S: A Review of the Diagnosis and Treatment of Limbal Stem Cell Deficiency. Front Med (Lausanne). 2022; 9: 836009. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIbrahim Al-Mashahedah AM, Kanwar RK, Kanwar JR: Utility of nanomedicine targeting scar-forming myofibroblasts to attenuate corneal scarring and haze. Nanomedicine (Lond.). 2019; 14: 1049–1072. Publisher Full Text\n\nGhosh A, Singh VK, Singh V, et al.: Recent Advancements in Molecular Therapeutics for Corneal Scar Treatment. Cells. 2022; 11: 3310. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMatthyssen S, Van den Bogerd B, Dhubhghaill SN, et al.: Corneal regeneration: A review of stromal replacements. Acta Biomater. 2018; 69: 31–41. PubMed Abstract | Publisher Full Text\n\nBrunette I, Roberts CJ, Vidal F, et al.: Alternatives to eye bank native tissue for corneal stromal replacement. Prog. Retin. Eye Res. 2017; 59: 97–130. Publisher Full Text\n\nChen Z, You J, Liu X, et al.: Biomaterials for corneal bioengineering. Biomed. Mater. 2018; 13: 032002. Publisher Full Text\n\nZhang B, Xue Q, Li J, et al.: 3D bioprinting for artificial cornea: Challenges and perspectives. Med. Eng. Phys. 2019; 71: 68–78. PubMed Abstract | Publisher Full Text\n\nKinoshita S, Kiorpes TC, Friend J, et al.: Goblet cell density in ocular surface disease. A better indicator than tear mucin. Arch. Ophthalmol. 1983; 101: 1284–1287. PubMed Abstract | Publisher Full Text\n\nPrice MO, Mehta JS, Jurkunas UV, et al.: Corneal endothelial dysfunction: Evolving understanding and treatment options. Prog. Retin. Eye Res. 2021; 82: 100904. Publisher Full Text\n\nBurton MJ, Ramke J, Marques AP, et al.: The Lancet Global Health Commission on Global Eye Health: vision beyond 2020. Lancet Glob. Health. 2021; 9: e489–e551. Publisher Full Text"
}
|
[
{
"id": "223571",
"date": "15 Dec 2023",
"name": "Denise Loya Garcia",
"expertise": [
"Reviewer Expertise Cornea",
"External Diseases",
"Refractive 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 a very interesting and complete paper focused on the role of prevention in corneal blindness.\n\nThey mention the significance of epidemiological research and the attention that needs to be taken into account for a better understanding of risk factors, behavior and challenges of these conditions. Despite the challenges, conducting epidemiological research in developing countries is essential for appreciating and addressing the unique health issues faced by these populations.\n\nThe prevention strategies that they present can help organize and focus on the efforts that need to be done on each level. By focusing on early detection, addressing the root causes, and promoting public awareness, it is possible to reduce the incidence of corneal diseases and their associated blindness, thereby improving overall eye health and wellbeing in these populations.\n\nFigures 2-3 legends are accidentally misplaced, figure 2 legend focuses on corneal scar after ocular trauma and the image and text are on ocular burns, the same is true regarding legend and figure 3, please address this.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "11164",
"date": "13 Apr 2024",
"name": "Sayan Basu",
"role": "Author Response",
"response": "We thank the reviews for their insightful comments and for pointing out the error in the figures. The figure 2 and 3 have been swapped to match their legends"
}
]
},
{
"id": "249004",
"date": "27 Feb 2024",
"name": "Martina Kropp",
"expertise": [
"Reviewer Expertise gene therapy",
"retina culture",
"neuroretinal degeneration",
"AMD",
"diabetic retinopathy",
"personalized medicine",
"regenerative medicine",
"iPSC",
"international ophthalmology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article summarizes current knowledge and state of the art prevention and treatment of corneal blindness. Authors state that current strategies in developing countries are insufficient and propose a 4-level prevention strategy to reduce prevalence of corneal blindness. The topic is of high importance and well addressed by the authors. They discuss the different reasons for corneal blindness in industrialized vs. developing countries pointing out that the different causes also need significantly different strategies to fight against it. A main difference is the fact that in developing countries many cases of corneal blindness are preventable and can thus, effectively avoided by mitigation strategies that are applied before patients become severely visually handicapped like eye protection with glasses or dietary vitamin A supplementation. The authors propose a comprehensive 4-level prevention strategy able to intervene at different stages of ocular care starting with primordial prevention (e.g., eye hygiene) to primary prevention (e.g., promoting eye safety practices) to secondary prevention (e.g., health education and screening programmes) to tertiary prevention (e.g., treatment infrastructure development). In the following, all options at all levels are mentioned and discussed including improvement of current care and potential future treatment approaches. The article is well written using an understandable style that is complete but compact. All factual statements and arguments are well justified by current literature. The only minor comment to make is that the text within the figures is quite small and it would be good, if the font size could be increased.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "11165",
"date": "13 Apr 2024",
"name": "Sayan Basu",
"role": "Author Response",
"response": "We thank the reviewer for the suggestion and the size of the text in the figures has been increased to enable better visualization."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1309
|
https://f1000research.com/articles/12-1377/v1
|
19 Oct 23
|
{
"type": "Research Article",
"title": "Epidemiology of maxillofacial injuries during monsoon and non-monsoon season in India: a data-based retrospective study from a tertiary care dental teaching hospital",
"authors": [
"Anand Deep Shukla",
"Srikanth G",
"Kalyan Chakravarthy",
"Ayusha Kaushal",
"Hariti M Udeshi",
"Anand Deep Shukla",
"Kalyan Chakravarthy",
"Ayusha Kaushal",
"Hariti M Udeshi"
],
"abstract": "Background: Maxillofacial Injury (MFI) is a major public health concern that is multifactorial in etiology-road traffic accidents (RTAs), falls and violence. RTAs are the major cause of maxillofacial injuries (MFIs) in countries like India. Recent studies have shown that maxillofacial fractures (MFF) constitute a significant proportion of facial injuries seen in hospitals (56.5%). The incidence of maxillofacial fractures can vary depending on several factors, including age, gender, and environmental factors. Of particular concern is the impact of seasonal variations, such as the monsoon season, which lead to high incidence of maxillofacial fractures due to hazardous conditions. Methods: A retrospective review of medical records was done in a tertiary-care dental teaching hospital was done. Results: Data of 200 subjects including 154 males (77%) and 46 females (23%) with a mean age of 35.38 ± 16.541 years; age range: 1 – 80 years was analyzed. A total of 200 MFI’s were recorded between 2021 and 2022. Soft tissue injuries were reported in 37.5% of the cases in non-monsoon season and 42.3% of the cases during the monsoon season. Dentoalveolar fractures were reported in 6.2% of the cases during the non-monsoon seasons and 7.7% during the monsoon season. In this study, mandible was the most fractured bone (n=104,52%) followed by zygomatic complex (n=50, 25%). The frequently observed pattern among mandibular fracture was condyle 8.3% during the non-monsoon season and 2.9% during the monsoon season). Conclusions: The results of the study indicate that mandibular fractures are most commonly seen in maxillofacial fractures, followed by fractures of the zygomatic complex. The study also reveals a higher incidence of soft tissue injuries and dentoalveolar fractures during the monsoon season. Further research is warranted to explore the factors that contribute to the seasonal variation in maxillofacial fractures for effective interventions to reduce their occurrence.",
"keywords": [
"Maxillofacial injuries",
"Road Traffic Accidents"
],
"content": "Introduction\n\nMaxillofacial injury (MFI) is a broad term used to describe any form of damage or trauma to the structures of the face, including the jaw, teeth, and facial bones and associated soft tissues.1 Maxillofacial fractures (MFF), on the other hand, specifically refer to fractures or breaks in one or more of the facial bones, such as the mandible or zygomatic complex. It is important to note that while MFFs are a type of MFI, not all MFIs involve fractures.\n\nMFIs are a significant public health concern, with a wide spectrum of severity that can range from minor injuries to life-threatening conditions.2 The incidence of maxillofacial fractures can vary depending on several factors, including age, gender, and environmental factors.\n\nRecent studies have demonstrated that maxillofacial fractures are among the most frequent types of facial injuries seen in hospitals 56.5%.3,4 These fractures can involve different components of the facial skeleton, including the mandible, maxilla, zygoma, and orbital bones.3,4\n\nAdditionally, it is important to consider how environmental factors may affect the number of maxillofacial fractures in hospital settings. The monsoon season, for example, may result in an increase in maxillofacial fractures owing to slippery roads and pavements, reduced visibility, and fallen trees and electrical wires.\n\nHealthcare providers must be aware of these trends and take steps to predict and manage maxillofacial injuries. Therefore, this research paper aims to compare the incidence and pattern of maxillofacial trauma in a hospital-based setting with a focus on environmental factors.\n\n\nMethods\n\nThe present study was conducted in the Department of Oral and Maxillofacial Surgery, Manipal College of Dental Sciences Manipal, Udupi, Karnataka, India. This study was based on a systematic computer-assisted database search that allowed extraction of retrospective data of the patients who reported to our outpatient unit with injuries from RTA from December 2021 to December 2022.\n\nData collection was initiated only after requisite approvals were obtained from the Scientific Committee and the Institutional Ethics Committee of Hospital (IEC:57/2022).\n\nThe requirement for informed consent was waived in view of the retrospective nature of the study and there being no direct contact with the study subjects. This study did not involve any intervention or therapy, and the research involved no risks to the subjects. Subjects’ names and identity were not disclosed in any way during or after this database review study. Subjects were identified by subject ID numbers only, and hence, patient data confidentiality has been maintained.\n\nPatients of both sexes and all age groups with clinically and radiographically diagnosed maxillofacial fractures (with or without contiguous bodily fractures/injuries) were included in this study. Patients with incomplete records were excluded from the study. Patients with isolated skull fractures and only minor superficial soft tissue injuries were excluded from our study.\n\nNo formal sample size was calculated and all 200 patients who met the inclusion criteria during the study period were included.\n\nThe hospital records were assessed and data on age, sex and season during which injury occurred was collected. Data was also recorded for anatomic location of facial fractures, associated soft tissue and dentoalveolar injury. In records fractures had been classified as fractures of the mandible, zygomatic-maxillary complex (OZMC), orbital floor, nose, Lefort I,II,III and naso-orbital-ethmoid (NOE) fracture. Mandibular fractures included fractures of the symphysis, Para symphysis, body, angle, ramus, coronoid, and condyle (Tables 3 and 4).\n\nStatistical analysis was performed using SPSS-20.0 for the Windows Statistical Package (IBM Corporation, Armonk, NY, USA) and a p value of ≤0.05 was considered statistically significant.\n\nDescriptive data were presented as mean ± SD or number (%), unless specified. Univariate analysis was done by Student’s t-test. Data for incidence of soft tissue injuries, dentoalveolar Injuries and various facial fractures were compared between the two seasons i.e., monsoon and non-monsoon.\n\n\nResults\n\nIn one year, period between December 2021 to December 2022, data of a total of 200 subjects were recorded and analyzed. Out of these, 154 (77%) were males while only 47 (23%) were females (Table 2). Male to female ratio was 3.28:1 (rounded to two decimal places) (Figure 1). The mean age of study population was 35.38 ± 16.541 years (age range: 1-80 years) (Table 1).\n\n\nDiscussion\n\nMaxillofacial trauma can be caused by various factors including falls, assaults, sporting injuries and road traffic accidents. Of these, road traffic accidents and monsoon weather conditions have been identified as significant contributors to the incidence of maxillofacial injuries. Given the increasing prevalence of road traffic accidents and unpredictable weather patterns, it is important to understand the epidemiology of maxillofacial injuries and identify any underlying patterns or trends that may exist to help reduce their incidence.\n\nSome regions show a correlation between monsoon season and an increase in facial fractures, possibly due to broken and slippery roads/pavements,5,6 falling objects, electrical wires, poor visibility and increased traffic congestion. This can lead to an increase in road traffic accidents and facial injuries. However, there is evidence to suggest that monsoon periods may have fewer cases of facial fractures as people may prefer to stay indoors in anticipation of rain.7\n\nUnderstanding these trends and patterns can help develop preventive measures to improve public safety, especially in areas where monsoons are severe.\n\nThe incidence of maxillofacial fractures is higher in developing countries than in developed ones due to several factors such as the lack of adequate safety measures, poor road infrastructure and social factors.5,8\n\nThe increase in both the frequency and severity of maxillofacial injuries can be linked to the high dependence on road transportation and the growth of socio-economic activities in developing countries. Contributing to these injuries are poor road safety awareness, unsuitable road conditions, underdeveloped motorways, speeding, outdated vehicles without safety features, and a lack of helmets and seat belts, as well as violations of traffic laws.5,9 All these factors come together to create a high number of road traffic accidents in developing countries.\n\nMen show higher incidence for MFI’s due to their greater involvement in high-risk activities, outdoor activities, anatomical differences, and behavioral differences such as risk-taking in comparison to women as only few of them drive a vehicle. This has resulted in an increase in the male: female ratio this is found to be consistent with the findings reported in other research papers.4,5,8\n\nOn analyzing the data, we found that soft tissue injury and dentoalveolar injury are not significantly associated with monsoon season, while zygomatic arch, zygomaticomaxillary complex, frontal, orbital floor and orbital rim fractures are significantly more common during monsoon season.\n\nIn this study the incidence of maxillofacial trauma due to RTA during the monsoon season was found to be lesser but the severity of trauma was found to be greater.7\n\nOur study was conducted in an environment with better road infrastructure and easy access to immediate medical care, which may have contributed to a lower incidence of maxillofacial trauma. This contrasts with previous studies that have reported a higher incidence of maxillofacial trauma in low-income countries with poor infrastructure and limited access to healthcare services.\n\nFuture studies that are planned shall have a database which includes patients over a longer period of time so that the database is much wider.",
"appendix": "Data availability\n\nFigshare: Data for the study on epidemiology of maxillofacial trauma, https://doi.org/10.6084/m9.figshare.23558628.v2. 10\n\n- Data updated.xlsx\n\n- data legend.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\nKaur G, Singh A, Mahajan A: Maxillofacial Trauma. Indian J. Anaesth. 2003 Jul 1; 47(4): 290–293.\n\nAkhlaq M, Ali S, Asghar R, et al.: Pattern and etiology of maxillofacial fractures in Lahore, Pakistan. J. Ayub Med. Coll. Abbottabad. 2014; 26(1): 58–61.\n\nBali RK, Sharma P, Garg A, et al.: A comprehensive study on maxillofacial trauma conducted in Yamunanagar, India. J. Inj. Violence Res. 2013; 5(1): 38–50. Publisher Full Text\n\nBoffano P, Kommers SC, Karagozoglu KH, et al.: Aetiology of maxillofacial fractures: a review of published studies during the last 30 years. Br. J. Oral Maxillofac. Surg. 2014; 52(10): 901–906. PubMed Abstract | Publisher Full Text\n\nGurung US, Singh G, Mishra M, et al.: Maxillofacial Injuries Related to Road Traffic Accidents: A Five Year Multi Center Analysis. Craniomaxillofacial Trauma & Reconstruction Open. 2020; 3: s-0039-1694708. Publisher Full Text\n\nAgnihotri A, Garg R, Alok A: A study of pattern of maxillofacial trauma in a tertiary care hospital in North India. Natl. J. Maxillofac. Surg. 2011 Jul-Dec; 2(2): 150–154.\n\nJohnson AG, Ravindran V, Ravindran Nair KS, et al.: Variation of Incidence of Maxillofacial Trauma due to Road Traffic Accidents during monsoon and non-monsoon period in Malabar region, Kerala, India. Int. J. Curr. Res. 2020; 12(11): 14505–14509.\n\nAleksanyan LV, Poghosyan AY, Misakyan MS, et al.: Epidemiology of maxillofacial injuries in “Heratsi” No 1 university hospital in Yerevan, Armenia: a retrospective study. BMC Oral Health. 2022 Apr 12; 22(1): 123. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhan TU, Rahat S, Khan ZA, et al.: Etiology and pattern of maxillofacial trauma. PLoS One. 2022 Sep 29; 17(9): e0275515. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShukla AD: Data for the study on epidemology of maxillofacial trauma. figshare. [Dataset]. Figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "217295",
"date": "31 Oct 2023",
"name": "Amit Sethi",
"expertise": [
"Reviewer Expertise Dentoalveolar surgery",
"Anesthesia",
"Medicine",
"Trauma"
],
"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 done well to highlight the influence weather and environmental conditions can play on the number and type of maxillofacial injuries seen.\nThe authors have brought up a very unique factor which could influence the number of patients presenting with maxillofacial trauma. The authors have also done well to classify patients based on age, sex and type of injury. Sex of patients may be important and evolve in coming years as more women take up driving.\nThe authors mention that the effect of rains may be mitigated by the fact that some people choose to stay home because of impending rain. This study is a good pilot study for a more elaborate study to be done in which a) duration can be longer b) the years with \"good\" or \"bad\" monsoon can be studied and data analyzed c) comparison can be done across different hospitals situated in places with light / moderate / heavy rain and then compare the variability in type and number of patients coming to emergency rooms with maxillofacial trauma\nOverall the article is a good read and discusses an important topic in an objective manner.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "243082",
"date": "20 Feb 2024",
"name": "Rui Santos",
"expertise": [
"Reviewer Expertise Statistical inference",
"data science",
"meta-analysis and epidemiology",
"mainly applied to the areas of Medicine and Forensic Science."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors present a retrospective study of the etiology and the type of maxillofacial injuries depending on factors such as sex, age and monsoon season in India.\nIn this study, 200 maxillofacial injuries are analyzed from the medical records of a tertiary-care dental teaching hospital. The critical analysis of the results is interesting, but there are some aspects that should be clarified and/or improved, namely:\n- The authors state \"Univariate analysis was done by Student’s t-test\". What was the t-test used for?\n- Tables should be presented (and numbered) in the order in which they are referred to (table 2 is referred to before table 1).\n- Figure 1 and Table 2 have the same information (and neither adds information in relation to what is in the text). I think they can be both removed.\n- All information in Table 1 is referred to in the text (this table can also be removed).\n- All information from Table 3 is included in the first lines of Table 4, so this table must be removed.\n- In Table 4, the column headings are clearer if are used in the same way as those in Table 3 (i.e., \"Non-monsoon season\" and \"Monsoon season\" instead of 0 and 1). The same occurs in the line designations, where \"Absent\" and \"Present\" are clearer than 0 and 1 (even with the explanation in a footnote to the table).\n- The results section should be developed in order to clarify the results presented, in particular which p-value is presented in Table 4 (i.e., which test was carried out, as it appears to be a comparison test of the proportions observed between the two seasons, but the only test referred in the text is the univariate t-test which is not suitable for this purpose). Moreover, in Table 4, why is \"Sig\" (significant) the p-value \"0.053\" on the \"FRONTAL BONE\", but the p-value \"0.021\" is not significant in the \"ORBITAL FLOOR\"?\n- Some discussion and references are related to the etiology of maxillofacial injuries, such as road traffic accidents, falls, assaults, sports injuries, and violence. Moreover, it is stated that \"In this study the incidence of maxillofacial trauma due to RTA during the monsoon season was found to be lesser but the severity of trauma was found to be greater\". Can the authors provide the data (for example in a table) on which they based this statement? In fact, in the Results section nothing is presented about the etiology of the maxillofacial injuries. If the analyzed data contains information about the etiology, it would be relevant to include this information in summary form in the Results section. Please note that the provided data does not contain any information about the etiology.\n- In the discussion, differences in terms of sex are also mentioned (\"Men show higher incidence\"...). Since the analyzed data contains information about the sex of the patients, what can be concluded from the analysed data? Is it possible to add results (in the Results section) that highlight the differences between the sexes in the maxillofacial injuries?\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": "11127",
"date": "13 Apr 2024",
"name": "anand deep shukla",
"role": "Author Response",
"response": "Thank you for reviewing the manuscript. Below are the comments raised by the 2nd reviewer along with the replies Query: The authors state \"Univariate analysis was done by Student’s t-test\". What was the t-test used for? Reply : Apologies for the confusion. We have corrected the same. “Data for incidence of soft tissue injuries, dentoalveolar Injuries and various facial fractures were compared between the two seasons i.e., monsoon and non-monsoon using Chi-square or Fishers exact test.” Query: Tables should be presented (and numbered) in the order in which they are referred to (table 2 is referred to before table 1). Reply: Tables have been numbered accordingly. Query: Figure 1 and Table 2 have the same information (and neither adds information in relation to what is in the text). I think they can be both removed. Reply: Both Figure 1 and Table 2 have been removed. Query: All information in Table 1 is referred to in the text (this table can also be removed). Reply: The table has been removed Query: All information from Table 3 is included in the first lines of Table 4, so this table must be removed. Reply: The table has been removed Query: In Table 4, the column headings are clearer if are used in the same way as those in Table 3 (i.e., \"Non-monsoon season\" and \"Monsoon season\" instead of 0 and 1). The same occurs in the line designations, where \"Absent\" and \"Present\" are clearer than 0 and 1 (even with the explanation in a footnote to the table). Reply: The column headings are changes to Non monsoon and monsoon season as instructed. Query: The results section should be developed in order to clarify the results presented, in particular which p-value is presented in Table 4 (i.e., which test was carried out, as it appears to be a comparison test of the proportions observed between the two seasons, but the only test referred in the text is the univariate t-test which is not suitable for this purpose). Moreover, in Table 4, why is \"Sig\" (significant) the p-value \"0.053\" on the \"FRONTAL BONE\", but the p-value \"0.021\" is not significant in the \"ORBITAL FLOOR\"? Reply: The statistical analysis that was carried out was Chi-square or Fishers exact test, the same has been corrected in the manuscript. The p value of 0.021 for orbital floor has been changed to significant as pointed out. Query: Some discussion and references are related to the etiology of maxillofacial injuries, such as road traffic accidents, falls, assaults, sports injuries, and violence. Moreover, it is stated that \"In this study the incidence of maxillofacial trauma due to RTA during the monsoon season was found to be lesser but the severity of trauma was found to be greater\". Can the authors provide the data (for example in a table) on which they based this statement? In fact, in the Results section nothing is presented about the etiology of the maxillofacial injuries. If the analyzed data contains information about the etiology, it would be relevant to include this information in summary form in the Results section. Please note that the provided data does not contain any information about the etiology. Reply: We have omitted the line as per the suggestion. The included cases were only due to RTA as etiology. Query: In the discussion, differences in terms of sex are also mentioned (\"Men show higher incidence\"...). Since the analyzed data contains information about the sex of the patients, what can be concluded from the analyzed data? Is it possible to add results (in the Results section) that highlight the differences between the sexes in the maxillofacial injuries? Reply: The data highlighting the sex distribution in maxillofacial injuries has been added."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1377
|
https://f1000research.com/articles/11-144/v1
|
03 Feb 22
|
{
"type": "Systematic Review",
"title": "Corporate governance and shareholders’ confidence in cooperative corporations: a systematic literature review",
"authors": [
"Arasu Thangaveloo",
"Magiswary Dorasamy",
"Abdul Aziz Bin Ahmad",
"Siva Barathi Marimuthu",
"Jayamalathi Jayabalan",
"Abdul Aziz Bin Ahmad",
"Siva Barathi Marimuthu",
"Jayamalathi Jayabalan"
],
"abstract": "Background: The confidence of Bottom 40 (B40) shareholders is crucial for cooperative corporation’s sustenance within wider corporate governance. An in-depth study on cooperatives is needed, as they play a crucial role in the Malaysian economic system and contribute greatly to the country’s social development. However, in the current landscape, confidence among shareholders is at stake. This study aims to identify the research gap into corporate governance for cooperative corporations in relation to B40 shareholder confidence, as well as identify current study challenges and develop a conceptual framework for future research. Methods: We conducted a systematic literature review, with the use of agency theory to assess shareholders’ confidence. Emerald, ProQuest, InderScience, Scopus and Science Direct were the online databases used in this study to search five keyword phrases: corporate governance, confidence, cooperative, agency theory and Bottom 40% (B40) household. Tranfield’s five stages were used to conduct the systematic review. Results: Only 5 of the 324 studies assess shareholders’ confidence in cooperatives, as well as one paper on B40 and two papers on agency theory. Our review presents three major findings. First, research in the context of B40 shareholder’s confidence in cooperative corporations is limited. Second, the challenges related to shareholders’ confidence in B40 are major issues in the context. Third, research on agency theory in the context of shareholders’ confidence within cooperative corporations and corporate governance is still scant. Conclusions: This review urges the research community to conduct more studies based on the highlighted research gaps.",
"keywords": [
"Cooperative corporations",
"corporate governance",
"shareholders",
"B40",
"Malaysia",
"confidence",
"agency theory"
],
"content": "Introduction\n\nMalaysia’s cooperative movement began in the early twentieth century. A cooperative corporation is an organisation whose purpose is to enhance its members' economic value in line with cooperative goals. Consumer cooperatives, labour cooperatives, finance or banking cooperatives, and community cooperatives are only a few examples of cooperatives from various industries. Cooperative corporations play a crucial part in the Malaysian economic system and contribute greatly to the country’s social development. Their contributions are valued at the same level as those made by other businesses, in terms of the value-added to the national economy.1 This study considers the corporate governance of cooperative corporations and its relation to shareholders’ confidence. Corporate governance is a system of internal rules, procedures and employees that meets shareholders and other stakeholders' requirements via the management and control of management operations with strong business skills, objectivity, responsibility and integrity.\n\nA lack of confidence in the ability of the cooperative management, can in turn, could trigger a financial crisis within the corporation. Thus, the failure of a cooperative could become inevitable, which may eventually damage shareholders willingness to provide future investment.2 The effect of shareholders’ views is even more critical in the case of cooperative corporations, because these companies often have political influence. Politically linked companies can possess bad corporate governance practices and higher-level corporate issues because they depend heavily on the federal government.3 Thus, studying corporate governance’s impact on the confidence levels of shareholders in cooperative corporations is essential. Serious consequences may arise if it affects the confidence of Bottom 40 (B40) household shareholders. B40 refers to the bottom 40% in Malaysian household income; categorized as low-income householders earning below 4850 Malaysian Ringgit (RM) per month (approximately USD$1158). Various cooperatives corporation offered a share to the B40 employees or B40 members as one of the cooperatives benefits. Such cooperatives in Malaysia include the Armed Forces Cooperative, National Land Finance Co-operative Society (NLFCs), Koperasi Permodalan Felda Berhad and many more. Factors such as transparency, trustworthiness, integrity and good governance, are the key factors in creating shareholder confidence, and ensuring cooperative organisations remain competitive.\n\nMalaysia’s awareness of the importance of corporate governance began after the 1997 financial crisis, which hit many Southeast Asian countries, resulting in a tremendous decline in share prices and currency value.4 One major cause of the situation was the absence of confidence and honesty, as well as poor corporate governance within many organisations.5–7 One of the country's oldest cooperatives, Malay Officers Cooperative Credit and Investment Society (MOCCIS), was declared bankrupt in 2008. The government also seized the accounts of three cooperatives in December 2008, after it was discovered that they had misled over 5,000 members into investing RM80 million in unlawful get-rich-quick schemes. Koperasi Taqwa Malaysia Berhad (Kotaqwa), Koperasi Ushahawan Malaysia Berhad (KUMB), and Koperasi Birr Berhad (Birr) were the three cooperatives (Consumers’Association of Penang). Literature has documented evidence that a reliable corporate governance framework can have a significant impact in improving strong efficiency along with emerging economic situations.5–7\n\nFor most scholars, researching the confidence of shareholders in a cooperative organisation is a challenge because of limited literature linking confidence to cooperative corporation. Therefore, in this study, we seek to describe the notion of shareholders’ confidence, in order to understand how it related to the cooperative corporation’s effectiveness. Agency theory may help to shed some light on the existing body of knowledge, to address the problems within this context.\n\nAccording to agency theory, businesses operate as agents for their shareholders. That is, shareholders engage in corporate ownership and pledge their assets to the management of the corporation's directors and officers. The relationship between cooperative governance and shareholder confidence is examined using the agency theory.8 Agency theory is a relevant theory in this context that influences Malaysia’s corporate governance structures. This study’s analysis provides valuable information on how business management and shareholder confidence.\n\nThe research questions for this study are as follows:\n\n1. Is there a research gap in B40 shareholders’ confidence in the cooperation corporation sector?\n\n2. What are the challenges related to shareholders’ confidence in B40?\n\n3. What will be the conceptual framework for B40 shareholders’ confidence in the cooperation corporation sector?\n\nThe objectives of this proposal are as follows:\n\n1. To identify if there is a research gap in B40 shareholders’ confidence in the cooperation corporation sector.\n\n2. To understand the challenges related to shareholders’ confidence in B40.\n\n3. To propose a conceptual framework for B40 shareholders’ confidence in cooperation corporation sector.\n\nTwo primary reasons for conducting a systematic literature review are as follows; firstly it enables researchers to locate and systematise existing literature on a specific research topic and determine the level of interest that scholars have shown in investigating a particular topic. Secondly, it adds to our understanding of the types of relationships studied in the context. This study aims to understand and evaluate the B40 shareholders’ confidence in cooperative corporations, concerning risk, expected return and confidence in future investment possibilities. This study is an initiative to identify the major challenges involved in corporate governance practices in cooperative firms.\n\n\nMethods\n\nThis study was approved by the Research Ethical Committee of Multimedia University, Malaysia (EA2712021).\n\nThis study is designed to present a literature review, research gap analysis, conceptual framework and insights gained on cooperative corporations and their relation to B40 shareholder’s confidence. The literature review is based on the five stages of systemic review proposed by Tranfield et al.9\n\nFigure 1 below depicts the systematic flowchart of the review methodology.\n\nArticles investigating the confidence components in corporate governance within the context of cooperative corporations, do not specifically discuss the confidence of shareholders particularly in cooperative corporation. This study found that the Malaysian Code on Corporate Governance (MCCG) did not apply to cooperative corporation investors, in terms of there being no explicit regulations for how and when their practices may be improved. Effective corporate governance structure improves B40 shareholders confidence in terms of transparency, trustworthiness, integrity and good governance. As a result, we opted to check the number of publications for the specified keywords as the first step. The keywords range from broad themes (corporate governance) to more targeted terms (corporate governance/confidence/cooperative/B40).\n\nCriteria of inclusion and exclusion\n\nIn order to conduct the search for this study, the following exclusion and inclusion criteria was used, detailed in Figure 2 also. Papers were selected if they were published between year 2000 and 2021, had been peer-reviewed, written in English, and if they addressed non-profit cooperative corporations and corporate governance. Journals, conference proceedings, dissertations and special issues were included in the inclusion criteria. Five major databases that were used to conduct the searches; Emerald, Scopus, Science direct, Inderscience and ProQuest.\n\nKeywords\n\nIn order to review the literature comprehensively, we followed Tranfield et al.,’s systematic literature review methods, and used Emerald, ProQuest, InderScience, Scopus and Science Direct to search the following keywords: (1) corporate governance, (2) confidence, (3) cooperative, (4) agency theory and (5) B40.9 The phrases searched included: ‘corporate governance’, ‘corporate governance and investors/shareholders confidence’, ‘corporate governance and investors/shareholders confidence and cooperative’, ‘corporate governance and investors/shareholders confidence and B40’ and ‘corporate governance and investors/shareholders confidence and cooperative and B40’. The search began with more general searches using the terms ‘corporate governance’ and/or ‘confidence.’ The searches were conducted between 1st June 2021 and 15th June 2021.\n\nSearch strategy\n\nThe search strategy was based on the keyword search, in order to investigate papers in the five major online databases, including Emerald, ProQuest, InderScience, Scopus and Science Direct. This selection was based on these databases’ widespread use and high level of academic merit.11 Furthermore, these databases include a large number of periodicals devoted to business and cooperatives. The keywords selected were combined into five possible combinations, as shown in Table 1. The search on ‘corporate governance’ alone initially produced 77,864 publications. When searched with ‘corporate governance and investors/shareholders confidence’, the number dropped to 2,304. When we used the keyword combinations of ‘corporate governance and investors/shareholders confidence and cooperative,’ the number was 324. Subsequently, we found only one publication when we searched for ‘corporate governance and investors/shareholders confidence and B40’. The same was also true when we searched for ‘corporate governance and investors/shareholders confidence and cooperative and B40’; only one publication was found.\n\nWe used the following technique to extract papers from the major web databases mentioned above, summarised in Figure 3. Only confidence in cooperative cooperation papers linked to the B40 group, were selected for further evaluation.\n\n\nResults\n\nFrom the 324 papers found through searching for ‘corporate governance and investors/shareholders confidence and cooperative, we found five papers relevant to our investigation. Only 5 of the 324 studies assess shareholders’ confidence in cooperatives, as well as one paper on B40 and two papers on agency theory. The findings are summarised in Table 2.\n\nAlthough most of these studies have focused on the direct impact of confidence in cooperative corporations, some authors are interested in investigating the confidence effect that significant shareholders can exert. Only 5 of the 324 studies, displayed in Table 2, discuss shareholders’ confidence in cooperatives, including one paper on B40, two papers on agency theory and none on non-profit cooperatives. The results of the analysis are presented in Table 3.\n\nTable 3 lists two papers with agency theory and six other theories, which were used in the studies based on different context.\n\n\nDiscussion\n\nThere are several gaps identified in this study. There are limited studies on corporate governance related to B40 shareholders confidence in the context of cooperative corporations. More research and case studies are crucial for cooperative corporations to understand and adopt any possible recommendations; the implication of which would be to encourage B40 shareholders to invest in such corporations.\n\nA limitation of our study is the number of keywords selected; it would have been possible to obtain more papers in our search if the keywords were expanded to broader fields of study, not so specific in nature, such as B40. This could possibly lead to publication biases.\n\nResearch gap in B40 shareholders’ confidence in the cooperation corporation sector\n\nVery few papers discuss the importance of the B40 shareholders’ confidence in cooperative corporations. Filling the research gap is vital to building more knowledge of B40 shareholders in investment portfolios; which will help cooperative corporations build confidence in shareholders as a critical feature. The data are shown in Tables 4 and 5.\n\nChallenges related to shareholders’ confidence in B40\n\nThe main challenges with shareholders confidence in cooperative corporation is that it doesn't stand alone. The challenges related to shareholders’ confidence, in general, can be grouped into four categories, including external, internal, government related and population size. The external challenges include corporate tax and social behaviour of shareholders. Restrictive government policies and the high populations in B40 groups are another challenge related to shareholders confidence in B40s. However, these challenges do not sufficiently address the issues faced by B40 shareholders, which is one of the research gaps this study has identified. Furthermore, B40 shareholders are generally illiterate and need more knowledge about investment portfolio.\n\nConceptual framework for B40 shareholders’ confidence in the cooperation corporation sector\n\nAgency theory has not been tested for B40 shareholders, particularly to address shareholders’ confidence in cooperation corporations. Shareholder’s confidence is a missing piece within the agency theory; especially in cooperative corporations. Protecting the interests of B40 shareholders who invest in the company and have expectations about the business and their investments, are critical.12 Thus, we propose the following conceptual framework for further studies.\n\n\nFuture recommendations\n\nResearchers looking into the association between B40 shareholder confidence, corporate governance and cooperative corporations could use the primary findings of this publication, to generate ideas for future research. Two primary research themes could be considered in the future and we hope the academic community conduct more research on the following:\n\nFuture studies should focus more on the Middle 40 (M40) shareholders, because they are the main contributors to the national GDP. M40 households make up 40% of Malaysia’s population, includes mostly wage earners, in public and private sectors, earning between RM4850-10959 per month.\n\n\nConclusion\n\nThe purpose of this study is to update corporate governance and cooperative corporations research communities about research gaps, namely in the areas of shareholder confidence, particularly among B40 shareholders. No unique confidence metric exists today, nor a case study explicitly dedicated to confidence. In this study, we used a five-stage technique to review papers based on a thorough examination of the literature in a particular field. According to our in-depth analysis of these papers, there are three primary areas which have room for research. Firstly, there is a pressing need for researchers to standardise the terminologies used the discuss corporate governance, cooperative corporations and shareholder confidence. Secondly, more research is needed to determine whether corporate governance, cooperative corporations, shareholder’s confidence and the B40 groupto form the basis for more effective policy formulation and the basis for guiding the next generation of effective investment. In this context, the extent of the commonalities between shareholder confidence and B40 could be investigated further. Finally, further empirical research is needed to understand the elements that influence B40 shareholders’ confidence in the context of corporate governance and cooperative corporations.\n\n\nData availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nFigshare: Prisma checklist and data flow diagram doi.org/10.6084/m9.figshare.16822225\n\nThis project contains the following extended data:\n\n• Data file 1. (Checklist, DOCX format)\n\n• Data file 2. (Flow diagram, PDF format)",
"appendix": "Acknowledgement\n\nWe thank the Multimedia University, Malaysia for the support and opportunity to write this paper.\n\n\nReferences\n\nHashim MK, Zakaria M: Strengths, Weaknesses, Opportunities and Threats of Cooperatives in Malaysia. Journal of the Asian Academy of Applied Business (JAAAB). 2015.\n\nHossain B: Directors’ remuneration and performance: Evidence from the textile sector of Bangladesh. J. Asian Finance Econ. Bus. 2020; 7(6): 265–275. Publisher Full Text\n\nMohammed NF, Ahmed K, Ji XD: Accounting conservatism, corporate governance and political connections. Asian Rev. Account. 2017; 25(2): 288–318. Publisher Full Text\n\nHong H, Stein JC: A unified theory of underreaction, momentum trading and overreaction in asset markets. J. Financ. 1999; 54: 2143–2184. Publisher Full Text\n\nCG Watch Report: 2018. Reference Source\n\nZhou H, Owusu-Ansah S, Maggina A: Board of directors, audit committee, and firm performance: Evidence from Greece. J. Int. Account. Audit. Tax. 2018; 31(1): 20–36. Publisher Full Text\n\nAl-ahdal WM, Alsamhi MH, Tabash MI, et al.: The impact of corporate governance on financial performance of Indian and GCC listed firms: An empirical investigation. Res. Int. Bus. Finance. 2020; 51(1): 101013–101083. Publisher Full Text\n\nJensen MC, Meckling WH: Theory of the Firm: Managerial Behavior, Agency Costs, and Ownership Structure. J. Financ. Econ. 1976; 3(no. 4) (October 1976), 305–360. Practice. London: Sage. Publisher Full Text\n\nTranfield D, Denyer D, Smart P: Towards a Methodology for Developing Evidence-Informed Management Knowledge by Means of Systematic Review. Br. J. Manag. 2003; 14(3): 207–222. Publisher Full Text\n\nPatton MQ: Qualitative evaluation and research methods. SAGE Publications, Inc.; 1990.\n\nGuide 2 Research, Top Journals for Computer Science and Electronics. © 2021 Guide 2 Research. All Rights Reserved. Reference Source\n\nTricker RI: The cultural dependence of corporate governance. Keeping Good Companies. 2012; 64(1): 27–31.\n\nShahid MS, Abbas M: Does corporate governance play any role in investor confidence, corporate investment decisions relationship? Evidence from Pakistan and India. J. Econ. Bus. 2019; 105: 105839. Publisher Full Text\n\nGould DM, Melecky M, Panterov G: Finance, growth and shared prosperity: Beyond credit deepening. J. Policy Model. 2016; 38(4): 737–758. Publisher Full Text\n\nZekos GI: MNEs, globalisation and digital economy: legal and economic aspects. Managerial Law. 2003; 45: 1–296. Publisher Full Text\n\nNorman ID, Norman BMA: Juxtaposition of Hohfeldian Rights, Principle-Based Ethics, Functionings, and the health-Seeking Behavior of Sub-Saharan Africa. Advances in Applied Sociology. 2016; 06(10): 344–362. Publisher Full Text\n\nMardini GH, Lahyani FE: Impact of firm performance and corporate governance mechanisms on intellectual capital disclosures in CEO statements. J. Intellect. Cap. 2020. ahead-of-print. Publisher Full Text"
}
|
[
{
"id": "122501",
"date": "21 Feb 2022",
"name": "Ravichandran K. Subramaniam",
"expertise": [
"Reviewer Expertise I have done Corporate governance-related papers and as such I am fine to review this paper"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper has been well written with a clear introduction, comprehensive literature, search strategy, and overall results. The theory is sound and backed up with research questions and objectives. However, here are my pointers for the authors to improve the article in order for it to be of indexable quality:\nMain Issues:\nAs there were no info/data available on 'Non-profit Cooperatives', then it is better to just stick to a study on 'Cooperatives' as otherwise, we will be misrepresenting the research.\n\nBased on the overall literature sourced, there has only been one study on B40 out of 77,864. So the authors need to emphasize the scarcity of this study instead of downplaying it by saying it is merely limited. This is a significant finding.\n\nWith regards to contribution the authors could mention the rationale for such low research and how this could be addressed in the future.\n\nUsing the words 'Cooperative corporations', is rather confusing. Suggest simplifying it to the word 'Cooperatives'.\nOther Issues:\nNeed to have a clear definition of 'Cooperatives' to avoid ambiguity.\n\nSuggest elaborating on the term 'corporate governance framework'.\n\nUnder the research questions and objectives portion, instead of 'Cooperatives', the authors misspelled it as 'cooperation' and this has been repetitive.\n\nIn Figure 2, indicated as 'remove non-profit Cooperatives' and exclude 'profit Cooperatives' to rectify appropriately.\n\nVery few papers discuss the importance of the B40 shareholders’ mentioned under the heading \"Research gap in B40 shareholders’ confidence in the cooperative corporation sector\" is not correct as there were only one (as per table 1).\n\nTable 4 & 5 on the non-profit corporations, can be removed to maintain clarity and consistency.\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",
"responses": []
},
{
"id": "122503",
"date": "07 Feb 2024",
"name": "Rajeswari R",
"expertise": [
"Reviewer Expertise Marketing",
"International Business",
"and Logistics and Supply Chain 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 paper has been well drafted with a precise introduction, research strategy, results drawn, and the conclusion derived. The research questions and objectives set for the study clearly suit the purpose of the study. However, the study can be improved to make it error free.\nMain issues:\nSince the word “Cooperative Cooperation” may be new to many readers, it would be appropriate to clarify if the term “Cooperations” and “Cooperative Cooperative” have different meanings.\n\nCan mention more about the bottom 40 shareholders and the ways in which it can change the economic development of Malaysia.\n\nEven though, the authors have stated about the scarcity of resources for collection of data on such a topic, authors should emphasise more on this matter, collect the data, analyse it and take the required information for the study.\n\nMisspelled “cooperations” as “cooperatives” in many areas of the study.\n\nIt will be better if the authors have more suggestions on the future of such a topic and to influence more people to conduct study in this subject.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-144
|
https://f1000research.com/articles/12-809/v1
|
11 Jul 23
|
{
"type": "Research Article",
"title": "Long-term effect of non-severe COVID-19 on pulmonary function, functional capacities and physical activities: a cross-section study in Sakaka Aljouf",
"authors": [
"Maha Alshammari",
"ALSAYED SHANB",
"Mohammed Alsubaiei",
"Enas youssef",
"Maha Alshammari",
"Mohammed Alsubaiei",
"Enas youssef"
],
"abstract": "Background: COVID-19 has serious consequences on different body systems particularly the respiratory system with its impact on pulmonary function, functional capacities, physical activities, and personal performance. This study aimed to investigate the long-term effect of COVID-19 on pulmonary function, functional capacities, and physical activities in patients with non-severe COVID-19. Methods: 160 individuals were selected to participate in a cross-section study. Group-I: 80 male and female patients with non-severe COVID-19 at least 3 months after the recovery time. Group-II:80 male and female matched participants. The spirometer, six-minute walk test (6MWT), and International Physical Activity Questionnaire (IPAQ) were used to assess pulmonary function, functional capacities, and physical activities respectively. Shapiro–Wilk’s test was used to test normality of data. The Mann–Whitney and independent t-tests were used to compare the significant differences between both groups.\nResults: The results show significant differences in pulmonary function, functional capacities, and physical activities, between both COVID-19 and matched groups. Conclusion: Pulmonary function, functional capacities, and physical activities are negatively influenced by COVID-19 as long-term consequences indicating the need for extended health care, and prescription of proper rehabilitative training programs for such patients whatever their severity degree of infection or history of hospitalization. Outcome reflections of the current results raise awareness for physical therapists to tailor the proper rehabilitative training programs for such patients.",
"keywords": [
"COVID-19",
"Pulmonary Function",
"Physical Activities",
"Functional Capacities"
],
"content": "Introduction\n\nCoronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which began spreading on 31 December 2019 and had spread globally in the first months of 2020.1 Although many patients with COVID-19 do not suffer from any symptoms and recover spontaneously without medical interventions, one in every six patients develops breathing difficulties and becomes seriously ill.1 Until 29 September 2022, there had been 613,942,561 confirmed cases, including 6,520,263 deaths worldwide due to COVID-19.2 Public health was forced to take specific protocols and precautions to prevent rapid spread of pandemic, and its associated economic crisis.3 Tens of millions lost their jobs and increased poverty levels.4 Consumption, investments,5 work absenteeism, productivity, hospitality sectors and closures of factories all impacted negatively on income and supply.5,6 COVID-19 affects people of all ages and seriously impacts different body systems.7\n\nPost-COVID-19 syndrome means the sequelae that develop during or after a SARS-CoV-2 infection and persist for more than 12 weeks.8 It encompasses multi-organ sequelae beyond the acute phase of infection which ranges from physical and cognitive abnormalities to functional limitations, exercise impairments and deterioration of quality of life.9,10 A massive number of humans suffered from multi-organ impairments resulting from wide distribution of angiotensin converting enzyme2 (ACE-2) receptors in extra-pulmonary tissues.11,12 The pulmonary and cardiovascular systems are the most important impacted organs with their reflection on patient’s pulmonary function, functional capacities, physical activities, and quality of life. Similar coronavirus infection (SARS-CoV) caused impairments for two years after infection which are expected to occur for the survivors of COVID-19.13 COVID-19 causes marked impairments in the diffusing lung capacity for carbon monoxide (DLCO), total lung capacity, forced expiratory volume in one second and forced vital capacity ratio FEV1/FVC ratio, in addition, restrictions in small airways,14–16 restrictive and obstructive patterns of the pulmonary function,15 low quality of life15,16 consolidation patterns with multifocal ground-glass opacities in computed tomography scans,17 restrictions in both the 2MWT and FVC,17 respiratory muscles dysfunction and lung fibrosis,18,19 in addition to formation of pneumocytes.20 Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) are the two previous viral infection outbreaks like the current COVID-19.20 Abnormalities of the lung function are classified according to the American Thoracic Society as: normal, if both FVC and the FEV1/FVC ratio are in the normal range; obstructive pattern, if FEV1/FVC ratio is <70% of the normal predicted value and FEV1 <80% of the predicted; restrictive pattern, if FEV1/FVC ratio is ≥70% of the normal predicted value, and the total lung capacity <80% of the predicted value. If total lung capacity is not available, a reduction in the FVC <80% of predicted is considered as a restrictive pattern, small airway disease, if forced expiratory flow between 25% and 75% of FVC (FEF25-75%) is <65% of predicted value.21 COVID-19 patients with cardiovascular and pulmonary comorbidities are more vulnerable to hospitalization,22,23 and for developing neurological events, e.g., acute cerebrovascular disease, conscious disturbance, and skeletal muscle injury.19 Even though vaccination against COVID-19 can prevent hospitalization and severe infection. It has been adequate protection only against some long-COVID-19 symptoms, including cognitive dysfunction, sleeping disorders, and kidney diseases.24\n\nEven after recovery of survivors of COVID-19, almost 10-20% may suffer long-term consequences including fatigue, dyspnea, and impairments in both cognitive and daily functions.7 Also, COVID-19 patients may be complicated with bladder dysfunction, severe urinary symptoms,25–27 higher liver enzymes,28 gastrointestinal symptoms,29 psychotic disorders30 and poly-neuromyopathy.31 However, there were restrictions in the physical performance, physical activities, and impairments in sleep quality detected at 12 weeks post-COVID-19 infections.32 Although time of walk improved significantly at the sixth month it still reduced on comparison with time of walk spent before COVID-19 for the same patients,33 also, the physical activities and the one-minute standing test were impaired at discharge of patients with COVID-19.34 Evidence of persistent physiological and radiographic changes is available in most patients who recovered from severe COVID-19, exercise capacity and dyspnea score improved over time to 12 months.35 Patients with persistent dyspnea had several abnormalities during the 6MWT e.g., greater restriction on spirometry, reduced functional capacity, and increased exertional symptoms.36 As a result of variations in epidemiology and treatments for long-term sequels of COVID-19, it is considered as a new area of research.7,37,38 There is need for more studies to investigate effects of COVID-19, particularly the long-term impact on the lungs and its reflections on the pulmonary function, physical activities, and functional capacities. The authors mainly concentrated on investigating hospitalized survivors and who experienced severe infection.19,39–41 Non-severe COVID-19 survivors might be ignored during the pandemic so; further research was recommended particularly for those patients with mild and moderate degree of COVID-19 after recovery time.32,33 Therefore, the current study aimed to investigate long-term effect of COVID-19 on pulmonary function, physical activities, and functional capacities in patients with non-severe degree after three months from recovery time in addition, evaluating time effect on the associated consequences.\n\n\nMethods\n\nA cross-section study.\n\nThe sample size was calculated by using an online tool (http://www.stat.ubc.ca/~rollin/stats/ssize/n2a.html). It was based on the FEV1% (μ1 = 94.2, μ2 = 100.3, sigma = 13.1, and SD = 13.1 in the previous study.42 The significant value is 0.05 with a power of.80.\n\nEthical approval\n\nAll procedures of the study were approved by the Ethics Research Committee of the Institutional Review Board of Imam Abdualrahman bin Faisal University (IRB-PGS-2021-03-427). Also, by the Research Ethics Committee in Qurayyat Health Affairs, Ministry of Health, Project no: 083, Saudi Arabia. This study was conducted in accordance with the Declaration of Helsinki at the out-patient clinic of the Physical Therapy Department of King Abdulaziz Specialist Hospital in Sakaka Aljouf, Ministry of Health- Saudi Arabia between September 2021 to June 2022. Prior to participation, all participants signed a consent form, and they were informed that the collected data would be submitted for publication.\n\nSubjects\n\n600 participants were screened from out-patient clinic of the Physical Therapy Department of King Abdulaziz Specialist Hospital in Sakaka Aljouf including COVID-19 group: 80 male and female patients (based on external examination of body characteristics) with confirmed non-severe COVID-19 at least 3 months from recovery time. Recovery is being free from fever and respiratory symptoms for at least 3 days followed by two negative polymerase chain reaction (PCR) tests 24 hours apart, or if PCR was not available, resolution of the clinical manifestations for 3 days and at least 10 days have passed from the appearance of the first symptom.43 Matched Group: 80 male and female matched individuals (non-infected with COVID-19, their PCR was negative for COVID-19, no signs or symptoms of infection) who were invited to participate as control group.\n\nInclusion criteria\n\nMale and female patients who diagnosed with non-severe COVID-19 at least after three months from recovery time and matched non-infected with COVID-19 participants, their age range from 25 to 55 years.\n\nExclusion criteria\n\nAll participants including non-infected individuals with COVID-19 and patients with COVID-19, acute infections, recent surgeries, unstable cardiovascular conditions, chronic respiratory diseases, neurological disease, mental illness, critically ill patients with intubation any other medical condition that contradict conduction of this research, who cannot walk, and smokers were excluded.44–46\n\nDemographic data were recorded including weight, body mass index (BMI), oxygen saturation, heart rate, blood pressure, comorbidities, admission to the intensive care unit or hospitalization, severity degree of infection according to the classification of WHO progression scale.47 This scale classifies severity of COVID-19 infection into five categories: 1-Uninfected with a 0 score, 2- Mild disease with a score ranging from 1-3, 3-Moderate disease with a score ranging from 4-5, 4-Severe disease with a score ranging from 6-9, and 5-Dead with score 10.\n\nAll participants underwent these outcome measures:\n\na) Pulmonary function was measured by using the Spirobank II spirometer (MIR www.spirometry.com). It is a validated device used for diagnosing and evaluating pulmonary diseases.48 All participants underwent the test according to guidelines of the American Thoracic Society and European Respiratory Society (ATS/ERS).46 The obtained parameters are FVC, FEV1, FEV1/FVC ratio, FEF 25-75%, and peak expiratory flow (PEF). All measurements of pulmonary function testing (PFT) were expressed as absolute and percentage of predicted normal values (% predicted), the percentage of predicted normal values was calculated automatically based on age, sex, height, and ethnicity.49 Each participant completed three accepted maneuvers and the highest value was recorded and used in the statistical analyses.\n\nb) Physical activity was measured by using the International Physical Activity Questionnaire (IPAQ- Arabic version) which is valid and reliable.50 It assesses physical activity during the last seven days throughout four domains: work-related physical activity, transportation-related physical activity, domestic and yard, and leisure time physical activity. Every participant was asked to answer each question in all domains. The scores are calculated for each domain and expressed as metabolic equivalent minutes per week (MET-minutes/week). The total physical activity score is calculated by summating the total scores for all domains, the physical activity score is classified into high, moderate, and low as 3000,600 and <300 MET-minutes/week respectively.51\n\nc) Functional capacity was measured by using the 6MWT: It is valid and reliable, and it has been approved to estimate sub-maximal exercise performance, daily physical activities,52 physical endurance in older adults53–55 and post-COVID-19 patients over 18 years.39 Each participant was asked to walk independently on flat ground in 30-meters space for 6 minutes as fast as possible without oxygen inhalation, the results were expressed in meters.52\n\nd) Pulse oximeter is a valid and reliable device that was used to detect oxygen saturation and heart rate for every participant during 6MWT.56\n\ne) Modified Borg scale of dyspnea is a scale rated from 0 to 10. It was used to monitor severity of self-reported breathlessness during 6MWT.57\n\nThe collected data were analyzed using SPSS statistical software (version 25) and were tested for normality using Shapiro Wilk’s test. Group comparisons were done using independent t-test or Mann–Whitney test for data that had normal and abnormal distribution respectively. The Chi-squared test was used to compare the categorical variables. The COVID-19 group was divided into pre - and post 6-months sub-groups to determine time effect on the associated consequences whereas the Kruskal- Wallis’s test (Pairwise comparison) and one way ANOVA (post hoc tests) were used to determine the significant differences among three groups. Statistical significance was set at P-value <0.05 with a confidence interval of 95%.\n\n\nResults\n\n80 male and female patients with confirmed diagnosis of COVID-19 (COVID group), and another 80 matched participants non-infected with COVID-19 (Matched group) were recruited in this study (Figure 1). Demographic and clinical characteristics of both groups including age, sex, BMI, and comorbidities were matched (P-value > 0.05), (Table 1). There were significant differences in oxygen saturation between both groups (P-value = 0.003), 30 patients (37.5%) had comorbidities. The most common co-morbidities were obesity (31.25%), hypertension (2.5%) & diabetes (3.75%). Severity of infection was 32 patients (40%) with mild and 48 patients (60%) with moderate, 25 patients (31%) had restrictive pattern, and 13 participants (16%) in matched group, (P-value = 0.026), 17 patients (21%) with dyspnea & 48 patients (60%) were hospitalized (Table 1).\n\na Chi-squared.\n\nb Mann–Whitney test.\n\n† Non-significantly differences (P-value > 0.05).\n\n* Significantly differences (P-value < 0.05).\n\nAfter 3 months from time of recovery the results of pulmonary function tests show significant reductions in mean values of FVC%, FEV1%, FEV1/FVC Ratio%, FEF25-75%, and PEF% in COVID-19 group on comparison with matched group (P-value <0.05) (Table 2). Also, mean values of distance of 6MWT and four domains of physical activity including work, transportation, domestic & yard, and leisure & free time reduced significantly in COVID-19 group on comparison with matched group (P-value < 0.05) (Table 2).\n\nb Mann Whitney test was used to determine significant differences in abnormal distributed variables.\n\nc Independent t-test was used to determine significant differences in normal distributed variables.\n\n* Significantly difference P-value < 0.05. FEF25-75% of pred: forced expiratory flows at 25-75% of FVC percentage of predicted, FEV1% of pred: Forced expiratory volume in the first second percentage of predicted, FEV1/FVC% of pred: forced expiratory volume in the first second and forced vital capacity ratio percentage of predicted, FVC% of pred: forced vital capacity percentage of predicted, PEF% of pred: peak expiratory flow percentage of predicted, 6MWT: Six minute walking test. IPAQ: international physical activities questionnaire, PA: physical activity.\n\nThe COVID-19 group was divided pre and post 6 months into two sub-groups to investigate the time effect on post-COVID-19 consequences. On comparison of pulmonary function and four domains of the IPAQ the results of the Kruskal-Wallis’ test show significant differences among three groups (P-value <0.05) except the predicted PEF% (P-value = 0.057) (Table 3), also the results of one-way ANOVA test show significant differences in distance of the 6MWT among three groups (P-value = 0.01) (Table 3).\n\nd Kruskal Wallis test detects significant differences among three groups for abnormal distributed variables.\n\ne One way ANOVA tests significant differences among three groups for normal distributed variables.\n\n* Significantly difference P-value < 0.05.\n\n† Non significantly difference P-value > 0.05.\n\nThe pairwise comparisons for pulmonary function and domains of the IPAQ in addition the post hoc tests for the 6MWT distance show significant differences on comparison of pre 6 months sub-group with matched group (P-value < 0.05) except the predicted PEF% (P-value = 0.057), and domestic & yard domain (P-value = 0.17) (Table 4), while on comparison of the post 6 months sub-group with matched group the pairwise comparison and post hoc tests show significant differences in mean values of pulmonary function, 6MWT in addition only the both physical activity of domestic & yard and physical activity of leisure time domains of the IPAQ (P-value < 0.05) (Table 5). In addition, there were non-significant differences between the pre-6 and post-6 months sub-group in all outcome measures (P-value > 0.05).\n\nf The Pairwise comparison significant differences among three groups for abnormal distributed variables.\n\ng Post hoc tests showed significant differences among three groups for normal distributed variables.\n\n* Significantly difference P-value < 0.05.\n\n† Non significantly difference P-value > 0.05.\n\nf The Pairwise comparison show significant differences among three groups for abnormal distributed variables.\n\ng Post hoc tests show significant differences significant differences among three groups for normal distributed variables.\n\n* Significantly difference P-value < 0.05.\n\n† Non significantly difference P-value > 0.05.\n\n\nDiscussion\n\nCOVID-19 is a new rapidly spreading epidemic, its initial symptoms may progress to long-term consequences. Results of the current study indicate that post-COVID-19 patients may experience chest abnormalities including reductions in pulmonary function, decreased functional capacity, and physical activities up to one year after recovery time. Sights of researchers were attracted to investigate them all over the world. Our findings agree with the results of Abdallah et al, Lorent et al & Salem et al they found significant reductions in mean values of FVC, FVC% predicted, FEV1, PEF, PEF% predicted at the third month of recovery on comparison with matched participants.40,58,59 Restrictive pattern of impairments was observed in 50% of COVID-19 patients’ sample of Salem et al.40 while it was 31% in the current study. A greater percent of restrictive pattern in findings of Salem et al.40 may be due to their patients’ sample was COVID-19 patients with pneumonia or hospitalized (more complicated), whereas the current patients’ sample was selected with mild or moderate degree of infection. The current findings of pulmonary function are consistent with the findings of previous studies. Salem et al found significant reductions in pulmonary function of the survivors of COVID-19 after three months of discharge on comparison with matched controls.40 Also, Abdallah et al. found reductions in the measured FVC, total lung capacity (TLC), and DLCO at the third month in hospitalized patients with severe COVID-19.58 In contrast to our results the findings of Lerum et al. show normal pulmonary outcomes including lung function, 6MWT distance, oxygen saturation, dyspnea prevalence measured at the third month after hospital discharge.60 Also, Eksombatchai et al. found non-significant differences in the pulmonary function of mild and moderate survivors COVID-19 with pneumonia.61 The authors highlighted the absence of PFT data for their patients’ samples prior to occurrence of COVID-19.40,62\n\nThe underlying mechanisms for COVID-19 multiple findings may be due to acute lung injury with diffuse alveolar damage which is associated with fibrotic changes and microthrombi in the pulmonary vasculature.63 The restrictive impairment of the lung function may be caused by fibrotic changes in the lung and increase proinflammatory cytokines which recruit fibroblasts resulting in lung fibrosis.64 The decline in pulmonary function results from the respiratory muscles fatigue as a significant improvement of PFT after pulmonary rehabilitation for COVID-19 survivors,65 the results of PFT are also influenced by several factors e.g., sex and body type.66\n\nOur findings show significant reductions in measured parameters of pulmonary function, 6MWT distance and domains of physical activities in patients with COVID-19 after 3 months, pre 6 months and post 6 months on comparison with the matched group. There are progressive improvements on comparison of pre with post 6 months as a time effect and being non-significant may be due to patients’ sample of pre 6 months was not the same patients’ sample of post 6 months. The current results are consistent with findings of Magdy et al. determined lower limits in lung function (<80%) and non-statistically significant differences in the pulmonary function at 3 and 6 months post-infection.67 whereas existing significant improvements at one year follow-up.59 This finding does not contradict with our results as they compared the same patients at 3 months, 6 months and after one year not the case in the current study where the patients’ sample was compared at 3 months, pre 6 months and after 6 months to matched control. Also, Zhang et al. found 20% of the survivors of COVID-19 had FEV1/FVC below 70% of predicted values at the eighth month.62\n\nThe current results contradict the findings of Wu et al. as they found significant increases in pulmonary function at 3, 6, 9 and 12-month interval measures post-infection (time effect)35 this may be also due to the authors did interval assessments for the same COVID-19 patients. They found high rate of dyspneic patients (81%) measured at the third month whereas it was 21% in the current study. This may be their sample included only severe COVID-19 patients whereas the sample in the current study included both mild and moderate degree of COVID-19. Also, Madrid-Mejía et al. determined improvements in PFTs at the sixth month of infection compared to the results of the same participants at the third month after infection.68 The variations in the time of evaluation in different studies may explain the differences in the results.15,40,69\n\nIn our study, despite the result of the functional capacities (6MWT distance) show significant reductions in the COVID-19 group after 3 months, pre and post 6 months from recovery on comparison with the matched control, there are non-significant increases at both pre and post 6 months. This finding is consistent with the results of Magdy et al. who determined significant reductions in the 6MWT results of the survivors of COVID-19 on comparison with the normative data,40 whereas a significant improvement was determined in the 6MWT at the sixth month in regarding the third-month follow-up.40 They referred their findings to the extended period of hospital stay and extra usage of corticosteroids which could influence the muscles resulting in muscle wasting and myopathy.40,70,71 also, Calabrese et al. demonstrated significant reductions in the FVC %, DLCO, low oxygen saturation (SpO2) (>90%) during the 6MWT with higher dyspnea.41 In addition, Raman et al. found significant reductions in the distance of the 6MWT for COVID-19 patients on comparison with controls.72 They referred this limited exercise capacity to muscle wasting that caused by the catabolic state resulting from severe illness, and potentially inflammation.72–74 While Abdallah et al. reflected the persistence of breathlessness and limitation in exercise capacity at the third month to the residual defects in TLC.58 In addition, the recovery of the physical function within the first 6 months of patients after SARS-COV was incomplete as it lasts for one to two years.13 In addition, Magdy et al. found significant increases in the 6MWT distance at the 6-month follow-up.67 Accordingly, the lower results of the 6MWT distance may be attributed to the higher BMI, and high number of female participants in the current study. The distance of the 6MWT is negatively influenced by sex and body type.52 On contrary to the current findings Wu et al determined significant improvements in the 6MWT at 3-, 6-, 9-, and 12-month interval measures post-infection.35\n\nOur results agree with the findings of Belli et al. they found patients with COVID-19 suffer from impairments in physical functions and fitness, as 33.3% of patients had impaired physical fitness, and 17.5% with moderate scores in activities of daily livings performance.75 Cao et al. also stated that performance in the 6MWT was significantly lower in post COVID-19 patients than in health controls.76 Lower performance in the 6MWT was reported in patients with severe/critical COVID-19 compared to patients with mild/moderate disease at baseline.77 On contrary to the results of the current study the findings of Lerum et al. they concluded non-significant differences in the results of the 6MWT between ICU and non-ICU groups and Eksombatchai et al. they found statistically typical results for the 6MWT among three groups, while the severe infection group showed lower results when compared with the mild and moderate infection groups but not statistically significant.60,61 The results of oxygen saturation show non- significant differences (p = 0.201) among groups for both pre and post 6MWT. They referred the reductions in their results to the higher BMI and older age in the severe group.\n\nIn the current study, the results of the IPAQ significantly reduced in all domains in the COVID-19 survivors’ group on comparison with the matched group after 3 months. The current findings are supported with the results of Tanriverdi et al. found poor physical activities and impaired hand grip power at least three months of survivors of COVID-19.32 Paneroni et al. who determined impaired physical activities at the discharge time.34 As a result of improvements in physical activities with time effects on comparing survivors of COVID-19 of pre and post 6 months with the matched controls, significant differences were determined in some IPAQ domains. Also, the current findings supported the findings of Delbressine et al. who found significant improvements in physical activities in the survivors of COVID-19 at the sixth month compared with results at the third month post-infection.33 In the current study, the IPAQ questionnaire was used to assess the physical activities during the last seven days only, which may not give an accurate perception of the physical activities as it could be affected by other factors e.g., the work domain could be lower for some participants because they were on vacation for the last seven days. The transportation domain may be lower for some patients because they must use vehicles due to the hot weather. Some participants did not have gardens or backyards, which reduces their domestic and yard scores. Other participants may have lower leisure time domain scores because they did not feel well to walk or did exercise during the last seven days in convalescent stage. Although results of outcome measures show significant reductions in pulmonary function, physical activities, and functional capacity after 3 months, pre 6 months and post 6 months on comparison to matched participants there are general progressive improvements as time effects but in comparison with matched control still need extended health care and prescribed proper rehabilitative training programs whatever severity of infection or history of hospitalization.\n\nThere was a lack of data on health conditions of patients prior to contracting COVID-19 so the authors tried to overcome this limitation by including a matched control group, small sample size, usage of simple spirometry approach, lack of DLCO and plethysmography. Despite these limitations, the authors believe that the results of this study contribute to filling a significant knowledge gap about consequences of COVID-19 after 3 months of recovery time.\n\nFurther studies to investigate effectiveness of COVID-19 long-term complications and follow-up for patients with different severity of infections and effectiveness of individualized comprehensive rehabilitative programs for such patients.\n\n\nConclusion\n\nPulmonary function, functional capacities, and physical activities are negatively influenced by COVID-19 as long-term consequences indicating the need for extended health care, and proper rehabilitative training programs for those patients whatever the severity degree of infection or history of hospitalization. Gaining the deepest knowledge that enables physical therapists to tailor the appropriate rehabilitative training program for such patients.",
"appendix": "Data availability\n\nFigshare: Sensory perception, https://doi.org/10.6084/m9.figshare.23153540.v1. 78\n\nThis project contains the following underlying data:\n\n- BASE DE DATOS EVALUACIÓN SENSORIAL 24 05 2023.xls (Data for tastings carried out with students. The samples were 4 cereal bars made with cereal grains and with different percentages of ant flour.)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgement\n\nThe authors would like to thank the Head of the Physical Therapy Department, Dean of scientific research in IAU, the Ministry of Health, Aljouf health affairs, and King Abdul-Aziz Specialist Hospital. 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Publisher Full Text\n\nGiannitsi S, Bougiakli M, Bechlioulis A, et al.: 6-minute walking test: a useful tool in the management of heart failure patients. Ther. Adv. Cardiovasc. Dis. 2019; 13: 175394471987008. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHolland AE, Spruit MA, Troosters T, et al.: An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur. Respir. J. 2014; 44(6): 1428–1446. PubMed Abstract | Publisher Full Text\n\nGraham BL, Steenburggen I, Miller MR, et al.: Standardization of spirometry 2019 update. An official American thoracic society and European respiratory society technical statement. Am. J. Respir. Crit. Care Med. 2019; 200(8): e70–e88. Publisher Full Text\n\nMarshall J, Murthy S, Diaz J, et al.: A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect. Dis. 2020; 20(8): e192–e197. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDegryse J, Buffels J, Van Dijck Y, et al.: Accuracy of office spirometry performed by trained primary-care physicians using the MIR Spirobank hand-held spirometer. Respiration. 2012; 83: 543–552. Publisher Full Text\n\nQuanjer P, Stanojevic S, Cole T, et al.: (Mult)i-ethnic reference values for spirometry for the 3–95-yr age range: the global lung function 2012 equations. Eur. Respir. J. 2012; 40(6): 1324–1343. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHelou K, El Helou N, Mahfouz M, et al.: Validity and reliability of an adapted Arabic version of the long international physical activity questionnaire. BMC Public Health. 2018; 18(1): 1–8. Publisher Full Text\n\nThe IPAQ Group: Guidelines for data processing and analysis of the international physical activity questionnaire (IPAQ) - short and long forms.2005. Reference Source\n\nAmerican Thorax Society Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories: ATS statement: Guidelines for the six-minute walk test. Am. J. Respir. Crit. Care Med. 2002; 166(1): 111–117. Publisher Full Text\n\nEnright PL: The six-minute walk test. Respir. Care. 2003; 48(8): 784–785.\n\nRikli R, Jones C: The reliability and validity of a 6-minute walk test as a measure of physical endurance in older adults. J. Aging Phys. Act. 1998; 6(4): 363–375. Publisher Full Text\n\nEnright PL, Sherrill DL: Reference equations for the six-minute walk in healthy adults. Am. J. Respir. Crit. Care Med. 1998; 158(5): 1384–1387. Publisher Full Text\n\nBuekers J, Theunis J, De Boever P, et al.: Wearable finger pulse oximetry for continuous oxygen saturation measurements during daily home routines of patients with chronic obstructive pulmonary disease COPD over one week: observational study. JMIR Mhealth Uhealth. 2019; 7(6): e12866. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKendrick K, Baxi S, Smith R: Usefulness of the modified 0-10 borg scale in assessing the degree of dyspnea in patients with COPD and asthma. J. Emerg. Nurs. 2000; 26(3): 216–0222. PubMed Abstract | Publisher Full Text\n\nAbdallah S, Voduc N, Corrales-Medina V, et al.: Symptoms, pulmonary function, and functional capacity four months after COVID-19. Ann. Am. Thorac. Soc. 2021; 18(11): 1912–1917. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLorent N, Weygaerde YV, Claeys E, et al.: Prospective longitudinal evaluation of hospitalised COVID-19 survivors 3 and 12 months after discharge. ERJ Open Res. 2022; 8(2): 00004–02022. Publisher Full Text\n\nLerum TV, Aaløkken TM, Brønstad E, et al.: Dyspnoea, lung function and CT findings 3 months after hospital admission for COVID-19. Eur. Respir. J. 2021; 57(4): 2003448. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEksombatchai D, Wongsinin T, Phongnarudech T, et al.: Pulmonary function and six-minute-walk test in patients after recovery from COVID-19: a prospective cohort study. PLoS One. 2021; 16(9): e0257040. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang S, Bai W, Yue J, et al.: Eight months follow-up study on pulmonary function, lung radiographic, and related physiological characteristics in COVID-19 survivors. Sci. Rep. 2021; 11(1): 1–13.\n\nHaft JW, Atluri P, Ailawadi G, et al.: Adult cardiac surgery during the COVID-19 pandemic: a tiered patient triage guidance statement. J. Thorac. Cardiovasc. Surg. 2020; 160(2): 452–455. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcDonald LT: Healing after COVID-19: are survivors at risk for pulmonary fibrosis? Am. J. Physiol. Lung Cell. Mol. Physiol. 2021; 320: L257–L265. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu K, Zhang W, Yang Y, et al.: Respiratory rehabilitation in elderly patients with COVID-19: a randomized controlled study. Complement. Ther. Clin. Pract. 2020; 39(101166): 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTalaminos Barroso A, Márquez Martín E, Roa Romero LM, et al.: Factors affecting lung function: A Review of Literature. Archivos de Bronconeumología (English Edition). 2018; 54(6): 327–332. Publisher Full Text\n\nMagdy DM, Metwally A, Tawab DA, et al.: Long-term COVID-19 effects on pulmonary function, exercise capacity, and health status. Ann. Thorac. Med. 2022; 17(1): 28. Publisher Full Text\n\nMadrid-Mejía W, Gochicoa-Rangel L, Padilla P, et al.: Improvement in walking distance lags raise in lung function in post-COVID-19 patients. Arch. Bronconeumol. 2022; 58(3): 261–263. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTorres-Castro R, Vasconcello-Castillo L, Alsina-Restoy X, et al.: Respiratory function in patients post-infection by COVID-19: a systematic review and meta-analysis. Pulmonology. 2020; 27(4): 328–337. Publisher Full Text\n\nLau HMC, Lee EWC, Wong CNC, et al.: The impact of severe acute respiratory syndrome on the physical profile and quality of life. Arch. Phys. Med. Rehabil. 2005; 86(6): 1134–1140. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOng KC, Ng AK, Lee LU, et al.: Pulmonary function and exercise capacity in survivors of sever acute respiratory syndrome. Eur. Respir. J. 2004; 24(3): 436–442. PubMed Abstract | Publisher Full Text\n\nRaman B, Cassar MP, Tunnicliffe EM, et al.: Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. Eclinicalmedicine. 2021; 31: 100683. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHerridge MS, Tansey CM, Matte A, et al.: Functional disability 5 years after acute respiratory distress syndrome. N. Engl. J. Med. 2011; 364(14): 1293–1304. Publisher Full Text\n\nHaddad F, Zaldivar F, Cooper DM: IL-6-induced skeletal muscle atrophy. J. Appl. Physiol. 2005; 98(3): 911–917. Publisher Full Text\n\nBelli S, Balbi B, Prince I, et al.: Low physical functioning and impaired performance of activities of daily life in COVID-19 patients who survived hospitalisation. Eur. Respir. J. 2020; 56(4): 2002096. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCao J, Zheng X, Wei W, et al.: Three-month outcomes of recovered COVID-19 patients: Prospective observational study. Ther. Adv. Respir. Dis. 2021; 15: 175346662110094. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAnastasio F, Barbuto S, Scarnecchia E, et al.: Medium-term impact of COVID-19 on pulmonary function, functional capacity, and quality of life. Eur. Respir. J. 2021; 58: 2004015. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLozada-Urbano M, Bendezu Ccanto J, Rivera-Lozada O: Sensory perception. Dataset. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "186229",
"date": "16 Aug 2023",
"name": "Ashraf Abdelaal Mohamed Abdelaal",
"expertise": [
"Reviewer Expertise Physiotherapy for cardiovascular/pulmonary disorders and geriatrics",
"cardiopulmonary rehabilitation."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis cross-sectional study investigated the long-term effect of mild-moderate COVID-19 infection on the pulmonary, functional capacity and physical activities variables in patients living in Sakaka Aljouf Saudi Arabia. 160 participants of both genders were allocated to either: group-I that included 80 non-severe COVID-19 patients at least 3 months after the recovery time, and group-II that included 80 healthy matched participants.\nEvaluations of the pulmonary variables (using the spirometer), the physical capacity (using the six-minute walk test), and the physical activities variables (using the International Physical Activity Questionnaire) were done for both groups.\nResults showed significantly reduced pulmonary, functional capacity and physical activities levels (at least 3-months post-Covid-19 recovery) in patients affected with COVID-19 (group-I) compared with healthy matched participants (group-II).\nAbstract:\nBackground:\n“Personal performance”: better to change it to “physical performance”.\n\nResults: “The results show significant differences in…”, please provide the means and SD as well as p-values.\nConclusion:\nThe sentence “whatever their severity degree of infection or history of hospitalization”: It is better to modify this sentence or remove it since the current study is limited to mild-moderately affected patients and did not provide full details regarding the history of hospitalization.\n\nThe sentence “reflections of the current results raise awareness for physical therapists to tailor the proper rehabilitative training programs for such patients”: it is better to add “on long term-basis” at the end of the sentence.\n\nIntroduction:\nAbbreviations (e.g., 2MWT, FVC and so on) need to be written first in full term, then to be abbreviated after that within the text.\n\nMethods:\nInclusion criteria:\nPlease provide more details about the Non-sever COVID-19 as it is the main inclusion criteria (at least add “who diagnosed with mild-moderate COVID-19).\n\nExclusion criteria:\nIt is better to remove or modulate the sentence of “All participants including non-infected individuals with COVID-19” since the study included non-infected healthy matched group.\n\nProcedure of the study:\nPlease provide the full details (version, model, manufacture) of the used instrument to evaluate the Pulmonary function.\n\nPlease provide more clarification/details about the differences between (at least 3-months post-COVID-19 recovery), (pre 6-months), (post 6-months).\n\nResults:\nWere there correlations between the severity and duration post COVID-19 infection on one hand and the evaluated variables on the other hand?\n\nThe word “sex” is better to be replaced with “gender”.\n\nIn table 4 and 5; please provide the numbers of participants in each group.\n\nDiscussion:\nPlease correct the following sentence: “Results of the current study indicate that post-COVID-19 patients may experience chest abnormalities including reductions in pulmonary function, decreased functional capacity, and physical activities up to one year after recovery time”. Since the average post COVID-19 duration of this study is 7.9 months.\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": "10106",
"date": "28 Mar 2024",
"name": "ALSAYED SHANB",
"role": "Author Response",
"response": "Comments of reviewer one: Abstract Background: “Personal performance”: better to change it to “physical performance”. Author Response: Personal performance was changed to physical performance. Results: “The results show significant differences in…”, please provide the means and SD as well as p-values. Author Response: The means and SD as well as p-values were added. Conclusion: The sentence “whatever their severity degree of infection or history of hospitalization”: It is better to modify this sentence or remove it since the current study is limited to mild-moderately affected patients and did not provide full details regarding the history of hospitalization. The sentence “reflections of the current results raise awareness for physical therapists to tailor the proper rehabilitative training programs for such patients”: it is better to add “on long term-basis” at the end of the sentence. Author Response: The sentence “whatever their severity degree of infection or history of hospitalization was removed. On long term-basis was added at the end of the sentence. Introduction: Abbreviations (e.g., 2MWT, FVC and so on) need to be written first in full term, then to be abbreviated after that within the text. Author Response: Abbreviations (e.g., 2MWT, FVC and so on) were done. Methods: Inclusion criteria: Please provide more details about the Non-sever COVID-19 as it is the main inclusion criteria (at least add “who diagnosed with mild-moderate COVID-19). Author Response: The patient sample was selected by pulmonologist. The severity of the infection was classified according to the WHO regression scale (Marshall et al., 2020). The scale classifies the severity of COVID-19 infection into five categories: 1-uninfected with a 0 score, 2- a mild disease with a score ranging from 1-3, 3- a moderate disease with a score ranging from 4-5, 4- a severe disease with a score ranging from 6-9, and 5- dead with score 10. Exclusion criteria: It is better to remove or modulate the sentence of “All participants including non-infected individuals with COVID-19” since the study included non-infected healthy matched group. Author Response: Patients with COVID-19 who cannot walk, acute infections, recent surgeries. Procedure of the study: Please provide the full details (version, model, manufacture) of the used instrument to evaluate the Pulmonary function. Author Response: Medical international research Manufacturer’s address: MIR S.p.A. - Medical International Research via del Maggiolino, 125 00155 ROME (ITALY) Tel + 39 0622754777 Fax + 39 0622754785 Web site: www.spirometry.com Email: mir@spirometry.com MIR USA, Inc. 5462 S. Westridge Drive New Berlin, WI 53151 - USA Tel + 1 (262) 565 – 6797 Fax + 1 (262) 364 – 2030 Web site: www.spirometry.com Email: mirusa@spirometry.com https://spirometry.com/en/products/spirobank-ii-basic Please provide more clarification/details about the differences between (at least 3-months post-COVID-19 recovery), (pre 6-months), (post 6-months). Author response: The covid group was selected at least 3 months from recovery after that they are classified into two groups, pre 6 months, & post 6 months after recovery time. Results: Were there correlations between the severity and duration post COVID-19 infection on one hand and the evaluated variables on the other hand? The word “sex” is better to be replaced with “gender”. In table 4 and 5; please provide the numbers of participants in each group. Author Response: The spearman's correlation with the severity of infection showed that positive correlation between 6 MWT physical activity transportation, and physical activity domestic &yard (r= 0.005 &0.03 respectively also presence of positive correlation between FEFa & FEF 25-75 (r= 0.042) , While the results show negative correlation BMI & physical activity transportation & leisured and free time (r= 0.015 &0.012) respectively whereas presence of positive correlation between 6MWT & FEV1 (r= 0.014). In addition to time factor the results show negative correlation between BMI & both physical activity of work and transportation (r= 0.015&0.027 and 0.001&0.046) in pre 6 months and post 6 months subgroup respectively . The number of patients was written in the statistical part pre-6 months (30patients) and post 6-months(50 patients) sub-groups The word “sex” was replaced with “gender”. Discussion: Please correct the following sentence: “Results of the current study indicate that post-COVID-19 patients may experience chest abnormalities including reductions in pulmonary function, decreased functional capacity, and physical activities up to one year after recovery time”. Since the average post COVID-19 duration of this study is 7.9 months. Author Response: Results of the current study indicate that post-COVID-19 patients may experience chest abnormalities including reductions in pulmonary function, decreased functional capacity, and physical activities within the average time 7.9 months after recovery Thanks for your valuable comments."
}
]
}
] | 1
|
https://f1000research.com/articles/12-809
|
https://f1000research.com/articles/11-648/v1
|
13 Jun 22
|
{
"type": "Research Article",
"title": "Assessment of heavy metals in food and drug packaging materials",
"authors": [
"Senna Mukhi",
"Rukmini M. S.",
"Poornima Ajay Manjrekar",
"Reghupathi Iyyaswami",
"Sindhu H.",
"Senna Mukhi",
"Poornima Ajay Manjrekar",
"Reghupathi Iyyaswami",
"Sindhu H."
],
"abstract": "Background: Food and drug packaging materials are an integral part of our everyday life. Noxious elements can inadvertently be included in packaging materials in various stages of their production. Adulterants, adhesives, colorants and heavy metal interference are the common sources of contamination in food packaging materials. Heavy metal toxicity has far-reaching ill effects on living organisms. The present study aimed at qualitatively and quantitatively analysing heavy metal contamination of various materials that are used for food and drug packaging in India. Methods: The qualitative detection was done by rapid assay and heavy metals were quantified with the help of inductively coupled plasma-optical emission spectrometry (ICP-OES). A total of 13 types of food and drug packaging materials were procured from local market and analysed for four heavy metals viz. arsenic (As), vanadium (V), mercury (Hg) and cadmium (Cd). The concentration of each heavy metal in the samples was compared with permitted values published by the European Council. Results: Of the 13 samples, heavy metals were qualitatively detected in 10 samples. ICP-OES values for quantitative estimation showed presence of heavy metal above permissible range in 10 of the studied samples for vanadium, all samples for arsenic, two samples for mercury and one sample for cadmium. Arsenic was found to be the commonest heavy metal contaminant, present in 13 samples above permissible limit. Conclusions: The significantly higher concentration of heavy metal poses a potential health risk to the consumer and affects the quality of the food.",
"keywords": [
"Drug",
"Food",
"Heavy Metal",
"ICP-OES",
"Packaging Material"
],
"content": "Introduction\n\nPackaging materials are defined as any substance or item that comes in contact with food and drug including containers, cans, bottles, cartons, boxes, cases and covering material such as foil, film, metal, paper, wax paper or cloth.1 The main objective of packaging is to provide protection from foreign materials while in-transit and help in maintaining the shelf life of food products. Packaging is a field combining science and technology used for protecting products during distribution, storage, sale and use. It can also be applied to the procedure of evaluating, designing and manufacturing a packed item. Storage and preservation instructions, directions for use, expiry or use by date, and design of packaging materials among others are crucial information which give cognoscibility to the brand and increase the visibility on the shelf.2,3\n\nAll the above processes result in migration of additives, adulterants and toxins such as colourants and adhesives from packaging material into the food, as shown by previous research.4–6 Leaching can be explained as any process that allows transfer from surface to the core particles.7 With reference to food packaging, the term “leaching” can be defined as the movement of undesirable particles from packaged materials to the packaged particle. The European Council Standard requires that various contaminants like aromatic amines, benzophenones, polyaromatic hydrocarbons, plasticizers and heavy metals be controlled and analyzed in food packages.8 Heavy metals are a huge source of environment pollution.9 The toxicity of heavy metals has harmful effects on biological systems as they do not undergo biodegradation. They accumulate in living organisms, causing several diseases and disorders even when present in very low concentrations.10\n\nThe toxic effects of vanadium are particularly seen in lung and stomach tissues, resulting in pneumonia, bronchitis and breach in the gastric mucosal lining.11 Increased concentration of arsenic in humans can induce epigenetic changes and genetic mutations causing cancer.12 Cadmium has been used in industries for a long time. Toxicity due to cadmium can affect kidneys, and the reproductive, skeletal, and respiratory systems, causing proteinuria, kidney stones, loss of bone density and mineralisation, destruction of mucous membranes, pneumonitis, testicular necrosis, and affects steroid hormone synthesis.13 Mercury pollution impacts human health leading to developmental flaws in children and Minamata disease14 Metals like vanadium and mercury may be added as additives as a part of manufacturing process or may be an unintentional adulterant released from the moulds used specifically in the plastic industry.15\n\nConsidering the wide applications of the packaging material, the concentration of high amounts of heavy metals in them requires fine regulation. The Environmental Defence Fund16 states that these heavy metals can be toxic and the route of ingestion can be packaging materials.17 Sometimes, odorous compounds from the food packaging may get transferred to the food items and affect the foods’ flavour. This results in considerable nutritional loss and consumer dissatisfaction. Although food and drug packaging are a multi-billion industry, studies on the presence of heavy metal in these packaging materials in India are lacking. The interest of the present work lies in qualitative and quantitative assessment of arsenic, vanadium, cadmium and mercury levels in locally procured food and drug packaging materials.\n\n\nMethods\n\nThis study was conducted at the Department of Biochemistry, Kasturba Medical College, Mangalore, Karnataka and Department of Chemical Engineering, National Institute of Technology, Suratkal, Karnataka. The Institutional Ethics Committee (IEC) approval was obtained prior to the conduct of the study.\n\nA total of eleven food packaging samples and two drug packaging materials were bought from the local market.\n\nThe samples included aluminium cans, leak-proof bags, cardboard, tetrapaks, cellophane, tissues, sachets, aluminium bags and boxes, plastic bags and containers, as well as medicinal blister packets and medicinal closures.\n\nThe packaging materials were collected, cleaned with distilled water and dried in a hot air oven. The samples were cut into small pieces using scissors and metal cutters, and 10 grams each of the sample were weighed using a calibrated electronic weighing scale. The following tests were performed in triplicates.\n\nPackaging material was collected and cleaned as mentioned above. A total of 10 grams of weighed samples were digested using standard acid digestion technique as described by USEPA 305 (United States Environmental Protection Agency amendment no 3050(B).18 Operating conditions for microwave-assisted extraction were followed as per the USEPA 3051. The operating conditions were followed as per original protocol only. Digested solutions were cooled at room temperature and filtered through 0.45-μm microfilters. Prior to inductively coupled plasma-optical emission spectrometry (ICP-OES) analysis, the samples were again filtered using 0.25-μm filters ensuring a clear filtrate. Analytical grade reagents such as concentrated hydrochloric acid (36%), sulphuric acid (98%) and nitric acid (68%) procured from Sigma Aldrich Chemicals Private Ltd, Bangalore, India were used. Double distilled water was procured from the Chemical Engineering lab at the National Institute of Technology, Karnataka using Accumax Distillation Unit for the extraction of the probable toxins from the samples.\n\nPost extraction of the sample, preliminary tests were performed to qualitatively confirm the presence of heavy metals.\n\nSpot test for vanadium: The extracted solution was treated with 0.1% sodium salicylate solution in a medium of 20 ml syrupy phosphoric acid. A turquoise blue colour obtained indicated a positive result.19 The blue colour in the test is formed when vanadium forms a complex called vanadium hydroxyamide naphthol ternary complex with the hydrogen-free radical.19\n\nSenSafe Boris’s mercury detection strips were used for the quick and easy detection of low levels of mercury procured by Industrial Test Systems Ltd, U.S.A. Dithizone in the extractant fluid acts as a sensitive reagent for the determination of mercury in acidic media. Dithizone forms coloured primary and secondary dithizonates complexes with mercury.20 The presence of a yellow to ochre colour indicates a positive result for presence of mercury.\n\nSwab test for cadmium: a clean cotton swab was dipped in 70% alcohol and dried, after which it was immersed in the extract and air-dried. The indicator was prepared in a small cup containing 1,5- diphenycarbazone and alcohol (70%) in a concentration of 70:30. The cotton swab dipped in the indicator turns violet-blue colour when confirming the presence of cadmium. The coloured complex is formed when cadmium reacts with diphenycarbazone.21\n\nAquasol arsenic detector kit was used following the manufacturer’s instructions. Briefly, (i) an arsenic silica reagent (ASR) test paper was placed on the black lid of the test bottle, using a forceps provided and making sure that the hole in the lid was covered by the test paper. (ii) The blue disc on the black lid was fixed gently. (iii) Precaution was taken not to touch the test zone. (iv) A 5 ml sample extract was taken in the test bottle with the syringe provided. (v) Three demitasse spoons of ASR-1 were added and gently swirled for a minute. (vi) Six demitasse spoons of ASR-2 were added to the above and immediately tightly screw-capped with the blue disc as prepared above. (vii) The test bottle was allowed to stand for 15 minutes, with intermittent swirling. (viii) The ASR test paper was removed from the lid and dipped in water for two seconds and excess water shaken off. The colour obtained on the test paper was compared with the colour comparison chart provided, at the end of five and eight minutes. A yellow tint indicated a positive test.\n\nAll thirteen samples were extracted as described above, labelled and subjected to ICP-OES to quantify the chosen heavy metals. Multi-element standard (REICPCAL29A) was used to standardize and calibrate the metal concentration.22 Standards of all four metals were run in triplicates using an inductively coupled optical plasma emission spectrophotometer (ICP-OES) from Agilent Technologies (U.S.A) with Expert software version of 7.100.6821.61355 and firmware version of 2994.\n\n\nResults\n\nAll tests were run in triplicates to ensure consistency in results. The average of the three readings was taken for computation and analyses.\n\nMicrowave-assisted extraction was carried out using hydrochloric acid and sulphuric acid in a concentration of 80:20 used for samples like aluminium can and leak-proof bag. Dehydrator aid proof extraction using a combination of sulfuric acid and nitric acid in the ratio of 80:20 was used for medicinal blister packets, tetrapak, sachets, plastic containers and medicinal closures. Acid digestion with a combination of hydrochloric acid and nitric acid in ratio of 80:20 respectively was employed for the extraction of cellophane, tissue cardboard, aluminium bags, box and plastic container. The time taken for extraction ranged from 210 minutes to 34 minutes (Table 1).\n\n\n\nA) Qualitative analysis\n\nCardboard, medicinal blister packets and closures were positive for the presence for vanadium. Mercury was qualitatively identified in eight samples viz. aluminum can and bag, leak-proof bags, sachet, plastic bag, cellophane, medicinal blister packets and closure. Arsenic was present in samples: aluminum bag and box, sachet, cellophane and leak-proof bags. Cadmium was detected in plastic bag, aluminum bag, sachet, cardboard and leakproof bag (Table 2).\n\nHeavy metals were detected in the all the thirteen samples. The levels of heavy metals ranged from 0.29 – 40.8 ppm for vanadium,1.7 – 236.2 ppm for arsenic, 1.53 – 546 ppm for mercury and 2.2 – 337 ppm for cadmium. The maximum permitted quantity (ppm) as suggested by the European Council for Food Packaging Association is; As-0.002 ppm, V-0.01 ppm, Hg and Cd being 100 ppm.23 Vanadium was found within the permissible limits in three samples (tissue, sachet, cellophane). Arsenic was above the permissible limit in all the studied samples. Similarly, cadmium was found to be above the acceptable limits only in the sachet. Arsenic was the most common heavy metal contaminant and cadmium was the least (Table 3).\n\nBold values indicate values of heavy metals in packaging materials below the or under acceptable amount that is within the given range and not higher than the prescribed limit.\n\n\nDiscussion\n\nIn the current study, eleven commercially available food packaging materials and two drug packages were analysed for the presence of four heavy metals, namely vanadium, arsenic, mercury and cadmium. Packaging materials constitute the mainstay of the modern food industry. Hence, it is important to study their interference with food/drug present within the packaging material. As research has shown leaching of toxins from packaging materials, monitoring the heavy metal leaching is essential to prevent harmful effects to the human body.6\n\nVanadium is a heavy metal which is used as an additive in stainless steel as well as a catalyst for manufacturing sulfuric acid. It is also used in glass coating and lacquering in aluminum cans to give strength to the material. Vanadium is used as an amalgam in manufacturing cans with stainless steel to give it tensile strength. Vanadium toxicity is known to cause abdominal discomfort by interfering with mucosal lining leading to nausea, bloating, diarrhea and vomiting in the initial stages. Prolonged exposure can result in renal and neural damage.24 Qualitative tests detected the presence of vanadium in only three samples. However, ICP-OES values showed presence of vanadium higher than permissible amounts in 10 samples. The study by Imtiaz et al.25 stated that vanadium causes oxidative stress in human cells and alteration in human metabolism, reduces enzymatic activities and disturbs membrane integrity in humans.25 This oxidative stress leads to the formation of pentavalate vanadium which is its most toxic and mobile form.\n\nArsenic, found in higher concentration in all the study materials (detected by six samples qualitatively), is a heavy metal that can act as a toxin due to its high presence in water which is used for material cleaning and lacquering processes.26 Arsenic is also known to be present as one of the food packaging colorants used in the packaging industry.27 Arsenic could enter the food packaging material during the cleaning process or as an adulterant of iron source. Arsenic has been used as a common ingredient in many pesticides and herbicides in the past. It is known to cause skin lesions and cancer in humans.28 The International Agency for Research on Cancer (IARC), a part of the World Health Organisation (WHO) has stated that exposure to arsenic is the leading cause of lung, bladder and skin cancer.29 The National Toxicology Programme (NTP) is composed of several different government agencies, including the National Institute of Health (NIH), the Center for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA). In its most recent Report on Carcinogens, the NTP classifies arsenic and inorganic arsenic compounds as known to be human carcinogens. The study by Park et al. stated that arsenic is present in paper in contact with food such as any kind of wrapping, and paper board, and presents a risk to consumer safety as increased ingestion in humans can cause skin lesions and gastric cancers.30\n\nMercury dissolves in aluminum at room temperature and is added as an additive in aluminum cans and foils to enhance the shelf-life of the seafood packed inside.31 Ingestion of mercury is the leading cause of Minamata disease. Mercury was detected qualitatively in eight samples and quantitatively in amounts greater than those permissible in sachet and plastic bag only. The mercury absorbed in the body mainly concentrates in the kidneys and brain.32 The half-life of mercury in the body is about 70 days. Inorganic mercury is mainly absorbed through the respiratory tract, but is also absorbed through the skin to a small extent (3-4%) or gastrointestinal (GI) tract (2–10%). Methylmercury is easily absorbed into the GI tract (≥95%) and into the respiratory tract (≈80%). About 90% of methylmercury is excreted through the faeces via bile, and less than 10 % through urine. The absorbed mercury is distributed throughout all tissues within 30 hours. Its half-life ranges from 45 to 70 days.33 Higher concentrations (more than 100 ppm) of mercury have been known to cross the placenta and result in foetal defects.14 Toxic effects of mercury have been reported even at lower concentrations in humans.34–36 Therefore, it would be worthwhile to study the leaching from the packaging material and reconsider the admissible limit if proven.\n\nIngestion of cadmium in higher concentration creates oxidative stress in the cells and increases the level of antioxidant uptake to protect against macromolecular cell damage, thus leading to prolonged exposure to cadmium, causing depletion of antioxidant levels in the body. Cadmium is generally a contaminant present as residues of the recycling and manufacturing processes, and hence determining their suitability in packaging materials coming in direct contact with foodstuffs is imperative. During the recycling process and cooling of cans, cadmium enters the food production system due to changes in temperature or as an additive used in the metal and glass industry. Cadmium can cause respiratory illnesses, lung fibrosis and cancer.37 Huff et al., found cadmium to be the major causative agent of lung cancer, and possibly prostate cancer. Studies in experimental animals have demonstrated that cadmium concentrations higher than those set by regulations (100 ppm) cause tumours at multiple tissue sites, by various routes of exposure, and in several species and strains.38\n\nIt is alarming to find high concentrations of toxic metals in several of the packaging materials studied. While cadmium seemed to be the least abundant contaminant, arsenic was the most prevalent heavy metal contaminant. Of all the types of packaging materials studied, sachets, which are manufactured using a plastic and aluminium amalgam, had the highest concentration of all the heavy metals.\n\n\nConclusions\n\nIn summary, a wide variety of food and drug packaging materials from an Indian market were tested for the presence of heavy metal, namely vanadium, arsenic, cadmium and mercury. Our study shows the presence of heavy metals in routinely used food packaging materials, measured quantitatively and qualitatively. All samples, irrespective of the results of qualitative analysis, were subjected to quantitative analysis, as ICP-OES is a sensitive technique for the detection of heavy metals. Of the thirteen samples analysed, arsenic was found in all samples at concentrations above regulated limits; cadmium was present in higher than regulated concentrations only in sachets. Arsenic was present in all samples, whereas vanadium was present in lower concentration in tissue, cellophane and sachets; mercury was present in higher concentration in sachets and plastic bags. Leaching of these heavy metals into the packaged food/drug may be potential health hazard that severely compromise the well-being of humans. This study calls for stringent regulatory guidelines and strict monitoring of packaging materials at all stages, starting from raw material selection, storage and production until it reaches the consumer. The post-packaging handling, transport, storage and conservation of the supply chain requirements further add to prospective leaching, which may be the scope of future studies.\n\n\nData availability\n\nMendeley data: ICP-OES data for “Assessment of toxins in food and drug packaging materials”, https://data.mendeley.com/datasets/gnwy7nzpnt/1.39\n\nThis project contains the following underlying data:\n\n- SENNA As KMC 6.12.21.docx (Arsenic ICP-OES data)\n\n- SENNA Hg KMC 6.12.21.docx (Mercury ICP-OES data)\n\n- SENNA KMC Cd 6.12.21.docx (Cadmium ICP-OES data)\n\n- SENNA kmc V 6.12.21.docx (Vanadium ICP-OES data)\n\n- Table 1. docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nFood Packaging - an overview|ScienceDirect Topics.Accessed Jan. 28, 2021. Reference Source\n\nMuschiolik G: The Wiley Encyclopedia of Packaging Technology. Second Edition. Edited by A. L. Brody and K. S. Marsh. XII and 1023 pages, numerous figures and tables. John Wiley & Sons, Inc., New York, Chichester, Weinheim, Brisbane, Singapore, Toronto 1997. Price: 150.00 £. Food Nahrung. Jan. 1997; 41(6): 381–381. Publisher Full Text\n\nUse Reusables: Fundamentals of Reusable Transport Packaging. US Environmental Protection Agency; 2012. Accessed Mar. 18, 2021.Reference Source\n\nArvanitoyannis IS, Kotsanopoulos Kv: Migration Phenomenon in Food Packaging. Food-Package Interactions, Mechanisms, Types of Migrants, Testing and Relative Legislation-A Review. Food Bioprocess Technol. Jan. 2014; 7(1): 21–36. Publisher Full Text\n\nBitel IS, Levitskii IA, Zayats NI: Migration of harmful substances from colored glazes into model media. Glas. Ceram. May 2007; 64(5–6): 201–205. Publisher Full Text\n\nDong Z, Lu L, Liu Z, et al.: Migration of toxic metals from ceramic food packaging materials into acid food Simulants. Math. Probl. Eng. 2014; 2014: 1–7. Publisher Full Text\n\nNerín C, Asensio E: Migration of organic compounds from a multilayer plastic-paper material intended for food packaging. Anal. Bioanal. Chem. Sep. 2007; 389(2): 589–596. PubMed Abstract | Publisher Full Text\n\n(PDF) Migration of organic compounds from a multilayer plastic–paper material intended for food packaging|Cristina Nerin - Academia.edu.Accessed Mar. 11, 2022. Reference Source\n\nSood S, Sharma C: Levels of Selected Heavy Metals in Food Packaging Papers and Paperboards Used in India. J. Environ. Prot. 2019; 10: 360–368. Publisher Full Text\n\nTangahu BV, Sheikh Abdullah SR, Basri H, et al.: A review on heavy metals (As, Pb, and Hg) uptake by plants through phytoremediation. Int. J. Chem. Eng. 2011; 2011: 1–31. Publisher Full Text\n\nRehder D: Vanadium. Its role for humans. Met. Ions Life Sci. 2013; 13: 139–169. PubMed Abstract | Publisher Full Text\n\nMohammed Abdul KS, Jayasinghe SS, Chandana EPS, et al.: Arsenic and human health effects: A review. Environ. Toxicol. Pharmacol. Nov. 2015; 40(3): 828–846. Publisher Full Text\n\nGodt J, et al.: The toxicity of cadmium and resulting hazards for human health. Journal of Occupational Medicine and Toxicology. Sep. 2006; 1(1): 1–6. Publisher Full Text\n\nEisler R Mercury hazards to living organisms. CRC Press;2006. Accessed Mar. 17, 2021.Reference Source\n\nMoskalyk RR, Alfantazi AM: Processing of vanadium: A review. Miner. Eng. 2003; 16(9): 793–805. Elsevier Ltd. Publisher Full Text\n\nEnrique Conti M: Heavy Metals in Food Packagings.Nov. 2006; pp. 339–362. Publisher Full Text\n\nGodt J, et al.: The toxicity of cadmium and resulting hazards for human health. J. Occup. Med. Toxicol. 2006; 1(1): 22. PubMed Abstract | Publisher Full Text\n\nO. US EPA: U.S. State and Local Waste and Materials Characterization Reports.Accessed Jun. 23, 2021.Reference Source\n\nTandon SG, Bhattacharyya SC: Spot Test for the Detection of Vanadium(V). Anal. Chem. Jun. 1964; 36(7): 1378–1379. Publisher Full Text\n\nWang S, et al.: Development of cellulosic paper-based test strips for mercury (II) determination in aqueous solution. J. Anal. Methods Chem. 2018; 2018: 1–7. PubMed Abstract | Publisher Full Text\n\nFriberg L: Cadmium. Annu. Rev. Public Health. 1983; 4: 367–373. Publisher Full Text\n\nEvaluation of heavy metal migration from plastic food packaging materials to aqueous simulants by ICP-MS: SHIMADZU (Shimadzu Corporation).Accessed Mar. 21, 2022. Reference Source\n\nIndustry and trade Nordic guidance for authorities, “Food contact materials - metals”. Norden. Accessed Mar. 11, 2022. Reference Source\n\nJin S, et al.: Urinary vanadium concentration in relation to premature rupture of membranes: A birth cohort study. Chemosphere. Nov. 2018; 210: 1035–1041. PubMed Abstract | Publisher Full Text\n\nImtiaz M, et al.: Vanadium, recent advancements and research prospects: A review. Environ. Int. Jul. 2015; 80: 79–88. PubMed Abstract | Publisher Full Text\n\nNachman KE, Graham JP, Price LB, et al.: Arsenic: A roadblock to potential animal waste management solutions. Environ. Health Perspect. Sep. 2005; 113(9): 1123–1124. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCharles JA: Early Arsenical Bronzes-A Metallurgical View. Am. J. Archaeol. Jan. 1967; 71(1): 21–26. Publisher Full Text\n\nGibaud S, Jaouen G: Arsenic-based drugs: From Fowler’s solution to modern anticancer chemotherapy. Top. Organomet. Chem. 2010; 32: 1–20. Publisher Full Text\n\nWHO|Arsenic: WHO. 2019. Accessed Mar. 27, 2021.Reference Source\n\nPark D, Yang H, Jeong J, et al.: A Comprehensive Review of Arsenic Levels in the Semiconductor Manufacturing Industry. Ann. Occup. Hyg. November 2010; 54(8): 869–879. Publisher Full Text\n\nVane CH, Jones DG, Lister TR: Mercury contamination in surface sediments and sediment cores of the Mersey Estuary, UK. Mar. Pollut. Bull. Jun. 2009; 58(6): 940–946. PubMed Abstract | Publisher Full Text\n\nBernhoft RA: Mercury Toxicity and Treatment: A Review of the Literature. J. Environ. Public Health. 2012; 2012: 1–10. PubMed Abstract | Publisher Full Text\n\nScoullos MJ, Vonkeman GH, Thornton I, et al.: Mercury, Cadmium, Lead: Handbook for Sustainable Heavy Metals Policy and Regulation. Springer;2001. Accessed Mar. 17, 2021.Reference Source\n\nZahir F, Rizwi SJ, Haq SK, et al.: Low dose mercury toxicity and human health. Environ. Toxicol. Pharmacol. Sep. 2005; 20(2): 351–360. Publisher Full Text\n\nScoullos MJ, Mercury, Cadmium, Lead: Handbook for Sustainable Heavy Metals Policy and Regulation. Springer, 2001. Accessed Mar. 17, 2021.Reference Source\n\nPeng X, Fu H, Hu J, et al.: Investigation on mercury migration discipline in different paper-plastic food packaging containers. J. Food Sci. Apr. 2020; 85(4): 1186–1192. PubMed Abstract | Publisher Full Text\n\nLuevano J, Damodaran C: A review of molecular events of cadmium-induced carcinogenesis. J. Environ. Pathol. Toxicol. Oncol. 2014; 33(3): 183–194. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuff J, Lunn RM, Waalkes MP, et al.: Cadmium-induced cancers in animals and in humans. Int. J. Occup. Environ. Health. 2007; 13(2): 202–212. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSenna M, Rukmini MS, Poornima AM, et al.: ICP-OES data for “Assesment of toxins in food and drug packaging materials”. Mendeley Data. 2022; V1. Publisher Full Text"
}
|
[
{
"id": "154512",
"date": "11 Nov 2022",
"name": "Mahesh Ganesapillai",
"expertise": [
"Reviewer Expertise Solid Waste Management",
"Closed loop",
"Nutrient recovery",
"Separation Technology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study conducted is well aligned with the scope of the journal and boasts considerable novelty in its approach. However, there are a few possible revisions which may alleviate the overall quality of the work:\nThe objective of the study needs to be clearly outlined in the last paragraph of introduction. Please refer the following articles for a proper understanding of the expected phrasing1,2,3.\n\nIntroduction: Information on the various quantitative analyses conducted must be mentioned in this section. Such details provide readers with valuable context for the study and improves the logical flow of the manuscript.\n\nExtraction: “…a concentration of 80:20 used…” Why was this composition chosen? Please provide valid reference for the same.\n\nTable 2: The data represented lacks clarity. Consider incorporating a legend representing the symbols.\n\nThere are several abbreviations in the manuscript – please include a nomenclature table for the convenience of readers.\n\nConclusions: The section needs further improvement and inclusion of better inferences. The mere mention of the presence of heavy mental entities does not conclude the study adequately.\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": "9038",
"date": "22 Nov 2022",
"name": "Rukmini M S",
"role": "Author Response",
"response": "1. The objective of the study will be clearly stated and suggestions will be incorporated. 2. The changes suggested in the introduction will be made. 3. Regarding the extraction procedure: 'The Aqua Regia is a standard acid mixture of HCl:HNO3 (volume ratio is usually 4 parts concentrated hydrochloric acid to 1 part concentrated nitric acid) prepared to digest most of the samples for the metal analysis.' 4. Table 2: The legends have been inadvertently omitted while editing. We will make the changes as per the suggestion. 5. We will include a nomenclature table for abbreviations or incorporate the complete metal name, wherever applicable."
}
]
},
{
"id": "178554",
"date": "29 Jun 2023",
"name": "Xin-Yuan Huang",
"expertise": [
"Reviewer Expertise Plant ionomics"
],
"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 manuscript, authors quantified four heavy metals in 13 types of food and drug packaging materials, including arsenic (As), vanadium (V), mercury (Hg) and cadmium (Cd). They found that 10 of 13 samples are above the permissible range for vanadium, all samples for arsenic, two samples for mercury and one sample for cadmium. This manuscript was well written but I have the following concerns.\nConcentrations of the 4 heavy metals shown in Table 3 are presented as parts per million (ppm), which represent the concentrations of these 4 heavy metals in the extract buffer (probably after dilution but not mentioned in the methods). The concentrations of heavy metals in the extract buffer depends on the amount of the food and drug packaging materials used for extraction. So the concentrations must be normalized to the weight of the materials.\n\nThe same extraction method was used for all eleven food packaging samples and two drug packaging materials. How to make sure they have the same extraction efficiency?\n\nQuantitative analysis of 4 heavy metals were determined by ICP-OES. What are detection limits for arsenic (As), vanadium (V), mercury (Hg) and cadmium (Cd) in this instrument?\n\nBlank control samples must be included when run samples on ICP-OES. Without blank controls, it is hard to rule out the presence of heavy metal coming from the samples or simply from reagents for extraction or the comtamination during the extration.\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?\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": [
{
"c_id": "9848",
"date": "07 Jul 2023",
"name": "Rukmini M S",
"role": "Author Response",
"response": "1. As per standard deduction method it represents the digestion of each packaging material having concentration of vanadium, arsenic, mercury and cadmium, when 10 gram of sample was digested. Accordingly, the experiment is performed and analysed and the concentration of heavy metal is determined in ppm. 2. The word used in place of extraction is digestion, the same correction would be made in the updated version of the manuscript. Digestion of complete sample takes places in the process leaving the heavy metal in solution form and therefore the accuracy was 100%. 3. The detection for arsenic (As), vanadium (V), mercury (Hg) and cadmium (Cd) for our study was carried out in ppm (parts per million). The machine is highly sensitive and detects these heavy metals in ppm (parts per million), ppb (parts per billion ) and ppq (parts per quadrillion). For heavy metal samples ICP -OES can detect heavy metals from 0.0002ppm to 1000ppm range. This information would be added in the updated version of the manuscript. 4. The analysis was done with standards of heavy metals namely vanadium, cadmium, mercury and arsenic. For all these heavy metals, calibration curve was developed using standard solution and then the concentration was determined. Thus, no control was required as same solution was used for digestion."
}
]
}
] | 1
|
https://f1000research.com/articles/11-648
|
https://f1000research.com/articles/12-1495/v1
|
23 Nov 23
|
{
"type": "Systematic Review",
"title": "The antimicrobial effect of Limosilactobacillus reuteri as probiotic on oral bacteria: A scoping review",
"authors": [
"Nissia Ananda",
"Dewi Fatma Suniarti",
"Endang Winiati Bachtiar",
"Dewi Fatma Suniarti",
"Endang Winiati Bachtiar"
],
"abstract": "Dysbiosis among oral microbial community in the oral cavity can lead to several oral diseases. Probiotic therapy is known to correct these imbalances. Limosilactobacillus reuteri is one of the most studied strains of probiotics and can control oral microbiota through reuterin, a wide-spectrum antimicrobial agent. The objective of this review was to evaluate the effect of the antimicrobial activity of Limosilactobacillus reuteri on the oral bacteria of humans. This review used PubMed, Scopus, EMBASE, ScienceDirect, and Google Scholar databases as bibliographic resources. Studies with matching keywords were analyzed and screened with PRISMA-ScR recommendations. Sixteen articles were selected for this review, which included a total of 832 patients. Based on this review, Limosilactobacillus reuteri has a strong antibacterial effect against Streptococcus mutans in healthy individuals but is not effective against Lactobacillus. Additionally, it has a significant antibacterial effect against Porphiromonas gingivalis in patients with periodontitis, although its effectiveness is not stable in patients with peri-implant infections. Furthermore, Limosilactobacillus reuterihas varying results against other bacteria, indicating the need for further extensive research to ensure its efficacy.",
"keywords": [
"antimicrobial",
"dentistry",
"Limosilactobacillus reuteri",
"Lactobacillus reuteri",
"oral bacteria",
"oral microbiome",
"oral probiotic"
],
"content": "Introduction\n\nMicrobiome is the community of microbial residents in human body and oral microbiome is the microorganisms resided in the oral cavity. It is known that oral microbiome is the second largest microbial habitat in humans after the gut and oral bacteria are the main components of this oral microbiota.1 It is a home for more than 700 bacterial species because oral cavity can provide a favorable habitat for the growth of microorganisms.1,2 Bacteria could have a stable environment to survive in oral cavity with the constant average of temperature is 37°C and steady pH of 6.5-7.1\n\nGenerally oral microbiome consists of a core microbiome and a variable microbiome. The core microbiome is community of predominant species that are present in various parts of the body under healthy condition. Meanwhile, a variable microbiome is a community of microorganisms species that varies and is exclusive between individuals because it has evolved in response to unique lifestyle and genotypic determinants.1\n\nThe fetus inside the uterus is usually sterile. The baby comes in contact with the microflora for the first-time during delivery, specifically with the uterine microflora and the mother’s vaginal microflora. At birth, the baby then also comes into contact with atmospheric microorganisms. Normally, the newborn’s oral cavity is sterile and regularly inoculated with microorganisms from the first feeding onward, and the process of acquisition of resident oral microflora begins.1 Previous studies suggest that there were significant changes in the composition of the microbiome over time in humans, and this was caused by many factors. One of the influencing factors is the decrease in salivary flow rate and oral pH as an individual gets older.3\n\nOral microbiomes usually reside in the oral cavity as biofilms. Maintaining the homeostasis of this biofilm is important to protect the oral cavity.1 The physiology and ecology of the microbiota are closely related to the host, this has an impact on the promotion of health or the development of disease. Since the oral cavity is the main gateway to the body, it can also lead to the spread of infection to other parts of the body causing systemic disease.4 It is currently recognized that unresolved inflammation promotes conversion to a dysbiotic community, and host-related intrinsic factors and defense mechanisms may play a major role in disease pathogenesis.2,5 Antibiotics are commonly used in dentistry to treat oral diseases, not infrequently they are also used as prophylactic treatment.6 On the other hand, excessive use of antibiotics can increase the risk of developing antimicrobial resistance.7 Unfortunately, the current condition of antimicrobial resistance has been declared by the WHO (World Health Organization) as a global public health emergency and is known as a silent pandemic.8\n\nProbiotics are living and viable microorganisms which in adequate quantities will provide benefits to the host.9 Probiotics can improve oral flora through a bacteriotherapy mechanism which is increasing the composition of harmless microflora to maintain or restore beneficial oral flora and modulating the oral microbiota to prevent pathogen colonization.10 In addition to bacteriotherapy mechanisms, probiotics can also prevent or treat oral microbiota dysbiosis through stimulation of the host’s immune system and produce molecules or substances with antimicrobial effects.9,11,12 These concept provides an alternative therapy to fight infection with fewer side effects and is safer than antibiotics.10\n\nOver the past few years, probiotic therapy has been used as an adjunct treatment in clinical dentistry.13 For oral or dental purposes, probiotics need to survive in the oral ecosystem.14 In terms of oral health, Limosilactobacillus reuteri has been extensively researched and is considered one of the most studied probiotics.15 Limosilactobacillus reuteri is known for its ability to control oral microbiota through reuterin, a wide-spectrum antimicrobial agent.16 However, some studies discovered that the Limosilactobacilluss reuteri probiotic should not be recommended as an adjunct treatment for oral infection as there were no microbiota alterations between the test and control groups.11,17,18 The purpose of this study is to provide a comprehensive overview of the existing literature on the antimicrobial effect of Limosilactobacillus reuteri on oral bacteria. This review aims to synthesize and map out prior research in order to identify knowledge gaps and research needs related to this topic. By examining the breadth and depth of available literature, this review will evaluate the quality and quantity of existing research on the subject, and inform future research and practice. Ultimately, this scoping review aims to provide a foundation for future research and practice in this important area of alternative antimicrobial drug research.\n\nThis review evaluated the effect of the antimicrobial activity of Limosilactobacillus reuteri on the oral microbiota of humans.\n\n\nMethods\n\nTo achieve this study’s objective, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews (PRISMA-ScR) were applied.\n\nWhat is known from the literature about the antibacterial effect of Limosilactobacillus reuteri on oral bacteria in humans?\n\nWe ran a search for full-text manuscripts written in English in several databases, such as PubMed, Scopus, EMBASE, ScienceDirect, and Google Scholar. There were no limitations regarding the articles’ publishing date at the search stage. The search was performed by identifying studies with the terms “(Lactobacillus reuteri OR Limosilactobacillus reuteri OR Probiotic) AND (Antimicrobial OR Antibacterial) AND (Oral OR Dental)”. Google Scholar was included in our search strategy to ensure a comprehensive search. However, due to the large number of results obtained from Google Scholar, we limited our screening to the first 10 pages of results, which were sorted by relevance.\n\nRayyan, developed and manufactured by Qatar Computing Research Institute in Doha, Qatar, was used as a tool for the screening and selection of studies for inclusion in this study. We imported the search results into Rayyan, de-duplicated them, and then two reviewers (NA and DFS) screened the title and abstract of each study to determine its relevance to the research question. Studies that were deemed potentially relevant by either reviewer were included for full-text review. During the full-text review stage, each reviewer independently assessed the eligibility of each study based on predetermined inclusion and exclusion criteria. Any disagreements were resolved through discussion or by involving a third reviewer (EWB). Finally, the studies that met the inclusion criteria were selected for data extraction and analysis. Rayyan was used to record the results of the screening and selection process, including the number of studies included and excluded at each stage, and to facilitate the creation of a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.\n\nThe inclusion criteria for the studies in this review were based on PICOS.\n\ni. Population, or participants and conditions of interest: Oral or Dental bacteria in humans\n\nii. Interventions or exposures: Exposure to Limosilactobacilluss reuteri\n\niii. Comparisons or control groups: a control group of microbiomes that was not exposed to Limosilactobacillus Reuteri\n\niv. Outcomes of interest: Quantity of Oral Bacteria (Antimicrobial effect)\n\nv. Study designs: Randomized controlled trials (RCTs) and non-RCTs, case-control studies, cross-sectional, as well as prospective and retrospective cohort studies were considered for inclusion. Systematic review studies were also included to explore the studies in the review that are relevant to this study.\n\nThe exclusion criteria for this review were letters to editors, commentaries, case reports, articles with non-human samples, and non-oral/dental research articles.\n\nData were extracted from each study based on the author, year, country, study design, subject criteria, number of samples, groups in the research, strain of Limosilactobacillus reuteri used, delivery systems, other accompanying treatment, duration of intervention, bacteria affected, and the statistical analysis of oral bacteria count.\n\nWe used version 2 of the Cochrane Risk-Of-Bias (RoB 2) Tool, developed and manufactured by Cochrane Collaboration, a non-profit organization based in London, United Kingdom, to assess the methodological quality of the studies. The risk of bias in each individual study was assessed by two reviewers, independently. The criteria of this assessment consisted of the following five domains: the randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result.\n\n\nResults\n\nThe electronic literature research process was conducted in April 2023, and 14352 studies were identified. The studies were obtained from the following four databases: PubMed, Scopus, EMBASE, ScienceDirect, and Google Scholar. A total of 1962 studies were eliminated due to duplication, 12355 studies were excluded by title and abstract screening. From the remaining thirty-five studies, nineteen studies were also excluded due to the following reasons: their subject was not human, there was no microbiome outcome in the study, the studies in the systematic review did not met the criteria, the study was only study protocol with no result, and the probiotic used was not Limosilactobacillus reuteri or Limosilactobacillus reuteri mixed with other bacteria. Therefore, sixteen studies were selected in this review for analysis (Table 1). The PRISMA flowchart of this systematic review is presented in Figure 1.\n\n\n\n- Baseline\n\n- 1 week\n\n- 2 week\n\n- 4 week\n\nFifteen of the selected studies were randomized controlled trials (RCTs), and one study was a non-RCT experimental study. These studies were published between 2004 and 2021. Of the sixteen studies, six articles utilized healthy human subjects (four articles used healthy young adult humans, and two articles used healthy children). Three studies included in this study were conducted with peri-implant mucositis patients, two studies used peri-implantitis patients, and one study used both peri-implantitis and peri-implant mucositis patients. Additionally, one study was conducted with gingivitis patients, two studies used periodontitis patients, and one study used periodontitis patients with Diabetes Mellitus condition. A total of 832 patients were included in these studies. The duration of intervention in the included studies ranged from 10 days to 24 weeks. On the other hand, the observation periods in these studies also ranged from baseline to 26 weeks.\n\nIn two studies originating from Turkey, a combination of Limosilactobacillus reuteri ATCC 55730 and ATCC PTA 5289 strains were used, while another two studies used only the Limosilactobacillus reuteri ATCC 55730 strain. Meanwhile, one study used only the Limosilactobacillus reuteri DSM 17938 strain, and eleven other studies used a combination of Limosilactobacillus reuteri DSM 17938 and ATCC PTA 5289 strains.\n\nDuring the quality assessment, it was found that the “low” percentage dominated the included articles, although there were still a few articles with the conclusion of “some concerns”. Additionally, only one article had a “high” result, and this article was a non-RCT experimental study. Therefore, it was reasonable to have a high bias value during this assessment (as shown in Figure 2 and Table 2). As a result, we concluded that all the studies included in this review are of good quality based on the Cochrane Risk-Of-Bias (RoB 2) Tool.\n\n\nDiscussions\n\nAntibiotic resistance is progressively increasing. This emphasizes the urgency of finding alternative antibacterial substances.19 Many studies have tried to find alternative methods, other than antibiotics, to treat oral cavity diseases, one of which is through biofilm inhibitors. Quorum sensing (QS) research is one of the new frontiers in this regard.20 Quorum sensing is a chemical signaling process of microorganisms that aims to monitor and regulate their population density. This chemical signaling system allows bacteria to coordinate their behavior and enhance their survival skills to respond to environmental changes through the growth and synthesis of biofilm matrix, enabling them to increase their resistance to conventional therapies such as antibiotics and antiseptics.20,21\n\nGenerally, oral biofilms consist primarily of commensal species that are harmless to the host, but this balance may be altered by local or systemic causes, leading to a dysbiotic state or a condition characterized by increased number of pathogenic species. The involvement of quorum sensing mechanisms in facilitating biofilm formation helps bacteria perpetuate this dysbiotic state.20 On the other side, interest in probiotics has tremendously risen over the last 10 years, and several health claims have been made regarding probiotics’ antibacterial activity.19,21 In digestive studies, probiotics have a good adhesion to the gut, effectively enhancing intestinal epithelial homeostasis and interfering with the quorum sensing that favors a dysbiotic state.22 Since probiotics act on biofilm composition, this current review is important as a preliminary knowledge to identify the effect of Lactobacillus reuteri on pathogenic bacteria in the oral cavity.15\n\nSix studies in this review analyzed the antibacterial properties of Limosilactobacillus reuteri against Mutans streptococci in healthy humans. Despite variations in probiotic delivery mechanisms, intervention duration, and observation periods, these studies found an overall positive antibacterial effect. Additionally, among the six studies, four used Limosilactobacillus reuteri ATCC 55730, and two studies combined this strain with Limosilactobacillus reuteri ATCC PTA 5289.23–27 Two study performed by Alamoudi et al. (2018) and Badri et al. (2020) also used Limosilactobacillus reuteri DSM 17938 and ATCC PTA 5289.27,28 Nikawa et al. (2004) conducted a study with a 2-week intervention period where Limosilactobacillus reuteri was administered via yoghurt, and the count of Mutans streptococci was observed for 4 weeks.26 Five other studies observed the count of Mutans streptococci immediately after the intervention duration.23–25,28 The results of these studies showed that Limosilactobacillus reuteri has an immediate and long-term effect of up to two weeks against Mutans streptococci. Related to this result, Caglar et al. (2009) conducted a study to investigate whether Limosilactobacillus reuteri ATCC 55730 survived in the oral cavity after the discontinuation of intervention. They found that Limosilactobacillus reuteri decreased gradually, where after 1 week, only 8% of bacteria were detected, and after 5 weeks, the bacteria were completely undetected.29\n\nOne limitation of the findings on Mutans streptococci presented in this scoping review is that the subjects included in the literature are all healthy individuals. While these studies provide valuable insights into the prevalence and distribution of Streptococcus mutans in healthy populations, they may not necessarily reflect the same patterns observed in individuals with other oral health conditions. In fact, other studies have shown that there are significant differences in the levels of Mutans streptococci in individuals with severe periodontitis compared to healthy individuals.30 Therefore, future research should aim to explore the distribution of Mutans streptococci in a more diverse range of populations, including those with varying levels of oral health conditions. This will help to better understand the role of Mutans streptococci in the development and progression of oral diseases and inform more targeted prevention and treatment strategies.\n\nFour of the six previously mentioned studies also analyzed salivary lactobacilli count as a dependent variable. All of the studies performed with healthy adults had the result that Limosilactobacillus reuteri has no significant antibacterial effect on salivary lactobacilli.23–26 However, a study by Alamoudi et al. (2018) with healthy children as participants, discovered a positive antibacterial effect of Limosilactobacillus reuteri on salivary lactobacilli.27 This result may be influenced by the dental hygiene performed by the children using the provided fluoride toothpaste. It may also be due to the absence of salivary lactobacilli in newborns, and 40% of the 3-year-old population have it to varying degrees. Whereas salivary lactobacilli in adults depend on ecological conditions, such as pits and fissures or partially erupted wisdom teeth which provide an environment that supports its growth.31\n\nThe studies performed on healthy subjects concerning Mutans streptococci and salivary lactobacilli count were based on the prior knowledge that both microbiomes are related to dental caries. One of the salivary lactobacilli species, Lactobacillus acidophilus, has characteristics that will increase significantly 2-3 months before dental caries appear. This phenomenon is called the “explosion of Lactobacillus”. However, the main oral acid production was not from lactobacilli, thereby making it only a secondary microbiome in dental caries. Lactobacillus cannot adhere to tooth surfaces on their own, as they need retention niches. On the other hand, Streptococcus mutans could produce extracellular polysaccharides to help them adhere to the tooth structure. Streptococcus mutans’ main feature is its acidophilic nature. This allows it to become the dominant bacteria in the oral cavity during acidic conditions. Moreover, the intracellular polysaccharides in Streptococcus mutans create energy reserves, so the level of acid produced, especially lactic acid, remains constant even when external sugar intake is low. Hence, Mutans streptococci and salivary lactobacilli are strongly associated with dental caries.32\n\nLaleman et al. (2019), Tada et al. (2017, and Galofre et al. (2017) used peri-implantitis patients as their research subjects. These three studies analyzed the antibacterial effect of Limosilactobacillus reuteri DSM 17938 and ATCC PTA 5289 on Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans. Furthermore, Tada et al. (2019) and Galofre et al. (2017) also analyzed Treponema denticola and Tannerella forsythia, whereas only Galofre et al. (2017) analyzed Peptostreptococcus micros, Campylobacter rectus, and Eikenella corrodens. All of the patients received non-surgical mechanical debridement of the peri-implant sites.18,33,34 Two of these studies found that there were no significant differences between the treated and control groups in microbiome counts after 24 weeks and 30 days of intervention with Limosilactobacillus reuteri lozenges.18,34 However, the study conducted by Laleman et al. (2019) that used probiotic drops as the drug delivery mechanism found different results compared to the other two studies. The intervention period was 12 weeks and the observation time was the baseline, week 6, week 12, and week 24. This study also evaluated the microbiome counts in the following three sites: saliva, tongue, and subgingival. The count of Porphyromonas gingivalis was only reduced in the saliva of the treated group at the week 6 observation. The count of Aggregatibacter actinomycetemcomitans significantly decreased in the saliva and tongue at week 12. On week 24, the count of Aggregatibacter actinomycetemcomitans also decreased in the saliva. Next, the count of Prevotella intermedia in the tongue of the treated group showed a significant decrease in all of the observation periods, and a decrease was also found in the subgingival area on week 24.33 These varying results may be influenced by the drug delivery mechanisms and the sites evaluated. Nevertheless, we can conclude that the number of peri-implant microbiota evaluated at the subgingival site was generally not affected by Limosilactobacillus reuteri, whether administered by lozenge or drops. Thus, similar studies need to be conducted for the tongue area and saliva evaluation, and a larger number of samples needs to be used to obtain conclusive results.\n\nRegarding peri-implant mucositis patients, four of the selected studies analyzed the antibacterial effect of Limosilactobacillus reuteri DSM 17938 and ATCC PTA 5289 on Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola.11,34–36 Three of the previous four studies also analyzed Prevotella intermedia, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Campylobacter rectus. Two of these three studies analyzed Peptostreptococcus micros and Eikenella corrodens, whereas the other study analyzed Fillifactor alocis, Porphyromonas endodontis, and Parvimonas micra.34–36 Overall, it can be concluded that Limosilactobacillus reuteri had no antibacterial effect on Tannerella forsythia and Treponema denticola in peri-implant mucositis patients as there was no positive result from the four studies despite differences in the intervention period, observation time, and drug delivery mechanisms.11,34–36 Similar negative results from the three studies were also noted in Prevotella intermedia, Aggregatibacter actinomycetemcomitans, and Campylobacter rectus. Additionally, Eikenella corrodens was found to be not affected by Lactobacillus reuteri in two studies.34–36\n\nPorphyromonas gingivalis in peri-implant mucositis patients was found to be significantly affected by Limosilactobacillus reuteri application via probiotic lozenge for thirty days. However, this result was only positive on day-90 observation time while the study also performed observation on days 30 and 60. Nevertheless, as previously described, Porphyromonas gingivalis in the saliva of peri-implantitis patients was significantly affected by Limosilactobacillus reuteri in the week-6 of observation and there was no significant difference in the week 12 and week 24 samples. However, these results were considered inconclusive due to the small number of samples and require further research.34\n\nPena et al. (2018) conducted a study with no statistically significant different results between the treated and control group in all peri-implant microbiota after administering Limosilactobacillus reuteri tablets from day 15 until day 45 of the study. However, he also analyzed the difference between the bacteria count on the day of observation and at the beginning of the study in each group, then he compared those numbers between both groups. This method resulted in significantly reduced Peptostreptococcus micros in the treated group compared to the control group, as indicated by the difference in bacterial counts between day 15 and day 45, and between day 135 and baseline. Another positive result was also found in Fusobacterium nucleatum in bacterial count on day 135 minus the bacterial count on the baseline.36\n\nOne study conducted by Iniesta et al. (2012) provided evidence that the administration of Lactobacillus reuteri DSM 17938 and PTA 5289 probiotic tablets for 28 days effectively reduced the total anaerobic bacteria counts in saliva samples after 4 weeks and Prevotella intermedia counts after 8 weeks in gingivitis patients. This probiotic combination exhibited inhibitory effects against various periodontopathogens, such as Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Parvimonas micra, Campylobacter rectus, Capno, Eikenella corrodens, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans in saliva samples. However, despite the significant total microbiological changes observed, these reductions in the target species did not translate into any clinically significant outcomes, as the inter-group differences in the clinical variables were not significant. This lack of clinical efficacy could be attributed to either the sample population or the short evaluation period. On the other hand, a significant reduction was observed only in Porphyromonas gingivalis counts in the subgingival sample from baseline to 4 weeks. These findings suggest that using Lactobacillus reuteri DSM 17938 and PTA 5289 probiotic tablets as an adjunct therapy could be promising for managing gingivitis and its associated periodontal pathogens, particularly Porphyromonas gingivalis.37\n\nThree articles in this scoping review examined the use of Limosilactobacillus reuteri DSM 17938 as a probiotic intervention in periodontitis patients. Of these three studies, one included diabetic patients with periodontitis, while the other two used healthy individuals with no systemic disease. The probiotic was administered in two studies as a tablet containing a combination of Limosilactobacillus reuteri DSM 17938 and ATCC PTA 5289, while the third study used only Limosilactobacillus reuteri DSM 17938 in the form of a suspension delivered through a blunt syringe to subgingival sites.38–40 Interestingly, the study with diabetic patients showed a significant reduction in the number of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola after three weeks of probiotic tablet use, which was sustained after a three-month evaluation.38 On the other hand, in line with the previous result, the study conducted by Vivekananda with a split-mouth study design in India found that only the treatment modalities that included the Limosilactobacillus reuteri tablet, either alone or in combination with scaling root planing, were able to significantly reduce the counts of pathogens tested (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia).39 Lastly, the study conducted by El-bagoory et al. (2021) showed a significant reduction in the number of Porphyromonas gingivalis on the three-month and six-month evaluations after only four applications of the probiotic suspension delivered to subgingival sites, even though it was administered only at baseline, week 1, week 2, and week 4.40\n\nThe effectiveness of Limosilactobacillus reuteri in treating specific periodontal pathogens in peri-implant mucositis and periodontitis patients can vary depending on the distinct microbial network shape present in these niches. Peri-implant biofilm is more homogeneous and similar to supragingival biofilm than subgingival biofilm, while subgingival biofilm in periodontitis patients contains a higher number of microorganisms. In addition to this, the host response and habitat structure surrounding implants and teeth can also affect the microbial community structure and the effectiveness of probiotics.41 Furthermore, the rough surface of dental implants increases the rate of biofilm formation around the implant, and surface roughness contributes to increased plaque buildup.42\n\nBased on our review, it was found that Limosilactobacillus reuteri is a probiotic bacterium that exhibits varying levels of antimicrobial activity against different pathogens. However, its effectiveness can be further enhanced by combining it with other clinical care and active ingredients such as natural compounds or prebiotics. For instance, Holm et al. (2022) showed that the antimicrobial effectiveness of Limosilactobacillus reuteri (ATCC PTA 5289) can be improved by combining it with glycerol against periodontal pathobionts and anaerobic commensals. This may be attributed to the increased production of reuterin by Limosilactobacillus reuteri from glycerol.43 Hence, combining Limosilactobacillus reuteri with other active ingredients such as natural compounds or prebiotics may be a useful strategy for improving its antimicrobial efficacy. However, further details on this strategy need to be explored, including relevant references and future research perspectives. It is worth mentioning that some newly introduced compounds have a significant influence on the oral environment. The use of paraprobiotics, lysates, and postbiotics can modify clinical and microbiological parameters in periodontal patients.44–46 Therefore, these products should be considered in combination with Limosilactobacillus reuteri in future clinical trials.\n\nIn conducting a scoping review, it is important to consider the limitations of the study design in order to interpret the findings in a meaningful way. One limitation of the current scoping review is the potential for bias in quality assessment due to the inclusion of a non-randomized study with a high risk of bias. However, the review also included 15 other studies, all of which were randomized control trials. Of these, 9 studies were found to have a low risk of bias, while 6 studies had “some concerns” regarding risk of bias based on the Cochrane Risk-Of-Bias (RoB 2) Tool. Although the non-randomized study may have impacted the overall quality of the evidence included in the review, the findings of the randomized control trials provide important insights into the effectiveness of the interventions studied. Moreover, the inclusion of grey literature in the search strategy can help to enhance the comprehensiveness of the review. Overall, while limitations should be acknowledged and considered in the interpretation of the findings, the scoping review still provides valuable insights and can serve as a foundation for future research in the field.\n\nFurthermore, in this scoping review, it was found that several studies included in the analysis received materials and funding from a sponsor. Additionally, one author from a study received a PhD grant from the sponsor, while another author received a lecturing fee. Nonetheless, the authors of these studies stated that the involvement of the sponsor did not have any impact on the results of their research. It is essential to acknowledge the presence of external funding sources and their potential influence on study outcomes, as transparency in reporting is crucial in scientific research. Despite the presence of sponsorship, the authors of the reviewed studies made it clear that the research conducted was not compromised, and their findings were not influenced by the sponsors. However, it is necessary to approach the results with caution, as the presence of external funding sources can still potentially affect the outcome of research studies.\n\n\nConclusions\n\nLimosilactobacillus reuteri exhibits a strong antibacterial effect on Streptococcus mutans and has a less significant impact on Lactobacilli in healthy individuals. Additionally, Limosilactobacillus reuteri has antibacterial properties against Porphyromonas gingivalis in periodontitis and gingivitis patient although its effectiveness is not stable in patients with peri-implant infections. The study suggests that Lactobacillus reuteri does not have a noteworthy impact on Campylobacter rectus and Eikenella corrodens. However, the effectiveness of Limosilactobacillus reuteri varies concerning other bacteria such as Prevotella intermedia, Peptostreptococcus micros, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and Fusobacterium nucleatum. Further research is essential to examine the antibacterial properties of Limosilactobacillus reuteri on the oral/dental microbiomes, taking into account variations in the strains used, intervention periods, subjects, and observation times. This research is crucial in advancing our understanding of Limosilactobacillus reuteri’s potential as a probiotic for maintaining oral/dental health.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nHarvard Dataverse: Search Strategy for the Article “The Antimicrobial Effect of Limosilactobacillus reuteri as Probiotic on Oral Bacteria: A scoping review”, https://doi.org/10.7910/DVN/IPHU9X. 47\n\nHarvard Dataverse: PRISMA-ScR Checklist for the Article “The Antimicrobial Effect of Limosilactobacillus reuteri as Probiotic on Oral Bacteria: A scoping review”, https://doi.org/10.7910/DVN/EIGWI1. 48\n\nHarvard Dataverse: PRISMA Flow Diagram for the Article “The Antimicrobial Effect of Limosilactobacillus reuteri as Probiotic on Oral Bacteria: A scoping review”, https://doi.org/10.7910/DVN/VJLVI9. 49\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\nDeo PN, Desmukh R: Oral microbiome: Unveiling the fundamentals Priya. J. Oral Maxillofac. Pathol. 2019; 23(1): 122–128. 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PubMed Abstract | Publisher Full Text\n\nIniesta M, Herrera D, Montero E, et al.: Probiotic effects of orally administered Lactobacillus reuteri-containing tablets on the subgingival and salivary microbiota in patients with gingivitis. A randomized clinical trial. J. Clin. Periodontol. 2012; 39(8): 736–744. PubMed Abstract | Publisher Full Text\n\nElsadek MF, Ahmed BM, Alkhawtani DM, et al.: A comparative clinical, microbiological and glycemic analysis of photodynamic therapy and Lactobacillus reuteri in the treatment of chronic periodontitis in type-2 diabetes mellitus patients. Photodiagn. Photodyn. Ther. 2020; 29(September 2019): 101629. PubMed Abstract | Publisher Full Text\n\nVivekananda MR, Vandana KL, Bhat KG: Effect of the probiotic Lactobacilli reuteri (prodentis) in the management of periodontal disease: A preliminary randomized clinical trial. J. Oral Microbiol. 2010; 2(2010): 1–10.\n\nEl-bagoory GKM, El-Guindy HM, Shoukheba MYM, et al.: The adjunctive effect of probiotics to nonsurgical treatment of chronic periodontitis/A randomized controlled clinical trial. Indian Soc. Periodontol. 2021; 25(May): 525–531. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSousa V, Nibali L, Spratt D, et al.: Peri-implant and periodontal microbiome diversity in aggressive periodontitis patients: a pilot study. Clin. Oral Implants Res. 2017; 28(5): 558–570. PubMed Abstract | Publisher Full Text\n\nDhir S: Biofilm and dental implant: The microbial link. J. Indian Soc. Periodontol. 2013 Jan; 17(1): 5–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVan Holm W, Verspecht T, Carvalho R, et al.: Glycerol strengthens probiotic effect of Limosilactobacillus reuteri in oral biofilms: A synergistic synbiotic approach. Mol. Oral Microbiol. 2022 Dec 1; 37(6): 266–275. PubMed Abstract | Publisher Full Text\n\nButera A, Gallo S, Maiorani C, et al.: Management of gingival bleeding in periodontal patients with domiciliary use of toothpastes containing hyaluronic acid, lactoferrin, or paraprobiotics: A randomized controlled clinical trial. Appl. Sci. 2021; 11(18). Publisher Full Text\n\nButera A, Gallo S, Pascadopoli M, et al.: Home Oral Care of Periodontal Patients Using Antimicrobial Gel with Postbiotics, Lactoferrin, and Aloe Barbadensis Leaf Juice Powder vs. Conventional Chlorhexidine Gel: A Split-Mouth Randomized Clinical Trial. Antibiotics. 2022; 11(1). PubMed Abstract | Publisher Full Text | Free Full Text\n\nVale GC, Mayer MPA: Effect of probiotic Lactobacillus rhamnosus by-products on gingival epithelial cells challenged with Porphyromonas gingivalis. Arch. Oral Biol. 2021; 128(March): 105174. PubMed Abstract | Publisher Full Text\n\nAnanda N, Bachtiar EW, Suniarti DF: Search Strategy for the Article “The Antimicrobial Effect of Limosilactobacillus reuteri as Probiotic on Oral Bacteria: A scoping review”. Harvard Dataverse. 2023; V1. Publisher Full Text\n\nAnanda N, Bachtiar EW, Suniarti DF: PRISMA-ScR Checklist for the Article “The Antimicrobial Effect of Limosilactobacillus reuteri as Probiotic on Oral Bacteria: A scoping review”. Harvard Dataverse. 2023; V1. Publisher Full Text\n\nAnanda N, Bachtiar EW, Suniarti DF: PRISMA Flow Diagram for the Article “The Antimicrobial Effect of Limosilactobacillus reuteri as Probiotic on Oral Bacteria: A scoping review”. Harvard Dataverse. 2023; V1. Publisher Full Text"
}
|
[
{
"id": "226213",
"date": "19 Dec 2023",
"name": "Firdaus Hariri",
"expertise": [
"Reviewer Expertise Metagenomic",
"oral health",
"oral and maxillofacial 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\nWell done to the team of researchers for this valuable review.\n1) In general, the paper is well written and very structured. 2) The objective and research question are clear and the methodology used to achieve the objective is comprehensively described supplemented with the application of appropriate review protocol. 3) Results are well structured, supplemented with excellent summary tables. 4) Discussion: - as Limosilactobacillus reuteri has been widely used as valuable probiotic in human, may I recommend a brief paragraph, either in 'Introduction' or at beginning of 'Discussion' on its usage in general health (authors only described its potential role in oral health). - to supplement the discussion on paragraph 12 (on diabetic patients) with studies about the role of Limosilactobacillus reuteri in diabetes mellitus (e.g metabolic or beneficial effect).\nThank you.\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",
"responses": [
{
"c_id": "11138",
"date": "13 Apr 2024",
"name": "Nissia Ananda",
"role": "Author Response",
"response": "Thank you for your insightful comments as a reviewer of my article. I have taken your suggestions into consideration. I added a brief explanation about the usage of Limosilactobacillus reuteri in general health in the discussion section, and I also included a paragraph discussing the relationship between Limosilactobacillus reuteri and diabetes mellitus."
}
]
},
{
"id": "226208",
"date": "07 Feb 2024",
"name": "Norifumi Nakamura",
"expertise": [
"Reviewer Expertise Oral and Maxillofacial Surgery",
"Reconstructive Surgery",
"Odontogenic Tumors"
],
"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 antimicrobial activity of Limosilactobacillus reuteri, one of the probiotic strains, is of great interest and brings useful information to the field of dentistry However, the following major and minor problems are observed and should be corrected before acceptance.\nMajor problems. 1. It would be required to describe the results of the evaluation of the effect of the antibacterial activity of Limosylactobacillus reuteri on human oral bacteria based on the 16 papers that were finally selected. 2. The discussion contains too many results and seems redundant. The discussion should be organized into important items with small headings. 3. What are the criteria for arranging the 16 papers summarized in Table 1? Wouldn't it be easier for readers to read them if they were sorted by year of publication or evidence level of study design?\nMinor problems 4. The article by Badari (2020), which was selected for Systematic review, is not in the list of references. 5. The year in the text is different from the year in the list of references 5. The text is well written, but is divided into too many small paragraphs.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": [
{
"c_id": "11140",
"date": "13 Apr 2024",
"name": "Nissia Ananda",
"role": "Author Response",
"response": "Thank you for your valuable feedback as a reviewer of my article. I have carefully considered your suggestions. Below, I will address each of your comments individually: Major problems 1. I have summarized the findings from the selected articles in the discussion section. However, it cannot be generalized as a whole because the target bacteria of each article are not the same. Therefore, by adding subheadings in the discussion section, the results presented can be clarified. 2. I subdivided the discussion section into smaller subheadings. 3. I have reordered the articles in the table to be sorted by year of publication. Minor problems 4. The article by Badari was previously miswritten as Matuq in reference number 28 5. The years of the references have already been synchronized between the manuscript and the references. 6. I believe that the division of my article into numerous smaller paragraphs is not an issue. It follows the standard convention that a paragraph typically consists of at least three sentences."
}
]
},
{
"id": "237795",
"date": "09 Feb 2024",
"name": "Rizky Aditiya Irwandi",
"expertise": [
"Reviewer Expertise oral microbiology and 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\nThe authors provide a rather extensive review of the per-oral probiotics research, specifically its influence on oral microbiome not limited to oral-derived pathogens. Overall, the scoping review has adhered to the standardized criteria and all relevant information relevant to the review has been well delivered in detail. To achieve this, I would strongly recommend the authors to revise some aspects detailed below: Introduction Paragraph 1: It would be concise to exclude the first paragraph. Paragraph 2: As the second paragraph becomes the first one, consider removing the word “Generally” would be appropriate. Paragraph 3: It would be concise to exclude the third paragraph. Paragraph 4: Consider removing “usually” from the first sentence and combining the first two sentences with conjunction words such as “and” would be more concise. For instance: “Oral microbiomes reside in the oral cavity as biofilms and maintaining their homeostasis is important to protect the oral cavity as the main gateway to the body. The shifted oral microbial balance may lead to diseases and antibiotics are a common antimicrobial approach to regain the oral microbiota equilibrium. Over-reliant antibiotic administration, however, increases the risk of developing antimicrobial resistance which WHO declared as one of the global health emergencies and is also known as a silent pandemic. Therefore, an alternative intervention such as probiotics gains attention to maintain oral biofilm homeostasis” Paragraph 5: removing “will” in the first sentence and “can” in the second and third as well as replacing “which is” with “by” in the second sentence and correcting the typo “pathogen” to “pathogenic” would help readers to better understand the ideas delivered by the authors. Results The authors included RCT studies. I would recommend the authors include the RCT registration ID by clinicaltrial.gov or any other relevant RCT databases and present them in Table 1. This is particularly important to objectively assess each study confirming that indeed the RCTs designed by certain studies have fulfilled the criteria of the commonly used RCT databases. The authors mentioned that the review adheres to the PRISMA-ScR and that it would be easier for the reader to have a completed fillable checklist. This can be provided as supplemental information to the article. The authors may refer to this webpage for the checklist: http://www.prisma-statement.org/documents/PRISMA-ScR-Fillable-Checklist_11Sept2019.pdf Discussion Paragraph one: the authors delivered ideas about the need for alternatives to antimicrobial approaches (in this case antibiotics) by harnessing bacterial quorum sensing. At the same time, however, the authors mentioned that quorum sensing leads to antibiotic resistance. I found this conflicting and this likely confuses the reader. I would recommend the authors revisit by restructuring this part. The use of active voices is, I would suggest, preferable to strengthen the clarity of ideas delivered. For example, the first sentences could be: “Oral biofilms consist primarily of commensal species that are in equilibrium and harmless to the host. However, both oral and systemic-derived insults are capable of inducing the alteration towards microbial dysbiosis leading to an increased number of pathogenic microbial species.” Minor errors: Paragraph 2: Replace “on the other side” with “moreover” Paragraph 3: Replace “conditions” with “disorders” The authors comprehensively discussed the studies included in the review. The detailed mechanisms of probiotic actions (for example, how probiotics are likely to influence bacterial quorum sensing) would provide a strong rationale for continuing the use of probiotics to regain the balance of oral microbiota. The ideas would be even more robust if the authors could expand more on the aspect such as to what extent the use of the probiotics is strongly recommended and perhaps any potential side effects should be highlighted (if no side effects are available, considering the explanation of the possible mechanism of this would be recommended).\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",
"responses": [
{
"c_id": "11141",
"date": "13 Apr 2024",
"name": "Nissia Ananda",
"role": "Author Response",
"response": "Thank you for your perceptive feedback as a reviewer of my article. I have carefully considered your suggestions, and I will address each of your comments point by point below: Introduction I deleted the first and third paragraph I removed the “Generally” word on the second paragraph (the new first paragraph) I have incorporated your suggestion regarding the writing and wording of the 4th and 5th paragraphs. Results Thank you for your suggestion to include RCT registration IDs for the articles selected in our scoping review. However, after careful consideration, we have decided not to pursue this request for several reasons. Firstly, it's important to note that not all selected articles may have RCT registration IDs available, particularly if they were published before mandatory registration policies were implemented or if they encompass a range of study designs beyond RCTs. Additionally, obtaining RCT registration IDs for older studies may not be feasible due to logistical constraints. Moreover, the primary focus of our scoping review is not on assessing the registration status of RCTs but rather on mapping existing literature on the topic at hand. Therefore, including RCT registration IDs for each article may not align with the scope and objectives of our review. Furthermore, while RCT registration is an important aspect of research transparency, the absence of registration IDs does not necessarily imply lower quality or validity of the included studies. We have ensured the trustworthiness of the literature reviewed through other rigorous inclusion criteria. Lastly, considering the space constraints and journal requirements, including RCT registration IDs for each article may unnecessarily lengthen the manuscript and detract from the main findings and discussion. We appreciate your input and understanding regarding our decision not to include RCT registration IDs in our scoping review The PRISMA-ScR checklist has been provided in the datasets, with the link to access it written in the data availability section. Discussion I added a brief explanation of quorum quenching, which inhibits quorum sensing. I have implemented your suggestion regarding the writing and wording of the 2nd and 3rd paragraphs. I also have applied your suggestion concerning the use of active voice. I have included additional discussion on the mechanism of quorum quenching, which inhibits quorum sensing in probiotics, affecting pathogenic bacteria. Furthermore, I have elaborated on the cytotoxicity of Limosilactobacillus reuteri on human gingival fibroblasts."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1495
|
https://f1000research.com/articles/12-1199/v1
|
25 Sep 23
|
{
"type": "Study Protocol",
"title": "Comparative study of Nishaamalaki and metformin in obese patients of type 2 diabetes mellitus (Madhumeha): A study protocol",
"authors": [
"Dr. Aman Chhabra",
"Vaishali Kuchewar",
"Twinkle Joshi",
"Vaishali Kuchewar",
"Twinkle Joshi"
],
"abstract": "Background: Poor synthesis of insulin by beta cells present in the pancreas combined with resistance of insulin in peripheral organs is referred to as type 2 diabetes mellitus. Insulin resistance leads to an increase in plasma fatty acids, which reduces transfer of glucose within the cells of muscles and increases breakage of lipids, resulting in an increase in hepatic glucose production. Nishamalaki (a formulation of turmeric and Indian gooseberry) is suggested in the therapy of all kinds of Madhumeha (diabetes mellitus) in Ayurveda classics. Turmeric and Indian gooseberry are the two main ingredients. Both are considered as effective medicines in the management of Madhumeha individually as well as in combined form. Aim: To compare the efficacy of Nishaamalaki and metformin in obese patients of type2 diabetes mellitus. Methods: The study will include 60 obese type 2 diabetes mellitus patients who were distributed into two distinct categories, each with 30 patients. Nishamalaki Churna with honey 3gm two times a day before food with warm water for 60 days in Group N (Experimental Group) and 500 mg metformin tablets twice daily before meals for 60 days in Group M (Control Group). Every 15th day, an assessment was made (15th, 30th, 45th and 60th day). Results: Objective outcomes will be assessed. Conclusion: From this study protocol, it can be depicted that the trial formulation of turmeric and Indian gooseberry (Nisha-amalaki) is as effective in obese patients suffering from type- 2 diabetes mellitus as compared to metformin tablets.",
"keywords": [
"Nishaamalaki Churna",
"Metformin",
"Obese Type2 Diabetes Mellitus"
],
"content": "Introduction\n\nPoor pancreatic beta-cell insulin production accompanied by peripheral insulin resistance is referred to as type 2 diabetes mellitus.1 Insulin resistance causes an increase in fatty acids in the plasma, resulting in reduced glucose transport into muscle cells and increased fat breakdown, which leads to an increase in hepatic glucose production. For type 2 diabetes mellitus to develop, insulin resistance and pancreatic-cell failure must both occur at the same time. Insulin resistance affects everyone who is overweight or obese, but diabetes only develops in those who don’t have enough insulin production to meet their level of insulin resistance.\n\nThe prevalence of obesity has increased recently, highlighting the issue’s importance on a global scale. In the United States, almost two thirds of adults are thought to be overweight or obese. In many parts of the world, identical trends may be found.2 Numerous physical, psychological, and social problems have been linked to obesity, the most significant of which is type 2 diabetes. 171 million individuals were predicted to have type 2 diabetes mellitus after the completion of this era, and by 2030, this figure is projected to reach 360 million.3 The drug metformin is now routinely used to treat diabetes mellitus. With lifestyle changes, it is now regarded as the first line of treatment for type 2 diabetes mellitus because of its outstanding safety standards, effectiveness, tolerability, and high hypoglycaemia.4 Excitingly, epidemiological, and preclinical studies have recently shown that metformin has positive effects in addition to its effects on Glycaemic indices. It has been demonstrated to lower body weight, reduce cancer incidence and death, and extend longevity.4 Metformin has been a popular study topic for disorders related to obesity and ageing as a result of these effects.\n\nNishaamalaki is suggested in the management of obese patients suffering from diabetes mellitus in Ayurveda classics.5 Turmeric and Indian gooseberry are the two main ingredients. Both are individually as well as in combined form are considered as effective medicines in the management of Madhumeha (diabetes mellitus). In experimental animal models, its rhizomes were shown to exhibit anti-diabetic characteristics. Curcumin, the key component, was shown to have anti-diabetic properties, according to researchers.6 In one animal study, it is also found to be a weight reducing agent.7\n\nIndian gooseberry contains Ellagic acid which exhibits blood sugar lowering effects by stimulating insulin production and decreasing glucose intolerance in diabetic rats. Immunohistochemistry of the pancreas revealed that in diabetic rats, Indian gooseberry increased Beta cell size as well as its count. Additionally, it decreased the glucose intolerance of diabetic rats and raised the generation of insulin stimulated by blood glucose from isolated islets.8 Some of the main compounds in the fruits of Emblica officinalis (such as gallotanin, corilagin, and ellagic acid) have blood glucose lowering qualities due to their characteristics of free radical scavenging, according to studies. Hyperglycaemia, heart problems, diabetic nephropathy, neuropathy, cataractogenesis, and other conditions have all been linked to it.9\n\nAmalaki is rich in vitamin C. It has been shown that taking extra vitamin C helps diabetics with sorbitol build-up in their red blood cells. Vitamin C also lessens capillary fragility, which increases the risk of complications from diabetes.10 Additionally, previous research indicates that prolonged vitamin C treatment has advantageous effects on lipid and glucose metabolism in T2DM patients.11\n\nType 2 diabetes mellitus and obesity are progressive and rapidly spreading metabolic diseases. Both have strong correlation. In modern medicine, it is studied that metformin has antidiabetic as well as anti-obesity effect. There are numerous studies on Nisha-amalaki showing its antidiabetic effect, but it is not studied in obese type 2 diabetic patients hence this study is planned.\n\n\nMethods\n\nThis single-blind, randomised, standard-controlled experiment included a parallel group. A 60-day treatment term and a 15-day follow-up period were both included in the trial.\n\nA total of 60 patients were chosen for the trial, and they will be distributed into 2 equal groups according to the allocation ratio. Group M is a conventional standard group while Group N is a trial group.\n\nRecruitment of patients will take place at MGACH&RC, Wardha, from the OPD and IPD of the Department of Kayachikitsa. Patients were also chosen from a variety of peripheral camps with diverse specialties.\n\nTrial registration number: This trial has the CTRI registration number CTRI/2021/10/037263.\n\nDiagnostic criteria: The patients will be assessed based on blood sugar level (Fasting and Postprandial) and Body Mass Index.\n\nEligibility criteria: Age between 30 to 60 years of either sex. Patients having Fasting Blood Sugar Level >126 mg/dL and/or Postprandial Blood Sugar Level >200 mg/dL. B.M.I. in between 25-30 kg/m2.\n\nGroup N – Nishamalaki Churna with honey 3 gm two times a day before meals.\n\nGroup M – 500 mg metformin tablets two times a day before meals.\n\nParticipants met the criteria for randomization, and they were assigned to the experimental and control groups in a 1:1 ratio. A lottery-based randomization system that operates remotely provided researchers with access to the treatment allocation for each eligible participant. A total of 60 patients were chosen for the trial, and they were distributed into 2 equal groups. The experimental group is Group N, while the usual controlled group is Group M.\n\nThe assignments will be kept a secret until the trial is finished. The will all be blinded. Throughout the trial, doctors evaluate all of the participants. Using the lottery-based method of randomization of patients, the practitioner applied for a randomised assignment for each eligible patient, and a prescription for “Nishamalaki Churna with honey before meal two times a day” was written. The patients will then be escorted to the Dattatraya Rasa Shala’s designated drug managers, accompanied by a study assistant. All of the medications are packed in the same way. The actual names of both the groups, i.e., standard as well as trial groups will be kept blinded unless any adverse event or side effect of any of the group is observed.\n\nScreening investigations (base line): Fasting Blood Sugar, Postprandial Blood Sugar, Body Mass Index\n\nInvestigation (end line): Fasting Blood Sugar, Postprandial Blood Sugar.\n\nWithdrawal criteria\n\n• Subjects will be withdrawn from the trial if any unintended occurrence, signs of reaction of medication, adverse or side effect emerged, and the therapy will be supplied to such a patient totally free of cost until the difficulty subsided. We will measure the amount of Churna consumed to assess and monitor drug adherence, and the subject will be monitored during therapy.\n\nFollow-up\n\nFollow up of patients will be done in every 15 days during treatment.\n\nResults\n\n• Primary: Clinicians will examine the impact of therapeutic drugs on blood sugar levels (Fasting and Post meal).\n\n• Secondary: To compare the effectiveness of the experimental population to those of the standard group, check for the disease’s recurrence, monitor any adverse drug effects, and check for recurrence of the ailment\n\n• Durable efficacy: Respondents will be categorised as durable efficacy responders if they get desirable improvement for a minimum of one month during treatment.\n\nA level of significance of 5% (two-sided) will be regarded statistically significant. Intention-to-treat and in accordance with protocol populations will be used in the analysis. For each group, baseline characteristics will be offered, as well as predicting factors. We shall express discrete variables with percentages and frequencies from baseline to each time point, whereas for data with a distribution that is normal, variables that are continuous can be characterised by the mean or standard deviation, or by the median and interquartile range, for data with an irregular distribution. Paired and unpaired t tests will be performed to assess the Results for each time point’s comparisons between the trial and standard groups.\n\nPredictive factor analysis will be performed with the following two steps:\n\nThe univariate analysis is the initial phase. The sufficient alleviation follow-up responder rates (day 15 and 30) will be employed as dependent variables, with predictor variables such as demographic and clinical features, as well as important elements of NishamalakiChurna with honey, serving as independent variables. An analysis of logistic regression will be carried out. The independent variable’s selection criteria are defined as = 0.1. Multivariate analysis is the next phase. The predicted factors chosen in initial phase will be incorporated into 2 different models of regression with the desirable improvement pattern of the patient as the variable which is dependent on the other one (day 45). It was decided to do a sensitivity analysis. The main and safety outcomes will be compared across all randomised respondents.\n\nRandomisation: Randomisation of patients will be done through lottery method.\n\nRecruitment: The patients will be enrolled and assigned by the principal investigator.\n\nMethods: Data collection, analysis, and management\n\nObjectives: BS-PP, FBS (at the start and end of the treatment). The assessment will be done using the values at the start of the study, and on the 60th day (after treatment). The therapeutic strategy will be overseen by the main examiner, who contacted the respondents and kept track of their progress in paperwork.\n\nPlan to ensure that participants are retained, and that all follow-up is completed: By getting the patient’s phone number, we may stay in touch while giving them timely medication and advice for the follow-up, with the information from the follow-up being justifiably stored in the paperwork.\n\nPatients’ data will be gathered through clinical examination. The main examiner will enter the data into the master sheet, assess it using the appropriate statistical method, and code the data.\n\nBefore the trial begins, patients will be asked for their written informed permission.\n\nThe study was approved by the Institutional Ethics Committee,letterno. MGACHRC/IEC/July/2021/331.\n\n\nResults\n\nThe methods worked to lower blood sugar levels (fasting and post-meal) in the trial group. Implementing suitable dietary regimen and proper exercise during treatment decreased the likelihood of return of symptoms compared to taking regular metformin tablets for the patient.\n\n\nDiscussion\n\nThis study will compare the therapeutic efficacy of Nishamalaki Churna with honey and metformin tablets in individuals with type 2 diabetes mellitus who are obese. Nishamalaki is mentioned as the effective management of Madhumeha (Type-2 DM) in Ayurveda classics, according to ayurvedic literature. Haridra (Curcuma longa L) is a preferred medicine for type 2 diabetes mellitus. Both Nishamalaki Churna with honey and metformin tablets were found to effectively lower FBS and BS-PP levels. Turmeric and Indian gooseberry are found in Nishamalaki Churna. Haridra (turmeric) in Veerya (potency) is Ushna (hot), and Tikta Rasa (bitter) is useful in Kaphaja Vikaras (disorders related to kapha biohumour). These substances contain qualities such as Ruksha (dry), Ushna (hot), Tishna (bitter), and Katu Vipaka (pungent), which aid in Samprapti Vighatana (pathogenesis) and hence aid in managing the obese patients suffering from Type-2 DM. However, in this work, we looked at the differences in both formulations and their influence on objective metrics. In obese type 2 diabetes mellitus, the total effects revealed which formulation is extremely effective.\n\n\nConclusions\n\nIt can be concluded that Nishamalaki Churna will be as effective as Tablet Metformin in treating the obese patients suffering from Type-2 Diabetes Mellitus.",
"appendix": "Data availability\n\nNo data is associated with this article.\n\n\nReferences\n\nKasuga M: Insulin resistance and pancreatic β cell failure. J. Clin. Investig. 2006; 116(7): 1756–1760. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTsai AG, Williamson DF, Glick HA: Direct medical cost of overweight and obesity in the USA: a quantitative systematic review. Obes. Rev. 2011; 12(1): 50–61. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcKeigue PM, Shah B, Marmot MG: Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet. 1991; 337(8738): 382–386. PubMed Abstract | Publisher Full Text\n\nAmerican Diabetes, A: Standards of Medical Care in Diabetes-2019 Abridged for Primary Care Providers. Clin. Diabetes. 2019; 37(1): 11–34. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAgnivesha C: Charaka Samhita reprint: 2011, edited by Vaidya Yadavaji Trikamji Acharya, Chaukhamba Surbharati Prakashana, Varanasi. Chikitsasthana Prameha Chikitsa Adhyaya 6/26;447.\n\nPerera PK, Li Y: Functional herbal food ingredients used in type 2 Diabetes Mellitus. Pharm. Rev. 2012; 6(11): 37–45. Jan-Jun. Publisher Full Text\n\nDawane JS, Pandit V: Study the efficacy of herbal formulation Niśha-āmalakī in animal model of polycystic ovarian disease syndrome. ASL. 2019; 37(2): 86–93.\n\nFatima N, Hafizur RM, Hameed A, et al.: NurulKabir, Ellagic acid in Emblicaofficinalis exerts anti-diabetic activity through the action on β-cells of pancreas. Eur. J. Nutr. 2017 Mar; 56(2): 591–601. PubMed Abstract | Publisher Full Text\n\nD’Souza JJ, D’Souza PP, Fazal F, et al.: Anti-diabetic effects of the Indian indigenous fruit EmblicaofficinalisGaertn: active constituents and modes of action. FoodFunct. 2014 Apr; 5(4): 635–644. Publisher Full Text\n\nCunningham JJ, Mearkle PL, Brown RG: Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent Diabetes Mellitus. J. Am. Coll. Nutr. 1994; 13: 344–350. PubMed Abstract | Publisher Full Text\n\nSrivasuki KP: Nutritional and health care benefits of Amla. J. Pharmacogn. 2012; 3(2): 141–151."
}
|
[
{
"id": "213867",
"date": "16 Nov 2023",
"name": "Naushira Pandya",
"expertise": [
"Reviewer Expertise Diabetes management in older adults"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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:\n1.The mechanisms for T2 diabetes could be expanded (eg; hepatic glucose production, renal reabsorption etc). What is meant by completion of this era in paragraph 2 of the Introduction?\n2. How was the number of study subjects decided?\n\n3. Are the subjects also on other treatments for diabetes, or even metformin at higher doses?\n4. Will there be assessment of glycemic control in subjects prior to intervention with A1C levels?\n5. The term \"diabetics\" is no longer used due to patients' objections. They are people with diabetes, and not defined by diabetes.\n\n6. How is the dosage of Nishamalaki standardized? Will the honey cause a rise in blood glucose? If drugs are packaged in the same way, will metformin also be dosed the same way?\n\n7. Will subjects who may withdraw still be counted in the final results (intention to treat)? Removing their data will bias the results.\n8. How often will fasting and postprandial BG be checked? The Analytics section mentions day 15, 30, 45 but the Objectives state measurements at the start and day 60.\n9. Secondary outcomes is poorly formulated. Subjects already have the disease, so disease recurrence does not seem valid and is repeated in the text. Monitoring for adverse effects is standard and is not a secondary outcome. Unless specific outcomes such as hospitalization, hypoglycemia, weight loss are being studied.\n10. Randomization through lottery method needs to be explained further. If randomized, they cannot be assigned to a control or treatment group.\n\n11. Since this is a methods paper, the Results section cannot possibly predict the results. The same applies to the Discussion section which mentions both metformin and Nishamalaki were effective in lowering blood glucose levels without any data to prove this.\n\n12. Other agents in food or spices that are thought to lower blood glucose may be in the introduction to provide context, but NOT in the Discussion of the paper which is based on a specific research question.\n\n13. Similarly the Conclusion section is premature without data or proof.\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? No\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": [
{
"c_id": "10599",
"date": "30 Nov 2023",
"name": "Dr. Aman Chhabra",
"role": "Author Response",
"response": "Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond on each comments given by you and do the necessary corrections in the study protocol as asked. I request you to kindly review the responses and corrections and give the approval if you find it appropriate as early as possible. 1. The mechanisms of T2 Diabetes mellitus will be explained in detail in the Introduction part. In paragraph 2 of the introduction part, by the end of this era means with the start of next generation. 2. The number of subjects are decided as per the appropriate statistical formula for calculating the sample size. 3. Subjects are not on any other treatment or any higher doses of metformin. They are asked to participate after the completion of a washout period of other previous medicines if any. 4. Assessment of glycemic control with HbA1C levels prior to intervention will not be done due to non-affordability of the patients to perform HBA1C test. 5. The term \"diabetics\" will be removed from the manuscript and will be replaced by \"the patients suffering from Diabetes\". 6. The dosage of Nishaamalaki is standardized by the dosage mentioned in classical texts of Ayurveda. Honey will not cause any rise in blood glucose level. A supporting mother article for this fact is available. Metformin and Nishamalaki, both are packaged and dosed in the same way. 7. Subjects who may withdraw the study will not be counted but will get replaced by other subjects until the calculated sample size gets completed. Therefore, it will not cause any bias. 8. Fasting and postprandial Blood glucose levels will be checked on day 0 and at day 60 as mentioned in the assessment criteria. 9. Secondary outcome will be properly formulated by mentioning the study of lowering BMI score. 10. Randomization through lottery method will be explained properly. 11. Result and discussion are just an expectation of the outcome, which will be completely based on the data received after the completion of study. 12. Other agents like food or spics that helps in the management of Diabetes Mellitus will be mentioned in the Introduction section instead of Discussion. 13. Conclusion will be formed only after receiving the data after completion of the study. Currently, it is merely an expectation."
}
]
},
{
"id": "213873",
"date": "21 Nov 2023",
"name": "Supriya Bhalerao",
"expertise": [
"Reviewer Expertise Obesity",
"Type 2 Diabetes",
"NAFLD",
"PCOS"
],
"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 protocol is for assessing the efficacy of Nishamalaki in obesity, then why the introduction refers more to diabetes?\n\n‘Type of trial’ is wrong term. It should be ‘study design’.\n\nHow the blinding is possible? The nature of study drug and control drug is completely different-it should be an open study.\n\nThere are no variables reflecting improvement in obesity e.g. body composition or circumferences, lipid profile. How the FBS and PPBS can give idea about anti-obesity efficacy?\n\nThe authors need to decide whether they wish to demonstrate the efficacy of study drug in obesity or in diabetes.\n\nIs the rationale for, and objectives of, the study clearly described? No\n\nIs the study design appropriate for the research question? No\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": "10626",
"date": "30 Nov 2023",
"name": "Dr. Aman Chhabra",
"role": "Author Response",
"response": "Respected Mam, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments one by one. 1. As mentioned in the title, the study protocol is for assessing the efficacy of Nishaaamalaki and Metformin in obese patients suffering from Type-2 Diabetes Mellitus. The main focus is on Type-2 Diabetes Mellitus and not on obesity. Therefore, the Introduction refers more to Type-2 Diabetes Mellitus. 2. Type of trial is now replaced by Study design. 3. Blinding is for the allocation of groups not for the medicine. 4. Reduction in Body mass Index reflects improvement in obesity which is considered as the secondary outcome in this study. 5. It is totally clear and decided that the protocol is framed to compare the efficacy of trial and standard drug in obese patients suffering from Type-2 Diabetes Mellitus. I request you to kindly consider the responses and if you feel satisfied, then kindly give your necessary approval so that the peer review process can proceed further. Looking forward for your kind response. Thanks and Regards."
}
]
},
{
"id": "210017",
"date": "21 Nov 2023",
"name": "Srihari Sheshagiri",
"expertise": [
"Reviewer Expertise Ayurveda",
"Pediatrics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGrammatical errors needs corrections, in few area present tense and in few area past tense has been utilised by the authors.\n\nIn methods (abstract), inclusion of obese type 2 patients have been said a criteria for inclusion however in the article, BMI of 25-30 has been mentioned. One of the criteria to call a person obese is BMI above 30. Hence this needs clarity.\n\nComparing the efficacy of trial drug and standard group has been mentioned as secondary outcome. However, the same a been mentioned as the main aim in abstract and in conclusion of the article. The same needs clarification.\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? Partly",
"responses": [
{
"c_id": "10625",
"date": "30 Nov 2023",
"name": "Dr. Aman Chhabra",
"role": "Author Response",
"response": "Respected Sir, Thanks for your valuable review and comments on my manuscript. I would like to respond and clarify the comments given one by one. 1. Grammatical errors are now corrected and the entire manuscript is framed in future tense as per the guidelines for a protocol. 2. As per W.H.O., Obesity is a general term in which criteria of overweight has a classification of having B.M.I. score of 25-30 kg/m2, which is actually taken into consideration for this study protocol. , 3. The secondary outcome is now updated for better clarification. I request you to kindly review the corrected manuscript and if you feel satisfied with the corrections, kindly give your approval so as to proceed further in the peer review process. Looking forward for your kind response. Thanks"
}
]
}
] | 1
|
https://f1000research.com/articles/12-1199
|
https://f1000research.com/articles/12-511/v1
|
17 May 23
|
{
"type": "Research Article",
"title": "Knowledge, attitudes, and behaviour of college students in disposing used masks during the COVID-19 pandemic in DKI Jakarta Province",
"authors": [
"Avicenna Inovasanti",
"Dewi Susanna",
"Sandeep Poddar",
"Ema Hermawati",
"Aria Kusuma",
"Avicenna Inovasanti",
"Sandeep Poddar",
"Ema Hermawati",
"Aria Kusuma"
],
"abstract": "Background: The COVID-19 pandemic has increased the need for and production of masks. This creates a problem, namely the generation of mask waste which ends up in the environment without being managed. This research was conducted to determine the relationship between knowledge, attitudes, and sociodemographic factors with college student behaviours in managing household mask waste in Daerah Khusus Ibukota (DKI) Jakarta Province. Methods: This study used a quantitative approach and cross-sectional study design. Data collection was carried out using an online questionnaire consisting of the respondents' sociodemographic, knowledge, attitudes, and behaviours. Results: The majority of students had high knowledge (63.3%), positive attitudes (52.5%), and good behaviours (50.6%). Statistically, there was a significant relationship between knowledge and behaviours (p-value = 0.022), but there was no significant relationship between attitudes and behaviours (p-value = 0.269). In addition, the sociodemographic factor variables showed a significant relationship between place of residence and behaviours (p-value = 0.008). However, there was no significant relationship between age, gender, education, and study program groups and behaviours (p value> 0.05). Multivariate analysis showed that living with family was a dominant factor for bad behaviours (OR 1.664, 95% CI=1.124-2.464), and the second risk factor was the low level of knowledge has a significant relationship with the behaviours of mask waste management at home (OR=1.559, 95% CI=1.044-2.330). Conclusions: Students who live alone show better behaviour compared to students who live with their families. The place of residence variable has the greatest influence on the behaviour of mask waste management at the household, followed by the knowledge variable.",
"keywords": [
"COVID-19",
"knowledge",
"attitudes",
"behaviour",
"sociodemographic",
"college students",
"mask waste management",
"living alone"
],
"content": "Introduction\n\nThe world still tries to face a major disaster consequence of the COVID-19 pandemic. Preventive measures continue to be taken to control high transmission and spread, one of the effective steps that can be taken is to use a mask (Chowdhury, Chowdhury and Sait, 2020) (World Health Organization, 2020a). The decreasing cases of COVID-19 have made the Indonesian government decide to revoke Pemberlakuan Pembatasan Kegiatan Masyarakat (PPKM) under the Instructions of the Minister of Home Affairs Numbers 50 and 51 of 2022, but the government still advises the public to continue using masks properly (Menteri dalam Negeri Republik Indonesia, 2022a, 2022b). The high demand for masks has encouraged mass production and has experienced extraordinary growth (Du, Huang and Wang, 2022).\n\nThe generation of plastic waste in the world continues to increase due to masks amid the COVID-19 pandemic. If not handled properly, this mask waste may still carry pathogenic contaminants that can potentially become hazardous waste (Du, Huang and Wang, 2022). Disposable masks that are made from plastic base materials end up in public landfills and oceans without being managed, causing a big issue of the medical waste pollution in the environment (Saadat, Rawtani and Mustansar, 2020). According to Ocean Asia 2020 report, it is estimated that as much as 1.6 billion face masks globally end up in the oceans (Bondaroff and Cooke, 2020). Ministry of Environment and Forestry data shows that the mask waste generated in Indonesia has reached more than 3 million tons in 2020 (Meidiana, 2021). DKI Jakarta Province in 2020 is estimated to be the highest producer of medical waste of 1,125,154 kg per day. Research also estimates that, on average, people in DKI Jakarta Province produce 52.88 to 79.32 tons of mask waste per day (Sari et al., 2021).\n\nIn dealing with this issue, it is necessary to make prevention efforts by involving the community. The Indonesian government has made policies and guidelines for managing household mask waste (Amalia et al., 2020; Hesti, 2020). Disposable mask waste management is regulated starting from collecting and separating mask waste from domestic waste, spraying disinfectant on masks, changing the shape of masks before being disposed of by tearing or cutting them, wrapping mask waste in plastic bags or throwing it into a closed trash can, and washing hands with soap and running water or use hand sanitizer after disposing of mask waste (Kementerian Kesehatan RI, 2020; Menteri Lingkungan Hidup dan Kehutanan, 2020; Menteri Lingkungan Hidup dan Kehutanan Republik Indonesia, 2021).\n\nObedience in using masks is essential and heavily influenced by people’s knowledge, attitudes, and behaviours. According to Sukesih et al. (2020), a high level of knowledge encourages positive attitudes and good behaviours (Sukesih et al., 2020). By analysing the level of knowledge, attitudes, and behaviours, students can become important players in planning and ensuring preventive actions for the younger generation in preventing COVID-19 (Olaimat et al., 2020; Saefi et al., 2020). Other factors that influence public health behaviours are sociodemographic factors such as differences in age, gender, education, occupation, and region of origin (Moudy and Syakurah, 2020).\n\nSeveral studies have been conducted on the handling of COVID-19. However, the indirect impact of the pandemic still tends to be ignored such as managing household mask waste. College students become the object of this research as a generation with a high level of education and independency. Therefore, this study aimed to analyse the relationship between knowledge, attitudes, and sociodemographic factors with student behaviours in managing household mask waste in DKI Jakarta Province.\n\n\nMethods\n\nThis research was a quantitative study with a cross-sectional approach because the measurements of the dependent and independent variables were carried out only once at the same time. This study aimed to analyse the relationship between knowledge, attitudes, and sociodemographic factors with student behaviours in managing household mask waste in DKI Jakarta Province. The dependent variable studied was student behaviours in managing household mask waste and the independent variables were sociodemographic characteristics (age, gender, education, science groups, and place of residence), students’ knowledge, and attitudes in managing household mask waste.\n\nThe research was conducted in DKI Jakarta Province in October-November 2022 by distributing online questionnaires using the Google form platform via social media such as Line, WhatsApp, Instagram, and Twitter.\n\nThis study’s population was public and private university students over 18 years old with Diploma, Bachelor, Master, and Doctoral degrees in the Province of DKI Jakarta, totalling 698,368 students according to the BPS Province of DKI Jakarta in 2022 (Badan Pusat Statistik Provinsi DKI Jakarta, 2022).\n\nThe sample in this study were college students who had filled out a questionnaire according to the inclusion criteria. The samples were collected by purposive sampling using social media such as Line, WhatsApp, Instagram, and Twitter. The number of samples calculated using the Slovin Formula (Tejada and Punzalan, 2012):\n\nNotes:\n\nn = required sample size\n\nN = total number of students in DKI Jakarta province\n\ne = selected fault tolerance (0.05)\n\nBased on the results of sample calculations using the above formula, the rounded value of n (number of samples) is 400 samples of college students in DKI Jakarta Province. The inclusion criteria for research subjects were active students enrolled in tertiary institutions with Diploma, Bachelor, Master, and Doctoral degrees in the DKI Jakarta Province who were at least 18 years old and had the ability and willingness to fill out questionnaires distributed via the Google form. Exclusion criteria for research subjects were people who did not have status as students at tertiary institutions in the DKI Jakarta Province and respondents who gave multiple responses, did not fill out the questionnaire completely, and filled out the questionnaire outside the allotted time.\n\nThe respondent data was collected using an online questionnaire through the Google Forms platform and distributed using a purposive sampling method via social media, such as Line, WhatsApp, Twitter and Instagram. The target was college students who were studying at universities in DKI Jakarta Province. Of the 967 existing data then cleaning was carried out to determine samples that met the criteria. Then the first 425 respondents who met the inclusion criteria were selected. Respondents who did not meet the desired criteria including missing and incomplete data were removed from the research sample.\n\nThe instrument used in this study was an online questionnaire, which respondents filled out themselves using the Google form. A copy of the questionnaire can be found under Extended data (Susanna, Dewi, 2023). The questionnaire contained questions on age, gender, education, science groups, place of residence, level of knowledge, attitudes, and behaviours of students in managing household mask waste. The respondent had to approve the informed consent page before the research questionnaire page appeared. The informed consent page stated “All data, both personal data and the results of filling out the questionnaire will be kept confidential and only used for the needs of this research. This research is voluntary and subjects can withdraw at any time and there are no consequences. Completing this questionnaire takes time. about 10-15 minutes, without the risk that can occur during filling out the questionnaire”. The willingness question after the informed consent statement was “Are you willing to fill out this questionnaire?” with the answer options “willing” and “not willing”. If the respondent chose “willing” then they were directed to the questionnaire question page, and if they selected “not willing” they were directed to the last page. After all questions had been answered, the respondent clicked ‘submit’ to submit their response.\n\nThe questionnaire was made based on references to the questionnaires in previous research and based on legal aspects, which were then developed and modified by the researchers themselves.\n\nThe questionnaire used in this research contained four parts as follows: 1. Respondent’s identity, consisting of name, telephone number, type of e-wallet, age, gender, place of residence, education, name of college, and study program groups; 2. Knowledge about COVID-19; 3. The use of masks; 4. Mask waste management: disinfection of masks, changing the shape of masks, disposal in closed containers, separation of domestic waste, washing hands with soap before and after disposing of masks, and impact of masks waste disposal.\n\nThe distributed questionnaire consisted of 66 questions and sociodemographic data, knowledge, attitudes, and behaviours. Respondents who did not meet the desired criteria were removed from the research sample.\n\nValidity is the accuracy of a measuring instrument in measuring data in a study. This test is needed to determine whether the questions in the questionnaire are irrelevant. Validity and Reliability tests were carried out on 30 respondents. A variable will be said to be valid if the value of the Corrected Item – Total Correlation ≥0.361. The reliability test shows the degree to which the measurement results remain consistent if the measurement is carried out twice or more for the same symptoms and with the same measuring instrument. Reliability can be measured using the Cronbach Alpha method, measured based on a value of 0 to 1. A variable will be reliable if the Cronbach Alpha value shows a result ≥0.6. The results of invalid questions will be deleted so that the final questions total 27 questions on the knowledge variable, 17 on the attitude variable, and 13 on the behaviours variable.\n\nVariables are made binomial in the following way:\n\nGrouping of characteristics respondents are done by making the median the cut-off point because the data distribution is not normal. The groups of characteristics variable are: Age: ≥25 years and <25 years; Gender: Female and Male; Place of residence: Lives alone and Live with family; Education: Postgraduate (master and doctor) and Bachelor & Diploma; Study program groups: Health Clusters (Medicine, Pharmacy, Public Health, Dentistry, Nurse, and other health study programs) and Non-Health Clusters (Science, Social Sciences, Engineering, and Others); Knowledge variables are grouped into two categories: high (if result≥median (22)) and low knowledge (if result<median (22)); Attitude are grouped into two categories: positive (if result≥median (78)) and negative (if result <median (78)); Behaviours are grouped into two categories: Good (if the result≥median (55)) and bad (if the result <median (55)).\n\na. Univariate analysis\n\nUnivariate analysis aims to see the frequency and distribution of each independent and dependent variable. Univariate analysis of the knowledge variable was carried out to see the distribution of the frequency of correct answers to each question to find out how the respondents’ knowledge regarding the management of household mask waste is described. Univariate analysis of the attitude variable was carried out to see the results of the distribution of respondents’ answers to the attitude statement regarding the management of household mask waste. Univariate analysis of behavioural variables was carried out to see the frequency distribution of respondents’ answers to behaviour statements regarding the management of household mask waste.\n\nUnivariate analysis was also carried out to see the distribution of the percentage of answers regarding the behaviours of mask waste management in question number 9-13 in the behaviour section for respondents who have high knowledge and live alone. This analysis was conducted to find out which behaviours were most frequently performed by respondents. This distribution analysis was only carried out on the variables of knowledge and place of residence because only these two variables had a relationship with behaviour in this study.\n\nb. Bivariate analysis\n\nBivariate analysis used an association test between the independent and dependent variables. Bivariate analysis was performed using the Chi-Square test because the data used was categorical. Significance if the p-value ≤ α where the significance level α = 0.05, then there is a significant relationship between the independent and dependent variables. Conversely, if p-value > 0.05, there is no significant relationship between variable independents and dependent. Bivariate analysis was performed to determine candidate variables with a p-value ≤ 0.25 to be included in the multivariate analysis. The bivariate analysis also looked at the distribution of respondents’ frequencies and percentages for sociodemographic variables (age, gender, place of residence, education, and scientific background), high knowledge, low knowledge, positive attitudes, negative attitudes, good behaviours, and bad behaviours.\n\nc. Multivariate analysis\n\nMultivariate analysis was carried out to see which variables influence student behaviours in managing household mask waste. Multivariate analysis was performed using a logistic regression test with the enter method because it included all predictors into the analysis at once. Variables that will be included in this test are selected by selecting variables with a p-value ≤ 0.25 from the results of the bivariate test. After selecting the candidate variables, the initial modelling of multivariate analysis is carried out. If the results of the significance of the variables tested and the constants in the initial modelling are still > 0.05, then the variable with the greatest significant value is deleted. Logistic regression test was carried out again. If the results of the significance of each variable tested and the results of the significance of the subsequent test constants are ≤0.05 and there is no change in the OR value of more than 10%, then the test results become the final result of multivariate analysis. If the results of the logistic regression test are less than equal to α (p ≤ 0.05) then HI is accepted or there is a relationship between the independent and dependent variables. The exp(β) value determines the magnitude of the influence of a significant independent variable on the dependent variable.\n\nThis research has received ethical approval from the Commission of Research and Ethics Faculty of Public Health Universitas Indonesia No. Ket-156/UN2.F10.D11/PPM.00.02.2022. Written informed consent from participants was obtained.\n\n\nResults\n\nAn overview of knowledge was generated through univariate tests. Knowledge variables were measured using 18 questions. The following are the results of the descriptive analysis of the respondents’ knowledge (the full dataset can be found under Underlying data (Susanna D, 2023).\n\nBased on Table 1 it is known that most of the respondents have answered correctly. Questions about whether COVID-19 can be infected through droplets from sufferers when they cough or sneeze (Question no. 3) and whether masks that have been wet or dirty must be replaced immediately (Question no. 10) are the questions with the most correct answers (99.1%). The questions with the least number of respondents answered correctly were regarding mask disinfection with the answer choices being heated (31.8%), irradiated (22.4%), and with chemicals, for example chlorine or bleach (35.5%).\n\n* The highest number of respondents.\n\n** The fewest number of respondents.\n\nAn overview of attitudes was generated through a univariate test that was measured using 17 questions selected based on the five statements consisting of strongly disagree, disagree, neutral, agree and strongly agree answers. The following are the results of the analysis of respondents’ statements are shown in Table 2.\n\n* Amount most respondents.\n\nFrom the 425 respondents who already answered attitude questions, more than 50% of respondents choose the strongly agree option in all questions. Based on the results of the distribution, it can be seen that respondents strongly agree that disposable masks should not be reused (72.5%). There was still 0.7% of respondents who disagreed that COVID-19 is a real disease and masks that are dirty or wet should not be reused.\n\nAn overview of behaviours was generated through a univariate test that was measured using 13 questions selected based on five statements consisting of never, rarely, sometimes, often and always answers. The following are the results of the analysis related to the behaviour of the respondents.\n\nBased on Table 3, respondents always wear masks when going out of the house (70.8%). Respondents still rarely separate mask waste from domestic waste (11.8%). It was found that 16% of respondents had never disinfected masks before they were disposed of.\n\n* The highest number of respondents.\n\nBivariate analysis was conducted to see the relationship between the dependent and independent variables. This analysis can also be seen from the distribution of the frequency distribution of respondents from the grouping of knowledge (low and high), attitudes (negative and positive), behaviour (bad and good), and sociodemographic factors (age, gender, place of residence, education, and scientific background). Bivariate analysis was carried out with the Chi-Square test. The results obtained are as follows.\n\nBased on Table 4, the variables that have a significant relationship to behaviours are knowledge and place of residence with p < α (α = 0.05). The resulting p-value for the knowledge variable with behaviour is 0.022 (OR = 1.625, 95%CI = 1.092-2.418) while the place of residence variable has a p-value of 0.008 (OR = 1.722, 95% CI = 1.166-2.542). Attitude variable (p-0.269), age (p-0.557), gender (p-0.762), education (p-0.271), and scientific family (p-0.224) have a p-value > α so that they do not have a significant relationship with behaviour.\n\nMultivariate analysis was conducted using multiple logistic regression. The first step is to select variables from bivariate results with a significant level <0.25. The following are the results of the selection of bivariate analysis.\n\nBased on Table 5 shows that there are three variables included in the multivariate candidate: low knowledge, living with family, and non-health students. Bivariate analysis was carried out to select variables that could be used for multivariate analysis, namely variables with a p-value of more than 0.25.\n\n* p-value <0.25 is included in the multivariate candidate.\n\nFrom the results of the initial multivariate modelling in Table 6, it was found that the non-health students (study program group) variable still had a p-value > 0.05. The next step is to test the confounders by removing the independent variable with the largest p-value.\n\nBased on Table 7 there are no variables with changes in OR > 10%. Thus, the non-health students (study program group) variable is excluded from the modelling analysis. The following are the final modelling results of the logistic regression test:\n\nTable 8 is the final result of multivariate analysis using multiple logistic regression tests. From the table, the constant values show p-values < 0.05. Knowledge and behaviour variables show a positive regression coefficient with a value of p = 0.030 (OR = 1.559, 95% CI = 1.044-2.330). This result can suggest that students with low knowledge have a tendency to have a bad mask waste management behaviour 1.6 times greater than students who have high knowledge.\n\nLike the knowledge variable, the place of residence variable also shows a positive regression coefficient and significant relationship with behaviour with a p-value=0.011 (OR = 1.664, 95% CI = 1.124-2.464). This result means that students who live with their families are 1.7 times more likely to have bad mask waste management behaviour than those who live alone. The results of logistic regression also show that the OR value of living with family is greater than low knowledge so that the place of residence variable has the greatest influence on student behaviour in managing household mask waste.\n\n\nDiscussion\n\nStudents in this study had high knowledge (63.3%) and more than 90% respondents in 13 questions answered correctly. The easiest questions to answer are number three regarding COVID-19 which can be spread through droplets from sufferers when coughing or sneezing and number 10 regarding masks that have been wet or dirty must be replaced immediately (99.1%). Both of these questions have a high degree of ease for respondents to answer because information about the mode of transmission of COVID-19 and its prevention has been widely disseminated during the pandemic. Transmission of COVID-19 occurs through close contact with an infected person from the respiratory tract when coughing or sneezing (Zakianis et al., 2021). Preventing transmission through coughing or sneezing can be done by wearing a mask. However, if the mask is dirty or wet and not replaced immediately, it can cause difficulty breathing (Das et al., 2021). A study on the use of masks found that pathogens on the outer surface of masks that have been wet or dirty have a high risk of causing self-contamination so that masks are no longer effective at protecting against COVID-19 (Howard et al., 2021).\n\nThe most difficult question answered correctly by respondents regarding how to disinfect masks is in question number 16 in options a, b, and c. Only 22.4% chose irradiation, 31.8% heat, and 35.5% used chemicals, such as chlorine or bleach. Various actions including washing, boiling, baking, sun exposure, blowing a hair dryer, autoclaving, alcohol, or ultraviolet irradiation have been recommended to decontaminate mask pathogens. This can be done to protect the environment from pollution due to disposal of masks (Ma et al., 2020). The Ministry of Health of the Republic of Indonesia has also recommended disinfecting masks before disposal using a disinfectant liquid, chlorine or bleach (Kementerian Kesehatan RI, 2020). These questions are difficult to answer because information on how to disinfect masks is still difficult to access, both in the community and social media. Because of this, students need to increase their knowledge, especially in the management of mask waste because they are considered one of the main forces for raising awareness among families and communities.\n\nThe knowledge gap can have an adverse effects during a pandemic because it can increase confusion in society (Noreen et al., 2020). University students are widely described as opinion leaders in their local communities when it comes to health because of their perceived high levels of health literacy (Baker et al., 2021). The students in this study showed that they have a high level of literacy as well as technological advances in today’s information dissemination, especially from social media, which enabled them to answer almost every question correctly.\n\nStudents’ attitudes show positive results (52.5%). Most of them have a positive attitude towards using a mask that must cover their mouth, nose and chin (70.4%), agree that disposable masks cannot be reused (72.5%), and masks that are dirty or wet should not be reused (70.8%). These results indicate that respondents have a high awareness of using a good mask. The World Health Organization has recommended using a mask by covering the nose, mouth and chin and not reusing disposable masks. When the mask is dirty and wet it must be replaced immediately (World Health Organization, 2020b).\n\nMasks that must be replaced every four hours in question number seven became the statement with the most agree answer choices (35.3%). Masks can only effectively be used within 3-4 hours so if it has exceeded that time it should be replaced (Prata et al., 2021). The Ministry of Health of the Republic of Indonesia also recommends wearing masks for no more than four hours and always providing spare masks (Kementerian Kesehatan RI, 2021). In the statement regarding masks that must be disinfected with disinfectant liquid before being disposed of, it was found that 11.8% of respondents chose neutral and this was the highest percentage in the neutral choice. This shows that there are still 11.8% of respondents who do not realize the importance of disinfecting masks before disposal. Disinfection is necessary to reduce decontamination in the environment (Ma et al., 2020).\n\nAttitudes toward washing masks with soap/detergent still found 1.6% of respondents choosing to disagree. The World Health Organization has recommended washing masks using soap/detergent. This has to be done to reduce virus contamination found in masks (World Health Organization, 2020b). The Indonesian Ministry of Health through the Directorate of Health Promotion and Community Empowerment has distributed flyers on how to clean cloth masks, such as using soap and detergent (Direktorat Promosi Kesehatan Dan Pemberdayaan Masyarakat Kementerian Kesehatan RI, 2020). Increasing information and counselling from the government regarding mask disinfection and how to wash masks needs to be done so that a more positive attitude can be built and evenly shared by every student.\n\nThe question on whether COVID-19 is a real disease in question number one was the statement with the most strongly disagree answers (0.7%). Public distrust in the presence of COVID-19 can be caused by false information that is spread on various platforms. In the midst of a situation that makes people restless and sad, fake news about the coronavirus was circulating in various media, especially social media. The Ministry of Communication and Information on 17 April 2022 recorded 5,829 hoaxes about COVID-19 circulating in the media (Kementerian Komunikasi dan Informatika, 2022). In addition to these statements, the statement about masks that are dirty or wet should not be reused is also the statement with the most strongly disagree answers (0.7%) even though 70.8% of respondents voted strongly agree. When masks get wet or dirty, they should be changed immediately and should not be worn for a long time (Das et al., 2021). The need for masks, which then becomes higher when the replacement of masks is more frequent, allows for reluctance to purchase masks, especially among students.\n\nThe majority of students already have good behaviour (50.6%), but the percentage of students with bad behaviours is not too different. Thus, it can be said that there are still many students who have bad behaviour. The majority of respondents indicated that they always wear masks when going out of the house (70.8%). Since the COVID-19 pandemic was announced by WHO, everyone has been advised to wear masks, especially when going out of the house (World Health Organization, 2020a). In question number three regarding not reusing medical masks, the percentage of answer choices often is the most chosen by respondents (37.4%). There are still 23.8% of students sometimes changing masks every four hours. Not reusing medical masks and changing masks every four hours has been recommended by WHO because reusing medical masks is ineffective and allows viruses and bacteria to remain (World Health Organization, 2020a).\n\nThe behaviour of separating mask waste from domestic waste was found by 11.8% respondents who rarely practiced it. Mask waste is included in infectious waste which must go through special treatment and a sorting process separately from other waste before being disposed of in the domestic waste bin (Sumiarsih and Rasniah Sarumi, 2021). The Ministry of Environment and Forestry of the Republic of Indonesia has issued a circular to the public which advises to separate mask waste from domestic waste (Menteri Lingkungan Hidup dan Kehutanan Republik Indonesia, 2021). Facilities and infrastructure for sorting mask waste from domestic waste are inadequate so it is still difficult to carry out with students in this study. Solutions are needed to managed mask waste so it does not end up in the environment mixed with other domestic waste and become a source of hazardous waste.\n\nThere were also respondents who had poor behaviour in disinfecting masks before disposal. As many as 16% of students have never disinfected masks before disposing them. Mask disinfection before disposal is necessary to reduce contamination in the environment (Rubio-Romero et al., 2020). However, students’ knowledge, attitudes and behaviour towards mask disinfection is still poor. There needs to be education around the easiest methods for the community to disinfect masks, such as by using bleach, floor cleaning liquid, or disinfectant liquid which are widely available.\n\nKnowledge shows a significant relationship with students’ behaviour and is positively correlated with p=0.030 (OR = 1.559, 95% CI = 1.044-2.330). The students with low knowledge have a 1.6 times greater risk of poor behaviour in managing mask waste compared to those with high knowledge. This research is in line with research conducted in Vietnam that found there is a relationship between knowledge and behaviour with a p value <0.001 (Le An et al., 2021).\n\nThe group of respondents with good knowledge was also seen to frequently engage in mask waste management behaviour. From the results of the distribution, it was found that 57.6% of students with good knowledge had often damaged masks by cutting or tearing them, 32.7% had often disinfected masks before disposal, 52.8% had often disposed of mask waste in a closed bin, 34.2% had often separated mask waste with domestic waste, and 47.6% have washed their hands with soap and running water after disposing of masks.\n\nThis finding illustrates that the majority of respondents with high knowledge have often performed good behaviour in managing household mask waste. This explains that people who are highly knowledgeable tend to have better behaviour. Therefore, it is necessary to increase student knowledge about better management of mask waste to encourage behaviour. Counselling and education in increasing knowledge can be carried out through various media such as print media, electronic media, social media, to peer group approaches, and instructions or appeals from Regional Heads, both Governors and Regents/Mayors (Retnaningsih et al., 2020).\n\nIn this study, no significant relationship was found between attitudes and behaviour, so the hypothesis was rejected. This suggests that the level of behaviour may not increase even though their attitude is better. For example, the majority of respondents strongly agree that it is their responsibility to disinfect first with a disinfectant liquid before disposing of the mask (51.8%) but they might not do it properly. This may also occur due to a misunderstanding of the respondent in answering so that the results shown are not the actual attitude of the student. This result is inconsistent with the results of previous research which found a significant correlation between attitudes and behaviour, which explains that those with better attitudes will also have better behaviour (Islam et al., 2021).\n\nThe results of the analysis shows that the p-value of the age variable is 0.557 so that there is no significant relationship between age and behaviour. This is also seen in the variables of gender, education, and scientific family which produce a p-value>0.05 so that they do not have correlation with behaviour. The previous research conducted by Sulistyawati (2021) showed that there was a relationship between gender and behaviour but there was no relationship between age and education (Sulistyawati et al., 2021). Another study conducted by Le An et al. (2021) resulted in a relationship between gender and behaviour but there was no significant relationship between age, education level, and major or scientific groups (An et al., 2021). Health students should be the one who have better mask waste management behaviour. However, in this study, no relationship was found between scientific group and behaviour. This might happen because knowledge about managing mask waste in households is also still low. Information and socialization of policies regarding the management of mask waste is still very rare. Facilities and infrastructure in Indonesia are also inadequate so that students from both the health group and non-health group do not have a different influence on behaviour.\n\nOf the five sociodemographic factors, only the residence variable has a significant and positive correlation with students’ behaviour in managing mask waste. The analysis resulted in a p-value of 0.011 with an OR of 1.664 (1.124-2.464). The hypothesis in this case is accepted. Students who live with their families have a 1.7 times greater tendency to behave badly compared to students who live alone. The residence variable is the variable with the greatest influence on the behaviour of mask waste management followed by the knowledge variable. This result is not in line with research in Vietnam which did not have a significant relationship between place of residence and behaviour (p = 0.653) (Le An et al., 2021). Research in Korea also shows no relationship between where you live and behaviour (Lee, Kang and You, 2021).\n\nRespondents who live alone already have good mask waste management behaviour. From the results of the distribution analysis in a group of students who live alone and behaviour, it was found that 51.7% of students had always destroyed masks before they were disposed of, 35.4% had always disinfected, 48.9% had always disposed of them in closed bins, 38.2% had always separated them from domestic waste, and 38.8% had washed their hands frequently after disposing of the mask. The influence of the family when students live together affects their behaviour because they tend not to have their own autonomy and depend on the rules made by their parents (Hatabu et al., 2020). Living alone is one of the considerations for students who can show stronger self-control and take safer actions than others. Research conducted in Japan shows that place of residence is a significant factor in demonstrating safer behaviour (Hatabu et al., 2020). The place of residence variable is also the variable that has the greatest influence on the behaviour of household mask waste management.\n\nIncreasing knowledge is needed as a way to make people aware of the importance of managing household mask waste and encourage better behaviour. In the current situation, the government is experiencing difficulties in dealing with medical waste that appears from both hospitals and households. The public should be aware that if disposed of improperly, this waste can still carry traces of viral contaminants and can cause serious problems in the future (Dharmaraj et al., 2021). Policies related to the management of mask waste need to be tightened and balanced with adequate infrastructure so that behaviour improvement in the community can be carried out properly. Education on infectious waste management is also needed to increase public knowledge, awareness, and ability to sort, minimize, destroy, collect, package, and store waste properly (Sari et al., 2021). This is because mask waste that ends up in the environment can carry harmful pathogens that can pollute the environment (Du, Huang and Wang, 2022). In the case of the COVID-19 pandemic, this virus can survive for three days on plastic surfaces so that it can become a source of transmission for COVID-19 (Salian et al., 2021).\n\nThe strength in this study lies in the target population which was college students who are widely seen as a generation with high health literacy among their friends and social environment. There is also little research on the management of mask waste in Indonesia so this study can become a reference in making policies and more scientific approaches can be adopted to facilitate mask waste control. The participation of the central and regional governments is very important in monitoring and coaching the community. Without policies and government participation in terms of the importance of managing mask waste before it is disposed of in the community, it will be difficult to create good habits that can be carried out by the community in the household.\n\nThis study still has limitations because data collection was carried out online so that there is a potential for result bias and errors in interpretation of the questionnaire questions. To overcome this, questions in the questionnaire gave information and use language that was easier to understand. Validity and reliability tests were carried out to ensure that the data obtained was of high quality. The sample size may be sufficient for statistical analysis but the results can be more representative if a larger sample is used so further research is needed to solve this problem. Further research can also be carried out by analysing other factors that can influence the behaviour of mask waste management.\n\n\nConclusion\n\nCollege students in DKI Jakarta Province tend to have high knowledge, positive attitudes, and good behaviour in managing household mask waste. Knowledge and place of residence have a significant relationship with behaviour. However, attitude, age, gender, education and scientific group did not show a significant relationship with behaviour. The higher the student’s knowledge, the better behaviour will be encouraged. Students who live alone show better behaviour compared to students who live with their families. The place of residence variable has the greatest influence on the behaviour of mask waste management at the household, followed by the knowledge variable.\n\nFollowing the findings of this research, some recommendations were addressed for the governance of DKI Jakarta Province. The Provincial Government of DKI Jakarta can conduct outreach and education to the public both directly and digitally to provide information on how to properly manage household mask waste and improve facilities and infrastructure in the community environment so that mask waste management can be carried out properly in accordance with regulation. Policies that can support the improvement of mask waste management in households is also needed. Further research can examine variables and other factors related to the behaviours around household mask waste management and develop educational media regarding the management of mask waste.",
"appendix": "Data availability\n\nDryad: Relationship of knowledge, attitudes, and sociodemographic factors with behavior in the management of mask waste in households. https://doi.org/10.5061/dryad.8931zcrvm (Susanna D, 2023).\n\nThis project contains the following underlying data:\n\n- DATA_425_RECODE.sav-_NEW1.sav\n\nThis project contains the following extended data:\n\n- Questionnaire.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\nThe authors express many thanks to the Universitas Indonesia through the Directorate of Research and Development which has provided research funding assistance through International Indexed Publication Grants Q1.\n\n\nReferences\n\nAmalia V, et al.: Penanganan limbah infeksius rumah tangga pada masa wabah COVID-19. Lp2M. 2020; 2. 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Promotif: Jurnal Kesehatan Masyarakat. 2021; 11(2): 122–129. Publisher Full Text\n\nSusanna D: Relationship of knowledge, attitudes, and sociodemographic factors with behavior in the management of mask waste in households.16 February 2023. Publisher Full Text\n\nTejada JJ, Punzalan JRB: On the Misuse of Slovin’s Formula. Philipp. Stat. 2012; 61(1): 8.\n\nWorld Health Organization: Anjuran mengenai penggunaan masker dalam konteks COVID-19. Who; 2020a; p. 1. (April). Reference Source\n\nWorld Health Organization: Penggunaan Masker Dalam Konteks COVID-19. WHO; 2020b; pp. 1–23. Reference Source\n\nZakianis, et al.: Sociodemographic and environmental health risk factor of COVID-19 in Jakarta, Indonesia: An ecological study. One Health. 2021; 13(August): 100303. Elsevier B.V. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "208840",
"date": "06 Oct 2023",
"name": "Armin Šljivo",
"expertise": [
"Reviewer Expertise Public Health and 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\nThe paper entitled \"Knowledge, attitudes, and behaviour of college students in disposing used masks during the COVID-19 pandemic in DKI Jakarta Province\" provides us information regarding the other side of the COVID-19 pandemic. The paper is robust and need further clarification on some points.\nComments:\nAbstract.\nFirstly, I would advise the authors to use more complex sentence structures, as the first two sentences of the Background part could be merged.\nSecondly, in the Results section please put p= instead of p-value=, as we all know what p stands for.\nThirdly, put keywords according to the MESH browser.\nIntroduction: Just see if there are other similar research papers like this one, and add data from it.\nMethods.\nFirstly, does this study have an Ethical approval and if so, please add it in the Manuscript. If not, explain why and why doesn't it need the Ethical approval.\nSecondly, add us the explanation how did You manage to prevent multiple responses from one individual, as the platforms used in this setting doesn't prevent multiple responses. And if You used the one answer per e-mail method, please provide us the explanation how was anonymity preserved.\nThirdly, I would advise You to give us the example of the study questioner either in Table or Supplement and to give us information regarding the internal consistency. You have explained it in the Methods, but the numbers should be added.\nOverall, this part needs and extensive clarification also in the Limitations part of the Discussion as some points have flaws which could further pose a bias or a confounding.\n\nResults: They are appropriate\nDiscussion: Please add more literature and references and the futures of this study.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? 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": [
{
"c_id": "10765",
"date": "17 Jan 2024",
"name": "Dewi Susanna",
"role": "Author Response",
"response": "Dear Armin Šljivo, Thank you very much for your comments and recommendations for improvement. Here are we respond point by point as mentioned below: Comments: 1. Abstract. a. Firstly, I would advise the authors to use more complex sentence structures, as the first two sentences of the Background part could be merged. Responses: We have paraphrased it with a more complex sentence in the background section of the abstract (page 1). The COVID-19 pandemic has increased the need for mask production which has caused the problem of mask waste generating in the environment without being managed. b. Secondly, in the Results section please put p= instead of p-value=, as we all know what p stands for. Responses: We have revised some parts to use “p=” instead of “p-value=” (page 1, on result section of the abstract) Statistically, there was a significant relationship between knowledge and behaviours (p = 0.022), but there was no significant relationship between attitudes and behaviours (p = 0.269). In addition, the sociodemographic factor variables showed a significant relationship between place of residence and behaviours (p = 0.008). However, there was no significant relationship between age, gender, education, and study program groups and behaviours (p > 0.05). Also, in the text, all the changes of p value to be marked in yellow block. c. Thirdly, put keywords according to the MESH browser. Responses: We have revised the keywords using MESH. COVID-19, knowledge, attitudes, practice, sociodemographic factors, students, waste management, cross-sectional studies. 2. Introduction: Just see if there are other similar research papers like this one, and add data from it. Responses: We have added similar research papers on introduction and added data from it. Research conducted on students in Thailand shows that there was a positive correlation between facemask disposal knowledge and practices (p < 0.01) (Kaewchutima et al., 2023) A study conducted in 2021, shows a statistically significant association found among knowledge level and educational qualification (p < 0.0001) and gender (p < 0.001) (Jalal et al., 2021). 3. Methods. a. Firstly, does this study have an Ethical approval and if so, please add it in the Manuscript. If not, explain why and why doesn't it need the Ethical approval. Responses: We have added the ethical approval number on page 17 (word document) This research has received ethical approval from the Commission of Research and Ethics Faculty of Public Health Universitas Indonesia No. Ket-156/UN2.F10.D11/PPM.00.02.2022. b. Secondly, add us the explanation how did You manage to prevent multiple responses from one individual, as the platforms used in this setting doesn't prevent multiple responses. And if You used the one answer per e-mail method, please provide us the explanation how was anonymity preserved. Responses: We carried out screening by selecting samples that fit the inclusion criteria including sorting based on their email. Apart from that, we carry out cleaning by using a frequency distribution list. We only keep this data as a reference to differentiate samples, but we do not process their personal data so that we can ensure that each respondent's data will not be spread out c. Thirdly, I would advise You to give us the example of the study questioner either in Table or Supplement and to give us information regarding the internal consistency. You have explained it in the Methods, but the numbers should be added. Responses: We’ve added questionnaire on appendix 1 as additional information in this sheet. Overall, this part needs and extensive clarification also in the Limitations part of the Discussion as some points have flaws which could further pose a bias or a confounding. Responses: We’ve added strength and limitation on page 17 (word document). This research is using online platform, so it is easier to reach many respondents and cheaper. This research is also using a cross-sectional study so that it is able to explain the relationship between one variable and other variables in the population. However, it does not have the ability to explain the dynamics of changes in conditions in different time periods. Thank you for your valuable comments and suggestions. Best regards, Authors. Appendix 1: Questionnaire First Part - The Informed Consent “All data, both personal data and the results of filling out the questionnaire will be kept confidential and only used for the needs of this research. This research is voluntary and subjects can withdraw at any time and there are no consequences. Filling in this questionnaire takes time. about 10-15 minutes, without the risk that can occur during filling out the questionnaire\". The willingness question after the informed consent statement was. \"Are you willing to fill out this questionnaire?\" with the answer options \"willing\" and \"not willing\". If the respondent chooses \"willing\" then they will be directed to the questionnaire question page, while if the answer is \"not willing\" they will be directed to the last page. Second Part – Personal Information Respondent’s Name Gender (male, female) Age (18-24 y.o, 25-32 y.o, >32 y.o) Domicile (Jabodetabek, Outside Jabodetabek) Place of Residence Are you a student? Third Part – Respondent’s Education Information Education Level (Diploma, S1, S2, S3) University Location (Jakarta, Depok, Bekasi, Tangerang, etc) Name of college Study program groups Fourth Part - Knowledge Regarding COVID-19 and Mask Waste Management (True or False) Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the cause of COVID-19 COVID-19 can cause respiratory tract disease COVID-19 can be infected through droplets from sufferers when they cough or sneeze Using a mask properly can prevent transmission of COVID-19 How long can the mask be used? (4 hours) Cloth masks should be made of three layers Using a mask must cover the mouth and nose tightly Before using a mask, you must clean your hands with soap and running water or hand sanitizer Used masks cannot be reused Masks that have been wet or dirty must be replaced immediately Disposable masks should be disposed of immediately after removal Used mask waste should be disposed of separately from domestic waste After throwing away the used mask, you must clean your hands with soap and running water or hand sanitizer What should be done before throwing used disposable masks in the trash? Change the shape Discard in a closed trash can How to change the shape of the mask? Cut the masks Be destructed Ripped off Which are the way to disinfect masks? Heated Irradiated With chemicals, e.g. chlorine or bleach Which are the right way to wash cloth masks? Using soap or detergent Using hot water Soaked for 1 minute Which are the impact if used masks are not disposed of properly? Sources of COVID-19 transmission Environmental pollution Sources of Hazardous Waste Fifth Part – Attitudes Regarding COVID-19 and Mask Waste Management Notes: five statements consisting of strongly disagree, disagree, neutral, agree and strongly agree answers I believe that COVID-19 is a real disease Using a mask correctly can reduce the risk of being infected with COVID-19 Using a mask must cover the mouth, nose and chin Using a medical mask is more effective in reducing the risk of spreading COVID-19 compared to cloth masks Disposable masks should not be reused Masks that are dirty or wet should not be reused Mask should be changed every 4 hours Washing cloth masks should use hot water Washing the mask preferably using soap/detergent Before the mask is thrown away, it should be cut with scissors Before the mask is disposed of, it should be disinfected first with disinfectant liquid Used masks that are not disposed of properly can be a source of COVID-19 transmission Used masks that are not disposed of properly can pollute the environment Used masks that are not deformed by breaking or cutting can increase risk of being reused Mask waste should be disposed of separately from domestic waste Masks that have been used must be immediately disposed of in a closed bin After throwing away the masks, you should wash your hands using soap and running water Sixth Part – Behaviour Regarding COVID-19 and Mask Waste Management Notes: five statements consisting of never, rarely, sometimes, often and always answers I wear a mask covering mouth, nose and chin I wear a mask when I go out of the house I do not reuse medical masks I change the mask if it is already dirty or wet I change the mask every 4 hours I use hot water for washing cloth masks I use soap/ detergent for washing cloth masks I soaked the cloth mask for 1 minute before rinsed I cut or damaged the mask before disposed it I disinfect the mask before disposed it with liquid disinfectant I dispose used masks into closed bins I separate masks waste from domestic waste I wash my hands with soap and running water after disposed my mask Thank you very much again for reviewing this manuscript for improvement. Best regards, Authors."
}
]
},
{
"id": "214918",
"date": "18 Oct 2023",
"name": "Narisara Kaewchutima",
"expertise": [
"Reviewer Expertise Waste management/ Environmental management/ Environmental policy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear authors,\nAfter reviewing through the article, it is interesting study particularly in the used facemask management in university students. However, I have some comments for giving more discussion in detail as following:\n- Discussion: Although, several studies have recommended cutting facemasks into small pieces before discarding them to avoid reuse. However, the used facemasks are infectious waste, cutting them into small pieces may increase the volumes of infectious waste in the environment. So, this practice may also complicate waste disposal and have many consequences, particularly for humans and the environment. You may discuss more in this issue, because it is one of an important practices in facemask management.\n- Discussion: To further clarify the impact of a student's place of residence on facemask disposal behavior, it would be beneficial to provide additional details regarding the observed difference in behavior between students who live with their families and those who live alone. Specifically, it is essential to elaborate on the definition of \"living alone.\" Does this pertain to students who reside in university dormitories or those who have separate accommodations in houses or apartments? The distinction is crucial because, in university dormitories or private housing arrangements, facilities such as specific disposal bins may be available. The provision of these amenities could encourage students to consistently dispose of facemasks in the designated bins, ultimately promoting better disposal practices. These could be beneficial to support your result.\n- Discussion: If considered relevant, the authors could present more perspective of knowledge and practice among university students during the pandemic from the more or less same demographic (in this case, e.g., Southeast Asia). These following papers could be considered to be cited: https://doi.org/10.1371/journal.pone.0284492\nThank you\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?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "10764",
"date": "17 Jan 2024",
"name": "Dewi Susanna",
"role": "Author Response",
"response": "Responses to the Comments’ Reviewer-1 Dear Narisara Kaewchutima Department of Environmental Health and Technology, Walailak University, Thai Buri, Nakhon Si Thammarat, Thailand Nopadol Precha Environmental Health, Walailak University, Thai Buri, Nakhon Si Thammarat, Thailand Thank you very much for assessing our manuscript. Here are our responses in addressing point by point of your comments. The comments and responses: Dear authors, After reviewing through the article, it is interesting study particularly in the used facemask management in university students. However, I have some comments for giving more discussion in detail as following: - Discussion: Although, several studies have recommended cutting facemasks into small pieces before discarding them to avoid reuse. However, the used facemasks are infectious waste, cutting them into small pieces may increase the volumes of infectious waste in the environment. So, this practice may also complicate waste disposal and have many consequences, particularly for humans and the environment. You may discuss more in this issue, because it is one of an important practices in facemask management. Response: Cutting facemasks after using it is one of the ways to prevent from reuse. This way may increase the volumes of infectious waste in the environment so that is why the government's role in effective management of increasing medical waste is needed. We already add more information in page 16 (word document) as additional information. A constructive methodology or system must be adopted so that the increasing management of medical waste can be carried out effectively in every country in the world. Adequate waste recycling or its conversion to other energy forms may be an excellent solution that can be implemented by any government to control the current situation. Common techniques used for the COVID-19 waste treatment include the Incineration, Physical and Chemical methods. These techniques are applied to handle the different types of waste that are carried by the COVID-19. An alternative way to overcome the problem is improvised face mask production either made through nanotechnology or biomaterial instead of microplastic and should be completely biodegradable so that it may not harm the terrestrial as well as the marine ecosystem (Dharmaraj et al., 2021b). - Discussion: To further clarify the impact of a student's place of residence on facemask disposal behavior, it would be beneficial to provide additional details regarding the observed difference in behavior between students who live with their families and those who live alone. Specifically, it is essential to elaborate on the definition of \"living alone.\" Does this pertain to students who reside in university dormitories or those who have separate accommodations in houses or apartments? The distinction is crucial because, in university dormitories or private housing arrangements, facilities such as specific disposal bins may be available. The provision of these amenities could encourage students to consistently dispose of facemasks in the designated bins, ultimately promoting better disposal practices. These could be beneficial to support your result. Response: The additional explanation on page 16. In this study, living alone define students that are not live with their family whether they live in dormitory, in house, or apartments. - Discussion: If considered relevant, the authors could present more perspective of knowledge and practice among university students during the pandemic from the more or less same demographic (in this case, e.g., Southeast Asia). These following papers could be considered to be cited: https://doi.org/10.1371/journal.pone.0284492 Response: Thank you for your reference, we’ve added more information from those study case to introduction page 2 and 19 (word document) Research conducted on students in Thailand shows that there was a positive correlation between facemask disposal knowledge and practices (p < 0.01) (Kaewchutima et al., 2023) A study conducted in 2021, shows a statistically significant association found among knowledge level and educational qualification (p < 0.0001) and gender (p < 0.001) (Jalal et al., 2021). Jalal, S.M. et al. (2021) ‘Assessment of knowledge, practice and attitude about biomedical waste management among healthcare professionals during COVID-19 crises in Al-Ahsa’, Healthcare (Switzerland), 9(6). Available at: https://doi.org/10.3390/healthcare9060747. Kaewchutima, N. et al. (2023) ‘Knowledge and practice of facemask disposal among university students in Thailand: A new normal post the COVID-19 pandemic’, PLoS ONE, 18(4 APRIL). Available at: https://doi.org/10.1371/journal.pone.0284492. Thank you for your valuable comments and suggestions. Best regards, Authors."
}
]
}
] | 1
|
https://f1000research.com/articles/12-511
|
https://f1000research.com/articles/12-930/v1
|
03 Aug 23
|
{
"type": "Research Article",
"title": "Diagnostic strategies for muscular dystrophies: a cross-sectional study",
"authors": [
"Franklin Hanna Rodriguez",
"Jorge Mario Estrada-Alvarez",
"Juan Guillermo Murillo",
"Gloria Liliana Porras-Hurtado",
"Jorge Mario Estrada-Alvarez",
"Juan Guillermo Murillo",
"Gloria Liliana Porras-Hurtado"
],
"abstract": "Background: Muscular dystrophies are a wide heterogeneity group of neuromuscular diseases that very often constitutes a challenge for clinicians to perform an adequate diagnosis. Many patients remain underdiagnosed o misdiagnosed consequently affecting their prognosis and quality of life. Therefore, we aimed to establish clinical and molecular characteristics of patients with increased CPK levels and muscular dystrophies in our region to facilitate diagnosis and follow-up on patients with suspected muscular dystrophies. Methods: A cross-sectional study was made using a retrospective search of patients attended in Comfamiliar Risaralda between 2010 and 2021. The study included patients from both genders and all ages who presented with a diagnosis of polymyositis, myoclonus, myopathy, and muscular dystrophy between 2010 and 2022 in Comfamiliar Risaralda. Patients with CPK levels lower than 500 U/L were excluded. Results: A database analysis was carried out from 2010 to 2022 of 5219 patients treated in a fourth-level care institution in the Eje Cafetero region, finding 221 patients filtered by a diagnosis of myopathy, myoclonus, polymyositis, and dystrophy. We found a combined prevalence of all muscular dystrophies of 4.2 per 100.000 habitants, Duchenne muscular dystrophy of 0.6 per 100.000 habitants, limb-girdle muscular dystrophy of 0.6 per 100.000 habitants, facioscapulohumeral dystrophy of 0.5 per 100.000 habitants, Bethem dystrophy, type 2 Emery Dreifuss muscular dystrophy and merosin-deficient muscular dystrophy of 0.1 per 100.000 habitants. A diagnostic sequence was elaborated from clinical and paraclinical features found in our patients. Conclusions: Although muscular dystrophies consist of a heterogeneous group of neuromuscular diseases, there are still clinical and paraclinical features that can help physicians to detect any particular case and perform a good approach and follow-up. Our diagnostic sequence will facilitate physicians to determine any particular muscular dystrophy.",
"keywords": [
"muscular dystrophy",
"Duchenne",
"Facioscapulohumeral",
"Bethlem",
"Limb-girdle",
"strategies",
"Merosin-deficient",
"Emery Dreifuss."
],
"content": "Introduction\n\nCreatine phosphokinase (CPK) is an enzyme that catalyzes phosphocreatine to facilitate the release of the energy required by the muscle for its contraction.1 This enzyme is widely distributed in all tissues with high-energy demand. Approximately, 70% of CPK is found in the musculoskeletal system, 20-30% in the cardiac muscle, and 5-10% in the nervous system.2 CPK presents in three different molecular forms depending on the tissue: BB, MB, and MM.2 Blood levels of CPK are mainly from the muscle MM isoenzyme. The blood concentration of CPK depends on multiple factors such as gender, race, age, muscle mass, and physical activity.3,4 Normal values are: white female <= 325 IU/L, white male <= 504 IU/L, black female <= 621 IU/L, and black male <= 1200 IU/L.5 In general, the term CPKAEMIA is considered when CPK levels are greater than 1.000 IU/L or 1.5 times the upper limit of normal.5\n\nFor transient CPK elevations, multiple causes must always be ruled out in the initial diagnostic confrontation. Intense physical exercise, trauma, generalized tonic-clonic seizures, acute psychosis, systemic connective tissue diseases, renal or cardiac failure, viral diseases that cause myopathies such as influenza, coxsackie, adenovirus, prostate cancer, celiac disease, obstructive sleep apnea, moderate to severe hypothyroidism, drugs such as statins, fibrates, antiretrovirals, beta-blockers, clozapine, angiotensin II receptor antagonists, hydroxychloroquine, isotretinoin, and colchicine; neuromuscular diseases such as Guillain Barré, amyotrophic lateral sclerosis, myopathy due to the use of corticosteroids, hyperthyroidism, collagen diseases, alcoholism, procedures such as intramuscular injections and electromyography have been described as possible etiologies.6–12 Besides that, the most frequent causes of CPK elevation are genetic diseases such as muscular dystrophies, congenital myopathies, channelopathies, mitochondrial myopathies, and myotonic dystrophies, although exercise can also temporarily increase CPK levels due to rhabdomyolysis.2,13\n\nMuscular dystrophies are classified according to their genetic transmission mechanism, either autosomal dominant or recessive, and those linked to the X chromosome. It can also be done based on the structural and functional deficiency of the protein complex as dystrophinopathies (Duchenne muscular dystrophy and Becker), laminopathy (LGMD 1B and Emery dreifuss), sarcoglycanopathies (LGMD 2C, 2D, 2E, 2F), dysferlinopathies (LGMD 2B), calpainopathies (LGMD 2A), myotilinopathies (LGMD 1A), and caveolinopathies (LGMD 1C).14,15\n\nDystrophies can affect different stages of life. Its onset depends on the type of dystrophy: congenital or adulthood, present between 20 and 30 years of age, and it can even have such mild clinical manifestations that consultations for the disease are made only until an older age. In some cases a phenomenon called “anticipation” may occur, that is, when the clinical manifestations may occur earlier in the children than in their parents; or spontaneous mutations, such as the Duchenne type, which occur in children without a family history of the disease.\n\nRegarding affected muscles, each muscular dystrophy compromises similar or different muscular types. Duchenne and Becker muscular dystrophy affect striated and cardiac muscles with associated increased CPK levels between 10 and 50 times the upper limit of normal; facioscapulohumeral muscular dystrophy affects striated muscle and respiratory muscles with associated increased CPK levels between 1 and 10 times the upper limit of normal; Bethlem muscular dystrophy affects only striated muscle with associated increased CPK levels between 1 and 10 times the upper limit of normal; limb-girdle muscular dystrophy affects striated, cardiac and respiratory muscles with associated increased CPK levels between 1 and 50 times the upper limit of normal; Emery Dreifuss muscular dystrophy affects striated and cardiac muscles with associated elevated CPK levels from 1 to 10 times the upper limit of normal.\n\nEarly clinical complications of CPK elevation include liver dysfunction and arrhythmias; late complications include disseminated intravascular coagulation (DIC) and acute kidney injury (AKI).13 Thanks to new advances in gene therapy, there are current trials targeting to restore damaged genes in different dystrophies (Duchenne, limb-girdle, and Emery Dreifuss). These new therapies use adeno-associated virus to infect damaged tissues and deliver a cDNA copy of the functional gene. The results have not been published out yet but there are early promising reports, with studies in mice having demonstrated therapeutic efficacy.15–18\n\nLess common muscular dystrophies are congenital myopathies such as myosin storage myopathy 7A, which is an autosomal dominant disease with a heterozygous mutation in the MYH7 gene.19 It has phenotypic variability with an age onset ranging from early childhood to late adulthood. Affected individuals have proximal muscle weakness of the upper and lower limbs, and distal muscle weakness of the lower limbs, resulting in gait difficulties and scapular winging (scapuloperoneal myopathy).19 The severity is also variable, and CPK levels may be normal or elevated.19 The disease is usually slowly progressive and most patients remain ambulatory. Skeletal muscle biopsy can show a nonspecific myopathic pattern.19\n\nLastly, acute viral myositis is another cause of elevation in CPK levels that could mask muscular dystrophies. According to Cardin et al, it constitutes a syndrome that generates musculoskeletal impairment after upper airway disorders that results in temporarily limited ambulation, muscle pain, and lower-limb weakness, especially in the calves and thighs.20 The disease management is usually symptomatic of respiratory and musculoskeletal symptoms including analgesics or anti-inflammatory drugs.20\n\nRegarding the comments above, we aimed to establish clinical and molecular characteristics of patients with increased CPK levels and muscular dystrophies in our region to facilitate diagnosis and follow-up on patients with suspected muscular dystrophies.\n\n\nMethods\n\nA cross-sectional study was made using a retrospective search of patients attended in Comfamiliar Risaralda between 2010 and 2021. The study included patients from both genders and all ages who presented with CPK levels greater than 500U/L, and diagnosis of polymyositis, myoclonus, myopathy, and muscular dystrophy. Patients with CPK levels lower than 500 U/L were excluded to differentiate from those with any suspected muscular dystrophy.\n\nIn an initial instance of the study, a retrospective institutional active search was made through text mining in laboratory databases for all CPK measures carried out by the Comfamiliar Risaralda laboratory between 2010 and 2021. After that, the results were purified and organized under the criteria of registered CPK elevation, and again the search language in databases was made to extract new confirmed or repeated diagnoses that could explain the CPKemia.\n\nData collection was implemented through a study-specific case report form (CRF). A detailed data validation plan that identified missing data, out-of-range data and other data inconsistencies in the form of revision checking was implemented on the platform before the start of the study.\n\nThe collected information was entered into the RedCAP platform, where the CRF was previously located with validation and automated fields if applicable.\n\nDiscrepancies in the data were reported to the team as queries. Access to the database was restricted through password protection to authorized data management personnel.\n\nDescriptive statistics were obtained for numerical variables, including measures of central tendency such as mean and median. Descriptive statistics for categorical variables included a tabulation of frequencies with counts and percentages.\n\nThe estimation of prevalences was carried out employing Bayesian inference since they allow a greater gain in precision in the estimation of parameters with values below 10%, as well as it was carried out utilizing a beta-binomial model under the binom package of R software. Statistical analyzes were also performed in R software.\n\nThe study was approved by the Ethics Committee of the Comfamillar Risaralda Clinic (Approval number 0088; Approval date: May 16, 2022). All the participants gave informed consent for anonymous data usage.\n\n\nResults\n\nA database analysis was carried out from 2010 to 2022 of 5219 patients treated in a fourth-level care institution in the Eje Cafetero region. From those, we included 2170 patients who had CPK levels greater than 500 U/L, excluding 3049. Subsequently, we analyzed medical records to filter patients diagnosed with polymyositis, myoclonus, myopathy, and muscular dystrophy finding 221 patients and excluding 1949 patients with other causes of elevated CPK levels such as hypothyroidism, acute myocardial infarction, cardiac insufficiency, rhabdomyolysis, seizures, drugs including statins, fibrates, and nonclear causes. After reviewing the medical records of 221 patients located under ICD-10 codes for probable or confirmed dystrophies, we identified that 23 patients died from various causes, 48 patients did not accept participation in the study, and 98 patients did not meet the inclusion criteria for the investigation due to other causes of CPK elevation. Among these 98 patients, the other causes of CPK elevation that we found were drowning (submersion injuries), perinatal asphyxia, cranioencephalic trauma caused by a car accident, trauma caused by white weapons, and electrostatic discharge. We obtained 52 patients who were recruited for an initial medical evaluation (Figure 1).\n\nAfter performing the medical consultation with each patient, 23 were excluded because some did not meet the clinical criteria for any muscular dystrophy but for other causes of transient elevation of CPK levels, and others manifested discontinuation in the study (Table 1). In addition, the patients underwent a second medical consultation by a geneticist to corroborate and classify the remaining 29 patients. On the other hand, we found from the 29 patients, a mean CPK value of 3231.241, a standard deviation of 5019.543, and a maximum of 22670.\n\n\nDiscussion\n\nSeveral studies have described the different types of muscular dystrophy. However, there is poor evidence analyzing multiple muscular dystrophies within the same population. This leads to heterogeneity in studies regarding prevalences, clinical manifestations, and a good genotype-phenotype correlation. In our study, we found patients with Duchenne and Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, Emery Dreifus muscular dystrophy, merosin-deficient muscular dystrophy, and autosomal dominant congenital myopathy 7A (Table 2). Therefore, to identify a patient with a particular type of disease, clinicians should follow a diagnostic sequence not only for differentiating muscular dystrophy from other inflammatory myopathies but also to discriminate the specific type.\n\n* CrI: Credibility Intervals were estimated by Bayesian inference using Beta functions as prior.\n\n** Point Prevalence: It is a mean posterior distribution.\n\nIn our study, we analyzed the clinical and molecular characteristics of 29 patients with muscular dystrophy in Colombia. According to Mercuri and Muntoni, the prevalence of Duchenne muscular dystrophy is 8-29 per 100 000 boys; Becker muscular dystrophy has a prevalence of 7-29 per 100 000 boys; limb-girdle muscular dystrophy has a prevalence of 0.8-5.7 per 100 000 inhabitants; myotonic dystrophy has an estimated prevalence of 10-6 per 100 000 men, followed by facioscapulohumeral muscular dystrophy with a prevalence of three per 100 000 men, and myosin storage disease with noncurrent reported prevalence.14 We found a combined prevalence of all muscular dystrophies of 4.2 per 100.000 habitants, Duchenne muscular dystrophy of 0.6 per 100.000 habitants, limb-girdle muscular dystrophy of 0.6 per 100.000 habitants, facioscapulohumeral dystrophy of 0.5 per 100.000 habitants, Bethem dystrophy, type 2 Emery Dreifuss muscular dystrophy, merosin-deficient muscular dystrophy and myosin storage disease of 0.1 per 100.000 habitants. These prevalences are lower than those reported in the literature and can be explained due to a bias regarding the filter we used to find the patients. We included patients from both genders and all ages who presented with a diagnosis of polymyositis, myoclonus, myopathy, and muscular dystrophy. However, some other suspected cases could have been recorded with different diagnoses, due to misdiagnosis or underdiagnosis, leading to underestimation.\n\nIn general, the most common types of inflammatory myopathies are polymyositis, dermatomyositis, and inclusion body myositis.21 An adequate diagnosis is done on a clinical basis and confirmed by laboratory tests, muscle enzyme concentrations, autoantibodies, electromyography, and muscle biopsy.21 In our study, we included patients not only by CPK levels but also from diagnostic records. This is due to the fact that some patients are misdiagnosed with these kinds of inflammatory myopathies and not all patients had muscle enzyme concentrations. Consequently, from the initial diagnosis until the revision of clinic histories in our study, some patients with muscular dystrophies could have remained without optimal treatment. Therefore, an accurate diagnosis is crucial due to the impact on treatment and prognosis. Nava y Orozco-Barocio suggests that for differentiating muscular dystrophies from polymyositis, dermatomyositis, and inclusion body myositis, the diagnosis should be based on positive family history, the relatively insidious onset and slow progression of the disease.21\n\nMuscular dystrophies are a varied and complex group of neuromuscular diseases with a wide heterogeneity in clinical manifestations. Some other more frequent diagnoses might mask a real case of muscular dystrophy as in the case of a suspected acute viral myositis. Very often, physicians tend to approach these patients with symptomatic treatment for a short period without actually ruling out muscular dystrophy. In this study, 13.1% of patients diagnosed with polymyositis, myoclonus, myopathy, and probable muscular dystrophy ended with confirmed muscular dystrophy after performing a revision of their clinical histories and re-consultation of such patients. There is still a high probability of misdiagnosis or underdiagnosis that might result in lost patients with a likely deteriorated quality of life by the lack of optimal treatment. At least a 6-month follow-up should be implemented to rule out newly o persistently elevated CPK levels that might suggest a muscular dystrophy.\n\nNon-diagnosed patients with muscular dystrophy and associated complications can also dissuade physicians from diagnosing adequately. Depending on the type of muscular dystrophy, some complications such as restrictive lung disease, cardiomyopathy, scoliosis, corticosteroid side effects, and psychosocial issues can generally lead professionals to focus only on the direct acute cause of the signs and symptoms and not to search for a long-term systemic etiology like muscular dystrophy.22 Therefore, clinicians need to figure out that patients presenting with some acute diseases, especially in recurrent cases, might also be associated with muscular dystrophy to keep in mind.\n\nDuchenne muscular dystrophy age onset of symptoms is in early childhood around the age of 5 years, it is rapidly progressive and most patients lose ambulation around 10-15 years old, leading them wheelchair dependent.23 Becker muscular dystrophy symptoms can start around 10-20 years old but in some cases, permanent asymptomatic until adulthood even >30 years, and remain ambulant even until their 60s.23,24 In our study, we found that most patients had similar features as previously reported in the literature. Three patients were revealed with the c.6439-?_6912+?del p.(Glu2146_Val2304del) mutation who presented with a mild phenotype of Becker muscular dystrophy. At the moment of consultation, they had a mean age of 48 years (SD 40-54). All of them presented with hyporeflexia, mild muscle weakness, age onset of symptoms between 10 and 20 years old, and any of the three patients were wheelchair dependant. Greer et al. reported this same mutation in a patient with Becker muscular dystrophy who lost ambulation by the age of 15 years.25 They suggest that patients with apparently identical exonic deletions are almost certainly going to have different genomic breakpoints and therefore will be missing different intronic regions, and potentially, splicing motifs resulting in different phenotypes.25 Vengalil et al. also identified that patients with deletions of exons 45-47 are clinically related to the development of cardiomyopathy and earlier wheelchair dependence.26 Further studies analyzing genotype-phenotype correlation in patients with muscular dystrophy would be helpful to better understand the pathogenesis, and predict phenotypes.\n\nFacioscapulohumeral dystrophy has an onset around 10-20 years old. Still, there are some unusual cases where the symptoms are present at the moment of birth, and some others remain asymptomatic their whole life. By the age of 20 years, 50% of the cases have developed symptoms, and eventually, 20% of the affected require a wheelchair, which is consistent with our study where patients with facioscapulohumeral dystrophy developed symptoms after 20 years old.27\n\nIn Bethlem muscular dystrophy, the symptoms can range from congenital to mid-adulthood, been the congenital cases extremely rare.28 The progression is slow and more than 2/3 of the affected older than 50 years require supportive means (cane, crutches, wheelchair) for outdoor mobility.29 This is consistent with our study where we found one patient with Bethlem muscular dystrophy who presented as a congenital case that also had supportive means for outdoor mobility.\n\nLimb-girdle muscular dystrophy is an extremely heterogeneous group. Over 30 distinct subtypes have been identified, in which the onset of symptoms is at any age with some severe congenital cases and some mild cases starting in adulthood; the severity is also variable.30 As stated in the literature, we found four patients with variable phenotypes ranging from mild disease with onset of symptoms over 20 years old to more severe cases with early onset of symptoms in childhood.\n\nEmery Dreifuss muscular dystrophy onset of symptoms begins in the first two or three decades of life.31 The progression is slow, and loss of ambulation can occur in the autosomal dominant variant but is rare in the X-linked variant.32 We found one patient with Emery Dreifuss muscular dystrophy whose symptoms corresponded with those reported in the literature.\n\nMerosin-deficient muscular dystrophy is a severe type with symptoms present at the moment of birth, with neonatal profound hypotonia, poor spontaneous movements, and respiratory failure;33 most affected children do not acquire independent walking. It has been reported that only 15% of individuals acquired independent ambulation,34 and only a few patients gained the ability to walk with assistance but subsequently lost the ability.35 In our study, we identified one patient with Merosin-deficient muscular dystrophy who presented with profound hypotonia since birth and was diagnosed at two months old with CPK levels and molecular test. Currently, this patient can adequately sit but has problems with gait. These features correspond with phenotypes previously reported in the literature but without respiratory compromise.\n\nWe also found a patient with autosomal dominant congenital myopathy 7A with a phenotype that presented in early childhood at 14 months old, with significant proximal and distal muscle weakness. In addition, the patient presented with a severe restrictive pulmonary pattern, and a myopathic pattern in electromyography without cardiac alterations. Currently, at his adult age, this patient has proximal and distal quadriparesis and hypoesthesia of the left hemibody. These features correspond with the previously reported in the literature.\n\nOn the other hand, 12 patients with muscular dystrophy remained unclassified despite their clinical suspicion and after undergoing molecular tests. As previously exposed, patients with similar exonic deletions are going to have different genomic breakpoints. The number of genetic alterations that can be involved in muscular dystrophies is huge. Therefore, performing a single molecular test sometimes is not enough to identify the specific mutation related to the phenotypic presentation of the patient. Table 3 shows a brief review of the clinical and paraclinical approach to the different types of muscular dystrophy. Table 4 shows the detailed classification of each type of muscular dystrophy.\n\nBarohn et al. propose a series of steps regarding the patient’s symptoms by establishing which muscle-related symptoms patients demonstrate; determining the temporal evolution of the symptoms; interrogating if there is a family history of a myopathic disorder; finding out if there are precipitating factors that trigger episodic weakness or stiffness; asking if there are associated systemic symptoms or signs; and lastly, identifying the distribution of Weakness.36 After completing the 6 steps, clinicians could now attempt to classify a myopathic disorder according to the patterns of muscle weakness. The findings on the physical examination, particularly the distribution of muscle weakness, should provide additional information in determining the correct diagnosis.36\n\nSubsequently, CPK levels are extremely helpful for the evaluation of patients with a suspected myopathy. The CPK levels are usually elevated in most patients with muscle disease but may be normal in slowly progressive myopathies.36 Depending on the degree of CPK levels, it can be useful in distinguishing different forms of muscular dystrophy. As in the case of Duchenne muscular dystrophy, CPK levels can be elevated from 10 to more than 100 times the upper limit of normal, whereas in Facioscapulohumeral muscular dystrophy, the CPK levels are expected to be elevated from 1 to 10 times the upper limit of normal. We also must rule out nonmyopathic factors that can alter CPK levels such as profound muscle wasting, corticosteroid administration, collagen diseases, alcoholism, or hyperthyroidism.36\n\nLater, we should look for electromyography and nerve conduction studies. These studies can help to distinguish primary neuropathic from myopathic disorders by confirming that the muscle is the correct site of the lesion and that weakness is not the result of an underlying motor neuron disease, neuropathy, or neuromuscular junction disorder.36 However, their sensitivity and specificity are low. Normal results provide evidence of a nonsevere neuromuscular disorder.5\n\nA few years ago, if the electrodiagnostic features suggested a myopathic pattern, a muscle biopsy was recommended. Additionally, we can now diagnose muscular dystrophies through molecular tests without performing muscle biopsies in all suspected patients. Table 5 shows the patterns of muscular dystrophy applied to the 29 participants of the study.\n\nThe strengths of this study are the diagnostic sequence to classify muscular dystrophy, and the fact that this was the first study exploring multiple types of muscular dystrophy within the same population in this region. Regarding limitations, a bias in the filter we used to find the patients could have allowed for underestimation in some frequencies. Some prevalences that we found need confirmation in further studies.\n\n\nConclusions\n\nAlthough muscular dystrophies consist of a heterogeneous group of neuromuscular diseases, there are still clinical and paraclinical features that can help physicians to detect any particular case and perform a good approach and follow-up. In our region, many patients with muscular dystrophy remain underdiagnosed or misdiagnosed, which in consequence it compromises their prognosis without adequate treatment. Therefore, our diagnostic sequence will facilitate physicians to identify any of the most frequent muscular dystrophies.",
"appendix": "Data availability\n\nZenodo: Diagnostic strategies for muscular dystrophies: a Cross-Sectional Study, https://doi.org/10.5281/zenodo.7992665. 37\n\nThis project contains the following underlying data:\n\n• ProyectoDistrofiaMus_DATAv2.csv\n\n• Table 3 sequencing.xlsx\n\n• Table 4 muscular dystrophies.xlsx\n\n• Table 5 duchenne patients.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\nRowland, Willner, Cerri: Approaches to the membrane theory of muscular dystrophy. Muscular Dystrophy Adv. New Trends. 1980; 3: 3–20. Publisher Full Text\n\nSteccone MA, Cattani A, Imbelloni MI: Rabdomiólisis: causas y consecuencias de CPK elevada desde el laboratorio de análisis clínicos. Rev Bioquímica Patol Clínica. 2021 Apr 22; 85(2): 43–50.\n\nNanji AA: Serum creatine kinase isoenzymes: A review. Muscle Nerve. 1983 Feb; 6(2): 83–90. Publisher Full Text\n\nWong ET, Cobb C, Umehara MK, et al.: Heterogeneity of Serum Creatine Kinase Activity among Racial and Gender Groups of the Population. Am. J. Clin. Pathol. 1983 May 1; 79(5): 582–586. Publisher Full Text\n\nMoghadam-Kia S, Oddis CV, Aggarwal R: Approach to asymptomatic creatine kinase elevation. Cleve. Clin. J. Med. 2016 Jan; 83(1): 37–42. Publisher Full Text\n\nChesson AL, Kasarskis EJ, Small VW: Postictal Elevation of Serum Creatine Kinase Level. Arch. Neurol. 1983 May 1; 40(5): 315–317. PubMed Abstract | Publisher Full Text\n\nNoakes TD: Effect of Exercise on Serum Enzyme Activities in Humans. Sports Med. 1987; 4(4): 245–267. Publisher Full Text\n\nSiegel AJ, Silverman LM, Holman BL: Elevated creatine kinase MB isoenzyme levels in marathon runners. Normal myocardial scintigrams suggest noncardiac source. JAMA. 1981 Nov 6; 246(18): 2049–2051. PubMed Abstract | Publisher Full Text\n\nHagberg M, Michaelson G, Ortelius A.: Serum creatine kinase as an indicator of local muscular strain in experimental and occupational work. Int. Arch. Occup. Environ. Health. 1982 Oct; 50(4): 377–386. PubMed Abstract | Publisher Full Text\n\nGriffiths PD: Serum levels of ATP: Creatine phosphotransferase (creatine kinase). The normal range and effect of muscular activity. Clin. Chim. Acta. 1966 Apr; 13(4): 413–420. Publisher Full Text\n\nNúñez Gil IJ, Álvarez-Rodríguez E, Amérigo García MJ, et al.: Miositis viral aguda del adulto. An. Med. Interna. 2006 Feb; 23(2): 98–98. PubMed Abstract | Publisher Full Text\n\nSwash M, Schwartz MS, Carter ND, et al.: BENIGN X- LINKED MYOPATHY WITH ACANTHOCYTES (MCLEOD SYNDROME): ITS RELATIONSHIP TO X-LINKED MUSCULAR DYSTROPHY. Brain. 1983; 106(3): 717–733. Publisher Full Text\n\nLippi G, Schena F, Ceriotti F: Diagnostic biomarkers of muscle injury and exertional rhabdomyolysis. Clin. Chem. Lab. Med. CCLM. 2018 Dec 19; 57(2): 175–182. PubMed Abstract | Publisher Full Text\n\nMercuri E, Muntoni F: Muscular dystrophies. Lancet. 2013 Mar; 381(9869): 845–860. Publisher Full Text\n\nPozsgai E, Griffin D, Potter R, et al.: Unmet needs and evolving treatment for limb girdle muscular dystrophies. Neurodegener. Dis. Manag. 2021 Oct; 11(5): 411–429. PubMed Abstract | Publisher Full Text\n\nDuan D, Goemans N, Takeda S, et al.: Duchenne muscular dystrophy. Nat. Rev. Dis. Primers. 2021 Feb 18; 7(1): 13. Publisher Full Text\n\nMercuri E, Bönnemann CG, Muntoni F: Muscular dystrophies. Lancet. 2019 Nov; 394(10213): 2025–2038. Publisher Full Text\n\nWaldrop MA, Flanigan KM: Update in Duchenne and Becker muscular dystrophy. Curr. Opin. Neurol. 2019 Oct; 32(5): 722–727. Publisher Full Text\n\nCassandra LK: CONGENITAL MYOPATHY 7A, MYOSIN STORAGE, AUTOSOMAL DOMINANT. CMYP7A; 2023 [cited 2023 Mar 31]. Reference Source\n\nCardin SP, Martin JG, Saad-Magalhães C: Clinical and laboratory description of a series of cases of acute viral myositis. J. Pediatr. 2015 Sep; 91(5): 442–447. PubMed Abstract | Publisher Full Text\n\nNava A, Orozco-Barocio G: Abordaje en el diagnóstico diferencial de las miopatías inflamatorias. Reumatol. Clínica. 2009 Nov; 5: 32–34. PubMed Abstract | Publisher Full Text\n\nYiu EM, Kornberg AJ: Duchenne muscular dystrophy. J. Paediatr. Child Health. 2015 Aug; 51(8): 759–764. Publisher Full Text\n\nDarras BT, Urion DK, Ghosh PS: Dystrophinopathies.Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993 [cited 2023 Feb 3]. Reference Source\n\nYazaki M, Yoshida K, Nakamura A, et al.: Clinical Characteristics of Aged Becker Muscular Dystrophy Patients with Onset after 30 Years. Eur. Neurol. 1999; 42(3): 145–149. PubMed Abstract | Publisher Full Text\n\nGreer K, Mizzi K, Rice E, et al.: Pseudoexon activation increases phenotype severity in a Becker muscular dystrophy patient. Mol. Genet. Genomic Med. 2015 Jul; 3(4): 320–326. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVengalil S, Preethish-Kumar V, Polavarapu K, et al.: Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Confirmed by Multiplex Ligation-Dependent Probe Amplification: Genotype-Phenotype Correlation in a Large Cohort. J. Clin. Neurol. 2017; 13(1): 91–97. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPreston MK, Tawil R, Wang LH: Facioscapulohumeral Muscular Dystrophy.Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993 [cited 2023 Feb 3]. Reference Source\n\nFoley AR, Mohassel P, Donkervoort S, et al.: Collagen VI-Related Dystrophies.Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993 [cited 2023 Feb 3]. Reference Source\n\nJöbsis GJ, Keizers H, Vreijling JP, et al.: Type VI collagen mutations in Bethlem myopathy, an autosomal dominant myopathy with contractures. Nat. Genet. 1996 Sep; 14(1): 113–115. Publisher Full Text\n\nMurphy AP, Straub V: The Classification, Natural History and Treatment of the Limb Girdle Muscular Dystrophies. Lochmüller H, editor. J. Neuromuscul. Dis. 2015 Jul 22; 2(s2): S7–S19. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBonne G, Leturcq F, Ben Yaou R: Emery-Dreifuss Muscular Dystrophy.Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993 [cited 2023 Feb 3]. Reference Source\n\nBonne G, Mercuri E, Muchir A, et al.: Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene. Ann. Neurol. 2000 Aug; 48(2): 170–180. PubMed Abstract | Publisher Full Text\n\nJones KJ: The expanding phenotype of laminin alpha2 chain (merosin) abnormalities: case series and review. J. Med. Genet. 2001 Oct 1; 38(10): 649–657. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGeranmayeh F, Clement E, Feng LH, et al.: Genotype–phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations. Neuromuscul. Disord. 2010 Apr; 20(4): 241–250. PubMed Abstract | Publisher Full Text\n\nOliveira J, Parente Freixo J, Santos M, et al.: LAMA2 Muscular Dystrophy.Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993 [cited 2023 Feb 3]. Reference Source\n\nBarohn RJ, Dimachkie MM, Jackson CE: A Pattern Recognition Approach to Patients with a Suspected Myopathy. Neurol. Clin. 2014 Aug; 32(3): 569–593. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEstrada-Alvarez JM, Porras-Hurtado GL, Hanna FA: Diagnostic strategies for muscular dystrophies: a Cross-Sectional Study. [Data set]. F1000 Res (Version 1). Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "204452",
"date": "22 Sep 2023",
"name": "Prajnya Ranganath",
"expertise": [
"Reviewer Expertise Clinical Genetics",
"Genetic Neuromuscular Disorders"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe title is inappropriate. The study describes the spectrum of muscular dystrophies seen in a hospital-based set-up and the discussion is mostly focused on the utility of serum CPK. There is very little mention of other diagnostic strategies.\n\nOnly 29 cases have been finally categorized as muscular dystrophies. The number is very small and it is a very heterogeneous group which includes dystrophinopathies, LGMD, myotonic dystrophy, congenital muscular dystrophy and FSHD.\n\nIt is not clear how the authors have derived the population prevalence of the various muscular dystrophies based on a study done in a hospital setting/ hospital-based registry.\n\nAs per Table 5, a significant number of patients (12 out of 29) do not have conclusive molecular test reports to confirm the diagnosis and to accurately establish the type of muscular dystrophy. The molecular reports, wherever available, which are mentioned, are mostly not as per standard variant notation guidelines.\n\nElevation of serum CPK in muscular dystrophies and the different ranges of serum CPK expected in different types of muscular dystrophies are very well studied and well established and this study does not add anything novel to the existing knowledge about muscular dystrophies.\n\nInflammatory myopathies, viral myositis and other acquired causes of muscle involvement are discussed in length - this does not appear to be very relevant to the topic.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "10449",
"date": "04 Mar 2024",
"name": "Comfamiliar Risaralda",
"role": "Author Response",
"response": "Dear editor-in-Chief: Thank you for reviewing our manuscript titled “Diagnostic strategies for muscular dystrophies: a cross-sectional study\". We thank the reviewers for their overall positive comments and for the pertinent points they have raised. The recommendations were considered and incorporated into the new version of the manuscript. Please find attached our responses to the comments point-by-point. We have indicated clearly in each case the revisions to the manuscript that address their questions and suggestions. We feel that the manuscript has improved significantly from their critique, and we hope that you will find it acceptable now for publication in F1000Research. Yours sincerely, EIC comments: 1. The title is inappropriate. The study describes the spectrum of muscular dystrophies seen in a hospital-based set-up and the discussion is mostly focused on the utility of serum CPK. There is very little mention of other diagnostic strategies. Reply: We greatly appreciate the EIC comments. Following your suggestions, we reviewed the discussion again so that the types of dystrophies were clear. 2. Only 29 cases have been finally categorized as muscular dystrophies. The number is very small and it is a very heterogeneous group which includes dystrophinopathies, LGMD, myotonic dystrophy, congenital muscular dystrophy and FSHD. Reply: We greatly appreciate the EIC comments. Indeed, we analyzed a base of 750.000 users treated in a reference hospital in central-western Colombia that has an average of 2 million inhabitants. Only 29 cases had these diagnoses according to elevated CPK levels and diagnoses with probable dystrophy. 3. It is not clear how the authors have derived the population prevalence of the various muscular dystrophies based on a study done in a hospital setting/ hospital-based registry. Reply: We greatly appreciate the EIC comments. The prevalences reported in this study are related to a population of patients who were tested for multiple indications including CPK levels. Therefore, the underlying population for the estimation was this group of patients who consulted to our institution. Thus, the annotation regarding population prevalence is valid, and it may be a translation error to report prevalence per 100,000 inhabitants. Due to limitations of the study, we cannot talk of a population prevalence but rather of a hospital prevalence. We also have a related paragraph in the discussion section that explains how we searched for the population: “These prevalences are lower than those reported in the literature and can be explained due to a bias regarding the filter we used to find the patients. We included patients from both genders and all ages who presented with a diagnosis of polymyositis, myoclonus, myopathy, and muscular dystrophy. However, some other suspected cases could have been recorded with different diagnoses, due to misdiagnosis or underdiagnosis, leading to underestimation.” The corrections were made in the following way in the discussion section: “We found a combined prevalence of all muscular dystrophies of 4.2 per 100.000 habitants among patients treated in our hospital base, Duchenne muscular dystrophy of 0.6 per 100.000 habitants, limb-girdle muscular dystrophy of 0.6 per 100.000 habitants, facioscapulohumeral dystrophy of 0.5 per 100.000 habitants, Bethem dystrophy, type 2 Emery Dreifuss muscular dystrophy, merosin-deficient muscular dystrophy and myosin storage disease of 0.1 per 100.000.” 4. As per Table 5, a significant number of patients (12 out of 29) do not have conclusive molecular test reports to confirm the diagnosis and to accurately establish the type of muscular dystrophy. The molecular reports, wherever available, which are mentioned, are mostly not as per standard variant notation guidelines. Reply: We greatly appreciate the EIC comments. Indeed, patients in our country do not generally have access to molecular tests, so we perform a clinical characterization based on CPK levels, electromyography, and physical examination. We hope in further studies to have the possibility of performing molecular confirmation. 5. Elevation of serum CPK in muscular dystrophies and the different ranges of serum CPK expected in different types of muscular dystrophies are very well studied and well established and this study does not add anything novel to the existing knowledge about muscular dystrophies. Reply: We greatly appreciate the EIC comments. You are right, we do not have anything novel to the existing knowledge about muscular dystrophies, but it is considered for general physicians to have a broad perspective and the different causes of an elevated CPK when they treat them in the emergency room, as it will allow patients with dystrophy to be diagnosed earlier. In addition, CPK was used in this study mostly to search for patients with probable dystrophy or confirmed muscular dystrophy. 6. Inflammatory myopathies, viral myositis and other acquired causes of muscle involvement are discussed in length - this does not appear to be very relevant to the topic. Reply: We greatly appreciate the EIC comments. You are right, two paragraphs concerning inflammatory myopathies from the discussion section were summarized in the following way: “Frequently, many patients with muscular dystrophies can remain without optimal treatment due to confusion with other inflammatory myopathies such as polymyositis, dermatomyositis, and inclusion body myositis.21 In this study, 13.1% of patients diagnosed these other myopathies ended with confirmed muscular dystrophy after performing a detailed revision of their clinical histories and re-consultation of such patients. At least a 6-month follow-up should be implemented to rule out newly o persistently elevated CPK levels that might suggest a muscular dystrophy.” Additional changes: 1. According to your comments, we decided to implement a few other changes to the manuscript. In the Methods section, we would like to add the following paragraphs: Study design A cross-sectional study was made using a retrospective search of patients attended in Comfamiliar Risaralda between 2010 and 2021. The study included patients from both genders and all ages who presented with CPK levels greater than 500U/L, and diagnosis of polymyositis, myoclonus, myopathy, and muscular dystrophy. Patient selection process See linked image. A database analysis was carried out from 2010 to 2022 of 5219 patients treated in a fourth-level care institution in the Eje Cafetero region. As shown in Figure 1, 1949 patients were excluded with other causes of elevated CPK levels such as hypothyroidism, acute myocardial infarction, cardiac insufficiency, rhabdomyolysis, seizures, drugs including statins, fibrates, and nonclear causes. After reviewing medical records, 98 patients did not meet the inclusion criteria for the investigation due to other causes of CPK elevation such as drowning (submersion injuries), perinatal asphyxia, cranioencephalic trauma caused by a car accident, trauma caused by white weapons, and electrostatic discharge (Figure 1). The remaining 52 patients underwent medical consultation and 23 were excluded because some did not meet the clinical criteria for any muscular dystrophy but for other causes of transient elevation of CPK levels, and others manifested discontinuation in the study (Table 1). Finally, the patients underwent a second medical consultation by a geneticist to corroborate and classify the remaining 29 patients. *Insert Table 1 Data collection and Statistical analysis In an initial instance of the study, a retrospective institutional active search was made through text mining in laboratory databases for all CPK measures carried out by the Comfamiliar Risaralda laboratory between 2010 and 2021. After that, the results were purified and organized under the criteria of registered CPK elevation, and again the search language in databases was made to extract new confirmed or repeated diagnoses that could explain the CPKemia. Data collection was implemented through a study-specific case report form (CRF). A detailed data validation plan that identified missing data, out-of-range data and other data inconsistencies in the form of revision checking was implemented on the platform before the start of the study. The collected information was entered into the RedCAP platform, where the CRF was previously located with validation and automated fields if applicable. Discrepancies in the data were reported to the team as queries. Access to the database was restricted through password protection to authorized data management personnel. Descriptive statistics were obtained for numerical variables, including measures of central tendency such as mean and median. Descriptive statistics for categorical variables included a tabulation of frequencies with counts and percentages. The estimation of prevalences was carried out employing Bayesian inference since they allow a greater gain in precision in the estimation of parameters with values below 10%, as well as it was carried out utilizing a beta-binomial model under the binom package of R software. Statistical analyzes were also performed in R software. 2. According to your comments, we decided to implement a few other changes. In the Results section, we would like to add the following paragraphs: Results We found 29 patients with clinical muscular dystrophy in our hospital-based registry, with a mean CPK value of 3231.241, a standard deviation of 5019.543, and a maximum of 22670. We found a combined prevalence of all muscular dystrophies of 4.2 per 100.000 patients attended in our hospital base, Duchenne muscular dystrophy of 0.6 per 100.000, limb-girdle muscular dystrophy of 0.6 per 100.000, facioscapulohumeral dystrophy of 0.5 per 100.000, Bethem dystrophy, type 2 Emery Dreifuss muscular dystrophy, merosin-deficient muscular dystrophy and myosin storage disease of 0.1 per 100.000. 3. According to your comments, we decided to implement a few other changes. In the Discussion section, we would like to add the following paragraphs: Discussion Several studies have described the different types of muscular dystrophy. However, there is poor evidence analyzing multiple muscular dystrophies within the same population. This leads to heterogeneity in studies regarding prevalences, clinical manifestations, and a good genotype-phenotype correlation. In our study, we found patients with Duchenne and Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, Emery Dreifus muscular dystrophy, merosin-deficient muscular dystrophy, and autosomal dominant congenital myopathy 7A (Table 2). Therefore, to identify a patient with a particular type of disease, clinicians should follow a diagnostic sequence not only for differentiating muscular dystrophy from other inflammatory myopathies but also to discriminate the specific type. *Insert Table 2 In our study, we analyzed the clinical and molecular characteristics of 29 patients with muscular dystrophy in Colombia. According to Mercuri and Muntoni, the prevalence of Duchenne muscular dystrophy is 8-29 per 100 000 boys; Becker muscular dystrophy has a prevalence of 7-29 per 100 000 boys; limb-girdle muscular dystrophy has a prevalence of 0.8-5.7 per 100 000 inhabitants; myotonic dystrophy has an estimated prevalence of 10-6 per 100 000 men, followed by facioscapulohumeral muscular dystrophy with a prevalence of three per 100 000 men, and myosin storage disease with noncurrent reported prevalence.14 We found a combined prevalence of all muscular dystrophies of 4.2 per 100.000 among patients treated in our hospital base, Duchenne muscular dystrophy of 0.6 per 100.000, limb-girdle muscular dystrophy of 0.6 per 100.000, facioscapulohumeral dystrophy of 0.5 per 100.000, Bethem dystrophy, type 2 Emery Dreifuss muscular dystrophy, merosin-deficient muscular dystrophy and myosin storage disease of 0.1 per 100.000. These prevalences are lower than those reported in the literature and can be explained due to a bias regarding the filter we used to find the patients. We included patients from both genders and all ages who presented with a diagnosis of polymyositis, myoclonus, myopathy, and muscular dystrophy. However, some other suspected cases could have been recorded with different diagnoses, due to misdiagnosis or underdiagnosis, leading to underestimation. Non-diagnosed patients with muscular dystrophy and associated complications can also dissuade physicians from diagnosing adequately. Depending on the type of muscular dystrophy, some complications such as restrictive lung disease, cardiomyopathy, scoliosis, corticosteroid side effects, and psychosocial issues can generally lead professionals to focus only on the direct acute cause of the signs and symptoms and not to search for a long-term systemic etiology like muscular dystrophy.22 Therefore, clinicians need to figure out that patients presenting with some acute diseases, especially in recurrent cases, might also be associated with muscular dystrophy to keep in mind. Duchenne muscular dystrophy age onset of symptoms is in early childhood around the age of 5 years, it is rapidly progressive and most patients lose ambulation around 10-15 years old, leading them wheelchair dependent.23 Becker muscular dystrophy symptoms can start around 10-20 years old but in some cases, permanent asymptomatic until adulthood even >30 years, and remain ambulant even until their 60s.23,24 In our study, we found that most patients had similar features as previously reported in the literature. Three patients were revealed with the c.6439-?_6912+?del p.(Glu2146_Val2304del) mutation who presented with a mild phenotype of Becker muscular dystrophy. At the moment of consultation, they had a mean age of 48 years (SD 40-54). All of them presented with hyporeflexia, mild muscle weakness, age onset of symptoms between 10 and 20 years old, and any of the three patients were wheelchair dependant. Greer et al. reported this same mutation in a patient with Becker muscular dystrophy who lost ambulation by the age of 15 years.25 They suggest that patients with apparently identical exonic deletions are almost certainly going to have different genomic breakpoints and therefore will be missing different intronic regions, and potentially, splicing motifs resulting in different phenotypes.25 Vengalil et al. also identified that patients with deletions of exons 45-47 are clinically related to the development of cardiomyopathy and earlier wheelchair dependence.26 Further studies analyzing genotype-phenotype correlation in patients with muscular dystrophy would be helpful to better understand the pathogenesis, and predict phenotypes. Facioscapulohumeral dystrophy has an onset around 10-20 years old. Still, there are some unusual cases where the symptoms are present at the moment of birth, and some others remain asymptomatic their whole life. By the age of 20 years, 50% of the cases have developed symptoms, and eventually, 20% of the affected require a wheelchair, which is consistent with our study where patients with facioscapulohumeral dystrophy developed symptoms after 20 years old.27 In Bethlem muscular dystrophy, the symptoms can range from congenital to mid-adulthood, been the congenital cases extremely rare.28 The progression is slow and more than 2/3 of the affected older than 50 years require supportive means (cane, crutches, wheelchair) for outdoor mobility.29 This is consistent with our study where we found one patient with Bethlem muscular dystrophy who presented as a congenital case that also had supportive means for outdoor mobility. Limb-girdle muscular dystrophy is an extremely heterogeneous group. Over 30 distinct subtypes have been identified, in which the onset of symptoms is at any age with some severe congenital cases and some mild cases starting in adulthood; the severity is also variable.30 As stated in the literature, we found four patients with variable phenotypes ranging from mild disease with onset of symptoms over 20 years old to more severe cases with early onset of symptoms in childhood. Emery Dreifuss muscular dystrophy onset of symptoms begins in the first two or three decades of life.31 The progression is slow, and loss of ambulation can occur in the autosomal dominant variant but is rare in the X-linked variant.32 We found one patient with Emery Dreifuss muscular dystrophy whose symptoms corresponded with those reported in the literature. Merosin-deficient muscular dystrophy is a severe type with symptoms present at the moment of birth, with neonatal profound hypotonia, poor spontaneous movements, and respiratory failure;33 most affected children do not acquire independent walking. It has been reported that only 15% of individuals acquired independent ambulation,34 and only a few patients gained the ability to walk with assistance but subsequently lost the ability.35 In our study, we identified one patient with Merosin-deficient muscular dystrophy who presented with profound hypotonia since birth and was diagnosed at two months old with CPK levels and molecular test. Currently, this patient can adequately sit but has problems with gait. These features correspond with phenotypes previously reported in the literature but without respiratory compromise. We also found a patient with autosomal dominant congenital myopathy 7A with a phenotype that presented in early childhood at 14 months old, with significant proximal and distal muscle weakness. In addition, the patient presented with a severe restrictive pulmonary pattern, and a myopathic pattern in electromyography without cardiac alterations. Currently, at his adult age, this patient has proximal and distal quadriparesis and hypoesthesia of the left hemibody. These features correspond with the previously reported in the literature. On the other hand, 12 patients with muscular dystrophy remained unclassified despite their clinical suspicion and after undergoing molecular tests. As previously exposed, patients with similar exonic deletions are going to have different genomic breakpoints. The number of genetic alterations that can be involved in muscular dystrophies is huge. Therefore, performing a single molecular test sometimes is not enough to identify the specific mutation related to the phenotypic presentation of the patient. We made Table 3 as a tool that shows a brief review of the clinical and paraclinical approach to the different types of muscular dystrophy. Table 4 shows the detailed classification of each type of muscular dystrophy. Barohn et al. propose a series of steps regarding the patient’s symptoms by establishing which muscle-related symptoms patients demonstrate; determining the temporal evolution of the symptoms; interrogating if there is a family history of a myopathic disorder; finding out if there are precipitating factors that trigger episodic weakness or stiffness; asking if there are associated systemic symptoms or signs; and lastly, identifying the distribution of Weakness.36 After completing the 6 steps, clinicians could now attempt to classify a myopathic disorder according to the patterns of muscle weakness. The findings on the physical examination, particularly the distribution of muscle weakness, should provide additional information in determining the correct diagnosis.36 Subsequently, CPK levels are extremely helpful for the evaluation of patients with a suspected myopathy. The CPK levels are usually elevated in most patients with muscle disease but may be normal in slowly progressive myopathies.36 Depending on the degree of CPK levels, it can be useful in distinguishing different forms of muscular dystrophy. As in the case of Duchenne muscular dystrophy, CPK levels can be elevated from 10 to more than 100 times the upper limit of normal, whereas in Facioscapulohumeral muscular dystrophy, the CPK levels are expected to be elevated from 1 to 10 times the upper limit of normal. We also must rule out nonmyopathic factors that can alter CPK levels such as profound muscle wasting, corticosteroid administration, collagen diseases, alcoholism, or hyperthyroidism.36 Later, we should look for electromyography and nerve conduction studies. These studies can help to distinguish primary neuropathic from myopathic disorders by confirming that the muscle is the correct site of the lesion and that weakness is not the result of an underlying motor neuron disease, neuropathy, or neuromuscular junction disorder.36 However, their sensitivity and specificity are low. Normal results provide evidence of a nonsevere neuromuscular disorder.5 A few years ago, if the electrodiagnostic features suggested a myopathic pattern, a muscle biopsy was recommended. Additionally, we can now diagnose muscular dystrophies through molecular tests without performing muscle biopsies in all suspected patients. Table 5 shows the patterns of muscular dystrophy applied to the 29 participants of the study. Patients in our country do not generally have access to molecular tests, so we perform a clinical characterization based on CPK levels, electromyography, and physical examination. We hope in further studies to have the possibility of performing molecular confirmation. Conclusions Although muscular dystrophies consist of a heterogeneous group of neuromuscular diseases, there are still clinical and paraclinical features that can help physicians to detect any case and perform a good approach and follow-up. In our region, many patients with muscular dystrophy remain underdiagnosed or misdiagnosed, which in consequence it compromises their prognosis without adequate treatment. Therefore, our diagnostic sequence will facilitate physicians to identify any of the most frequent muscular dystrophies. Moreover, many patients with muscular dystrophies can remain without optimal treatment due to confusion with other inflammatory myopathies such as polymyositis, dermatomyositis, and inclusion body myositis.21 In this study, 13.1% of patients diagnosed these other myopathies ended with confirmed muscular dystrophy after performing a detailed revision of their clinical histories and re-consultation of such patients. For this reason, we suggest implementing at least a 6-month follow-up to rule out newly o persistently elevated CPK levels that might indicate a muscular dystrophy."
}
]
}
] | 1
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https://f1000research.com/articles/12-930
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https://f1000research.com/articles/11-385/v1
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01 Apr 22
|
{
"type": "Research Article",
"title": "Association of ARRDC3 and NFIA variants with bovine congestive heart failure in feedlot cattle",
"authors": [
"Michael P. Heaton",
"Gregory P. Harhay",
"Adam S. Bassett",
"Halden J. Clark",
"Jaden M. Carlson",
"Erin E. Jobman",
"Helen R. Sadd",
"Madeline C. Pelster",
"Aspen M. Workman",
"Larry A. Kuehn",
"Theodore S. Kalbfleisch",
"Heather Piscatelli",
"Michael Carrie",
"Greta M. Krafsur",
"Dale M. Grotelueschen",
"Brian L. Vander Ley",
"Gregory P. Harhay",
"Adam S. Bassett",
"Halden J. Clark",
"Jaden M. Carlson",
"Erin E. Jobman",
"Helen R. Sadd",
"Madeline C. Pelster",
"Aspen M. Workman",
"Larry A. Kuehn",
"Theodore S. Kalbfleisch",
"Heather Piscatelli",
"Michael Carrie",
"Greta M. Krafsur",
"Dale M. Grotelueschen"
],
"abstract": "Background:\n\nBovine congestive heart failure (BCHF) has become increasingly prevalent among feedlot cattle in the Western Great Plains of North America with up to 7% mortality in affected herds. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. Genes associated with BCHF in feedlot cattle have not been previously identified. Our aim was to search for genomic regions associated with this disease. Methods: A retrospective, matched case-control design with 102 clinical BCHF cases and their unaffected pen mates was used in a genome-wide association study. Paired nominal data from approximately 560,000 filtered single nucleotide polymorphisms (SNPs) were analyzed with McNemar’s test. Results: The most significant genome-wide association was in the arrestin domain-containing protein 3 gene (ARRDC3), followed by the nuclear factor IA gene (NFIA, mid-p-values, 1x10-8 and 2x10-7, respectively). Animals with homozygous risk alleles at either gene were approximately eight-fold more likely to have BCHF than their matched pen mates without those risk alleles (CI95 = 3-17). Animals with homozygous risk alleles at both genes were 28-fold more likely to have BCHF than all others (p-value = 1x10-7, CI95 = 4-206). A linked missense variant in ARRDC3 (C182Y) represents a potential functional variant as the C182 codon is conserved among all other jawed vertebrate species observed. A DNA test with two markers showed 29% of 273 BCHF cases had homozygous risk alleles in both genes, compared to 2.5% in 198 similar unaffected feedlot cattle. This DNA test may be useful for identifying feedlot animals with the highest risk for BCHF in the environments described here. Conclusions: Although pathogenic roles for ARRDC3 and NFIA variants associated with BCHF are unknown, their discovery facilitates classifying animals by genetic risk and allows cattle producers to make informed decisions for selective breeding and animal health management.",
"keywords": [
"Bovine",
"Congestive Heart Failure",
"ARRDC3",
"NFIA",
"GWAS"
],
"content": "Introduction\n\nBovine congestive heart failure (BCHF) is a significant cause of death in feedlot cattle at the low to moderate elevations of the Western Great Plains of North America (800 to 1,600 m) (Jensen et al., 1976; Neary et al., 2016). Mortality from BCHF has reached 7.5% in severely affected pens of cattle, with annual losses exceeding $250,000 for a single operation (Heaton et al., 2019). Consequently, reducing the impact of BCHF is a priority for the cattle industry. The clinical features of BCHF in feedlot cattle are those caused by pulmonary hypertension (PH), right heart failure, and passive liver congestion (Figure 1). BCHF shares some similarities with the high-elevation “brisket disease” disorder that has been known in the Rocky Mountains of Colorado and Utah for more than 100 years, including severe ventral edema of the chest tissues (Glover and Newsom, 1914, 1918). In the high-elevation disorder, the reduced partial pressure of oxygen causes pulmonary hypoxia, vascular resistance, arterial remodeling, and pulmonary hypertension. This condition has been attributed to “cor pulmonale” and eventually causes right ventricular overload and enlargement, ultimately leading to heart failure (Hecht et al., 1962). In BCHF, pulmonary arteries and arterioles also have lesions consistent with hypoxia-induced pulmonary hypertension (Moxley et al., 2019). However, it is unclear whether hypobaric hypoxia is the underlying cause. Some evidence suggests that left heart dysfunction may also play a role in initiating BCHF (Krafsur et al., 2019). Thus, disease pathogenesis of BCHF in feedlot cattle maintained at moderate elevations remains unclear.\n\nPanel A, matched pair number 26 with the clinical case (right) showing ventral edema and a drop in the withers (arrows). The latter occurs as the fluid accumulates in thorax pushing the shoulders outward. Panel B, the affected heart of case 26 (right) compared with a normal heart of a fattened American Angus heifer. Abbreviations: RV, right ventricle; LV, left ventricle; PA, pulmonary artery. Panel C, PA distension and mandibular edema in case 26 (arrows). Panel D and E, clinical case number 91 with ascites (arrow) and enlarged heart with dilated RV. Panel F, Enlarged, encapsulated liver of case 91 with “nutmeg liver” appearance in cross section due to hepatic venous congestion, and atelectasis in lungs (arrow).\n\nEvidence suggests that genetic factors may influence the risk of PH and BCHF. For example, dozens of inherited DNA sequence variants are known to directly or indirectly affect biological processes involved with cardiopulmonary disease in humans (Morrell et al., 2019; Reza and Owens, 2020). Moreover, interviews with feedlot personnel at multiple affected operations indicated that cattle from different sources varied markedly in their incidence of BCHF, in spite of being from the same breed and raised in the same general region with similar management conditions. Personnel also noted every year that cattle from the same sources have a fairly stable and predictable prevalence of BCHF in their feedlot environment (Heaton, M.P., 2017 unpublished). These observations are consistent with the hypothesis that genomic DNA sequence variants are influencing BCHF incidence, and each herd has its own frequency of the risk alleles. Based on comparative mammalian genetics, together with these anecdotal observations, we hypothesize that underlying genetic risk factors are influencing BCHF in feedlot cattle.\n\nCandidate gene variants have not been confirmed as risk factors for BCHF in feedlot cattle. A first potential candidate gene variant was reported for cattle with high-altitude pulmonary hypertension (Newman et al., 2015). American Angus cattle affected with pulmonary hypertension at altitudes of 1,478 to 2,618 m had a higher frequency of the endothelial PAS domain-containing protein 1 gene (EPAS1) encoding a hypoxia-inducible factor 2 alpha (HIF2α) missense variant. In addition, six other HIF2α polypeptide sequences were identified in cattle for evaluating their potential impact on the adaptive response to chronic hypoxia in U.S. cattle (Heaton et al., 2016). However, a retrospective study with 102 matched case-control pairs of feedlot cattle showed that none of the HIF2α isoforms encoded by EPAS1 were associated with BCHF and indicated the need for a wider search (Heaton et al., 2019).\n\nHere we used the same retrospective matched case-control design and the same 102 pairs of cattle from affected feedlots in the Western Great Plains (Table S1, Extended data, [Heaton et al., 2019]), together with 778,000 single nucleotide polymorphisms (SNPs), to identify two major genetic risk factors associated with BCHF. Cases were matched with contemporary pen mates to reduce confounding association signals that could be caused by population stratification and environmental differences. The strongest association signals were in the arrestin domain-containing protein 3 (ARRDC3) gene, and the gene for nuclear factor IA (NFIA). The results have implications for underlying disease mechanisms, selection of breeding animals with reduced risk, and management of animals with high-genetic risk for BCHF.\n\n\nMethods\n\nThe experimental design and procedures used during this research project were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Nebraska-Lincoln as previously described (Experimental Outline numbers 139 and 1172 [ Workman et al., 2016; Heaton et al. 2019]). The animals were privately owned by commercial feeding operations, and the owners and management approved the use of animals for this study. In every instance, all efforts were undertaken to reduce animal suffering. In addition, animal welfare for these facilities was in accordance with the National Cattlemen’s Beef Association’s Beef Quality Assurance Feedyard Welfare Assessment program (http://www.bqa.org/).\n\nPaired samples from 102 affected feedlot cattle and their 102 unaffected matched pen mate controls were identified from approximately 140,000 total animals collected from four feedlots in Nebraska and Wyoming at elevations ranging from 1,163 to 1,280 m, in a 16-month period spanning January 2017 to April 2018 (Heaton et al., 2019). Briefly, end-stage BCHF cases were identified and euthanized by feedlot personnel based on clinical presentation as previously described. The case definition included multiple clinical signs specific and non-specific to BCHF as described previously in detail (Heaton et al., 2019). Cases were enrolled in the study only if there was a postmortem presumptive diagnosis of congestive heart failure at necropsy. Unaffected pen mate controls were matched for source, arrival date, gender, and coat color. The 102 case-control pairs originated from 30 different sources with the largest single source contributing 32 pairs (Heaton et al., 2019). The pen sizes ranged from 100 to 300 animals, and control animals were selected based on their willingness to be moved to the sampling area by riders on horseback.\n\nNone of the unaffected matched pen mate animals developed clinical BCHF signs prior to their processing into beef. Overall, the group of 204 calves was 93% solid black, 70% castrated males, and none had visible horns (Heaton et al., 2019). Most of the 204 calves were from known, well-managed herds that use American Angus genetics. However, breed information was not available for all animals. Tissue samples for genomic DNA isolation included V-shaped ear notches and EDTA whole blood. The ear tissue was desiccated with granular NaCl in the field and stored at -20°C upon return. The plasma and cellular fractions of EDTA whole blood were separated and frozen in liquid nitrogen en route and stored at -80°C upon return. Postmortem whole hearts used for gross morphological comparisons representing unaffected cattle were collected during federally-inspected beef processing at the USMARC abattoir from 21 purebred American Angus heifers raised and fattened at an elevation of 578 m.\n\nA panel of 96 unrelated individuals from popular U.S. beef breeds (USMARC Beef Diversity Panel version 2.9 [MBCDPv2.9]) was used for genetic comparisons with case-control animals (Heaton et al., 2016). The panel design was based on a previous set of commercially-available sires from 19 breeds with minimal pedigree relationships (Heaton et al., 2001). Pedigrees were obtained from leading suppliers of U.S. beef cattle semen and analyzed to identify the least related individuals for inclusion. On the basis of the number of registered progeny, the breeds were estimated to represent more than 99% of the germplasm used in the U.S. beef cattle industry. Based on pedigrees, the panel members contained more than 187 unshared haploid genomes (of 192 possible) and allowed a 95% probability of detecting any allele with a frequency greater than 0.016.\n\nUnless otherwise indicated, reagents were molecular-biology grade. DNA from ear notches was extracted by standard phenol/chloroform procedures, dissolved in a solution of 10 mM TrisCl, 1 mM EDTA (TE, pH 8.0) and stored at 4°C. (Heaton et al., 2008). SNP genotypes for variants on the BovineHD BeadChip array were scored at GeneSeek Inc. (Lincoln, NE, USA), according to manufacturer’s instructions (Illumina, Inc., San Diego, CA, USA). The unfiltered map and ped files from the 102 BCHF case-control animals (Files S1 and S2, Extended data) were analyzed for association with BCHF with PLINK v1.90b6.5 64-bit (13 September 2018) software (Chang et al., 2015). The pairs (1 to 102) were designated in the PLINK family ID field. SNPs were removed for having a minor allele frequency less than 0.05 (--maf option). This cutoff was conservative since the frequency of the affected individuals was set at 0.50 a priori in this matched case-control design. The missing genotype rate threshold was set at 0.05 (--geno option) and the Hardy-Weinberg equilibrium test with the mid-p adjustment threshold was set to 0.0001 (--hwe midp option) (Graffelman and Moreno, 2013). These filters were applied for 204 samples of which 142 were listed as males (steers) and 62 were listed as females (heifers). The animal genders were tested with the --check-sex option and a control animal was identified as being misclassified as a male, leaving 141 steers and 63 heifers, and pair 21 mismatched for sex with the case being a steer and the control being a heifer (Files S3 and S4, Extended data).\n\nSince unrecognized population stratification among individuals may obscure association signals and lead to incorrect findings (Deng, 2001; Cardon and Palmer, 2003), multidimensional scaling (MDS) was used with a matrix of pairwise identity-by-state (IBS) distance to visually evaluate the similarity between individuals and pairs. Using PLINK software, unfiltered input map and ped files from the 102 BCHF case-control animals (Files S1 and S2, Extended data) were merged with likewise unfiltered input map and ped files from the USMARC Beef Cattle Diversity Panel version 2.9 (MBCDP v2.9) genotyped with BovineHD BeadChip array (Heaton et al., 2016) (Files S5 and S6, Extended data). Once merged, the data was filtered as described above to produce a new map and ped files (Files S7 and S8, Extended data). MDS data was produced with PLINK software v1.9 and plotted with Microsoft Office 365 Excel software. The IBS/IBD computation was run on the filtered SNP sets with the --genome option. The computation excluded 12,591 variants on non-autosomes from the IBD calculation. Plotting the --cluster output values in the first and second dimensions (i.e., C1 values against C2) gave a scatter plot in which each point is an individual; the two axes correspond to a reduced representation of the data in two dimensions, which facilitates cluster identification. Standard classical (metric) multidimensional scaling was used.\n\nThe McNemar’s test (McNemar, 1947) is a statistical test for paired nominal data. Unlike a traditional case-control GWAS where the scope of inference is over two large groups of individuals, a McNemar’s test analysis for a case-control GWAS uses many pairs of individual animals. In addition, McNemar’s test analysis is not formally available as a convenient option in commonly used, open-source GWAS toolsets that can analyze 560,000 SNPs such as PLINK (v1.90b6.5). The Cochran-Mantel-Haenszel (CMH) test (Mantel and Haenszel, 1959) is available in PLINK and can be run as a specialized case with two clusters; however, it has limited options and access to essential McNemar raw data is not available. Thus, a custom workflow was developed with a programming and numeric computing platform (MatLab v.2021.2, MathWorks, Inc., Natick, MA) to produce the critical tables of binomial outputs and McNemar statistics for the filtered SNP genotypes.\n\nIn McNemar’s test, informative pairs are those which contain exactly one animal with the hypothetical risk allele(s), i.e., Table 1, quadrants b and c. The ratio of these discordant pairs (b/c) provides evidence to reject the null hypothesis. At each biallelic SNP locus, alleles were tested separately in three scenarios as a potential disease risk factor: 1-copy, 1- or 2-copies, and 2-copies, producing six sets of McNemar’s test statistics. The presence of a potential risk allele(s) was scored for both animals in every matched pair and used to populate the McNemar’s 2 × 2 contingency table for a given SNP. The presence (+) or absence (-) of a possible genetic risk factor was assigned to each animal and the matched pair was then classified by one of four possible binomial outcomes (Table 1, quadrants). A genetic “risk” allele was indicated in the 102 matched pairs when quadrant b was greater than quadrant c (i.e., odds ratio (OR) > 0). Conversely, a “protective” allele was indicated when quadrant c was greater than quadrant b (i.e., OR < 0).\n\na Each binomial outcome is a case-control pair, i.e., (case, control) with the sign indicating the presence or absence of the risk allele. For example, (+,-) indicates an informative outcome where the case has the risk allele and the control does not. The uninformative pairs are (+,+) and (-,-) where each member of the pair has identical risk allele status. Note that this table can be set up for scenarios of 1, 1 or 2, and 2 copies of risk alleles.\n\nMcNemar’s test analysis for a GWAS imposes statistical constraints at the SNP level that are not present in conventional GWAS. The McNemar’s test p-values for rejection of the null hypothesis were computed with the binomial distribution. This is unlike a conventional retrospective case-control GWAS, where the theoretical distribution of p-values may be modeled with Fisher’s exact test statistics (or derivative). The binomial distribution generated discrete p-values (e.g., exact p and mid p) at each SNP site that were dependent on the discordant pairs observed (i.e., b + c and b/c) for each inheritance model (e.g., 1-copy, 1- or 2-copies, and 2-copies). Thus, p-values were computed de novo at each locus. To the best of our knowledge, the theoretical genome-wide distribution of McNemar’s p-values at the SNP level has not been previously described in the GWAS context. Briefly, input files were PLINK map and ped files with the ped file modified to include the pair identifier in the first column, and the rows sorted in descending pair order from 1 to 102 with the unaffected animal listed first in the pair. The case and control phenotype were coded in the sixth column, with the unaffected control animal coded with 1 (PHENO = 1) and the affected case animal with a 2 (PHENO = 2). The analysis evaluated each SNP for possible risk alleles in the context of McNemar’s test as described in README.md file in the GitHub code repository McNemarsSNPAnalysis. Alternatively, the analysis pipeline can be run online within a copy of the McNemar’s SNP Analysis Compute Capsule at CodeOcean. The PLINK map and ped files contained 141 steers and 63 heifers, and SNPs assigned to chromosome 0 through 32 (i.e., included unassigned SNPs, chromosome X, Y, and mitochondrial DNA; Files S9 and S10, Extended data). In the first stage of the workflow, biallelic SNP heterozygous animal genotypes were converted to a one-letter International Union of Pure and Applied Chemistry and International Union of Biochemistry and Molecular Biology (IUPAC/IUBMB) ambiguity codes used for nucleotides (i.e., R = a/g, Y = c/t, M = a/c, K = g/t, S = c/g, W = a/t (‘Nomenclature Committee for the International Union of Biochemistry [NC-IUB]. Nomenclature for incompletely specified bases in nucleic acid sequences. Recommendations 1984’, 1986) and homozygous animal genotypes were converted to a one-letter code of the same letter (i.e., A, C, T, G).\n\nThe McNemar mid-p test was used, since it is an improvement over the exact conditional test (Fagerland et al., 2013). Briefly, the McNemar mid-p-value was calculated with equation 1:\n\nThe quantile-quantile (Q-Q) plots of the distribution of the test statistics are challenging to produce because McNemar’s test data are discrete for a given number of total pairs and the fraction of discordant pairs ((b + c)/n, Table 1). This requires the computed theoretical expected distribution of p-values to mirror the dependency of the observed distribution of p-values on the fraction of discordant pairs. Thus, for a given informative pair (b + c) value, theoretical p-values in Q-Q plots were computed by multiplying the number of observed p-values by the predicted normalized binomial distribution of all possible b and c values, as defined by the p-value metric used, e.g. exact p or mid p. The fraction of discordant pairs is also influenced by minor allele frequency, as the opportunity for the observation of discordant pairs diminishes with frequency.\n\nSystematic use of q-values in genome-wide tests provides a balance between the number of true and false positives while being automatically calibrated and readily interpreted (Storey and Tibshirani, 2003). The q-value of a genome-wide data set is the expected proportion of false positives incurred (Storey and Tibshirani, 2003). For instance, a q-value threshold of 5% results in the false discovery rate (FDR) of 5% of the significant features being truly null. The mafdr function in the Matlab Bioinformatics Toolbox (version 2021.2) was used to compute the q-values from input p-values according to procedures previously described (Storey, 2002). The tuning parameter, λ, was used to estimate the a priori probability that the null hypothesis is true (equation 2):\n\nThe six sets of McNemar’s pair classifications and test statistics were tallied for each SNP allele and exported to a text file for importation into spreadsheet software (Excel Version 1902, Build 11328.20420). A spreadsheet environment allowed for the SNP set to be used in calculations for McNemar’s statistics such as odds ratios (OR), p-values, and McNemar Chi-squared statistics. After McNemar’s testing, SNPs were removed due to their assignment to chromosomes 0, 31, and 32. These SNPs represent markers on unmapped chromosomes, SNPs on chromosome Y, and mitochondrial SNPs. SNPs were also removed if there were no informative pairs resulting from their pairwise analysis (i.e., McNemar quadrants b + c = 0).\n\nThe upper and lower CI95 for the OR were calculated in equations 3 and 4:\n\nThe spreadsheet format allowed for custom labeling of column headers, row sorting, and color-coded heat mapping. For example, it was useful to sort each of the six sets of data by their best McNemar’s p-value in descending order and color code the rows in blocks of 100 (e.g. purple, red, yellow, dark green, light green). This helped visually identify the top 500 best markers in each data set. When sorted by chromosome and position, this produces an obvious visual symmetry due to the biallelic nature of SNPs and the dichotomous phenotype.\n\nThe spreadsheet format also allowed for manual production of Manhattan plots from McNemar’s data for three inheritance models of the two alleles for each SNP. Briefly, the ARS-UCD1.2 reference assembly SNP coordinates from the PLINK map file (i.e., chr and position) were converted to a linear genome position for the x-axis of the Manhattan plot so that every SNP had a new relative coordinate on a whole genome scale from 1 to 2,651,083,094 bp. This was accomplished by adding the position value of the most terminal SNP on chromosome 1 to each of the SNP position values on chromosome two. This was repeated for each consecutive chromosome (1 to 29 and X). The Bonferroni correction for multiple testing was used at the 0.05 significance level (α) as a conservative genome-wide estimate of significance (Johnson et al., 2010) (Equation 5):\n\nSample size power analysis for the McNemar’s test was performed with PASS 2019 Power Analysis and Sample Size Software, version 19.0.2 (NCSS, LLC., Kaysville, Utah, USA). The sample size of 102 matched pairs achieved 95% power to detect an OR of 8.51 and 2.94 with a two-sided McNemar’s test and a corrected significance level of 0.01 (α) within the range of 25% and 70% discordant pairs, respectively. Power is the probability of rejecting a false null hypothesis, while α is the probability of rejecting a true null hypothesis.\n\nMcNemar’s test analysis was compared to that obtained with the CMH association statistic (Mantel and Haenszel, 1959) in PLINK v1.90b6.5. The 102 matched pairing assignments were coded in the fam file in the third column to identify 102 “clusters” (e.g., Pair1, Pair2, Pair3, …Pair102) for use with the CMH association statistic. The --adjust option was also used to produce a sorted list of CMH association results. The Q-Q plot of the distribution of the test statistics was produced with the qqman R package on CRAN: (Turner, SD. 2014. bioRxiv) with 64-bit R version 3.5.1 (2018-07-02).\n\nBlood samples from BCHF cases and controls were tested for infection with BVDV, a possible confounding disease condition of feedlot cattle that is easily detected. However, since these animals were not serially sampled, a positive test result would not distinguish between acute and persistent infection. Blood samples for the first 13 case-control pairs were collected as EDTA whole blood, stored at -80oC, and used for BVDV testing. Blood samples for the remaining 89 case-control pairs were processed by first separating the plasma by centrifugation, and storing it separately at -80oC prior to its use in BVDV testing. EDTA blood or plasma was pooled into groups of five or 10, respectively, and total RNA was extracted with a mono-phasic solution of phenol and guanidinium thiocyanate (TRIzol LS, Invitrogen-Thermo Fisher Scientific, Waltham, MA, USA) according to the manufacturer’s specifications. BVDV genomic RNA was detected with a previously published, real-time assay that used quantitative reverse transcription polymerase chain reaction (RT-qPCR) primers (5′-GGGNAGTCGTCARTGGTTCG-3′; 5′-GTGCCATGTACAGCAGAGWTTTT-3′) and probe (5′-6-FAM-CCAYGTGGACGAGGGCAYGC-BHQ1-3′) (Mahlum et al., 2002). The assay reagents were purchased as a commercial kit (Qiagen OneStep RT-PCR, Germantown, MD) and used according to the manufacturer’s instructions. Briefly, cyclic amplification was conducted in a 25 μL reaction containing 5 μL of extracted RNA, 4.5 mM magnesium chloride, 400 μM dNTP, 0.4 μM of each forward and reverse primer, 0.2 μM probe, and 1 μL of an enzyme mix containing reverse tran-scriptase and a “hot-start” Taq polymerase. Cycling conditions included reverse transcription at 50°C for 30 minutes, inactivation of the reverse transcriptase enzyme and activation of the Taq polymerase at 95°C for 15 minutes, and 40 cycles of 94°C for 30 seconds, 55°C for 60 seconds, and 72°C for 60 seconds. Positive, negative, no-template, and extraction control samples were included in each group of samples tested.\n\nCustom SNP genotype tests were developed on a commercially available genotyping platform that uses “padlock” oligonucleotide probes, combined with fluorescently-labeled probes and isothermal rolling circle amplification technology, for the qualitative detection of alleles (MatMaCorp, Lincoln, NE, USA). Padlock probes are long oligonucleotides whose ends are complementary to adjacent target sequences. The primary target SNPs included ARRDC3 C182Y (ARS-UCD1.2 chr7:90845941, BovineHD0700027239, BCHF5) and NFIA intron 4 (ARS-UCD1.2 chr3:84578325, BovineHD0300024307, BCHF31). However, genotyping tests involving tightly linked SNPs were also used on occasion. The assay steps consisted of sample processing (blood and ear notch), target amplification, and detection. Samples were processed and analyzed on the Solas 8 instrument per the manufacturer’s instructions. Briefly, samples were mixed with a proprietary lysis buffer and heated for three minutes at 95°C. Kit reagents were added to perform an initial PCR amplification with padlock probes. The machine assay conditions were SNP-specific and uploaded to the machine via the internet by the supplier: an initial heating phase at 93° for 3 min, followed by 30 cycles at 93° for 20 s and 57°C for 30 s. Detection of the ligated circular oligonucleotide products in the Solas 8 instrument was accomplished with fluorescently labeled probes and isothermal rolling circle amplification. The total reaction time was approximately two hours, and the genotype assignments were made in real time by the instrument, and the real-time graphical outputs were visually reviewed for quality assurance. Assay performance was validated with known genotypes derived from whole genome sequencing and the BovineHD BeadChip array from a beef cattle diversity panel (Heaton et al., 2016). Ambiguous genotype results from animals of unknown genotypes were resolved by repeat testing with a second assay designed for the opposite strand of ARRDC3 C182Y (ARS-UCD1.2 chr7:90845941, BovineHD0700027239, BCHF5r) and the linked NFIA intron 4 SNP (ARS-UCD1.2 chr3:84580655, BovineHD0300024308, BCHF32).\n\n\nResults\n\nApproximately 778,000 SNPs were scored for 204 animals in matched case-control pairs with a total genotyping rate of 0.99 (Files S1 and S2, Extended data). Subsequent filtering removed 216,000 SNPs with either low minor allele frequencies, missing genotypes, or deviation from Hardy-Weinberg expectations (173,000, 42,000, and 1,000, respectively). Approximately 560,000 remaining SNPs (Files S3 and S4, Extended data) were used for MDS analysis of pairwise IBS distances of the 204 animals from the 102 matched pairs, together with a 19-breed beef diversity panel. The feedlot animals from the 102 matched pairs were tightly clustered with purebred American Angus and Red Angus cattle (Figure 2A). A higher resolution plot with the 102 pairs of BCHF cases and matched controls showed there were seven outliers from one feedlot group, of which five were cases and two were controls (Figure 2B, lower right quadrant). However, many of the matched pairs had short IBS distances, indicating close genetic relationships between random penmates, as would be expected from animals originating from the same ranch. Based on the relatively low number of outliers that were BCHF cases, and the distances of their matched pairs, corrections for population stratification were not made in subsequent analyses.\n\nPanel A, genetic distances between BCHF case-control animals and diverse purebred bulls from 19 U.S. beef breeds. Panel B, genetic distances between matched pair from different feedlot groups and locations in Nebraska (NE) and Wyoming (WY). Lines connecting dots identify each matched pair with numbers corresponding to the pair ID (Table S1) and the clinical case.\n\nThe CMH test was first used to analyze the data set with PLINK software, since it was available and tests for SNP-disease association conditional on clustering of the individuals and is a generalization of McNemar’s test. The CMH test is expected to give the same results as McNemar’s test when each cluster contains a pair of individuals since their test statistics are identical when each stratum shows a pair. However, CMH output in PLINK did not provide easy access to the individual McNemar’s quadrants results for each SNP nor the ability to test 1-copy, 1 or 2-copy, and 2-copy risk allele models. Thus, we sought to develop a custom process on a programming and numeric computing platform as described in the Methods section. After producing the tables of McNemar test statistics (File S11, Extended data), 704, 668, 31, and 1 SNPs were further removed because they had no informative pairs, were unmapped, on the chromosome Y, or on the mitochondrial genome, respectively (File S12, Extended data). A Manhattan plot of the resulting SNPs revealed that the most significant genome-wide associations were clustered on chromosome 7 at the ARRDC3 gene (Figure 3). No other genomic region contained SNPs that met the Bonferroni threshold at the 0.05 genome-wide significance level (-log10 = 7.05).\n\nThe mid-p-values from the McNemar’s association test were used with major (left) and minor alleles (right). In both panels, the inset shows the Q-Q plot of the distribution of the test statistics and the red horizontal line shows the Bonferroni correction at an α of 0.05.\n\nWhile the Bonferroni correction protects against Type I errors (false positives), it is vulnerable to Type II errors (false negatives). To strike a balance between the number of true and false positives, q-values were calculated for the McNemar data set to identify regions surpassing a 5% FDR. The q-value threshold is the expected proportion of significant SNP associations that are false leads. There were 53 genome-wide autosomal SNPs passing the 5% FDR: 49 were associated with ARRDC3 on chromosome 7, five were associated with NFIA on chromosome 3, and one SNP each was associated with a region on chromosomes 4, 10, and 19 (Figure 4, File S13 Extended data). Since the three SNPs on chromosomes 4, 10, and 19 correspond to the expected proportion of false leads, these regions were dismissed for the purposes of the present study. The remaining genomic regions associated with ARRDC3 and NFIA genes were further characterized.\n\nThe q-values for SNPs were evaluated for the two-copy risk allele model and plotted by chromosome. Numbers in parentheses are linked SNPs with q-values less than 0.05. Red dots and parentheses represent multiple linked SNPs with equivalent q-values.\n\nThe best associated region spanned 52 kb and was roughly centered on the ARRDC3 gene. This region contained eight equivalent linked SNPs with -log10 mid-p-values of 7.86 (Figure 5A) and contained a missense variant in ARRDC3 codon 182 in exon 4 encoding cysteine (C, tgt) or tyrosine (Y, tat). The homozygous major alleles for the eight best SNPs (and ARRDC3 Y182) were associated with increased BCHF risk (OR 8.4, CI95, 3.3 to 21, Table 2). Conversely, one or two copies of the minor alleles for these eight SNPs (and ARRDC3 C182) were associated with reduced BCHF risk (OR = 0.12, File S12, Extended data). Heterozygosity (i.e., having one risk allele) was also associated with reduced BCHF risk (0.26). The second best associated region spanned a 2.3 kb region in NFIA intron 4, and there were no SNPs present on the BovineHD BeadChip array predicted to affect the NFIA coding sequence. The 2.3 kb region contained two equivalent linked SNPs with -log10 mid-p-values of 6.60 (Figure 6). The homozygous major alleles for these two SNPs were associated with increased BCHF risk (OR 7.4, CI95, 2.9 to 19, Table 2). Conversely, one or two copies of the minor alleles for these two SNPs were associated with reduced BCHF risk (OR = 0.14, File S12 Extended data). Heterozygosity was also associated with reduced BCHF risk (0.40). Thus, two copies of the major ARRDC3 and NFIA haplotype alleles were associated with BCHF risk.\n\nThe mid-p-values from the McNemar’s association test of the most frequent SNP alleles were used. Panel A, test requiring the presence of homozygous risk alleles. Panel B, test requiring the presence of either 1- or 2-copies of the risk alleles. Panel C, test requiring heterozygosity for the risk alleles. The red horizontal line shows the Bonferroni correction at the 0.05 significance level. The red numbers in parentheses are McNemar's informative pairs from quadrants b and c (i.e., “b/c“, Table 1). The ratio of informative pairs indicates the strength of the association, and whether the allele is positively or negatively associated with BCHF (i.e., b/c > 0 or < 0).\n\na The SNPs were sorted by chromosome and genomic position. Makers within each genomic region are considered to be statistically equivalent within the margin of error.\n\nb A1 was defined as the most frequent allele in the group of 204 cases and controls and is consistent with the sense strand nt of each gene. The bolded red allele is associated with risk.\n\nc McNemar's chi-squared with continuity correction (see Methods section).\n\nd Log10 of the mid-p-value.\n\ne Log10 of the q-value.\n\nf The effect size (Cohen's g) for the McNemar test ranges from 0 to 0.5 where 0.5 is the maximum effect. It is the larger value of: the larger of: (b/(b+c) or c/(b+c)) - 0.5.\n\ng The proportion of informative pairs is (b+c)/n.\n\nh The polygenic risk factor value is the (effect size) x (proportion of informative pairs) and represents a value for summing an animal's polygenic risk score.\n\ni SNP BovineHD0700027239 corresponds to ARRDC3 C182Y (codon tRt) in exon 4 where tGt encodes C182 and tAt encodes Y182.\n\nj SNP BovineHD0300024366 was included for comparison, since it was used in early analyses for obtaining frequency data of U.S. cattle breeds in Table 4.\n\nThe mid-p-values from the McNemar’s association test of the most frequent SNP alleles were used. Panel A, test requiring the presence of homozygous risk alleles. Panel B, test requiring the presence of either 1- or 2-copies of the risk alleles. Panel C, test requiring heterozygosity for the risk alleles. The red horizontal line shows the Bonferroni correction at the 0.05 significance level. The red numbers in parentheses are McNemar's informative pairs from quadrants b and c (i.e., “b/c“, Table 1). The ratio of informative pairs indicates the strength of the association, and whether the allele is positively or negatively associated with BCHF (i.e., b/c > 0 or < 0).\n\nThe association of a missense variant in ARRDC3 with BCHF raised the possibility that the amino acid substitution could affect protein function and thereby increase the risk of disease in feedlot cattle. A comparison with ARRDC3 codons at position 182 in the jawed-vertebrate species (Gnathostomes) showed that cysteine residues were invariant throughout the 41 representative species examined (Figure 7). Examples of Gnathostome species with alternative residues at the equivalent position were not observed in any genus. The conservation of the C182 residue throughout the Gnathostomes is consistent with the hypothesis that the C182 residue is critical for normal ARRDC3 protein function and that homozygosity of the B. taurus-specific Y182 variant may have a deleterious effect.\n\nTMRCA is the estimated time to the most recent common ancestor in millions of years (Hedges et al., 2015). The full length ARRDC3 protein is 414 residues in cattle and most of the Amniota species. The letters are IUPAC/IUBMB codes for amino acids. The dots are amino acid residues identical to those in cattle.\n\nA custom two-SNP test was designed on a commercially available platform to genotype cattle for the major ARRDC3 and NFIA risk alleles. The platform uses “padlock” oligonucleotide probes, combined with fluorescently labeled probes and isothermal rolling circle amplification technology, for the qualitative detection of alleles. Using reference DNA from animals with known genotypes, the call rate and accuracy typically exceeded 97% and 99%, respectively. This included repeated testing of approximately 10% of the samples due to ambiguous allele calls on the first pass. Using custom genotypes to resolve errors in the original BovineHD BeadChip array, the BCHF OR for calves with homozygous risk alleles at both genes increased to 28-fold more (b/c = 28/1, p-value = 1.1 × 10-7, CI95 = 4-206). Testing an independent set of 171 BCHF cases from the same feedlots showed approximately 29% were homozygous for both ARRDC3 and NFIA risk alleles, compared to 29% of the BCHF 102 cases used in the GWAS (Figure 8). Conversely, an independent set of feedlot cattle persistently infected with BVDV had about 2% homozygosity for both ARRDC3 and NFIA risk alleles, which was similar to the 3% observed with the 102 unaffected animals used in the GWAS. Assuming a 5% BCHF prevalence in the most severely affected pens of feedlot cattle, the adjusted negative and positive predictive values were 0.99 and 0.10, respectively, with a sensitivity and specificity of 0.91 and 0.58. Thus, genetic testing with two SNPs has significant power to identify which animals have the least genetic predisposition for developing BCHF in feedlots, while having less power to predict which animals will develop disease. ARRDC3 and NFIA genotype configurations and their corresponding expected disease and allele transmission risks, together with their allele frequency estimates by breed, are presented in Tables 3 and 4, respectively. Although imperfect, these genetic associations and DNA tests provide a starting point for reducing BCHF risk in the most affected herds.\n\nTwo-SNPs were used for identifying feedlot cattle with homozygous risk alleles (BovineHD0700027239 [ARRDC3] and BovineHD0300024308 [NFIA]). Bovine cohorts: USMARC beef cattle diversity panel v2.9 (19 breeds (Heaton et al., 2016), Kansas feedlot calves persistently infected with bovine viral diarrhea virus (BVDV PI (Workman et al., 2016), pen matched BCHF controls (this study), BCHF cases (this study), independent BCHF validation cases (this study). The BCHF validation cases were collected by pen riders experienced in BCHF diagnosis, however, they were not confirmed at necropsy by veterinarians and researchers. All 204 of the BCHF case-control cattle tested negative for BVDV, and thus were not persistently infected with BVDV.\n\na Diploid combinations of risk alleles for each gene with markers BovineHD0700027239 (ARRDC3) and BovineHD0300024308 (NFIA).\n\nb The risk of developing BCHF in a feedlot with animals and environments like those described here.\n\nc The relative breeding rank of an animal based on risk genotypes for ARRDC3 and NFIA from best (1) to worst (5).\n\na Registered cattle chosen for minimal pedigree relationships (Heaton et al., 2016).\n\nb The risk allele definitions are listed in Table 2.\n\nc Note that the LD is only moderate (r2 ~ 0.47) between BCHF2 (BovineHD0300024366) and the SNPs most associated NFIA: BCHF31 (BovineHD0300024307), and BCHF32 (BovineHD0300024308). Thus, the BCHF2 allele values in this table are rough estimates of those for BCHF31 and BCHF32.\n\nd As described in Table 3.\n\ne As described in Table 3.\n\n\nDiscussion\n\nThe present report describes a GWAS with clinical cases of BCHF and their matched controls from feedlots in the Western Great Plains, where outbreaks are severe and ongoing. The 102 clinical cases used in this study were screened by pen riders from more than 140,000 feedlot cattle over the span of 18 months and were derived from 30 ranch sources. The most significant associations were attributed to genomic regions containing the genes for ARRDC3 and NFIA where multiple linked SNPs in each gene were associated with BCHF in feedlot cattle. Two copies of risk alleles in either gene increased the odds of disease by approximately eight-fold and homozygosity of risk alleles at both genes increased the odds of BCHF by 28-fold. Thus, specific DNA sequence variations in ARRDC3 and NFIA are major risk factors underlying BCHF in feedlot cattle in the Western Great Plains. Neither gene has been previously reported as being associated with heart failure in any species.\n\nARRDC3 is a member of the family of alpha arrestins involved in regulating metabolism in mammals. ARRDC3 has been linked to regulation of adrenergic signaling through interaction and regulation of ubiquitination and trafficking of the β2-adrenergic receptor in humans and mice (Han et al., 2013; Tian et al., 2016). When thermogenesis is needed during cold stress, for example, β-adrenergic receptors present on the cell surface signal activation of uncoupling protein-1 and the production of heat. ARRDC3 also modulates insulin action and glucose metabolism in the liver and binds directly to the insulin receptor (Batista et al., 2020). In cattle, ARRDC3 has been reported as being associated with growth and conformation traits (Saatchi et al., 2014; Bolormaa et al., 2014; Seabury et al., 2017; Abo-Ismail et al., 2017; Jiang et al., 2019; Smith et al., 2019). An important feature of some BCHF clinical cases in the present study was disease signs within 30 days of feedlot arrival (i.e., prior to fattening) (Heaton et al., 2019). This is consistent with the hypothesis that fattening is not the underlying cause of disease in these cattle. However, in humans, increased ARRDC3 expression was associated with an increase in body mass index, while ARRDC3 knockout mice were resistant to age-related obesity and have increased insulin sensitivity (Patwari et al., 2011). Of note, is that significant perinatal mortality (71%) was observed in the homozygous ARRDC3 knockout mice. In cattle, the ARRDC3 C182Y missense variant may reduce, or possibly obliterate, the normal function of the protein. This suggestion is based on the observation that only cattle have the Y182 variant while all other jawed vertebrates have C182. The Gnathostomes account for 99% of all living vertebrate species, including cattle, humans, and mice (Brazeau and Friedman, 2015). Regardless, the normal function of ARRDC3 in cattle has not been reported, and any potential biological mechanisms underlying the influence of this genomic region on BCHF are presently unknown.\n\nNFIA is a transcription factor that controls cellular differentiation. For example, it controls the onset of gliogenesis in the developing spinal cord (Deneen et al., 2006). NFIA is also a regulator of brown adipocyte differentiation and controls adipogenic and myogenic gene programs (Hiraike et al., 2020). NFIA activates adipogenesis, as well as actively suppressing myogenesis by binding to brown-fat-specific enhancers before differentiation, and later facilitates the binding of the master transcription factor of adipogenesis: peroxisome proliferator-activated receptor γ (PPARγ) (Hiraike et al., 2017). A reduction in NFIA activity shifts the balance towards myogenesis and the muscle gene program, while an increase in NFIA activity shifts the balance towards the brown fat program and brown/beige adipocytes (Hiraike et al., 2020). Thus, it is tempting to speculate that NFIA variants in beef cattle have been selected for reduced activity leading to increased muscle; however, there is no evidence for this. To the best of our knowledge, a significant association with NFIA has not been previously reported with a beef cattle phenotype. Still, an intriguing but unproven connection may exist between ARRDC3 and NFIA functions relating to cold stress, regulation of adrenergic signaling and thermogenesis. Anecdotally, the incidence of feedlot BCHF increases dramatically each year during the first wave of bitter cold weather, when many animals succumb to BCHF in a short period of time (Personal communication between authors (MPH and BLVL) and Nebraska feedlot owners). In any event, the biological mechanisms explaining how either of these genes may influence BCHF pathogenesis remain to be determined.\n\nA strength of this study was collecting clinical cases in the environment and geographic region where the disease problem is most apparent, and actively involving experienced feedlot pen riders with the identification of animals displaying disease signs. Feedlot personnel were incentivized to monitor more than 140,000 head from representative feedlots to find those animals most likely to have terminal BCHF and euthanize them before they died. The financial loss of each terminal case enrolled in the study was offset by a $500 indemnity when identified early and euthanized for necropsy. The diverse ranch sources, clinical cases matching, and custom McNemar allele analysis were also strengths of this study. Approximately 20% of the collected cases were dismissed due to inadequate pair-matching criteria. Weaknesses of the study included the relatively low number of total pairs (102) that met the qualifications for the study. However, the cost of indemnifying more clinical cases, combined with the time and resources needed for researchers to conduct careful necropsies and sample collections significantly affected the feasibility of going much beyond 100 matched pairs. Ideally, the study would have benefited from 200 matched pairs for discovery, and another 200 matched pairs for validation. Our validation set of 171 clinical cases consisted of unmatched cases that were either animals suspected of having BCHF and shipped early to a salvage beef processor, or those that died in the feedlot.\n\nGenetic testing of young cattle from affected herds can identify animals predisposed to developing BCHF in Western Plains feedlot environments. Using a two-SNP test with markers for ARRDC3 and NFIA risk alleles, BCHF cases are expected to occur in animals with homozygous ARRDC3 and NFIA risk alleles at a rate 28-fold higher than those without homozygous risk alleles. Although the confidence interval around this OR estimate is wide (four- to 206-fold), the test provides a starting point for applying costly BCHF interventions to a smaller group of animals rather than the whole pen. For example, a subset of high risk animals could be moved to a lower elevation for fattening, or they could be fattened with less energy-dense feed for a longer interval based on genetic testing. The two-SNP test used here has a high negative predictive value (0.99) that is powerful for identifying sires without these major risk alleles. Using low-risk sires and either conventional breeding or artificial insemination would have an immediate impact on reducing BCHF in the next generation of calves.\n\nThe choice of which ARRDC3 and NFIA markers are best for genetic testing is based on results presented in Table 2. In the ARRDC3 gene region, there are eight perfectly linked SNPs (r2 = 1.0, Figure S2, Extended data) that have the highest statistical association with BCHF and flank the C182Y missense mutation (BovineHD0700027239). The linkage of C182Y with these eight SNPs and a proximal ninth SNP is nearly perfect (r2 = 0.91 and 0.95, respectively). However, the difference in the OR based on informative pairs between the flanking SNPs and C182Y is within the margin of error (b/c = 42/5 and 42/6, respectively). Thus, any of the nine linked SNPs can be used as a proxy for the C182Y SNP in exon 4, which is hypothesized here as the disease-causing site when Y182 is homozygous. In the NFIA gene region, there are two tightly linked SNPs in intron 2 (r2 = 0.94) that have the highest statistical association with BCHF, and a third SNP in NFIA antisense (AS) 2 region (r2 = 0.49 and 0.45, respectively). The difference in the OR between the NFIA intron 2 SNPs and the NFIA AS2 SNP was not insignificant (b/c = 37/5 and 41/11, respectively). Thus, we recommend using either of the NFIA intron 2 SNPs for genotyping (BovineHD0300024307, BovineHD0300024308).\n\nFuture prospects for improved and additional BCHF genetic markers are promising. The 560,000 BovineHD BeadChip array SNPs used in the present GWAS represent less than 5% of 12 million variants in the Angus genome (Low et al., 2020). Thus, whole genome sequencing in the 102 case-control pairs may reveal variants with increased positive predictive values in the ARRDC3 and NFIA regions. Genome sequencing will also allow a deeper analysis by using millions of genome-wide variants that may be associated with BCHF. Additional markers from prospective associated regions could potentially be used in genetic tests to calculate polygenic risk scores for individual animals, and further improve disease risk prediction by stratifying populations into risk groups (Knowles and Ashley, 2018; Torkamani et al., 2018; Wise et al., 2019; Claussnitzer et al., 2020). Thus, a two-SNP test for ARRDC3 and NFIA risk alleles represents the first genetic tool for identifying an animal’s genetic risk for BCHF, and may be helpful in determining whether the ARRDC3 and NFIA markers are also associated with the high-elevation “brisket disease” disorder in the Rocky Mountain region of Colorado and Utah. Regardless of the outcome, additional DNA markers may be needed to increase risk prediction accuracy for BCHF in feedlot cattle.\n\n\nConclusions\n\nDNA sequence variation in ARRDC3 and NFIA was discovered to be associated with BCHF in feedlot cattle at moderate elevations, and thus may play a role in pathogenesis. Animals that were homozygous for risk alleles in both genes were 28-fold more likely to develop heart failure than those without. A custom DNA-based test showed 29% of clinical cases had homozygous risk alleles in both genes, compared to less than 2.5% in 198 similar unaffected feedlot cattle. This type of test may be useful for identifying feedlot animals at the highest risk for BCHF in the Western Great Plains of North America. In herds affected by BCHF, knowledge of which cattle have the highest and lowest genetic risk for disease allows producers to make informed decisions for selective breeding and animal health management.\n\n\nData availability\n\nFigshare: Additional files for the article entitled, Association of ARRDC3 and NFIA variants with bovine congestive heart failure in feedlot cattle, https://doi.org/10.6084/m9.figshare.c.4331114.v2 (Heaton, 2022).\n\nThis project contains the following data files:\n\n• Table S1. Metadata for 102 BCHF cases and their matched controls\n\n• Figure S1. Calculation of expected theoretical q- and mid p-values\n\n• Figure S2. Linkage disequilibrium between SNPs associated with BCHF in ARRDC3 and NFIA\n\n• Files S1 and S2. Unfiltered map and ped files (777,962 SNPs) for 102 BCHF matched case-control pairs, filename: BCHF102pairsHD778 (28.9 and 605.4 Mb, respectively.)\n\n• Files S3 and S4. Filtered map and ped files (563,042 SNPs) for 102 BCHF matched case-control pairs, Filename: BCHF102pairsHD770Filtered (20.9 and 438.2 Mb, respectively.)\n\n• Files S5 and S6. Unfiltered map and ped files (777,962 SNPs) for 102 BCHF pairs and 96 MBCDPv2.9 bulls, filename: BCHF102_MBCDP29_HD778 (27.6 and 890.3 Mb, respectively.)\n\n• Files S7 and S8. Filtered map and ped files (604,746 SNPs) for 102 BCHF pairs and 96 MBCDPv2.9 bulls, filename: BCHF102_MBCDP29_HD778Filtered (21.5 and 692.1 Mb, respectively.)\n\n• Files S9 and S10. Filtered map and ped files (563,087 SNPs) for 102 BCHF matched case-control pairs, filename: BCHF102pairsHD778FFFSortFiltered (20.9 and 438.2 Mb, respectively.)\n\n• File S11. Unformatted McNemar output file (563,087 SNPs) for 102 BCHF matched case-control pairs, filename: BCHF102pairsHD778FFFSortFiltered.McNemarsResults.csv (468.74)\n\n• File S12. McNemar’s test statistics for 561,683 filtered SNPs, filename: BCHF102PairsHD778FFFSortFiltered.McNemarsResults17.xlsx (450.8 Mb)\n\n• File S13. Genome-wide SNPs passing the 5% FDR. Filename: BCHF102PairsHD778FFFSortFilteredExtractTwoHF_q_LT_0_05_MPH3.xlxs (90k)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nMatLab analysis code available at GitHub: https://github.com/greg-harhay/McNemarsSNPAnalysis\n\nExecutable MatLab code available at Code Ocean: https://doi.org/10.24433/CO.0870729.v1\n\nData are available under the terms of the UnLicense.",
"appendix": "Acknowledgments\n\nWe thank D. George, J. Nierman, D. Ridgway, and S. Schmidt for secretarial and administrative support; S. Johnson for sample collection support; R. Carman, G. Darnall, P. Miller, T. Williams, and their outstanding pen riders for identifying clinical cases, assisting with sample acquisition, and sharing their knowledge of animals with disease; J. Pollak, and M. Boggess for leadership and support during the design and execution of the project. Dr. D. Sjeklocha for assistance with BVDPI calf samples; Dr. A. Oommen and MatMaCorp scientists (Lincoln, NE, USA) for outstanding technical assistance in SNP assay development. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. 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Psychometrika. 1947; 12: 153–157. Publisher Full Text\n\nMorrell NW, Aldred MA, Chung WK, et al.: Genetics and genomics of pulmonary arterial hypertension. Eur. Respir. J. 2019; 53: 1801899. PubMed Abstract | Publisher Full Text\n\nMoxley RA, Smith DR, Grotelueschen DM, et al.: Investigation of congestive heart failure in beef cattle in a feedyard at a moderate altitude in western Nebraska. J. Vet. Diagn. Investig. 2019; 31: 509–522. PubMed Abstract | Publisher Full Text\n\nNeary JM, Booker CW, Wildman BK, et al.: Right-Sided Congestive Heart Failure in North American Feedlot Cattle. J. Vet. Intern. Med. 2016; 30: 326–334. PubMed Abstract | Publisher Full Text\n\nNewman JH, Holt TN, Cogan JD, et al.: Increased prevalence of EPAS1 variant in cattle with high-altitude pulmonary hypertension. Nat. Commun. 2015; 6: 6863. PubMed Abstract | Publisher Full Text\n\nNomenclature Committee for the International Union of Biochemistry (NC-IUB): Nomenclature for incompletely specified bases in nucleic acid sequences. Recommendations 1984. Mol. Biol. Evol. 1986; 3: 99–108.\n\nPatwari P, Emilsson V, Schadt EE, et al.: The arrestin domain-containing 3 protein regulates body mass and energy expenditure. Cell Metab. 2011; 14: 671–683. PubMed Abstract | Publisher Full Text\n\nReza N, Owens AT: Advances in the Genetics and Genomics of Heart Failure. Curr. Cardiol. Rep. 2020; 22: 132. PubMed Abstract | Publisher Full Text\n\nSaatchi M, Schnabel RD, Taylor JF, et al.: Large-effect pleiotropic or closely linked QTL segregate within and across ten US cattle breeds. BMC Genomics. 2014; 15. PubMed Abstract | Publisher Full Text\n\nSeabury CM, Oldeschulte DL, Saatchi M, et al.: Genome-wide association study for feed efficiency and growth traits in U.S. beef cattle. BMC Genomics. 2017; 18: 386. PubMed Abstract | Publisher Full Text\n\nSmith JL, Wilson ML, Nilson SM, et al.: Genome-wide association and genotype by environment interactions for growth traits in U.S. Gelbvieh cattle. BMC Genomics. 2019; 20: 926. PubMed Abstract | Publisher Full Text\n\nStorey JD: A direct approach to false discovery rates. Journal of the Royal Statistical Society: Series B (Statistical Methodology). 2002; 64: 479–498. Publisher Full Text\n\nStorey JD, Tibshirani R: Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. 2003; 100: 9440–9445. PubMed Abstract | Publisher Full Text\n\nTian X, Irannejad R, Bowman SL, et al.: The α-Arrestin ARRDC3 Regulates the Endosomal Residence Time and Intracellular Signaling of the β2-Adrenergic Receptor. J. Biol. Chem. 2016; 291: 14510–14525. PubMed Abstract | Publisher Full Text\n\nTorkamani A, Wineinger NE, Topol EJ: The personal and clinical utility of polygenic risk scores. Nat. Rev. Genet. 2018; 19: 581–590. PubMed Abstract | Publisher Full Text\n\nWise AL, Manolio TA, Mensah GA, et al.: Genomic medicine for undiagnosed diseases. Lancet. 2019; 394: 533–540. PubMed Abstract | Publisher Full Text\n\nWorkman AM, Heaton MP, Harhay GP, et al.: Resolving Bovine viral diarrhea virus subtypes from persistently infected U.S. beef calves with complete genome sequence. J. Vet. Diagn. Investig. 2016; 28: 519–528. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "129614",
"date": "20 Apr 2022",
"name": "Alan L. Archibald",
"expertise": [
"Reviewer Expertise Farmed animal genetics and genomics"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nA thorough analysis of potential associations between genetic factors and susceptibility to bovine congestive heart failure (BCHF) in feedlot cattle is presented. Genetic variants at the ARRDC3 and NFIA loci are shown to be associated with increased risk of BCHF. The SNP variants in these loci do not fully explain the risk of BCHF, nor have causal genetic variants been identified. Genetic tests to identify animals at risk of BCHF and/or at risk of transmitting increased risk to their offspring are proposed. The analysis of genetic variation associated with risk of BCHF is limited to SNP variants present on the Illumina HD SNP chip. Given the strong signal associated with the ARRDC3 locus in particular it would have been useful to sequence this locus in multiple individuals of known BCHF phenotype in order to identify candidate causal or risk variants. The authors highlight a missense variant ARRDC3 C182Y for which there is an assay as BovineHD0700027239 on the Illumina HD SNP chip. They note that a cysteine residue is found at this position in the ARRDC3 protein in a wide range of animals separated by millions of years of evolutionary time.\nMultiple sequence variants have been reported in the bovine ARRDC3 locus including several other missense mutations and premature stop codons as summarised here: Link\nSeveral of these missense and premature stop variants are predicted by SIFT analysis to be deleterious whereas the ARRDC3 C182Y variant is not predicted by SIFT analysis to be deleterious.\nSequence analysis of the ARRDC3 locus in individuals of known BCHF phenotypes might reveal candidate causal or risk variants.\nIn order to link the SNP information reported in the manuscript more readily to other data sources it would be useful to add rs numbers. For example, the rs number for the ARRDC3 C182Y variant for which there is an assay as BovineHD0700027239 on the Illumina HD SNP chip is rs109901274.\nThe frequencies of the ARRDC3 risk alleles as summarised in Table 4 are very high in some breeds, including Angus, Red Angus, Murray Grey and i) pose a challenge to selective breeding in these breeds to reduce the risk of BCHF and ii) raises questions about why the incidence of BCHF is not higher.\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": "11058",
"date": "13 Apr 2024",
"name": "Michael Heaton",
"role": "Author Response",
"response": "AUTHORS' RESPONSE TO REVIEWER 1 The authors appreciate and are grateful for both reviewers’ thoughtful reviews of our article. Below we have provided point-by-point responses to their suggestions and comments: Reviewer 1, point 1: “Sequence analysis of the ARRDC3 locus in individuals of known BCHF phenotypes might reveal candidate causal or risk variants.” Authors response 1: We agree. We attempted to indicate this point in the last paragraph of the discussion. However, to further underscore this point and make our intentions unambiguous, we have revised the first paragraph of the discussion: “It is unknown whether the associated SNPs are merely linked to variants responsible for the elevated BCHF risk, or whether they are involved directly in pathogenesis. Whole genomic sequence (WGS) analyses are underway for the 102 case-control pairs of animals and may unlock further insights in the future.” The last paragraph of the discussion was also revised to emphasize this point: “Any novel variants with increased association would potentially represent candidates for functional variants conferring BCHF risk. A WGS analysis may also identify any newly associated genomic regions previously missed due to ascertainment bias in the SNP selection for the BovineHD BeadChip array. For these reasons, we are endeavoring to produce and analyze 15-fold WGS coverage from these 204 animals.” Reviewer 1, point 2: “In order to link the SNP information reported in the manuscript more readily to other data sources it would be useful to add rs numbers.” Authors response 2: We agree and have added rs numbers to Table 2 for the 12 SNPs most associated with BCHF. To provide additional unique molecular information defining these 12 SNP, we also added Table 5 which includes 200 bp of adjacent context nucleotide sequence from the ARS-UCD2.1 bovine reference assembly, together with flanking SNP variants greater than 0.015 frequency as identified in a 96-member beef cattle diversity panel. Together, these details are important for designing accurate assays to score genotypes at SNP sites associated with BCHF in feedlots of the Western Great Plains. Reviewer 1, points 3 and 4: “The frequencies of the ARRDC3 risk alleles as summarised in Table 4 are very high in some breeds, including Angus, Red Angus, Murray Grey and i) pose a challenge to selective breeding in these breeds to reduce the risk of BCHF and ii) raises questions about why the incidence of BCHF is not higher.” Authors response 3 and 4: We agree and have added two sequential paragraphs to the Discussion section: “The high frequencies of ARRDC3 and NFIA risk alleles in some affected breeds (> 0.65) raise the question of why the disease prevalence is relatively low even in outbreaks (> 0.07)? This phenomenon may be due to the multifactorial nature of complex disease. The development of BCHF in cattle is presumed to be influenced by exposure to non-genetic factors, such as elevation (hypoxia), extreme weather conditions, feeding schedules, ionophores, feed grade antibiotics, steroid hormone implants, and beta-adrenergic agonist feed additives (Krafsur et al, 2019, Neary et al. 2018). These environmental and management factors may play significant but unknown roles in disease development. In addition, most complex diseases are considered polygenic with variation at many genes having small effects (Khera et al. 2018). DNA sequence variation identified here in ARRDC3 and NFIA genomic regions may predispose cattle to BCHF under certain conditions, despite the absence of any known causal pathogenic mutations. The high frequencies of risk alleles observed in some breeds also poses a challenge for selective breeding. Although estimates for the positive predictive value of the ARRDC3 and NFIA markers were low (0.10), the negative predictive value was quite high (0.99). Consequently, identifying breeding stock lacking these risk factors could prove useful for reducing a herd's overall risk. The challenge is finding sires without the ARRDC3 and NFIA risk alleles in breeds with a high prevalence of high-risk alleles. For instance, the largest affected breed in the United States, American Angus, has more than 300,000 bulls registered annually in its association. However, less than 5% (15,000) are expected to possess the optimal low-risk genotypes at both the ARRDC3 and NFIA gene regions (M. Heaton, L. Kuehn, and B. Vander Ley 2022, unpublished). To identify the best bulls for decreasing BCHF risk alleles in their herds, cattle producers may need to obtain genotypes from hundreds of candidate sires. Unfortunately, this information is not widely available for most bulls at present. Despite these challenges, there are a number of reasonable selection strategies that could help reduce the risk of BCHF in the long term, depending on the specific goals and circumstances of the cattle producer. “"
}
]
},
{
"id": "129617",
"date": "26 Apr 2022",
"name": "Cord Drögemüller",
"expertise": [
"Reviewer Expertise Animal genetics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study aims to identify a possible genetic cause for the occurrence of BCHF in North American feedlot cattle. The case control study using high density SNP genotypes revealed significant associations to two different genomic regions. This indicates a possible genetic predisposition, at the same time the presented genotype distributions indicate that it is highly likely a complex inheritance, since the genotypes of the markers in these two genomic regions do not alone explain the emergence of the clinical symptoms.\nThe two protein-coding genes annotated in the two mapped chromosomal regions have not been associated with heart disease in humans or animals. In principle, this could be of great biomedical interest, as it is well known that in animal phenotypes we often have the possibility to assign a (new or further) previously unknown function to more or less well characterized genes. Especially the missense variant in the ARRDC3 gene seems to be possibly of pathogenic nature due to the presented conservation of the affected amino acid. What speaks against this is the fact that this variant is obviously not rare in cattle in general, otherwise the SNP would not be present on the commercial 777k array. Table 4 shows impressively that the variant occurs similarly frequently in many other breeds or populations, in all of which there has been no mention of a risk for BCHF. Therefore, because no genome sequence data were available, it is rather to assume that in both cases the identified SNPs are only coupled markers and hardly the molecular cause. This should be clearly differentiated in the paper. It remains unclear whether potentially interesting candidate genes for cardiac dysfunction are located in the vicinity of the two association signals and, given the complex development of the disorder, regulatory variants can be assumed as the cause rather than protein-coding variants, which sometimes lead to phenotypes that manifest themselves at birth or at the beginning of life.\nOverall, the work is partly difficult to read because too many methodological details are listed and, on the other hand, the text often remains vague in the biological interpretation. Therefore, the broadly presented possibility of implementing these first results in practical breeding work seems too offensive to me. In my opinion, an even broader validation study with many more affected animals is needed before these markers are directly considered in selection. The study represents a very interesting first step, but the results should be considered with caution, especially since there is always a residual risk of coupled unknown pleiotropic variants on traits desired for breeding.\nFurther comments:\n'Fedlot cattle' is not a clear term outside of North America, so it would be better to speak of the breed involved (Angus?).\n\nWere there any other pathological (histological) data on the disease?\n\nWhat is known about the possible inheritance of BCHF? Have segregation analyses been performed? What is the heritability?\n\nIf about 5% of feedlot cattle are at risk for BCHF, why have only about 100 affected animals been identified when over 1400000 cattle have been considered? Is the disease rarer than assumed?\n\nThe nomenclature of variants, especially the representation of ARRDC3 alleles, should necessarily follow the current recommendations, see Richards et al. 20151.\n\nThe intronic variant in the NFIA gene remains functionally absolutely unclear, therefore talk about a linked marker rather than a possible causal variant.\n\nIn the methods section, the races in the panel of 96 unrelated controls should be mentioned.\n\nThe actual linkage disequilibrium between markers in the two associated genomic regions remains unclear in places. In particular, the question arises whether the SNPs mentioned at the end of the methods section are really located with a LD of 1 to the NFIA variant in intron 4 of the gene.\n\nThe wording \"homozygous major alleles\" on page 10 is unfortunate. Would it not be better to say homozygous for the major allele? An allele itself cannot be homozygous, but the genotype is either hetero- or homozygous for two or one allele.\n\nIn Figure 7 the accession numbers of the listed protein sequences are missing.\n\nOn page 15, a section on the evaluation of the pathogenicity of the missense variant in the ARRDC3 gene is missing next to the presentation of evolutionary conservation. For example, programs such as MutPred2, SIFT or Provean could be used.\n\nTable 4 would be easier to understand if actual genotype distributions were listed. Also missing is a clear table on the genotype distribution of the two highlighted markers for the animals from the discovery and confirmation cohorts to clearly assess the results. Table 3 is then a further transformation towards possible practical application, but this original publication should include the true genotypes clearly and legibly.\n\nThe second paragraph of the discussion states \"an important feature of some BCHF clinical cases...\" What exactly does \"some\" mean here? This should be clarified.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "11059",
"date": "13 Apr 2024",
"name": "Michael Heaton",
"role": "Author Response",
"response": "AUTHORS' RESPONSE TO REVIEWER 2 The authors appreciate and are grateful for both reviewers’ thoughtful reviews of our article. Below we have provided point-by-point responses to their suggestions and comments: Reviewer 2, point 1: “The study aims to identify a possible genetic cause for the occurrence of BCHF in North American feedlot cattle.” Authors response 1: Our aim has been subtly misstated above, but in an important way. Our stated aim in the Abstract was “to search for genomic regions associated with this disease”. Our search was designed to test the null hypothesis that no significant association exists between HD770 SNPs tagging genomic regions and BCHF. We have indicated throughout the article that we are reporting the association of SNP alleles and not the pathogenic roles for ARRDC3 and NFIA variants associated with BCHF. Our focus has been on the strength and reproducibility of the detected associations, not their likelihood of being causal. To underscore our stated aim, we have modified the Introduction section final paragraph to include this text: “… to test the null hypothesis that significant association does not exist between haplotype tagging SNPs and BCHF. Our results rejected the null hypothesis and identified two distinct genomic regions harboring major genetic risk factors associated with BCHF.” Reviewer 2, point 2: “Therefore, because no genome sequence data were available, it is rather to assume that in both cases the identified SNPs are only coupled markers and hardly the molecular cause. This should be clearly differentiated in the paper.” Authors response 2: We agree and have modified the 4th and 5th sentences of the discussion to state: “The most significant genome-wide associations were limited to two regions containing ARRDC3 and NFIA genes, respectively. In each region, multiple linked SNPs were associated with BCHF in feedlot cattle. It is unknown whether the associated SNPs are merely linked to variants responsible for the elevated BCHF risk, or whether they are involved directly in pathogenesis.“ As described in our response to Reviewer 1, we underscore this point and make our intentions unambiguous in the last paragraph: “Thus, WGS analysis of the 102 case-control pairs would refine the bounds of the genomic region most strongly associated with BCHF and identify the complete set of tagging SNPs appropriate for use in genotyping by sequencing. Any novel variants with increased association would potentially represent candidates for functional variants conferring BCHF risk. A WGS analysis may also identify any newly associated genomic regions previously missed due to ascertainment bias in the SNP selection for the BovineHD BeadChip array. For these reasons, we are endeavoring to produce and analyze 15-fold WGS coverage from these 204 animals.” Reviewer 2, point 3: “'Fedlot cattle' is not a clear term outside of North America, so it would be better to speak of the breed involved (Angus?).” Authors response 3: We recognize that the details of North American beef production may not be well known around the world. Moreover, it varies greatly within the US. Feedlots may receive all types of beef, dairy, and composite cattle. Overall, Angus-influenced black cattle represent about 70% of the fattened cattle in the study region. In the method section we describe a group of 204 calves as 93% solid black, 70% castrated males, and none had visible horns. Although the cases were defined by clinical presentation, they seemed roughly representative of the feedlots we sampled. We have inserted the following sentence in the third line of the Introduction section: “Feedlot cattle in this region are typically a mix of germplasm derived from popular British and Continental European breeds with more than 60% of the animals having a black hide from Angus contributions.“ Reviewer 2, point 4: “Were there any other pathological (histological) data on the disease?” Authors response 4: Systematic histological data was not collected on the 102 pairs of cases and controls. Tissues were collected from the clinical cases at necropsy, but the tissues of healthy controls were processed into beef and unavailable. Reviewer 2, point 5: “What is known about the possible inheritance of BCHF? Have segregation analyses been performed? What is the heritability?” Authors response 5: To date, there have been no reports of inheritance, segregation analysis, or heritability of clinical BCHF. Also, no other studies have used a BCHF phenotype to directly obtain an estimate that could correspond to our study. We used a clinically-defined binary phenotype to represent BCHF, specifically, end-stage congestive heart failure mortality in Western Great Plains feedlot cattle. By comparison all matched pen mate control animals were normal and passed their antemortem inspection at beef processing facilities. Thus, with only two phenotypic states, the use of variance as a convenient mathematical quantity was not appropriate for estimating heritability. Moreover, our BCHF study used animals raised in multiple environments and populations, while heritability is a statistical measure defined in the context of a specific environment and a specific population. For these and other reasons, heritability has not been measured for BCHF. Since our publication, a report used cardiomegaly observed at slaughter as a proxy for “BCHF” (Buchanan, JW et al., Front. Genet. 2023; 14:1148301). However, healthy animals with enlarged hearts cattle that have passed antemortem inspection do not meet our criteria for BCHF and would be considered unaffected controls in our study. Reviewer 2, point 6: “If about 5% of feedlot cattle are at risk for BCHF, why have only about 100 affected animals been identified when over 1400000 cattle have been considered? Is the disease rarer than assumed?” Authors response 6: The 5% number is the mortality in severely affected pens of cattle. It was not the percentage of cattle at risk. To clarify reasons for the case enrollment rate, we have added this text to the Methods section, “The case enrollment rate of 102 cases per 140,000 feedlot cattle monitored (0.073%) was negatively affected by: 1) removal of sick animals for emergency salvage slaughter, 2) removal of matched unaffected pen mates for beef processing, 3) the rapid onset of congestive heart failure and death, 4) reluctance of overburdened personnel to commit valuable time despite the $500 indemnity offer for each matched pair identified early, and 5) exclusion of necropsied animals meeting some, but not all, of the case definition criteria.” We also suspect that the disease is underreported due to worker misclassification at necropsy. Reviewer 2, point 7: The nomenclature of variants, especially the representation of ARRDC3 alleles, should necessarily follow the current recommendations, see Richards et al. 20151. Authors response 7: The Richard et al. 2015 article (“Standards and guidelines for the interpretation of sequence variants”) provides detailed criteria for classifying pathogenic variants in genes known to cause human diseases. As noted in Authors response 1 above, our stated aim was “to search for genomic regions associated with this disease”. We are not reporting the pathogenicity of variants in this report. We have added the rs numbers for the variants highlighted in Table 2 and added context sequence information in a new Table 5. Reviewer 2 point 8: The intronic variant in the NFIA gene remains functionally absolutely unclear, therefore talk about a linked marker rather than a possible causal variant. Authors response 8: Although it is not clear which sentence in the manuscript that Reviewer 2 is referring, we agree. Other than the possibility of the ARRDC3 C182Y missense SNP affecting protein function, all other SNPs associated with BCHF are presumed to be linked variants. Likewise, it is also possible that the ARRDC3 C182Y missense SNP is merely linked to a functional variant. To emphasize this point we have modified this sentence towards the end of the first paragraph of the Discussion section: Thus, specific DNA sequence variants within ARRDC3 and NFIA are markers for BCHF risk in feedlot cattle in the Western Great Plains, either through linkage to causal variants or direct effects. Reviewer 2, point 9: In the methods section, the races in the panel of 96 unrelated controls should be mentioned Authors response 9: We agree. This information was in our original submission to F1000Research. We have restored this content in the Methods section of the revised article. Reviewer 2, point 10: The actual linkage disequilibrium between markers in the two associated genomic regions remains unclear in places. In particular, the question arises whether the SNPs mentioned at the end of the methods section are really located with a LD of 1 to the NFIA variant in intron 4 of the gene. Authors response 10: We agree and have rewritten the penultimate paragraph of the article to clarify and discuss the strength of LD between the BCHF-associated SNPs in the two separate genomic regions. With regards to the two best associated NFIA variants spanning 2.32 kb in intron 4, their LD was high (r2 = 0.94). These two SNPs were only moderately linked to a SNP 127 kb upstream in NFIA AS2 (r2 = 0.49 and 0.45, Figure S2). Reviewer 2, point 11: The wording \"homozygous major alleles\" on page 10 is unfortunate. Would it not be better to say homozygous for the major allele? An allele itself cannot be homozygous, but the genotype is either hetero- or homozygous for two or one allele. Authors response 11: We agree this was terribly worded. The sentence on page 10 line 6 now states, “Homozygosity for the major allele of either of these two SNPs was associated with increased BCHF risk (OR 7.4, CI 95, 2.9 to 19, Table 2).” Reviewer 2, point 12: In Figure 7 the accession numbers of the listed protein sequences are missing. Authors response 12: Figure 7 summarizes the results of a much larger ARRDC3 peptide alignment with 80 accession numbers. We have added this larger alignment with its accession numbers to the extended and underlying data section (Table S2. Extended comparison of ARRDC3 residues near the C182Y position in the Gnathostomes. https://doi.org/10.6084/m9.figshare.22213495 Reviewer 2, point 13: On page 15, a section on the evaluation of the pathogenicity of the missense variant in the ARRDC3 gene is missing next to the presentation of evolutionary conservation. For example, programs such as MutPred2, SIFT or Provean could be used. Authors response 13: We respectfully disagree. As emphasized above in Author response 1, our aim here was not to evaluate the pathogenicity of associated SNPs. In our opinion, such analyses are premature for bead array SNPs, which have a strong selection biased for high minor allele frequencies and represent a only small fraction of the total genetic variation in the region. In silico predictions of pathogenicity of missense variants would be more appropriate once WGS for these regions is available, and the full scope of associated variants is known. However, to increase our understanding of the Y182 variant on the predicted ARRDC3 tertiary structure, we have added alignments from de novo AlphaFold2 predicted structure in Figure 9 and introduced a hypothesis for testing (Discussion section). Reviewer 2 point 14: Table 4 would be easier to understand if actual genotype distributions were listed. Also missing is a clear table on the genotype distribution of the two highlighted markers for the animals from the discovery and confirmation cohorts to clearly assess the results. Table 3 is then a further transformation towards possible practical application, but this original publication should include the true genotypes clearly and legibly. Authors response 14: We are happy to provide additional lists of genotypes for figures. We recognize that extracting these genotypes from the provided 770k SNP bead array PLINK file (Supplementary Files S1 through S9) is not trivial. In addition, the revised article now contains genotypes corresponding to the 12 SNPs represented Table 2 for the 204 animals (Table S3), the two SNPs from 566 animals represented in Figure 8 (Table S4), and two SNPs for the 1203 animals listed in Table 4 (Table S5). We also note that the homozygous NFIA bar chart data in Figure 8 have changed slightly for the 96 Diversity beef bulls and the 96 persistently infected (BVD) feedlot cattle panels. Their bars increased due to inadvertent initial use of a 3-SNP NFIA haplotypes instead of just the single NFIA SNP rs133192205 (ie., BovineHD0300024308 or BCHF32). Since the 3-SNP NFIA haplotypes were not available for the 171 validation cases, we reverted to using only the single NFIA SNP for all cohorts. Reviewer 2, point 15: The second paragraph of the discussion states \"an important feature of some BCHF clinical cases...\" What exactly does \"some\" mean here? This should be clarified. Authors response 15: We agree. The sentence has been rephased to read: “More than 50% of the BCHF cases in our study died in the first half of the fattening period.”"
}
]
}
] | 1
|
https://f1000research.com/articles/11-385
|
https://f1000research.com/articles/13-158/v1
|
01 Mar 24
|
{
"type": "Research Article",
"title": "Minimum work associated with separating nitrogen from air: An exergy analysis",
"authors": [
"Garrett Rinker"
],
"abstract": "Background Nitrogen is essential for a variety of industries, including heat treatment, laser cutting, fire protection, and food packaging. Many companies in these industries obtain nitrogen via on-premises air separation processes. The three main processes for separating nitrogen from ambient air are cryogenic distillation, membrane separation, and pressure-swing adsorption (PSA). Improvements to these processes will likely focus on increasing efficiency, resulting in reduced environmental impact owing to less electrical power demand and opportunities for economic incentives. Regardless of the process utilized, a minimum theoretical amount of work input is required to obtain nitrogen gas at different pressures and concentrations compared to ambient conditions.\n\nMethods An equation was derived to evaluate the total exergy (including thermo-mechanical and chemical exergy) of product and exhaust mixtures resulting from air separation, indicating the minimum theoretical work input as a function of the product pressure, purity, and process recovery rate. This analysis considered an air separation system as a black box, with the input, output, and exhaust assumed to be ideal gas mixtures of nitrogen and oxygen at 15°C. The analysis applies to cryogenic distillation if the product and exhaust mixtures return to the gas phase.\n\nResults In general, the minimum required work input increases with product purity and recovery rate. Plots of minimum theoretical work versus product purity and recovery rate were made for two product pressures (atmospheric and 800 kPa) to show the behavior of the derived equation.\n\nConclusions The analysis allows for direct efficiency (based on the second law of thermodynamics) comparisons between existing processes and future technological innovations in the field of air separation. Actual air separation systems have low efficiencies compared to ideal systems; actual PSA systems were estimated to have second law efficiencies of 5.5–11.2%. Therefore, there is great potential for improvements to current air separation systems.",
"keywords": [
"Air Separation",
"Exergy",
"Nitrogen Generation"
],
"content": "Introduction\n\nNitrogen is essential for a variety of industries, including heat treatment, laser cutting, fire protection, and food packaging. The nitrogen requirements for a process are usually specified by purity (expressed as the percentage form of the mole fraction) and flow rate at a certain pressure. Most processes require nitrogen purities in the range of 95–99.999%. The three main processes for obtaining nitrogen from ambient air are cryogenic distillation, membrane separation, and pressure-swing adsorption (PSA). The selection of the process depends on the product flow rate, purity, and state (liquid or gas). Cryogenic distillation was first introduced by Carl von Linde in 1895 and patented in 1903.1 PSA and membrane separation technologies became more popular in the 1980s, and these technologies can provide sufficient nitrogen purity and flow rates for a wide range of applications at a much lower cost than cryogenics.2\n\nCryogenic distillation is the most energy intensive of the three main air separation processes; cryogenic systems typically have an energy consumption of 2.56 kWh/kg of liquid nitrogen, whereas PSA systems typically require 0.31–0.63 kWh/kg of nitrogen gas.3 This usually makes cryogenic distillation economically viable for large-scale production. However, cryogenic distillation can provide greater nitrogen purity (>99.999%4) than membrane separation and PSA. In addition, some industries require nitrogen in the liquid form, which cannot be obtained via membrane separation or PSA. Membrane systems operate via selective permeation, where differences in gas molecule diffusion rates drive separation through a packed container of hollow fibers. Membrane systems typically provide nitrogen with a purity range of 95–99.5%.4 PSA systems typically utilize two sieve beds filled with carbon molecular sieves (CMS), a material that selectively adsorbs gas molecules at pores on its surface. PSA systems can provide nitrogen purities in the range of 95–99.999%.5\n\nMany examples of exergy analyses performed for gas separation via cryogenic distillation,6–9 PSA,10–12 and membrane systems13–15 exist in the literature, most of which focus on specific realistic processes. Entropy generation (directly proportional to exergy destruction) has also been used to describe the performance of gas separation systems.16 Weber et al.17 utilized the concept of a “physical optimum” to compare the energy efficiencies of cryogenic and PSA processes for oxygen production. This “physical optimum” identifies avoidable and unavoidable losses as modifications of exergy analysis.\n\nRegardless of the approach, a minimum theoretical amount of work input is required to obtain gas at different pressures and concentrations than under ambient conditions. This article presents a theoretical exergy analysis of air separation, indicating the minimum theoretical work input as a function of the product pressure, purity, and process recovery rate. This analysis considered an air separation system as a black box, with the input, output, and exhaust assumed to be ideal gas mixtures of nitrogen and oxygen at 15°C.\n\n\nMethods\n\nAssumptions\n\nThe following assumptions will be made for the analysis:\n\n• Air is composed of 79% nitrogen and 21% oxygen (all other constituents were neglected).\n\n• Gas mixtures will be treated as ideal gases.\n\n• The feed (initial state) air was standard atmospheric air at zero gauge pressure (15°C and 101.325 kPa),18 representing the dead state.\n\n• The exhaust and product mixtures were equal to that of the dead state temperature.\n\n• The exhaust gas pressure will be equal to that of the dead state.\n\n• Kinetic and potential energy changes are negligible.\n\n• Only the initial and final states of gas mixtures are required.\n\nPerformance of air separation systems\n\nFor this analysis, the minimum theoretical work required to obtain nitrogen at the specified purities and pressures was determined by calculating the useful work potential (exergy) of the product and exhaust gas mixtures. Exergy describes how much work a reversible system could produce as the contents of the system proceed from a specified state to the dead state, a condition in which the contents are in thermodynamic equilibrium with the environment. Under reversible conditions, the work required to separate a gas mixture is equal to that required for the mixing of its individual components.\n\nThe efficiency of a work-consuming device (such as an air separation system) in terms of the second law of thermodynamics can be described by:\n\nwhere ηII is the second law efficiency, Wrev is the theoretical reversible work required for a process, and Wa is the actual work input to the process.\n\nThe purity and recovery of nitrogen in the product affect the amount of work required to perform the separation process. Purity (θ) is equivalent to the mole fraction of nitrogen in the product gas (Equation 2). The recovery (r) of nitrogen from the input air is given by Equation 3.\n\nDerivation of the exergy equation\n\nPal19 described the exergy of a gas mixture φ as being composed of two parts, namely the thermo-mechanical exergy φTM and chemical exergy φC:\n\nOn a unit mass basis, the thermo-mechanical exergy of a closed system is expressed as20:\n\nThe portion of Equation 8 concerning the specific volume can be written as (assuming an ideal gas):\n\nSubstituting Equation 9 and Equation 10 into Equation 8:\n\nFollowing the assumption that the temperature of all states is equal to that of the dead state, the specific internal energy terms in Equation 11 are eliminated because the specific internal energy of an ideal gas is only a function of temperature. Simplifying Equation 11 with the constant temperature assumption:\n\nPal19 expressed the molar chemical exergy of an ideal gas mixture as follows:\n\nConsidering the process shown in Figure 1, one can observe the minimum work required to obtain the separated product and exhaust gas mixtures is the sum of their exergy values. Note that the exhaust gas mixture has no thermomechanical exergy, as it is at the dead state temperature and pressure. Therefore, in this case, Equation 6 becomes:\n\nEquation 15 is expanded to determine the total exergy (Φ) of the product and exhaust mixtures as follows:\n\nSubstituting Equation 12 and Equation 14 into Equation 16:\n\nThe following expression can be substituted into Equation 17 to obtain terms with similar units:\n\nSubstituting:\n\nEquations 20 through 24 can be utilized to express Equation 19 in terms of product pressure, total volume (V), purity, and recovery:\n\nSubstituting into Equation 19 and simplifying:\n\nThe second-law efficiency of an actual air separation system can be determined via Equation 1 by utilizing the calculated values from Equation 25 as Wrev, provided the final state of the product from the actual process as a gas at the dead state temperature. Expressing Equation 25 in kJ/m3:\n\nEquations 25 and 26 are valid within the following ranges for the purity and recovery:\n\n\nResults\n\nA source code for plotting results for Equation 26 has been made available on Zenodo.21 Figure 2 and 3 show graphical depictions of Equation 26 for the product nitrogen gas at atmospheric pressure and 800 kPa, respectively. Figure 2 shows the condition in which the product gas has no thermomechanical exergy. It can be observed that no work input is required at 79% product purity, regardless of the recovery rate, because it was assumed that the ambient air is 79% nitrogen; therefore, the product gas has neither thermomechanical exergy nor chemical exergy. As shown in Figure 3, the work input is still required for a product purity of 79%, which essentially represents the reversible compression of ambient air. This work input value is constant at a product purity of 79% for any value of recovery and is determined using Equation 12.\n\n\nDiscussion\n\nThe work input for actual air separation systems will always be greater than the value determined by utilizing Equation 26, owing to irreversibility. Cryogenic distillation, membrane separation, and PSA all experience heat loss, friction, and unrestrained gas expansion, among other irreversibilities. Friction exists at all locations where there is relative motion between a fluid and a solid, and all gases exhausted to the atmosphere represent an unrestrained expansion of gas. One of the most notable sources of irreversibility is during compression, as heat rejection from a compressor is usually within 60–90% of the power input.20\n\nTo compare realistic air separation processes to an ideal process, an average PSA system was assumed to provide 99.9% pure nitrogen at 800 kPa within a recovery range of 15–50%. As shown in Figure 4, the minimum required work input for this process was between 1,151–1,198 kJ/m3 (an average of 1,174.5 kJ/m3). It is also assumed that the typical PSA input power range of 0.31–0.63 kWh/kg provided by Syakdani et al.3 applies to these conditions. At 800 kPa, this input power range was equivalent to 10,446–21,228 kJ/m3. Utilizing Equation 1, this represents a second law efficiency of only 5.5–11.2%.\n\n\nConclusions\n\nA theoretical exergy analysis of air separation is presented in this article, indicating the minimum theoretical work input as a function of the product pressure, purity, and process recovery rate. The air separation system was considered a black box, with the input, output, and exhaust gases assumed to be binary mixtures of nitrogen and oxygen at 15°C. Equations 25 and 26 derived from this analysis are only valid for cases where the feed, product, and exhaust mixtures are in the gas phase and at a dead state temperature of 15°C. These equations are still valid for cryogenic distillation, even though the process involves phase changes, assuming that the feed to the system is ambient air and the product and exhaust mixtures are brought back to the gas phase. The following conclusions were drawn from this analysis:\n\n• This analysis may be utilized for direct efficiency (based on the second law of thermodynamics) comparisons between existing processes and future technological innovations in the field of air separation.\n\n• Actual air separation systems have low efficiencies compared to ideal systems; actual PSA systems were estimated to have second law efficiencies of 5.5–11.2%. Therefore, there is great potential for improvements in the current air separation systems.",
"appendix": "Data availability\n\nAll underlying data are available as part of the article and no additional source data are required.\n\n\nReferences\n\nLinde C: Process of Producing Low Temperatures, the Liquefaction of Gases, and the Separation of the Constituents of Gaseous Mixtures. US Patent 727,650, 1903.\n\nIvanova S, Lewis R: Producing nitrogen via pressure swing adsorption. Chem. Eng. Prog. 2012; 108(6): 38–42.\n\nSyakdani A, Bow Y, Rusdianasari, et al.: Analysis of Cooler Performance in Air Supply Feed for Nitrogen Production Process Using Pressure Swing Adsorption (PSA) Method. J. Phys. Conf. Ser. 2019; 1167(1): 012055. Publisher Full Text\n\nTesch S, Morosuk T, Tsatsaronis G: Comparative Evaluation of Cryogenic Air Separation Units from the Exergetic and Economic Points of View. Low-Temperature Technologies. 2019. Publisher Full Text\n\nMarcinek A, Guderian J, Bathen D: Performance determination of high-purity N2-PSA-plants. Adsorption. 2020; 26(7): 1215–1226. Publisher Full Text\n\nCornelissen RL, Hirs GG: Exergy analysis of cryogenic air separation. Energy Convers. Manag. 1998; 39(16–18): 1821–1826. Publisher Full Text\n\nvan der Ham LV , Kjelstrup S: Exergy analysis of two cryogenic air separation processes. Energy. 2010; 35(12): 4731–4739. Publisher Full Text\n\nFu C, Gundersen T: Using exergy analysis to reduce power consumption in air separation units for oxy-combustion processes. Energy. 2012; 44(1): 60–68. Publisher Full Text\n\nTaniguchi M, Asaoka H, Ayuhara T: Energy saving air separation plant based on exergy analysis.2015.\n\nBanerjee R, Narayankhedkar KG, Sukhatme SP: Exergy Analysis of Pressure Swing Adsorption Processes for Air Separation. Chem. Eng. Sci. 1990; 45(2): 467–475. Publisher Full Text\n\nMcLean CR: Energy Efficiency of Gas Separation by Pressure Swing Adsorption. The University of British Columbia; 1996.\n\nKearns DT, Webley PA: Application of an adsorption non-flow exergy function to an exergy analysis of a pressure swing adsorption cycle. Chem. Eng. Sci. 2004; 59(17): 3537–3557. Publisher Full Text\n\nXu J, Agrawal R: Gas Separation Membrane Cascades I. One-Compressor Cascades with Minimal Exergy Losses Due to Mixing. J. Membr. Sci. 1996; 112(2): 115–128. Publisher Full Text\n\nSiefert NS, Litster S: Exergy and Economic Analysis of Advanced IGCC-CCS and IGFC-CCS Power Plants. Appl. Energy. 2013; 107: 315–328. Publisher Full Text\n\nVilardi G, Bassano C, Deiana P, et al.: Exergy and Energy Analysis of Three Biogas Upgrading Processes. Energy Convers. Manag. 2020; 224(15): 113323. Publisher Full Text\n\nMagnanelli E, Wilhelmsen Ø, Johannessen E, et al.: Energy efficient design of membrane processes by use of entropy production minimization. Comput. Chem. Eng. 2018; 117: 105–116. Publisher Full Text\n\nWeber SA, Volta D, Kuck J: Comparison of the Energetic Efficiency of Gas Separation Technologies Using the Physical Optimum by the Example of Oxygen Supply Options. Energies. 2022; 15(5). Publisher Full Text\n\nVaughan WW: Standard Atmosphere. Encycl. Atmos. Sci. 2003; 2107–2113.\n\nPal R: Chemical exergy of ideal and non-ideal gas mixtures and liquid solutions with applications. Int. J. Mech. Eng. Educ. 2019; 47(1): 44–72. Publisher Full Text\n\nCengel YA, Boles MA: Thermodynamics: An Engineering Approach. 6th ed.McGraw-Hill; 2008.\n\nRinker G: grinker4821/Isothermal-Air-Separation-Exergy: Code Release.2024. Publisher Full Text"
}
|
[
{
"id": "289636",
"date": "04 Jul 2024",
"name": "Yousaf Ayub",
"expertise": [
"Reviewer Expertise Biomass waste valorization",
"Sustainability",
"Artificial Intelligence"
],
"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 introduction section is haphazard and there is no proper literature review through which academic validity of the manuscript can be justified. Therefore, improve the academic validity of the manuscript through literature review. What others have done and why are you doing this research? Introduction section: Summarize each paragraph in the last line of paragraph. What is minimum theoretical work? What is the logic behind the assumptions made in mathematical modelling? From where you have taken this definition? Add reference “Exergy describes how much work a reversible system could produce as the contents of the system proceed from a specified state to the dead state, a condition in which the contents are in thermodynamic equilibrium with the environment. Under reversible conditions, the work required to separate a gas mixture is equal to that required for the mixing of its individual components.” Support the Equation 1-5 with proper reference. It seems not reliable, and I am also not sure as a reader how you developed these equations? Similarly, for other equations which are not supported by literature. Add further explanation to the methodology section about your study framework. How do you differentiate between result and discussion section? Both sections seem the same, and the explanation needs further improvement. Conclusion is extremely concise, and it is not clear from current version whether you have achieved your study objectives or not? Study limitations are also missing.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "289640",
"date": "15 Jul 2024",
"name": "Bhalchandra Shingan",
"expertise": [
"Reviewer Expertise Natural Gas Engineering",
"LNG",
"City Gas Distribution",
"Pipeline Engineering",
"Industrail Gases",
"Modelling",
"Simulation & Optimization."
],
"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\nComments for research paper- Minimum work associated with separating nitrogen from air: An exergy analysis.\nMajor Comments\nIn this study, Minimum work associated with separating nitrogen from air: An exergy analysis was presented. The research has significant shortcomings. Notably, the literature review is inadequate. It is recommended to incorporate a more comprehensive background review of previous studies focused on improving the energy efficiency of cryogenic air separation units. Additionally, many references are outdated and do not adhere to the general standards of international publications. The manuscript's overall quality does not meet the standards of the F1000 research. Specific comments are given below [Comment 1] : Abstract: The abstract lacks research gaps which should be stated clearly. The authors may use a single paragraph as abstract to (1) present the significance of the study, let us know the important of the study. (2) present the aim of the study. (3) present the research methodology, and (4) present the major conclusion drawn from the study.\n[Comment 2] : There is no background information on previous studies regarding the energy efficiency of a cryogenic cycle which does not highlight the importance of this research paper. The introduction needs to be more emphasized the research work more with a detailed explanation of the past, present and how it can be controlled in the future. Additionally, the introduction does not have a strong literature review to provide research gaps and should be updated with more recent research papers. Some of the very important parameters are missing details in this paper.\n\n[Comment 3] : The methodology and analysis sections of the paper are inadequately presented. The description of the cryogenic air separation process is missing, and there is a need for a detailed flow diagram of the air separation process.\n[Comment 4]: Equations for Exergy analysis are not provided.\n[Comment 5]: As a reviewer, I have concerns regarding the assumptions made in the mathematical modeling. Specifically, the assumptions that \"gas mixtures will be treated as ideal gases\" that are not valid at higher pressures (800 kPa). Could the authors please provide the rationale behind these assumptions?\n[Comment 6]: The title of the research paper is “Minimum work associated with separating nitrogen from air: An exergy analysis. “However, we can’t find any results of exergy analysis? Exergy destruction?\n[Comment 7]: The Figure 2 & figure 3 are not explained in detail.\n[Comment 8]: The results presented in the article lack significance and fail to showcase any noteworthy findings.\n[Comment 9]: Authors are advised to add few different sections that includes details of symbols, dimensionless parameter, Greek symbols, subscripts and abbreviations in the nomenclature section. To make paper more readable also add full form of any abbreviation first time (like CNT)\n[Comment 10]: Authors are also advised to make pointwise conclusions, addressing research gap.\nIn my personal opinion, authors have huge potential to update this article as per recommendations and can improve the quality of their work. As in its current form, the manuscript requires substantial revisions to address the highlighted issues in insight, novelty, methodology, analysis, results, presentation standards, and language. A thorough review and revision process is recommended to bring the research article up to acceptable standards for indexing.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? 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": "293248",
"date": "10 Sep 2024",
"name": "Fulin Kong",
"expertise": [
"Reviewer Expertise my research field is mainly in the direction of energy savings in air separation processes by cryogenic distillation",
"energy system energy conservation",
"which includes energy storage (heat and cold storage",
"liquid air energy storage)",
"renewable energy sources (solar energy and wind energy)",
"power grids",
"power generation",
"gas transmission and so on. Here is my intruduction: https://scholar.google.com.hk/scholar?start=10&q=fulin+kong&hl=zh-CN&as_sdt=0",
"5"
],
"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 study presents the minimum theoretical power consumption for separating nitrogen from air. This work itself helps to understand the power consumption levels of existing nitrogen production technologies. 1. Different oxygen/nitrogen technologies do not have the same minimum energy consumption. This is because the technology itself cannot be separated from the equipment and process. Therefore, the calculation of the minimum energy consumption of oxygen/nitrogen technologies does not make sense, leaving aside the equipment and process. 2, I do not agree with the simplification in this study that air is composed mainly of oxygen, nitrogen, and argon, accounting for about 21%, 78%, and 0.9%, respectively. It is difficult to assess the reasonableness of considering only oxygen and nitrogen. Also, I have a bit of writing advice. Variables in formulas should be italicized, which is ignored in this paper.\nThis article provided sufficient details of methods, and the source data underlying the results are available to ensure full reproducibility. So I thinks the conclusions are adequately supported by the results. (However, the method is not right.)\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?\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/13-158
|
https://f1000research.com/articles/12-55/v1
|
13 Jan 23
|
{
"type": "Research Article",
"title": "Antioxidant of the putat air (barringtonia racemosa) as a herbal remedy to improve sperm quality due to cigarette smoke in rats",
"authors": [
"Dahril Dahril",
"San Winata Badiri",
"Dasrul Dasrul",
"Vivi Keumala Mutiawati",
"Said Alfin Khalilullah",
"San Winata Badiri",
"Dasrul Dasrul",
"Vivi Keumala Mutiawati"
],
"abstract": "Background: The objective of this study is to analyse the antioxidant in putat air (barringtonia racemosa) as an herbal to improve sperm quality due to cigarette smoke. Methods: An experimental study was conducted at animal laboratory, Faculty Veteriner University of Syiah Kuala, Banda Aceh, Indonesia. A total of 30 male rats (Rattus norvegicus) were divided into 5 treatment groups. Group 1 as a negative control (N) were not exposed to cigarette smoke. Group 2 as a positive control (P) were exposed to cigarette smoke. Group 3 as treatment 1 (P1) were exposed to cigarette smoke and 100 mg/kg BW/day of the barringtonia racemosa seed extract. Group 4 as treatment 2 (P2) were exposed to cigarette smoke and given 150mg/kg BW/day of the barringtonia racemosa seed extract. Group 5 as treatment 3 (P3) were exposed to cigarette smoke and given 200 mg/kg BW/day of the barringtonia racemosa seed extract. The cigarette smoke exposure was carried out in a smoking chamber for a total of 1 hour/rat, and the barringtonia racemosa seed extract is given orally once a day for 30 days. Results: The results of this study were analyzed by one-way ANOVA showed significant differences in the quality of the sperm group that received cigarette smoke exposure (p <0.05) compared to the administration of the barringtonia racemosa. Improved sperm quality was seen better with the administration of barringtonia racemosa 150 kg/kg BW/day compared with 100 and 200 kg. Conclusions: Antioxidants from barringtonia racemosa can improve sperm quality due to cigarette smoke.",
"keywords": [
"Barringtonia racemosa",
"seed extract",
"cigarette smoke",
"sperm quality"
],
"content": "Introduction\n\nMale infertility is a problem that shows an increase the incidence in last decade. Lifestyle factors such as smoking have shown to be responsible for reducing infertility.1–3 Data from World Health Organization (WHO) in 2018, more than 2.9 billion of the world's population smoked and 80% lived in developing countries.4–6 While the number of smokers in Indonesia reached 72 million population in 2015 and is predicted to increase to 83 million in 2020 with the proportion of men at 75.2% and the highest age group is 40-54 years.7 Around 100 toxic compounds such as tar, nicotine, nitrosamine, carbon monoxide, PAH compound (Polynuclear Aromatic Hydrogen), phenol, carbonyl, chlorindioxin, furan, and its smoke contains very high free radicals (ROS). These chemicals have the potential to damage the function of the testes and germ cells.8\n\nAntioxidants have recently gained popularity due to their lower toxicity as compared to synthetic agents, also can naturally balance the scavenging system, and reduce intracellular ROS which will prevent decreased sperm quality due to substances from cigarette smoke.9 Antioxidant activity is essential as a research tool for evaluating the scientific basis for known traditional herbal treatments that claim to have antioxidant effects.\n\nBarringtonia racemose, locally known as putat air in Indonesia, is a species of mangrove plant that grows in rice fields, originally originating from East Africa and Madagascar to Sri Lanka, India, and continuing into the Southeast Asian region, East Asia, northern Australia and the Micronesia and Polynesia Islands.10 As traditional remedy, this fruit have been used in the treatment of abscess, cough, asthma and diarrhea.11 Several studies have succeeded in isolating some antioxidants from the leaves, kernels, fruit, roots, and stems of these plants such as polyphenols, flavonoids, and triterpenoids.10,12 The capacity of polyphenols, flavonoids, and triterpenoids as antioxidants is stronger than vitamins C and E.7\n\nDespite a few isolated studies on certain parts of the plants, information on the antioxidant activity of the barringtonia racemose is still limited. The antioxidant properties of the plant extract may have given information on the mechanism relating to the plant's bioactive. This study evaluated the effect of the antioxidant in barringtonia racemosa as an herbal to improving sperm quality due to cigarette smoke.\n\n\nMethods\n\nThis study was registered to the Medical and Health Research Ethics Committee (362/EA/FK-RSUDZA/2019) and approved by the appropriate institutes’ ethics committee by Komite etik penelitian kesehatan Faculty of medicine, Universitas Syiah Kuala, Dr. Zainoel Abidin General Hospital. We collect data from 30 male rats (Rattus norvegicus) and were divided into five treatment groups. The period of study was 30 days. The interventions of cigarette smoke exposure were carried out in a smoking chamber for a total of one hour/rat for 30 days.\n\nAll the chemicals and reagents used were of analytic grade and were obtained from the laboratory our institution. Baringtonia racemosa is obtained from rice fields in Aceh, Indonesia and then the seed extraction process is carried out in a laboratory. The male rats (Rattus norvegicus) in good health were also obtained from the same laboratory.\n\nThe tools used were rat cages, rat drinking places, smoking rooms, gastric sonde, gloves, small surgical instruments, knives, filter paper, incubators, vacuum rotary evaporators, water baths. Digital scales, glass objects, hot plates, cover glass, rotary microtomes, light microscopes, and cigarettes were also used.\n\nMale adult rats (Rattus norvegicus) strain of Wistar were healthy and aged 16-20 weeks from the animal laboratory of veterinary faculty with a bodyweight of 180-200 grams. All animals (n=30) were housed in rat cages and were fed on standard laboratory diet daily food and water ad libitum. Rats were kept on laboratory conditions, with standard temperature (25±2)°C, relative humidity of (40%–60%) and 12h/12h light and dark cycle.\n\nThe experimental rats were randomly divided into five groups, with 6 rats in each group. Group one as a negative control (N) in which the rats were not exposed to cigarette smoke. Group two-five received cigarette smoke exposure where group two as a positive control (P) and three-five were treated with barringtonia seed extract at doses of 100, 150, and 200 mg/kg BW/day orally.\n\nIn this study federer’s formula was used to calculate the sample size and the minumum sample is five each group. At the end of the experiment, the animals were sacrificed with cervical dislocation; both testicular regions along with the epididymis were dissected out to collect the sperm for further analysis. We carry out this procedure under animal anesthesia to reduce pain, suffering and distress. No unexpected adverse events were found during the experiment.\n\nThe quality of sperm were analyzed using the WHO 2010 method which included the amount, motility, viability and morphology.\n\nSpermatozoa from the rat epididymis were aspirated using an erythrocyte pipette. Then, with the same pipette, 0.9% NaCl was sucked up to a limit of 101 so that 200 times the dilution results were obtained. Then, the mixture was discarded three drops and dropped into the Neubauer counting chamber. Observe and count the number of sperm under a light microscope with 400 times magnification using the formula N x 107 sperm/ml.\n\nAll data were analysed using the IBM SPSS 23.00 (IBM Corp., Chicago) and by using one-way analysis of variance (ANOVA). Shapiro–Wilk tests were used to analyze the normality of data. The data were expressed as mean ± standard deviation (mean±SD). Duncan test was applied for the comparison between the control group and each treated group individually. P<0.05 was considered statistically different.\n\n\nResults\n\nThe phytochemical test results of the barringtonia racemosa can be seen in Table 1.\n\nIn our experiment, it was found that the steroid compounds, terpenoid, saponins,flavonoids, phenolics, and tannins in barringtonia racemosa seed extract but not found alkaloids.\n\nFrom results of sperm analysis after barringtonia racemosa seed extract administration for 30 days showed that sperm quality improved (Table 2).\n\n+ (negative control) normal rats without exposure to cigarette\n\n* (positive control) normal rats exposed to cigarette smoke\n\n** normal rats exposed to cigarette smoke + 100 mg/kgBW barringtonia racemosa seed extract\n\n# normal rats exposed to cigarette smoke + 150 mg/kgBW barringtonia racemosa seed extract\n\n## normal rats exposed to cigarette smoke + 200 mg/kgBW barringtonia racemosa seed extract\n\nTable 2 shows that sperm quality improved after administration of barringtonia racemosa seed extract in the treatment group (P1-3) compared with the positive control group (P) with statistical analysis (ANOVA) showing a significant difference (p <0.05). Further analysis with the Duncan test showed that administration of barringtonia racemosa seed extract at a dose of 150 mg/kgBW/day (P2) had a statistically significant improvement in sperm quality (P <0.05) compared with a dose of 100 mg/kg/day (P1) and 200 mg/kgBW/day (P3).\n\n\nDiscussion\n\nThis study shows a decrease in sperm quality in animal models due to exposure to cigarette smoke containing nicotine, tar, nitrosamine, carbon monoxide, phenol, carbonyl, chlorindioxin, and PAH compounds (Polynuclear Aromatic Hydrogen).2–5\n\nNicotine is a toxic alkaloid found in tobacco smoke. Nicotine enters the brain quickly in about ten seconds. Nicotine can cross the brain barrier and circulate in all brain cells, then decrease rapidly, and circulate throughout the body within 15-20 minutes at the time of last exposure.13 Nicotine can stimulate the adrenal medulla to release catecholamines which can affect the central nervous system, thereby disrupting the mechanism of hormonal synthesis between the hypothalamus, anterior pituitary, and Leydig cells. Thus it will disrupt the process of spermatogenesis.14 Nicotine also interferes with cellular respiration processes in the mitochondria which leads to increased formation of reactive oxygen species (ROS) and induces the formation of oxidative stress by increasing pro-oxidants and reducing protection from antioxidants.13 Increased free radicals in the circulation will damage the spermatogenic cell membrane, DNA, spermatogenic cell growth, and disrupt the transport of important ions in proliferation thereby increasing sperm apoptosis and inhibiting spermatogenesis.15\n\nOne study reported that mice treated with cigarette smoke experienced DNA (Deoxiribo Nuclear Acid) fragmentation, decreased motility of the sperm, and reduced fertility rates.8 In previous studies conducted on animal experiments, it is known that cigarette smoke affects spermatogenesis in the seminiferous tubules and affects testosterone levels.8,9\n\nIn this study, we found that the extract of barringtonia racemosa seed significantly improve sperm quality due to cigarette smoke (p < 0.05). this antioxidant can effectively protect body cells from oxidative stress including neutralizing free radicals caused by cigarette smoke and reducing sperm cell damage caused by ROS thereby avoiding a decrease in sperm quality.16 The barringtonia racemosa seed extract contains polyphenol compounds such as phenols, phenolic acids, flavonoids, and tannins that have potential as antioxidants. Polyphenol is an antioxidant carotenoid pigment that can bind a single oxidant ten times higher than vitamin C and one hundred times higher compared to α-tocopherol (vitamin E) and carotenoids.17,18 Flavonoids are a group of polyphenol compounds as exogenous antioxidants that are useful in preventing cell damage due to oxidative stress, there are two mechanisms of flavonoids as antioxidants, which donate hydrogen ions to neutralize the toxic effects of free radicals and increase the expression of endogenous antioxidant genes through nuclear factor erythroid 2 related to factor 2 (Nrf2), increases genes that play a role in the synthesis of endogenous antioxidant enzymes.19 The strength of flavonoid antioxidant activity depends on the number and position of the -OH groups present in the molecule.20 These phenolic antioxidants block the oxidation of lipids and other molecules by donating hydrogen atoms to radical compounds to form phenoxyl radical intermediates. The phenoxyl radical intermediate compounds are relatively stable so they are no longer able to initiate further radical reactions. High biological activity in these phenolic compounds lies in the position and number of the -OH group.21\n\nBarringtonia racemosa seed extract also contains alkaloids, saponins, and triterpenoids which have activity in reducing MDA levels. Alkaloid compounds can act as scavengers of free radicals and prevent lipid peroxidation in microsomal hepatic preparation.22,23 Triterpenoids can potentially induce Nrf2 gene expression and activate the ARE (Antioxidant Response Element) pathway in neuronal cells. Nrf2/ARE will regulate more than 200 genes including antioxidant genes.24 Saponin compounds can act as antioxidants and have the ability to capture free radicals. The ability of saponin compounds can reduce oxidative stress in alloxan-induced mice.21\n\nThe highest sperm quality improvement was achieved at the concentration of barringtonia racemosa seed extract 150 mg/kg BW. This is caused by the difficulty of absorption of barringtonia racemosa seed extract with a higher concentration, so that the active ingredient of barringtonia racemosa seed extract is slow. On the other hand, decreased sperm quality in the treatment group of 200 mg/kg/day can also be caused by an increase in the active ingredient of barringtonia racemosa extract in the body. The high concentrations of antioxidant activity also will turn into prooxidants which can damage cells. When the dose of antioxidant and prooxidant is not balanced or high levels of oxidants while the low antioxidant, then the body will form prooxidant compounds to balance the levels with antioxidants.25 This will increase the production of free radical cells. Prooxidant activity can reduce the level of antioxidant enzymes in the body such as glutathione peroxidase and catalase.26 The imbalance between antioxidant enzymes and prooxidants in the body will damage spermatogenic cells, which will cause the formation of sperm to decrease.27\n\nOur study has several limitations due to the small sample size. However, the data's reliability can be maintained to avoid bias. Future studies with high-quality data is needed to evaluate this finding.\n\nIn conclusion, Antioxidants from barringtonia racemosa can improve sperm quality due to cigarette smoke. The Barringtonia racemosa extract at a dose of 150 mg/kgBW/day is better than the dose of 100 mg/BW/day and 200 mg/BW/day. This indicates that the optimum dose is 150 mg/BW/day.",
"appendix": "Data availability\n\nFigshare. Antioxidant of the Putat Air (Barringtonia racemosa) as a Herbal to Improve Sperm Quality due to Cigarette Smoke in rats. https://doi.org/10.6084/m9.figshare.21610341.v1. 28\n\nFigshare. ARRIVE guidelines checklist. DOI: https://doi.org/10.6084/m9.figshare.21746648.v1. 29\n\n\nReferences\n\nGibson G: Respiratory Medicine. London:W. B. Saunders; 1995; Volume I. : 533–535.\n\nColagar A, Jorsaraee G, Marzony E: Cigarette smoking and the risk of male infertility. Biol Sci. 2007; 1.\n\nNg M, Freeman M: Smoking prevalence and cigarette consumption in 187 countries. JAMA. 2014; 311(18): 183–192. PubMed Abstract | Publisher Full Text\n\nJing-Bo D, Zhao-Xia W, Zhong-Dong Q: The hazardous effects of tobacco smoking on male fertility. Asian J. Androl. 2015; 17(9): 954. Publisher Full Text\n\nSayuti K, Yenrina R: Antioksidan Alami dan Sintetik. I. Padang:Andalas University Press;2015.\n\nSandhiutami NMD, Desmiaty Y, Anbar A: Efek Antioksidan Ekstrak Etanol Biji Pepaya (Carica papaya L.) terhadap Aktivitas Enzim Superoksida Dismutase dan Kadar Malondialdehid pada Mencit Stress Oksidatif dengan Perenangan Antioxidant Effect of Ethanol Extract from Papaya Kernel Carica papay. J. Ilmu. Kefarmasian Indones. 2016; 14(1): 23–26.\n\nSuarsana IN, Wresdiyati T, Suprayogi A: Respon Stres Oksidatif dan Pemberian Isoflavon terhadap Aktivitas Enzim Superoksida Dismutase dan Peroksidasi Lipid pada Hati Tikus. JITV. 2013; 18(2): 146–152.\n\nChu DSSD: Germ Cell Development in C. elegans.2013. Tersedia pada. Publisher Full Text\n\nMeeker J, Benedict M: Infertility, pregnancy loss and adverse birth outcomes in relation to maternal secondhand tobacco smoke exposure. Curr Womens Heal Rev. 2013; 9(41): 41–49. Publisher Full Text\n\nAditama TY: Penyakit Akibat Merokok, Masalah Merokok dan Penanggulangannya. Penerbit I. Jakarta.2001.\n\nOng HC: Kuala Lumpur, Malaysia: Utusan Publications and Distributors. Tumbuhan Liar: Khasiat Ubatan and Kegunaan Lain.2004; pp. 160–163.\n\nRamlau-Hansen C, Thulstrup A, Aggerholm AJA: Is smoking a risk factor for decreased semen quality? A cross-sectional analysis. Hum. Reprod. 2007; 22(1): 188–196. PubMed Abstract | Publisher Full Text\n\nCondorelli R, La Vignera S, Giacone F, et al.: In vitro effects of nicotine on sperm motility and bio functional flow cytometry sperm parameters. Int. J. Immunopathol. Pharmacol. 2013; 26(7): 739–746. PubMed Abstract | Publisher Full Text\n\nTurek P:Male Infertility. Smith’s General Urology. San Fransisco:McGraw Hill Medical Inc; 17th ed.2008; 684–716.\n\nHaque O, Vitale J, Agarwal A d PS: The effect of smoking on male infertility. In In: Male Infertility. New York:Springer;2014; 19–30.\n\nMachado D, Cunha M, Neis V, et al.: Antidepressantlike effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L. Food Chem. 2013; 136(9): 999–1005. PubMed Abstract | Publisher Full Text\n\nSutanto EB, et al.: The effect of vitamin C and E combination on sperm quality and cement 8-OHdG level of smoke exposed rats. World Nutrition Journal. 2017; 1(1): 28–33. Publisher Full Text\n\nTurek P:Male Infertility. Smith’s General Urology. San Fransisco:McGraw Hill Medical Inc; 17th ed.2008; 684–716.\n\nWayan IS, Made IJ: Ekstrak Air Daun Ubi Jalar Ungu Memperbaiki Profil Lipid dan Meningkatkan Kadar SOD Darah Tikus yang Diberi Makanan Tinggi Kolesterol. Medicina. 2012; 43(2): 67–70.\n\nAmic D, et al.: Structure-Radical Scavenging Activity Relationships of Flavonoids. Croat. Chem. Acta. 2002; 6(1): 55–61.\n\nNzaramba MN: Relationships Among Antioxidants, Phenolics, and Specific Gravity in Potato Cultivars, and Evaluation of Wild Potato Species for Antioxidants, Glycoalkaloids, and Anti-Cancer Activity on Human Prostate and Colon Cancer Cells In vitro. Disertasi. August 2014; 1(2): 115. Texas A&M University.\n\nDinara JM, et al.: Antioxidant Properties of β-Carboline Alkaloids are Related to Their Antimutagenic and Antigenotoxic Activities. Mutagenesis. 2007; 22(4): 293–302. Publisher Full Text\n\nTse SY, Mak IT, Dickens BF: Antioxidative properties of harmane and beta-carboline alkaloids. Biochem. Pharmacol. 1991;15; 42(3): 459–464. PubMed Abstract | Publisher Full Text\n\nPhillips DVS: DNA and protein adducts in human tissues resulting from exposure to tobacco smoke. Int. J. Cancer. 2012; 131(2): 2733–2753. PubMed Abstract | Publisher Full Text\n\nSuryani N, Endang T, Aulanni'am: Pengaruh Ekstrak Metanol Biji Mahoni terhadap Peningkatan Kadar Insulin, Penurunan Ekspresi TNF-α dan Perbaikan Jaringan Pankreas Tikus Diabetes. Jurnal Kedokteran Brawijaya. 2013; 27(3): 137–145. Publisher Full Text\n\nDurgo K, Vukovi L, Rusak G, et al.: Effect of Flavonoids on Glutathione Level, LipidPeroxidation and Cytochrome P450 CYP1A1 Expression in Human Laryngeal Carcinoma Cell Lines. Food Technol. Biotechnol. 2007; 45(1): 69–79.\n\nAgarwal A, Prabakaran S: Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology. Indian J. Exp. Biol. 2005; 43(9).\n\nDahril, Badiri SW, Dasrul D, et al.:Antioxidant of the Putat Air (Barringtonia racemosa) as a Herbal to Improve Sperm Quality due to Cigarette Smoke in rats. Dataset. figshare. 2022. Publisher Full Text\n\nDahril: author checklist ARRIVE guideline. figshare. Presentation.2022. Publisher Full Text"
}
|
[
{
"id": "171633",
"date": "23 May 2023",
"name": "Oghenerobor B. Akpor",
"expertise": [
"Reviewer Expertise Plant growth promotion",
"bioactive properties of plants",
"microbial metabolites"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nBackground: What is indicated in the background more of an aim/objective. There is no indication of background at all.\nMethods Tools: The authors do not need to mention the materials used. They should naturally reflect as the procedures are explained\nSample collection: Show how the Federer's formula was applied to arrive at five animals per grouping\nPhytochemical: Qualitative screening alone is not adequate for the study. It would have been more ideal to carry out quantitative screening\nGeneral comments/observation Based on the title of the paper, the work was aimed at assessing the antioxidant and sperm quality improvement potential of Barrintonia racemosa. Based on the results of the study, there is no indication of antioxidant but just qualitative determination of phytochemical components. There was no study on antioxidant properties/potential.\nBesides, the data on sperm quality are not rich enough to justify a possible improvement in sperm quality. The authors will need to include histomorphological data. Data on testosterone profile and Malondialdehyde (MDA), which is a vital indicator of oxidative stress is also vital. In addition, data on luteinizing hormone (LH) levels, which in important in sexual development and functioning should be provided.\nI will not recommend indexing of the paper in the present form. The data generated is extremely too scant to make the claim.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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": "10127",
"date": "16 Nov 2023",
"name": "Dahril Dahril",
"role": "Author Response",
"response": "Dear Oghenerobor B. Akpor. Thank you for your reviewers our manuscript. We are very grateful for your input for the improvement of our manuscript. but related to that, we need to convey a number of things that Barringtonia racemose, locally known as putat air in Indonesia, is an anti-oxidant, as we have stated in the introduction. Besides that, additional examinations as you suggest such as histomorphological data, testosterone level, LH level and others are very informative data and can provide more information not only about sperm quality but also more complete sexual quality. We really hope that this preliminary study can continue with evaluation of more complex variables such as additional data as you mentioned above."
}
]
},
{
"id": "183392",
"date": "16 Aug 2023",
"name": "Talukdar Dibyajyoti",
"expertise": [
"Reviewer Expertise Animal reproduction",
"Gyneacology",
"Obstetrics",
"Assisted Reproduction",
"Andrology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nBackground of the study is not clear. Please rewrite.\n\nSperm analysis methodology needs to be rewritten with proper references.\n\nPhytochemical: quantitative screening may be more appropriate.\n\nThe barringtonia racemosa; name should be italic in the text.\n\nSome of sentences should be rephrase in the text.\n\nIn key word, please add the word rat\n\nGeneral comments: The aim of the study is to assess the antioxidant property of barringtonia racemosa which may be used as a herbal remedy to improve sperm quality due to cigarette smoke in rats. The present result of qualitative determination phytochemical compound of barringtonia racemosa does not claim the antioxidant property of barringtonia racemosa; quantitative screening need to be incorporated in the findings. The sperm analysis parameters i.e. sperm motility, viability, concentration and sperm abnormality are not rich enough to claim the possible improvement of sperm quality due to cigarette smoke in rats. The authors need to be include the plasma membrane integrity, acrosomal integrity, mitochondrial membrane integrity, DNA fragmentation of sperm cells, testosterone level, MDA level and if possible the sexual characteristics too.\nFinally, I will not recommend the paper in the present form. The article needs to be modified and if possible the above mentioned parameters need to be incorporate.\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? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "10239",
"date": "16 Nov 2023",
"name": "Dahril Dahril",
"role": "Author Response",
"response": "Thank you reviewer for your input. According to your input, we have made corrections to our manuscript. Regarding your suggestion to add plasma membrane integrity, acrosomal integrity, mitochondrial membrane integrity, DNA fragmentation of sperm cells, testosterone level and MDA level, we hope that we can continue this in our next study."
}
]
}
] | 1
|
https://f1000research.com/articles/12-55
|
https://f1000research.com/articles/12-964/v1
|
10 Aug 23
|
{
"type": "Systematic Review",
"title": "Monkeypox and oral lesions associated with its occurrence: a systematic review and meta-analysis",
"authors": [
"Hiroj Bagde",
"Ashwini Dhopte",
"Ferdous Bukhary",
"Naif Momenah",
"Fatema Akhter",
"Okba Mahmoud",
"Krishna Prasad Shetty",
"Maher AL Shayeb",
"Huda Abutayyem",
"Mohammad Khursheed Alam",
"Ashwini Dhopte",
"Ferdous Bukhary",
"Naif Momenah",
"Fatema Akhter",
"Okba Mahmoud",
"Krishna Prasad Shetty",
"Maher AL Shayeb",
"Huda Abutayyem",
"Mohammad Khursheed Alam"
],
"abstract": "Background: A zoonotic, double-stranded DNA virus belonging to the genus Orthopoxvirus, the monkeypox virus is most common in tropical regions of Central and West Africa. The frequency of monkeypox cases, however, has sharply climbed globally since May 2022. Objectives: To establish the threat of monkeypox in terms of the oral lesions caused in sufferers. Materials and methods: After a thorough study of the literature identified in the PubMed, Web of Science, and Cochrane library databases using the PRISMA framework, 103 papers were found. Using inclusion and exclusion criteria, we chose research that was relevant for our review before shortlisting 14 papers that conformed to the review's guidelines. Results: In the 14 selected studies, it was found that oral lesions were among the first clinical signs of a monkeypox affliction, with ulcers on the dorsal surface of tongue lips being the most common areas affected. Conclusion: The rarely observed oral lesions of monkeypox infection may help in the diagnosis and management of this condition. It is critical to keep in mind that recognising and detecting oral lesions in monkeypox patients opens the door to more research and efficient patient management.",
"keywords": [
"Monkeypox",
"Oral lesions",
"Outbreak",
"Systematic review",
"Zoonotic virus"
],
"content": "Introduction\n\nThe monkeypox virus is an uncommon zoonotic disease that causes monkeypox. Both the smallpox and monkeypox viruses are members of the Orthopoxvirus genus in the Poxviridae family. In the Democratic Republic of the Congo, the first case of monkeypox on a human was documented in 1970.1 Since that time, monkeypox has spread over western and central Africa. Up until recently, 47 non-endemic nations in Europe, North and South America, Asia, North Africa, and Australia had reported cases of the disease. More than 4,100 confirmed cases had been reported as of 2022, the count increasing by the minute. Notably, 87% of occurrences have happened in nations in Europe.2 It is thought that the termination of smallpox vaccination, which offered some cross-protection against monkeypox but was not the primary cause of the new outbreak, led to an increase in human-to-human transmission. Generally speaking, human-to-human transmission happens when contaminated objects including linens, bedding, electronics, and clothing come into direct physical contact with an infected person's ulcerated skin or mucosa, respiratory droplets, or both. Through the placenta, pregnant women can spread the virus to unborn children.3 Monkeypox virus airborne transmission is still a contentious topic. Even if it does, it could not be the primary method of transmission. The incubation period for monkeypox infection lasts for 7–14 days or 5–21 days and is not contagious. Patients do not have any symptoms during this time.4\n\nTable 1 represents the clinical characteristics of monkeypox as generally observed in sufferers. Notably, lesions in patients with monkeypox in non-endemic locations are more confined and have a different distribution of rashes, whereas symptoms in patients with monkeypox in endemic regions are more severe and result in a certain proportion of fatalities. There have been no reports of patient deaths from non-endemic regions up to this point.5\n\nThe beginning phase of monkeypox includes a fever, chills, headache, backache, myalgia, asthenia, and lymphadenopathy. Patients that are infected may be contagious during the prodromal stage. It's interesting to note that the fundamental distinction between the symptoms of monkeypox and smallpox is that smallpox does not result in lymphadenopathy but monkeypox does. Submandibular, cervical, axillary, and inguinal lymph nodes may be bilaterally or unilaterally affected in monkeypox.6 Lesions may form in the mouth, oropharynx, or throat after the prodrome before spreading to the skin. The face and extremities, such as the palms of the hands and soles of the feet, are typically where the skin rash is more intense. The lesions develop in stages, going from macule to papule to vesicle to pustule to crust. Until all lesions have crusted over, patients are deemed contagious. The sores are frequently characterised as hurting initially, then becoming irritating. After scabs have peeled off, scars with hyper/hypopigmentation may develop. Usually, the disease lasts 2-4 weeks. Patients in the latest outbreak's non-endemic areas present with unusual symptoms that are very dissimilar from those in western and central Africa. Genital, perianal, and perioral/oral rash, fever, lymphadenopathy, and swallowing pain are a few of these. Lesions on the oral mucosa and vaginal region may first emerge before or without spreading to other body areas, pointing to sexual contact as the likely mode of transmission.7 Many individuals first had pustules before becoming feverish. Patients with a few small, isolated skin lesions sometimes show no signs of pain. It's interesting to note that the same people can have lesions in various stages. Pain, haemorrhage, proctitis, and tenesmus can all result from anus and rectum lesions.\n\nPatients in the endemic area have never before reported having these symptoms. Patients in the current outbreak locations generally experience milder symptoms than those in the endemic zone. There haven't been many documented hospitalizations, and the two most common causes were pain management and subsequent infection care.8 Prior to skin rashes, monkeypox might present with oral and oropharyngeal lesions. It is stated that mouth sores, along with fever and enlarged lymph nodes, are common symptoms in monkeypox patients. Notably, the CDC stated that lesions in the mouth and on the tongue were seen in 70% of people. These findings imply that the virus can be carried in the saliva and spread via oral-skin and/or oral-anogenital contact. Therefore, it's crucial for dentists and other dental professionals to be aware of and able to identify monkeypox oral lesions. Starting with macule, papule, vesicle, and pustule, the progression of oral lesions should resemble that of skin lesions.9\n\nUlceration with pseudomembrane occurs after the roofs of the vesicle or pustule break off. A male patient who was a returning tourist from Nigeria experienced right cervical lymphadenopathy, multiple 2-4-mm pustules, and central umbilication of the skin, particularly on the face, neck, and hands. The oral lesions were described as a single intact pustule on the lower labial mucosa and a few round 2-3 mm erosions on the mucosa, indicating that the original vesicles or pustules have already broken off.9\n\nHence, by the means of this systematic review and subsequent meta-analysis, we aimed to establish the threat of monkeypox in terms of the severity of oral lesions that are caused due to it.\n\n\nMethods\n\nThis systematic review was performed as per the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) strategy and rules from the Cochrane group and the book Orderly reviews in Health care: Meta examination.10 We also utilised the PICO strategy to identify and evaluate the relationship between monkeypox and oral lesions. The population of interest included individuals with confirmed cases of monkeypox. The intervention of interest was the presence of monkeypox, while the comparison group consisted of individuals without monkeypox. The outcome of interest was the occurrence of oral lesions associated with monkeypox.\n\nThis systematic review aimed to analyse, by the means of selecting studies, to review the correlation between the incidence of monkeypox and the oral lesions occurring in patients because of it at various stages of the disease.\n\nThere were a total of 103 documents discovered after extensive search on the online journals and 54 of the papers were selected initially. Following that, 22 similar/duplicate articles were eliminated, which resultantly made 32 separate papers available at first. The abstracts and titles of submissions were then reviewed, and a further 18 papers were eliminated. Finally, 14 documents that met the inclusion and exclusion criteria were chosen, which included study articles and randomised/non-randomised control trials (Figure 1).\n\nFor this systematic review, we employed the PICOS (Participants, Interventions, Comparison, Outcome, Study design) framework for assessment of studies fit for our investigation.\n\nThe following were excluded from the scope of our systematic review: incomplete data, individuals in whom antimicrobial treatment had begun only recently, seminar presentations, scholarly articles, placebo controlled studies, and opinion articles.\n\nSince the literature available on this topic is quite scant in volume, we did not limit our search in terms of the time period when the studies were published i.e. we took into account all the papers that were published with context to our topic (where the number of papers itself was found to be quite sparse in number).\n\nPlacebo-controlled studies were not included in the analysis. Also excluded were literature reviews and cases published in languages other than English.\n\nUsing relevant keywords, reference searches, and citation searches, the databases PubMed-MEDLINE, Web of Science, Cochrane, and Scopus were all searched. “Monkeypox,” “Oral lesions,” “Zoonotic viruses” and “Oral manifestations” were the search terms used to access the database.\n\nTwo independent reviewers located the relevant papers by using the right keywords in various databases and online search tools. The chosen articles were compared, and a third reviewer was brought in if there was a dispute.\n\nAfter choosing the articles, the same two reviewers independently extracted the following data: author, year of publication, country, kind of publication, study topic, population demographics (n, age), outcome measure(s), relevant result(s), and conclusion (s). The data was compared and any differences were discussed with the third reviewer. The evaluation of risk analysis was also performed, the detail of which have been furnished in Figure 2.\n\nThe AMSTAR-2 protocol11 was employed for the assessment of the risk of bias in our selected studies. As a critical evaluation tool for systematic reviews, AMSTAR 2 joins a number of other instruments that have been published for this purpose. It consists of a 16-point checklist, as shown in Table 2 below. The development of the original AMSTAR tool was based on two instruments that have received a lot of attention. Two instruments that have been released are exact copies of the original AMSTAR. The domains listed in the Cochrane risk of bias instruments for systematic reviews are identified by the AMSTAR 2 risk of bias items. These represent an agreement that was reached after input from more than 30 methodology specialists in each case.\n\n\nResults\n\nTable 3 as given below includes the findings of the systematic review as well as information on the 14 studies that were selected for the review. The results of the meta-analysis (conducted using RevMan 5 software) are displayed in Figures 3, 4 and 5 below in the form of a forest plot that reflects and ranks all the studies included in this systematic review. After data on the sample size, variables analysed, and various components of the investigations selected for our systematic review were entered into the Revman 5 programme, a forest plot illustrating the risk ratio, odds ratio, and risk difference was obtained as part of the meta-analysis for our study.\n\nFigures 3, 4 and 5 represent the forest plots obtained after meta-analysis of the incidence of the oral lesions in patients of monkeypox that were a part of the studies that were selected for our systematic review.\n\n\nDiscussion\n\nMany diseases, including chickenpox, measles, bacterial skin infections, scabies, syphilis, and medication-induced allergies, share characteristics of the mucocutaneous lesions with monkeypox.26 Based solely on the clinical appearance, it might be challenging to discern between these disorders in some cases. When comparing monkeypox to chickenpox or smallpox, lymphadenopathy during the prodromal stage might be used to make the distinction. Healthcare professionals should gather a sample if monkeypox is suspected so that it can be further examined using polymerase chain reaction (PCR), a method that has strong specificity and sensitivity for finding the monkeypox virus.27 The fluid from vesicles, pustules, or dry crusts should be collected, preserved in a dry, sterile tube without viral transport media, and kept cold. An optional method for making the diagnosis is a biopsy.28\n\nAs evident by the finding mentioned in Table 3 depicting the selected studies, oral lesions are primarily present at the start of the monkeypox affliction. For example, in the study by Tarín-Vicent et al,22 lesions in the oral and perioral area were present in 78 people (or 43%). In all the studies, oral lesions were present in some form or the other (as ulcers or vesicular rash most commonly around the tongue or lower lip area) during the prodromal stage of monkeypox which was accompanies by symptoms such as fever, myalgia, and general malaise and, in some cases, a pruritic rash. The case reviews by Iamaroon et al14 and Samaranayake et al20 also provide with literature evidence of oral lesions in monkeypox patients. One of the documented cases29 in these reviews mention of a male patient who was a returning tourist from Nigeria experienced right cervical lymphadenopathy, multiple 2-4-mm pustules, and central umbilication of the skin, particularly on the face, neck, and hands. The oral lesions were described as a single intact pustule on the lower labial mucosa and a few round 2-3 mm erosions on the mucosa, indicating that the original vesicles or pustules have already broken off. In the study by Girometti et al,13 oral mucosal enanthema were more frequently recorded among unvaccinated individuals than among those who had received vaccinations. This condition can occur in more than 70% of cases. This might represent the aspect of oral lesions occurring more in unvaccinated individuals which might prompt strengthening of the already stringent vaccination laws around the world especially in terms of traveling. Speaking of traveling, seven of the 14 studies that we selected for our review involved individuals who were traveling from one country to another which again warrants a separate investigation into the transmission of monkeypox or monkeypox-like infectious diseases within a particular defined area (such as a city, state or country) and how it might differ from the outcomes obtained in our investigation.\n\nFigures 3, 4 and 5 represent the meta-analysis results of our investigation. Although the heterogeneity levels in the three different assessments are particularly high (91%, 89% and 97%), it is due to the fact that the studies that were selected had sample sizes that were lesser than what could be considered ideal and more importantly, the methodological differences in the studies selected contribute to the high levels of heterogeneity of the forest plots. The fixed effect model was employed in the odds ratio, risk ratio and the risk difference assessments so as to keep uniformity in terms of our interpretations and reduce bias that occurs resultantly after selection of studies with such variations in methodology and sample sizes.\n\nThe nasopharyngeal swab bio sample has been the gold standard for the detection of severe acute respiratory syndrome coronavirus 2 since the start of the COVID-19 pandemic (SARS-CoV-2). Saliva has recently become a practical and affordable bio fluid for COVID-19 diagnostics and may someday take the place of a nasopharyngeal swab.30 Saliva collection requires no specialised equipment, is non-invasive, and uses a straightforward approach. Since monkeypox infection frequently appears in the oral cavity, patient saliva may contain monkeypox virions and hence might be used as a bio sample to identify the virus. These patients will greatly benefit from further research to validate the use of saliva for monkeypox diagnoses.31 Vesicular or pustular lesions are the terms used to characterise monkeypox oral symptoms. The ulceration occurs following the vesicle or pustule rupture. Monkeypox patients' lesions may mirror those caused by other viral diseases of the oral cavity, such as COVID-19, chickenpox, measles, measles-mumps-rubella, measles, and herpes zoster. Vesiculobullous lesions predominate in monkeypox oral lesions. The vesicles/bullae readily separate, resulting in numerous uncomfortable, superficial sores on the oral mucosa and lips. Recurrent lesions are more confined and frequently affect the keratinized oral mucosa and lip vermilion.32\n\nFortunately, the majority of people with monkey pox infection recover on their own. To reduce gastrointestinal fluid losses, those with gastrointestinal symptoms (such as vomiting or diarrhoea) will need oral or intravenous rehydration. Several antivirals have been licenced for the management of smallpox based on animal models, but they may also be beneficial in treating monkeypox infections. Human dose studies for these medications have been carried out, but their effectiveness has not been fully explored. The first antiviral approved for the treatment of smallpox in adults and children weighing at least 3 kg is tecovirimat, and it is regarded as the preferred method of care.33 Dual therapy with tecovirimat and brincidofovir may be utilised in patients with advanced illness. By blocking the last steps in viral maturation and release from the infected cell, the viral envelope protein VP37—by which Tecovirimat functions—inhibits the transmission of the virus within an infected host.34 Although its effectiveness in treating monkeypox in people has not been investigated, investigations on animals treated with tecovirimat at various illness phases have shown better survival from lethal monkeypox virus infections in comparison to animals given with a placebo.35–36 The side-effect profile of the placebo was generally identical to that of tecovirimat in an enlarged safety study with 359 human volunteers given tecovirimat. Since June 2021, brincidofovir has also been authorised for the treatment of monkeypox in the US.37 An oral counterpart of the injectable medicine cidofovir, brincidofovir, may have a better safety profile than cidofovir, such as reduced renal damage.38 These medications function by preventing viral DNA polymerase.39 The effectiveness of brincidofovir against orthopoxvirus infections has been established, despite the paucity of studies examining its usage in treating monkeypox infections in animal models.40 The FDA has authorised the hyperimmune globulin known as Vaccinia Immune Globulin (VIG) for the treatment of specific vaccine-related side effects.41 These include vaccinia infections in people with skin disorders, aberrant infections brought on by the vaccinia virus, progressive vaccinia, severe widespread vaccinia, and eczema vaccinatum (except in cases of eye-related infections).41\n\nAs far as limitations go, our systematic review had a few to being with. For starters, the sample size observed in our selected studies were fewer than what would be considered ideal, but, since the number of articles which had documented the oral manifestations observed in patients suffering from monkeypox are very scarcely available, we selected the ones best suited for our objectives. Additionally, prior to the outbreak in May 2022, monkeypox had a limited clinical relevance, therefore it was frequently overlooked in the differential diagnosis. Other infectious illnesses could be in the differential diagnosis list. The countries of Central and Western African regions, where this disease is endemic, do not have a lot of data available on monkeypox due to the extremely limited number of studies performed, which as such necessitates the importance of documenting monkeypox and its effects observed in the form of symptoms such as the occurrence of oral lesions.\n\n\nConclusion\n\nAll the 14 articles selected in this review have reported the incidence of oral lesions in monkey pox sufferers, in at least the beginning stages of the disease, which have then blown up into full-fledged symptoms. As such, the identification and treatment of this illness may be aided by the seldom observed oral features of monkeypox infection. Acute onset oral signs (as seen in nearly all our selected studies) should be differentially diagnosed for monkeypox, especially in people who are more likely to experience this ailment. It is crucial to remember that recognising and identifying oral lesions in patients with monkeypox paves the way for additional research, effective care, and the prevention of cross-infection between patients and medical staff.\n\n\nAuthor contributions\n\nConceptualization, HA, AD, FB, NM, FA, OM, KPS, MAS, HA, MKA; methodology, HA, AD, MKA; software, HA, AD, MKA; validation, HA, AD, MKA; formal analysis, HA, AD, MKA; investigation, HA, AD, MKA; resources, HA, AD, MKA; data curation, HA, AD, MKA; writing—original draft preparation HA, AD, FB, NM, FA, OM, KPS, MAS, HA, MKA; writing— review and editing. HA, AD, FB, NM, FA, OM, KPS, MAS, HA, MKA; visualization, HA, AD, MKA; project administration, HA, AD, MKA; funding acquisition, none. All authors have read and agreed to the published version of the manuscript.\n\n\nReporting guidelines\n\nFigshare. PRISMA flowchart. DOI: https://doi.org/10.6084/m9.figshare.23626704.v1\n\nFigshare. PRISMA checklist. DOI: https://doi.org/10.6084/m9.figshare.23626695.v1",
"appendix": "Data availability statement\n\nAll data are available within the manuscript.\n\n\nReferences\n\nPetersen E, Kantele A, Koopmans M, et al.: Human monkeypox: Epidemiologic and clinical characteristics, diagnosis, and prevention. Infect. Dis. Clin. N. Am. 2019; 33(4): 1027–1043. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBunge EM, Hoet B, Chen L, et al.: The changing epidemiology of human monkeypox – A potential threat? A systematic review. PLoS Negl. Trop. Dis. 2022; 16(2): e0010141. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLanese N: Monkeypox may present with unusual symptoms. CDC warns. Accessed June 28, 2022. Reference Source\n\nPan American Health Organization and World Health Organization: Epidemiological update. Monkeypox in non-endemic countries. Accessed June 13, 2022. Reference Source\n\nCabanillas B, Valdelvira R, Akdis CA: Monkeypox outbreak in Europe, UK, North America, and Australia: A changing trend of a zoonotic disease. Allergy. 2022; 77(8): 2284–2286. PubMed Abstract | Publisher Full Text\n\nWorld Health Organization: Multi-country monkeypox outbreak: Situation update. Accessed June 27, 2022. Reference Source\n\nCenters for Disease Control and Prevention: Monkeypox Signs and Symptoms. Accessed October 15, 2022. Reference Source\n\nAntinori A, Mazzotta V, Vita S, et al.: Epidemiological, clinical and virological characteristics of four cases of monkeypox support transmission through sexual contact, Italy, May 2022. Euro Surveill. 2022; 27(22): 2200421. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCenter for Infectious Disease Research and Policy: WHO says it’s investigating monkeypox DNA in semen. Accessed October 15, 2022. Reference Source\n\nPage MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. PLoS Med. 2021; 18(3): e1003583. [15p.]. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShea BJ, Reeves BC, Wells G, et al.: AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017 Sep 21; 358: j4008. Publisher Full Text\n\nBenslama L, Foy JP, Bertolus C: Monkeypox oral lesions. J. Stomatol. Oral Maxillofac. Surg. 2022 Sep 9; 123: 596. S2468-7855(22)00255-5. Epub ahead of print. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGirometti N, Byrne R, Bracchi M, et al.: Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis. Lancet Infect. Dis. 2022 Sep; 22(9): 1321–1328. Epub 2022 Jul 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIamaroon A: Oral manifestations of monkeypox: Brief review. Dent. Med. Probl. 2022 Jul-Sep; 59(3): 483–487. PubMed Abstract | Publisher Full Text\n\nMartins-Filho PR, de Souza MF , Oliveira Góis MA, et al.: Unusual epidemiological presentation of the first reports of monkeypox in a low-income region of Brazil. Travel Med. Infect. Dis. 2022 Sep 27; 50: 102466. Epub ahead of print. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNoe S, Zange S, Seilmaier M, et al.: Clinical and virological features of first human monkeypox cases in Germany. Infection. 2022 Jul 11; 51: 265–270. Epub ahead of print. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPatel A, Bilinska J, Tam JCH, et al.: Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series. BMJ. 2022 Jul 28; 378: e072410. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPeiró-Mestres A, Fuertes I, Camprubí-Ferrer D, et al.: Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022. Euro Surveill. 2022 Jul; 27(28): 2200503. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPeters SM, Hill NB, Halepas S: Oral Manifestations of Monkeypox: A Report of 2 Cases. J. Oral Maxillofac. Surg. 2022 Aug 6; 80: 1836–1840. Epub ahead of print. S0278-2391(22)00715-7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSamaranayake L, Anil S: The Monkeypox Outbreak and Implications for Dental Practice. Int. Dent. J. 2022 Oct; 72(5): 589–596. Epub 2022 Aug 5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSukhdeo S, Tan DHS, Mishra S: Human monkeypox: cutaneous lesions in 8 patients in Canada. CMAJ. 2022 Oct 3; 194(38): E1323–E1327. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTarín-Vicent EJ, Alemany A, Agud-Dios M, et al.: Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study. Lancet. 2022; 400: 661–669. Published online Aug 8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThornhill JP, Barkati S, Walmsley S, et al.: Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022. N. Engl. J. Med. 2022 Aug 25; 387(8): 679–691. Epub 2022 Jul 21. PubMed Abstract | Publisher Full Text\n\nYadav PD, Reghukumar A, Sahay RR, et al.: First two cases of Monkeypox virus infection in travellers returned from UAE to India, July 2022. J. Infect. 2022 Nov; 85(5): e145–e148. Epub 2022 Aug 10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYinka-Ogunleye A, Aruna O, Dalhat M, et al.: Outbreak of human monkeypox in Nigeria in 2017-18: a clinical and epidemiological report. Lancet Infect. Dis. 2019 Aug; 19(8): 872–879. Epub 2019 Jul 5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Health Organization: Monkeypox. Accessed May 19, 2022. Reference Source\n\nLa Voce di New York: Italy’s monkeypox cases are all men. Accessed June 3, 2022. Reference Source\n\nNg OT, Lee V, Marimuthu K, et al.: A case of imported monkeypox in Singapore. Lancet Infect. Dis. 2019; 19(11): 1166. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCostello V, Sowash M, Gaur A, et al.: Imported monkeypox from international traveler, Maryland, USA, 2021. Emerg. Infect. Dis. 2022; 28(5): 1002–1005. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHammerschlag Y, MacLeod G, Papadakis G, et al.: Monkeypox infection presenting as genital rash, Australia, May 2022. Euro Surveill. 2022; 27(22): 2200411. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPublic Health England: Monkeypox: Information for primary care. Accessed December 2019. Reference Source\n\nMorand A, Delaigue S, Morand JJ: Review of poxvirus: Emergence of monkeypox [in French]. Med. Sante. Trop. 2017; 27(1): 29–39. PubMed Abstract | Publisher Full Text\n\nTPOXX (tecovirimat) [Package Insert]. Corvallis, OR: SIGA Technologies, Inc.2018. Reference Source\n\nRusso AT, Grosenbach DW, Chinsangaram J, et al.: An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications. Expert Rev. Anti-Infect. Ther. 2021; 19: 331–344. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGrosenbach DW, Honeychurch K, Rose EA, et al.: Oral tecovirimat for the treatment of smallpox. N. Engl. J. Med. 2018; 379: 44–53. PubMed Abstract | Publisher Full Text | Free Full Text\n\nQuenelle DC, Buller RML, Parker S, et al.: Efficacy of delayed treatment with ST-246 given orally against systemic orthopoxvirus infections in mice. Antimicrob. Agents Chemother. 2007; 51: 689–695. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUS Food and Drug Administration: FDA approves drug to treat smallpox. http\n\nChittick G, Morrison M, Brundage T, et al.: Short-term clinical safety profile of brincidofovir: a favorable benefit–risk proposition in the treatment of smallpox. Antivir. Res. 2017; 143: 269–277. PubMed Abstract | Publisher Full Text\n\nLanier R, Trost L, Tippin T, et al.: Development of CMX001 for the treatment of poxvirus infections. Viruses. 2010; 2: 2740–2762. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSmee DF: Progress in the discovery of compounds inhibiting orthopoxviruses in animal models. Antivir. Chem. Chemother. 2008; 19: 115–124. PubMed Abstract | Publisher Full Text\n\nWittek R: Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy. Int. J. Infect. Dis. 2006; 10: 193–201. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "195852",
"date": "30 Aug 2023",
"name": "Gururaj Arekeri",
"expertise": [
"Reviewer Expertise OMFS"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for asking me to review the article \"Monkeypox and oral lesions associated with its occurrence: a systematic review and meta-analysis\":\nComments:\nThe article addresses an important and timely topic given the recent global outbreak of monkeypox cases. Understanding the oral manifestations can aid healthcare providers in early detection and diagnosis.\n\nThe authors clearly state the objectives to establish the association between monkeypox and oral lesions through a systematic review and meta-analysis.\n\nThis review synthesizes important evidence on monkeypox oral manifestations from multiple case reports and observational studies. It will help inform clinicians in this critical area.\n\nThe methods are sound and align with guidelines for rigorous systematic reviews. The number of studies included is understandable given monkeypox's emerging nature.\n\nThe article is comprehensive in summarizing prior literature and relevant clinical details on oral lesions in monkeypox. This will aid differential diagnosis.\n\nThe authors note study limitations appropriately and suggest implications for future research.\n\nThe topic is highly relevant currently. This review makes a valuable contribution to the literature on this unfolding outbreak.\nOverall, I recommend approval of this well-conducted systematic review for indexing.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "208362",
"date": "26 Sep 2023",
"name": "Bruno Hernaez",
"expertise": [
"Reviewer Expertise poxvirus immune evasion"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe present systematic review addresses the association between mpox (formerly monkeypox) and the presence of oral lesions in the patients. This is clearly an interesting topic given the relevance of this disease, especially since the 2022 outbreak affecting non-endemic regions. However, I have some comments and concerns that hopefully will contribute to improve this manuscript.\nIn my opinion, the introduction can be improved. For instance, Monkeypox virus is NOT an uncommon zoonotic disease as the authors state in their first sentence of the introduction. Monkeypox virus is the name for the virus causing the disease monkeypox. In addition, after the 2022 outbreak there is consensus to follow the WHO nomenclature recommendations: the disease is now “mpox” and the virus is “mpox virus (MPXV)”. Please change through the entire text.\n\nThe authors state in Table 1: “There have been no reports of patient deaths from non-endemic regions up to this point”. This needs an update since at this moment 157 deaths have been reported (file:///Users/bh/Downloads/20230919_mpox__external-sitrep-28.pdf).\n\nViable virus in saliva was first described by our group in a study published in The Lancet Microbe (doi: 10.1016/S2666-5247(22)00291-9). The incorporation of this reference would support the affirmation “ These findings imply that the virus can be carried in the saliva and spread via oral-skin and/or oral-anogenital contact”.\n\nIn line with this, I wonder why this study is not included in the present review. The study by Hernaez et al (Monitoring monkeypox virus in saliva and air samples in Spain: a cross-sectional study) included 44 confirmed patients with mpox from the 2022 outbreak in Madrid (Spain), and the clinical symptoms (including the presence of oral lesions) can be found in an exhaustive table as Supplementary material. In my opinion the authors should contemplate its incorporation now, perhaps by adding the term “saliva” to the search strategy.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required.\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-964
|
https://f1000research.com/articles/13-154/v1
|
01 Mar 24
|
{
"type": "Brief Report",
"title": "The CT Scan Lung Severity Score and Vaccination Status in COVID-19 patients in India: Perspective of an Independent Radiology Practice",
"authors": [
"Revat Lakhia",
"Jaimin Trivedi",
"Revat Lakhia"
],
"abstract": "Background Patients with COVID-19 often undergo a high-resolution CT scan to determine the extent of lung involvement. The aim of this study was to determine lung involvement in confirmed/suspected COVID-19 patients (encountered at an independent radiology practice) and its correlation to vaccination status amidst the second COVID-19 wave in India.\n\nMethods We retrospectively queried our data from April 2021 to identify adult patients (>17 years) who had confirmed (positive RT-PCR or antigen test) or suspected COVID-19 (classic symptoms but negative RT-PCR) and received a high-resolution CT scan to determine the extent of lung involvement using the CT severity (CT-SS) score. The patients were classified into three groups based on their vaccination status to determine their correlation with the CT-SS score: fully vaccinated, partially vaccinated, and unvaccinated. Basic descriptive statistics, univariate tests, and multivariate linear regression analyses were performed.\n\nResults We identified 229 patients (median age, 45 years; 60% male), of whom 205 (89%) had confirmed COVID-19 (positive RT-PCR) and 24 had suspected disease (negative RT-PCT but classic symptoms). Of 229 patients, 29 (13%) had complete vaccination, 38 (17%) had partial vaccination, and 162 (70%) had no vaccination. The CT score of the completely vaccinated patients was significantly lower than that of the partially or unvaccinated patients (median 0 v. 3.5 v. 10, respectively p<.01).\n\nConclusion Here, we present real-world findings from an independent radiology practice (a unique and common practice model) in India amid the second COVID-19 wave, showing significantly lower CT severity scores in fully or partially vaccinated patients compared to unvaccinated patients. Complete vaccination of patients may be critical in preventing severe lung disease.",
"keywords": [
"Covid-19",
"vaccination",
"CT scan",
"CT score",
"lung involvement"
],
"content": "Introduction\n\nThe novel coronavirus (SARS nCOV-2) has affected over 160 million people worldwide, causing severe respiratory illness in many patients with a mortality rate of over 2%.1 Countries such as the USA, UK, and South Africa have seen deadlier second waves due to highly infectious mutated strains; one such (B1617 or delta) impacted India in April 2021, which led to higher hospitalizations and mortality.2 Some patients had symptomatic disease but negative RT-PCR or rapid antigen test results. These patients often undergo high-resolution CT to determine the extent of their lung involvement and aid in further management.3\n\nUnlike in Western countries, radiology practice in India is largely performed by independently operated groups (without affiliations to hospitals or care centers).4 A common patient is often referred to these independent practices, including suspected/confirmed COVID-19, to determine the degree of lung involvement. We had seen several patients in our practice during the second COVID-19 wave (delta) who had negative RT-PCR test results but presented with classic symptoms such as fever, fatigue, body aches, and occasional shortness of breath. Our case mix included fully, partially, or completely unvaccinated patients. At the time of the study, two vaccines were approved in India, both of which required two doses for complete vaccination.5 The aim of this study was to determine lung involvement in patients with confirmed or suspected COVID-19 and its correlation with vaccination status.\n\n\nMethods\n\nThe ACEAS independent ethical committee in Ahmedabad, India, reviewed our protocol and approved our study. The requirement for a waiver of informed consent was approved, considering the retrospective nature of the study. We retrospectively queried our data from April 2021 to June 2021 to identify adult patients (>17 years) who had confirmed (positive RT-PCR or antigen test) or suspected COVID-19 (classic symptoms but negative RT-PCR) and received a high-resolution CT scan to determine the extent of lung involvement using the CT severity score (CT-SS).6 The duration between April and June 2021 was chosen because it represented the second COVID-19 wave duration.\n\nWe accessed the data between August 3, 2021, and September 10, 2021, during which the investigators had access to the patient identifying information. It should be noted that the patients who underwent the CT scan were between April 2021 and June 2021, and their data were accessed for research between August and September 2021. Patient identification information was removed once data collection was complete. The data was uploaded on the Figshare platform and is available at https://doi.org/10.6084/m9.figshare.25033796.v1. Along with the RT-PCR results, we recorded vaccination status at the time of the CT scan. Patients with both doses completed 1 week prior to the CT scan were considered fully vaccinated, whereas patients receiving the CT scan 2 weeks after the 1st dose or within 1 week of 2nd dose were considered partially vaccinated, and the rest of the patients (not receiving any vaccine or within 2 weeks of 1st dose) were considered unvaccinated.7 Based on the vaccination age eligibility criteria, we stratified the cohort into three groups: 18-44 years, 45-59 years, and ≥ 60 years.\n\nWe used descriptive statistics (median (interquartile range) and % (N)), univariate tests (non-parametric Kruskal (Wallis) for continuous variables, and chi-square test for categorical variables), and multivariate logistic regression analysis to determine the association of the CT-SS score with RT-PCR and vaccination status. All analyses were conducted using the SAS software (version 9.4; SAS Inc. Cary, NC, USA) https://www.sas.com/en_us/software/base-sas.html with a 95% confidence interval. The STROBE guidelines were followed and the checklist was also uploaded along with dataset https://doi.org/10.6084/m9.figshare.25153271.v1.\n\n\nResults\n\nWe identified 229 patients, of whom 205 (89%) had confirmed COVID-19 (positive RT-PCR) and 24 had suspected disease (negative RT-PCT but classic symptoms). The median age of the cohort was 45 (36-58) years and 138 (60%) patients were male. The median CT severity score of the entire cohort was 9 (2-13). There were 49% (n=112), 29% (n=67), and 22% (n=50) of patients in age groups 18-44 years, 45-59 years and > 60 year age groups, respectively. The median CT severity scores in patients age group 18-44 years were 9 (0-12), 45-60 years was 11 (6-15) and >60 years was 8 (1-11).\n\nOf 229 patients, only 29 (13%) had complete vaccination, 38 (17%) had partial vaccination, and 162 (70%) had no vaccination. Of the RT-PCR-positive patients, 29 (14%) had complete vaccination and 32 (15%) had partial vaccination (Figure 1). The median ages of the fully vaccinated, partially vaccinated, and non-vaccinated groups were 42, 48, and 43 years, respectively, and the difference was not statistically significant (p=0.32, Table 1). There were more male patients in the unvaccinated group than in the fully or partially vaccinated groups (67% vs. 42% vs. 47%, p<0.01). The overall CT score in the RT-PCR-positive cohort was significantly higher than that in the RT-PCR-negative cohort (median 10 vs. 0, p<0.01) cohort (Figure 2).\n\nThe CT score of the completely vaccinated patients was significantly lower than that of the partially or unvaccinated patients (median 0 (full) v. 3.5 (partial) vs. 10, p<0.01, Figure 3). Within the RT-CPR-positive cohort, patients with complete vaccination had significantly lower CT-SS scores than partially or unvaccinated patients (median 0 vs. 4 vs. 11, p=0.02). Figure 4 shows the CT scan images stratified by vaccination status, showing significant lung involvement in unvaccinated patients and minimal lung involvement in fully vaccinated patients.\n\nA multivariate logistic regression model adjusted for age, sex, and RT-PCR showed that unvaccinated patients (Odds Ratio = 12.3 (2.8-54), p<0.01) had a higher likelihood of higher CT severity score compared to fully vaccinated patients (Table 2).\n\n\nDiscussion\n\nThe second COVID-19 wave, during April and June 2021, put extreme pressure on India’s healthcare system, affecting several younger patients.2 We observed that almost half of all the patients in our cohort were 45 years or younger, which correlated with the national vaccination guidelines (vaccination for healthcare and frontline workers had been performed since January 2021 and vaccination for the general population aged over 45 years had just started in April 2021). One of the primary findings of our research was that patients with complete or even partial vaccination had lower CT severity scores than unvaccinated patients, which reattributes the effectiveness of the vaccines in preventing severe disease.7\n\nEven though radiology practice in India is predominantly independent, they likely encountered a majority of COVID-19 cases requiring imaging studies, including severely ill patients who might have been admitted to hospitals for further treatment.4,8 Our study represents a unique and common practice across India and reports real-world evidence of the CT scan findings and its association with vaccination status and RT-PCR positivity in COVID-19 patients. Our study not only demonstrated lower lung involvement with full vaccination using univariate analysis, but also on the multivariable regression model adjusted for age, sex, and RT-PCT status.\n\nVaccine effectiveness has been scrutinized with the emergence of SARS nCOV-2 variants, as B1617 (delta) or B117 (alpha) mutants had higher transmissibility and case fatality than the unmutated version of the virus.9,10 Previous studies have suggested that vaccines are effective against variants in preventing severe disease.11,12 A recent report from India suggested that fully vaccinated patients may still be infected with the delta (B1617) variant; however, no mortality or high-grade fever were predominant symptom.13 Similarly, our study showed that 29 fully vaccinated patients had a positive RT-PCR test result (all 29), but their median CT severity score was 0. Although genomic sequencing data in our cohort were unavailable, based on a previous study, the delta variant (B1617) could be predominantly responsible, as our patients were from the same time frame and geography. It should also be noted that all the patients in our study received the CoviShield vaccine (Oxford-AstraZaneca-Serum Institute).\n\nOur study showed that compared to unvaccinated patients, completely or partially vaccinated patients had significantly lower CT severity scores, irrespective of their RT-PCR status, which corroborates the evidence that vaccines are particularly effective tools in preventing severe COVID-19, even if effectiveness in limiting the spread could be lower in leu of emerging variants.7,12,13 This finding of reduced lung involvement with full or partial vaccination could be crucial in highlighting the role of vaccines as effective tools in combating severe COVID-19. We found 11% of patients with RT-PCR negative but with classic COVID-19 symptoms, which could be due to false negative tests or the timing when the nasopharyngeal swabs were taken (very early or late testing); however, these patients had a lower degree of lung involvement, which could also suggest the possibility of non-COVID illness.14,15\n\nOur study has several limitations, including its retrospective single-center design. We did not have patient details other than their basic demographics, COVID-19 RT-PCR status, vaccination status, or CT severity score. Patient details, such as oxygen saturation, hospital admission status, other laboratory findings, comorbidities, and mortality, were not available. The data presented here are not extensive because our center is not an academic institution that is not affiliated with any other academic center with academic infrastructure. Given the retrospective nature and specific approval from the ethical committee, we did not reach any of the patients after their initial imaging study.\n\nIn conclusion, we presented here the real-world findings from an independent radiology practice (a unique and common practice model) in India amid the second COVID-19 wave (of delta variant) showing significantly lower CT severity scores in fully and partially vaccinated patients than in unvaccinated patients. We report a higher CT severity score in patients with positive RT-PCR results. Complete vaccination of patients may have been critical in preventing severe lung disease.\n\n\nEthical approval\n\nThis study received ethical approval from the ACEAS independent ethical committee (US DHHS Reg No. IRB00011046) with protocol number 001/06/2021. The approval was granted on July 10, 2021.\n\n\nConsent to participate\n\nSince this was a retrospective data driven study the requirement for informed consent was waived and the approval was granted by the independent ethical committee.",
"appendix": "Data availability statement\n\nThe data and accompanying STROBE checklist for the, “The CT Scan Lung Severity Score and Vaccination Status in COVID-19 patients in India: Perspective of an Independent Radiology Practice” are available at below link.\n\nhttps://figshare.com/projects/COVID-19_CT_scan_vaccine/194810 OR https://doi.org/10.6084/m9.figshare.25033796.v1. 16\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nRoser M, Ritchie H, Ortiz-Ospina E, et al.: Coronavirus Pandemic (COVID-19). Our World in Data; 2020.\n\nLancet T: India’s COVID-19 emergency. Lancet (London, England). 2021; 397(10286): 1683. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXie X, Zhong Z, Zhao W, et al.: Chest CT for typical coronavirus disease 2019 (COVID-19) pneumonia: relationship to negative RT-PCR testing. Radiology. 2020; 296(2): E41–E45. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJankharia GR: Commentary-radiology in India: the next decade. Indian J. Radiol. Imaging. 2008; 18(3): 189–191. PubMed Abstract | Publisher Full Text\n\nBagcchi S: The world’s largest COVID-19 vaccination campaign. Lancet Infect. Dis. 2021; 21(3): 323. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang R, Li X, Liu H, et al.: Chest CT severity score: an imaging tool for assessing severe COVID-19. Radiol.: Cardiothorac. Imaging. 2020; 2(2): e200047. Publisher Full Text\n\nPilishvili T, Fleming-Dutra KE, Farrar JL, et al.: Interim estimates of vaccine effectiveness of Pfizer-BioNTech and Moderna COVID-19 vaccines among health care personnel—33 US sites, January–March 2021.2021.\n\nAhuja G, Verma M, Patkar D: Financial impact of COVID-19 on radiology practice in India. Indian J. Radiol. Imaging. 2021; 31(Suppl 1): S31–S37. PubMed Abstract | Publisher Full Text\n\nDavies NG, Abbott S, Barnard RC, et al.: Estimated transmissibility and impact of SARS-CoV-2 lineage B. 1.1. 7 in England. Science. 2021; 372(6538). PubMed Abstract | Publisher Full Text | Free Full Text\n\nGrint DJ, Wing K, Williamson E, et al.: Case fatality risk of the SARS-CoV-2 variant of concern B. 1.1. 7 in England, 16 November to 5 February. Eurosurveillance. 2021; 26(11): 2100256. Publisher Full Text\n\nAbu-Raddad LJ, Chemaitelly H, Butt AA: Effectiveness of the BNT162b2 Covid-19 Vaccine against the B. 1.1. 7 and B. 1.351 Variants. N. Engl. J. Med. 2021; 385: 187–189. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBernal JL, Andrews N, Gower C, et al.: Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. BMJ. 2021; 373.\n\nSingh UB, Rophina M, Chaudhry R, et al.: Genomic analysis of symptomatic SARS-CoV-2 vaccine breakthrough infections from a tertiary care centre in India.2021.\n\nArevalo-Rodriguez I, Buitrago-Garcia D, Simancas-Racines D, et al.: False-negative results of initial RT-PCR assays for COVID-19: a systematic review. PLoS One. 2020; 15(12): e0242958. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTahan S, Parikh BA, Droit L, et al.: SARS-CoV-2 E gene variant alters analytical sensitivity characteristics of viral detection using a commercial RT-PCR assay. J. Clin. Microbiol. 2021; 59. JCM. 00075-21. Publisher Full Text\n\nTrivedi J: The CT Scan Lung Severity Score and Vaccination Status in COVID-19 patients in India: Perspective of an Independent Radiology Practice Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "269547",
"date": "17 May 2024",
"name": "Jasmit Shah",
"expertise": [
"Reviewer Expertise Public health",
"biostatistics"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study aimed to investigate the extent of lung involvement in confirmed or suspected COVID-19 patients and its association with vaccination status during the second wave in India. Data from 2021 were retrospectively analyzed, focusing on adult patients who underwent high-resolution CT scans. Patients were classified based on vaccination status (fully vaccinated, partially vaccinated, unvaccinated), and CT severity scores (CT-SS) were compared. The findings indicate significantly lower CT severity scores in fully or partially vaccinated patients as compared to unvaccinated individuals, suggesting that complete vaccination may play a critical role in preventing severe lung disease.\nComplete vaccination may play a critical role in reducing the risk of severe lung disease. These real-world findings underscore the importance of vaccination in combating the COVID-19 pandemic.\nThe sample size of 229 patients from a single independent radiology practice may limit the generalizability of the findings. To enhance representativeness, a multicenter study could provide more robust evidence. The study does not account for potential confounding variables such as comorbidities, previous COVID-19 infection, or socioeconomic factors, which could influence both vaccination status and disease severity. Adjusting for these factors through multivariate analyses or propensity score matching could improve the accuracy of the findings.\nMinor edits needed in grammar and also in the methods in background, to be changed to multivariate logistic regression, rather than linear regression.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Yes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-154
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https://f1000research.com/articles/13-152/v1
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01 Mar 24
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{
"type": "Case Report",
"title": "Case Report: Recalcitrant oral lichen planus involving bilaterally buccal mucosae treated with a combination of photodynamic and photobiomodulation therapies",
"authors": [
"Juthamast Trakarnboonkij",
"Suwat Tanya",
"Wilairat Sarideechaigul",
"Ajiravudh Subarnbhesaj",
"Peera Tabbon",
"Sajee Sattayut",
"Juthamast Trakarnboonkij",
"Suwat Tanya",
"Wilairat Sarideechaigul",
"Ajiravudh Subarnbhesaj",
"Peera Tabbon"
],
"abstract": "Background Managing recalcitrant oral lichen planus (OLP) can be challenging. Laser therapy has been suggested as an alternative to corticosteroids for treatment. Photodynamic therapy (PDT) is a non-invasive technique that enables the removal of lesions without surgery. Photobiomodulation therapy (PBMT) can promote healing and recovery of the lesions.\n\nCase presentation The objective was to treat unresponsive bilateral OLP of the whole buccal mucosae with a combination of PDT and PBMT.\n\nResults A 43-year-old Thai male presented with the severe painful reticular type of OLP of bilateral buccal mucosae involving upper and lower vestibular areas. The lesions were not remitted with either prednisolone systemic steroids or fluocinolone topical corticosteroids. After undergoing ten sessions of PDT with 10% 5-Aminolevulinic acid (5-ALA) in the form of thermoplastic gel and a 635 nm diode laser at 100 to 400 mW with an energy density of 20 to 30 J/cm2 in continuous wave mode, combined with five interim-sessions of PBMT using a 635 nm diode laser at 200 to 300 mW with an energy density of 6 to 10 J/cm2 in continuous wave, the patient reported relief of burning sensation beside remission of lesions without any complications.\n\nConclusion The wide-spreading recalcitrant OLP with burning sensation can be managed by combining PDT and PBMT.",
"keywords": [
"Oral lichen planus",
"Burning sensation",
"Photosensitizer",
"Low-intensity laser therapy"
],
"content": "Introduction\n\nOral lichen planus (OLP) is a chronic mucocutaneous inflammatory condition affecting the oral mucosa.1 Among various causes, the cell-mediated immune response is postulated to be a primary factor of this lesion. OLP typically affects the oral cavity bilaterally, including buccal mucosae, tongue, and gingivae.2 It has several types, including reticular, papular, plaque-like, atrophic, erosive, and bullous.3,4 OLP is a potentially malignant disorder, according to WHO.5,6 The risk of developing cancer during observational periods ranging from 0.5 to 20 years is between 0.4% and 5%.7,8 and is higher for smokers, drinkers, and those with hepatitis C.8\n\nMost cases of OLP are incurable lesions. The goal of treating OLP is to reduce lesion size, alleviate symptoms, and improve daily activities. This can decrease the risk of malignant transformation.1 A scoring system ranging from 0 to 5 can be used to evaluate treatment success.9\n\nOLP can be managed by pharmacological and non-pharmacological treatment. Topical corticosteroids are the first-line treatment for frequent recurrences of the condition. However, long-term use or higher doses may be required. Unfortunately, these medications can cause side effects, such as candidiasis, xerostomia, and mucosal atrophy.10,11 In addition, a study revealed that approximately 20% of patients did not experience any improvement with topical corticosteroid use.12\n\nLaser therapy has been reported as an alternative non-pharmacological treatment for treating recalcitrant OLP.11,13–15 Systematic reviews and meta-analysis studies have shown that photodynamic therapy (PDT) and photobiomodulation therapy (PBMT) are effective laser therapy techniques used for OLP without clinical complication and side effect.15,16\n\nPDT utilizes light to activate a photosensitizer, which alters tissue oxygen forms, reducing hyperproliferation and inflammation. The success of PDT depends on factors such as available tissue oxygen, light source, and type of photosensitizer used.11 Diode lasers with a wavelength from 600 to 800 nm are frequently employed as light sources.17 An effective photosensitizer for treating OLP is 5-ALA,18–21 but it can be diluted by saliva. It was suggested that formulating 5-ALA in a gel could enhance its effectiveness.22 Currently, the 5-ALA gel is not yet available in any commercial products for use on oral mucosa.\n\nPBMT uses a low-intensity laser to stimulate natural biological processes like cell metabolism, tissue regeneration, and healing. This therapy has a biphasic mechanism. An optimal low-intensity laser dosage enhances biostimulatory effects, while high dosages inhibit cellular activities. This leads to analgesic, anti-inflammatory, and immune modulatory effects. PBMT is a non-invasive and safe treatment without any clinical complications. Studies suggest that PBMT is an alternative treatment for OLP as it can effectively reduce pain and inflammation.16,23\n\nThis case report describes the use of PDT and PBMT to treat oral lichen planus with burning sensation. The report also includes information on the properties and preparation of 5-ALA gel.\n\n\nCase report\n\nThis case report was approved by the Khon Kaen University Ethics Committee for Human Research, with reference number HE662013. The written informed consent in Thai language for publication of his clinical details and images was obtain from the patient. This consent was also submitted to the ethics committee.\n\nA 43-year-old Thai man complained of a severe burning sensation in his bilateral buccal mucosae for one month. The patient experienced worsened symptoms when consuming hot or spicy foods. Despite receiving treatment with 0.1% Fluocinolone acetonide four times a day and taking 10 mg prednisone twice daily, there was no noticeable improvement in the lesion size or symptoms. Therefore, he was referred to the Laser Clinic at the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Khon Kaen University.\n\nThe patient had no systemic disease based on physical examination and laboratory investigation. He was categorized into ASA PS I.\n\nThere was no history of medical and psychological disorders of the patient and his family.\n\nFrom extraoral examination, no significant skin lesions were identified on the patient. The intraoral examination revealed several lesions of the oral mucosae which are shown in Figure 1. The patient had white striae networks in the upper and lower vestibule and retromolar regions on both sides of the buccal mucosae. Additionally, white patches were also present on both the dorsal and ventral surfaces of the tongue.\n\nAn incisional biopsy was performed on the left buccal mucosa using a CO2 laser at 4W with the continuous wave mode to obtain a specimen. The representative area is shown in Figure 2. Upon histopathological investigation (Figure 3), a piece of soft tissue covered by parakeratotic acanthotic stratified squamous epithelial with some foci of liquefactive degeneration of the basal cell and apoptotic keratinocytes was observed. The epithelial layer was densely infiltrated by lymphohistiocytic cells in a band-like pattern. These histological features were interpreted as oral lichen planus. No evidence of dysplasia or malignancy was observed in this section. The definitive diagnosis was oral lichen planus. Three weeks later, the affected area showed signs of a recurrent lesion, and the mucosal coverage was complete (Figure 4).\n\nThe carbonized zone was so narrow at less than 40 microns. This did not interfere with the oral pathologist's observation of the histological sample. (3A magnification at 40x, 3B magnification at 100x).\n\n\n\n• Photodynamic therapy\n\n1. Preparation and physical properties of gel phase\n\nThe thermoplastic gel used in our PDT underwent gelation through temperature increase. The in-situ gel was prepared by adding 15% (w/w) poloxamer 407 and 0.1% (w/w) sodium benzoate to the mixture on a weight basis (Center for Research and Development of Herbal Health Products, Faculty of Pharmaceutical Sciences, Khon Kaen University, Thailand). Firstly, sodium benzoate was dissolved in cold water, and then poloxamer 407 was added to the solution. The mixture was stirred until it was completely dissolved. Finally, the gel was sterilized using an autoclave (Hariyama HICLAVE HV-85II, Japan).\n\n2. Physical properties of photosensitizing-containing gel\n\nTo demonstrate the process of gel formation due to thermal increase, we determined the gelation temperature by visually inspecting the sample. We transferred the gel to a test tube and placed it in a water bath with the temperature initially set at 20°C, which 1°C increased until it reached 40°C. We observed the samples visually to see when a gel was formed.\n\nIn vitro, release was investigated using a modified Franz diffusion cell with the non-porous membrane (Cellu Sep, T4). The receiver chamber, equipped with a magnetic stirrer, was filled with Phosphate buffer saline as the receiver medium, and stirred at 300 rpm. The temperature was set at 37±0.5°C. We placed 500 mg of gel in the donor compartment chamber and covered it tightly with paraffin film.\n\nWe collected 0.5 mL of the receiver medium at 0, 15, 30, 60, 90, 120, and 180 min and refilled with 0.5 mL of the warmed fresh medium. The 5-ALA in the medium was converted into a fluorescent derivative with fluorescamine and analyzed by high-performance liquid chromatography with fluorescence detector.24 This method confirmed the favorable properties of the 5-ALA gel preparation, as shown in Table 1.\n\n3. The preparation of photosensitizing agent (Figure 5)\n\nTo prepare a fresh batch of gel for 5-ALA, the 5-ALA powder from a vial was mixed with a fluid gel base. The gel base was stored in a 1-ml syringe at 20°C. The resulting mixture was then drawn back into the syringe while still fluid and left at room temperature to solidify. The 5-ALA gel with photosensitizing properties was now ready to use.\n\n4. Application of a photosensitizing agent on the intraoral lesion\n\nThe sterile gauze was used to clean and dry the mucosa. A fresh gel with 10% of 5-ALA was then applied to the affected area as shown in Figure 6 and left for 30 minutes.\n\n5. Laser activation of the photosensitizing agent (Figure 7)\n\nA 635 nm diode laser was used as a light source to activate the tissue that was applied with the 5-ALA gel. During laser irradiation at 400 mW, the patient experienced a burning sensation. As a result, the laser settings for the first and second sessions were reduced to 100 mW with an energy density of 20 J/cm2 in continuous wave mode. These sessions were conducted every 2 weeks. As the patient could tolerate, the laser dose was increased to 400 mW with an energy density of 30 J/cm2 in continuous wave mode every 3 weeks. In total, there were 5 episodes.\n\n\n\n• PBMT as an interim therapy\n\nAfter completing 5 sessions of PDT, the patient underwent PBMT as an interim therapy to aid in the healing process of the affected areas. The therapy involved using a 635 nm diode laser with a power output of 200 to 300 mW and an energy density of 6 to 10 J/cm2 in continuous wave mode. The power and energy density were adjusted incrementally as the patient experienced no discomfort during treatment. A total of 5 sessions were conducted every 2 weeks.\n\n• PDT after PBMT\n\nThe patient underwent PDT for an additional 5 sessions by using 10% 5-ALA gel fresh preparation irradiated with a 635 nm at 400 mW with an energy density of 30 J/cm2 in continuous wave mode. The patient received the treatment once every 3 or 4 weeks.\n\nDuring the initial 5 sessions of PDT and subsequent 5 sessions of PBMT, the patient visited for follow-up appointments every two weeks. The patient reported a decrease in the burning sensation. The lesion size had reduced with a smoother surface of the oral mucosa after the third session of PDT. Gradually, over time, the clinical signs and symptoms improved. Upon completion of 10 PDT sessions, including 5 PBMT sessions in between, the patient successfully reduced lesion size and burning sensation without any clinical complications within a 12-month, as illustrated in Figure 8.\n\nThe affected areas, which are the right buccal mucosa (8A), the left buccal mucosa (8B), the ventral tongue (8C), and the dorsal tongue (8D), were examined and showed no signs of significant lesions.\n\nAfter completing the treatment, the patient consistently attended follow-up appointments every 1 to 2 months for the 3-year follow-up period. During these visits, the patient reported no discomfort or symptoms while consuming spicy food. Additionally, the patient expressed their willingness to return for further evaluation if any symptoms arose.\n\n\nDiscussion\n\nThe primary difficulty in this case was the patient experiencing a burning sensation caused by reticular type OLP, which affected widespread areas of the oral mucosae. Despite using both topical and systemic steroids, there was no significant improvement in the lesions. Due to the size of the oral lesion, it was not possible to remove it surgically with high-intensity laser therapy. Moreover, the previous lesion recurrence after CO2 laser biopsy showed that surgery would not be an effective treatment in this particular case. Based on the reasons previously stated, non-pharmacological treatments such as PDT and PBMT seem to be the only viable options for treating this unresponsive case of OLP. These laser therapies are non-invasive and have been proven to treat OLP effectively.16,23\n\nAfter undergoing 10 sessions of PDT combined with 5 sessions of interim PBMT, the patient showed partial remission of the lesion. The patient reported a decrease in pain score over a 12-month period. These results align with previous studies using PDT to treat OLP. In fact, a systematic review conducted by Nagi et al. in 2023 found that PDT was an effective treatment option for managing symptomatic OLP that was unresponsive to corticosteroid therapy. This review analyzed ten clinical studies and found that PDT effectively reduced lesion size and VAS scores both during follow-up sessions and after treatment. Furthermore, four of the studies noted that PDT was more effective than topical corticosteroids in reducing the signs and symptoms of OLP, with a p-value < 0.01.25 Another systematic review by Al-Maweri et al. also found that PDT was a successful treatment option for patients with symptomatic OLP.11\n\nA study conducted by Sulewska et al. on 50 patients with 124 lesions showed that PDT using 5% 5-ALA and 630 nm lights was effective in treating reticular type OLP. PDT was administered every two weeks for a total of 10 weeks, which resulted in a 62.91% reduction in the size of the lesions.19 Our study administered PDT biweekly, using 10% 5-ALA gel, over a 12-month monitoring period. The higher photosensitizer concentration led to a further reduction in lesion size and decreased pain intensity. Using thermoplastic gel, we also developed an easy method for applying 5-ALA on oral mucosa. The gel form of 5-ALA was partially resistant to saliva dilution and exhibited adhesive properties, facilitating its absorption from the mucosal surface. This was supported by Chen et al.’s study using a 20% 5-ALA sol-gel concentration to treat oral hyperplasia and leukoplakia.22\n\nAnother factor of the effectiveness of PDT is highly dependent on the laser parameters used. A systematic review conducted by Al-Maweri et al. reported a lack of consistency in laser parameters used in the included studies. There was a wide range of variation observed in power density (10 to 500 mW/cm2), energy density (1.5 to 15.6 J/cm2), duration of laser irradiation (2 to 10 minutes), and the number of sessions (1 to 8 sessions). Despite these variations, PDT is an effective treatment for symptomatic OLP.11 In this case study, we employed a 635 nm diode laser in continuous wave mode, with a power output that varied between 100 and 400 mW, and an energy density that ranged from 20 to 30 J/cm2. We reduced the dose’s power and energy density to prevent the patient from experiencing a burning sensation during irradiation. In this case, we aimed to induce apoptosis in the hyperkeratotic areas of the lesions while treating symptomatic OLP and promoting mucosal healing. To achieve this, we combined PBMT with PDT. PBMT has a significant impact on biological processes, both biostimulatory and inhibitory. Specifically, it has analgesic effects by increasing the production of ß-endorphins and enkephalins, decreasing the levels of bradykinin and histamine, and modulating pain signalling pathways through C-fiber. Additionally, PBMT can enhance the release of leukocytes into oral tissues and modulate mast cell function, which contributes to inflammation control in the oral mucosa.23\n\n\nConclusions\n\nUsing a 635 nm diode laser with 10% 5-ALA-mediated PDT and PBMT was an alternative treatment for recalcitrant OLP. The thermoplastic gel utilized as a base for the photosensitizing agent was suitable for intraoral application.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nFigshare: CARE flowchart and Checklist for Case report: Recalcitrant Oral Lichen Planus Involving Bilaterally Buccal Mucosae Treated with A Combination of Photodynamic and Photobiomodulation Therapies, https://doi.org/10.6084/m9.figshare.24925383.v1. 26\n\n\nAcknowledgements\n\nWe would like to thank Assoc Prof Dr Poramaporn Klanrit for kindly assisting in producing the histopathological section photographs.\n\n\nReferences\n\nAlrashdan MS, Cirillo N, McCullough M: Oral lichen planus: a literature review and update. Arch. Dermatol. Res. 2016; 308(8): 539–551. Publisher Full Text\n\nChiang CP, Yu-Fong Chang J, Wang YP, et al.: Oral lichen planus – Differential diagnoses, serum autoantibodies, hematinic deficiencies, and management. J. Formos. Med. Assoc. 2018; 117(9): 756–765. PubMed Abstract | Publisher Full Text\n\nRotaru D, Chisnoiu R, Picos A, et al.: Treatment trends in oral lichen planus and oral lichenoid lesions (Review). Exp. Ther. Med. 2020; 20(6): 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFarhi D, Dupin N: Pathophysiology, etiologic factors, and clinical management of oral lichen planus, part I: facts and controversies. Clin. Dermatol. 2010; 28(1): 100–108. PubMed Abstract | Publisher Full Text\n\nWarnakulasuriya S, Kujan O, Aguirre-Urizar JM, et al.: Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis. 2021; 27(8): 1862–1880. PubMed Abstract | Publisher Full Text\n\nWarnakulasuriya S, Johnson NW, Van Der Waal I: Nomenclature and classification of potentially malignant disorders of the oral mucosa. J. Oral Pathol. Med. 2007; 36(10): 575–580. PubMed Abstract | Publisher Full Text\n\nEisen D, Carrozzo M, Sebastian JVB, et al.: Oral lichen planus: Clinical features and management. Oral Dis. 2005; 11(6): 338–349. PubMed Abstract | Publisher Full Text\n\nVan Der Meij EH, Schepman KP, Smeele LE, et al.: A review of the recent literature regarding malignant transformation of oral lichen planus. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1999; 88(3): 307–310. PubMed Abstract | Publisher Full Text\n\nThongprasom K, Luangjarmekorn L, Sererat T, et al.: Relative efficacy of fluocinolone acetonide compared with triamcinolone acetonide in treatment of oral lichen planus. J. Oral Pathol. Med. 1992; 21(10): 456–458. PubMed Abstract | Publisher Full Text\n\nChamani G, Rad M, Zarei MR, et al.: Efficacy of tacrolimus and clobetasol in the treatment of oral lichen planus: A systematic review and meta-analysis. Int. J. Dermatol. 2015; 54(9): 996–1004. PubMed Abstract | Publisher Full Text\n\nAl-Maweri SA, Ashraf S, Kalakonda B, et al.: Efficacy of photodynamic therapy in the treatment of symptomatic oral lichen planus: A systematic review. J. Oral Pathol. Med. 2018; 47(4): 326–332. PubMed Abstract | Publisher Full Text\n\nFahimeh R, Neshat A, Jannan G: Oral lichen planus resistency to topical corticosteroid therapy. Middle-East J. Sci. Res. 2013; 16(9). Publisher Full Text\n\nGarcía-Pola MJ, González-Álvarez L, Garcia-Martin JM: Treatment of oral lichen planus. Systematic review and therapeutic guide. Med. Clin (Barc). (English Edition). 2017; 149(8): 351–362. PubMed Abstract | Publisher Full Text\n\nAkram Z, Javed FD, Hosein M, et al.: Photodynamic therapy in the treatment of symptomatic oral lichen planus: A systematic review. Photodermatol. Photoimmunol. Photomed. 2018; 34(3): 167–174. PubMed Abstract | Publisher Full Text\n\nHoseinpour Jajarm H, Asadi R, Bardideh E, et al.: The effects of photodynamic and low-level laser therapy for treatment of oral lichen planus—A systematic review and meta-analysis. Photodiagn. Photodyn. Ther. 2018; 23: 254–260. PubMed Abstract | Publisher Full Text\n\nPavlic V, Vujic-Aleksic V: Phototherapy approaches in treatment of oral lichen planus. Photodermatol. Photoimmunol. Photomed. 2014; 30(1): 15–24. PubMed Abstract | Publisher Full Text\n\nZhu TC, Finlay JC: The role of photodynamic therapy (PDT) physics. Med. Phys. 2008; 35(7): 3127–3136. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRakesh N, Ben CJ, Reddy SS, et al.: Clinical evaluation of photodynamic therapy for the treatment of refractory oral Lichen planus – A case series. Photodiagn. Photodyn. Ther. 2018; 24: 280–285. PubMed Abstract | Publisher Full Text\n\nSulewska M, Duraj E, Sobaniec S, et al.: A clinical evaluation of efficacy of photodynamic therapy in treatment of reticular oral lichen planus: A case series. Photodiagn. Photodyn. Ther. 2019; 25: 50–57. PubMed Abstract | Publisher Full Text\n\nKvaal SI, Angell-Petersen E, Warloe T: Photodynamic treatment of oral lichen planus. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2013; 115(1): 62–70. Publisher Full Text\n\nSulewska M, Duraj E, Sobaniec S, et al.: A clinical evaluation of the efficacy of photodynamic therapy in the treatment of erosive oral lichen planus: A case series. Photodiagn. Photodyn. Ther. 2017; 18: 12–19. PubMed Abstract | Publisher Full Text\n\nChen HM, Yu CH, Tu PC, et al.: Successful treatment of oral verrucous hyperplasia and oral leukoplakia with topical 5-aminolevulinic acid-mediated photodynamic therapy. Lasers Surg. Med. 2005; 37(2): 114–122. PubMed Abstract | Publisher Full Text\n\nAl-Maweri SA, Kalakonda B, Al-Soneidar WA, et al.: Efficacy of low-level laser therapy in management of symptomatic oral lichen planus: a systematic review. Lasers Med. Sci. 2017; 32(6): 1429–1437. PubMed Abstract | Publisher Full Text\n\nNamjoshi S, Caccetta R, Edwards J, et al.: Liquid chromatography assay for 5-aminolevulinic acid: Application to in vitro assessment of skin penetration via Dermaportation. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2007; 852(1-2): 49–55. PubMed Abstract | Publisher Full Text\n\nNagi R, Muthukrishnan A, Rakesh N: Effectiveness of photodynamic therapy (PDT) in the management of symptomatic oral lichen planus -A systematic review. J Oral Biol Craniofac Res. 2023; 13(2): 353–359. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSattayut S: CARE flow and checklist: Recalcitrant Oral Lichen Planus Involving Bilaterally Buccal Mucosae Treated with A Combination of Photodynamic and Photobiomodulation Therapies: A Case Report. figshare. Journal contribution. 2024. Publisher Full Text"
}
|
[
{
"id": "264352",
"date": "26 Apr 2024",
"name": "Chun Hung Chu",
"expertise": [
"Reviewer Expertise Preventive Dentistry",
"Community Dentist",
"Fluoride Research",
"Dental LASER"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript is well-organised and provides valuable laser application parameters for treating oral lichen planus (OLP). It offers significant guidance for clinical laser applications targeting OLP. Here are some minor suggestions: 1. In the abstract, the case presentation section could include the patient's main complaint, the progression of the disease, and the clinical examination. For example, it would be helpful to mention the duration of the disease, previous therapies attempted (to correspond with the title \"recalcitrant\"), and the size of the oral lesion. By incorporating this information, the beginning part of the results section could be moved to the case presentation section. 2. For figures 1 and 8, it would be beneficial if the authors adjusted the pictures to the same size, as it would improve the overall appearance and tidiness. 3. As a follow-up case report, it would be more compelling if the authors could provide contrasting intraoral photos after the initial 5 sessions of photodynamic therapies and subsequent 5 sessions of photobiomodulation therapies, as well as photos taken after a 3-year follow-up. This additional evidence would strengthen the article. Overall, this manuscript is meaningful and provides valuable insights.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": [
{
"c_id": "11763",
"date": "14 Jun 2024",
"name": "Sajee Sattayut",
"role": "Author Response",
"response": "We are grateful to the reviewer for their valuable and insightful comments on our report. We are incorporating the suggestion of modification and will provide an updated version shortly."
}
]
},
{
"id": "275899",
"date": "08 Jun 2024",
"name": "Alberto Rodriguez-Archilla",
"expertise": [
"Reviewer Expertise Oral pathology and 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\nThis is an interesting case report of a recalcitrant oral lichen planus treated with a combination of photodynamic with photobiomodulation therapies. The manuscript contains four keywords, eight figures with twelve sections, one table, and twenty-six references. Overall, it is a correct, complete, and well-documented case report.\nStudy Strengths - The authors report a case of a 43-year-old male patient with oral lichen planus (OLP) whose lesions did not resolve with either prednisolone systemic steroids (prednisolone) or topical corticosteroids (fluocinolone). After undergoing ten sessions of photodynamic therapy (PDT) with 10% 5-Aminolevulinic acid (5-ALA) in the form of thermoplastic gel and a 635 nm diode laser at 100 to 400 mW with an energy density of 20 to 30 J/cm2 in continuous wave mode, combined with five interim-sessions of photobiomodulation therapy (PBMT) using a 635 nm diode laser at 200 to 300 mW with an energy density of 6 to 10 J/cm2 in continuous wave, the patient reported relief of burning sensation beside remission of lesions without any complications. - As this paper highlights, some oral lichen planus (OLP) lesions do not respond adequately to corticosteroid therapy. Photodynamic and photobiomodulation therapies could be an alternative therapeutic option for the treatment of recalcitrant OLP lesions. Photodynamic therapy (PDT) favors the removal of lesions without surgery. Photobiomodulation therapy (PBMT) can promote healing and recovery of the OLP lesions.\nStudy Weaknesses - Case reports include some limitations such as they can have the bias to publish particularly favourable results; they have no epidemiological value because it is not possible to infer causality; they are necessarily retrospective, so they may lack some important uncollected data. - A single case report is not sufficient to adequately assess the efficacy of therapeutic alternatives (PDT, PBMT) in the treatment of oral lichen planus.\nSome additional remarks are made on different sections of the manuscript.\nKeywords The manuscript presents four keywords. For keywords, where possible, please use Medical Subject Headings terms (MeSH Terms). Strictly, none of them is a MeSH term. Some alternative MeSH terms proposed could be “lichen planus, oral” better than “oral lichen planus”; \"photosensitizing agents\" rather than “photosensitizer”; \"low level light therapy\" or \"laser therapy\" instead of “low-intensity laser therapy”. Nevertheless, these suggestions about keywords are optional, not mandatory.\nOther manuscript sections Abbreviations and acronyms, even well-known ones, should be explained the first time they are used, e.g. 5-ALA, ASA PS I, etc. To make text understanding easier, if the author's name appears in the text, place the reference number immediately after the name, not at the end of the sentence or paragraph. Please, revise this, especially in the discussion section.\nReferences Total number of the manuscript references: 26.\nFigures Total number of the manuscript figures: 8 (figure 1 A, B, C, and D; figure 2; figure 3 A and B; figure 4; figure 5; figure 6 A and B; figure 7 A and B; figure 8 A, B, C, and D). The figures have appropriate figure legends.\nTables Total number of the manuscript tables: 1. The table has an appropriate title and information. Nevertheless, the abbreviation 5-ALA should be explained.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": [
{
"c_id": "11764",
"date": "14 Jun 2024",
"name": "Sajee Sattayut",
"role": "Author Response",
"response": "We greatly appreciate the reviewer for bringing important issues to our attention in the case report. We are aware of the limitations of the case report and planning further studies. We will also consider your kind suggestion regarding the keywords."
}
]
}
] | 1
|
https://f1000research.com/articles/13-152
|
https://f1000research.com/articles/13-149/v1
|
01 Mar 24
|
{
"type": "Study Protocol",
"title": "An observational prospective study of mucocutaneous adverse effects of chemotherapeutic drugs and radiotherapy",
"authors": [
"Kaveri Rusia",
"Bhushan Madke",
"Bhushan Madke"
],
"abstract": "Background There is an enormous advancement in chemotherapeutic drugs and radiotherapy. With the advancement, the adverse effects in patients receiving chemotherapeutic drugs and radiotherapy have also increased. Hence identifying and treating adverse effects of chemotherapeutic drugs and radiotherapy is of utmost importance for patients. This study will help us to find out the various mucocutaneous adverse effects associated with various new chemotherapeutic drugs and radiation. Our objective is to find out the frequency of mucocutaneous manifestation in patients receiving chemotherapy and radiotherapy and also to know and assess the various patterns and severity of mucocutaneous involvement in chemotherapy and radiotherapy.\n\nMethods This will be an observational prospective study that will be conducted in a tertiary care cancer hospital [Siddharth Gupta Memorial Cancer Hospital] and patients coming to OPD of AVBRH in the Department of Dermatology from 15th December 2023 to 15 September 2024, who will be presenting with the mucocutaneous adverse effects. Detailed History and Cutaneous examination will be performed and graded according to Common Terminology Criteria for Adverse Events v5. The various mucocutaneous adverse effects will be compiled and grading will be done. This study will help us to find out the various mucocutaneous adverse effects associated with various new chemotherapeutic drugs and radiation.\n\nResults We will study the various mucocutaneous manifestations in patients with solid organ malignancy or hematological malignancy receiving chemotherapy and radiotherapy.",
"keywords": [
"Chemotherapeutic drugs",
"Radiation",
"mucocutaneous adverse effects",
"nail discoloration",
"alopecia",
"hormone therapy",
"radiation dermatitis",
"chemotherapy"
],
"content": "Introduction\n\nOur understanding of cancer and treatment approaches has advanced significantly over the years. The management of cancer has become more difficult as cancer prevalence rises, making it a challenge for modern clinical care. Cancer patients are currently being treated using a variety of methods, including radiotherapy, chemotherapy, combination therapy, immunotherapy, and hormone therapy.1 Modernized equipment and increasingly sophisticated restorative regimens have revolutionized functionality and greatly reduced, but not eliminated, the negative effects they produce on the body. The negative effects of chemotherapy on the skin, nails, and hair can significantly lower the quality of life and cause therapy to be discontinued. significant advancements. The creation of anticancer agents has seen significant advancements. The importance of genetic changes is particularly highlighted by the development of targeted treatments for the treatment of solid cancers. Through this advancement, cancer patient’s chances of survival and quality of life have increased, and hematological and non-specific toxicities have decreased in tandem. A new and broad spectrum of dermatologic adverse effects have, however, also emerged as a result of the introduction of newer drugs.2\n\nHyperpigmentation, alopecia, radiation recall, hand-foot syndrome, hypersensitivity, extravasation injuries, and nail dystrophies are among the most common cutaneous reactions. Although most post-chemotherapy side effects are not life-threatening, they can nonetheless be stressful for the patient, especially if they result in baldness. In rapidly growing cells like skin, adnexa, and mucous membranes, chemotherapeutic drugs’ toxicities, and unfavorable effects can be noticed. While other adverse effects including erythema, hyperpigmentation, rash, and hypersensitivity happen less frequently, the side effects that occur in these rapidly reproducing cells are typically dose-dependent. The administration of chemotherapy medications needs to be done cautiously since extravasation of intravenous chemotherapy medications might result in serious skin irritation and necrosis.3\n\nPhototoxicity, the recall phenomenon, and radiation enhancement are three examples of cutaneous adverse effects that are linked to the interaction between chemotherapy and radiation. Other, less common side effects such as sclerodermiform dermatitis, Raynaud’s phenomenon, and hypersensitivity syndrome are also discussed. Sometimes cutaneous side effects are rather exclusive to a particular class of medication. Taxanes are most frequently connected to capillary leak syndrome. Perhaps as a result of the drug’s prolonged use, hydroxyurea causes certain odd cutaneous side effects (ulcerations, pseudodermatomyositis). Despite the frequent and occasionally severe mucocutaneous adverse effects of chemotherapy, stopping the offending medication is rarely necessary. However, dose adjustments or measures to prevent some of these adverse effects are still required.4\n\nAlopecia is one of the most frequent dermatologic adverse effects of chemotherapy. Drugs frequently target the rapidly producing hair cells. As a result, the production of hair shafts is lost, resulting in weak, frizzy hair. The scalp’s terminal hair follicles, which produce hair more quickly than axillary, pubic, or slower-growing brow, eyelash, or axillary hair, are more affected. Chemotherapy-induced alopecia is reversible, and hair regrowth occurs with a change in texture and color (switching from straight to curly).2\n\nThe Palmar-plantar erythrodysesthesia, also called the hand-foot condition, is characterized by erythematous, painful lesions on the skin that affect the palms and soles. and was first noticed in patients receiving high doses of cytarabine medication.2 After 2 to 12 days of medication exposure, the patient often has a burning feeling on their hands and feet, which is followed by a severe erythema that is symmetrical and well-defined. The dorsal and lateral fingers, as well as the periungual skin, are frequently affected after the lesions are initially noticed on the thenar and hypothenar eminences of the palms.5 Eventually, the entire hand or foot may be affected, causing swelling and potentially the appearance of vesicles or bullae. After weeks to years of radiation, doxorubicin, in particular, causes the development of radiation dermatitis. Dermatologic symptoms can be desquamation, vesicle development, and maculopapular eruptions with erythema. From a minor rash to a serious case of skin necrosis, reactions can vary in severity. Nail alterations for chemotherapy patients happen regularly. The presence of transverse ridges is indicative of cyclic damage to the nail matrix.2\n\nIonizing radiation is a crucial therapeutic option for cancer patients. Tissues can undergo a variety of functional and structural changes as a result of radiation. The overall radiation dose, the amount of tissue exposed, and the duration between radiation doses are just a few of the variables that affect how much radiation damage there is. The highly oxygenated cells and proliferative cells are the most vulnerable to radiation damage. The most radiosensitive cells in the integumentary system are basal keratinocytes, hair follicle stem cells, and melanocytes.6\n\nHypersensitivity responses, contact dermatitis, vasculitis, and fixed drug eruptions are frequent misdiagnoses for the skin symptoms brought on by chemotherapy and radiotherapy. Patients receiving chemotherapy and radiotherapy frequently experienced changes in skin, nails, hair, and mucosa as serious side effects. To increase patient compliance, it is crucial to understand the range and presentation of mucocutaneous symptoms in those undergoing chemotherapeutic medicines and radiation therapy.\n\nWith the introduction of newer modalities and upgradation in the treatment of cancer there is an increase in the survival rate of cancer patients but at the same time, there is an increase in adverse effects of chemotherapeutic drugs and radiotherapy. The administration of chemotherapeutic drugs can lead to a host of mucocutaneous manifestations ranging from adverse effects that are specific to drugs like flagellate dermatitis caused by bleomycin to non-specific toxic reactions like painful erythema involving hands and feet, intertriginous areas by a variety of drugs like Cytarabine, Doxorubicin, Capecitabine, Paclitaxel. The skin manifestations caused by chemotherapy and radiotherapy are often misdiagnosed as hypersensitivity reactions, contact dermatitis, vasculitis, and fixed drug eruptions. Therefore, it is important to identify the various presentations of mucocutaneous manifestations in patients receiving chemotherapeutic drugs and radiotherapy to improve the compliance of the patient.\n\n\nObjectives\n\n\n\n• To find out the frequency of mucocutaneous manifestation in patients receiving chemotherapy.\n\n• To find out the frequency of mucocutaneous manifestation in patients receiving radiotherapy.\n\n• To know the various patterns of mucocutaneous involvement in chemotherapy.\n\n• To know the various patterns of mucocutaneous involvement in radiotherapy.\n\n• To assess the severity of mucocutaneous involvement with the chemotherapeutic drugs.\n\n\nMethods\n\nAn observational prospective study.\n\nSetting: Tertiary care cancer hospital [Siddharth Gupta Memorial Cancer Hospital] or Acharya Vinoba Bhave Rural Hospital, Sawangi\n\nLocation: Rural Central India\n\nRecruitment: 15th December 2023 to 15th September 2024.\n\n150 patients having malignancy receiving chemotherapy or radiotherapy including both genders and all age groups coming to OPD of Tertiary Care Cancer Hospital [Siddharth Gupta Memorial Cancer Hospital] and OPD of Acharya Vinoba Bhave Rural Hospital, Sawangi will be enrolled.\n\n\n\nWhere Z α/2 is the level of significance at 5% i.e., 95%\n\nAlpha [α] is 0.05\n\nThe estimated proportion of malignancy [p] is 84%\n\nEstimated error [d] is 6%\n\nSample size [n] = 144\n\nSample size [n] = 150\n\n\n\n• Patients receiving chemotherapy and radiotherapy irrespective of their age and sex.\n\n• Patients willing to participate.\n\n\n\n• Patient with mucocutaneous manifestation due to malignancy.\n\n• Known Prior primary dermatoses\n\n• Drug reaction due to Non-Chemotherapeutic Drugs\n\n• Mucocutaneous manifestation of Paraneoplastic syndromes\n\nThe approval for the study was given by the Institutional Ethics Committee on 15th July 2022 [DMIMS (DU)/IEC/2022/24]. Informed consent will be taken from the patients.\n\nAll patients will be asked to voluntarily participate and provide their written and signed informed permission. A thorough history will be taken, along with a dermatological examination. Additionally, to other clinical information, mucocutaneous side effects will be included. The parameter includes patient demographic information (age, gender, occupation, address, marital status), cancer diagnosis and prognosis information, and treatment information (drugs/routine, formulation, bolus/infusion, route of administration, frequency of administration, cycles of drug therapy, duration of treatment) as well as information on the drugs used and their dosages. According to this grading, mucocutaneous adverse effects will be classified from Grade 1 to Grade 5. The grading will be based on Common Terminology Criteria for Adverse Events v5. 0.\n\nAll the results will be calculated using SPSS version 22 (RRID:SCR_002865). Demographic data for the study variable will be tabulated in frequency, percentage, and median for qualitative analysis. Comparative evaluation of chemotherapy and radiotherapy cycles will be analyzed for adverse effects on frequency and percentage basis.\n\nIt is a hospital-based study, not a population-based study.\n\nFor the prevention of selection bias, random selection will be followed for the selection of participants.\n\n\nDiscussion\n\nIt is highly common for patients following chemotherapy and radiation therapy to present with a variety of mucocutaneous symptoms. If these symptoms occur frequently, it can lower the patient’s quality of life. The adverse effects might be asymptomatic observations, incapacitating symptoms, or a combination of these.\n\nIn a descriptive study of 226 patients, Naveed S et al.2 found that the most common symptom was nail changes (194; 5.84%). Discoloration of nails was more common in patients receiving combination therapy than chemotherapy alone. The second most common manifestation was skin changes (191; 84.51%), followed by hair changes (159; 70.35%), mucosal involvement (34; 15.04%), and other non-specific presentations. The most frequent negative impact on the skin was skin pigmentation. Other skin abnormalities included hirsutism, hypertrichosis, and alopecia.2\n\nSusser et al.7 in a study has found that the most common adverse effect of cancer chemotherapy was Alopecia. Anagen effluvium was most commonly produced by Anticancer agents. Oral mucositis although was a dose-limiting side effect, affects almost 40% of individuals. The drugs most commonly associated with oral mucositis were bleomycin, docetaxel, and daunorubicin.7\n\nBiswal SG et al.8 conducted an observational study of 1000 receiving chemotherapy. Out of 1000 patients, 384 presented with any one of the dermatological manifestations. Anagen Effluvium was the most common affecting 78.6% of patients. The other less common manifestations were Sweet syndrome and Bullous Photodermatitis.8\n\nLalla RV et al.9 conducted a study and reported the oral complication in patients receiving chemotherapy and radiotherapy was Oral mucositis affecting 20 to 40% of patients. The pain associated with oral mucositis has led to a reduction in chemotherapy and radiotherapy doses.9\n\nGabriella et al.10 in their study of 100 patients receiving chemotherapeutic drugs. The patients on EGFR inhibitor developed papulopustular reaction [55.8%], dry skin [41.17%], nail alterations [29.41%], and alopecia [17.64%].10\n\nIn their descriptive analysis of 53 chemotherapy patients, Pavey et al.11found that the most prevalent mucocutaneous adverse effects were changes to the nails (33; 62.2%), then changes to the hair (20; 37.7%), skin (19; 33.9%), and mucosa (2; 3.7%).11\n\nIn a study conducted by Zeynep Utlu et al.12 total of 128 patients were enllored and divided into two groups one receiving classic chemotherapeutic agents and the other receiving targeted agents The majority of the adverse effects, xerosis, were observed in 93 (72.7%) of the 128 individuals. Alopecia, mucositis, pruritus, pigmentation of skin, and hand-foot erythema were other common adverse effects. In the traditional chemotherapeutic group, xerosis, pruritus, alopecia, and nail alterations were the most frequently reported adverse effects, occurring in 71 (75.5%) individuals, 50 (53.2%), 49 (52.1%), and 43 (45.7%) of the patients. In the targeted chemotherapeutic group, xerosis (22/64.7%), nail alterations (17/50%), alopecia (15/44.1%), and pruritus (13/38.2%) were the most frequently reported adverse effects.12\n\nHospital-based observational research was carried out by Menon A et al.13 with the participation of 100 patients, including 37 female and 63 male patients. Hair was the most often seen adverse impact among the cutaneous side effects, followed by changes in the skin, changes in nails, and mucosal involvement. The most often noted negative effects on the skin were hyperpigmentation and xerosis.13\n\nThapa DP et al.14 performed hospital-based research in which 62 patients in all were included. Eczema accounted for 39% of all dermatoses, with infection coming in at 25%, pruritus at 14%, insect bite hypersensitivity at 3.2%, pilosebaceous unit disorder at 3.2%, urticaria at 3.2%, pigmentary alterations at 3.2%, nail involvement at 3.2%, drug rash at 2%, vesiculo-blistering disorder at 2%, and cutaneous metastases at 2%.14\n\nThe expected outcome variables include xerosis of skin, hyperpigmentation, and hypopigmentation of skin, erythema multiforme, eczema, photosensitivity, palmoplantar erythrodysesthesia syndrome, purpura, maculopapular rash, acneiform eruptions, urticaria, skin ulceration about the skin. The involvement of hair in the form of Alopecia which is defined as a decrease in the density of hair compared to normal for a given individual at a given age and body location. Other hair abnormalities are hypertrichosis, hirsutism, and changes in hair texture and color. Nail changes can be nail discoloration which is a change in the color of the nail plate, nail loss, and nail ridging. Oral mucosa involvement in the form of oral mucositis, and oral candidiasis. Other miscellaneous changes are pruritus, hyperhidrosis, hypohidrosis, and erythroderma. These changes will then be graded according to the Common Terminology Criteria for Adverse Events v5. 0. into 5 grades from Grade 1 to Grade 5 and will be evaluated for adverse effects in frequency and percentage. Association with the demographic variables will be performed using chi-square and odd analysis.\n\nEthical approval was obtained and recruitment of the study participants has not yet begun.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nHood AF: Cutaneous side effects of cancer chemotherapy. Med. Clin. North Am. 1986 Jan 1; 70(1): 187–209. Publisher Full Text\n\nNaveed S, Thappa DM, Dubashi B, et al.: Mucocutaneous adverse reactions of cancer chemotherapy and chemoradiation. Indian J. Dermatol. 2019 Mar; 64(2): 122–128. PubMed Abstract | Publisher Full Text\n\nAlley E, Green R, Schuchter L: Cutaneous toxicities of cancer therapy. Curr. Opin. Oncol. 2002 Mar 1; 14(2): 212–216. Publisher Full Text\n\nGuillot B, Bessis D, Dereure O: Mucocutaneous side effects of antineoplastic chemotherapy. Expert Opin. Drug Saf. 2004 Nov 1; 3(6): 579–587. Publisher Full Text\n\nPrussick R: Adverse cutaneous reactions to chemotherapeutic agents and cytokine therapy. Semin. Cutan. Med. Surg. 1996 Dec 1; 15(4): 267–276. PubMed Abstract | Publisher Full Text\n\nBaskar R, Lee KA, Yeo R, et al.: Cancer and radiation therapy: current advances and future directions. Int. J. Med. Sci. 2012; 9(3): 193–199. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSusser WS, Whitaker-Worth DL, Grant-Kels JM: Mucocutaneous reactions to chemotherapy. J. Am. Acad. Dermatol. 1999 Mar 1; 40(3): 367–398. Publisher Full Text\n\nBiswal SG, Mehta RD: Cutaneous adverse reactions of chemotherapy in cancer patients: a clinicoepidemiological study. Indian J. Dermatol. 2018 Jan; 63(1): 41–46. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLalla RV, Saunders DP, Peterson DE: Chemotherapy or radiation-induced oral mucositis. Dent. Clin. North Am. 2014 Apr 1; 58(2): 341–349. PubMed Abstract | Publisher Full Text\n\nFabbrocini G, Cameli N, Romano MC, et al.: Chemotherapy and skin reactions. J. Exp. Clin. Cancer Res. 2012 Dec; 31(1): 1–6. Publisher Full Text\n\nPavey R, Kambil S, Bhat R: Dermatological adverse reactions to cancer chemotherapy. Indian J. Dermatol. Venereol. Leprol. 2015 Jul 1; 81(4): 434. PubMed Abstract | Publisher Full Text\n\nUtlu Z, Bilen H: Evaluation of cutaneous side-effects associated with chemotherapeutic use in oncological patients. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2021 Nov 1; 37(1).\n\nMenon A, Handattu S, Shetty J, et al.: Study of cutaneous adverse effects of cancer chemotherapy. Clin. Dermatol. Rev. 2018 Jan 1; 2(1): 19. Publisher Full Text\n\nThapa DP: Dermatological manifestations in cancer patients: a hospital-based study. Nepal Med. Coll. J. 2018 Dec 31; 20(4): 128–132. Publisher Full Text"
}
|
[
{
"id": "268034",
"date": "14 May 2024",
"name": "Madjid Soltani",
"expertise": [
"Reviewer Expertise Transport Phenomena in Tissues Mathematical Cancer Modeling Biomedical Engineering Image Based Cancer Modeling CFD"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 was carefully studied and examines the adverse mucocutaneous effects of chemotherapy and radiotherapy drugs. The author first introduces the different types of these complications, and then describes the mechanisms of their creation. This article also addresses the challenges involved in studying and treating these complications. The strengths of this article include providing a comprehensive overview of these complications, citing authoritative scientific sources, and providing useful information for medical professionals and patients. However, the paper could have been stronger by focusing more on specific complications, patient management and providing a clear summary at the end of the paper. The following are also presented as tips for improving the article: 1- While the background is informative, it doesn't explicitly state how the study adds new knowledge. Consider emphasizing the specific gap you're addressing in the research on mucocutaneous side effects. 2-The objectives could be more specific. For example, instead of just \"find out the frequency\" of side effects, you could focus on comparing frequencies between chemotherapy and radiotherapy or across different patient demographics. 3-While you mention using chi-square and odds analysis, you could elaborate on how you'll be using these tests to analyze your data. 4-Provide more details on chemotherapy drugs and radiotherapy techniques included in this study. 5-It seems that by using more recent articles in this field, you can well describe the background of the research and the work that has been done in this field so far.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Partly\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "11559",
"date": "26 Jun 2024",
"name": "Kaveri Rusia",
"role": "Author Response",
"response": "Thank you for your valuable response. I will keep in mind the changes suggested by you."
},
{
"c_id": "13216",
"date": "27 Jan 2025",
"name": "Kaveri Rusia",
"role": "Author Response",
"response": "Thank you for your valuable opinion."
}
]
}
] | 1
|
https://f1000research.com/articles/13-149
|
https://f1000research.com/articles/11-1460/v1
|
09 Dec 22
|
{
"type": "Method Article",
"title": "Bayesian Multi-View Clustering given complex inter-view structure",
"authors": [
"Benjamin D. Shapiro",
"Alexis Battle",
"Benjamin D. Shapiro"
],
"abstract": "Multi-view datasets are becoming increasingly prevalent. These datasets consist of different modalities that provide complementary characterizations of the same underlying system. They can include heterogeneous types of information with complex relationships, varying degrees of missingness, and assorted sample sizes, as is often the case in multi-omic biological studies. Clustering multi-view data allows us to leverage different modalities to infer underlying systematic structure, but most existing approaches are limited to contexts in which entities are the same across views or have clear one-to-one relationships across data types with a common sample size. Many methods also make strong assumptions about the similarities of clusterings across views. We propose a Bayesian multi-view clustering approach (BMVC) which can handle the realities of multi-view datasets that often have complex relationships and diverse structure. BMVC incorporates known and complex many-to-many relationships between entities via a probabilistic graphical model that enables the joint inference of clusterings specific to each view, but where each view informs the others. Additionally, BMVC estimates the strength of the relationships between each pair of views, thus moderating the degree to which it imposes dependence constraints. We benchmarked BMVC on simulated data to show that it accurately estimates varying degrees of inter-view dependence when inter-view relationships are not limited to one-to-one correspondence. Next, we demonstrated its ability to capture visually interpretable inter-view structure in a public health survey of individuals and households in Puerto Rico following Hurricane Maria. Finally, we showed that BMVC clusters integrate the complex relationships between multi-omic profiles of breast cancer patient data, improving the biological homogeneity of clusters and elucidating hypotheses for functional biological mechanisms. We found that BMVC leverages complex inter-view structure to produce higher quality clusters than those generated by standard approaches. We also showed that BMVC is a valuable tool for real-world discovery and hypothesis generation.",
"keywords": [
"clustering",
"multi-view",
"Bayesian models",
"gene expression",
"methylation",
"multi-omics",
"public health"
],
"content": "Introduction\n\nIn biomedicine, public health, and a number of other fields, an unprecedented availability of increasingly diverse large-scale data related through complex mechanisms, both known and unknown (e.g. multi-omic patient information in combination with clinical and demographic data), has sparked the need for unsupervised machine learning methods that leverage both quantity and diversity of information. For many years, the field of machine learning has primarily emphasized questions of data abundance (e.g. high dimensionality). However, approaches tailored to integrative analysis and multi-view learning have recently come into focus. By leveraging the structure shared between multiple views of the same system, we expect to improve the quality of data clustering in any given view. We are thus able to construct a more informed representation of the latent structure and any properties unique to a particular modality. Discovery of this kind can improve our understanding of both the high- and low-level functional mechanisms that describe the system. As the heterogeneity and complexity of data sources steadily increases, it is critical to scientific advancement that we conceive of more flexible and interpretable machine learning approaches to understanding diverse, multi-modal collections of related data.\n\nSeveral useful frameworks for multi-view clustering exist to-date, but these share the assumption that the cross-domain relationships between entities are one-to-one, i.e. that each view measures the same set of units. One of the most utilized models in this class, iCluster1 and its extensions2–4 use a joint latent variable model to integrate all data types and produce a single integrated clustering. These consensus-focused approaches employ a variety of strategies to learn an integrated representation rather than individual clusterings of the views. In contrast, the Multiple Dataset Integration (MDI) approach5 aims to learn individual clusterings at a view-per-view granularity while incorporating known dependencies. Bayesian Consensus Clustering6 and Clusternomics7 also produce individual clusterings and jointly infer explicit global structure. These approaches provide more insight into the underlying mechanisms and unique properties governing the structure in each view than might be available when using consensus-focused approaches but are limited by their one-to-one assumption.\n\nCritically, the one-to-one assumption quickly breaks down in many applications where sets of entities differ across views. In these cases there may be a many-to-one or many-to-many correspondence between views, and certain entities may not have corresponding related entities measured across all domains. For example, we may want to cluster epigenetic data across the genome (view 1) alongside related gene expression (view 2) and protein level (view 3) measurements. Methylation profiles in particular typically consist of many more entities (probes) than gene expression profiles (genes) with multiple probes mapping to, or near, a single gene; in some cases, a probe may not correspond to any of the measured genes. A gene may likewise correspond to more than one protein product due to alternative splicing effects8 or to no protein if the gene is not protein-coding. Across domains, one common solution to this problem is to condense each dataset in order to force a strict one-to-one correspondence between views by combining or discarding measurements via some heuristic. The first shortcoming of this approach is that it eliminates information across modalities thereby reducing power. Furthermore, it can lead to downstream models which fail to account for important inter-view relationships. In addition, the extent to which relationships between views should bias estimates of intra-view structure is not always obvious. As such, another critical task is to learn the degree to which clusterings should inform one another. These challenges motivate methods of multi-view clustering that can intelligently account for more complex relationships between views.\n\nMost recent efforts to address these challenges rely on extensions of non-negative matrix factorization9 or its multi-view variant multiNMF.10 Co-regularized Graph Clustering (CGC)11 poses the problem as a multi-view graph clustering and, as we do, assumes that the inter-view relationships are known a priori. Given a primary view of interest (the view “in focus”), CGC estimates the relative contributions of all other views to the overall clustering. Complex Mapping Multi-View Clustering (CMMVC)12 takes a similar approach and additionally proposes a method for estimating unknown inter-view relationships as a pre-processing step. These approaches lack some of the flexibility and interpretability of probabilistic approaches like the model we propose here, and also require some additional assumptions such as choosing a primary view. Similar efforts have been to made to perform multi-view clustering in contexts where data is incomplete. Incomplete multi-view clustering algorithms (IMC)13–16 often rely on matrix factorization, graph learning, kernel and/or deep approaches to construct a representation of the data from which a consensus clustering can be learned from the incomplete data. These solutions relate to part of the problem we pose here where relationships may be missing but not where relationships may extend beyond a one-to-one mapping. There may also be cases where an entity in one view may not be related to an entity in another view, but not due to missing data; in these cases, the assumption of incompleteness made by IMC is not always appropriate. Finally, it is again important to note that little to none of the existing work in this area has taken a fully Bayesian approach.\n\nHere we propose Bayesian Multi-View Clustering (BMVC), an approach that uses a novel graphical model to jointly learn the strength of every pairwise relationship between views, along with a separate clustering within each view that takes into account user-supplied inter-view relationships. A key contribution of BMVC is that it is a Bayesian approach based on mixture models, similar to that used in MDI.5 This flexible probabilistic framework allows users to model a variety of data types; quantify uncertainty; and incorporate a variety of assumptions by specifying priors on the mixture component distributions, the sparsity of component weights, and the weight of the inter-view dependency. The cluster base distribution used in BMVC may be chosen to fit key assumptions regarding the latent distribution of the data (e.g. allowing Gaussian process component priors to model clusters of time series data). Most importantly, to the best of our knowledge, BMVC is the first Bayesian clustering approach to rigorously leverage complex inter-view relationships between entities – such as one-to-many, many-to-many or one-to-zero relationships – to improve clustering quality.\n\n\nMethods\n\nLet v ∈ 1…V index the corresponding view in a V-view clustering application, and let k ∈ 1…K index a cluster. For ease of notation, assume the same total number of clusters K across all views, although the full model permits specification of Kv on a per-view basis. Note that even with fixed K, the true numbers of clusters learned in each view are not required to be the same or exactly K; they may be arbitrarily smaller if elements are assigned to only a subset of clusters and others are left empty in the most likely clustering found via inference. The BMVC model likelihood can be viewed as a modification of the joint likelihood of V independent mixture models with an additional term encouraging related entities to cluster similarly across views. The probabilistic graphical model is shown in plate notation in Figure 1.\n\nFurther views may be incorporated in a similar fashion. Gray nodes denote variables known a priori.\n\nLet x be the data, Gv be the probability density function of the component distribution parameterized by θ, z be the component assignments and π be the K-dimensional vector of mixture weights. Further, we specify priors on the θ using a base distribution G0 parameterized by β, and Dirichlet priors on the mixture weights (πv) parameterized by α. Let v and i respectively index the view and entities of the data such that xvi refers to entity i in view v and zvi refers to the corresponding cluster assignment. Assume the following prior distributions:\n\nFor simplicity, we denote the number of entities for view v as Nv. Building up from a standard mixture model with no ties between views, the conditional joint probability of all the component assignments Z of V independent Gaussian mixture models is merely a product of their priors dictated by π:\n\nIn addition to the standard mixture model priors described above, we specify three additional variables R, C and ϕ:\n\n• Let Rvu be a known, user-specified indicator matrix that encodes the graph of related entities between two views indexed v and u. Note that R may also have continuous positive values that describe known relationship weights. Specifically, assume that Rvu [i, j] is non-zero if a relationship exists between entity xvi and xuj. For example, if the views respectively measure gene expression and methylation, then R should be non-zero where gene i is regulated by methylation probe j.\n\n• Let Cvu be a latent indicator matrix that encodes the graph of related matrices between two views indexed v and u, where every row and column has exactly one indicator. This reflects the assumption that every cluster in a view has a single corresponding cluster in another. Specifically, assume that Cvu [k, l] is non-zero if cluster k in view v relates to cluster i in view u.\n\n• Let ϕvu∈ℝ+ be a latent variable representing the overall strength of the relationship between views v and u.\n\nWe place a conditional joint prior on the traditional mixture model cluster assignments as follows:\n\nComparing the assignment strategy that results from this prior with that of the traditional mixture model, we see that BMVC increases the probability of a clustering assignment for a given entity if any related entity across views is assigned to a cluster with the same label. Note that the expression requires a normalization constant to define a distribution (as in a Markov random field). The normalization constant Z¯ is computed by summing this quantity over all possible cluster assignments of all the entities across the views. Assume each view v ∈ 1…V is associated with a number of clusters Kv, and a number of entities Nv:\n\nWe perform approximate inference to jointly learn the optimal values for the cluster weights π, cluster distribution hyper-parameters θ, cluster assignments z, and the latent ϕ. To learn the model we conduct a modified hard expectation maximization procedure. In the E-step we compute the expected cluster assignments given the other model parameters. Note that R is comprised of connected components of related entities across views. All assignments are dependent within a connected component of R; thus, an exact estimate of the expected assignment of any entity with relationships requires considering all possible combinations of assignments to all entities in the corresponding component of the relationship graph. Given complex relationships across multiple views with many related entities, this computation can quickly become intractable. To address this complexity, we perform the E-step in an iterative, alternating fashion by greedily estimating the cluster assignments within each view conditioned on the assignments made in the others, effectively performing coordinate ascent.\n\nThe M-step is comprised of three sub-steps. We compute the analytical maximum likelihood estimates of the cluster distribution parameters θ, which are conditionally independent of the other parameters given the assignments chosen in the E-step. Next, we attempt to maximize the likelihood with respect to the cluster relationship matrices C by iteratively evaluating re-assignment of relationships between possible pairs of clusters across views. The inclusion of C in our model thus allows us to switch cluster dependencies during our inference procedure as we converge to clusterings where new cluster relationships form. Finally, we are able to use black box mean field variational inference (BBVI)17 or a direct optimization via ADAM18 to update the cluster weights and parameters ϕ. To reduce the variance of the BBVI gradient estimate and increase the efficiency of the method, we choose Gaussian variational distributions and utilize the reparameterization trick.19\n\nIn the M step, it is necessary to estimate the normalization constant of the conditional prior on the cluster assignments. Unfortunately, as the number of clusters, views, and/or the size of the related groups of entities go up; this computation eventually becomes intractable. In these cases, we utilize the pseudolikelihood20 to approximate the partition function tractably. The pseudolikelihood performs comparably to the full likelihood in all of our simulations.\n\nThe coordinate ascent algorithm for performing the E-step in conjunction with the expectation-maximization algorithm and the BBVI algorithm each guarantee local optima. As such, we employed random restarts to explore local optima and ultimately improve the quality of the results.\n\nTo test the efficacy of BMVC, we simulated a fully dependent two-view dataset where samples are drawn in each view from the same two independent clusters (A and B) defined by two-dimensional Gaussians. In this framework, related samples are generated by the same Gaussian distribution in each view. However, half the samples from A in the second view are shifted independently along the axis between the two cluster means, thus simulating data which are generated by cluster A but confounded by other effects in the second view. Such an effect might occur in a related modality with predictable underlying mechanistic differences. Let xA and xB be samples generated from A and B and let s be the shift percentage. We sample respectively:\n\nTo shift a sample xAi closer to μB we apply the following transformation:\n\nThus, sample membership inference is confounded in the second view due to the proximity of some of the A samples to B (see Figure 2, left). We varied the shift degree s and tested our ability to recover the correct clustering in both views given three structural cases: a semi-missing one-to-one simulation in which half the samples of view 2 have one-to-one relationships to samples in view 1; a complete one-to-one case without missingness; and finally a two-to-one simulation in which view 2 has twice as many samples, which map in pairs to individual view 1 samples. We compared Gaussian BMVC to a baseline model with ϕ set to zero; this produced two independent mixture models optimized with respect to hard cluster assignments (H-GMM).\n\nA: The first view of an example simulation with 100 samples from each cluster. B: Depicts the shift in view 2 dictated by variable si for sample xi (shown as a green star in the first view). Means of the Gaussians used to generate the data are depicted in black. C: Shows the first view of an example 4-cluster simulation. D: Demonstrates two types of confounding added in the second view (a shift and a binomial randomization effect) for use in comparing BMVC to the naive consensus clustering.\n\nIn order to test our ability to estimate ϕ given varying levels of dependence between views, we adapted a previous approach to introduce randomness into the dependence of the cluster assignments.7 This was accomplished by re-assigning samples which would normally belong to cluster A some of the time per a binomial distribution parameterized by p chosen between 0 and 0.5. Within this framework, a baseline cluster A sample is generated by cluster A with probability p and is otherwise generated by cluster B with probability 1 − p; likewise, a cluster B sample is generated by cluster B with probability 1 − p. Thus, a p closer to 0.5 will reduce the dependence between views. We constrained the degree of relatedness of the datasets by introducing this modification into the data generated in the second view and observed our estimation of ϕ as we reduced the relatedness of the datasets.\n\nIn order to explore the performance of BMVC in comparison to a baseline, multi-view approach, we generated a more complex four-cluster simulation with similar elements of confounding. In addition to original simulation clusters A and B, we generated data from two additional clusters C and D. In view 2, we confounded these randomly such that half of the cluster C samples in view 2 were related to cluster C samples in view 1, and half were related to cluster D samples in view 1. Similarly, half of the cluster D samples in view 2 were related to cluster C samples in view 1 rather than cluster D samples. Figure 2 (right) demonstrates the ground truth clusters of view 1 and their confounded relatives in view 2. Additionally, we introduced the same shift-based confounding as used previously between clusters A and B in view 2. We compared BMVC clusterings of these data to the naive consensus clustering produced by concatenating these two datasets along one dimension and applying a single Gaussian mixture model.\n\n\nResults\n\nTo measure the quality of our simulations, we computed the adjusted Rand index (ARI) of the clustering generated by the model in comparison to the ground truth of the simulation and computed the average of this statistic over both views. The adjusted Rand index measures the similarity between two clusterings while accounting for chance groupings of the elements. We ran each simulation ten times and Figure 3 shows the results of each trial. As expected, BMVC and the baseline model (H-GMM) performed comparably at either end of the spectrum of shift degrees. When the shift was negligible, the true clustering was easily recoverable in view 2 without leveraging view 1. When the shift was too great, the shifted samples became so confounded with cluster B that we were no longer able to reasonably separate them. When shifts were substantial but did not significantly overlap cluster B, BMVC was able to leverage the known relationships between the two views to determine the correct cluster memberships, whereas H-GMM was not able to make such a distinction. Notably, the margin in improvement increased considerably as we added relationships in the complete one-to-one simulation (Figure 3, middle) and then doubled the structure again in the two-to-one case (Figure 3, bottom).\n\nOn the left, we show the adjusted Rand index of simulations with one-to-one half-missing relationships (A), one-to-one complete relationships (B), and two-to-one relationships (C) over varying degrees of shift. Solid lines represent the median score and demonstrate the improvement of BMVC over H-GMM. To the right, we plot the corresponding BMVC estimates of the dependence strength parameter ϕ over varying degrees of shift and view independence p.\n\nFigure 3 also shows the strength parameter learned by BMVC over combinations of the binomial parameter p and shift distance. There is a clear effect of the artificial randomness injected by p. As expected, BMVC estimated a higher dependence strength for simulations in which p was lower, and, thus, the inter-view dependence was more complete. This effect was stronger when there were more inter-view relationships.\n\nIn our 4-cluster simulations with two types of confounding, we found that both baselines (individual clusterings [H-GMM] and the naive consensus clustering [M-GMM]) produce insufficient interpretations of the data. The individual clusterings were unable to effectively deal with shift-based confounding while the naive consensus clustering approach was unable to capture the different structures present in the two views. In contrast, BMVC leveraged the known relationships to separate the shift-based confounding while also allowing for separate interpretations of the remaining data in the two views. Figure 4 demonstrates the improvement of BMVC over the two other approaches in terms of ARI.\n\nTo examine BMVC’s ability to leverage inter-view relationships and its utility for real-world problems, we first turned to an easily interpretable application in public health. We applied BMVC to survey data collected from 3,299 households and 9,522 individuals,21 which details access to various resources along with individual demographics and statuses of residents of Puerto Rico following Hurricane Maria. For the purpose of clustering, features in both views (individual-level and household-level) were filtered to feature sets common to all samples. The data includes general information such as household size and barrio, as well as information regarding the impact of the hurricane on households such as loss of access to medical facilities/equipment, loss of electricity, or loss of water. Individual data includes age, gender, whether the individual moved into their home that year, and their current status. Table 1 provides a heuristic guide to categorical feature values visualized in Figure 5. BMVC is ideally suited to fully leverage the multi-view structure present in the data because household size, and thus the degree of many-to-one relationships, varies from one individual to as many as 13.\n\nScaled means of the BMVC clusters of households and individuals in the Puerto Rico dataset are shown at the top. Features are scaled across clusters in each view to ease the interpretation of the feature importances of each cluster relative to the others. Structural affinity maps (bottom) are shown alongside score box plots that depict affinity scores along each map row with blue stars denoting the score of the matched cluster.\n\nTo increase the interpretability of the experimental results, we ran a sample BMVC clustering on the data using a prior on the ϕ parameter which favors highly related clusters across the views (i.e. prefers large ϕ; all exact parameters of the run can be found in the provided Github repository). We found that the high degree of many-to-one relationships in the data made optimization of the full model likelihood intractable; as such, we utilized the pseudo-likelihood during inference. To assist in our analysis of the resulting clustering, we computed the proportion – for every pair (A and B) of inter-view clusters – of the relatives of cluster A entities that are in cluster B and of the relatives of cluster B entities that are in cluster A. The average of these statistics (hereafter referred to as’structural affinity’) represents the degree to which the learned clusters adhere to the structural assumptions coded by R.\n\nFigure 5 shows the cluster means (top) produced by BMVC as well as the structural affinity scores (bottom) of the BMVC clustering of the data and the hard-GMM clustering of the data for comparison. Structural affinity tends to be maximal along the diagonals much more often for the BMVC clustering than for the H-GMM, which demonstrates that the model successfully biases related entities to cluster more often under the paired labels encoded by C in contrast to two standard independent clusterings. Notably, clusters in the independent H-GMM household clustering do not tend to have uniquely high affinity scores with any particular individual clusters apart from the largest clusters (individual clusters 3 and 13), which are inherently more likely to contain individuals related to a given household. As such, the independent clustering of the data did not demonstrate many observable trends across views. In contrast, inspection of the cluster pairs with the highest structural affinity along the diagonal in the BMVC affinity map demonstrates that the model accurately captures and integrates some fundamental relationships between household conditions and individual demographic trends along with some additional, more complex causal relationships between household conditions and individual status (Table 2).\n\nCluster labels for which we estimated the lowest structural affinity across views in this clustering demonstrate the unique properties of the individual views in cases where the latent structure is not related across the views; thus, these represent a form of negative control for inter-view structure. For example, individual cluster 19 does not demonstrate structural affinity across the views and corresponds to missing individuals. Household cluster 18 does not demonstrate structural affinity across the views and corresponds to households where members reported significantly fewer neighbor deaths than the average. Household cluster 7 describes households which lost access to dialysis for an average of 2.25 days and does not demonstrate structural affinity across the views in this clustering, which suggests that such cases may not have significantly contributed to mortality in this study. Previous findings suggest that end-stage renal failure typically results in death after an average of seven days in hospice patients without dialysis.22 This could explain why the clustering does not reflect a significant relationship between this medical issue and a mortality event or relocation.\n\nIntuitively, we noted a correlation between rarer negative outcomes and lower structural affinity, which might reflect smaller sample sizes and the less deterministic relationships between worsening household conditions and individual outcomes. For example, household cluster 2 describes households that were more likely to require assistance at a temporary aid center and demonstrates only moderate structural affinity to a cluster containing slightly older individuals and some deaths. Household cluster 9 describes households where access to medical care was limited by affordability and has even less structural affinity to an individual trend given by this clustering.\n\nFinally, we turn to an examination of the clusters with the highest structural affinity across views. Because half the features in the individual view are purely demographic, households with relatively few adverse events cluster alongside various demographic groups of individuals with uneventful status (i.e. that did not move or die) such as in clusters 1, 3, 5, 8, 12; further, households with widespread issues with electricity, water, cell availability, and that reported known deaths of neighbors were more likely to cluster alongside younger individuals who left despite having recently moved in (cluster 6). However, we are also able to make more specific observations about the relationships between very particular household factors and the individuals in those households; for example, households that reported a loss of access to respiratory machinery due to power failure (CPAP, BiPAP or nebulizers) clustered strongly alongside men averaging middle aged (cluster 17), coinciding with previous findings that sleep apnea and COPD are more likely to be diagnosed and to occur in older men.23,24 This is an example of the way in which BMVC can be used for mechanistic hypothesis generation.\n\nWe now turn to a two-view genomic data application in which we clustered gene expression and methylation. This gave us the opportunity to more rigorously test BMVC’s ability to both improve clustering interpretability and increase clustering quality as measured by biological homogeneity.\n\nUsing patient data from The Cancer Genome Atlas (TCGA),25 we examined a set of 1,819 genes identified as intrinsically related to breast cancer subtype in four different studies of breast cancer patients and further studied by TCGA. We selected 1,363 methylation probes which fell within the gene bodies of the intrinsic genes according to available Infinium HumanMethylation27 BeadChip annotations26 and which also fell into the top 50% of probes with the highest variance over the 466 patients for which data was available across all’omics platforms. Before filtering to the selected genes and probes, we mean-centered and scaled each subject in each view over all loci. A total of 366 genes in our target set mapped to more than one probe in the high variance set, and 1,019 of them were unmapped. Of the probes, 23 were related to more than one gene. As such, this biological application includes both many-to-one relationships and missing relationships that are crucial to fully understanding the available structure. Before clustering, we performed principal component analysis on the full dataset and removed the first principal component in each view of the data as a conservative measure to account for potential technical artefacts. We then projected the data in each view onto the top 10 principal components – accounting for the highest 41% and 30% of the remaining variances in the expression and methylation views respectively – to avoid any cluster quality issues related to dimensionality. Consequently, we clustered the genes and methylation probes each in 10-dimensional space.\n\nTo test the capability of BMVC to produce biologically homogeneous clusters in the presence of confounding signal, we designed a preliminary experiment wherein we produced two dependent pseudo-simulated views from the gene expression data by independently adding standard Gaussian noise in each view. We then duplicated 25% of the entities at random in one of the views in order to simulate many-to-one relationships. Finally, we removed 25% of the edges from the resulting true relationship graph to simulate cases where some entities have no known relationships across views. We ran twenty initializations of BMVC with a Gaussian base distribution on this data alongside H-GMM and compared the Adjusted Rand Index (ARI) of the H-GMM and BMVC clusterings relative to a single-view H-GMM clustering of the original expression data without noise (henceforth referred to as the ‘ground truth’ GMM or GT-GMM) in order to determine whether BMVC is able to leverage the artificial inter-view structure to recover signal closer to the latent ground truth despite the inclusion of the random signal. We evaluated the biological homogeneity of the clusterings in terms of the similarity of the genes in each cluster using a similarity metric derived from the pairwise Gene Ontology Term Overlap (GOTO)27 statistic, which is similar to that used by.5 The GOTO score of a pair of genes is computed by retrieving Gene Ontology (GO) terms and their ancestors for each gene and estimating the pairwise intersection; thus, higher scores indicate a stronger relationship between gene products. We average these scores over pairs within a cluster. Then, we take a weighted average of the cluster scores over the clusters (where cluster sizes are the weights). We computed GOTO scores in each of three GO categories (Biological Process, Molecular Function, Cellular Component) as well as with respect to all GO terms regardless of category.\n\nAs in our preliminary experiment, we ran BMVC on the true TCGA data using a Gaussian base distribution. We evaluated the quality of the clusterings in contrast to H-GMM cluster labels for twenty random initializations. For methylation probes with multiple related genes, we estimated a GOTO score by averaging over all possible gene pairs. This process is further detailed in an included GitHub repository (see Extended data).\n\nFinally, we ran Gene Set Enrichment Analysis (GSEA)28 on the resulting gene expression clustering. GSEA is known to be biased when applied to methylation data,29 but we were able to interpret much of the learned structure due to the natural cluster alignment produced by BMVC’s inter-view dependence.\n\nIn our preliminary pseudo-simulated experiment, we found that BMVC clusterings had a higher average ARI than H-GMM clusterings (Figure 6), where we took ground truth to be the clustering of the true expression data. Correspondingly, BMVC GOTO scores (Figure 7) were higher on average than those produced by H-GMM in both views and in all GO conditions, and, thus, they were closer in the first view to the GOTO scores produced by the reference GT-GMM clustering. Note that the duplication of entities in the second view of our pseudo-simulated data changed the baseline distribution of the data, and as such there was no ground truth; thus, we were not able to generate GOTO scores for GT-GMM in the second view (Figure 7), nor did we compute ARI in the second view (Figure 6). The correlation between an improvement in the ARI and an improvement in GOTO score suggests that GOTO is a reasonable, if approximate, measure of true biological homogeneity. Given this assumption, an improvement in GOTO by BMVC over H-GMM when applied to the true biological data would suggest that BMVC is able to successfully leverage the known inter-view relationships to produce an improved multi-view clustering.\n\nThe H-GMM clustering of the true expression data was considered to be ground truth for the purpose of ARI computation. BMVC captured true underlying biological structure more accurately than H-GMM on average. ARI was only computed in the first view due to the lack of ground truth in view 2 caused by duplication of the data.\n\nNotably, ground truth clusterings of the noiseless data (in green, GT-GMM) can only be observed in the first view of the pseudo-simulated data, which contains no duplication. These clusterings achieve the highest scores, which supports the use of GOTO as a measure of biological homogeneity when measuring the performance of BMVC.\n\nWe ran BMVC and the independent GMMs on the processed expression and methylation datasets together, each with 60 random but identical initializations and no added noise (in contrast to our pseudo-simulations). Figure 8 compares the performance of BMVC and H-GMM in terms of average GOTO scores across the views and demonstrates that BMVC improves the overall biological homogeneity of the joint clustering.\n\nNotably, the improvement in the methylation view when using BVMC is larger than in the expression view (Table 3), which is consistent with the observation that methylation data is generally noisier25 and so may benefit more from transfer learning. GOTO scores of methylation clusterings may also increase more when informed by gene expression clusterings because GOTO is defined with respect to gene products rather than epigenetic processes. This could explain why biasing gene expression clusterings to more closely resemble the structure found in the epigenetic data does not increase the GOTO score in the expression view as much.\n\nWe performed GSEA for biological processes of the BMVC gene expression clusters over all trials alongside the corresponding H-GMM clusters using KEGG and Reactome Canonical Pathway genesets from MSigDB,28,30 using the Benjamini-Hochberg correction at a FDR threshold of 0.1. We compiled a list of the enrichments found by BMVC but not the GMMs in each trial. We then compiled the list of enrichments found by the GMMs but not by BMVC in each trial; we counted the occurrences of the enrichments in each list and subtracted the counts of the second list from the first in order to control for random effects due to initialization. Finally, we examined the top scoring enrichments that were found in three or more remaining BMVC trials in order to determine what biological effects were most often recovered by BMVC clusterings but not by the independent Gaussian mixture models.\n\nWe found that by incorporating the dependency between the views, we were more likely to recover enrichments consistent with previous findings of the role of methylation in alternative splicing in breast cancers as well as and in regulation of pre-mRNA splicing (KEGG_SPLICEOSOME, REACTOME_MRNA_SPLICING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CON-TAINING_PRE_MRNA).31,32 We were also more likely to recover enrichments of the S phase (REACTOME_S_PHASE), which is consistent with previous work suggesting the existence of a methylation ‘loss clock’ which links late S-phase genome replication with a reduction of tumor methylation and an accumulation of methylation errors in breast cancer tumors.33 The top scoring enrichments also included processes related to G-protein coupled receptor signaling, which have been repeatedly implicated in tumorigenesis34 and in particular secretin receptors (REACTOME_SIGNALING_BY_GPCR, REACTOME_CLASS_B_2_SECRETIN_FAMILY_RECEPTORS) which have previously been shown to be hypermethylated and downregulated in breast cancer tissues35 and to be regulators of tumor cell proliferation. We additionally found three overrepresented enrichments for pyrimidine metabolism, the lysosomal system and basal cell carcinoma development (REACTOME_PYRIMIDINE_METABOLISM, KEGG_LYSOSOME and KEGG_BASAL_CELL_CARCINOMA) for which there are clearly documented relationships to cancer progression in the existing literature.36–38 However, we found limited or no clear evidence for known mechanisms by which these processes are regulated by methylation. For example, previous findings38 demonstrate that patients with frequent basal cell carcinomas may be more susceptible to the development of breast cancers due to germ-line defects in DNA repair genes. Other work stipulates that epigenetic silencing of said DNA repair genes could be a factor in tumorigenesis in cancers,39 but further investigation is required to determine whether there is a specific epigenetic link between basal cell carcinomas and breast cancer development. Separately, recent work suggests that epigenetic mechanisms may underlie lysosomal storage disorders,40 but that such a claim warrants further investigation. A different possible interpretation of these enrichments is that some of them represent gene expression mechanisms that are not directly affected by cis-regulatory methylation, but rather are much more identifiable in our clusterings when we account for the effects of methylation regulatory processes.\n\nWe further examined the clustering run that achieved the highest average biological process GOTO score through the lens of the structural affinity metric used for the previous public health analysis (Figure 9). Among the enriched clusters with high structural affinity scores, we found enrichment for immune system processes, interferon signaling and immune cytokine signaling (cluster 19, e.g.: REACTOME_IMMUNE_SYSTEM, REACTOME_INTERFERON_ALPHA_BETA_SIGNALING, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM), which previous work shows are processes significantly correlated with genomic demethylation across tumour types.41 Notably, cluster 19 was also enriched for KEGG_LYSOSOME, lending further credence to the potential for the regulation of lysosomal processes via methylation in breast cancer and potentially in lysosomal storage disorders in general as previously suggested.40 We found further evidence for lipid-related processes in cluster 6 including enrichment for the peroxisome proliferator-activated receptor pathway (KEGG_PPAR_SIGNALING_PATHWAY), which is critical to metabolic and lipid-related processes and has also been found to regulate and be regulated by epigenetic processes including by DNA methyltransferases.42\n\nBlue stars denote the structural affinity scores of the methylation cluster respectively paired with each expression cluster.\n\nInspection of low-affinity clusters was also informative. Cluster 2 was enriched for KEGG_PRIMARY_IMMUNODEFICIENCY and KEGG_HEMATOPOIETIC_CELL_LINEAGE. A class of rare disorders, primary immunodeficiency diseases (PIDs) are often treated with hematopoietic cell transplants and increase the risk of a cancer diagnosis.43 While secondary immunodeficiencies may be caused by environmental or epigenetic factors, PIDs are caused by genetic mutations, and thus genes implicated in PIDs are much less likely to be regulated by methylation in this context.44 The low structural affinity of cluster 2 in the BMVC clustering supports this claim and is another example of the way in which BMVC is able to provide a highly interpretable result with inferred relationships that are useful for hypothesis generation. Gene expression cluster 11 was not enriched for any terms, which might suggest that the corresponding methylation cluster represents an effect that does not functionally cis-regulate expression at the loci measured in this study; as such, this could warrant further investigation.\n\n\nDiscussion\n\nAn assumption of one-to-one relationships between entities often does not sufficiently represent structure across domains in multi-view applications. We show that BMVC can be used to effectively capture latent structure in multi-view data without imposing a one-to-one assumption. BMVC is the first fully Bayesian approach to accomplish this goal, and as such it provides a flexible framework that allows many other possible configurations of the model that may be appropriate for specific applications, including user’s choice of priors on latent variables and base distributions for a given data type. Furthermore, our applications in public health and genomics highlight the ability of BMVC to generate natural interpretations of latent multi-view structure and to support mechanistic multi-view hypothesis generation. This shows promise for multi-view applications that commonly require formulation of novel hypotheses such as drug discovery and patient diagnosis.\n\nThe experiments presented here also demonstrate that our alternating inference procedure, in combination with gradient-based methods applied to the pseudo-likelihood, yields a relatively efficient inference approach capable of estimation with large numbers of entities and many clusters and relationships. Scalability will become increasingly important as the diversity and quantity of multi-view data increases across domains.\n\nSome limitations of BMVC are worth noting. One is its reliance on a priori known relationships encoded by the user-specified matrix R. Care must be taken to ensure that the relationships encoded by R reflect real and high-quality relationships, e.g. by filtering to relationships or entities that are correlated with particular outcomes or that have higher variance as we did in our biological analysis. Additionally, extra work may be needed to account for different kinds of real-world relationships. While using known relationships is likely to be a more robust approach than an attempt to automatically infer such relationships as a pre-processing step (such as in CMMVC12), future work might include estimation or refinement of entity relationships as part of the clustering process itself. Another limitation of BMVC is that it uses hard cluster assignments, thus imposing discrete assumptions of cluster membership. The hard assignments directly determine the impact of ϕ on the overall clustering, and also contribute to the efficiency of the inference procedure proposed here. An effort to incorporate uncertainty into the estimation of cluster assignments by using soft expectation maximization could further improve the accuracy and robustness of the multi-view clustering.\n\nThere are also significant opportunities for extensions and further work in complex multi-view structure learning. It will continue to be important to ensure that these models are interpretable, especially in critical settings such as the clinic. Here, we presented post-hoc interpretations of the inter-view cluster relationships by visualizing structural affinity scores. Future work could focus on Bayesian approaches that explicitly consider more fine-grained representations of the relationships in the data, e.g. by including a different latent variable for every pair of clusters between two views. Further, future approaches could include efforts to account for continuous structure beyond clusters, such as through factorization, and further complex dependencies between these structures, such as via hierarchical or tree-based models. We expect that flexible approaches like BMVC that can incorporate increasingly complex assumptions will continue to improve the application of multi-view models in real-world contexts.",
"appendix": "Data availability\n\nData from The Cancer Genome Atlas used in this work is available publicly through the Genomic Data Commons at https://gdc.cancer.gov/about-data/publications/brca_2012. The public health data surveying individuals and households in Puerto Rico following Hurricane Maria is available under the Creative Commons Attribution 3.0 license and can be found at https://github.com/c2-d2/pr_mort_official .\n\nThe source code for BMVC can be found on GitHub at https://github.com/bshapiro/bmvc-paper . The archived source code at time of publication is available at https://doi.org/10.5281/zenodo.7250670. 45\n\nAn implementation of GOTO score computation for both expression and methylation data in Python can be found at https://github.com/bshapiro/gotopy. The archived source code at time of publication is available at https://doi.org/10.5281/zenodo.7250678. 46\n\nAll software is distributed under the BSD 3-Clause License. Any additional information required to replicate any results reported in this paper is available from the lead contact upon request.\n\n\nReferences\n\nShen R, Olshen AB, Ladanyi M: Integrative clustering of multiple genomic data types using a joint latent variable model with application to breast and lung cancer subtype analysis. Bioinformatics. 2009; 25(22): 2906–2912. PubMed Abstract | Publisher Full Text\n\nShen R, Wang S, Mo Q: Sparse integrative clustering of multiple omics data sets. Ann. Appl. Stat. 2013; 7(1): 269–294. PubMed Abstract | Publisher Full Text\n\nMo Q, Wang S, Seshan VE, et al.: Pattern discovery and cancer gene identification in integrated cancer genomic data. Proc. Natl. Acad. Sci. U. S. A. 2013; 110(11): 4245–4250. PubMed Abstract | Publisher Full Text\n\nMo Q, Shen R, Guo C, et al.: A fully Bayesian latent variable model for integrative clustering analysis of multi-type omics data. Biostatistics. 2018; 19(1): 71–86. 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PubMed Abstract | Publisher Full Text\n\nLin CM, Davidson TM, Ancoli-Israel S: Gender differences in obstructive sleep apnea and treatment implications.2008.\n\nPerez TA, Castillo EG, Ancochea J, et al.: Sex differences between women and men with COPD: A new analysis of the 3CIA study. Respir. Med. 2020; 171: 106105. PubMed Abstract | Publisher Full Text\n\nKoboldt DC, Fulton RS, McLellan MD, et al.: Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490(7418): 61–70.\n\nZhou W, Laird PW, Shen H: Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes. Nucleic Acids Res. 2017; 45(4): e22. PubMed Abstract | Publisher Full Text\n\nMistry M, Pavlidis P: Gene Ontology term overlap as a measure of gene functional similarity. BMC Bioinformatics. 2008; 9: 1–11.\n\nSubramanian A, Tamayo P, Mootha VK, et al.: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U. S. A. 2005; 102(43): 15545–15550. PubMed Abstract | Publisher Full Text\n\nGeeleher P, Hartnett L, Egan LJ, et al.: Gene-set analysis is severely biased when applied to genome-wide methylation data. Bioinformatics. 2013; 29(15): 1851–1857. PubMed Abstract | Publisher Full Text\n\nLiberzon A, Birger C, Thorvaldsdóttir H, et al.: The Molecular Signatures Database Hallmark Gene Set Collection. Cell Systems. 2015; 1(6): 417–425. PubMed Abstract | Publisher Full Text\n\nPant D, Narayanan SP, Vijay N, et al.: Hypoxia-induced changes in intragenic DNA methylation correlate with alternative splicing in breast cancer. J. Biosci. 2020; 45(1): 1–24. Publisher Full Text\n\nMaunakea AK, Chepelev I, Cui K, et al.: Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition. Cell Res. 2013; 23(11): 1256–1269. PubMed Abstract | Publisher Full Text\n\nBatra RN, Lifshitz A, Vidakovic AT, et al.: DNA methylation landscapes of 1538 breast cancers reveal a replication-linked clock, epigenomic instability and cis-regulation. Nat. Commun. 2021; 12(1): 1–13. Publisher Full Text\n\nLappano R, Jacquot Y, Maggiolini M: GPCR modulation in breast cancer. Int. J. Mol. Sci. 2018; 19(12). PubMed Abstract | Publisher Full Text\n\nKang S, Kim B, Kang HS, et al.: SCTR regulates cell cycle-related genes toward anti-proliferation in normal breast cells while having pro-proliferation activity in breast cancer cells. Int. J. Oncol. 2015; 47(5): 1923–1931. PubMed Abstract | Publisher Full Text\n\nWang W, Cui J, Ma H, et al.: Targeting Pyrimidine Metabolism in the Era of Precision Cancer Medicine. Front. Oncol. 2021; 11(May): 1–17. Publisher Full Text\n\nTang T, Yang Z y, Wang D, et al.: The role of lysosomes in cancer development and progression. Cell Biosci. 2020; 10(1): 1–18.\n\nCho HG, Kuo KY, Li S, et al.: Frequent basal cell cancer development is a clinical marker for inherited cancer susceptibility. JCI insight. 2018; 3(15). PubMed Abstract | Publisher Full Text\n\nLahtz C, Pfeifer GP: Epigenetic changes of DNA repair genes in cancer. J. Mol. Cell Biol. 2011; 3(1): 51–58. PubMed Abstract | Publisher Full Text\n\nHassan S, Sidransky E, Tayebi N: The role of epigenetics in lysosomal storage disorders: Uncharted territory. Mol. Genet. Metab. 2017; 122(3): 10–18. PubMed Abstract | Publisher Full Text\n\nJung H, Kim HS, Kim JY, et al.: DNA methylation loss promotes immune evasion of tumours with high mutation and copy number load. Nat. Commun. 2019; 10(1): 1–12.\n\nPorcuna J, Mínguez-Martínez J, Ricote M: The pparα and pparγ epigenetic landscape in cancer and immune and metabolic disorders. Int. J. Mol. Sci. 2021; 22(19). PubMed Abstract | Publisher Full Text\n\nMortaz E, Tabarsi P, Mansouri D, et al.: Cancers related to immunodeficiencies: Update and perspectives. Front. Immunol. 2016; 7(SEP): 1–13. Publisher Full Text\n\nMartínez-Cano J, Campos-Sánchez E, Cobaleda C: Epigenetic Priming in Immunodeficiencies. Front. Cell Dev. Biol. 2019; 7(July). PubMed Abstract | Publisher Full Text\n\nShapiro BD: bshapiro/bmvc-paper: 0.1.0.Oct. 2022.Publisher Full Text\n\nShapiro BD: bshapiro/gotopy: 0.1.0.Oct. 2022.Publisher Full Text"
}
|
[
{
"id": "158015",
"date": "16 Jan 2023",
"name": "Sara Mostafavi",
"expertise": [
"Reviewer Expertise Computational Biology",
"Gene regulation"
],
"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 present a Bayesian multi-view clustering methods called BMVC that can be applied to multi-modal data. The methods presented is sound, and has novel statistical properties (such as estimating uncertainty, and modifying model to incorporate different types of prior depending on the input data types). BMVC is applied and carefully evaluated in three very different settings, 1) simulation data, 2) public health data, and 3) gene expression paired with DNA methylation data. The authors do a nice job in demonstrating that BMVC leads to improved results over the baseline clustering approaches.\n\nI specifically appreciate the detailed analysis the authors performed on the cancer gene expression + DNA methylation data. I have no major comments to be addressed.\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": "220444",
"date": "10 Nov 2023",
"name": "Max Moldovan",
"expertise": [
"Reviewer Expertise Data science"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 presented a Bayesian Multi-View Clustering (BMVC) method that allows identifying clusters in multi-view systems. Such systems are especially common in biology, being often characterised by multiple distinct but inter-dependent information layers, such as gene expression, DNA methylation and proteomic profiles. As presented by the authors, the proposed BMVC approach is able to utilise between-views relationships when recovering clustering within each individual view. The authors have tested the method with simulated data and based on two different empirical datasets. The authors have also provided Python codes for the method implementation on the dedicate github.\nThe method is practically attractive and can be used in various data-rich fields. While reading the paper, I had some remaining questions regarding the method. Firstly, model estimation requires maximisation of a complex function containing multiple local optima. What is the variation of resulted clustering outcomes due to alternative attained local optima, and especially with respect to the global optimum?\nSecondly, the authors recognise that their approach relies on hard cluster assignments (i.e. each node can belong to a single cluster only) and list this as a method limitation. How hard would it be to implement fuzzy cluster assignments in the suggested method? Would it be an extension of the proposed method, or perhaps a new method with outcomes greatly different for hard and fuzzy cluster assignments even if applied to the same dataset?\nFinally, how sensitive clustering outcomes are to misspecification of R matrix (the matrix that codes between-view relationships)?\nTo summarise, the authors have presented a practically relevant and implementation promising method for assigning clusters within multi-view systems. The authors have provided Python codes for the method implementation, which would hopefully be replaced by more formal and better documented Python and R packages.\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? Yes\n\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? Yes",
"responses": [
{
"c_id": "10997",
"date": "05 Apr 2024",
"name": "Benjamin Shapiro",
"role": "Author Response",
"response": "Author response: The authors thank Max Moldovan for his feedback and insightful questions. Below we have provided some additional details that we hope will clarify some of the finer points of the model and the points made by the reviewer. What is the variation of clustering outcomes due to local minima? One of the primary purposes of our experiments with simulated data was to explore the degree to which the convergence of BMVC was optimal (in cases where such a thing clearly exists) and to understand how often local minima could pose a challenge. The simulations demonstrate that BMVC is able to recover the “ground truth” clustering represented in view A for both simple and somewhat more complex simulations even in the presence of significant confounding due to the inclusion of shift and relationship randomization effects. To further investigate your question here, we have run additional experiments in order to observe the distribution of the actual log likelihoods to which the algorithm converges in different scenarios and with random initializations. We wish to clarify that the simulation results in the paper are generated using random effects in the simulated data as well as random initialization seeds. The seeds are used to initialize the k-means algorithm, the output of which is then used as a starting point for the main clustering task. The k-means results themselves are extremely stable, and thus the vast majority of the variation shown in the simulation results are due to the randomness in the simulated data. We recommend this approach to initialization as it reduces the time to convergence and also stabilizes the variability in convergence outcomes. To demonstrate this, we ran our log likelihood experiments using both fully random initializations and random k-means initializations. Our figures show that while convergence to local optima occurs in each randomly initialized run, convergence to the most likely clustering (with the highest log likelihood for that shift) is the mode result in the majority of the simulations. In cases where the simulation is complex and shift is significant (thus confounding the clustering) , the algorithm sometimes converges more often to a nearby suboptimal local maximum,, one that is close to the presumed global optimum. Notably, a similar degree of occasional convergence to local optima persists when clustering with the hard-labeled GMM (H-GMM), which suggests that convergence to local optima is not a direct consequence of the complexity of BMVC but rather the complexity of the data and the inherent challenge of discovering a global optimum in such data when initializing randomly. In contrast, our runs with k-means initializations show that the k-means initialized BMVC runs always converge to the highest log likelihoods achieved by random initializations, supporting our recommendation for this approach. The fitted kernel density estimates shown are intended to convey the degree of variation that exists in each case. For the purpose of these figures, we focused on the most complex simulation (the 4-cluster simulation in our paper). https://f1000research.s3.amazonaws.com/linked/597180.126215-_Author_response-_fig_1.pdf Fig 1. The log likelihoods to which BMVC converges at each shift used in the 4-cluster simulation. Each simulation is run with 10 trials with random initializations. https://f1000research.s3.amazonaws.com/linked/597184.126215-Author_response_fig-2.pdf Fig 2. The log likelihoods to which H-GMM converges at each shift used in the 4-cluster simulation. Each simulation is run with 10 trials with random initializations. https://f1000research.s3.amazonaws.com/linked/597185.126215-_Author_response_fig-3.pdf Fig 3. The log likelihoods to which BMVC converges at each shift used in the 4-cluster simulation. Each simulation is run with 10 trials with random initializations and the pseudo-likelihood objective is optimized. We employ the pseudolikelihood in our larger real-world applications. https://f1000research.s3.amazonaws.com/linked/597186.126215-Author_response_-fig_4.pdf Fig 4. The log likelihoods to which BMVC converges at each shift used in the 4-cluster simulation. Each simulation is run with 10 trials with randomly seeded K-Means initializations. Notably, these converge uniformly to the highest log likelihoods achieved by random initializations. It is not possible to define global vs. local optima in the case of real empirical data because, as is often the case with biological data, there is no absolute truth. However, our pseudo-simulated data show that BMVC recovers clusterings that are more biologically homogeneous than independent clustering approaches. This is all we can guarantee in real-world applications due to a lack of objective ground truth. How hard is it to implement soft clustering? How greatly would soft vs. hard clustering methods differ? The main consequence of a soft clustering approach is that it requires the incorporation of the cluster weights into the joint likelihood, rather than the actual cluster assignments. Despite this challenge, a soft clustering approach could be beneficial because it may more closely model real world applications wherein samples could reasonably ‘belong’ to multiple clusters to various degrees. Soft clusterings may be especially accurate or useful in cases where this is an important assumption. The current formulation of the model likelihood relies on tests for whether the cluster assignments are related through the latent indicator matrix C. Since a soft clustering formulation would remove the notion of a single cluster assignment for any given sample, it presents the following challenge: how can we model the similarity or relatedness of cluster ‘assignments’ when presented with cluster weights rather than labels? A naive way to solve this problem could be to test whether the most likely cluster assignments are related for a given pair of related samples. This means cluster relatedness would be determined in a ‘hard’ manner, but cluster assignments would still be soft. A more sophisticated approach could measure the relatedness of the sets of cluster weights for two related entities via a correlation metric (or similar); this could feasibly be used in place of the C indicator. The resulting changes to the likelihood function could be significant; as such, changes to optimization strategy may be required. How sensitive are the clustering outcomes to misspecification of the R clustering matrix? This is an important consideration for people who want to use BMVC. BMVC is very sensitive to the specification of R because R is the only source of information that BMVC uses to determine the multi-view relationships. This is partly why we filtered the known relationships specified by R to a subset of high-variance probes in our real-world applications.This approach made it more likely that the relationships described by R constitute real biological effects. We suggest that users take care to ensure that the relationships specified in the R matrix are likely to represent genuine multi-view effects. Users can avoid injecting bias into the algorithm by preferring false negatives over false positives when including relationships in the R matrix. If, however, the user has a strong prior that relatedness exists even beyond what is implied directly by correlated signal in the data, then they may use R to intentionally bias the outcome. It’s important to note that the purpose of the learned random variable phi is to regulate the strength of the effect of the known relationships on the clustering. As a result, even when R indicates false relationships that could bias BMVC, such an effect will be mitigated by phi during inference. The prior on phi can also be specified, should the user wish to change their confidence in the effects of R on the objective."
}
]
}
] | 1
|
https://f1000research.com/articles/11-1460
|
https://f1000research.com/articles/12-115/v1
|
31 Jan 23
|
{
"type": "Brief Report",
"title": "Heatwave 1987: the Piraeus versus Athens case",
"authors": [
"Stella Geronikolou",
"Stelios Zimeras",
"Stephanos Tsitomeneas",
"George P Chrousos",
"Stelios Zimeras",
"Stephanos Tsitomeneas",
"George P Chrousos"
],
"abstract": "Background: Heatwaves represent the main indices of climate change, while mortality is one of the established markers of their human effects. Populations adapt to temperature variations/challenges differently for unknown reasons. Thus, heatwave evaluations should be enriched by historical context and local data, to allow better precision and prediction. Methods: The mortality data for 1987 were collected from the Piraeus municipality registry, whereas data for Athens were obtained from literature retrieved from PUBMED. Ambient characteristics were derived from Geronikolou’s 1991 thesis and the reports of national organizations. From the death events, the odds ratio and relative risk in Athens compared to the Piraeus 1987 event were calculated. Finally, a simple neural network proposed the dominant ambient parameter of the heatwave phenomenon in each place. Results: The 1987 heatwave was more lethal (seven-fold) in Athens than in Piraeus and was found to be dependent on nitric oxide (NO) concentration (with probability 0.999). In the case of Piraeus in 1987, ozone characterized the phenomenon. Conclusions: The odds of dying due to a heatwave are highly dependent on lifestyle, population sensitivity to preventive measures and public health policy, while the phenomenon was mainly moderated by ozone in Piraeus in 1987, and NO in Athens irrespective of year.",
"keywords": [
"heatwaves",
"Eastern Mediterranean Sea",
"mortality",
"heatwave 1987",
"Athens 1988",
"Athens 1992",
"odds ratio",
"relative risk",
"mortality",
"neural networks",
"ozone",
"NO"
],
"content": "Introduction\n\nExcessive ambient temperatures represent the main indices of climate change, while mortality is one of the most established markers of its human effects. In the last few decades, the annual incidence of extreme weather event disasters has tended to rise1. Thus, in the last 50 years, 22,173 all-cause disasters (conflicts, biological, natural, technological) have taken place, causing 6.2 million deaths globally2. The same report also suggests that 8% of the 89% of the observed total all-cause mortalities that were registered in the Emergency Events Database (EM-DAT) of the Center for Research on the Epidemiology of Disasters (CRED)1,2 were attributed to heatwaves1.\n\nHigh ambient temperatures are closely related to mortality increases in most countries3, and this risk is expected to rise in the near future, as they are closely related to climate change4–7. Daily deaths and high ambient summer temperatures have been correlated irrespective of city heterogeneity, as shown in the Assessment and Prevention of Acute Health Effects and Weather Conditions in Europe (PHEWE) project8,9. Daily deaths and weather and air quality data for 15 European cities were analyzed over 11 years, and it was concluded that the warm season heat-mortality curve was J-shaped, with Mediterranean cities having higher temperature thresholds and steeper slopes than Central and Northern European cities.\n\nPopulations adapt to temperature variations or challenges differently, for unknown reasons10. Location, lifestyle, genetic predisposition, environmental pollution are ongoing research targets in our attempts to calculate their impact on individuals and populations. Such data are important for authorities to make correct decisions regarding public health and city planning. Public health measures should adapt to these considerations in order to appropriately mitigate heatwave effects. The evaluation of heatwaves should be enriched by historical context and local events to allow better precision in data analysis and more accurate predictions of future crises. This study aims to contribute with a heatwave report for Piraeus in 1987 published as part of a dissertation in the Public Hygiene Department11, as this is a representative urban population (ranked third in growth) and the biggest port in the Mediterrannean Sea. The Piraeus 1987 case will be examined it in the light of the mortality odds, and more importantly, will be compared with other heatwaves in the same geographical area at the same and different times.\n\n\nMethods\n\nA retrospective study was designed comprising of the daily deaths of all causes during the summer of 1987 in Piraeus11. The above heatwave was compared to diverse heatwaves in the Attica area: Athens in 198712–14, Athens in 198812–14, and Athens in 199215.\n\nThe data extracted by these studies were processed to calculate:\n\n• the odds ratio as follows: OR=π/(1-π), where π: incidence (risk)16.\n\n• the relative risk of dying in each heatwave (v) compared to the Piraeus 1987 heat wave mortality risk:\n\nRR= πV/πPiraeus 16\n\nDiscomfort index (DI) is an index of the discomfort felt in warm weather as a result of the combined effects of the temperature and air humidity. It was calculated using Thom’s formula17 as follows:\n\nDI=T- 54*(0.55-0.0055*RH)*(T-14.5),\n\nwhere T: temperature; RH: relative humidity.\n\nOzon and nitric oxide (NO) measurements derived either from the included studies and/or\n\nWe also collected and present pollution and solar activity data (sunspot numbers) for each month that the heatwave under investigation had been observed. The sunspot numbers are related to cosmic rays and are investigated for their influence on the climate and for their impact on health18.\n\n\nResults\n\nDaily mortality events were based on Geronikolou’s (1991) thesis that included a study of all death events archived in the city of Piraeus between June 1st 1987 and August 31st 1987. In these 92 days, 263 death events were archived, with 62 of them occurring during the heatwave11. Concerning the Athens data, they were extracted by the publications12–15.\n\nIn Table 1 the registered population in each municipality census (for both Piraeus and Athens) are listed\n\nn/a: not available; Source: Hellenic National Statistic Authority\n\nIn Table 2 the geography and pollution characteristics and the calculated DI are illustrated.\n\nn/a: not available\n\nIn Table 2, to overcome the problem with the missing values (noted as n/a), two interpolation methods were calculated considering:\n\n1. Lagrange interpolation polynomial19–21 and\n\n2. Cubic spline interpolation21,22.\n\nDue to the uncertainty in the form (direction) of the data, the proposed method is the computation of the average between the two interpolation methods. Results are as illustrated inside the bracket of the data.\n\nIn Table 3 the calculated probabilities of heat-related mortality are presented.\n\n# : Calculations are based on dead/survived+dead\n\nUsually, neural networks are applied to big data analysis cases, but in this case, their use is as a pilot for data processing. Regarding the effect of the factors influencing the occurrence of heatwaves, a simple neural network- developed taking into consideration the proposing parameters from Table 2: NO, ozone, temperature, discomfort index and sunspot. The idea behind this model is to predict the importance of the parameters affecting the heatwaves. The model xi i=1,..,n consists of the proposing parameters and wi i=1,..,n represents the corresponding weights. In our case all the parameters have the same weight (wi =1);\n\nΣ is denoted as the summation of the multiplication between parameters and weights (wi xi); f(x) is the activation function.\n\nThe activation function is an integral part of a neural network. Without an activation function, a neural network is a simple linear regression model. This means the activation function gives non-linearity to the neural network. The proposed formula for the function is the softmax with [33–36]\n\nThe exponential acts as the non-linear function. The values were divided by the sum of exponential values to normalize and then convert them into probabilities.\n\nBased on the proposed neural network (Figure 1) the important parameters for different years are:\n\nPiraeus 1987 - ozone probability 0.993\n\nAthens 1987 - NO probability 0.999\n\nAthens 1988 - NO probability 0.999\n\nAthens 1992 - NO probability 0.999\n\n\nDiscussion\n\nThe Eastern Mediterranean Sea is surrounded by highly diverse regions as North Africa, the Middle East and Asia Minor. Socioeconomic, environmental and population inequities have been associated with anthropogenic dryness and climate change. For millennia, ambient temperature exposure influences the human body leading to physiologic responses that may be even morbid or lethal (Figure 2). The ancient Greek physician Hippocrates, known as the father of Western medicine, in his work “On airs, waters and places”, documented the human physiology and clinical manifestaions variations amid populations living under different environmental conditions (wind flow, density and direction, soil type, temperature, humidity, waters, etc.). On the other hand, Roman mythology, by attributing the heat phenomena to the rise of the “dog star” (Sirius) defined the time periods of heatwaves between 3rd of July and 11th of August each year12. Coincidentally, the heat events studied herein took place during July. Currently, we have real-time and historical records to evaluate the heatwave effects and plan future mitigations via public health measures.\n\nIn this study, we focus on the largest port of Southeast Europe and the Eastern Mediterranean Sea, Piraeus. According to the National Oceanic and Atmospheric Administration (NOAA), the location’s latitude is 37.873° and longitude is 23.675, while its coordinates are 37°56′34.8″N 23°38′49″E. It is a rather flat (highest elevation/hill) 87 m (285 ft) coastal urban city covering 50.417 km2 (19.466 sq mi). Piraeus’s seaport is only 7 km from the Athens city center. It usually has temperature which is 3 °C lower than Athens, with blowing sea winds and a higher humidity12,13. Piraeus is flat, including only one hill of 87 m height, while the mountains are in the far distance. Athens, on the contrary, includes hills and mountains, and is characterized by vast urban density and numerous heat-islands due to stone pedestrian areas, narrow roads and high buildings. In Piraeus the urban density is clearly lower and the roads are wider, allowing the sea winds to cool the city. In addition, the sea water vapor, enhanced by extreme heat, contributes to the deleterious effects of carbon dioxide while being transported inland by the blowing western winds23 It should be noted herein that this water vapor percipitates by 0.04 p/million annually23.\n\nThe seven-fold relative risk in mortality of Athens compared to Piraeus in 1987 may be explained by the geography (Athens city basin is surrounded by four mountains and includes four hills), the urban density, and the microclimatic characteristics (sea jets, mostly plain ground, etc). The photochemistry pollution emitted by the industries located in the greater Piraeus area (beyond the Piraeus municipality borders) is transported to Athens city center by the western wind and/or jets, possibly influencing the population, but not the surface ozon concentration, as established by Varotsos et al.24 The same study and Kiraly25 suggested that temperature, wind flows and humidity may be responsible for the in situ variations of pollution and relevant episodes. Although the calculated discomfort index was at medical emergency levels (> 32) and more or less equivalent in Piraeus and Athens, the deaths observed were clearly fewer than those that occurred in the Athens municipality (Table 2).\n\nThe differences in death events between the Athenian heatwaves are attributed to preventive measures and daily practice followed by the population. Most, if not all, houses took sun shading and air conditioning provisions immediately following the 1987 heat. Greek authorities imposed restrictions on outdoor working hours (for blue collar workers, construction workers, farmers, etc.) and advised the population to stay at home or under shade during the most dangerous hours of 11am–4pm.\n\nPollution parameters are directly and indirectly affected by solar activity26. Solar activity contributes to stroke-related mortality (thrombotic events), as demonstrated by previous studies27, although it has been established that it does not to climate change26. Thus, we added the relevant data, herein, for future consideration with future heatwave events. Finally, the 1987 heatwave results were of great importance because confounding factors, such as lifestyle, dietary preference variations, high pollution exposure, and genetic heterogeneity were absent at the time27. Our study was limited to death events reported by the municipality and not the greater area of Piraeus or Athens. The health impacts of exposure to overheating include hyperthermia, triggering bleeding disorder either through thrombosis in small vessels or disseminated intra-vascular coagulation. The resultant bleeding disorder may lead to multi-organ dysfunction syndrome and/or death (Figure 2).\n\nThe 1987 heatwave in Greece had been a real milestone in public health policy and citizens’ daily practice. Until this heatwave, construction practices followed a certain manner, which neglected traditional methods which were used to protect from prolonged extreme weather events in the past. More specifically, citizens had no provision for sun shading or air conditioning. After the 1987 heatwave, the Greek authorities and the population took measures to better prepare against such events in the future. This was mirrored in the lower mortality rates due to extreme heat events in 1988 and 1992. Some of the excess mortality risk (about 47%) observed in 1992 is probably explained by a significant change in population consistency as a result of a vast immigration flow from the northern borders of the country, that was in progress at the time and not registered in the 1991 census.\n\nFinally, these results confirm the findings of Dimitriadou et al., Ebi et al. and Mazaraki et al., indicating that public health warning systems need to be created which consider locality, including geography, microclimatic parameters, population consistency and behavior28–30.\n\nThe probability of NO affecting each heatwave was found to be higher in Athens irrespective of year. The lack of significant fluctuations of NO in time has been noted by Varotsos24. In Piraeus 1987, ozone probability (certainty) to regulate the heatwave effect on strokes was higher. Additionally, it is established that ozone levels show a positive linear correlation to ambient temperature31, man-made pollution and moisture32. Thus, we believe that, during the Piraeus heatwave in 1987, seawater evaporated, entraining industrial pollution and subsequently increasing tropospheric ozone through photochemical reactions.\n\n\nConclusions\n\nThe 1987 heatwave had a decisive role in Greek reality. From the same heat-stress event, Piraeus, a coastal city, experienced less mortality than the neighboring continental Athens. The heatwave events that followed had milder effects because of the newly established public health prevention policy and citizens’ adaptation to the new measures. The heatwaves were affected by NO in Athens every year and ozone in Piraeus in 1987, as observed using probabilities extracted via network evaluations.",
"appendix": "Data availability\n\nPiraeus Mortality data may be found in Geronikoulou et al.27. The rest of the mortality data is derived from the included publications. All pollution measurements (ozone and nitric oxide) were calculated from the measurements included in the Hellenic Ministry of Environment and Energy reports, whereas humidity and temperature measurements were derived from literature as well as the Hellenic National Meteorological Service archives\n\nFigure 1 Our created network\n\nFigure 2 Our created summary of heat-related physiology mechanisms for non-health educated readers convenience\n\n\nReferences\n\nKeim ME: The Epidemiology of Extreme Weather Event Disasters (1969-2018). Prehosp Disaster Med. 2020; 35(3): 267–71. PubMed Abstract | Publisher Full Text\n\nCenter for Research on the Epidemiology of Disasters (CRED): EM-DAT:The International Disaster Database. In: Ecole se Sante Publique UCdL. editor. Brussels, Belgium, 2019.\n\nBasu R: High ambient temperature and mortality: a review of epidemiologic studies from 2001 to 2008. Environ Health. 2009; 8(1): 1–13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHajat S, Vardoulakis S, Heaviside C, et al.: Climate change effects on human health: projections of temperature-related mortality for the UK during the 2020s, 2050s and 2080s. J Epidemiol Community Health. 2014; 68(7): 641–8. PubMed Abstract | Publisher Full Text\n\nHuang C, Barnett AG, Wang X, et al.: Projecting future heat-related mortality under climate change scenarios: a systematic review. Environ Health Perspect. 2011; 119(12): 1681–90. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKnowlton K, Lynn B, Goldberg RA, et al.: Projecting heat-related mortality impacts under a changing climate in the New York City region. Am J Public Health. 2007; 97(11): 2028–34. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHeaviside C, Tsangari H, Paschalidou A, et al.: Heat-related mortality in Cyprus for current and future climate scenarios. Sci Total Environ. 2016; 569–570: 627–33. PubMed Abstract | Publisher Full Text\n\nMichelozzi P, Kirchmayer U, Katsouyanni K, et al.: Assessment and prevention of acute health effects of weather conditions in Europe, the PHEWE project: background, objectives, design. Environ Health. 2007; 6: 12. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaccini M, Biggeri A, Accetta G, et al.: Heat effects on mortality in 15 European cities. Epidemiology. 2008; 19(5): 711–9. PubMed Abstract | Publisher Full Text\n\nArbuthnott K, Hajat S, Heaviside C, et al.: Changes in population susceptibility to heat and cold over time: assessing adaptation to climate change. Environ Health. 2016; 15 Suppl 1(Suppl 1): 33. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGeronikolou S: Public Health in Piraeus 1985-1989, Public Hygene, TIE Athens 1991.\n\nGiles BD, Balafoutis C: The Greek heatwaves of 1987 and 1988. Int J Climatol. 1990; 10(5): 505–517. Publisher Full Text\n\nGiles BD, Balafoutis C, Maheras P: Too hot for comfort: the heatwaves in Greece in 1987 and 1988. Int J Biometeorol. 1990; 34(2): 98–104. PubMed Abstract | Publisher Full Text\n\nKatsouyanni K, Trichopoulos D, Zavitsanos X, et al.: The 1987 Athens heatwave. Lancet. 1988; 2(8610): 573. PubMed Abstract | Publisher Full Text\n\nBaccini M, Kosatsky T, Analitis A, et al.: Impact of heat on mortality in 15 European cities: attributable deaths under different weather scenarios. J Epidemiol Community Health. 2011; 65(1): 64–70. PubMed Abstract | Publisher Full Text\n\nStare J, Maucort-Boulch D: Odds Ratio, Hazard Ratio and Relative Risk. Advances in Methodology and Statistics. 2016 01/01; 13: 59–67. Publisher Full Text\n\nThom EC: The discomfort index. The weatherwise. 1959; 12(2): 57–61. Publisher Full Text\n\nHanson EA, Okeke FN: Impacts of sunspot number and Geomagnetic aa-index on climate of Wet Zone West Africa during solar cycles 22–24. Sci Rep. 2021; 11(1): 11500. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMilovanovic GV, Mitrinovic DS, Rassias TM: Topics in Polynomials: Extremal Problems, Inequalities, Zeros. Singapore: World Scientific Publishing Co; 1994. Publisher Full Text\n\nCorless RM, Fillion NA: Graduate Introduction to Numerical Methods. New York, USA, 2013. Reference Source\n\nBurden RL, Faires JD: Numerical analysis. 9th ed. ed. Boston, MA: Brooks/Cole, Cengage Learning; 2011. Reference Source\n\nCheney W, Kincaid D: Numerical mathematics and computing. 6th ed. Boston, MA: Brooks/Cole, Cengage Learning; 2013. Reference Source\n\nMcElroy MB: The Atmospheric Environment. Princeton University Press; 2002. Reference Source\n\nVarotsos C, Efstathiou M, Tzanis C, et al.: On the limits of the air pollution predictability: the case of the surface ozone at Athens, Greece. Environ Sci Pollut Res Int. 2012; 19(1): 295–300. PubMed Abstract | Publisher Full Text\n\nKiraly A, Bartos I, Janosi IM: Correlation properties of daily temperature anomalies over land. Tellus A. 2006; 58(5): 593–600. Publisher Full Text\n\nTan C, Tan B, Liu B: Investigation of the relationship between the air pollution and solar activity. Astrophysics and Space Science. 2017; 362(8): 139. Publisher Full Text\n\nGeronikolou S, Leontitsis A, Petropoulos V, et al.: Cyclic stroke mortality variations follow sunspot patterns [version 2; peer review: 2 approved]. F1000Res. 2020; 9: 1088. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEbi KL, Schmier JK: A stitch in time: improving public health early warning systems for extreme weather events. Epidemiol Rev. 2005; 27: 115–21. PubMed Abstract | Publisher Full Text\n\nMatzarakis A, Muthers S, Rutz F: Application and comparison of UTCI and PET in temperate climate conditions. Finisterra. 2014; 49(98). Publisher Full Text\n\nDimitriadou L, Nastos P, Zerefos C: Defining Heatwaves with Respect to Human Biometeorology. The Case of Attica Region, Greece. Atmosphere. 2021; 12(9): 1100. Publisher Full Text\n\nCamalier L, Cox W, Dolwick P: The Effects of Meteorology on Ozone in Urban Areas and their use in Assessing Ozone Trends. Atmos Environ. 2007; 41(33): 7127–37. Publisher Full Text\n\nEbi KL, McGregor G: Climate change, tropospheric ozone and particulate matter, and health impacts. Environ Health Perspect. 2008; 116(11): 1449–55. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "185613",
"date": "28 Jul 2023",
"name": "Alexandros G. Georgakilas",
"expertise": [
"Reviewer Expertise Applied Physics and Biological effects of radiations from UV to ionizing."
],
"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, the authors have studied the important role of heatwaves due to climate change. Heatwave associated mortality is one of the established markers of their human effects. Populations adapt to temperature variations/challenges differently for unknown reasons. Thus, heatwave evaluations should be enriched by historical context and local data, to allow better precision and prediction. The authors, present mortality data for 1987 collected from the Piraeus municipality registry, whereas data for Athens were obtained from literature retrieved from PUBMED. Ambient characteristics were derived from a thesis and the reports of national organizations. From the death events, the odds ratio and relative risk in Athens compared to the Piraeus 1987 event were calculated. Finally, a simple neural network proposed the dominant ambient parameter of the heatwave phenomenon in each place.\nThe study is well-thought and organized but the authors need to consider the following :\nComments:\nLanguage in general must be more carefully looked at and read for more proper English.\n\nPlease rephrase the sentence \"The same study and Kiraly\".\n\nIf there is a detailed chart/map (from National Metereological Agency in Greece: EMY) of the winds blowing in the area during the heat wave of 1987 which is maybe not available on the internet, this reviewer thinks it's worth to provide these data since it will support the claims of the work.\n\nPlease explain why the sunspots were included and if there is any correlating data or literature that mention in 1987 in Athens and Piraeus areas morbidity rates for elderly people due to possible exposure to the high temperatures during not recommended hours like between 12-5.\n\nThe PubMed database - does it contain any relative biological data for such conditions?\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Yes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "10453",
"date": "29 Feb 2024",
"name": "Stella Geronikolou",
"role": "Author Response",
"response": "In this study, the authors have studied the important role of heatwaves due to climate change. Heatwave associated mortality is one of the established markers of their human effects. Populations adapt to temperature variations/challenges differently for unknown reasons. Thus, heatwave evaluations should be enriched by historical context and local data, to allow better precision and prediction. The authors, present mortality data for 1987 collected from the Piraeus municipality registry, whereas data for Athens were obtained from literature retrieved from PUBMED. Ambient characteristics were derived from a thesis and the reports of national organizations. From the death events, the odds ratio and relative risk in Athens compared to the Piraeus 1987 event were calculated. Finally, a simple neural network proposed the dominant ambient parameter of the heatwave phenomenon in each place. The study is well-thought and organized but the authors need to consider the following: Comments: Language in general must be more carefully looked at and read for more proper English. We have appropriately edited the MS. Please rephrase the sentence \"The same study and Kiraly\". We rephrased as follows: “This study same as that of Kitaly et al …” If there is a detailed chart/map (from National Metereological Agency in Greece: EMY) of the winds blowing in the area during the heat wave of 1987 which is maybe not available on the internet, this reviewer thinks it's worth to provide these data since it will support the claims of the work. Actually, there is such a map in the National Metereological Agency in Greece (EMY) in printed but not digital archives. We have added it as Figure 3.tiff Please explain why the sunspots were included and if there is any correlating data or literature that mention in 1987 in Athens and Piraeus areas morbidity rates for elderly people due to possible exposure to the high temperatures during not recommended hours like between 12-5.The underlying mechanism linking solar cycle length and earth surface temperature is poorly understood. Total solar irradiance as a valid marker of solar energy increases in solar activity maxima (sunspots increase) and decreases in solar minima accordingly. Lane et al suggested that the sensitivity of the climate to the solar irradiance is 27% higher than its sensitivity to greenhouse warming effects. http://www-das.uwyo.edu/~geerts/cwx/notes/chap02/sunspots.html Lane, L.J., M.H. Nichols, and H.B. Osborn 1994: Time series analyses of global change data. Environ. Pollut., 83, 63-68. Aquila, V., Swartz, W. H., Waugh, D. W., Colarco, P. R., Pawson, S., Polvani, L. M., & Stolarski, R. S. (2016). Isolating the roles of different forcing agents in global stratospheric temperature changes using model integrations with incrementally added single forcings. Journal of Geophysical Research: Atmospheres, 121(13), 8067–8082. https://doi.org/10.1002/2015JD023841 Kopp, G., Krivova, N., Wu, C.J. et al. The Impact of the Revised Sunspot Record on Solar Irradiance Reconstructions. Sol Phys 291, 2951–2965 (2016). https://doi.org/10.1007/s11207-016-0853-x Geronikolou S, Leontitsis A, Petropoulos V, Davos C, Cokkinos D, Chrousos G. Cyclic stroke mortality variations follow sunspot patterns. F1000Res. 2020 Sep 3;9:1088. doi: 10.12688/f1000research.24794.2. PMID: 33224479; PMCID: PMC7667520. The highest temperature is observed between the hours 12.00-17.00. No death event was observed in ages 0-50 y in Piraeus. Most deaths occurred in the age groups over 65 in Piraeus during this heatwave. Greek women usually buy bread before lunchtime (from 12.00-15.00), thus the idea of the Reviewer seems real. The PubMed database - does it contain any relative biological data for such conditions? Many heatwaves have been reported in the PubMed database. No other publication refers to Southeastern Mediterranean cities before 1992. We added a new citation, that of Geronikolou S, Leontitsis A, Petropoulos V, Davos C, Cokkinos D, Chrousos G. Cyclic stroke mortality variations follow sunspot patterns. F1000Res. 2020 Sep 3;9:1088. doi: 10.12688/f1000research.24794.2. PMID: 33224479; PMCID: PMC7667520. where we explain how electromagnetic perturbations affect human physiology: by a preserved physiology mechanism in ages and species (R1)."
},
{
"c_id": "11192",
"date": "14 Jun 2024",
"name": "Alex Georgakilas",
"role": "Reviewer Response",
"response": "The authors have carefully addressed all comments raised by this reviewer."
}
]
},
{
"id": "161963",
"date": "08 Sep 2023",
"name": "Themis P. Exarchos",
"expertise": [
"Reviewer Expertise Data mining",
"decision support systems"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article presents an analysis and comparison of the heatwaves of Piraeus and Athens in 1987. Mortality data were collected from registries and literature, whereas ambient characteristics were collected by previous research and open national reports. The odds ratio of death events of the two cities were calculated and compared. The major outcome found was that the heatwave was seven-fold more lethal in Athens than in Piraeus, dependent on nitric oxide (NO) concentration.\nThe article is well written and results are presented in an easy to understand way for the readers.\nComments to the authors: Please extend the introduction section with additional references and state of the arts in similar works (other heatwaves, other parameters taken into account, comparison models etc).\nIn addition, please add some more details on the identification of the following probabilities: Piraeus 1987 - ozone probability 0.993 Athens 1987 - NO probability 0.999 Athens 1988 - NO probability 0.999 Athens 1992 - NO probability 0.999\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Yes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "10454",
"date": "29 Feb 2024",
"name": "Stella Geronikolou",
"role": "Author Response",
"response": "This article presents an analysis and comparison of the heatwaves of Piraeus and Athens in 1987. Mortality data were collected from registries and literature, whereas ambient characteristics were collected by previous research and open national reports. The odds ratio of death events of the two cities were calculated and compared. The major outcome found was that the heatwave was seven-fold more lethal in Athens than in Piraeus, dependent on nitric oxide (NO) concentration. The article is well written and results are presented in an easy to understand way for the readers. Comments to the authors: Please extend the introduction section with additional references and state of the arts in similar works (other heatwaves, other parameters taken into account, comparison models etc). We have added 3 more references (11-13) targeting to the same nearer-geographical area, as well as one (10) that establishes the need for studies like ours. In addition, please add some more details on the identification of the following probabilities: Piraeus 1987 - ozone probability 0.993 Athens 1987 - NO probability 0.999 Athens 1988 - NO probability 0.999 Athens 1992 - NO probability 0.999 We added the following text: The values were divided by the sum of exponential values and then converted into probabilities. According to previous analyses, the opted softmax function translated the resultiant numbers into a probability distribution. Thus, the output of the function can be interpreted by a percentage number representing the probability of an event to occur."
}
]
}
] | 1
|
https://f1000research.com/articles/12-115
|
https://f1000research.com/articles/10-1028/v1
|
11 Oct 21
|
{
"type": "Study Protocol",
"title": "Disease burden and adverse pregnancy outcomes due to cardiovascular conditions complicating pregnancy in Sri Lanka: a protocol",
"authors": [
"Ayesh Hettiarachchi",
"Niroshan Lokunarangoda",
"Thilini Agampodi",
"Suneth Agampodi",
"Niroshan Lokunarangoda",
"Thilini Agampodi",
"Suneth Agampodi"
],
"abstract": "Background Cardiovascular diseases (CVD) are the commonest indirect medical cause of maternal deaths worldwide, both in high-income and low and middle-income countries. To minimize the effects of CVD in pregnancy, proper risk assessment and appropriate referral is required. In Sri Lanka, cardiovascular disease complicating pregnancy is a significant cause of maternal mortality, second only to postpartum hemorrhage. Screening for CVD in pregnancy in Sri Lanka is limited to a routine clinical assessment. Evidence-based guidelines are yet to be developed, and this deficit may have resulted in a substantial underestimation of the CVD burden. This study aims to determine the burden of CVD in early pregnancy and develop a risk prediction model to be used in field pregnancy clinics in Sri Lanka to reduce CVD effects in pregnancy. Methods A prospective cohort study was carried out in the Anuradhapura district, Sri Lanka. Following registration to the antenatal care, pregnant women fulfilling the eligibility criteria were invited to attend a special clinic at their relevant Medical Officer of Health (MOH) area. Risk assessment was done through history and a clinical examination, and suspected/probable cases were referred for an echocardiogram by a consultant cardiologist. All the recruited participants in the first trimester were prospectively followed up and screened again between 24–28 weeks of the period of amenorrhoea (POA). Antenatal ward admissions with CVD complicating pregnancy will be extracted, and a telephone interview will be carried out between 6–12 weeks after the expected delivery date to cover postpartum morbidities. Discussion This proposed study will be the largest of its kind carried out in the local setting. The study's findings will be beneficial for policymakers to develop guidelines to reduce maternal cardiovascular disease morbidities and mortalities in Sri Lanka.",
"keywords": [
"maternal",
"heart disease",
"pregnancy",
"cardiovascular",
"Sri Lanka",
"Anuradhapura"
],
"content": "Introduction\n\nIn 2017, an estimated 295,000 (uncertainty interval 279,000–340,000) women died due to pregnancy-related complications, with 86% of these deaths occurring in sub-Saharan Africa and south-east Asia1. The sustainable development goal target 3.1, reducing the global maternal mortality ratio (MMR) to less than 70 per 100,000 live births United Nations: Transforming our world, seems still too far away with an estimated MMR of 211 per 100,000 live births currently. Despite global interventions, obstetric hemorrhage still accounts for 27·1% (19·9–36·2) of all maternal deaths, followed by hypertension (14·0%, 11·1–17·4), sepsis (10·7%, 5·9–18·6) and abortions (7·9%, 4·7–13·2)2. While the direct causes are still contributing to most deaths, 27.5% are due to indirect causes, and the proportion is increasing. Despite this increasing trend, there is little focus by the leading international maternal health non-governmental organizations and UN organizations on these causes3.\n\nCardiovascular diseases (CVD) are the commonest indirect medical cause of maternal deaths worldwide, both in high-income countries (HIC) and low and middle-income countries (LMIC)2. Although CVD affects only 1–4% of pregnant women, cardiomyopathy is reported as a leading cause of indirect maternal death4. The general hemodynamic changes during pregnancy with 40–45% increase of blood volume, up to 50% increase in cardiac output, 15–30% increase in heart rate together with changes in vascular resistance, renal blood flow, red cell volume, and structural changes5 put the system into a state of stress, which can greatly increase the risk of CVD related mortality and morbidity during pregnancy. To minimize the effects of CVD in pregnancy, proper risk assessment and appropriate referral are required6. The use of a risk index is always preferred for predicting maternal cardiac risk7,8. Several risk assessment models have been suggested for this purpose and are being used in many HICs. These include the CARPEG score by the Cardiac Disease in Pregnancy Study8,9, the Zahara model10, and the World Health Organization (WHO) risk classification11.\n\nIn Sri Lanka, cardiovascular disease complicating pregnancy is a major cause of maternal mortality, second only to postpartum hemorrhage12,13. National Maternal Mortality Reviews 2016 outcome dissemination12 shows 120 maternal deaths in 2016, and of those, 24 (20%) were related to cardiovascular disease. These included, complicated congenital heart condition (n=5), rheumatic valvular heart disease (n=3), myocarditis (n=2), cardiomyopathy (n=1), HELLP syndrome (n=3), eclampsia (n=4), and other hypertensive disorders (n=2). In the year 2017, maternal deaths due to cardiovascular diseases were 20 out of 127 total maternal deaths, and it was only second to dengue hemorrhagic fever in that year14.\n\nScreening for CVD in pregnancy in Sri Lanka is limited to a routine clinical assessment. Evidence-based guidelines are yet to be developed for the screening of cardiovascular disease in pregnancy. This lack of proper screening may lead to a substantial underestimation of the CVD burden. Although it is the second leading cause of maternal deaths, locally available data on cardiovascular conditions complicating pregnancy are limited13,15, probably due to late diagnosis and underestimation.\n\n\nObjectives\n\nThe present study's main objective is to determine the burden of CVD in early pregnancy and determine the incidence of CVD during pregnancy. Findings of this study will be used to develop a risk prediction model to be used in field pregnancy clinics in Sri Lanka to reduce the effects of CVD in pregnancy.\n\n\nMethods\n\nThis study was conducted as a part of large ongoing cohort study in Anuradhapura district, Sri Lanka, Rajarata Pregnancy Cohort (RaPCo). Details of the study setting, study population, sampling procedure, and the study sample of the RaPCo study are published elsewhere16. The specific protocol for cardiac disease complicating pregnancy is described here.\n\nThis is a prospective cohort study developed to determine the prevalence and the incidence of common CVD conditions in a cohort of pregnant females in the Anuradhapura district.\n\nThe present study was carried out in the Anuradhapura district, the largest Sri Lanka district. According to 2017 Department of Census and Statistics data17, it covers 7,179 km2 with a total population of 917,748. The total fertility rate of the district is 2.4 births per woman, one of the highest values in Sri Lanka18.\n\nIn Sri Lanka, the field maternal and child health services are mainly provided by the public health administrative units named \"Medical Officer of Health\" (MOH) areas. In each MOH area, a Medical Officer of Health (MOH) is in charge and leads a team of ground-level health care workers, including public health midwives (PHM), public health nursing sisters (PNS), and public health inspectors. In Anuradhapura, this service for pregnant women is provided through 22 MOHs, and currently 17 PNS and more than 250 PHM are working in the area. Spatial distribution of those MOH areas is displayed in Figure 1.\n\nThis figure shows the 22 MOH areas in the district. It has been reproduced with permission from Agampodi TC et al. The Rajarata Pregnancy Cohort (RaPCo): study protocol. BMC Pregnancy Childbirth [Internet]. 2020 Jun 26 [cited 2020 Nov 30];20(1):374. Available from: https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-020-03056-x\n\nCurative services are provided through 56 hospitals/primary care units, including one teaching hospital (tertiary care unit) and three base hospitals (secondary care units). Almost all deliveries (99.5%) take place in government hospitals18. The study was conducted in all 22 MOH areas covering all the antenatal clinics.\n\nAll pregnant females in Anuradhapura district.\n\nAll pregnant females visiting antenatal clinics in the Anuradhapura district from July to September 2019.\n\nPregnant women:\n\n1. Registered by field midwives and visiting field antenatal clinics in the Anuradhapura district.\n\n2. Period of amenorrhoea (POA) less than 12 weeks by the time of recruitment.\n\n1. Pregnant women planning to leave the study area for childbirth or after childbirth.\n\n2. Pregnant women who are not registered at field antenatal clinics.\n\nAll the pregnant females registered at field antenatal clinics in Anuradhapura within three months from the beginning of the study were screened (Figure 2). The usual number of pregnant mothers registered in each quarter is around 4000. However, 15–20% are registered after a POA of 10 weeks. Around 3000 pregnant women were recruited as the sample size. We hypothesized that the incidence of CVD complicating pregnancy among those who were without risk factors would be around 5% compared to 2% among those who did not have risk factors. With a conservative estimate of unexposed to exposed ratio 5:1, power of 80%- and two-sided confidence at 95% a sample of at least 1529 pregnant women (Kelsey formula) were required for the study. With around 15% early pregnancy miscarriages and 10% expected attrition, a minimum of 1911 pregnant women were required, and the number was well within the number recruited. Based on the actual rate of CVD, we will calculate the power of the study to detect the expected outcomes retrospectively.\n\nThe flow chart shows the developed methodology to achieve the study objectives. Following the registration to the antenatal care, pregnant women fulfilling the eligibility criteria were invited to attend a special clinic in their Medical Officer of Health area. Risk assessment was done through a specific interviewer-administered questionnaire, including clinical features of present cardiovascular diseases and a clinical examination. Based on these data and cardiac screening, suspected/probable cases with cardiovascular conditions were referred for an echocardiogram and consultant cardiologist's opinion. All the recruited participants in the first trimester were followed up between 24–28 weeks of the period of amenorrhoea at the routine antenatal clinic visit. They were screened again using a separate short interviewer-administered questionnaire (20) and were subjected to general and cardiac examination, referrals were done using a checklist (20). All antenatal ward admissions with cardiac disease complicating pregnancy and all intensive care unit admissions were also screened during the study period. A telephone interview was conducted during the antenatal period and between 6–12 weeks after the expected delivery date to cover all antenatal and postpartum morbidities.\n\nFollowing registration to the antenatal care, pregnant women fulfilling the eligibility criteria were invited to attend a special clinic in their relevant MOH area. This invitation was given by way of a leaflet provided to the antenatal women through the PHM. At the special clinic, potential participants were recruited by the data collectors who visit these special antenatal clinics (ANC) in the field. Data collectors visited each field antenatal clinic in all 22 MOH areas on the pre-planned special clinic day. Eligible pregnant mothers were educated about the research purpose and written informed consent was obtained before recruitment. Participants were informed that they might need to visit the Teaching Hospital, Anuradhapura, if the study suggested an echocardiogram. All the other data collection and follow-up was done at the routine antenatal clinics. Recruitment was carried out until the data collection period was over.\n\nWe carried out the risk assessment through a specific interviewer-administered questionnaire, including clinical features of present cardiovascular diseases19 and a clinical examination. The examination included a baseline physical examination and referral checklist, including a specific set of variables/signs, each defined previously, to improve the validity and reliability of data19. Measurement of blood pressure and CVS examination auscultation was done using standard protocols given to all medical officers doing the clinical assessment19. Specially trained medical graduates carried out data collection to use the above equipment using standard guidelines, which was issued in print for each procedure19.\n\nAccording to the baseline data, every recruited mother was classified according to the New York Heart Association (NYHA) classification. Based on that data and cardiac examination screening, suspected/probable cases with cardiovascular conditions were referred to the Professorial Unit, Teaching Hospital, Anuradhapura, for an echocardiogram and consultant cardiologist's opinion (Figure 2).\n\nWe developed this checklist with less stringent criteria to improve the sensitivity with low threshold values to develop a more refined screening checklist based on the results of the study. The development of the screening checklist was done after a literature review and expert opinions. We incorporated this checklist into the examination sheet to minimize the duplication of work.\n\nAs the objective was to determine the prevalence of common cardiac conditions in the first trimester of the pregnant female, the referral method was developed to have a low threshold. If any of the above signs or symptoms were positive, the participants were referred to the consultant cardiologist at the Professorial Unit, Teaching Hospital, Anuradhapura.\n\nAll screening positive patients were subject to a two-dimensional (2D) echocardiogram and an electrocardiogram (ECG) to evaluate cardiac electrical activity and rhythm. The ECG was taken using the Zonecare, iMAC 300 Three channel ECG machine, and the 2D echocardiogram using a Philips EPIQ 7.\n\nAll the recruited participants in the first trimester were followed up between 24–28 weeks of POA at the routine antenatal clinic visit. A separate short interviewer-administered questionnaire was used19. We also carried out a general and cardiac examination, and referrals were done using a checklist19.\n\nParticipants were followed up through the routine system, and all maternal morbidities and hospital admissions recorded through a specific hospital surveillance system. All antenatal ward admissions with cardiac disease complicating pregnancy were extracted and cross-matched with the initial cohort to determine whether there were conditions missed through the screening. This was done in two major hospitals with a consultant obstetrician where all pregnant mothers from Anuradhapura districts are transferred. To determine the near misses and severe complications, all intensive care unit admissions were also screened during the study period. We matched all pregnant admissions with the original cohort to identify any cardiac disease complicating pregnancy.\n\nA telephone interview was conducted with all study participants to document all antenatal morbidities in addition to the hospital admission screening. The interviews were carried out between 6–12 weeks after the expected delivery date to cover postpartum morbidities. Records relating to those who reported any hospital admissions were extracted from relevant hospitals. This approach was proposed to minimize unnecessary in-person contacts during the COVID-19 pandemic.\n\nTo reduce the bias in sample selection and recruitment all the mothers who have registered at the field antenatal clinics were given an equal opportunity to participate in the study. All the participants who fulfilled the inclusion and exclusion criteria were recruited to the study.\n\nWhen it comes to the examination to reduce the observer bias, digital blood pressure monitors were used with the same method in every clinic. Two readings are taken from both arms with a five-minute gap and the lower value recorded as the blood pressure. If a high blood pressure value is detected (SBP> 135mmHg or DBP >85mmHg), a third reading is taken after a rest period of five minutes. The same procedure is carried out in subsequent blood pressure measurements of the participants.\n\nTo reduce the bias when referring participants for further assessment, referrals were initiated based solely on screening positivity at the initial assessment.\n\nThe main focus of the study is to describe the actual disease burden of cardiovascular disease in pregnancy in Sri Lanka (prevalence and incidence). With a proper assessment of disease burden, we expect to propose strategies to be included in the national program.\n\nA field model will be developed using the findings for early detection of cardiovascular conditions during pregnancy at field level. With the appropriate inputs from the stakeholder, this model will be used to propose the required changes in strategies related to control and prevention of CVD complicating pregnancy in Sri Lanka.\n\nAll the data collection will be done using the electronic data collection method using a unique barcode and serial number. The database will be automatically formulated through this data collection platform. Access to the databases will be under restricted access. Access will be granted to principal investigators only. Two-dimensional echocardiogram reports will also be formulated via database management software, and a copy of the report will be provided to the participant. This database will also be accessible by the researchers only, and the data will be stored under the unique serial number.\n\nData will be analysed using the Statistical Package for Social Sciences (SPSS) version 26 (IBM SPSS Statistics, RRID:SCR_019096). An open-access alternative that can provide an equivalent function is the R stats package (R Project for Statistical Computing, RRID:SCR_001905).Point prevalence of cardiovascular diseases complicating pregnancy will be calculated with 95% confidence intervals (CI). The prevalence of each specific condition will also be presented as proportions. The cumulative incidence of heart disease incidence will be estimated, and the 95% CI will be calculated using a Poisson distribution. An analysis of factors associated with cardiovascular disease complicating pregnancy will be done, and relative risks will be calculated. A risk prediction model will be developed to identify the predictive factors of cardiac disease complicating pregnancy. This model will be used to develop a screening checklist for the public health system.\n\nAll study procedures were done following the Helsinki declaration. Research was carried out only after the informed written consent of the participant for participation and after agreeing to publication of data collected in an anonymized format. Participants have been provided with the opportunity to withdraw from the study at any time. Participant identification data will be kept under lock and key to protect confidentiality. All identified conditions will be managed and treated by the consultant cardiologists with appropriate investigations and referral without an additional cost to the participant. Ethical clearance for the \"Rajarata Pregnancy Cohort\" has been obtained from the Ethics Review Committee, Faculty of the Medicine & Allied Sciences, Rajarata University of Sri Lanka under the approval number ERC/2019/07.\n\nAll the recruited participants have been provided with a serial number and a unique bar code. All the material and data belonging to a participant will be labelled with the above serial number and bar code. All the consent forms will be stored separately under lock and key at the Maternal and Child Health Research Unit, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka. The participant has also received an identity card with basic details and a barcode.\n\nFindings will be published as research articles, abstracts, and presentations. Generated knowledge will be communicated with the local health care authorities, and nationally important findings will be published as policy briefs.\n\n\nDiscussion\n\nThis study on cardiovascular disease in pregnancy is the largest study conducted of its kind in Sri Lanka. The patterns and associations identified with regard to cardiovascular disease during pregnancy and its distributions among the population will give an idea about the true picture of the disease in the LMICs. As this study focuses on both prevalence and incidence of cardiovascular disease during pregnancy it will provide a wider understanding about risks and predictive symptoms and signs of CVD during pregnancy in Sri Lankans. This will enable development of a model for early CVD risk identification among pregnant females. Also, the findings will have an impact on policy change to go beyond routine screening methods.\n\nThis project proposal was developed in June 2019. Recruitment of participants was done from July to September 2019. The first round of referral and cardiovascular assessment and part of the second trimester assessment is already completed. However, the follow-up was interrupted due to the COVID-19 pandemic and lockdown since March 2020. Based on the country’s current situation, delivery and outcome data collection has been initiated through alternative methods. Telephone interviews and data extraction from labor rooms are also in progress. Records relating to those who reported any hospital admissions during the telephone interviews will be extracted from the relevant hospitals.\n\n\nData availability\n\nOpen Science Framework: Generating Evidence for Ending Preventable Maternal Deaths (GEEPMED) in Sri Lanka. Extended data for ‘Disease burden and adverse pregnancy outcomes due to cardiovascular conditions complicating pregnancy in Sri Lanka’, ‘Tools’. https://doi.org/10.17605/OSF.IO/RTDCG19\n\nThis project contains the following extended data:\n\n1. Baseline questionnaire\n\n2. Baseline physical examination and referral checklist sheet\n\n3. Definition of selected signs and symptoms\n\n4. Guide for blood pressure measurement\n\n5. Guide for CVS examination\n\n6. Follow-up questionnaire\n\n7. Follow-up examination and referral checklist sheet\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)",
"appendix": "References\n\nWHO: Trends in maternal mortality 2000 to 2017: estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division: executive summary. World Health Organization; 2019. Reference Source\n\nSay L, Chou D, Gemmill A, et al.: Global causes of maternal death: A WHO systematic analysis. Lancet Glob Health. 2014; 2(6): 323–33. PubMed Abstract | Publisher Full Text\n\nStorm F, Agampodi S, Eddleston M, et al.: Indirect causes of maternal death. Lancet Glob Health. 2014; 2(10): e566. PubMed Abstract | Publisher Full Text\n\nCoulter SA, Lew J, Jenny B: Heart Disease in Pregnancy - Valvular Heart Disease. In: Carabello BA, editor. London: Springer London; 2020; 237–83. Publisher Full Text\n\nPerales M, Nagpal TS, Barakat R: Physiological Changes During Pregnancy: Main Adaptations, Discomforts, and Implications for Physical Activity and Exercise. BT - Exercise and Sporting Activity During Pregnancy: Evidence-Based Guidelines. In: Santos-Rocha R, editor. Cham: Springer International Publishing; 2019; 45–56. Publisher Full Text\n\nScott NS: Management of cardiovascular disease during pregnancy. US Cardiology Review. Radcliffe Group Ltd; 2018; 12(2): 119–23. Publisher Full Text\n\nDrenthen W, Boersma E, Balci A, et al.: Predictors of pregnancy complications in women with congenital heart disease. Eur Heart J. 2010; 31(17): 2124–32. PubMed Abstract | Publisher Full Text\n\nSiu SC, Sermer M, Colman JM, et al.: Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation. 2001; 104(5): 515–21. PubMed Abstract | Publisher Full Text\n\nBalci A, Sollie-Szarynska KM, van Der Bijl AG, et al.: Prospective validation and assessment of cardiovascular and offspring risk models for pregnant women with congenital heart disease. Heart. 2014; 100(17): 1373–81. PubMed Abstract | Publisher Full Text\n\nPieper PG: Pre-pregnancy risk assessment and counselling of the cardiac patient. Neth Heart J. 2011; 19(11): 477–81. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNtusi NB, Mayosi BM: Aetiology and risk factors of peripartum cardiomyopathy: A systematic review. Int J Cardiol. 2009; 131(2): 168–79. PubMed Abstract | Publisher Full Text\n\nFamily Health Bureau Sri Lanka: National Maternal Mortality Reviews - 2016 Outcome Dissemination. 2016; 30. Reference Source\n\nHaththotuwa HR, Attygalle D, Jayatilleka AC, et al.: Maternal mortality due to cardiac disease in Sri Lanka. Int J Gynaecol Obstet. 2009; 104(3): 194–8. PubMed Abstract | Publisher Full Text\n\nFamily Health Bureau Sri Lanka: Annual Report of the Family Health Bureau 2017. Reference Source\n\nStephen SJ: Changing patterns of mitral stenosis in childhood and pregnancy in Sri Lanka. J Am Coll Cardiol. 1992; 19(6): 1276–84. PubMed Abstract | Publisher Full Text\n\nAgampodi TC, Wickramasinghe ND, Prasanna RIR, et al.: The Rajarata Pregnancy Cohort (RaPCo): study protocol. BMC Pregnancy Childbirth. 2020; 20(1): 374. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDepartment of Census and Statistics - Sri Lanka: Distict Statistical Handbook Anuradhapura. 2018. Reference Source\n\nDepartment of Census and Statistics, Ministry of National Policies and Economic Affairs: Sri Lanka Demographic and Health Survey - 2016 (Full Report). Reference Source\n\nHettiarachchi A, Agampodi SB: Tools. 2021. http://www.doi.org/10.17605/OSF.IO/RTDCG"
}
|
[
{
"id": "96617",
"date": "11 Nov 2021",
"name": "Anish Keepanasseril",
"expertise": [
"Reviewer Expertise Maternal medicine"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study aims to assess the burden of CVD among women in the first trimester of pregnancy and to develop a risk prediction model to be used in Sri Lankan hospitals.\nEven though the study has already started according to the protocol, the following are my suggestions:\nObjective\nIt needs to be more specific about the study. The incidence of CVD may be difficult to determine unless we have a pre pregnancy check up and have the details available. It may be better to use the prevalence, as it will include the cases which are there in pre pregnancy as well as those who develop during the pregnancy.\n\nKindly mention the outcome for which the predictive models are being developed. Is it to identify people with the CVS or for identifying those who are at risk of adverse outcomes. Risk models can stratify and you might need to consider a future study or a subset wherein this stratification is useful either by a temporal or an external validation of the model.\nMethodology\nThe design of the study, inclusion and exclusion criteria are well presented and helpful for performing/guiding a study to be planned else where. However, further reading it was unclear about the study design as well as about the intention of adding matched controls which is highlighted in point 3. If any secondary objective is planned please provide the details in the objectives section of the protocol.\n\nIt is unclear which are the diseases that are included as CVD. As heart disease, hypertension, stroke etc. could be taken as CVD. More clarity is required on the outcomes.\n\nHow and why was the matching performed under patient follow up? Did the matched controls also undergo the same procedure? How did you avoid the selection bias in choosing controls? Did you look at any nested case control design? If so all these need to be more clarified in the text. Being an observational study, this is the main area of interest to the reader.\n\nDetail about how the model will be built needs to be included.\n\nIs the rationale for, and objectives of, the study clearly described? No\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": [
{
"c_id": "7605",
"date": "20 Jan 2022",
"name": "Ayesh Hettiarachchi",
"role": "Author Response",
"response": "Thank you reviewing this paper. Please find a point by point response for the comments below. Comment 1 - The study aims to assess the burden of CVD among women in the first trimester of pregnancy and to develop a risk prediction model to be used in Sri Lankan hospitals. Response 1 - To clarify the confusion, this study aims to develop a risk prediction model to be used in Sri Lanka field health care setup not in the Sri Lankan hospitals. Comment 2 - It needs to be more specific about the study. The incidence of CVD may be difficult to determine unless we have a pre pregnancy check up and have the details available. It may be better to use the prevalence, as it will include the cases which are there in pre pregnancy as well as those who develop during the pregnancy. Response 2 - Thank you for the comment. And I’m sorry for the confusion. This study recruit first trimester pregnant females and screen them for CVD conditions. As you mentioned, we determine the prevalence of CVD conditions during the first trimester pregnant females. This change was done in the first objective. In addition, we do follow up the same cohort of pregnant females at the second trimester of their pregnancy. Then at the post-partum period. This follow up section of the study is planned to determine the incidence of CVD among the same cohort of pregnant females. This part is clearly shown in the flow diagram provided and at the outcomes section. To avoid the confusion, I’ve changed the first sentence under the subheading “objectives”. Comment 3 - Kindly mention the outcome for which the predictive models are being developed. Is it to identify people with the CVS or for identifying those who are at risk of adverse outcomes. Risk models can stratify and you might need to consider a future study or a subset wherein this stratification is useful either by a temporal or an external validation of the model. Response 3 -Thank you for the comment. This predictive model is being developed to identify pregnant women with adverse pregnancy outcomes due to existing or an emerging CVD condition. The objective is edited as suggested. Comment 4 - The design of the study, inclusion and exclusion criteria are well presented and helpful for performing/guiding a study to be planned else where. However, further reading it was unclear about the study design as well as about the intention of adding matched controls which is highlighted in point 3. If any secondary objective is planned please provide the details in the objectives section of the protocol. Response 4 - Thank you for the kind comment. There are no matched controls in this study. This is a cohort study where a selected group of individuals recruited, screening and then follow-up throughout the pregnancy and the post-partum period. It is unclear from where this confusion is arising. Probably the misunderstanding is about the sentence “All antenatal ward admissions with cardiac disease complicating pregnancy were extracted and cross-matched with the initial cohort”. This was not a matched control group. To make sure we are not missing data, we separately looked at hospital admissions during the period and confirmed whether there are patients from our cohort who are having CVD related complications, but not captured during the follow up. We have edited the sentence. Comment 5 - It is unclear which are the diseases that are included as CVD. As heart disease, hypertension, stroke etc. could be taken as CVD. More clarity is required on the outcomes. Response 5 - Thank you for the valuable comment. I have included a statement under the cardiovascular risk assessment section. All the acquired or congenital heart conditions and other related cardiovascular conditions including hypertension, heart failure and pulmonary hypertension and arrythmias considered as CVD related to this study. History Cerebrovascular events were taken during the data collection for the risk prediction of related CVD condition. Comment 6 - How and why was the matching performed under patient follow up? Did the matched controls also undergo the same procedure? How did you avoid the selection bias in choosing controls? Did you look at any nested case control design? If so all these need to be more clarified in the text. Being an observational study, this is the main area of interest to the reader. Response 6 - Kindly see my reply under your comment number 1 of methodology part. Comment 7 - Detail about how the model will be built needs to be included. Response 7 - Thank you for the comment. Details included under the data analysis section."
}
]
}
] | 1
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https://f1000research.com/articles/10-1028
|
https://f1000research.com/articles/12-589/v1
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01 Jun 23
|
{
"type": "Research Article",
"title": "The influence of indigenous knowledge on chemistry metacognition",
"authors": [
"Tavonga Tawanda",
"Awelani V. Mudau",
"Tavonga Tawanda"
],
"abstract": "Background: Chemistry is viewed as a difficult and challenging subject by many learners and teachers which leads to poor academic performance in the subject. The majority of the pre-service science teachers in Zimbabwean teachers’ colleges also find Chemistry to be a challenging subject. The focus of this study was to simplify and contextualize the teaching and learning of Chemistry concepts for life-long survival and problem-solving skills through exploring the influence of indigenous Chemistry knowledge on Chemistry metacognition. Methods: An embedded mixed methods case study was underpinned by the social constructivist theory, which is used to collect and analyse the data. Twenty-nine respondents were purposively sampled. Their metacognition awareness was determined through focus group interviews which are triangulated with a paper and pen test. The indigenous Chemistry knowledge possessed by the pre-service science teachers was collected using focus group interviews, which was then used in the intervention stage for Chemistry metacognition. Results: The findings suggest that indigenous knowledge influences chemistry metacognition in a positive way. Conclusions: Further research is required on the relationship between indigenous Chemistry knowledge and Chemistry metacognition. It is recommended that Chemistry educators should be capacitated with skills for identifying and applying indigenous Chemistry knowledge that is relevant to Chemistry metacognition.",
"keywords": [
"academic performance",
"African philosophical orientation",
"chemistry metacognition",
"contextualisation",
"indigenous chemistry knowledge."
],
"content": "Introduction\n\nThe learning in the schools can be influenced by the cultural background of leaners which inturn infleunces their learning style (Baker and Taylor, 1995). This results in two Chemistry knowledge perspectives (worldviews), indigenous cultural Chemistry knowledge and western cultural Chemistry knowledge which differ only on cultural perspective/views. Chemistry is a sub-culture of Western culture (Cobern and Aikenhead, 1997). African science learners in Sub-Sahara Africa experience many challenges in science education associated with the clashes between western science which is Eurocentric, and African indigenous knowledge due to the two knowledge systems’ social and cultural differences (Mhakure and Mushaikwa, 2014). Emphasis must be on the importance and benefits of identifying similarities between indigenous Chemistry and western Chemistry ways of knowledge construction and transmission to create an understanding of the natural world, which is more encompassing (Tsuji and Ho, 2002). It is crucial to have a blending of indigenous Chemistry knowledge and western Chemistry knowledge learning, which leads to an environment of shared learning whereby indigenous Chemistry knowledge is not assimilated by the dominant western Chemistry knowledge, but is thoroughly articulated and clearly heard, resulting in learning being reciprocal and making Chemistry learning meaningful to local Chemistry learners (Banner, 2016).\n\nPhilosophically, indigenous Chemistry knowledge is a form of knowledge that is generated locally which is real and disseminated through learning from social and environmental interactions by pre-service science teachers. Social constructivists view cognitive functions as dependent on social interactions with other individuals and the environment (Masciotra, 2005). Indigenous knowledge is a form of reality which comes from social invention that has solved and continues to solve Chemistry challenges in indigenous society. Social interactions and cultural influences result in shared meaning of indigenous Chemistry knowledge making it a human product. Indigenous Chemistry knowledge is an empirical form of knowledge as it has been tested over time and there is physical as well as chemical evidence of it and its uses (Mudau and Tawanda, 2022). Learning is a social process which in itself is active knowing that involves the activation and application of prior knowledge. Prior knowledge is the basis for all learning. Indigenous Chemistry knowledge is the prior knowledge which is a basis of learning. The advanced deliberate manipulation of mental or emotional effects of perception and reasoning directed towards a particular goal such as improving learning, which is the acquisition of knowledge, skills and affective states is called metacognition. Metacognition is recognition of the value of prior knowledge (Taylor, 1999) whilst chemistry metacognition is the recognition of the value of indigenous Chemistry knowledge (prior-knowledge).\n\nMetacognition has a positive impact in general on learner outcomes in terms of thinking and learning, particularly for learners with disabilities (Georghiades, 2004). Metacognition is encouraged by independent Chemistry knowledge (Smith, Black and Hooper, 2017; Somerville, 2017; Philling-Cormick and Garrison, 2007; Louca, 2003). Learners with high academic achievement have more metacognitive awareness and partake in a lot of self-regulation compared to lower academic achieving learners (Hartman, 2001). All learners are capable of metacognition as long as they have the ability to perform a skill (Schraw, 1998). In learners, metacognition is promoted through awareness by learners of the existence of metacognition, which differs from cognition, and thus academic success is increased (Schraw, 1998). An interactive approach that mixes teacher and expert modelling, direct instruction, group activities which allow learners to share the knowledge they have on cognition and reflection can be extremely effective (Schraw, 1998).\n\nThe perception held by many learners and teachers is that Chemistry is a difficult and challenging subject (Uzezi, Ezekiel and Auwal, 2017; Mahdi, 2014; Gafoor and Shilna, 2013). In Matabeleland North and other Zimbabwean provinces, the biology, Chemistry and physics subjects are believed to be extremely difficult by both learners and teachers (Regional Centre for Social Responsibility, 2012; Ogunkola and Samuel, 2011). A study in Zimbabwe showed that science education suffers because of a negative attitude from learners (Gadzirayi, Bongo, Ruyimbe, Bhukuvhani and Mucheri, 2016). The perception of Chemistry being exceedingly difficult is even stronger in rural secondary day-schools. Rural secondary schools are government-owned schools in rural areas, which are normally poorly resourced in terms of both human and material resources that negatively affects the teaching and learning process. Due to this perception, Chemistry is viewed as a subject for very intelligent or gifted learners only (Cardellini, 2017; Fu, Fitzpatrick, Conners, Clay, Toombs, Busby and Discoll, 2015). As a result, very few learners take up Chemistry as a subject in their studies. For the few who take it up, their performance is usually poor when compared to other subjects (Thondhlana, 2020). There are concerns in Tsholotsho North in Matabeleland North about the poor performance by learners in pure sciences and mathematics at ordinary level (Dube, 2016). There is poor academic performance in sciences, especially in Chemistry (Uchegbu, Oguoma, Elenwoke and Ogbuagu, 2016; Hassan, Ali, Salum, Kassim, Elmoge and Amour, 2015; Anditi, Okere and Muchiri, 2013; Ezeudu and Obi, 2013).\n\nThe researchers’ observation during the August Vacation School teaching of 2016 and 2017 in Tsholotsho (Matabeleland North) and of pre-service science teachers at the teachers’ college was that there was indeed poor performance by learners in Chemistry. The majority of the pre-service science teachers at the teachers’ college come from Matabeleland province schools, which have low pass rates and have learners who find Chemistry challenging. (Chikiwa, 2018; Nkala, 2018). Pre-service science teachers find Chemistry difficult and challenging as they struggle with the Chemistry knowledge, skills and attitudes, thus resulting in poor academic performance in Chemistry at the teachers’ college. (Mudzakir, 2017; Wheeldon, 2017; Cam, Topcu and Sulun 2015). Misconceptions or alternative conceptions, insufficient content knowledge, skills and attitudes contribute significantly to the pre-service science teachers’ ability to adequately learn Chemistry in terms of difficulties and challenges. Pre-service teachers were found to have electrochemistry misconceptions and inadequate content knowledge (Yilmaz and Bayrakceken, 2015; Bektas, Tuysuz, Kirbulut and Cetin-Dindar, 2011). The teaching and learning of Chemistry concepts are detached from the socio-economic daily life experiences of pre-service science teachers (Ugwu and Diovu, 2016) as it is conceptualised from the western and eastern philosophical orientations that are based on a universal approach towards knowledge generation and dissemination (Shumba, 2014).\n\nInternationally and regionally, research has shown that the acquisition and use of metacognition improves academic achievement and motivation of learners including, those who are intellectually limited, education resource disadvantaged, prior knowledge limited as well as culturally disadvantaged. A study of how the performance of secondary school students in Chemistry was impacted by metacognition awareness was studied in the Asian country of Pakistan (Rahman, Jumani, Chaudry, Chitsti and Abbasi, 2010). The findings were that; (i) metacognition is important in student’s academic achievement and, (ii) highly metacognitive students’ performance was better than those of low metacognitive skills (Rahman, Jumani, Chaudry, Chitsti and Abbasi, 2010). The function of metacognition among primary school learners in the African country of Kenya in everyday problem solving was studied (Aurah, Koloi-Keaikitse, Isaacs and Finch, 2011). The findings of the study were; (i) learners who were better problem solvers were those with higher metacognition level than learners who had low levels of metacognition and, (ii) high grade level learners were better in terms of metacognition and the ability to perform problem-solving (Aurah, Koloi-Keaikitse, Isaacs and Finch, 2011). Van Aswegen (2015) did a study on the metacognitive awareness development of intermediate phase young learners using stories for facilitation in South Africa. The finding of the research implied that the development of metacognitive awareness using story-based interventions yielded positive results (Van Aswegen, 2015).\n\nMost of the research that has been done has focused on the relationship between metacognition and academic achievement. However, there is a gap in knowledge on the contribution of indigenous Chemistry knowledge (pre-service science teachers’ prior knowledge and beliefs) to Chemistry metacognition in the Zimbabwean teachers’ college context. This research seeks to fill that gap in knowledge. The ideal Chemistry teaching and learning should be done from the African philosophical orientation that is locally contextualised and culturally relevant in terms of knowledge generation and dissemination that meets the needs and provides practical solutions to the everyday life chemical challenges and problems of the community.\n\nThe aim of this research was to explore the use of culturally contextualised indigenous Chemistry knowledge by pre-service science teachers in Chemistry metacognition. The following research questions guided the study:\n\n(i) What is the indigenous Chemistry knowledge possessed by pre-service science teachers?\n\n(ii) How relevant is the indigenous Chemistry knowledge to Chemistry metacognition?\n\n(iii) How effective is the indigenous Chemistry knowledge in Chemistry metacognition?\n\n\nMethods\n\nAn embedded mixed methods case design was employed which had 99% of qualitative and 1% of quantitative elements in which the interpretive paradigm was employed to study the influence of indigenous Chemistry knowledge on Chemistry metacognition. Focus group interviews and a test (paper and pen) were used to assess the metacognitive awareness level of the pre-service science teachers before and after the indigenous Chemistry knowledge intervention. Focus group interviews were also used to get the indigenous Chemistry knowledge possessed and practised by pre-service science teachers. This study was conducted with post ordinary level pre-service science teachers from a secondary teacher training college in Zimbabwe.\n\nThe University of South Africa college of education ethics review committee approved the study on 2019/07/24, and consent was sort of in a written form. The certificate has the following reference number 2019/07/24/63816997/18/MC. This article is written in in with SRQR guidelines (Mudau, 2023d).\n\nThe participants were 29 (15 males and 14 females) post ordinary level pre-service science teachers who were in their first term at college who had no previous exposure to tertiary chemistry education. The whole class was asked to participate and all agreed. There was no exclusion criteria. The highest academic qualification for 20 of the pre-service science teachers was ordinary level and 9 was advanced level. There are three major levels of education in Zimbabwe which are primary, secondary and tertiary level. The primary level consists of 9 years of schooling that are split into 4 years of infant education and 5 years of junior education which has an external public examination written at the end. Secondary level is split into junior high school and senior high school. Junior high school is 4 years which ends with an external public examination called ordinary level examination. A full certificate at ordinary level must have five subjects passed including English language, Mathematics and Combined Science (formally Integrated Science).\n\nThe ordinary level full certificate enables learners to: look for work, proceed to senior high school or go to tertiary institutions for professional training such as teachers’ colleges. Senior high school (advanced level) is two years (form 5 and 6) and is done after having passed five ordinary level subjects. Advanced level external public examinations are written in the second year (form 6) of senior high school. A complete certificate at advanced level consists of two subjects passed which enables learners to look for work or enroll at tertiary institutions.\n\nPurposive sampling was used to choose the participants. All the students in a particular class in the college of education were asked to participate using letters. They all accepted. Out of the 29 participants, those who had chemistry at ordinary level were five and those with chemistry at advanced level were 3 who were also part of the 5 who had chemistry at ordinary level.\n\nThe first author who is male and held a master degree at the time was the lecturer at the institution from which data was collected had to collected all the data. The data was part of his PhD studies. The first author gave the potential participants letters that were approved by the ethical committee of the university. The letters contained the purpose of the research and why they were requested to participate. Methodology triangulation was used to ensure that matters of biases are taken care of. The second author also read the trabnscripts to ensure that there was internal validity. In stage one, the metacognitive awareness levels of the pre-service science, teachers before the indigenous chemistry knowledge intervention were ascertained using an adapted metacognitive awareness inventory from Schraw and Dennison (1994). The adapted metacognitive awareness inventory was in the form of focus interview guide and paper and pen test for triangulation purposes. So the students were given the pen and pare test first and theerfater they were also interviewd. As indicated what was in the pen and paper instrument was also similar to what was in the interview guide. The tools were piloted to ensure that they were free to a certain degree of any biases or mistakes. This happened after contact teaching time. This happened between March and June in 2020. The adapted Metacognitive Awareness Inventory (MAI) ascertained the levels of all the metacognition sub-components which were: declarative knowledge, procedural knowledge, conditional knowledge (knowledge of cognition) and planning, information management strategies, comprehension monitoring, debugging strategies and evaluation (regulation of cognition).\n\nIn stage two, focus group interviews conducted by the first author were used for identifying the cultural indigenous Chemistry knowledge held and practised by pre-service science teachers. Each focus group had a maximum of nine participants and they were three groups with two of those having 10 students each. The interviews were recorded by an audio recording gadget. Each group varied from between 20 minutes to 30 minutes in duration. For all the tools that were used for this study field notes wrer also taken for triangulation purposes. Document analysis was also used for identifying the cultural indigenous Chemistry knowledge held and practised by pre-service science teachers in stage two. In stage three, focus group interviews and paper and pen test were used to assess the extent to which pre-service science teachers have acquired Chemistry metacognition after the cultural indigenous Chemistry knowledge intervention. The intervention was a series of four additional lesson wherein based on what was discovered from the stage 1 and 2 data collection procedures. The content ranged from fermentation processes from their homes to fractional distillation of liquid air process from their homes.\n\nObservations were done with pre-service science teachers in the Chemistry laboratory at the teachers’ college during Chemistry lecture times. Permission was asked for using the letters and consent forms as approved by the ethics committee. Document analysis was done using pre-service science teachers’ written tests, assignments and practical write-ups at the teachers’ college after marking the pieces of work. For stage four, document analysis was used to assess and find out the extent to which pre-service science teachers have acquired Chemistry metacognition through cultural indigenous Chemistry knowledge. The pieces of work that focused on the topics of atomic structure, redox reactions, stoichiometry, periodic table and periodicity as well as practical assessments were analysed. This was done over a period of eight weeks in which three tests, two assignments and two practical write-ups were done. The college minimum assessment requirements are one test, 1 assignment and 1 practical per term.\n\nMaterials used in this study can be found as Extended data (Mudau, 2023c).\n\nThe typology approach which was a constant comparison data analysis was used to analyse the metacognitive awareness levels of the pre-service science teachers before and after the indigenous chemistry knowledge intervention. In a typology approach themes and catergories are predetermined but this does not mean that if new themes and categories are identified whilst analysing data they are not included. The data analysis scheme was developed based on the research questions and literature reviewed. The indigenous chemistry knowledge possessed and practised by the pre-service science teachers for use in the indigenous chemistry knowledge intervention was also analysed using the constant comparison data analysis. Quantitative data was analysed using SPSS version 23.\n\n\nResults\n\nThe results are presented below from the sample described in the methodology. The raw results can be found as Underlying data (Mudau, 2023a, b).\n\nPre-service science teachers exhibited that they are a repository for indigenous Chemistry knowledge and skills. Indigenous Chemistry knowledge and skills possessed by pre-service science teachers cover most survival areas in their lives. Extensive use and effectiveness of indigenous Chemistry knowledge and skills were found in agriculture, environmental conservation, food processing, food preservation and health care. These verisimilitudes indigenous knowledge, skills and attitudes are shown in Tables 1 to 6.\n\nPre-service science teachers were of the opinion that Indigenous Chemistry knowledge has the same Chemistry ideas/concepts which are found in the western Chemistry knowledge. The indigenous Chemistry knowledge is the Chemistry prior knowledge for western Chemistry knowledge. Indigenous Chemistry knowledge and skills have numerous beneficial characteristics in most aspects of life in general. However, it is their invaluable assistance in understanding Chemistry concepts which was also mentioned by pre-service science teachers among other benefits in terms of Chemistry metacognition. The fact that they are passed from one generation to the next generation ensures continuity of chemistry prior knowledge which is a vital bridge between indigenous chemistry knowledge and western Chemistry knowledge. Pre-service science teachers were also in agreement that the indigenous Chemistry knowledge and skills are very efficient.\n\nIndigenous Chemistry knowledge and skills are seen as useful and reliable by pre-service science teachers to a larger extent. However, the pre-service science teachers identified the aspect of some of the indigenous Chemistry knowledge and skills as being seasonal that can pose challenges on reliability. The experiences of indigenous Chemistry knowledge and skills that have been had by the majority of the pre-service science teachers are positive. Having positive experiences with indigenous Chemistry knowledge and skills means the pre-service science teachers will less easily forget the acquired indigenous Chemistry knowledge and skills. They went on to say these indigenous Chemistry knowledge and skills are relatively easy to master, though it depends on the complexity of the indigenous Chemistry knowledge and skills to be mastered. This implies that the majority of pre-service science teachers have acquired some indigenous Chemistry knowledge, skills and attitudes from their everyday cultural experiences.\n\nThere are some common characteristics between indigenous Chemistry knowledge and western Chemistry knowledge that were identified by pre-service science teachers. These included taking precautions when using them, procedures and processes to be followed, formal chemistry is based on indigenous chemistry and serve the same purpose of providing chemical solutions to chemical challenges. Pre-service science teachers are aware that there is a relationship between indigenous Chemistry knowledge and formal Chemistry with the indigenous Chemistry knowledge being the known (prior chemistry knowledge) and college Chemistry the unknown in chemistry teaching and learning.\n\nA comparison of the focus group with pen and paper test metacognition awareness scores before intervention for the pre-service science teachers are shown in Figure 1.\n\nThe pen and paper test metacognition awareness scores are higher than for focus group metacognition awareness scores before the intervention. The Pearson product moment correlation was used to correlate the focus group metacognition awareness scores with those of the pen and paper test metacognition awareness scores before the indigenous Chemistry knowledge intervention. The correlation was found to be 0.79 which shows a strong positive correlation between the focus group metacognition awareness scores and pen and paper test metacognition awareness scores before intervetion. The variance of the focus group metacognitive awareness scores that is accounted for by the variance in the pen and paper test metacognition awareness scores is 62% before the intervetion.\n\nThe mean scores for focus group metacognition awareness as well as for pen and paper test metacognition awareness before intervention are indicated in Figure 2.\n\nThere is a slight difference in the mean scores implying a slight difference in metacognition awareness between focus group and pen and paper test before intervention. This indicates that the results of the focus group metacognition awareness are to a large extent confirmed by the pen and paper metacognition awareness test in terms of triangulation.\n\nIn the observations for the application of indigenous chemistry knowledge, the application of indigenous Chemistry knowledge in the lectures before the intervention phase was rare except for second lecture where it was medium standard. This was when the “Plum pudding” model of the atom was described using a positively charged pumpkin, which has pumpkin seeds acting as the electrons by one pre-service science teacher. However, after metacognition instruction using indigenous Chemistry knowledge as prior knowledge, there was a high standard of the application of indigenous Chemistry knowledge in Chemistry concepts. Also, in the two Chemistry practical assessments that were done, the application of indigenous Chemistry knowledge was high though most of the time negatively. This suggests that the indigenous Chemistry knowledge intervention was effective as pre-service science’s frequency of using indigenous Chemistry in the Chemistry lectures had improved.\n\nA comparison of the focus group with pen and paper test metacognition awareness scores after intervention for the pre-service science teachers are shown in Figure 3.\n\nThere was a high metacognition awareness for the focus groups when compared to pen and paper test in most of the metacognition components except for planning after the indigenous Chemistry knowledge intervention. This is the opposite for the scores before the indigenous Chemistry knowledge intervention in which the metacognition awareness for focus groups was lower when compared to the pen and paper test. There is no consistency in the increase of the scores.\n\nThe Pearson product moment correlation was used to correlate the focus group metacognition awareness scores with the pen and paper test metacognition awareness scores after the indigenous Chemistry knowledge intervention. The correlation was found to be 0.76 which shows a strong positive correlation between the focus group metacognition awareness scores when correlated to the pen and paper test metacognition awareness scores after the intervention. The variance of the focus group metacognitive awareness scores that is accounted for by the variance in the pen and paper test metacognition awareness scores is 58% after the intervention.\n\nThe mean score of focus groups when compared to the mean score of the pen and paper tests after the indigenous Chemistry knowledge intervention give the extent to which the two are in agreement. The mean scores for focus group metacognition awareness as well as for pen and paper test metacognition awareness before the indigenous Chemistry knowledge intervention are indicated in Figure 4.\n\nThere was no difference in the mean scores implying there was no difference in the metacognition awareness after the indigenous Chemistry knowledge intervention of the mean score of the focus groups when compared to the mean score of the pen and paper test after the indigenous Chemistry knowledge intervention. This indicates that the results of the focus group metacognition awareness were confirmed by the paper and pen metacognition awareness test after the indigenous Chemistry knowledge intervention in terms of triangulation. The impact of the indigenous Chemistry knowledge intervention on metacognitive awareness can be ascertained by comparing the focus group scores after the indigenous Chemistry knowledge intervention to those before the indigenous Chemistry knowledge intervention. A comparison of the scores after the indigenous Chemistry knowledge intervention and before the indigenous Chemistry knowledge intervention are shown in Figure 5.\n\nThe metacognition awareness scores are higher after the indigenous Chemistry knowledge intervention when compared to the metacognition awareness before the indigenous Chemistry knowledge intervention. The indigenous Chemistry knowledge intervention had an effect in the positive direction on the metacognition awareness. The indigenous Chemistry knowledge intervention had an effect of improving the metacognition awareness of the pre-service science teachers. Comparing the means scores of the focus group before and after the indigenous Chemistry knowledge intervention gives an idea of the degree of change after the indigenous Chemistry knowledge intervention. Figure 6 shows this comparison.\n\nThere is a sharp difference between the focus group metacognition awareness mean score before the indigenous Chemistry knowledge intervention and focus group mean score after the indigenous Chemistry knowledge intervention. The metacognition awareness mean score of the focus groups increased after the indigenous Chemistry knowledge intervention. This implies a sharp increase in metacognition awareness as a result of the indigenous Chemistry knowledge intervention. The impact of the indigenous Chemistry knowledge intervention can be found by comparing the pen and paper metacognition awareness scores after the indigenous Chemistry knowledge intervention to those before intervention. Figure 7 shows a comparison of the pen and paper metacognition awareness scores after the indigenous Chemistry knowledge intervention to those before the intervention.\n\nThe pen and paper test metacognition awareness scores are higher after the indigenous Chemistry knowledge intervention. The indigenous Chemistry knowledge intervention had an effect of increasing the metacognition awareness. There is a consistency in the increase in metacognition awareness for both the focus groups and pen and paper test after the indigenous Chemistry knowledge intervention. A comparison of the pen and paper test metacognitive awareness mean scores before and after the indigenous Chemistry knowledge intervention shows changes that might have occurred as a result of the intervention. Figure 8 shows a comparison of pen and paper metacognitive awareness scores before and after intervention for the pre-service science teachers.\n\nThere is a significant difference in metacognition awareness mean scores before and after the indigenous Chemistry knowledge intervention. The metacognition awareness mean score of the pen and paper test increased after the indigenous Chemistry knowledge intervention. The implication is that there is a significant increase in metacognition awareness as a result of the indigenous Chemistry knowledge intervention. The change in academic performance of the pre-service science teachers can be identified by the differences in the mean scores of assignments and tests before and after the indigenous Chemistry knowledge intervention. The mean scores for assignments and tests before and after the indigenous Chemistry knowledge intervention for pre-service science teachers are shown in Figure 9.\n\nThe pre-service science teachers’ mean scores of the Chemistry assignment one and chemistry test one before indigenous Chemistry knowledge intervention are lower than the mean scores of the assignment two and test two & three after intervention. This implies that the academic performance of the pre-service science teachers improved after the indigenous Chemistry knowledge intervention.\n\n\nDiscussion\n\nThe purpose of this embedded mixed methods case study was to explore the influence of indigenous Chemistry knowledge on Chemistry metacognition. This was achieved through interrogating; the indigenous Chemistry knowledge held by the respondents, the relevance and effectiveness of indigenous Chemistry knowledge to Chemistry metacognition. The sample size was a limiting factor even though in depth analysis of data was of paramount importance as the fidnings could relate to many context similar to this one.\n\nThe findings suggest that pre-service science teachers have a wealth of indigenous Chemistry knowledge in a variety of fields, including agriculture, environmental conservation, food processing, food preservation, and health care. The conclusions of this study are consistent with Mapara’s (2009) findings, which showed that local people still possess indigenous knowledge despite years of colonization. This knowledge includes fields like zoology, botany, agriculture, medicine, and artisan skills. These findings are in line with those of Ugboma (2014), whose research indicated that most people have access to and use indigenous knowledge. According to Senanayake’s (2006) research, experts in indigenous knowledge are typically members of society.\n\nThe results suggest a relevance of indigenous Chemistry knowledge to Chemistry metacognition as it is the prior knowledge for Chemistry metacognition. Metacognition requires a learner to have prior knowledge in order for one to learn it. Prior knowledge is required for the development of metacognitive skills as it facilitates and assist in the development of the cognitive skills states Alshammari (2015). The Chemistry concepts in indigenous Chemistry knowledge are the same as those found in western Chemistry knowledge, hence their relevance to Chemistry metacognition. As a result of this relevancy, there are calls for the integration of indigenous knowledge into science education.\n\nAspects of culture of non-western science learners such as indigenous knowledge (traditional and empirical knowledge), ways of knowing as well as indigenous world views should be taken into account and incorporated as science learning foundations (Quigley, 2009). This is in agreement with Ugwu and Diovu (2016), who opine that indigenous knowledge and their practices’ integration into the teaching of chemistry enhances learners’ Chemistry understanding and achievement. Another finding was that there are many similarities between indigenous Chemistry knowledge and western (college) Chemistry knowledge that exist. Tsuji and Ho (2002) emphasised the importance and benefits of identifying similarities between indigenous Chemistry knowledge and western Chemistry knowledge ways of knowledge construction and transmission so as to enhance understanding of the natural world.\n\nResults from this study imply that indigenous Chemistry knowledge is quite effective in improving Chemistry metacognition as there was an increase in terms of metacognition awareness after the indigenous Chemistry knowledge intervention. This is in agreement with Schraw (1998), who identified four ways of classroom metacognition awareness promotion. These are: highlighting metacognition importance, knowledge of cognition improvement, regulation of cognition improvement and metacognitive awareness environment fostering. This is a new insight into the relationship between indigenous Chemistry knowledge and Chemistry metacognition which has never been studied before. According to Schraw (2000), the reliability of the Metacognitive Awareness Inventory (MAI) in measuring metacognition is extremely high. A study by Van Aswegen (2015) focused on using stories to develop the metacognitive awareness of intermediate phase young learners in South Africa. Most studies have focused on the impact of metacognition on academic performance.\n\n\nConclusions and implications\n\nFrom the findings, the conclusion drawn is that Chemistry educators such as teachers and lecturers have access to indigenous Chemistry knowledge that is held and practiced by Chemistry learners in their everyday lives for survival. This indigenous Chemistry knowledge represents alternative Chemistry concepts or Chemistry misconceptions from the Chemistry learners’ social-cultural life which can either promote or disrupt the western Chemistry teaching and learning process. It is recommended that the indigenous Chemistry knowledge of chemistry learners should be identified and applied constructively in the Chemistry curriculum at teachers’ colleges, thereby contextualising the western Chemistry education.\n\nThe findings suggest that indigenous Chemistry knowledge is relevant to chemistry metacognition as it is the prior knowledge for Chemistry metacognition since it utilises empirical Chemistry ideas and concepts. As a result, the learners’ indigenous Chemistry knowledge assists in the understanding of western Chemistry concepts as it comes from learners’ everyday socio-cultural life experiences. It can be concluded that Chemistry metacognition can be successfully taught or increased in Chemistry learners by applying indigenous Chemistry knowledge in Chemistry education. What is recommended is that Chemistry educators should be capacitated with the knowledge and skills for identifying and applying learners’ indigenous Chemistry knowledge that is relevant to Chemistry metacognition.\n\nThe evidence suggests that indigenous Chemistry knowledge is quite effective in influencing Chemistry metacognition positively as there was an improvement of metacognition awareness after the intervention. The evidence also suggests that the intervention increased the academic performance of the pre-service science teachers in Chemistry. The conclusion drawn from the evidence is that Chemistry metacognition and the academic performance of Chemistry learners are significantly influenced by the use of indigenous Chemistry knowledge. The recommendation is that a deliberate systemic conscientisation of the importance of using indigenous Chemistry knowledge in Chemistry education for the purposes of Chemistry metacognition should be made to Chemistry learners and educators as well as other stakeholders.\n\nChemistry metacognition is the recognition of the value of one’s extensive and systematic native Chemistry knowledge (prior knowledge) with an accurate assessment of the demands of a challenging western Chemistry learning activity, what understanding and skills are needed, as well as the intelligence required to make the appropriate deduction on how to apply one’s native Chemistry knowledge reliably and effectively in a particular situation. The study has shown how the process of chemistry metacognition occurs as indicated in Figure 10.\n\nFour important major contributions to the literature on the influence of indigenous Chemistry knowledge on Chemistry metacognition have been made by this study due to the research in these four areas being relatively new and there is still limited related literature in this area. Figure 11 shows the major contributions of the study.\n\nFirst, the research participants were first year post ordinary level science pre-service science teachers who had no experience of Chemistry education at a tertiary level and found the Chemistry to be challenging, particularly for those who had no previous Chemistry education at any level of education. This study should contribute to the development of methods of identifying and collecting ideological, rational, communal and empirical indigenous Chemistry knowledge possessed by Chemistry learners for use in Chemistry education at this level. The sacred nature of some of the indigenous Chemistry knowledge as well as its visual or oral forms of transmission might pose challenges in terms of its accurate collection for use in Chemistry education.\n\nSecond, the study looked at the relevance of indigenous Chemistry knowledge in Chemistry metacognition research of which is almost non-existent when compared to the research on the effect of metacognition on academic performance (Van Aswegen, 2015; Aurah, Koloi-Keaikitse, Isaacs and Finch, 2011; Rahman, Jumani, Chaudry, Chitsti and Abbasi,2010). The findings of this study should enhance the literature on the relationship between indigenous Chemistry knowledge and Chemistry metacognition, particularly on how the former influences the latter.\n\nThird, the effectiveness of indigenous Chemistry knowledge on Chemistry metacognition was looked at in this study, which is not familiar to most Chemistry educators. The findings of this study might attract other Chemistry educators to the effect of indigenous Chemistry knowledge on Chemistry metacognition. There is more in-depth Chemistry learning and improved academic performance by Chemistry learners who have acquired Chemistry metacognition skills. Finally, this study on the influence of indigenous Chemistry knowledge on Chemistry metacognition improved the originality of the research. Although the impact of metacognition on academic performance has been analysed since the 1970s (Akman and Alagoz, 2018), the influence of indigenous Chemistry knowledge on Chemistry metacognition has never been done before. This study therefore contributes to new literature in this area.",
"appendix": "Data availability\n\nThe raw responses to the questionnaire cannot be shared as they cannot be effectively deidentifed. These data can be obtained directly from Dr Tavonga Tawanda at tavongatawanda@gmail.com.\n\nFigshare. The influence of indigenous knowledge on chemistry metacognition. https://doi.org/10.6084/m9.figshare.22666102.v1 (Mudau, 2023a).\n\nThe project contains the following underlying data:\n\n- Metacognition awareness asseesment before and after.docx\n\n- Phd assignment and test scores.docx\n\n- Unisa 2020 focus group demographic information.doc\n\n- Unisa 2020 group five indigenous chemistry knowledge focus group feedback.docx\n\n- Unisa 2020 group four indigenous chemistry knowledge group feedback.docx\n\n- Unisa 2020 group one indigenous chemistry knowledge focus group feedback.docx\n\n- Unisa 2020 group three indigenous chemistry knowledge focus group feedback.docx\n\n- Unisa 2020 group two indigenous chemistry knowledge focus group feedback.docx\n\nFigshare: Metacognition awareness assessment.xlsx. https://doi.org/10.6084/m9.figshare.22761347.v1 (Mudau, 2023b).\n\nFigshare: The influence of indigenous knowledge on chemistry metacognition. https://doi.org/10.6084/m9.figshare.22666135.v1 (Mudau, 2023c).\n\nThis project contains the following extended data:\n\n- Application of indigenous chemistry knowledge observation schedule.doc\n\n- Indigenous chemistry knowledge focus group questions.doc\n\n- Metacognition awareness focus group questions.doc\n\n- Metacognition awareness paper and pen test.doc\n\nFigshare. Completed SRQR checklist for “The influence of indigenous knowledge on chemistry metacognition’ https://doi.org/10.6084/m9.figshare.22666153.v1 (Mudau, 2023d).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nAn earlier version of this article can be found at the University of South Africa Library (https://hdl.handle.net/10500/29987).\n\n\nReferences\n\nAkman O, Alagoz B: Relation between metacognitive awareness and participation to class discussion of university students (Electronic version). Univ. J. Educ. Res. 2018; 6(1): 11–24. Publisher Full Text\n\nAlshammari MK: The effect of using metacognitive strategies for achievement and the trend toward social studies for intermediate schools students in Saudi Arabia. Int. J. Educ. Learn. 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International Journal of Social, Behavioral, Educational, Economic, Business and Industrial Engineering. 2015; 9(11).\n\nLouca E: The concept and instruction of metacognition. Teach. Dev. 2003; 7: 9–30. Publisher Full Text\n\nMahdi JG: Student attitudes towards Chemistry: an examination of choices and preferences (Electronic version). Am. J. Educ. 2014; 2(6): 351–356.\n\nMapara J: Indigenous knowledge systems in Zimbabwe: juxtaposing postcolonial theory. J. Pan Afr. stud. 2009; 3(1): 139–155.\n\nMasciotra D: Social constructivism: a theoretical framework for a competency-based curriculum. General basic education curriculum.2005. (Accessed on 27 February 2019). Reference Source\n\nMhakure D, Mushaikwa N: Science teachers’ indigenous knowledge identities. Mediterr. J. Soc. Sci. 2014; 5(20): 1554–1563. Publisher Full Text\n\nMudau AV: data. [Dataset]. figshare. 2023a. Publisher Full Text\n\nMudau AV: METACOGNITION AWARENESS ASSESSMENT.xlsx. [Dataset]. figshare. 2023b. Publisher Full Text\n\nMudau AV: THE INFLUENCE OF INDIGENOUS KNOWLEDGE ON CHEMISTRY METACOGNITION. Dataset. figshare. 2023c. Publisher Full Text\n\nMudau AV: THE INFLUENCE OF INDIGENOUS KNOWLEDGE ON CHEMISTRY METACOGNITION. Dataset. figshare. 2023d. Publisher Full Text\n\nMudau AV, Tawanda T: Pre-service science teachers’ views on the use of indigenous chemistry knowledge in chemistry metacognition. International e-Journal of Educational Studies. 2022; 6(12): 224–234. Publisher Full Text\n\nMudzakir HSA: The first year pre-service teachers’ chemical literacy in individual case using the fuel cell technology based-chemical enrichment book. AIP Conference proceedings of The 4th International Conference on Research, Implementation, and Education of Mathematics and Science (4th ICRIEMS). 2017.\n\nNkala S: Chiefs want preferential treatment for Matabeleland students. Newsday. 2018; 7.\n\nOgunkola BJ, Samuel D: Science teachers and students’ perceived difficult topics in the integrated science curriculum of lower secondary schools in Barbados. J. Educ. 2011; 1(2). Publisher Full Text\n\nPhilling-Cormick J, Garrison DR: Self – directed and self-regulated learning: conceptual links. Can. J. Univ. Contin. Educ. 2007; 33(2): 13–33.\n\nQuigley C: Globalization and science education: the implications for indigenous knowledge systems. Int. Educ. Stud. J. 2009; 2(1): 76–88. Publisher Full Text\n\nRahman F, Jumani NB, Chaudry MA, et al.: Impact of metacognitive awareness on performance of students’ in Chemistry. Contemp. Issues Educ. Res. 2010; 3(10): 39–44. Publisher Full Text\n\nRegional Centre for Social Responsibility: Regional social indaba on fulfilling the millennium development goals on education (MDG2) in Matabeleland. Harare: RCSR; 2012.\n\nSchraw G, Dennison RS: Assessing metacognitive awareness (Electronic version). Contemp. Educ. Psychol. 1994; 19: 460–475. Publisher Full Text\n\nSchraw G: Promoting general metacognitive awareness. Instr. Sci. 1998; 26: 113–125. Publisher Full Text\n\nSchraw G: 7. Assessing metacognition: implications of the Buro symposium.Scraw G, Impara JC, editors. Issues in the measurement of metacognition. Lincoln; Buros Centre for Testing; 2000.\n\nSenanayake SGJN: Indigenous knowledge as a key to sustainable development. Journal of Bibliographic Research. 2006; 2: 87–123. Publisher Full Text\n\nShumba O: Implications of socio-cultural research findings for science education reform in non-western developing countries (Electronic version). Zimb. J. Educ. Res. 2014; 26(2): 217–246.\n\nSmith A, Black S, Hooper LM: Metacognitive knowledge, skills and awareness; a possible solution to enhancing academic achievement in African American adolescents. SAGE Urban Education. 2017; pp. 1–15.\n\nSomerville MP: Metacognition. Cambridge: Cambridge Assessment International Education; 2017.\n\nTaylor S: Better learning through better thinking: developing student’s metacognitive abilities. J. Coll. Read. Learn. 1999; 30: 34–45. Publisher Full Text\n\nThondhlana B: Zimsec sounds alarm over ‘A’ level science subjects failure rate.2020. (Accessed on 16 October 2020). Reference Source\n\nTsuji LJS, Ho E: Traditional environmental knowledge and western science: in search of common ground. Can. J. Native Stud. XXII. 2002; 2: 327–360.\n\nUchegbu RI, Oguoma CC, Elenwoke UK, et al.: Peception of difficult topics in Chemistry curriculum by senior secondary school (ii) students in Imo state (Electronic version). AASCIT J. Educ. 2016; 2(3): 18–23.\n\nUgboma MU: Availability and use of indigenous knowledge amongst rural women in Nigeria. Chinese Librarianship: An International Electronic Journal. 2014; 38.\n\nUgwu AN, Diovu CI: Integration of indigenous knowledge and practices into Chemistry teaching and students’ academic achievement. Int. J. Acad. Res. Reflect. 2016; 4(4): 22–30.\n\nUzezi JG, Ezekiel D, Auwal AM: Assessment of conceptual difficulties in Chemistry syllabus of the Nigerian science curriculum as perceived by high school college students (Electronic version). Am. Educ. Res. J. 2017; 5(7): 710–716. Publisher Full Text\n\nvan Aswegen SL : Using stories to facilitate the development of metacognitive awareness among young learners in the intermediate phase. Doctoral dissertation. Stellenbosh University. 2015. Reference Source\n\nWheeldon R: Improving pre-service Chemistry teachers’ content knowledge through intervention activities (Electronic version). Int. J. Sci. Educ. 2017; 39(9): 1238–1261. Publisher Full Text\n\nYilmaz A, Bayrakceken S: Determining of the prospective teachers’ understanding of electrochemistry (Electronic version). Procedia. Soc. Behav. Sci. 2015; 174: 2831–2838. Publisher Full Text"
}
|
[
{
"id": "176497",
"date": "19 Jun 2023",
"name": "Maria Tsakeni",
"expertise": [
"Reviewer Expertise Innovative instructional strategies such as inquiry-based learning",
"practical work",
"instructional technologies and curriculum innovations such as STEM education",
"IKS and ESD in science classrooms"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 this study is important because it opens up opportunities to teach chemistry in context using IKS. Mixed methods were used. I think research question 1, What is the indigenous Chemistry knowledge possessed by pre-service science teachers? was addressed because the indigenous knowledge systems possessed by the students were identified. The insight out of the second research question, How relevant is the indigenous Chemistry knowledge to Chemistry metacognition? was that Indigenous chemistry serves as prior knowledge in chemistry classrooms.\nI however thought that if the authors had selected an IKS conceptual framework to use in the study they were going to be able to unpack this insight more deeply. The insights may help us to clarify the understanding of IKS or indigenous chemistry in this case, that it is in fact applied chemistry and that the two types of knowledge are not different from each other.\nI also have an issue with branding some of the identified knowledge/practices as non-western. Let's take just one example of tree planting to avoid soil erosion. I think that is a universal agricultural practice in the west in Africa and everywhere. This is why I say it would have been good to have a conceptual framework that shows the the overlaps and differences in any of the two knowledge systems. The research question is however addressed.\nThe third research question, How effective is the indigenous Chemistry knowledge in Chemistry metacognition? pertained to the quantitative methods used. My question is how comparisons were made between data from focus group interviews (which I assume to be qualitative) and data from papers tests (whose scores can be used as quantitative data). Until the authors explain how they got quantitative data from focus group interviews to be able to calculate correlations, this part is difficult to accept as valid. There is an need to look at the methods again and provide the missing information. For example it is not sufficient to say data were analyzed through SPSS version 23 without specifying the particular comparison tool used.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "10160",
"date": "02 Nov 2023",
"name": "Awelani Mudau",
"role": "Author Response",
"response": "1. I think this study is important because it opens up opportunities to teach chemistry in context using IKS. Mixed methods were used. I think research question 1, What is the indigenous Chemistry knowledge possessed by pre-service science teachers? was addressed because the indigenous knowledge systems possessed by the students were identified. Thank you for pointing this out. We concur with your comment. 2. The insight out of the second research question, How relevant is the indigenous Chemistry knowledge to Chemistry metacognition? was that Indigenous chemistry serves as prior knowledge in chemistry classrooms. I however thought that if the authors had selected an IKS conceptual framework to use in the study they were going to be able to unpack this insight more deeply. The insights may help us to clarify the understanding of IKS or indigenous chemistry in this case, that it is in fact applied chemistry and that the two types of knowledge are not different from each other Your observation on Indigenous Chemistry Knowledge being prior knowledge for Western Chemistry in the science classroom is on point. Thank you for your suggestion to use of IKS conceptual framework. It would have been intriguing to examine that aspect of using IKS conceptual framework. However, in this study, it appears slightly out of scope because it is the perfect theoretical framework to use on the influence of Indigenous Chemistry Knowledge on Chemistry metacognition. It is perfect as it focuses on the realization of the importance of context and culture in the learning of science. The indigenous chemistry knowledge is the learners’ culture and context which was applied to chemistry metacognition (science education). 3. I also have an issue with branding some of the identified knowledge/practices as non-western. Let's take just one example of tree planting to avoid soil erosion. I think that is a universal agricultural practice in the west in Africa and everywhere. This is why I say it would have been good to have a conceptual framework that shows the the overlaps and differences in any of the two knowledge systems. The research question is however addressed. You have raised an important idea here. However, we are of the opinion that in the context of the study, this is indigenous knowledge as it is knowledge that is localised, practiced and was developed over centuries by a local people in a particular geographical area. The overlaps of western science knowledge and indigenous science knowledge is an indicator that science is one irrespective of geographic location only differing on culture and context. Hence the application of indigenous chemistry knowledge as prior knowledge for western chemistry knowledge. 4. The third research question, How effective is the indigenous Chemistry knowledge in Chemistry metacognition? pertained to the quantitative methods used. My question is how comparisons were made between data from focus group interviews (which I assume to be qualitative) and data from papers tests (whose scores can be used as quantitative data). Until the authors explain how they got quantitative data from focus group interviews to be able to calculate correlations, this part is difficult to accept as valid. There is an need to look at the methods again and provide the missing information. For example it is not sufficient to say data were analyzed through SPSS version 23 without specifying the particular comparison tool used. You have raised another perception here. However, the research was a mixed method research though it was mainly qualitative with quantitative to a smaller extent. There were two types of questionnaires that were used in the study. The first questionnaire was qualitative which was on Indigenous Chemistry Knowledge known by respondents. The second questionnaire was quantitative since it was a metacognitive awareness inventory which generates quantitative scores by design that were used before and after indigenous chemistry intervention. The metacognitive awareness was done using focus groups and paper and pen test for purposes of correlating the responses on metacognitive awareness as well as triangulation. The purpose of the SPSS version 23 software was to convert the metacognitive awareness scores into bar graphs, line graphs and pie charts which were used to compare the scores before and after indigenous chemistry knowledge intervention"
}
]
},
{
"id": "185591",
"date": "25 Jul 2023",
"name": "Nadaraj Govender",
"expertise": [
"Reviewer Expertise Science and Indigenous Knowledge Education"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe area of research is unique and new to the field in indigenous knowledge connected to metacognition and makes a distinct contribution to education.\nHowever the literature and research focus must focus on Preservice teachers (PST) mostly and not on learners at school as the sample are PSTS and research questions based on PST. [see comments in doc]\n\nThe concept of metacognition is very briefly discussed in the beginning. This must be elaborated in depth as it is the KEY concept in the study. Do link with updated and well cited articles in chemistry education.\n\nAs Table 1-6 is a list of areas of IK, I think it’s not bringing out the experiences of the students and hence the data seems like it is a literature search. Possibly do add interviews on some aspects from Tables 1-6 which will add authenticity to the data.\n\nThere are lots of spelling errors. Suggest a thorough edit and check. [see doc]\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": "10188",
"date": "02 Nov 2023",
"name": "Awelani Mudau",
"role": "Author Response",
"response": "1. Is the work clearly and accurately presented and does it cite the current literature? Partly You have raised an important point here. The “partly” aspect is not clear on what it refers to exactly in this comment as there is clear and accurate as well as citing current literature in the comment. However, we are of the opinion that the presentation of the work was clear and accurate as it focused on the influence of indigenous knowledge on chemistry metacognition from, introduction, research questions, literture review, research methods, results and conclusion are clear and accurate as well as current literature was used at the time of the study 2. Is the study design appropriate and is the work technically sound?Yes Thank you for pointing this out. We concur with your comment 3. Are sufficient details of methods and analysis provided to allow replication by others?Partly You have raised an important point here. However, we are of the opinion that in the context of the study, the methods and analysis are sufficient for replication by others as they fully answered the research questions and met the the research objectives 4.If applicable, is the statistical analysis and its interpretation appropriate?Not applicable We take note of your view. However, we are of the opinion that the statistical analysis and interpretation is appropriate and applicable for this study as it gives the scientific degree to which the focus group and paper and test metacognition awareness scores are in agreement in terms of triangulation 5. Are all the source data underlying the results available to ensure full reproducibility?Yes Thank you for pointing this out. We concur with your comment 6. Are the conclusions drawn adequately supported by the results?Yes Thank you for pointing this out. We concur with your comment"
}
]
}
] | 1
|
https://f1000research.com/articles/12-589
|
https://f1000research.com/articles/11-76/v1
|
21 Jan 22
|
{
"type": "Brief Report",
"title": "Transmission of yellow fever vaccine virus from breast feeding mothers to their infants: reporting of yellow fever virus (YFV) RNA detection in milk specimens",
"authors": [
"Tarteel Hassan",
"Razan A. Bashir",
"Dina N. Abdelrahman",
"Hassan Madni",
"Abdel Rahim M El Hussein",
"Isam M. Elkidir",
"Khalid A. Enan",
"Tarteel Hassan",
"Razan A. Bashir",
"Hassan Madni",
"Abdel Rahim M El Hussein",
"Isam M. Elkidir",
"Khalid A. Enan"
],
"abstract": "Background: Because of yellow fever’s serious impact on health, vaccination is the principal strategy to control the disease. Administration of the yellow fever vaccine to breastfeeding women should be before they complete 9 months post-delivery, in order to prevent transmission of the yellow fever vaccine virus to their infants through breast feeding. This study aimed to confirm whether the excretion of yellow fever vaccine virus is in milk of vaccinated breastfeeding mothers and to confirm the probable transmission to their infants through breast milk. Methods: Samples were taken as follows: one serum specimen was taken 3-14 days after the date of the vaccination, and breast milk specimens were taken at four different time points between 3-4 days apart. Specimens were obtained from eight nursing mothers, who received the YVF vaccine (17DD). Mothers were asymptomatic before and after the vaccine administration but their infants developed symptoms after administration. Maternal serum samples were tested for YFV specific IgM antibodies through immuno-fluorescent assay (IFA). RNA was extracted from serum and breast milk specimens and YFV RNA screened using real-time polymerase chain reaction (RT-PCR). Results: In total, five mothers (62.5%) were positive for YFV and two mothers (25%) had YFV RNA in serum. Among milk specimens, YFV RNA was detected during the four different mentioned collection times as follows (positive milk specimens/total milk specimens): 3/8 (37.5 %), 4/6 (66.6%) and 1/4(25%). RNA was completely undetectable in the last collection time. Conclusions: YFV transmission from mothers to their babies through breast-feeding was highly probable indicated by the temporal relationship to mother’s YF vaccination.",
"keywords": [
"YFV",
"Vaccine",
"Milk",
"breast feeding mothers",
"Khartoum-Sudan"
],
"content": "Introduction\n\nThe yellow fever virus is a mosquito-borne flavivirus that causes yellow fever,1 a viral hemorrhagic fever that now occurs only in Africa, Central and South America,2 but historically has had many wide outbreaks in Europe and North America.2 Approximately 200,000 cases of yellow fever occur annually; 90% of them in Africa.2 Yellow fever severity ranges from self-limited fever illness to hemorrhagic syndrome and death.3 Most yellow fever patients are asymptomatic, but 15% develop severe illness,4 which appears as a systemic illness that affects the liver (jaundice and necrosis), renal system, and myocardial system resulting in hemorrhage and shock.5 Among the 15% of patients that develop severe illness, the mortality rate is 20%–60%.4 Reports show that yellow fever is responsible for 29,000 to 60,000 deaths in South America and Africa every year, and it’s the most severe form of mosquito-borne diseases in tropical areas.1\n\nBecause yellow fever is a potentially fatal disease, vaccination is the principal strategy to control the disease.4 An effective yellow fever 17DD vaccine was established in 1937, but there are still currently over 400 million unvaccinated people in the areas of high infection risk.1\n\nLive attenuated 17DD vaccine confers protection in more than 95% of recipients within a month after single dose vaccination. Its protection is attributed to both innate and adaptive immunity through production of neutralizing antibodies directly against the envelope protein. 17DD vaccine administration provides immunity for at least 10 years and probably can extend to give life-long immunity.17\n\nThe YFV vaccine can cause adverse side effects after its administration that range from mild to severe. The mild effects are headache, myalgia, and pain at the injection site, while severe effects can include anaphylactic shock, neurological diseases, and viscerotropic disease. The YFV vaccine is recommended to be administered after 9 months of age and from 6 months in endemic areas.6 Administration of the vaccine to breastfeeding women before 9 months post-delivery can transmit the yellow fever vaccine virus to their infants through breast milk. There are three case reports of confirmed transmission of the YFV vaccine strain from mothers to their infants through breastfeeding.7–9 The first case reported that the mother received the yellow fever vaccine 15 days after her delivery, and she had symptoms of headache, malaise, and fever after 20-22 days.7 The other two cases reported that the mothers received a yellow fever vaccine, and their infants had developed encephalitis 3-4 weeks later.6,8,9\n\nMany studies have reported the transmission and presence of other flaviviruses RNA in breast milk such as West Nile virus (WNV), Zika virus, dengue and chikungunya10–13; however, no previous study has reported the detection of YVF RNA in breast milk samples from vaccinated breast-feeding mothers in Sudan. Therefore, this study aimed to detect the yellow fever virus in breast milk and serum samples from vaccinated breastfeeding women whose infants got yellow fever illness to confirm whether the yellow fever vaccine virus is excreted and transmitted through breast milk. The mothers received the vaccine during an intensive YF vaccination campaign that involved millions of people in Khartoum State.\n\n\nMethods\n\nThe study approved by the ministry of health, Sudan (approval number 5688-2019). Verbal consent was taken from mothers due to some being unlettered and some afraid of providing written consent. This was deemed adequate and approved by the Ministry of health.\n\nThis study involved YFV testing in serum and breast milk specimens from eight nursing mothers (aged from 20-33 years) from Khartoum, Sudan in November 2019. The mothers had received the YFV vaccine (17DD) (Bio-Manguinhos/Fiocruz) during the 2019 YFV vaccination program in Khartoum within 9 months of delivery. They were not showing any symptoms of YVF before they got the vaccines; however, their infants (ages from 45 days to 8 months) developed symptoms of fever, diarrhea, jaundice, vomiting, and/or skin rashes after one week from their mother received the vaccines. Participants were approached via telephone through reports provided to the Ministry of Health to follow-up individuals who experience complications after getting vaccinated.\n\nThe samples were collected by Ministry of health medical staff from participants in different hospital vaccination points. Blood samples were collected from mothers in a plain blood container, then serum separated from the blood sample through centrifugation at 1100 rpm for 15 minutes using centrifuge (Hettich- ZENTRIFUGEN), then serum samples pipetted into clean Eppendorf tubes and stored at -80°c until their use. Milk specimens were collected in a clean glass jar by hand expression whilst the infant was nursing on the other breast and vice versa. The specimens from the breasts (right and left) were expressed into separate clean glass jars. Collection of milk specimens performed on four occasions: the first collection time was 3-14 days from the date of the vaccination. The three following collections were 3-4 days apart. Milk specimens were collected on all occasions, but serum samples were collected only in the first collection.\n\nMaternal serum samples were tested for YFV specific IgM antibodies using immuno-fluorescent assay (IFA) according to manufacturer instructions (Yellow fever virus IIFT (IgM), EUROIMMUN, Germany, catalogue number Fl 2665-1005 M).\n\nRNA was extracted from serum and breast milk specimens using a commercial RNA extraction kit (QIAamp viral RNA mini kit) according to the manufacturer instructions (Qiagen viral RNA, Germany). The extracted RNA was stored at −80°C until use.\n\nDetection of YFV RNA was performed using real-time PCR (Rotor 5 plex real-time PCR machine Qiagen, Germany). Commercial kit which developed to detect all YFV strains including vaccine strain (RealStar® Yellow Fever Virus RT-PCR Kit 1.0, Germany) was used according to manufactures protocol. The PCR program consisted of 55°C for 20 min, 95°C for 2 min, followed by 45 cycles consisting of 95°C for 15 sec, 55°C for 45 sec and 72°C for 15 sec.\n\nNo statistical analysis was needed. Data from participants were documented in an Excel sheet containing data for each mother and their infants. Rotor 5 plex real-time PCR thermo cycler software used to create Figure 3 while Figures 1 and 4 were created using word.\n\n\nResults\n\nThe eight breast feeding mothers in Khartoum state were aged between 20 to 33 years old.18 Participation per each phase of the study shown in Figure 1.\n\nFive mothers (62.5%) showed IgM antibodies against YFV using IFA technique (Figure 2). YFV RNA was detected by using real time PCR in 2 (25%) serum samples and 3 (37.5 %) in breast milk (Table 1). Results of the PCR are shown in Figure 3.\n\n(1) Positive sample for anti-YFV IgM, (2) Positive control for anti-YFV IgM, (3) negative control.\n\nPCR = polymerase chain reaction; YFV = yellow fever virus.\n\nIn this phase, only 6 samples were obtained, among them YFV RNA was demonstrated in 4 (66.6%) breast milk specimens (Table 2).\n\n* Means no sample obtained.\n\nFour mothers were enrolled in this occasion. Only 1 (25%) of the milk samples was positive for YFV RNA (Table 2).\n\nMilk specimens were obtained from 3 mothers, all specimens showed negative result for YFV RNAs (Table 2). Minimal clearance of the viral RNA in milk was 11 day after vaccination and the maximum time needed for the clearance was 24 days after vaccine administration.\n\nReal-time PCR results showed in Figure 1 and results of yellow fever virus (YFV) detection among different collection dates showed in Figure 4.\n\n\nDiscussion\n\nAccording to the universally applied recommendations for YF vaccine, breast-feeding mothers and their infants who are aged less than 9 months should avoid YF vaccination. However, when breastfeeding mothers must travel to a yellow fever–endemic area, these women should be vaccinated.16\n\nThis current study was the first study to confirm perinatal transmission of YFV, through detection of RNA in milk samples from vaccinated nursing mothers. In contrast a study by Eder Gatti (2020), reported that YFV RNA was not detected in serum and milk samples from vaccinated lactating mother.14\n\nBetween 2009 and 2020, YFV RNA was usually detected in samples other than milk such as CSF and serum. On the other hand, in April 2009 the first probable case of YF vaccine strain transmission through breast milk was reported in a Brazilian infant; yellow fever-specific IgM antibodies were detected in serum and CSF and yellow fever vaccine strain viral RNA was found in CSF of the infant. However, no breast milk or maternal serum was collected for yellow fever virus testing.\n\nOn March 2011, another case report study showed a baby was developing encephalitis after his mother had received the YFV vaccine when he was 10 days old.9 The authors claimed the probable transmission of the vaccine virus from the mother to her baby by detecting YF IgM in the infant’s serum and CSF. The clinical presentation, temporal relationship to the mother’s vaccination, and lack of other alternative pathogens were also strongly supportive of acute central nervous system infection with the vaccine strain of yellow fever.9\n\nYet another study reported on detection of YFV IgM in a 38 days-old infant’s serum and CSF who was exclusively being breast-fed. The baby suffered from meningoencephalitis 3 to 4 weeks after the YFV vaccine administration to his mother.9,15 The baby was discharged after the convulsive crises were controlled.\n\nMany studies have reported on the detection of flaviviruses RNA (Zika, West Nile, dengue, and chikungunya) in human milk.6 A study in 2017 described detection of viral RNA in serum and milk of three symptomatic breast-feeding mothers who were infected with Zika virus.12 And in another study WNV RNA and IgM antibodies were detected in breast milk samples from mothers whose babies developed West Nile virus.13 In one case of vertical transmission of dengue infection, the RNA of the virus was detected in blood samples from a mother and her child as well as in the mother’s breast milk.10 Furthermore, another study reported that chikungunya virus RNA was detected in serum, urine and milk samples of a breast-feeding mother at third day of symptoms onset.11\n\nThis study has some limitations; because objections by mothers, no samples were collected from the infants in order to exclude other causes of the observed illness and to rule out an asymptomatic transmission of the virus. Another limitation is that the detected YFV RNA must be sequenced to confirm the identity as 17DD vaccine strain.\n\n\nConclusion\n\nDespite limitations, this study suggests that YFV transmission from mothers to their babies through breast-feeding was highly probable indicated by the temporal relationship to mother’s YF vaccination. This also represents the first report on the detection of YFV RNA in human milk after YF vaccination in Sudan.\n\n\nData availability\n\nFigshare: Transmission of yellow fever vaccine virus from breast feeding mothers to their infants: reporting of yellow fever virus (YFV) RNA detection in milk specimens.\n\nhttps://doi.org/10.6084/m9.figshare.17206640.18\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nFaria NR, Kraemer MU, Hill S, et al.: Genomic and epidemiological monitoring of yellow fever virus transmission potential. Science. 2018; 361(6405): 894–899. PubMed Abstract | Publisher Full Text\n\nBarnett ED: Yellow fever: epidemiology and prevention. Clin. Infect. Dis. 2007; 44(6): 850–856. Publisher Full Text\n\nRomano APM, Costa ZGA, Ramos DG, et al.: Yellow fever outbreaks in unvaccinated populations, Brazil, 2008–2009. PLoS Negl. Trop. Dis. 2014; 8(3): e2740. PubMed Abstract | Publisher Full Text\n\nHamer DH, Angelo K, Caumes E, et al.: Fatal yellow fever in travelers to Brazil, 2018. Morb. Mortal. Wkly Rep. 2018; 67(11): 340–341. PubMed Abstract | Publisher Full Text\n\nMonath TP: Dengue and yellow fever—challenges for the development and use of vaccines. N. Engl. J. Med. 2007; 357(22): 2222–2225. PubMed Abstract | Publisher Full Text\n\nMann TZ, Haddad LB, Williams TR, et al.: Breast milk transmission of flaviviruses in the context of Zika virus: a systematic review. Paediatr. Perinat. Epidemiol. 2018; 32(4): 358–368. PubMed Abstract | Publisher Full Text\n\nCouto A, Salomão M, Schermann M, et al.: Transmission of yellow fever vaccine virus through breast-feeding-Brazil, 2009. Morb. Mortal. Wkly Rep. 2010; 59(5): 130–132.\n\nTraiber C, Coelho-Amaral P, Ritter VRF, et al.: Infant meningoencephalitis caused by yellow fever vaccine virus transmitted via breastmilk. J. Pediatr. 2011; 87(3): 269–272.\n\nKuhn S, Twele-Montecinos L, MacDonald J, et al.: Case report: probable transmission of vaccine strain of yellow fever virus to an infant via breast milk. CMAJ. 2011; 183(4): E243–E245. PubMed Abstract | Publisher Full Text\n\nBarthel A, Gourinat A-C, Cazorla C, et al.: Breast milk as a possible route of vertical transmission of dengue virus?. Clin. Infect. Dis. 2013; 57(3): 415–417. PubMed Abstract | Publisher Full Text\n\nCampos GS, Bandeira ACA, Rocha VFD, et al.: First detection of chikungunya virus in breast milk. Pediatr. Infect. Dis. J. 2017; 36(10): 1015–1017. PubMed Abstract | Publisher Full Text\n\nColt S, Garcia-Casal MN, Peña-Rosas JP, et al.: Transmission of Zika virus through breast milk and other breastfeeding-related bodily-fluids: A systematic review. PLoS Negl. Trop. Dis. 2017; 11(4): e0005528. PubMed Abstract | Publisher Full Text\n\nHinckley AF, O'Leary DR, Hayes EB: Transmission of West Nile virus through human breast milk seems to be rare. Pediatrics. 2007; 119(3): e666–e671. PubMed Abstract | Publisher Full Text\n\nFernandes EG, Nogueira JS, Porto VBG, et al.: The search for yellow fever virus vaccine in breast milk of inadvertently vaccinated women in Brazil. Rev. Inst. Med. Trop. Sao Paulo. 2020; 62: e33. PubMed Abstract | Publisher Full Text\n\nTraiber C, Coelho-Amaral P, Ritter V, et al.: Infant meningoencephalitis caused by yellow fever vaccine virus transmitted via breastmilk. J. Pediatr. 2011; 87(3): 269–272.\n\nStaples JE, Gershman M, Fischer M: Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep. 2010; 59(RR-7): 1–27. PubMed Abstract\n\nCollins ND, Barrett AD: Live attenuated yellow fever 17D vaccine: a legacy vaccine still controlling outbreaks in modern day. Curr. Infect. Dis. Rep. 2017 Mar 1; 19(3): 14. PubMed Abstract | Publisher Full Text\n\nBashir R, Hassan T, Abdelrahman N, et al.: Transmission of yellow fever vaccine virus from breast feeding mothers to their infants: reporting of yellow fever virus (YFV) RNA detection in milk specimens. figshare. Dataset. 2021. Publisher Full Text"
}
|
[
{
"id": "120678",
"date": "07 Feb 2022",
"name": "Leo G Visser",
"expertise": [
"Reviewer Expertise Vaccine immunology",
"alternative vaccination routes",
"yellow fever vaccine",
"rabies vaccine",
"mRNA 1273"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 report for the first time the presence of YVF RNA in breast milk specimens of five out of eight woman, three to fourteen days after receiving 17DD during vaccination campaign in Khartoum, Sudan.\nMajor comment\nAlthough transmission of YFV-17DD to the neonate through breastfeeding has been demonstrated before,1 attempts to isolate the vaccine strain from breast milk have been unsuccessful.2\nOn the other hand, wild YFV has been detected in breast milk before.3 Although there were no reports of a yellow fever outbreak in Khartoum state in November 2019, final proof would require to demonstrate that the nucleotide sequence of the amplified PCR product in the breast milk was identical to 17DD yellow fever vaccine virus. This limitation should be addressed in the discussion.\nMinor comments\nIntroduction:\nThe line “Administration of the vaccine to breastfeeding women before 9 months post-delivery can transmit the yellow fever vaccine virus to their infants through breast milk.” is confusing: breastfeeding is a risk factor for transmission irrespective of time post-delivery. However, the risk of YFV-associated neurological disease after transmission may occur in infants less than 6-9 months of age. The sentence should be corrected accordingly.\nMethod:\nWhat were the inclusion criteria? How were these woman selected? What is the cut-off CT-value for q-PCR result to be considered positive? Was a negative control included to check for contamination? What was the positive control for the YFV PCR?\nResults\nPresentation of the results in a single table would increase readability. The data provided in Figures 1 and 4, and Tables 1 and 2 could be compiled into one table (time and specimen in the upper row, and subjects in left column). Figure 2 is redundant.\nIn Figure 3 it is not clear from which specimen the amplification curves are presented? Is this serum or breast milk? The CT-values of 32 - 40 indicate very low levels of viral RNA. Maybe the authors could provide some more information on the CT-values in serum and breast milk.\nDiscussion\nCould the authors elaborate on how many weeks breast feeding should be interrupted to prevent transmission to the infant? The authors should discuss on the lack of confirmation that the nucleotide sequence of the amplified PCR product in the breast milk was identical to 17DD yellow fever vaccine virus.\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? Not 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/11-76
|
https://f1000research.com/articles/12-384/v1
|
12 Apr 23
|
{
"type": "Research Article",
"title": "Effects of Consumer Dispositional Attitude on Purchase Intention in an Emerging Market",
"authors": [
"A. Venugopal Shanbhogue",
"V. K. Ranjith",
"A. Venugopal Shanbhogue"
],
"abstract": "Background: Globalization trends have compelled multinational companies to change their marketing approach from multi-domestic marketing to global marketing. This strategy has had a major impact on the branding of companies. Due to these efforts by international companies, there has been a negative impact on local brands. Strong local brands always maintained the advantage of a high level of awareness among consumers, due to consumers’ close relationship with these brands, hence this resulted in strong and positive marketing investments in the home market. The purpose of this research is to evaluate the attitudinal dispositions towards global and local brands and purchase intention. The objective is to understand the underlying motives of consumers’ purchase decision. Methods: Consumer disposition and attitude towards brands are evaluated based on respondents’ purchase intention of a select brand. Data are collected from Bangalore and Chennai using the convenience sampling method. Evaluation of the measurement model was performed using the Smart PLS 4 software. Results: Findings suggest that consumer attitudinal disposition has a significant impact on consumers’ purchase intention. Attitude formation is the first step in consumers’ behavioural decision and making a purchase decision. Marketing managers/practitioners need to focus on forming this attitude in consumers’ minds, so that this attitude formation leads to a purchase decision. Conclusions: This research provides theoretical and managerial implications for marketers, especially those operating in an emerging market like India as this study has examined the role of consumer disposition on attitude formation and purchase intention. From a theoretical perspective, this study developed and tested a conceptual model describing the relationship between attitudinal disposition and purchase intention.",
"keywords": [
"Consumer disposition",
"Consumer Ethnocentrism",
"Consumer Cosmopolitanism",
"Attitude towards Brand",
"Purchase Intention",
"Globalization",
"Localization",
"Global Brands",
"and Local Brands."
],
"content": "Introduction\n\nBusiness organizations use branding to position their products in such a way that external economic and political factors do not affect their products. Branding is also evolving according to consumers’ tastes and preferences and is used as a strategic marketing tool (Rooney, 1995). Global brands have become assets to multi-national enterprises (MNEs). Due to a significant rise in globalization, global brands carry an appeal of investing in research and development due to their ability in achieving economies of scale and scope (Cleveland, Laroche, and Papadopoulos, 2015; Balabanis et al., 2019). Due to global brands’ presence all over the world, it projects certain values such as diversity and wide acceptance among consumers (Kjeldgaard and Ostberg, 2007; Bartsch et al., 2016). Due to globalization, international marketers are presented with challenges as well as opportunities. Challenges arise from competitors and opportunities are from trade policy relaxation which removes the barriers of entry into another country. Consequently, consumers are faced with brands competing in the marketplace. The attitude of consumers towards global brands has been of interest to consumer behaviour researchers for decades (Wang and Chen, 2004; Zeugner-Roth et al., 2015; Junaid et al., 2022).\n\nGlobalization trends have compelled multinational companies to change their marketing approach from multi-domestic marketing to global marketing. This strategy has had a major impact on the branding of companies. In the recent past, these international companies have focused their efforts on the development of global brands. Due to these efforts, there has been a negative impact on local brands. Most of the brands have opted to shrink their portfolio and eliminate the underperforming products in the market. Initially, this trend was seen in the fast-moving consumer goods (FMCG) sector, but recently it has occurred in other sectors as well such as banking, insurance, retail, and oil industries to name a few. Strong local brands always maintained an advantage of a high level of awareness among consumers, due to consumers’ close relationship with local brands over the years, hence this influenced strong and positive marketing investments in the home market (Thomas, Singh, and Ambady, 2020; De Mooij, 2021, Junaid et al., 2022).\n\nProduct category plays a major role in consumers choosing either global or local brands. Product categories such as household products and food items may be more advantageous for local brands because of the localization bandwidth available, whereas products that are more visible goods may be appealing for global brands to invest in. Visible goods refer to the flagship products of brands; after purchasing these products, consumers feel that they are a part of global citizens and also feel that they are more cosmopolitan. These products are technically advanced and considered sophisticated to use, because these types of products are high in aspirational value, are associated with status and modernity, and are technically advanced (Zhou and Belk, 2004; Dimofte, Johansson, and Ronkainen, 2008; Strizhakova, Coulter, and Price, 2008). One of the major advantages of a global brand is standardization. Standardization across product design, marketing, and advertising campaigns characterises a paradigm that is transferrable across countries giving global brands an edge against local competitors in a global industry (Strizhakova et al., 2008; Cavusgil et al., 2018; Christian and Wang, 2022).\n\nA global brand signals five underlying characteristics which form its position in the market, namely wider reach geographically and worldwide recognition; aspirational values which indicate excitement among consumers; higher perceived quality due to technical advancement and sophistication; display of ethical and environmental responsibilities; and standardization (Holt, Quelch, and Taylor, 2004; Dimofte, Johansson, and Ronkainen, 2008; Oyserman, 2015). The characteristic of standardization is where local brands differ from global brands. Local brands adapt to local culture, traditions, and preferences, signalling their differentiation factor to consumers. Local brands also signal two more characteristics that appeal to consumers, namely uniqueness and originality. Due to their adaptation to local consumers’ preferences and tastes, local brands increase brand awareness and are also available in local markets (Kapferer, 2005; Dimofte et al., 2008).\n\nThe objective of this paper is to evaluate the effects of consumer dispositional attitude on the purchase intention of global and local brands. Building on existing literature, this study aims to develop a conceptual framework, formulate hypotheses, and test the hypotheses with empirical data. The structure of the paper is as follows. The next section will cover the literature on global brands, local brands, consumer ethnocentrism, consumer cosmopolitanism, attitude towards brand, and purchase intention. This will provide a clear picture regarding consumer disposition, attitude towards brands, and purchase intention and thus provide a significant contribution to the literature on consumer behaviour.\n\n\nLiterature review\n\nBrands are widening their market reach to emerging nations, especially in a country like India. By venturing into emerging nations, managers of global brands are trying to understand consumer behaviour (Wang, He, and Barnes, 2017; Christian and Wang, 2022). Both global and local brand firms try to localize their products to attract consumers within a specified region, while at the same time signalling their aspirations to promote global consumer culture and get global recognition; symbolic signals are an integral part of marketing the brands because it is an important part of consumer culture identity (Manning and Uplisashvili, 2007; Manning 2010; Bardhi et al., 2012; Bjerrisgaard and Kjeldgaard, 2013). A brand is defined as global when it is recognized, marketed, accepted, and desired by consumers all over the world, and carries a similar product specification, marketing promotions, and positioning strategies. The products which are manufactured, advertised, and sold in a specific region or country, to meet the demand of local consumers’ tastes and needs are termed local brands (Özsomer, 2012).\n\nIn emerging economies, there is strong competition between global and local brands, particularly due to local brands’ ability to adapt to local consumers’ needs. Due to this, local brands are gaining significant market share, and pose a stern challenge to global brands (Dimofte et al., 2008). Global brands face a huge challenge to enter an emerging economy where local brands have already established a strong market presence and due to this, local brands become local icons, and use this as a marketing strategy to compete against global brands (Steenkamp et al., 2003; Özsomer, 2012; Mrad and Cui, 2020). Therefore, global and local brand managers target consumers who are individualistic or cosmopolitan and collectivist or ethnocentric, respectively. Ethnocentric consumers have a collectivist attitude, where they gain information through interpersonal communication, due to which they make their purchase decision based on feelings and trust in the brand, whereas cosmopolitan consumers have individualism, acquire information through media and friends which influences their purchase decision. So, brands targeting consumers of collectivist or ethnocentric disposition make their products focus more on product features rather than making products by adding value or abstract personality traits to influence consumers who are individualistic or cosmopolitan (De Mooij and Hofstede, 2010).\n\nThe significance of brands and brand preference has attracted researchers and practitioners in the past decade contributing to a vast body of knowledge (Strizhakova and Coulter, 2015; Zeugner-Roth, Zabkar, and Diamantopoulos, 2015; Davvetas and Diamantopoulos, 2016; Thomas, Singh, and Ambady, 2020). The scope involved in branding research is continuously evolving and demands a thorough enquiry. Hence, to address this gap in the literature, we have considered the following consumer dispositions and their effect on consumers’ attitude towards brands and their influence on purchase intention.\n\nThe term consumer ethnocentrism describes those consumers who believe in their own culture, see others only from their own set of values’ perspective and decline people who do not belong to their group or one who does not believe in their set of values and traditions. People with ethnocentric beliefs have an in-group and they tend to favour them and discard others who do not believe in their culture and traditions and are held in contempt (Shimp and Sharma, 1987).\n\nShimp and Sharma (1987) conceptualized “consumer ethnocentrism as the beliefs held by consumers about the appropriateness, indeed the morality, of purchasing locally-made products instead of foreign-made products”. For an ethnocentric consumer, their own country’s products are superior to a foreign country’s products, even though the quality of foreign products is superior, but still, they prefer their nation’s products (Raju, 1995; Riefler and Diamantopoulos, 2007). Ethnocentric consumers do not believe in buying foreign products as it is against their moral values, they believe it would hurt the domestic economy, thereby resulting in job losses for their fellow countrymen, not only that, but foreign brands also even pose a threat to indigenous companies (Cleveland et al., 2009).\n\nCosmopolitanism dates to the eighteenth century, when people assumed themselves to be citizen of the world and their desire to adopt different cultures made them stand out from others. Cosmopolitans are those who have an intention to be recognized beyond their nation and culture and those who spend their lives seeking experiences both within and outside their nation (Thompson and Tambyah, 1999; Cannon and Yaprak, 2002; Saran and Kalliny, 2012). In the early 1950s, many sociologists viewed cosmopolitans as outgoing people, beyond their community, and influenced by world culture more than their local traditions. Consumer cosmopolitanism is a construct that can be measured in two ways. One is that cosmopolitan consumers have cultural openness, where they are willing to adopt other cultures and are open to other cultural experiences, having a positive sense of competence towards foreign cultures.\n\nCosmopolitan consumers are outgoing, open to exploring other cultures and have world-mindedness. Even though they accept their local cultures, due to their yearning to be associated with a global identity they have a positive attitude towards global brands (Cleveland et al., 2011). The other view is that consumer cosmopolitanism shows that a consumer embraces foreign cultures through open-mindedness and the diversity it brings due to the products available from different nations as well as cultural origins and they are positive towards consumption of foreign-made products. In this context, cosmopolitan consumers have an unprejudiced opinion towards foreign cultures and in experiencing their authenticity (Riefler et al., 2012).\n\n“Attitude towards brand is defined as an individual’s internal evaluation of the brand” (Mitchell and Olson, 1981). A claim by Lutz (1991) says that for a consumer, attitudes function as a strainer for how they perceive an object. Past studies have confirmed the noteworthy effect of attitude towards purchase intention (Zhang et al., 2005). Jin and Kang (2011) have established that for Chinese consumers, attitude plays an important factor that predicts purchase intention of global apparel brands.\n\nConsumers evaluate products and services available to them before any purchase decision, so this evaluation finally results in a transaction which is termed as purchase intention (Zeithaml, 1988). Purchase intention is referred to as the probability that consumers are going to buy the given product (Schlosser et al., 2006). Alden et al. (1999) have argued in the literature that there is a belief that marketers are employing local and global consumption positioning for their products. Previous studies aimed to study the impact of consumers’ evaluation of global and local brands in both emerging and developed economies and their influence on purchase intention (Alden et al., 2006).\n\nResearchers in the past have previously studied consumer dispositions such as ethnocentrism, cosmopolitanism, etc. in various research contexts and extensive research has been conducted and has had a diverse view on its impact on attitude and purchase intention. The Figure 1 below shows the conceptual framework of this study.\n\nConsumer ethnocentrism is a psycho-social construct that is relevant to an individual-level personality trait, which initially evolved from being a sociological concept (Levine and Campbell, 1972). Consumers associated with certain beliefs, attitudes, behaviours, etc. have adopted certain social identities, which is also known as in-group, due to which the intention to buy local brand increases, hence promoting ethnocentrism and believing that they are superior to others (Turner et al., 1987).\n\nShimp and Sharma (1987) measured consumer ethnocentrism and concluded by saying that consumers have high ethnocentric tendencies and often purchase domestic products rather than global products, and also consider domestic products to be superior, as later supported by Netemeyer et al.(1991) and Chryssochoidis et al. (2007). Consumers, when deciding to buy between local and global brands, will favour products from countries that possess a similar culture (Sharma et al., 1995; Lantz and Loeb, 1996; Watson and Wright, 2000). Consumers consider the products made in their country as group related products and products of foreign countries are taken as unrelated group products, so naturally, they tend to favour products related to their group (Verlegh, 2007).\n\nConsumers in emerging economies are inclined to believe that local products are not as good as foreign products and favour global products more (Balabanis et al., 2001; John and Brady, 2011). The consumer’s love towards their nation results in high consumer ethnocentrism (Sharma, Shimp, and Shin, 1994). Due to this, the consumer’s evaluation of product influences in such a way that, they overestimate the domestic product’s quality and underestimate the foreign product’s quality. This would result in a positive attitude towards local products and a negative attitude towards global products (Sharma et al., 1995; Watson & Wright 2000).\n\nHence the following hypotheses\n\nH1a: There is a negative relationship between consumer ethnocentrism and attitude towards global brands.\n\nH1b: There is a positive relationship between consumer ethnocentrism and attitude towards local brands.\n\nCosmopolitan consumers are not affected by their home culture and are open to different cultures, they transcend any boundaries or setting to experience foreign cultures and, in a way, they are motivated to achieve social status by favouring global products (Thompson and Tambyah, 1999; Cannon and Yaprak, 2002). Cosmopolitan consumers are the ones who are outgoing, open-minded, and willing to explore other cultures with a motivation of understanding and learning from other cultures’ experiences (Weij et al., 2015). Cosmopolitans from developed as well as emerging economies generally prefer buying foreign products (Caldwell et al., 2006). But Riefler et al., (2012) argue that although cosmopolitan consumers may not prefer products from their nation, they are well-versed in their local traditions and culture.\n\nTherefore, we hypothesise that\n\nH2a: There is a positive relationship between consumer cosmopolitanism and attitude towards global brands.\n\nH2b: There is a negative relationship between consumer cosmopolitanism and attitude towards local brands.\n\nConsumers have a predisposition towards certain brands, be it global or local (Verlegh and Steenkamp, 1999; Magnusson, Westjohn, and Zdravkovic, 2011). This may be either positive or negative, and either way, it influences their purchase decision. Consumers’ attitude towards brands originates from their past experiences, and it affects their purchase intention (Costa et al., 2016; Herz and Diamantopoulos, 2017).\n\nHence the following hypotheses\n\nH3a: There is a significant relationship between attitude towards global brands and purchase intention.\n\nH3b: There is a significant relationship between attitude towards local brands and purchase intention.\n\n\nMethods\n\nThis study is aimed at understanding the underlying motives of consumer preference towards global and local brands. This research is based on a positivist paradigm, deductive reasoning, and quantitative approach. Aligned with this objective, this research adopts a quantitative approach built on an empirical survey to evaluate the conceptual model. Survey-based research allows us to understand the relationship between consumer ethnocentrism, consumer cosmopolitanism, attitude towards brand, and purchase intention. The target respondents were chosen from the metropolitan cities of Bangalore and Chennai in the southern part of India, the respondents were between the age group of 18 to 60 years. These two cities were selected for this study because, historically, states with higher gross added value (GVA) shares, including Maharashtra, Madhya Pradesh, Punjab, and Haryana, had declines whereas states like Tamil Nadu and Karnataka experienced increases over the past ten years (Kpmg, 2021).\n\nBased on a conceptual model, a questionnaire was developed in the English language. 800 questionnaires were distributed during data collection in the metropolitan cities of Bengaluru and Chennai. The sample observations collected in this study had either missing values or incomplete surveys in 44 survey forms. These 44 forms were eliminated from the data analysis, and finally, 756 responses were considered for the study. The responses of all the 756 respondents were separately investigated to verify the probability of the presence of straight lining. No straight-lining response pattern was found in any of the sample cases. Hence, there existed no necessity to remove any observations of any particular case.\n\nThe questionnaire consisted of scales concerning constructs of consumer ethnocentrism with 5 measurement items, consumer cosmopolitanism with 12 measurement items, attitude towards brands with 5 measurement items, and purchase intention with 5 measurement items. The study used a 5-point Likert scale labelled from 1 (strongly disagree) to 5 (strongly agree). For the measurement of the independent variables and dependent variables. Table 1 has a list of the measuring items.\n\nSampling is done in two stages. In the first stage, the sampling method is employed to draw the products for the consumer survey. Therefore, the judgment sampling technique is employed under the nonprobability sampling method to draw products and brands from the FMCG sector. The FMCG sector is identified for the study using these three criteria: (i) availability of global and local brands in the same product category, (ii) low price point of the products, and (iii) accessibility to a broad range of consumers (Narang, 2016).\n\nThe product category with higher penetration and higher market share identified for this research is biscuits from food and beverages. Since India is the highest consumer of biscuits in the world and these products have a low price point, easily accessible to consumers, it has consumers from all the strata (TRA Research, 2022).\n\nIn the second stage of sampling, data were collected using the convenience sampling method. Convenience sampling was particularly relevant in this research because researchers needed to choose respondents who are already familiar with the chosen brands (Narang, 2016). In addition to this, researchers chose respondents who were reasonably knowledgeable about global and local brands. A pilot study was done with a sample size of 84 to ensure that there are no major flaws in the study instrument and to check the reliability and validity of the scale used in this research.\n\nThe demographic description of the data was conducted using IBM-SPSS software (RRID:SCR_019096), and the evaluation of the measurement model was done using Smart PLS 4 (RRID:SCR_022040). Investigating the convergent validity and discriminant validity of the measurement model allowed for an evaluation of its quality. Outer loadings were checked to negate the measurement items with poor loadings, and such items were deleted from the analysis (Gefen and Straub, 2005).\n\nBefore distributing the survey questionnaire, all survey participants provided their written informed consent. Before asking for the respondents' signed informed consent, an information sheet outlining the research's goals, findings, and consequences was included in the form's content. It contains statements stating that any personal information will be kept confidential and that the data obtained will be used only for research and publication purposes (see Extended data, Shanbhogue & Ranjith, 2023). In addition, the Manipal Institute of Management ethics committee and doctoral advisory committee panel gave their approval before conducting this research (date of approval 24.02.2022).\n\n\nResults\n\nDescriptive statistics were estimated, and the output is presented in Table 2. The full data set can be found in the underlying data (Shanbhogue & Ranjith, 2023).\n\nAge-wise distribution of the sampled respondents shows that 42.5 percent of the respondents belong to the age group of 20-29 years, 0.3 percent of the respondents belong to the age group of 30-39 years, 30.6 percent belong to the age group of 40-49 years, and 26.7 percent of the respondents belong to the age group of 50-59 years. The sample population comprised 51.6 percent of males, and 48.4 percent of females.\n\nAmong the educational qualification category, 30.8 percent of the respondents are graduates, 47.1 percent of the respondents are postgraduates, and 22.1 percent of the respondents belong to others. In terms of relationship status, 52.5 percent of the respondents are married, and 47.5 percent of the respondents are single, never married. The employment status shows that 21.2 percent of the respondents are self-employed, 71 percent of the respondents are employed, and 7.8 percent of the respondents belong to others. 29.5 percent of the respondents have a household income of Rs 21000 to 40000 per month, 49.3 percent of the respondents earn Rs 41000 to 60000 monthly income, and 21.2 percent of the respondents have a monthly income of Rs 61000 to 80000.\n\nHair et al. (2012) describe that reliability and validity need to be assessed for the measurement model. The specific measures for internal consistency and reliability are composite reliability, convergent validity, and discriminant validity. As per Hair et al. (2012), composite reliability is used to evaluate internal consistency, and average variance extracted (AVE) is used to determine convergent validity. The researchers adopt the Fornell-Larcker criterion and the heterotrait-monotrait ratio (HTMT) to assess the discriminant validity Hair et al. (2012).\n\nThe first criterion of composite reliability has been assessed for internal consistency. Hair et al. (2012) recommend composite reliability for measuring the internal consistent reliability of the PLS-SEM approach rather than Cronbach’s alpha value. The threshold value for composite reliability is above 0.60. It is evident from Table 3, that internal consistent reliability among all constructs of the measurement model is acceptable as the values are above the threshold values. Since Cronbach alpha value and composite reliability value for all constructs are above 0.70, it is declared that the constructs used for the study have internal consistent reliability Hair et al. (2012). Therefore, all the values of composite reliability are greater than the average variance extracted for all the constructs. The average variance extracted (AVE) for each of the constructs exceeds the threshold value of 0.50, thus confirming the convergent validity of the scale (Nunnally, 1994).\n\nDiscriminant validity is about measuring the individuality of a construct among other constructs of the measurement model. It measures the extent of the distinctness of one construct from the other constructs. The researchers use the Fornell-Larcker criteria, and the HTMT to assess the discriminant validity.\n\nThe results of the Fornell-Larcker criteria for the discriminant validity in Table 4 demonstrate the square root of every construct exceeding its correlations with the other construct. Therefore, it is evident from the result that discriminant validity exists among the constructs used for the study.\n\nHenseler et al. (2015) proved through their simulation models that the HTMT ratio is better than the Fornell-Larcker criterion for discriminant validity. The heterotrait-hetro method correlations geometric mean is divided by monotrait-hetro method correlations average to derive the HTMT ratio.\n\nAs per Henseler et al.’s (2015) suggestion, to understand the discriminant validity that has been established among the constructs, the HTMT ratio value should be below 0.90. Table 5 indicates a good discriminant validity among the constructs since the HTMT ratio of all the constructs among other constructs is less than 0.80. After assessing the reliability, construct validity, and discriminant validity researchers find that there is good reliability and validity among the indicators. Therefore, structural model assessment and hypotheses testing are done in the next section.\n\nThe researchers validate the model with the PLS-SEM approach and examine the conceptual framework developed based on the literature support. The researchers adopt the PLS-SEM algorithm to compute the path coefficients of the structural model. The Figure 2 shows the structural model assessment of this study.\n\nA strong relationship between the constructs exists if the path coefficient values are not near zero. If the values are near zero, it indicates a weak relationship between the constructs Hair et al. (2012). The bootstrapping technique evaluates the significance level of the relationship between the constructs. The evaluation of the structural model will show the significance level, and the t-value above 1.96 declares the relationship between the constructs is significant.\n\nSince the coefficient determination is the criterion by which the structural model is measured for its predictive accuracy (Henseler et al., 2012; Hair et al., 2012), the coefficient of determination, i.e., the R2 value is considered to validate the model. The model stands weak, with a value of R2, the coefficient of determination being 0.013 for attitude towards global brands, weak with a value of 0.311 for attitude towards local brands, reasonably strong with a value of 0.644 for purchase intention of global brands, and 0.614 for purchase intention of local brands as shown in Table 6.\n\nFor model fit, the value of Standardized Root Mean Square Residual (SRMR) should be less than the threshold value of 0.08 or 0.10 according to Henseler et al. (2014). Since the value of SRMR is less than the threshold value as shown in Table 7, it represents a good model fit. Another indicator of a good model fit is Normed Fit Index (NFI). According to Lohmöller (1989), the value of NFI lies between 0 and 1, the closer the NFI is to 1, the better the fit. Since the value of NFI is closer to 1 as shown in Table 7, it is considered a good model fit.\n\nThe structural model assessment and bootstrapping results in Table 8 summarize the path coefficient values, t-values, p-values, significance levels, and bootstrap confidence intervals for the model. The results of hypothesis testing for the model are illustrated in Table 9.\n\n+ p < 0.10.\n\n* p < 0.05.\n\n** p < 0.01.\n\n*** p < 0.001.\n\n\nDiscussion\n\nThis study examined the effects of consumer disposition on consumers’ attitude towards a brand and their influence on purchase intention. It provides a better understanding of the underlying motives of consumers in their purchase decision. It shows how consumers form attitudinal dispositions towards brands. In this study, consumer ethnocentrism forms a negative attitude toward global brands (H1a) and forms a positive attitude toward local brands (H1b), these findings are compatible with other studies (Özsomer, 2012; Strizhakova and Coulter, 2015; Thomas, Singh, and Ambady, 2020). Ethnocentric consumers do favour local brands in comparison with global brands. The sense of supporting the local economy, and local culture is stronger compared to showing a favourable attitude in purchasing global brands.\n\nConsumer cosmopolitanism is not influencing consumers in forming a favourable attitude towards global brands (H2a), this finding is not in accordance with previous studies (Riefler et al., 2012; Weij et al., 2015; Mrad and Cui, 2020). The inference from this finding could be that consumers do not necessarily prefer purchasing global brands in the low involvement category where an alternative to that particular brand is offered by a local brand. Consumer cosmopolitanism does not show a negative influence on consumers buying local brands (H2b), this finding does not concur with previous studies (Zeugner-Roth et al., 2015; Mrad and Cui, 2020). This shows that cosmopolitan consumers may prefer buying global brands over local brands which shows their cultural openness, and open-mindedness but they may also not outrightly reject local brands originating from their own country or culture.\n\nConsumer ethnocentrism and consumer cosmopolitanism both form a strong attitude in consumers towards global and local brands (H3a) and (H3b). This finding supports past research (Xie et al., 2015; Eren-Erdoğmuş and Dirsehan, 2017; Cavusgil et al., 2018). Consumer attitudinal disposition has a significant impact on consumers’ purchase intention. Attitude formation is the first step in consumers’ behavioural decision and making a purchase decision. Marketing managers need to focus on forming this attitude in consumers’ minds so that this attitude formation leads to purchase decision. If the consumer is ethnocentric then brands should focus on integrating local culture, and traditions in their products so that it leads to positive attitude formation and ultimately translates into purchase transactions, similarly, if the consumer is cosmopolitan then brands should signal global attributes such as wider global reach, wider global acceptance of their products, and global consumer culture.\n\n\nConclusion\n\nThe theoretical and managerial implications of this study are significant for marketers, especially those working in an emerging market like India as this study has examined the role of consumer disposition on attitude formation and purchase intention. From a theoretical perspective, this study developed and tested a conceptual model based on attitudinal disposition and purchase intention. It suggests that ethnocentric consumers have a strong sense of oneness among their in-group, and significantly support local culture, traditions, and economy which leads to higher purchase intention towards local brands, and they form a negative attitude towards global brands which leads to lower purchase intention. It is also noted from the findings that cosmopolitan consumers do not have a negative attitude towards local brands which implies that if there is an alternative to the global brand in the market, cosmopolitan consumers will not outrightly reject the local brand in favour of the global brands.\n\nFrom managerial contribution, this study can help managers understand the phenomenon of positive attitude formation which in turn leads to purchase intention. The strategies could be developed in accordance with these findings to leverage the target consumer groups. Consequently, these research findings are valuable from more than just an academic standpoint and also for managers/practitioners of brands in an emerging economy like India to strategically plan marketing campaigns, promotions, and positioning of their brands. From a managerial implications perspective, it can be concluded that managers need to adopt a flexible strategy to excite the consumers to buy their products and at the same time make their brand more appealing not only at home but also in foreign markets (Zeugner-Roth et al., 2015).\n\nFirstly, the sample, given its homogeneity, does not perfectly represent the entire spectrum of consumers, as a high number of respondents in this study are college/university students. The difference among educational qualifications still exists, which might lead to differences in their behavioural aspects of attitude formation or attitudinal dispositions. Secondly, this study discusses a specific brand or product category, hence this limitation is also one of the scopes for future research to include more product categories or a set of specific brands for the consumers to evaluate and compare before making a purchase decision. Finally, this study has not considered any moderators in the research model. Top researchers in this discipline have advocated that consumer disposition constitutes differently depending upon the contextual factors in terms of consumption, therefore future research should replicate this study by accounting for such aforementioned factors influencing consumers’ attitude and purchase intention.",
"appendix": "Data availability\n\nFigshare: Data File.xlsx. https://doi.org/10.6084/m9.figshare.21988643 (Shanbhogue & Ranjith, 2023).\n\nThis project contains the following underlying data:\n\n• Data File.xlsx\n\nThis project contains the following extended data:\n\n• Questionnaire Parle G.docx (the survey form used during data collection)\n\n• Questionnaire Unibic.docx (the survey form used during data collection)\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\nAlden DL, Steenkamp JBE, Batra R: Brand positioning through advertising in Asia, North America, and Europe: The role of global consumer culture. J. Mark. 1999; 63(1): 75–87. Publisher Full Text\n\nAlden DL, Steenkamp JBE, Batra R: Consumer attitudes toward marketplace globalization: Structure, antecedents and consequences. Int. J. Res. Mark. 2006; 23(3): 227–239. 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Publisher Full Text"
}
|
[
{
"id": "169448",
"date": "02 May 2023",
"name": "Savita Bhat",
"expertise": [
"Reviewer Expertise Emerging economies",
"Firm competitiveness",
"quantitative techniques in economics and 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\nSummary of the Article:\nThe study analyzes the effects of consumer dispositional attitudes on the purchase intention of global and local brands. It explains how consumer ethnocentrism and consumer cosmopolitanism form attitudinal dispositions towards brands. The study considers the FMCG product category of biscuits with Parle G as a local brand and Unibic as a global brand. The data from 756 respondents are collected from two metropolitan cities of India, Bengaluru and Chennai, using a questionnaire survey method. The data is analyzed using Partial least squares structural equation modeling (PLS-SEM) approach. The study has performed the reliability assessment and discriminant validity tests using appropriate measures. The results, discussions, conclusion and limitations are also presented.\nOverall, the study is timely, and the results of the study will be helpful for researchers and marketers in an emerging market like India.\nThe following are some of the suggestions to improve the study.\nIn Table 9 on Hypothesis outcomes, it is clear that the study does not support the H1a hypothesis. Hence, in the discussions, the authors may avoid stating - In this study, consumer ethnocentrism forms a negative attitude toward global brands (H1a).\n\nFurther, the path coefficient from CET to ATBL is statistically significant with a negative sign (-0.568); it seems contradictory to the H1b hypothesis. The authors can clarify this.\n\nThe conclusion section can be appropriately modified after addressing the above two points.\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": "9645",
"date": "28 Nov 2023",
"name": "Venugopal Shanbhogue",
"role": "Author Response",
"response": "1. Since hypothesis H1a is not supported in this study as shown in table 9, the sentence in the discussion section – “In this study, consumer ethnocentrism forms a negative attitude toward global brands (H1a)” will be removed. 2. Although the path coefficient of CET=>ATBL is (-0.568) negative for hypothesis H1b as shown in the table 8, the relationship is statistically significant, the hypothesis H1b was formulated based on previous literature which suggested a positive relationship between consumer ethnocentrism (CET) and attitude towards local brand (ATBL). A study by Sharma et al. (1994) argues that the higher the product necessity lower is the influence of ethnocentrism on purchase intention among consumers. For example, ethnocentric consumers evaluate products that are a \"necessity\" differently compared to the products which are owned as status symbols. Since this study included only low involvement product (Biscuit) which is not a status symbol which explains the negative path coefficient between consumer ethnocentrism (CET) and attitude towards brand (ATBL). Conclusion The theoretical and managerial implications of this study is significant for marketers especially those working in an emerging market like India as this study has examined the role of consumer disposition on attitude formation and purchase intention. From theoretical perspective, this study developed and tested a conceptual model based on attitudinal disposition and purchase intention. It suggests that ethnocentric consumers have a strong sense of oneness among their in-group, significantly support local culture, traditions, and economy which leads to higher purchase intention towards local brands and also the finding suggests that ethnocentric effect reduces for low involvement products because of increased necessity as seen in this study. It is also noted from the findings that cosmopolitan consumers do not have a negative attitude towards local brands which implies that if there is an alternative to the global brand in the market, cosmopolitan consumers will not out rightly reject the local brand in favour of global brands. From managerial contribution, this study can help managers understand the phenomenon of positive attitude formation which in turn leads to purchase intention. The strategies could be developed in accordance with these findings to leverage the target consumer groups. Consequently, these research findings are valuable from more than just an academic standpoint and also for managers/practitioners of brands in an emerging economy like India to strategically plan marketing campaigns, promotions, and positioning of their brands. From managerial implications’ perspective, it can be concluded that managers need to adopt a flexible strategy in order to excite the consumers to buy their products and at the same time make their brand more appealing not only at home but also in foreign markets (Zeugner-Roth et al., 2015)."
}
]
},
{
"id": "185052",
"date": "19 Jul 2023",
"name": "Dr Irfan Sabir",
"expertise": [
"Reviewer Expertise Consumer Behavior",
"New Product Development",
"Social Entrepreneurship"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n1. Research problem is not justified, i.e. why was this study required to be conducted, and why in India?\n2. Majority of references are older than 5 years. Need to cite latest references, i.e. within past 3 years.\n3. Literature is well written.\n4. Consumer ethnocentrism has been discussed as a psycho-social construct, yet, the theoretical underpinnings is missing, i.e. which theory supports the conceptual model of this research.\n5. Sampling design is not appropriate, as the premise of this study is \"Global vs Local Brands\", so there seems to be a need for respondents who belong to more diverse cultures / backgrounds, but the respondents for this study are only from two cities in India. Either responses from some other country should be added or more justification for current respondents be provided.\n6. Product category selected (Biscuits) does not seem to be appropriate, as being \"low involvement products\". More justification be added.\n7. Analysis done is appropriate.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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": "10000",
"date": "29 Nov 2023",
"name": "Venugopal Shanbhogue",
"role": "Author Response",
"response": "Response to Query no 1: In an emerging economy like India, consumers with expendable income have more choice in terms of global brands and local brands. India is an emerging economy and with high ethnocentric tendencies. So, the need for study is to analyze the effects of consumer disposition and attitude towards brands on purchase intention. Therefore, the research problem states that “Does consumer disposition towards global and local brands have an impact on attitude towards brand and their purchase intention?” Consumers in emerging market have a negative attitude towards global brands and globalization because of the fear that it will eradicate their local culture due to the burden of western values by capitalistic global brands (Martin and Rey, 2006). However, consumers may not have intention to purchase due to multiple dispositions such as consumer ethnocentrism, consumer cosmopolitanism, nationalism (Fernandez-Ferrin et al., 2015; Bartikowski and Walsh, 2015). Marketing researchers over the period have recognized cultural identity markers which received a lot of attention due to nationalistic views worldwide. In the marketing literature, national identity is investigated and further classified into a belief system and ethnocentric tendencies (Varman and Belk, 2009; Westjohn et al., 2012; Prince et al., 2020). Although studies on constructs such as consumer ethnocentrism, consumer cosmopolitanism, attitude towards brands, and purchase intention were carried out previously in branding literature (Zeugner-Roth et al., 2015; Thomas et al., 2020). Limited attempts have been made to understand the combining effect of positive and negative disposition towards global and local brands (Srivastava et al., 2020). This happens when consumers embrace global consumer culture by purchasing or experiencing global products and services yet find themselves attached to their own local culture and traditions and cannot avoid being influenced by them. And consumers who are oriented more towards local consumer culture are aware of global brands and the threat it poses to indigenous brands; they are more grounded in nationalistic and patriotic behavior in an emerging economy like India (Oyserman, 2015, Mandler et al., 2021). There has been a considerable amount of research carried out in branding, specifically concerning global and local brands. Since the findings from past literature indicate contradictory results regarding brand preference among consumers (Eren-Erdogmus and Dirsehan, 2017; Cavusgil et al., 2018). Citing these contradictions (Balabanis et al., 2019) have recently called for new avenues of research in assessing consumer preferences for global brands over local brands or vice versa in emerging markets like India. In this study we aim to address this gap in knowledge and understand the underlying motives of consumer preferences and the factors influencing consumers' purchase intention of global and local brands. Response to Query no 2: Authors have included recent references i.e. within three years in this research, however the context of study is such that paucity of research in this area has compelled us to cite majority of the references from the time period when the research activity in this area of study was at its peak. Response to Query no 4: Consumer behaviour in emerging economies affects how consumers purchase brands, how markets are segmented, and how trade is conducted internationally. These opinions of foreign nations and their products can be positive or negative (Riefler, 2017; Papadopoulos et al., 2018). Consumer ethnocentrism, which can be seen as an exclusive response to the inflow of both local and foreign cultures, is one example of a disparaging nationalistic trait (Riefler, 2017). Entry strategies like partnerships with local partners will be chosen based on the market knowledge of customer ethnocentric tendencies (Paul, 2019). By offering a research model that incorporates numerous exclusionary responses and in-group and out-group orientations that are ignored in the marketing literature (Zeugner-Roth et al., 2015), the current study advances earlier research (Riefler and Diamantopoulos, 2007; Bartikowski and Walsh, 2015) and benefits from social identity theory. The theory of social identity is the foundation of the current investigation (Tajfel and Turner, 1979). In-group favouritism, which is defined as favouring members of one's group (in-group) above members of other groups, is examined by social identity theory (Turner et al., 1987), and it is helpful to understand the connections between consumer ethnocentrism and aversion to buying foreign goods. It also shows that individuals are driven to see their in-group as advantageous and superior to out-groups (Li et al., 2015). Response to Query no 5: Study Context India is an appropriate context to study global brand purchase phenomena. The country has witnessed significant changes in living standards because of an upsurge in income levels, creating opportunities for both domestic and multinational companies. These evolving trends inferred auspicious financial possibilities for global and local brands. The target population for this study consists of urban consumers, as global brand proliferation is prominent in urban areas of India relative to rural areas (Srivastava, Dey, and Balaji, 2020). The current study is not in the context of multi-cultural study, hence the respondents included in this study are only from India. And involving respondents from other countries in this study does not justify the scope of research. However, this could be an avenue for further research. Response to Query no 6: Scenario of biscuit industry in India India’s biscuit market stood at $3.9 billion in 2016, and is projected to grow at a compound annual growth rate (CAGR) of 11.27 per cent, in value terms, between 2017 and 2022, to reach $7.25 billion by 2022. Moreover, augmented disposable incomes, along with changing lifestyles, increasing awareness regarding healthy diets and changes in food consumption patterns, are some of the other factors expected to propel demand for biscuits over the course of the next five years (2023-2027). The biscuits and cookies industry in India has been growing at a CAGR of 10 per cent for the last three years, and is currently valued at Rupees 145 billion. India is currently the world’s largest biscuit consuming nation. Compared to other fast-moving consumer goods (FMCG) products, the penetration of biscuits and cookies, in both the urban and rural areas, is quite high 94 percent and 83 percent, respectively (Kachave, 2018; De Mooij, 2021, Junaid et al., 2022)."
}
]
},
{
"id": "179017",
"date": "12 Jun 2024",
"name": "Thamaraiselvan Natarajan",
"expertise": [
"Reviewer Expertise Marketing"
],
"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 is a very interesting read. It explores on effects of Consumer Dispositional Attitude on Purchase Intention in an Emerging Market like India. The authors have collected data from respondents of major metropolitan cities Bangalore and Chennai using the convenience sampling method. They have relied upon the SMART PLS software for their analysis. Their results give implications for the Marketing managers/practitioners to focus on consumers forming attitude in consumers’ minds so that this attitude formation leads to a purchase decision. The results also imply that attitude formation is the first step in consumers’ behavioral decision making a purchase decision. Overall. given the efforts taken by the authors to write this manuscript involving robust methodology, I feel the manuscript is ready for publication.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-384
|
https://f1000research.com/articles/11-1411/v1
|
30 Nov 22
|
{
"type": "Research Article",
"title": "Validation of a Thai artificial chatmate designed for cheering up the elderly during the COVID-19 pandemic",
"authors": [
"Somrudee Deepaisarn",
"Ek-uma Imkome",
"Konlakorn Wongpatikaseree",
"Sumeth Yuenyong",
"Ploi Lakanavisid",
"Rangsiman Soonthornchaiva",
"Panida Yomaboot",
"Angkoon Angkoonsawaengsuk",
"Napawan Munpansa",
"Somrudee Deepaisarn",
"Sumeth Yuenyong",
"Ploi Lakanavisid",
"Rangsiman Soonthornchaiva",
"Panida Yomaboot",
"Angkoon Angkoonsawaengsuk",
"Napawan Munpansa"
],
"abstract": "Background: The COVID-19 pandemic severely affected populations of all age groups. The elderly are a high-risk group and are highly vulnerable to COVID-19. Assistive software chatbots can enhance the mental health status of the elderly by providing support and companionship. The objective of this study was to validate a Thai artificial chatmate for the elderly during the COVID-19 pandemic and floods. Methods: Chatbot design includes the establishment of a dataset and emotional word vectors in which data consisting of emotional sentences were converted into the word vector form using a pre-trained word2vec model. A word vector was then input into a convolutional neural network (CNN) and trained until the model converges using sentence embedding and similarity word segmentation. Sentence vectors were generated by averaging each word vector using an averaged vector method. For approximate similarity matching, the Annoy library was used to create the indices in tree sorting. Data were collected from 22 elderly and assessed by the Post-Study System Usability Questionnaire (PSSUQ). Results: The study revealed that 72.73% of the respondents found the chatbot easy to learn and use, 63.64% of the respondents found the chatbot can autonomously determine the next course of action, and 59.09% of the respondents believed that troubleshooting guidelines were provided for overcoming errors. The accuracy of the chatbot providing a reasonable response is 56.20±13.99%. Conclusions: Most users were satisfied with the chatbot system. The proposed chatbot provided considerable essential insights into the development of assistance systems for the elderly during the coronavirus pandemic (COVID-19) and during the period of national disasters. The model can be expanded to other applications in the future.",
"keywords": [
"artificial chatmate",
"Elderly",
"mental health",
"COVID-19",
"health promotion"
],
"content": "Introduction\n\nThe COVID-19 pandemic has severely affected global public health, economics, education, and society. During the pandemic, technology’s use for companionship attracted considerable research attention. In addition to physical healthcare, ensuring the population’s mental health during the pandemic is critical. Therefore, this research developed personalized healthcare systems to support the elderly in their daily tasks and promote active and healthy aging. Validity, reliability, and sustainable measures are essential for the healthy aging of the population (Martinho et al., 2022).\n\nAs a result of the impact of COVID-19 outbreaks in Thailand since early 2020, the Ministry of Higher Education, Science, Research and Innovation promoted the health status and economic underpinnings of national strategic projects by using integrated development schemes related to four elements: a) creation of health technologies and applications for promoting community health, b) promotion of goods in community, c) promotion of tourism and d) promotion of circular economy. For this strategy, Thammasat University has applied the technology, knowledge, and expertise to help people in the healthcare domain. Every risk is assessed considering possible effects so that the risk can be addressed appropriately. The pilot project reveals that an efficient health technology system should be developed to deduce strategies to engage, persuade, and motivate older adults to promote positive behavioral changes and increase their awareness of other health conditions. The state quarantine and the physical distancing regulations of the first wave of the pandemic in Thailand significantly impact the elderly’s mental health status. These issues need to be addressed. Considering the Thai culture, older adults with problematic health conditions are typically assumed to spend most of their time alone in a private household, resulting in loneliness. Such people depend on other family members and require personal assistance to complete daily tasks and general chores. Thus, technological influence is essential in improving the preventive measures against mental health problems in the elderly population.\n\nArtificial Intelligence (AI) has been incorporated into many sciences and arts fields, including healthcare and support systems. Furthermore, AI technologies have been used in hospitals as well as health and well-being sectors. The implementation of AI in healthcare can provide cost-effective solutions for improving the health of people in modern society (Väänänen, Haataja, Vehviläinen-Julkunen and Toivanen, 2021). A chatbot can interact with the elderly and clarify their needs and emotions across the database and analytic system. Chatbots can replace the workforce required in many sectors, including chat. Chatbot exhibits considerable potential for integration into clinical practice and healthcare services. In medical and health research, chatbots have been used for food suggestions (Fadhil, 2018), smoking cessation (Wang et al., 2018), and cognitive behavior therapy (Fitzpatrick et al., 2017). Similar approaches have supported focused groups with health problems (Kumar and Rosé, 2014). Chatbot assists young adult or teenager groups in answering socially sensitive questions related to sexual health, drugs, and alcohol consumption. Users can “talk” to a programmed chatbot without fewer concerns and anxiety about sharing personal information with others (Crutzen et al., 2011). A well-designed chatbot can also give accurate guidance to the users. Thus, the first barrier to be overcome is the user's trust in the system. This can only be achieved if the system can ensure that the private information is non-identifiable and non-disclosable by any other means apart from undergoing a screening procedure that benefits the user and is authorized by that user only.\n\nFurthermore, chatbot systems provide a considerable advantage to people who want to obtain health information compared with conventional search engines (Bickmore et al., 2016) for enhancing their understanding of their health conditions, improving health-related behaviors, and making decisions for treatments.\n\nChatbot applications in primary healthcare are more cost-effective than other solutions, such as medical nursing and medical robots. Many people/patients can access such tools using various chatbot platforms, including text and voice interfaces (Kreps and Neuhauser, 2010). Voice interfaces are more efficient, especially for mental health counseling (Wang et al., 2015). Such systems provide suggestions for improving users’ health and quality of life. Therefore, in this study, “Ai-aun”, the artificial chatmate, was developed to promote the health of elderly people, especially during the COVID-19 pandemic and floods. The chatbots assess the similarity of the content cited in a spoken sentence and identified as an essential part of speech. Ai-aun can help the elderly adapt to stressful situations during the COVID-19 pandemic by maintaining good mental health, promoting healthy routines, and preventing dementia. The objective of this study was to validate the Thai artificial chatmate, “Ai-aun”, for the elderly people during the COVID-19 pandemic and during common disasters, such as floods. However, the use of the chatmate is not limited to such emergencies.\n\n\nMethods\n\nIn this study, a natural interface was used. The focus was on developing computers to understand human nature. Originally developed for linguistics, psychology, and computer science, natural interfaces can be applied to various fields where humans can conveniently communicate with computers/machines and convey empathy. Virtual reality is creating a virtual image or a simulation of an event using a computer system based on the interpretation of an ordinary human language. In this work, the development of the voice interface system allows humans to speak or operate efficiently with mobile devices.\n\nChatbot mechanism can respond to and aid users in comprehending the level of their health status and assist the users with the decision-making process to take care of themselves and improve their health. In such systems, user voice data are the inputs (i.e., voice interface). Next, the input is translated into text information. The association between the input text and the database is mapped using a trained model. This model is used to produce the output in the form of text. This result is translated back into voice and promptly conveyed to the user. The process is repeated for all user-triggered inputs, and each triggered input is regarded as an independent conversation.\n\nThe Ai-aun chatbot was developed using natural language processing, virtual reality, and hybrid AI systems. Trust in the system, and its usability is the central cores of this chatbot. In this study, a novel framework was created for the chatbot to produce a reasonable response to a user's message regarding content and emotional characteristics. To build the Ai-aun chatbot, three consecutive modules: namely emotional word vector, sentence embedding and similarity, and approximate similarity matching, were adopted. Figure 1 shows the framework with all components of the chatbot. The elderly can take care of themselves in six general areas: general health, medication, diet, exercising, sleep and rest, and family relationship. The chatbot can provide timely reminders to the elderly to take their medicine, exercise, and sleep to ensure they stay in good health, especially during the COVID-19 pandemic.\n\nThe chatbot responds to the elderly user’s conversation to improve their mental health on six underlying dimensions: general health, medication, diet, exercise, sleep and rest, and other activities. The database system records and monitors all input information so that the authorized administrators can access it. The system can generate a report for administrators for analysis. After using the system, users are asked to complete a trust survey containing 15 questions to understand their trust, confidence, and the quality of conversation. The system performance was assessed using Qualtrics (Corritore et al., 2005). An effective interface should provide simple and easy-to-use features, well-structured, and robust outputs. Higher scores indicate higher trust and usability levels. This is the conventional way of validating a chatbot. A statistical technique was also applied to assess the proposed artificial chatmate reliably. Ai-aun comprises three modules: emotional word vector, sentence embedding and similarity, and approximate similarity matching.\n\nModule 1: Emotional word vector\n\nTo convert a word into a vector for further analysis, data pre-processing and word2vec training are required.\n\nIn the pre-processing steps, raw input data are prepared. That is, text messages are proposed into a suitable format for analysis. These steps include word segmentation and stop word removal. This process was adjusted to suit the structure of the Thai language. Note that the variation of the user’s pronunciation can result in misinterpretation by the model and cause unintended outputs (i.e., amiss expression of emotion). This can be prevented with a proper pre-processing of data.\n\n• In Word segmentation, texts that appear in the sentence are divided into individual words. Binary classification is applied to search for a unique character as the starting point of each word in an input sentence. Cutkurn was selected as the Thai word tokenization library for constructing this system. Cutkurn is based on a recurrent neural network (RNN) model.\n\n• Stop word removal eliminates the words of minor significance in the sentence so that these words do not affect the sentence’s overall meaning. Examples of Thai-specific words in this category include the prefix or suffix of phrases expressing politeness or emphasis, conjunctions, and some ignorable adverbs.\n\nNext, the word2vec functions allow an appropriate model to be trained from the raw input by trying to map the vector representations of words using the process of word embeddings (Mikolov et al., 2013). Skip-gram and Common Bag of Words (CBOW) are used. Skip-gram considers the meaning of a word to predict multiple consecutive words and vice versa for the CBOW technique.\n\nThe working process of the emotional word vector module consists of two main steps.\n\n• Step 1: In this step, emotional information is inserted into the pre-trained word vector to add the semantic meaning of the emotion into the vector of individual words, typically pre-trained on a large, standard data corpus. Therefore, the syntax and syntactic aspects of each word are accurately captured, for example, in a way that the vector of the word “dog” is far away from the vector of the word “doctor”. However, the emotional dimension is not captured satisfactorily. Users find that the vectors for the words “sad” and “happy” are closer because these are adjectives. Thus, if the user applies this pre-trained vector to the emotional chatbot, the results will be inaccurate in terms of emotion.\n\n• Step 2: Word vectors from the trained word embedded models were re-adjusted via a Convolutional Neural Network (CNN) to improve the emotional dimension that should be optimized for each word. The first layer and word embedded layer constitute the first module. The weight of the word embedded layer is continuously optimized until converged in order to determine the emotional dimension.\n\nModule 2: Sentence embedding and similarity\n\nThe vector obtained from Module 1 is at the word level, which is converted into a vector of sentence embedding and similarity, as illustrated in Figure 2.\n\nWords from the sentence were segmented using the Python library developed for Thai word segmentation, called “Cutkum”, which was developed by Treeratpituk (2017). Next, each word is converted into a word vector using the emotional word vector model created in Module 1. Then, a sentence vector is generated from averaged word vectors. Finally, the vector similarity between the input sentence and all the sentences in the response database is computed using cosine similarity according to Equation (1), where A and B are the sentence embedding vectors to be compared.\n\nModule 3: Approximate similarity matching\n\nSimilarity matching consists of generating an index followed by the sorted-tree search. A sentence vector is compared to the existing library. Hence, an accurate answer can be suggested. However, real-time response is required for a chatbot to be sufficiently fast. This research uses the approximate nearest neighbors oh yeah (Annoy) library, where the vectors are rearranged in the response according to the index of the database. This exhibits a fast similar-items retrieval data structure that is ideal for use with chatbots with numerous sentences.\n\nEthical approval\n\nEthical approval for the study was obtained from the Ethics Review Committee for Research Involving Human Research Participants, Thammasat University, Thailand (COA No. 115/2564) on November 4, 2021. The scope, risks, and benefits of the study were explained to all participants. Before data collection, written and verbal consent was obtained directly from participants. Participation was voluntary, and participant anonymity and confidentiality were ensured.\n\nData collection\n\nThe elderly people were selected as participants through purposive sampling on November 11, 2021. People aged above 60 years who speak Thai as their first language and can read Thai were selected. However, the ability to read Thai was a soft requirement because this study focused on communication through the voice interface. Those who were unable to participate in at least 80% of the experiment and had health problems that hindered participation in the experiment were excluded.\n\nTwenty-two elderly participants, 18 women, and 4 men were selected from the population in Bang Krabue, Sam Khok, Pathum Thani, Thailand. The participants were interviewed to collect the sentences they would use to chat with the Ai-aun chatbot. Data collection was finalized with the saturation of the data. After that, the dataset was evaluated by the researchers (including computer scientists, physicians, psychologists, and psychiatric nurses) and submitted to three validators (i.e., a psychiatrist, a nurse who worked in the aging field, and a nursing lecturer in the aging field) to examine the content validity index. To qualify the datasets for the emotional word vector, sentence embedding and similarity word segmentation were performed to generate sentence vectors, followed by approximate similarity matching. Subsequently, the time spent with the chatbot, the rate of questions per minute, and the usability of the chatbot by the elderly were tested after 15 days of using the Ai-aun chatbot on a mobile device.\n\n\n\n• Demographic data were recorded, including age, gender, marital status, education, career, income, personal illness, social networking sites, and time on social networks.\n\n• A Post-Study System Usability Questionnaire (PSSUQ) was used to measure the usability variable, which consists of 15 questionnaires to assess users’ satisfaction with the chatbot interface in terms of language, graphics, and simplicity of the user interface (Lewis, 1995). Typically, PSSUQ scores range from 1 (strongly agree) to 7 (strongly disagree). The higher value means more excellent usability. The Content Validity Index (CVI) is 0.86.\n\n• Training dataset for the conversational chatbot agent: A sample scheme of questions and responses was utilized for the dataset validation. An appropriate answer was selected from the volunteering elderly from the community for training and testing the chatbot model. The CVI for the dataset is 0.95.\n\n• The time spent with the chatbot, recorded in the time log, was analyzed concerning the rate of questions per minute.\n\nAll parameters mentioned above were reported using descriptive statistics.\n\nTechnical performance test for accuracy\n\nThe accuracy of the chatbot providing reasonable responses was systematically tested by ten trained technicians. Each individual spoke 100 random questions based on how they would talk generally. The elderly conversations and answers from the chatbot were collected. One out of the four emotional states, i.e., positive, neutral, frustrated, and negative, was determined for each sentence. The predicted scores for such emotional states were calculated.\n\n\nResults\n\nThe sample consisted of 22 elderly people. The mean age was 68.86±2.56 years old. Out of the total participants, 81.82% were women, and 18.18% were men. People with physical illnesses accounted for 72.73% of the samples. Diabetes mellitus is the most common chronic illness (45.45%) among the participants.\n\nThe time spent with the Ai-aun chatbot was approximately 0.20-0.30 s, and the rate of the user asking questions to Ai-aun was 0.28 questions per minute. The Ai-aun chatbot had a moderate usability level (see the summary Table 1). After 15 days of using the Ai-aun chatbot, 59.09% of the participants were delighted with the system, indicating that it had all the functionalities and capabilities they expected. Additionally, the accuracy of the chatbot in terms of providing a reasonable response was 56.20±13.99%. The predicting scores for the emotional states ranged between 0.50 and 1.00, with the mean predicted score of 0.79±0.17.\n\nThe results revealed that 72.73% of the participants found the chatbot easy to learn and use, and 63.64% of participants thought the chatbot was sufficiently autonomous in determining its next course of action. In case of a system error, the system also provided troubleshooting guidelines according to 59.09% of participants.\n\n\nDiscussion\n\nIn this study, the Ai-aun chatbot was developed to cheer up elderly people during the COVID-19 pandemic. The time spent with the chatbot, the rate of questions per minute, and the usability of Ai-aun measured using the PSSUQ were the variables used in this study. The time spent with the Ai-aun chatbot was 0.2-0.3 s. The average rate of questions was 0.28 min-1. The dataset for the Ai-aun chatbot was designed for short spoken sentences as the input, and the average rate of questions per minute was fast. The usability of the Ai-aun chatbot was at a moderate level. The participants were happy that the Ai-aun system had all the functionalities and capabilities they expected from a chatbot, and the application device was easy to use. Furthermore, a young girl’s voice was adopted along with a friendly, easy-to-use interface (U2T, 2022). Therefore, familiarizing participants with the Ai-aun chatbot was essential. Elderly people were satisfied with the Ai-aun chatbot (Mehta et al., 2022). Moreover, a chatbot provides smooth conversation, including greeting, salutation, compromising, support, and guidance. For example, a simple sentence that sounds relaxing is added, such as “Have a nice day”, “Don’t worry…I will always be with you”, and “I love talking to you”. These sentences encouraged elderly people to interact with the Ai-aun. In addition, Ai-aun provides a feature for medication, rest, exercises, diet schedule, and reminders. The system was consistent with the mobile application developed by Puig (2021), +Approp, to support older and HIV-infected patients. It provides clinical history (e.g., vaccines and medication taken), educational feedback, and reminders of medical appointments. Positive responses were obtained regarding the usability and satisfaction of mobile healthcare applications.\n\nThe Ai-aun chatbot was developed by a paradigm suitable for accepting natural language input and processing computer instructions to enable users to achieve their health goals (Abdul-Kader and Woods, 2015; Fadhil, 2018). Participants enjoyed chatting with Ai-aun (U2T, 2022) (Figure 3). A positive experience and familiarity with the mobile application result in the satisfaction of use.\n\nThe application can be downloaded from the Google Play Store.\n\nThis study proposed a mobile chatbot system to support elderly people, which encourages the elderly to access and get familiarized with the technology to support their physical and mental health. Having enhanced the technological experience of the elderly, they can interact directly with Ai-aun confidently and successfully receive responses related to promoting their health conditions. Four emotional states of the conversation were determined to reflect the user’s actual sentiment. The effectiveness of the response from the chatbot system in terms of progress, interactions, participation, and satisfaction was assessed. Therefore, the system can be expanded to incorporate more functions that align with the users’ needs and applied to more participants.\n\nFor the current configuration, three consecutive modules: emotional word vector, sentence embedding and similarity word segmentation, and approximate similarity matching, were used to elicit a response from the database (Ng, Chia, Yap, & Goh, 2022). The accuracy of the chatbot providing a reasonable response was 56.20±13.99% which depends on the dialogue between the individual and chatbot. Such accuracy is typical for a chatbot that is expected to handle various sentences and sentiments. The accuracy can be improved by increasing the training dataset size to cover a broad variety of conversations. Based on this study, Ai-aun’s model – of the elderly language phenomenon should be studied further. The elderly’s visual and auditory impairment may be an obstacle to the kind of chatbot models.\n\nIn future work, the proposed chatbot system should be improved to consider higher-complexity conversations and to cover the requirements of people with more complicated behaviors, lifestyles, and health conditions. Various contexts and environments also affect the chatbot responses. We intend to incorporate the proposed chatbot with the improved models that can provide real-time data by directly monitoring the precise health conditions of individuals and the elderly. The system can be improved by (1) including additional users (family) that can provide additional content and rewards to the elderly person; and (2) establishing cognitive plans that can be evaluated.\n\n\nConclusion\n\nThis study revealed a moderate usability level. Several users were satisfied with the chatbot system, which provided basic information. They can be used as guidance in developing care and assistance systems for the elderly in the community during the coronavirus pandemic (COVID-19) and in national disasters, such as flood situations. Therefore, the chatbot can be potentially expanded for use in various scenarios. Future development of the Ai-aun chatbot is toward personalized healthcare and remote precision medicine for recognizing and monitoring the health status and behavior of the elderly. The chatbot should allow their family and the authorized caregivers to be in touch with the important updates related to the elderly health.",
"appendix": "Data availability\n\nFigshare: Chatbot Ai-aun, https://doi.org/10.6084/m9.figshare.19744933.v15 (Imkome, 2022).\n\nThis project contains the following underlying data:\n\n- Raw data.xlsx\n\n- The training dataset for the chatbot.docx\n\n- Demographic data.docx\n\n- The results of the interviews.docx\n\n- Source Code Aiaun.pdf\n\n- AiAunApp\n\n- ChitchatAiaun\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nThis study was supported by Thammasat University Research Unit in the innovation of Mental Health and Behavioral Healthcare: staff, laboratory research room, and research equipment.\n\n\nReferences\n\nAbdul-Kader SA, Woods JC: Survey on Chatbot Design Techniques in Speech Conversation Systems. Int. J. Adv. Comput. Sci. Appl. 2015; 6(7). 2156-5570\n\nBickmore TW, Utami D, Matsuyama R, et al.: Improving access to online health information with conversational agents: A randomized controlled experiment. J. Med. Internet Res. 2016; 18(1): e1. PubMed Abstract | Publisher Full Text\n\nCorritore C, Marble R, Wiedenbeck S, et al.: Measuring online trust of websites: Credibility, perceived ease of use, and risk. Paper presented at the 11th Americas Conference on Information Systems, Omaha, Nebraska. 2005.\n\nCrutzen R, Peters G-JY, Portugal SD, et al.: An artificially intelligent chat agent that answers adolescents' questions related to sex, drugs, and alcohol: An exploratory study. J. Adolesc. Health. 2011; 48: 514–519. PubMed Abstract | Publisher Full Text\n\nFadhil A; Can a chatbot determine my diet: Addressing challenges of chatbot application for meal recommendation. Comput. Intell. 2018. arXiv:1802.09100.Reference Source\n\nFitzpatrick KK, Darcy A, Vierhile M: Delivering cognitive behavior therapy to young adults with symptoms of depression and anxiety using a fully automated conversational agent (woebot): A randomized controlled trial. JMIR Ment. Health. 2017; 4(2): e19. PubMed Abstract | Publisher Full Text\n\nGoogle Code: word2vec.[cited 2020 Jul 17].Reference Source\n\nRyu H, Kim S, Kim D, et al.: Simple and Steady Interactions Win the Healthy Mentality. Proceedings of the ACM on Human-Computer Interaction. 2020; 4(CSCW2): 1–25. Publisher Full Text\n\nImkome E:Chatbot Ai-aun. figshare. [Dataset].2022. Publisher Full Text\n\nJudson TJ, Odisho AY, Young JJ, et al.: Implementation of a digital chatbot to screen health system employees during the COVID-19 pandemic.2020.Reference Source\n\nKolenik T, Gams M: Intelligent Cognitive Assistants for Attitude and Behavior Change Support in Mental Health: State-of-the-Art Technical Review. Electronics. 2021; 10(11): 1250. Publisher Full Text\n\nKreps GL, Neuhauser L: New directions in ehealth communication: Opportunities and challenges. Patient Educ. Couns. 2010; 78(3): 329–336. PubMed Abstract | Publisher Full Text\n\nKumar R, Rosé CP: Triggering effective social support for online groups. ACM Transactions on Interactive Intelligent Systems. 2014; 3(4): 1–32. Publisher Full Text\n\nLewis JR: Ibm computer usability satisfaction questionnaires: Psychometric evaluation and instructions for use. Int. J. Hum.-Comput. Interact. 1995; 7(1): 57–78. Publisher Full Text\n\nLiu WD, Chuang KY, Chen KY: The Design and Implementation of a Chatbot's Character for Elderly Care. 2018 International Conference on System Science and Engineering (ICSSE). 2018; pp. 1–5. Publisher Full Text\n\nManickam RN, Mu Y, Kshirsagar AV, et al.: Hospital readmissions reduction program (hrrp).2019.Reference Source\n\nMartinho D, Crista V, Carneiro J, et al.: An Intelligent Coaching Prototype for Elderly Care. Electronics. 2022; 11: 460. Publisher Full Text\n\nMehta R, Verghese J, Mahajan S, et al.: Consumers’ behavior in conversational commerce marketing based on messenger chatbots [version 1; peer review: awaiting peer review]. F1000Res. 2022; 11: 647. Publisher Full Text\n\nMikolov T, Chen K, Corrado G, et al.: Efficient Estimation of Word Representations in Vector Space.2013 [cited 2021 May 23].Reference Source\n\nNg H, Chia GJW, Yap TTV, et al.: Modelling sentiments based on objectivity and subjectivity with self-attention mechanisms [version 2; peer review: 1 approved, 2 approved with reservations]. F1000Res. 2022; 10: 1001. PubMed Abstract | Publisher Full Text\n\nTreeratpituk P: Cutkum: Thai Word-Segmentation with LSTM in Tensorflow.2017 [cited 2020 May 5].Reference Source\n\nPuig J, Echeverría P, Lluch T, et al.: A Specific Mobile Health Application for Older HIV-Infected Patients: Usability and Patient’s Satisfaction. Telemed. e-Health. 2021; 27: 432–440. [CrossRef] [PubMed]. PubMed Abstract | Publisher Full Text\n\nSafi Z, Abd-Alrazaq A, Khalifa M: Househ M Technical Aspects of Developing Chatbots for Medical Applications: Scoping Review. J. Med. Internet Res. 2020; 22(12): e19127. PubMed Abstract | Publisher Full Text Reference Source\n\nSrinivas KK, Peddi A, Srinivas BGS, et al.: Artificial Intelligence Techniques for Chatbot Applications. 2022 International Mobile and Embedded Technology Conference (MECON). 2022; pp. 292–296. Publisher Full Text\n\nSu MH, Wu CH, Huang KY, et al.: A chatbot using LSTM-based multi-layer embedding for elderly care. 2017 International Conference on Orange Technologies (ICOT). 2017; pp. 70–74. Publisher Full Text\n\nUniversity to Tambon Project (U2T):2022. Retrieved 3 August 2022.Reference Source\n\nVäänänen A, Haataja K, Vehviläinen-Julkunen K, et al.: AI in healthcare: A narrative review [version 2; peer review: 1 approved, 1 not approved]. F1000Res. 2021; 10: 6. Publisher Full Text\n\nWang C, Bickmore T, Bowen DJ, et al.: Acceptability and feasibility of a virtual counselor (vicky) to collect family health histories. Genet. Med. 2015; 17: 822–830. PubMed Abstract | Publisher Full Text\n\nWang H, Zhang Q, Ip M, et al.: Social media–based conversational agents for health management and interventions. Computer. 2018; 51(8): 26–33. Publisher Full Text"
}
|
[
{
"id": "176964",
"date": "19 Jun 2023",
"name": "Sheetal Kusal",
"expertise": [
"Reviewer Expertise Natural language processing",
"emotional detection",
"conversational agents",
"Artificial Intelligence."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 presents a Thai chatbot for the mental well-being of elderly people. The paper is very interesting to read. Although the authors have tried to make it technically sound, some points must be clarified to make the paper more technically sound.\nPoints to be discussed:\nSome sentences in the paper are repetitive. Could you remove the repetitiveness of sentences?\n\nLiterature review must be done thoroughly. It is advisable to make an LR table. The authors can refer to the format mentioned in the citation1.\n\nIn the text pre-processing, the authors have mentioned only segmentation and stop words removal. In NLP, text pre-processing involves many steps to make text appropriate for processing. So, have the authors performed them or which steps? And if not performed, why only stop word removal? Clarify.\n\nThe authors have mentioned emotion information inserted into the pre-trained word vectors. The authors are expected to elaborate more on how emotion information is inserted into pre-trained word vectors.\n\nMore discussion is expected on results and performance.\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": [
{
"c_id": "10865",
"date": "11 Jan 2024",
"name": "Ek-uma Imkome",
"role": "Author Response",
"response": "Dear Dr. Sheetal Kusal, Thank you for your time and valuable feedback on our manuscript. We have carefully reviewed your comments. As suggested, we provide a point-by-point response as below: 1. Some sentences in the paper are repetitive. Could you remove the repetitiveness of sentences? Authors: Thank you very much. We remove the repetitiveness of sentences on page 6 (line no. 4-6), page 10 (Line no. 4,5,7) 2. Literature review must be done thoroughly. It is advisable to make an LR table. The authors can refer to the format mentioned in the citation1. Authors: Thank you for your attention. The Literature review is our work and on the process of publication. 3. In the text pre-processing, the authors have mentioned only segmentation and stop words removal. In NLP, text pre-processing involves many steps to make text appropriate for processing. So, have the authors performed them or which steps? And if not performed, why only stop word removal? Clarify. Authors: Thank you very much. We addressed your comment in the Algorithms and System Design section (Page 6; Line no. 21-22 ) as below: “because the sentences were appropriate for content validity by three experts and the research teams before launching the language in NLP. Additionally, we need to check and remove some sentence errors during text pre-processing”. 4. The authors have mentioned emotion information inserted into the pre-trained word vectors. The authors are expected to elaborate more on how emotion information is inserted into pre-trained word vectors. Authors: Thank you very much. We added the inserted emoji into pre-trained word vectors on page 7 (Line no. 4-10) “The visual information in conversational agents may take affective states and thus is an appropriate indication of emojis in texts. The objective is to use emojis in the study for better interpretability of emotional user states, especially for short polysemous phrases of both positive and negative emotions in many scenarios. Understanding willingness, mood, and affect will help conventional agents respond to reliability, validity, and appropriateness. Additionally, Emojis are users’ reported labels of mood and affect to convey emotions in the context of communication interactions”. 5. More discussion is expected on results and performance. Authors: Thank you very much. We added new references on the part of the discussion to support our results in the text. “The agent provides proactive functions, sending messages to help elderly users educate and relax in general health, taking medication, diet, family relationships, exercise, rest, and sleep. Reminiscence strategies are considered challenging when related to design interfaces, conversation logic, and meaningful metrics directed at elderly adults, which benefit from screening and educating them (Kusal et al., 2022; Moreno, Sánchez-Anguix, Alberola, Julián, & Botti, 2024; Otero-González, Pacheco-Lorenzo, Fernández-Iglesias, & Anido-Rifón, 2024)”. References 1. Kusal S, Patil S, Choudrie J, Kotecha K, et al.: AI-Based Conversational Agents: A Scoping Review From Technologies to Future Directions. IEEE Access. 2022; 10: 92337-92356 2.Otero-González, I., Pacheco-Lorenzo, M. R., Fernández-Iglesias, M. J., & Anido-Rifón, L. E. (2024). Conversational agents for depression screening: A systematic review. International Journal of Medical Informatics, 181.https://doi.org/10.1016/j.ijmedinf. 2023.105272 3. Moreno, J. C., Sánchez-Anguix, V., Alberola, J. M., Julián, V., & Botti, V. (2024). An intelligent conversational agent for educating the general public about HIV. Neurocomputing, 563. https://doi.org/10.1016/j.neucom.2023.126902 ----------------------------------------------"
}
]
},
{
"id": "223095",
"date": "24 Nov 2023",
"name": "Sinan Chen",
"expertise": [
"Reviewer Expertise Smart healthcare",
"Web application",
"Human-computer interaction"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 reviewer appreciates the level of detail that the authors provide with accompanying data. Regarding the content described in this article, the reviewer made the following comments:\n(1) Is this conversation robot personalized? For example, how did you obtain pre-training data for emotional word vectors? Additionally, the author should provide a representative history of the conversation.\n(2) Although the author used PSSUQ to evaluate system usability, it is unclear which fine-grained aspects of improving users' mental health conditions are specifically reflected.\n(3) Regarding speech synthesis and recognition technology, what is the error tolerance rate? Will there be delays and bugs? How can the system provide 24-hour virtual care for the elderly who cannot use mobile phones?\nThat is all. Thanks\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?\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": "10866",
"date": "11 Jan 2024",
"name": "Ek-uma Imkome",
"role": "Author Response",
"response": "Dear Dr. Sinan Chen, We appreciate your time and valuable comments on our manuscript. We have carefully reviewed your suggestion. We provide a point-by-point response below: (1) Is this conversation robot personalized? For example, how did you obtain pre-training data for emotional word vectors? Additionally, the author should provide a representative history of the conversation. Authors: Thank you for pointing out the critical issue. Per your comment, we added more information on the revised manuscripts on page 6, line no. 19-24. “The data pre-training was obtained from the 30 elderly volunteers on the U2T project. The research teams checked for accuracy (general health; 193 datasets; family; 115 datasets; medication; 122 datasets; diet; 137 datasets; exercise; 118 datasets; sleep and rest and other activities; 151 datasets). After obtaining the accurate data set, the researcher teams submitted data to the three experts for the process of content validity testing. The dataset was addressed as the expert comment for the training sessions.” (2) Although the author used PSSUQ to evaluate system usability, it is unclear which fine-grained aspects of improving users' mental health conditions are specifically reflected. Authors: Thank you very much for your concern. The mental health improvement state is shown in the research results of another manuscript that is in the process of publication. (3) Regarding speech synthesis and recognition technology, what is the error tolerance rate? Will there be delays and bugs? How can the system provide 24-hour virtual care for the elderly who cannot use mobile phones? Authors: Thank you very much. These valuable comments address in limitation of the manuscript as below “The elderly may have benefited during the chatbot use, especially in physical and mental health aspects. These valid chatbots via mobile phone are very easy to learn and use, but the present study's error tolerance rate, delays, and bugs was not measured. This limitation existed but did not have a significant effect on the results. However, it is recommended to address these limitations in future studies”. That is all. Thanks"
}
]
}
] | 1
|
https://f1000research.com/articles/11-1411
|
https://f1000research.com/articles/12-1391/v1
|
23 Oct 23
|
{
"type": "Opinion Article",
"title": "Ten recommendations for organising bioimaging data for archival",
"authors": [
"Paul K. Korir",
"Andrii Iudin",
"Sriram Somasundharam",
"Simone Weyand",
"Osman Salih",
"Matthew Hartley",
"Ugis Sarkans",
"Ardan Patwardhan",
"Gerard J. Kleywegt",
"Paul K. Korir",
"Andrii Iudin",
"Sriram Somasundharam",
"Simone Weyand",
"Osman Salih",
"Matthew Hartley",
"Ugis Sarkans"
],
"abstract": "Organised data is easy to use but the growth of bioimaging, with improvements in instrumentation, detectors, software and experimental techniques has resulted in an explosion in the volumes of data being generated, making this an elusive goal. This guide offers a handful of recommendations whose implementation would contribute towards better organised data in preparation for archival. Based on our experience archiving large image datasets in EMPIAR, the BioImage Archive and BioStudies, we propose a number of strategies that we believe would make future data depositions more useful to the bioimaging community and that may also find use in other data-intensive disciplines. To facilitate the process of analysing data organisation, we present bandbox, a Python package that provides users with an assessment of their data by flagging potential issues that could be addressed before archival.",
"keywords": [
"Organising data",
"public archiving",
"data deposition",
"open data",
"bioimaging",
"EMPIAR",
"BioImage Archive",
"BioStudies"
],
"content": "Introduction\n\nResources such as EMPIAR (Iudin et al., 2016; Iudin et al., 2023) and the BioImage Archive (Ellenberg et al., 2018; Hartley et al., 2022) provide a valuable service to the life-science community by supporting the archival and reuse of imaging data, often acquired at considerable cost, in line with the aspirations of the FAIR Guiding Principles (Wilkinson et al., 2016). There are numerous advantages and benefits to reusing bioimaging data, including more economical use of limited resources such as instrumentation and highly skilled technical staff. Moreover, specimens may be unique, costly to acquire, or difficult to reproduce, meaning that such data may only be accessible via archives. Archived data can be mined for reanalysis, verification and validation, and for development of new analytical techniques and software tools, such as machine learning model training. Reuse of such data may also lead to improvements in how it is produced, both technologically and methodologically. As practitioners in bioimaging data archiving, it is our experience that handling large datasets presents several data-management challenges, particularly in recent years with the rapidly increasing volumes of bioimaging data (Ellenberg et al., 2018). For example, it took eight years for EMPIAR to archive a total of one petabyte of data, but the second petabyte took only 14 months (Iudin et al., 2023). Bioimaging datasets may comprise numerous and sometimes very large files in a variety of, sometimes proprietary, formats. Individual files may include multiple channels and time points and data and metadata from several specimens. Besides the raw image data, there may also be a need to archive processed data, reconstructed 3D volumes, segmentations, particle stacks and other derived or related data.\n\nThere are two related but distinct avenues for organising data: labelling (metadata) and arranging data items (order). Metadata are essential to make the data useful even though metadata standards are difficult to enforce. Therefore, metadata standardisation has received a lot of attention with initiatives such as Bioschemas, an effort to improve findability of datasets via standardised textual annotations, and MIAME (Brazma et al., 2001), recommendations for minimal metadata describing a microarray experiment, and the overarching FAIR Guiding Principles (Wilkinson et al., 2016). For bioimaging, REMBI (Sarkans et al., 2021) provides community-supported recommendations on how to describe all aspects of bioimaging experiments including sample preparation, data processing and analysis. Whereas there are several ongoing efforts towards standardising bioimaging data formats (OME-NGFF (Moore et al., 2021), DVID (Katz & Plaza, 2019), HDF5 (Pietzsch et al., 2015), etc.), we know of no efforts towards harmonising how to organise datasets for maximum usefulness with archival in mind. The organisation (order) of data is usually taken for granted and it falls upon refinements of the metadata to bear the burden of meaningfully describing the data.\n\n\nMotivation\n\nGood organisation (order) of data improves its usefulness and is the responsibility of the data depositors. Depositors are best placed to present data in a way that adequately captures the experimental design and outcomes. Organising a dataset to minimally convey a structure in line with the actual experimental output can improve its usability while the bulk of meaningful attributes can be expressed in the metadata. The degree of usefulness depends directly on the quality of organisation, and thoughtful consideration of users’ needs improves that usefulness. Good organisation also gives a dataset transparency and understandability: users are able to immediately distinguish the various experimental categories as well as plan how to analyse the data. Therefore, it helps to have a clear perspective of the various classes of users.\n\nIn general, we consider three classes of users: intra-domain scientists, inter-domain scientists and extra-domain scientists (Datta et al., 2021). (For the purpose of this article, we will refer to any such user of a dataset as a ‘scientist’, interested in extracting some knowledge from the archived data.) Intra-domain scientists are familiar with key attributes of the data and may be able to quickly assess the usefulness of a dataset. An example would be a structural biologist mining an electron cryo-tomogram to extract sub-volumes that have not been previously studied. Inter-domain scientists may want to mine the data for purposes tangential to some other domain. For example, a genomicist may want to include structural analyses in a genomics study and may turn to raw imaging data to accomplish this. Extra-domain scientists are only interested in data for its technical properties, i.e., for some purpose completely unrelated to the original purpose of the data’s collection. A computer scientist, for example, may want to assess the performance of a learning algorithm on fluorescent microscopy images when performing some classification task. It is likely to be a challenge to optimise the organisation of data for all classes of users simultaneously. In practice, organising the data to be useful to scientists with the least familiarity with the domain will most likely advance its usefulness for all classes of scientists and can thus be a good aspiration.\n\nThe task of organising data consists of making trade-offs in the use of ‘ways and means’ of effecting the organisation. We will refer to these ‘ways and means’ as organisational resources. A simple example would be the use of alphabetic ordering when organising a set of strings; the natural ordering according to some alphabet is our organisational resource and we exploit the fact that most users will perceive this as a convenience when traversing the data. In less trivial organisational tasks, we need to express complex relationships between the entities to be organised. For instance, a dataset that consists of the experimental measurements resulting from a sequence of treatments on a set of specimens measured at various points in time requires the use of specimen, treatment and time point identifiers as well as other experimental aspects (data formats, alternative perspectives, transformations of the data such as changes in units, etc.) to be captured in such a way as to preserve the main experimental relationships. In that case, we can expand our set of organisational resources to include a folder hierarchy and file formats in addition to the set of symbols (letters, numerals, punctuation, literal symbols, uppercase and lowercase and so on) used to create the various identifiers. Ideally, we would like to keep repetition to a minimum so that the nature of the experiment can be readily discerned.\n\nThe manner in which organisational resources are used affects the usability of the resulting organisation: using too few of them will obscure the meaning of the organisation while using too many will overwhelm potential users. For example, including redundant folders along any part of the hierarchy (folders that contain only a single folder which in turn contains the actual data) makes it tedious to navigate through a dataset. On the other hand, dumping all files into one folder will make it difficult for the end user to distinguish between groups of semantically related files, especially when thousands of files are present. Similarly, naming files and folders by referring to entities inaccessible to its intended users (e.g., private machine names or private accession codes that external users will not have access to or even fathom) consumes precious ‘name space’ without conveying any useful information. Organising data is thus an investment of time and effort with the ultimate aim of improving the usefulness of the data.\n\nWe can therefore formulate the organisation task as follows: given a set of related data items associated with an experiment, how may they be organised to best convey their relationships using as few organisational resources as possible while maximising their usability?\n\nTo achieve this, we define the term facet to refer to the various attributes germane to the experiment which may be included in the folder and file names. A non-exhaustive list of facets are: specimen names (organism, tissue, cell type/line), experimental roles (treatments vs. controls), time (developmental status, date, elapsed time), processing status (raw data, by algorithm, procedure), generally available equipment (microscopes, detectors, preparation equipment model names), replicates, file types (3D volumes, particle stacks), names of software used for processing, and so on.\n\nThis guide attempts to solve the organisation task by providing 10 recommendations that arise from our experience of handling hundreds of large image datasets in the public archives EMPIAR, BioImage Archive and BioStudies (Sarkans et al., 2018). Ideally, we would like to organise potentially numerous and voluminous data to maximise ease of use so as to facilitate the user’s ability to:\n\n1. quickly identify the suitability of (subsets of) the data;\n\n2. clearly distinguish between the various facets of the data;\n\n3. quickly verify the usefulness of the data (e.g., thumbnails, previews, summaries, READMEs, LICENCE files);\n\n4. retrieve only relevant subsets of the data.\n\nThis guide does not offer any recommendations for a detailed schema to describe experimental and analytical procedures; those may be captured in metadata for the various archives. Neither does it describe how to decide which experimental facets are appropriate (these are part of the experimental design), nor does it attempt to describe how to achieve organisation for automated analysis (we assume that the resulting organisation will be consumed by humans). It also ignores the universe of image formats in use and mainly includes examples from our experience archiving bioimaging data, but we anticipate it may be useful across other imaging disciplines. Good organisation improves data structure and format predictability and may facilitate automated processing. Therefore, our guide is intended to lead towards best practices rather than serve as a framework. Finally, this guide does not aim to achieve standardisation. We believe it is more practical to have a set of best practices and leave it up to the data authors to decide how best to apply them.\n\nWe believe that the recommendations outlined here may be of value to two principal groups of users: 1) data depositors, who need to design and prepare their data to improve its usability to the community, and 2) technologists (hardware, software and methods developers), who, by considering these recommendations in their designs, can greatly facilitate data organisation at the source.\n\nTo make our recommendations practical, we have developed bandbox (Korir et al., 2022), an open-source command-line interface (CLI) tool to help users understand how they can improve the organisation of their data in preparation for archival. The program offers two CLI commands: view and analyse. The view command displays a tree of a directory and all its contents; for every non-empty directory with files, bandbox provides a summary of the number of files in it, including a list of all the file formats encountered. The analyse command provides a listing of possible issues grouped into categories in line with those specified in the Recommendations section of this article. bandbox examines the tree associated with the nested hierarchy of files and folders in a dataset and then concurrently runs various heuristics on the tree which are controlled by configurations that the user may modify. The results produced by the analyse command are only suggestions for improvement; we understand that there may be practical limitations to implementing some of the suggested improvements as well as good reasons for keeping the data as is. Figures 1 and 2 show screenshots of the results of running bandbox on two different datasets.\n\nThe actual example dataset is provided with the bandbox source code (ASCII – American Standard Code for Information Interchange).\n\nThe actual example dataset is provided with the bandbox source code.\n\n\nRecommendations\n\nWe will motivate our guide by referring to a fictitious EMPIAR dataset. This dataset has a clear structure, but we propose that it can be further improved following the recommendations in the guide below.\n\nOur goal is to improve the file/folder structure shown in Figure 3 to better convey the relationships between the experimental facets while economising the organisational resources available. For clarity, we have refrained from listing several thousand raw TIFF files in the folders designated ‘Raw’.\n\nIssues include: 1) long file/folder names with spaces, non-ASCII characters (ö) and redundant directories (ASCII – American Standard Code for Information Interchange); 2) obscure sequences with inconsistent spelling, 3) inconsistency in folder hierarchy, 4) obscurity through meaningless symbol sequences, 5) verbosity in names, 6) subtle differences in spelling (in this case, a hyphen) and 7) inconsistency in typography due to character case and inclusion of different separator characters, e.g., spaces vs hyphens. See text for more details.\n\nThe example dataset illustrates several properties of its organisation that undermine the goal of being usable:\n\n• Verbosity typically presented by repetition of references which may be resolved using the file hierarchy, such as:\n\n○ Folders containing only a single folder which in turn contains the folder with the actual data. The child folder of ‘data’ only has the folder ‘A U Thör et al …’ in it that contains the folder ‘A folder with an overall description’ which has the actual data.\n\n○ Very long names of files/folders. The full path of the file ‘data/A U Thör et al - A very long relevant title that has most of the keywords in your paper/A Folder with an overall description/0923480928 - Treatement Tr1-323 Tissue/0923480928_Treatement_Tr1323_Organelle1-topology1.zip’ is ‘0923480928 Treatement Tr1-323 Segmentation/0923480928_Treatement_Tr1323_Organelle1-topology1.zip’, which might be outside the limits of legacy software; e.g., IMOD (Mastronarde, 2006) has a limit of 320 characters for input file names.\n\n○ Repetition of identifiers along the path. In the previous example, half of the files repeat the identifier ‘0923480928’ that conveys no meaningful information and which, if required at all, should only appear in the appropriate parent folder name.\n\n• Ambiguity occurs through incomplete identifiers either due to typos or non-standard characters.\n\n○ Is ‘Tr1-323’ the same as ‘Tr1323’?\n\n○ Use of spaces and non-ASCII characters can make processing the data complicated because of how software may handle path names with spaces. ASCII stands for the American Standard Code for Information Interchange and consists of plain characters used in many languages.\n\n• Inconsistency is perhaps the most common issue and is usually the result of manually introduced errors such as changes in spelling, e.g., naming similar folders ‘tomo’ and ‘tomogram’ for related files. In the above example we have:\n\n○ ‘Topology’ and ‘topology’\n\n○ ‘Treatment’ vs ‘Treatement’\n\n○ ‘Tr1-323’ and ‘Tr1323’\n\n○ Inconsistency may also be observed in folder structure. For example, only one of the treatment folders (the one with ‘3738932082’ in the name) has an extra child folder, breaking the trend of the others.\n\n• Obscurity tends to occur through the use of identifiers with no obvious meaning, e.g., references to external resources such as figure numbers in a related paper, machine identifiers, script names, etc.\n\n○ The numerical identifiers such as ‘0923480928’ have no obvious meaning in the context of the dataset.\n\n○ ‘Tr1-323’ may be an external reference but its meaning is unclear.\n\nUnderstandably, in certain cases such obscurity may be useful to keep identifiers which convey additional information. For example, in electron cryo-microscopy (cryo-EM) pipelines, the dataset may consist of multiple subsets obtained with different open-source software, e.g. particle picking by EMAN2 (Tang et al., 2007), beam-induced motion-correction by MotionCorr (Li et al., 2013), contrast-transfer function (CTF) correction by gCTF (Zhang, 2016), classification by RELION (Scheres, 2012), reconstruction by cryoSPARC (Punjani et al., 2017), etc.\n\nThe 10 recommendations we present below are divided into four groups: planning (one recommendation), structure (three recommendations), naming (three recommendations) and miscellaneous (three recommendations). We have provided further guidance within each group for related concepts.\n\n(1) Design before data collection. Plan beforehand, if possible, how the data may be structured.\n\na. If the experimental facets are known prior to data collection, the organisation suggestions that follow below will be easier to apply once and for all; it is harder to reorganise data, especially voluminous data on multiple networked drives or in a cloud resource after collection. At a minimum, consider organising the few top-level directories in terms of the experimental facets prior to archival.\n\nb. Consider employing a naming convention within a research group to ensure that data is consistent between creators of the data. This can even be specified in the microscope’s software to include imaging parameters in the file names automatically such as a base name, date and/or time, imaging parameters (e.g., resolution, section size) or even free text, among many others. We invite software vendors/creators who have not already done so to consider incorporating organisational concerns into their software that take these recommendations into account.\n\nThis section contains recommendations to address the hierarchical organisation of files and folders only.\n\n(2) Containing folder. Consider having one parent folder into which all sub-datasets are located. Such a container folder is also a good location to include auxiliary data that apply to the collection such as README or integrity (see recommendation 10) files, which provide users with the context of the data organisation.\n\n(3) Folder depth.\n\na. Consider limiting the folder depth to a reasonable maximum. As a rule of thumb, three to four directory levels is adequate for most applications but the fewer the better.\n\nb. Consider excluding folders which do not convey any additional information. For example, consider a dataset having only TIFF files. Including a folder called tiff in the path <condition>/tiff/files*.tif is redundant. By contrast, if the file format is instrumental then <condition>/<format1>/<files_of_format1> and <condition>/<format2>/<files_of_format2> and so on is meaningful.\n\nc. Consider an upper limit on the number of files in a folder and if necessary split large directories so they do not contain more than a certain maximum number of files (e.g., 10,000). If, for instance, a folder has one million files then it may instead be organised as a folder (parent_folder) with 100 sub-folders (child00 to child99), each containing 10,000 files. This is important because different file systems have different tolerances for handling large numbers of files. For example, the Second Extended Filesystem (ext2) imposes ‘soft’ limits of 10,000 files per directory because of the extra overhead when processing such large folders (The Second Extended Filesystem — The Linux Kernel Documentation). While modern file systems are capable of handling larger numbers of files, the re-usability of the data will increase when taking into account systems with more modest resources, such as web browsers that may need to list or process all files in a directory.\n\n(4) Folder contents.\n\na. Consider grouping related files unless it is instrumental to keep them separated. For example, group files by specimen, filetype, experimental purpose (treatment, control), etc. It may be instrumental to separate different data types into different folders (e.g., one for micrographs and one for particle stacks). Further sub-folders may be necessary for single- and multi-frame micrographs, unaligned and aligned micrographs, etc.\n\nb. Consider depositing data from different experimental techniques/sub-techniques as separate archive entries (e.g., single-particle data in one, tomography data in another). Most archives allow multiple separate entries to be linked or grouped.\n\nIn this section, we provide some suggestions to improve the naming of files and folders.\n\n(5) Meaningful names.\n\na. Consider naming files and folders using meaningful identifiers without specifying external references. For instance, while the name ‘Figure 5’ probably refers to a paper describing (some of) the data, users will require access to that manuscript, which may be behind a paywall. The names of files and folders should exclude any references that are tied to the instrument or your organisation, which are at best unhelpful for external users.\n\nb. Consider avoiding ambiguous attributes such as dates and times particularly in folder names. Mass renaming of files with dates and times can become non-trivial particularly if such attributes have subtle variations for related files (e.g., as date/time stamps are incremented) and is therefore best avoided.\n\n(6) Naming symbols.\n\na. Consider confining names to lowercase letters and numerals and replacing all spaces with underscores or hyphens for meaningful word (group) boundaries as this makes it substantially easier when working with the data. Preferably, consider underscores only for word boundaries and hyphens for keywords or other key attributes such as specimen names identifiable by the presence of a hyphen, e.g., covid-19. Consistent use of case also improves readability (Deissenboeck & Pizka, 2006).\n\nb. Consider avoiding certain characters which could lead to unintended consequences during processing such as ampersands (&), spaces, exclamation marks (!) and question marks (?). In general, stick to printable alphanumeric ASCII characters and avoid non-ASCII characters (e.g., ü, å or non-Roman scripts).\n\nc. Consider avoiding periods in names as this can lead to unpredictable behaviour for instance when attempting to determine formats. For example, while it is generally well known that the file file.tar.gz has two standard extensions, it may not be as widely known that file.ome.tiff, file.ome.tf2, file.ome.tf8 and file.ome.btf are all valid multi-extension bioimaging formats (OME-TIFF Specification — OME Data Model and File Formats 6.2.2 Documentation).\n\nd. Consider an upper limit on the length of file and folder names. We propose a working upper limit of 50 characters. Even though modern operating systems have no limitations on the lengths of names, end users will still struggle typing very long names which increases the likelihood of transcription errors. In some cases, software that is widely used by the bioimaging community imposes limits on the number of characters for file paths, e.g., IMOD (Mastronarde, 2006) imposes a file path limit of 320 characters. Bear in mind that, increasingly, users will interact with datasets via a web browser, which also has a practical limit (based on the device’s memory) on the number of files that can be selected in the browser’s select dialog.\n\n(7) Identity.\n\na. Ensure consistency when naming files and folders so that similar folders at different depths have the same names.\n\nb. Do not include personal identifiers in folder or file names.\n\nc. Some words to consider for exclusion in the names of internal files/folders: ‘files’, ‘data’, ‘images’ etc. or other words that convey no additional meaningful information.\n\nd. Think of folder names as applying to all the folders and files they contain as well: there should be no repetition in nested folder names, e.g., data/control.a/control.a.1/control.a.1.value/data/;\n\ne. When providing 3D data as slices, consider zero-padding the slice identifiers which facilitates correct assembly. For example, consider an image with 1000 images at a resolution of MxN representing sections/slices of some volume; splitting this file should result in files of the form file0001.tif to file1000.tif. If zero-padding is missing or done incorrectly (file1.tif to file1000.tif), the order of slices will be lost on operating systems that apply lexicographic rather than numerical sorting. This can be fixed using the rename shell utility, e.g., rename file file00 file??.tif will convert all files with 01 to 99 to have 0001 to 0099 and so on. rename is available on most Linux distributions and may be installed on macOS using Homebrew or from the source code. On Windows systems the Bulk Rename Utility can be used.\n\nFinally, this section includes some tips on how to handle other aspects of organisation not covered in the previous sections.\n\n(8) Friendly file formats.\n\na. Consider providing images in widely used file formats unless you are demonstrating a novel file format in which case it may be necessary to first get in touch with the archive to plan this. Additional information may be requested to provide users with guidelines on how to use and visualise the new format files including any conversion tools that are available and on providing the same data in a widely used file format as well.\n\nb. Even for file types that are widely used, it may be helpful to stick to open formats to ensure that users without access to proprietary software will have access to the data.\n\n(9) Document your data.\n\na. Consider including a README text file which provides an overview of how the data is organised.\n\nb. Consider testing the usability of your data by asking a colleague to peruse your data to assess whether the organisation is clear. This can be achieved by asking the tester to describe their understanding of what the data presents.\n\n(10) Integrity. If possible, consider including checksums, parity codes or hashes for each data file in a separate file, e.g., md5-sums.txt, imageset01.par2 or sha512-hashes.txt to facilitate content verification. These will allow users to verify that the data has not been corrupted during the deposition or download process. Each of these different ways to verify file integrity have corresponding tools available for all operating systems, but their operation is beyond the scope of this article (Chi Lianhua & Zhu Xingquan, 2017).\n\nApplying the recommendations above, we may revise the path:\n\ndata/A U Thör et al - A very long relevant title that has most of the keywords in your paper/A Folder with an overall description/0923480928 - Treatement Tr1-323 Tissue/0923480928_Treatement_Tr1323_Organelle1-topology1.zip’ is ‘0923480928 Treatement Tr1-323 Segmentation/0923480928_Treatement_Tr1323_Organelle1-topology1.zip\n\nto:\n\ndata/brief_description/treatment3_tissue/segmentation/organelle1_topology1.zip,\n\na reduction from 328 to 79 characters for the full path. The new organisation is presented in Figure 4.\n\n\nConclusion\n\nWe hope that these 10 recommendations will only be the beginning of a broader discussion on how to organise bioimaging data in particular and experimental data in general for maximum usefulness, not just to the bioimaging community, but to the wider scientific community. Given the breadth of applications of bioimaging techniques, good organisation would go a long way to helping scientists from other disciplines to benefit from using bioimaging data. There is still considerable scope to develop better ways of not only organising data, but also representing it to enable automated data analysis.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nThe authors are grateful to Alex J. Noble and Christopher J. Peddie for helpful feedback on the manuscript. This work aligns with the recommendations of the EuroBioimaging/ELIXIR Joint Strategy (https://elixir-europe.org/system/files/euro-bioimaging_elixir_image_data_strategy.pdf), in particular the need for standards and approaches for the organisation of image data storage in established and emerging reference image domains. We acknowledge both ELIXIR and Euro-BioImaging’s key roles in highlighting the importance of the effective organisation of biological image data.\n\n\nReferences\n\nBrazma A, Hingamp P, Quackenbush J, et al.: Minimum information about a microarray experiment (MIAME)—toward standards for microarray data. Nat. Genet. 2001; 29(4): 365–371. PubMed Abstract | Publisher Full Text\n\nLianhua C, Xingquan Z: Hashing Techniques. ACM Computing Surveys (CSUR). 2017. Publisher Full Text\n\nDatta S, Lakdawala R, Sarkar S: Understanding the Inter-Domain Presence of Research Topics in the Computing Discipline. IEEE Trans. Emerg. Top. Comput. 2021; 9(1): 366–378. Publisher Full Text\n\nDeissenboeck F, Pizka M: Concise and consistent naming. Softw. Qual. J. 2006; 14(3): 261–282. Publisher Full Text\n\nEllenberg J, Swedlow JR, Barlow M, et al.: A call for public archives for biological image data. Nat. Methods. 2018; 15(11): 849–854. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHartley M, Kleywegt GJ, Patwardhan A, et al.: The BioImage Archive - Building a Home for Life-Sciences Microscopy Data. J. Mol. Biol. 2022; 434: 167505. PubMed Abstract | Publisher Full Text\n\nIudin A, Korir PK, Salavert-Torres J, et al.: EMPIAR: a public archive for raw electron microscopy image data. Nat. Methods. 2016; 13(5): 387–388. PubMed Abstract | Publisher Full Text\n\nIudin A, Korir PK, Somasundharam S, et al.: EMPIAR: the Electron Microscopy Public Image Archive. Nucleic Acids Res. 2023; 51: D1503–D1511. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKatz WT, Plaza SM: DVID: Distributed Versioned Image-Oriented Dataservice. Front. Neural Circuits. 2019; 13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKorir PK, Iudin A, Somasundharam S, et al.: bandbox (v0.2.1). Zenodo. 2022. Publisher Full Text\n\nLi X, Mooney P, Zheng S, et al.: Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat. Methods. 2013; 10(6): 584–590. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMastronarde D: Tomographic Reconstruction with the IMOD Software Package. Microsc. Microanal. 2006; 12(S02): 178–179. Publisher Full Text\n\nMoore J, Allan C, Besson S, et al.: OME-NGFF: a next-generation file format for expanding bioimaging data-access strategies. Nat. Methods. 2021; 18(12): 1496–1498. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPietzsch T, Saalfeld S, Preibisch S, et al.: BigDataViewer: visualization and processing for large image data sets. Nat. Methods. 2015; 12(6): 481–483. PubMed Abstract | Publisher Full Text\n\nPunjani A, Rubinstein JL, Fleet DJ, et al.: cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods. 2017; 14(3): 290–296. PubMed Abstract | Publisher Full Text\n\nSarkans U, Chiu W, Collinson L, et al.: REMBI: Recommended Metadata for Biological Images—enabling reuse of microscopy data in biology. Nat. Methods. 2021; 18(12): 1418–1422. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSarkans U, Gostev M, Athar A, et al.: The BioStudies database-one stop shop for all data supporting a life sciences study. Nucleic Acids Res. 2018; 46(D1): D1266–D1270. PubMed Abstract | Publisher Full Text | Free Full Text\n\nScheres SHW: A Bayesian View on Cryo-EM Structure Determination. J. Mol. Biol. 2012; 415(2): 406–418. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTang G, Peng L, Baldwin PR, et al.: EMAN2: An extensible image processing suite for electron microscopy. J. Struct. Biol. 2007; 157(1): 38–46. PubMed Abstract | Publisher Full Text\n\nWilkinson MD, Dumontier M, Aalbersberg IJJ, et al.: The FAIR Guiding Principles for scientific data management and stewardship. Sci. Data. 2016; 3: 160018. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang K: Gctf: Real-time CTF determination and correction. J. Struct. Biol. 2016; 193(1): 1–12. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "217553",
"date": "01 Nov 2023",
"name": "Sjors Scheres",
"expertise": [
"Reviewer Expertise Structural biologist",
"software developer"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 recommendations for organizing imaging data from the life sciences for archival purposes. Coming from the EBI, which is responsible for a large proportion of image archiving in the field, this advice is important and worth of dissemination to the wider scientific community. I am therefore, in principle, enthusiastic about its publication in F1000Research. However, I do think that the manuscript and the explicit recommendations can be improved, as the phrasing is often vague and some of the recommendations are ignored by the authors themselves. I would therefore recommend a careful re-think and re-write, especially of the 10 recommendations, for a revised version.\nSpecific comments:\nAbstract: p1: The first sentence does not make sense: is 'organised data' an elusive goal?\nMotivation: p3: Would you not consider non-scientists looking at these images?\np3: \"in the use of 'ways and means' of effecting the organisation\" -> I have no clue what this means.\np4: \"To achieve this ... and so on\" -> These vague statements need rephrasing (e.g. 'we define [..] to the *various* attributes'). Also, what is 'generally available equipment'?\np5: it is not entirely clear to me from reading the paper what the bandbox program does. The paper states that it is based on the 10 recommendations that follow, but as explained below the re-organisation in Figure 4 still violates several recommendations... Perhaps some pseudo-code may be useful? Also, wouldn't it make more sense to first describe the recommendations and then introduce this program?\nRecommendations:\nExcept for recommendation (7), all recommendations start with the word 'consider'. Given these are recommendations, that is superfluous. It may be clearer to use an imperative to directly state the recommendation (like done in 7).\np6: How is a \"raw\" TIFF file defined?\n(3a) \"the fewer the better\" means a depth of 1 is best. This is probably not what the authors intended.\n(3b) Having a subfolder called 'tiff' is often a good idea, e.g. when there is also a file with metadata describing those tiff images (which is typically the case). In fact, the recommended Figure 4 has a 'raw' folder, which has exactly the same meaning, thus contradicting this recommendation.\n\n(5a) What are \"any references that are tied to the instrument\" and why should they be excluded? If these are references to the microscope used, they may be relevant to the user?\n(5b) Why would dates in filenames be ambiguous and should they be avoided? Many data acquisition softwares write files with date and times in their names. Renaming these would, as the authors themselves point out, indeed be complicated and possibly lead to errors.\n(7a) I have no clue what this means: \"similar folders at different depths have the same names\"\n(7b) What are \"personal identifiers\"?\n(7c) The name 'data' is actually used in the line below and in the recommended Figure 4. Also, I don't see why 'images' won't be an excellent name for a folder that contains images?\n(7e) This recommendation may not be limited to slices of 3D data, which seems an arbitrarily narrow example for such broad recommendations. I personally thought of zer-padding images when I first read this (apparently not careful enough!). Perhaps using a term like \"leading zeros\" may be less ambiguous? Albeit perhaps useful to some of the readers, this is the only recommendation that has an explicit explanation of how to do this on two specific computer systems. Wouldn't this be something that could only be implemented in the bandbox program, so it could be used on any computer?\n(8) What are \"friendly file formats?\". Also, the term \"widely used file formats\" is not well defined.\n(9a) The example in Figure 4 does not have a README file...\n(9b) \"This can be achieved ... data presents\" -> This sounds superfluous and condescending.\np11: The proposed path \"data/brief_description/treatment3...\" violates at least recommendations 3 (unused subfolder 'brief_description') and 7 (use of word 'data')\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": [
{
"c_id": "10979",
"date": "22 Mar 2024",
"name": "Gerard J Kleywegt",
"role": "Author Response",
"response": "Response to Reviewer #1 (in italics) Specific comments: Abstract: p1: The first sentence does not make sense: is 'organised data' an elusive goal? Organised data is not in itself an elusive goal. However, when the volume and variety of data increase by orders or magnitude then maintaining organisation and coherence in the data is difficult to achieve and by extension makes the data difficult to use. Therefore, organised data - in the context of large heterogeneous datasets - is an elusive goal. Motivation: p3: Would you not consider non-scientists looking at these images? In the article we use the term ‘scientist’ for anyone who aims to use data for some end. The claim is not that only scientists look at data; rather, anyone (formal scientist or not) who uses the data is referred to as a scientist. The order of terminology is important. p3: \"in the use of 'ways and means' of effecting the organisation\" -> I have no clue what this means. p4: \"To achieve this ... and so on\" -> These vague statements need rephrasing (e.g. 'we define [..] to the *various* attributes'). Also, what is 'generally available equipment'? We have rephrased vague statements in line with this remark. p5: it is not entirely clear to me from reading the paper what the bandbox program does. The paper states that it is based on the 10 recommendations that follow, but as explained below the re-organisation in Figure 4 still violates several recommendations... Perhaps some pseudo-code may be useful? Also, wouldn't it make more sense to first describe the recommendations and then introduce this program? We have moved the description of what bandbox does to the Software Availability section. Recommendations: Except for recommendation (7), all recommendations start with the word 'consider'. Given these are recommendations, that is superfluous. It may be clearer to use an imperative to directly state the recommendation (like done in 7). p6: How is a \"raw\" TIFF file defined? We have replaced this with the phrase ‘uncompressed TIFF files’. (3a) \"the fewer the better\" means a depth of 1 is best. This is probably not what the authors intended. We accept the correction and have clarified the argument based on the ISA (investigation, study, assay) framework. (3b) Having a subfolder called 'tiff' is often a good idea, e.g. when there is also a file with metadata describing those tiff images (which is typically the case). In fact, the recommended Figure 4 has a 'raw' folder, which has exactly the same meaning, thus contradicting this recommendation. We accept the correction and have revised the text for clarity that we are referring to intermediate folders where none are required. (5a) What are \"any references that are tied to the instrument\" and why should they be excluded? If these are references to the microscope used, they may be relevant to the user? We accept the correction and have revised the phrase. (5b) Why would dates in filenames be ambiguous and should they be avoided? Many data acquisition softwares write files with date and times in their names. Renaming these would, as the authors themselves point out, indeed be complicated and possibly lead to errors. The emphasis in the article is in having dates in folder names not file names. In (1b) we mention dates in file names as a possibility. Nevertheless, we do caution that date-time data on file names can also include subtle variations such as seconds so that numerous related files become non-trivial to work with due to these variations. (7a) I have no clue what this means: \"similar folders at different depths have the same names\" We have revised the recommendation and included an example with reference to Figure 3. (7b) What are \"personal identifiers\"? We have included a parenthetical remark with examples to illustrate what personal identifiers are. (7c) The name 'data' is actually used in the line below and in the recommended Figure 4. Also, I don't see why 'images' won't be an excellent name for a folder that contains images? These examples are purely for illustration purposes but are inspired by the actual structure used in EMPIAR in which the ‘data’ directory sits beside an XML file e.g. https://ftp.ebi.ac.uk/empiar/world_availability/10002/, which we have omitted here. They were generated from the examples provided in the git repository. We believe it is better to have descriptive folder names as opposed to generic names, which provide no meaningful information. The name ‘images’ does not convey any meaningful information. Better would be something like ‘tomograms’ or ‘particles’. Nevertheless, this is configurable in bandbox using the bandbox/obvious_files option in the configuration file. (7e) This recommendation may not be limited to slices of 3D data, which seems an arbitrarily narrow example for such broad recommendations. I personally thought of zer-padding images when I first read this (apparently not careful enough!). Perhaps using a term like \"leading zeros'' may be less ambiguous? Albeit perhaps useful to some of the readers, this is the only recommendation that has an explicit explanation of how to do this on two specific computer systems. Wouldn't this be something that could only be implemented in the bandbox program, so it could be used on any computer? We accept the correction and have rewritten the recommendation to clarify the context. We agree that implementing this in bandbox would enable a cross-platform solution and will plan this for a future release. (8) What are \"friendly file formats?\". Also, the term \"widely used file formats\" is not well defined. This has been revised to simply ‘File formats’. (9a) The example in Figure 4 does not have a README file… A README file has been added in the updated figure. (9b) \"This can be achieved ... data presents\" -> This sounds superfluous and condescending. This sentence has been deleted in the article. p11: The proposed path \"data/brief_description/treatment3...\" violates at least recommendations 3 (unused subfolder 'brief_description') and 7 (use of word 'data') As mentioned above, the example used here is purely illustrative and omits other content which would otherwise not violate this recommendation."
}
]
},
{
"id": "217555",
"date": "08 Nov 2023",
"name": "Kenneth H. L. Ho",
"expertise": [
"Reviewer Expertise Bioimage informatics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 timely as we are facing a deluge of bioimaging data with higher resolutions and automation. It is therefore an area that needs more discussions, sharing of good practices.\nI mostly agree with all the recommendations given, although I feel that the authors may need to make a good argument for some recommendations. Some choices seem arbitrary and I would like to see the rationale behind them.\nAfter reading the paper, I am a bit confused by the article’s intended target audience. Is the article recommendation aimed at most of the biologists who archive their bioimaging data mainly for the purpose of peer review and references? Or is the article and recommendation aiming for those database curators and producers of bioimaging databases, e.g. IDR (https://idr.openmicroscopy.org/) , SSBD (https://ssbd.riken.jp/database/), GDC (https://portal.gdc.cancer.gov/) , etc?\n\nOn page 4 under the heading ‘Motivation’, “We believe that recommendations outlined here maybe of value to two principal groups of users: 1) data depositors, who need to design and prepare their data to improve its usability to the community”. Does it include most biologists? I believe that most biologists archive their data to provide a record of their studies. Are the data depositors in the article and its intended audience refer to bioimaging database curators/producers instead of bench biologists?\nI believe that the ten recommendations would be equally applied to most biologists even though their aim is to provide a record of their studies, the recommendations would help those database curators to organise their bioimage data in more meaningful ways.\n\nI would like to see that part to be make clearer of its intended audience.\nWith regards to the recommendations, on page 8, ‘Naming’ (5) Meaningful names (b) “Consider avoiding ambiguous attributes such as dates and times. The argument that they have “subtle variations” is not obvious to me. Is it because of variations of date formats used in different countries? Would it be solved if ISO 8601 (https://en.wikipedia.org/wiki/ISO_8601) date format is used? Would that be a better recommendation? If not, would the authors care to expand their argument for that as dates are used frequently in filenames?\nOn page 9, (6) Naming symbols, (a) consider confining to lowercase letters. It seems to be rather arbitrary to confine names to lowercase, why would it not work for all uppercase letters instead?\nSimilarly, in (b) avoid non-ASCII characters. Shouldn’t we be more inclusive of other languages that are non-ascii, e.g., European characters, or double byte Japanese, Korean and Chinese characters?\nFrom a computer coding point of view, I intuitively understand the rationale for choosing ASCII but the article doesn’t seem to provide a valid argument for it. May I suggest the authors to use international standard for POSIX Portable Operating System Interface (IEEE 1003 ISO/IEC 9945) (ref: https://en.wikipedia.org/wiki/POSIX; https://www.ibm.com/docs/en/zos/2.2.0?topic=locales-posix-portable-file-name-character-set) instead. Choosing to use an international standard makes more sense instead of creating another separate standard specifically for bioimaging data. If the authors would like to keep their recommendations, I would like to see more justification for doing so.\nOn (d) upper limit on the length of file and folder names. The authors proposed a working upper limit of 50 characters. Again, it seems to be arbitrary, why not 80 characters, i.e. one line length on the old CRT terminal? The browser limit is a good reason, but I would like to see a more robust argument that 50 characters length is a good compromise.\nThe authors used an example of file path limit of 320 characters in the same paragraph, I believe it may cause confusion for the reader with filename length, which for most computer systems, is only 255 characters. (ref: https://en.wikipedia.org/wiki/Filename ). Since the authors also provide recommendation (3) on Folder depth and given example of path length problems on page 7 “Very long names of files/folders”, maybe the authors can discuss and recommend that together, under one section “filename length, path length and folder depth”. It may be easier for the reader to appreciate the choice that the authors make.\n\nOn recommendation (8) Friendly file formats. Maybe “Widely used file formats” is more applicable? I would prefer “Openly accessible file formats”, i.e., formats that there are readable by open-source tools. I guess widely used file formats would fit that description too and reflect more closely to what the authors want to convey. Proprietary software tools for accessing proprietary file formats may cause problems in the long run as companies often change hands, e.g., Olympus is now Evident, LaVision is now under Brunker. It is difficult to ensure that companies will keep supporting certain formats in their software tools in the future while funding bodies (in the UK) require archiving data for 10 to 20 years.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "10980",
"date": "22 Mar 2024",
"name": "Gerard J Kleywegt",
"role": "Author Response",
"response": "Response to Reviewer #2 (in italics) Specific comments: The article is timely as we are facing a deluge of bioimaging data with higher resolutions and automation. It is therefore an area that needs more discussions, sharing of good practices. I mostly agree with all the recommendations given, although I feel that the authors may need to make a good argument for some recommendations. Some choices seem arbitrary and I would like to see the rationale behind them. After reading the paper, I am a bit confused by the article’s intended target audience. Is the article recommendation aimed at most of the biologists who archive their bioimaging data mainly for the purpose of peer review and references? Or is the article and recommendation aiming for those database curators and producers of bioimaging databases, e.g. IDR (https://idr.openmicroscopy.org/) , SSBD (https://ssbd.riken.jp/database/), GDC (https://portal.gdc.cancer.gov/) , etc? On page 4 under the heading ‘Motivation’, “We believe that recommendations outlined here maybe of value to two principal groups of users: 1) data depositors, who need to design and prepare their data to improve its usability to the community”. Does it include most biologists? I believe that most biologists archive their data to provide a record of their studies. Are the data depositors in the article and its intended audience refer to bioimaging database curators/producers instead of bench biologists? I believe that the ten recommendations would be equally applied to most biologists even though their aim is to provide a record of their studies, the recommendations would help those database curators to organise their bioimage data in more meaningful ways. I would like to see that part to be make clearer of its intended audience. We accept the correction and have expanded the introductory paragraphs to outline specific audiences as well as clarified the type of user that ‘user’ refers to. With regards to the recommendations, on page 8, ‘Naming’ (5) Meaningful names (b) “Consider avoiding ambiguous attributes such as dates and times. The argument that they have “subtle variations” is not obvious to me. Is it because of variations of date formats used in different countries? Would it be solved if ISO 8601 (https://en.wikipedia.org/wiki/ISO_8601) date format is used? Would that be a better recommendation? If not, would the authors care to expand their argument for that as dates are used frequently in filenames? We accept the correction and have edited the text to better reflect the intended meaning. On page 9, (6) Naming symbols, (a) consider confining to lowercase letters. It seems to be rather arbitrary to confine names to lowercase, why would it not work for all uppercase letters instead? We accept the correction and include arguments why we think it is preferable for file and folder names to be defined using lowercase letters. Similarly, in (b) avoid non-ASCII characters. Shouldn’t we be more inclusive of other languages that are non-ascii, e.g., European characters, or double byte Japanese, Korean and Chinese characters? From a computer coding point of view, I intuitively understand the rationale for choosing ASCII but the article doesn’t seem to provide a valid argument for it. May I suggest the authors to use international standard for POSIX Portable Operating System Interface (IEEE 1003 ISO/IEC 9945) (ref: https://en.wikipedia.org/wiki/POSIX;https://www.ibm.com/docs/en/zos/2.2.0?topic=locales-posix-portable-file-name-character-set) instead. Choosing to use an international standard makes more sense instead of creating another separate standard specifically for bioimaging data. If the authors would like to keep their recommendations, I would like to see more justification for doing so. We accept the correction and now refer to POSIX as the standard to adhere to as well as provide reasons to do so. On (d) upper limit on the length of file and folder names. The authors proposed a working upper limit of 50 characters. Again, it seems to be arbitrary, why not 80 characters, i.e. one line length on the old CRT terminal? The browser limit is a good reason, but I would like to see a more robust argument that 50 characters length is a good compromise. The reviewer’s comment does raise a valid point. However, it is important to bear in mind that file and folder names add to one another and a length of 80 means that at a depth of three folders will admit paths of up to 240 characters. It is hard to precisely determine what would be reasonable: 20-30 characters may be too short for a lot of cases. One option would be to examine file lengths in current archives to determine the distribution of file name lengths but if the objective is to follow good rather than current practice this may not be sound. The authors propose the above limits to start a conversation with the community on what would be a sensible value or range. The authors used an example of file path limit of 320 characters in the same paragraph, I believe it may cause confusion for the reader with filename length, which for most computer systems, is only 255 characters. (ref: https://en.wikipedia.org/wiki/Filename ). Since the authors also provide recommendation (3) on Folder depth and given example of path length problems on page 7 “Very long names of files/folders”, maybe the authors can discuss and recommend that together, under one section “filename length, path length and folder depth”. It may be easier for the reader to appreciate the choice that the authors make. We accept the correction and have restructured the article as suggested. On recommendation (8) Friendly file formats. Maybe “Widely used file formats” is more applicable? I would prefer “Openly accessible file formats”, i.e., formats that there are readable by open-source tools. I guess widely used file formats would fit that description too and reflect more closely to what the authors want to convey. Proprietary software tools for accessing proprietary file formats may cause problems in the long run as companies often change hands, e.g., Olympus is now Evident, LaVision is now under Brunker. It is difficult to ensure that companies will keep supporting certain formats in their software tools in the future while funding bodies (in the UK) require archiving data for 10 to 20 years. We have revised the section title to simply ‘File formats’. We appreciate that there are file formats that are unavoidable but proprietary (e.g., from microscopes) but our emphasis is on the openness of the formats because this enables the prevalence of tools which can reliably read the data. We have updated 8(b) to reflect this point."
}
]
},
{
"id": "217556",
"date": "21 Nov 2023",
"name": "Sylvia Emmanuelle Le Dévédec",
"expertise": [
"Reviewer Expertise Biology",
"image-based phenotypic profiling",
"microscopist",
"data generator",
"core facility management",
"FAIR metadata"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 guideline presented by Korir and colleagues, who are recognized experts in data structure, data organization, and FAIRification, marks an important step toward fostering a comprehensive discussion on the management of bioimaging data. The authors, primarily developers and bioinformaticians dealing with intricate datasets, have assembled a set of recommendations that, while valuable, may be perceived as overly abstract, potentially posing challenges for experimentalists who serve as the primary data producers.\nOne critical aspect that emerges is the need for greater clarity regarding the intended audience for this guideline. Currently, it appears somewhat ambiguous, leading to potential misalignment with the individuals it should be primarily targeting. It is recommended that the authors explicitly define the community they aim to address at the outset of the manuscript. If, indeed, the target audience is the data producers, particularly experimentalists, then a comprehensive revision of the recommendations may be necessary. Consideration should be given to conveying the guidelines in a more accessible language, ensuring that the practical implications for experimentalists are clearly delineated. Additionally, the authors might explore the possibility of tailoring specific sets of guidelines for distinct roles, such as data managers and data producers, to enhance relevance and utility.\nBelow are listed some specific points of attentions:\nAbstract:\nThe abstract lacks clarity on the intended audience of these recommendations. It is essential to specify whether the guidelines primarily target core facility managers, data managers/stewards, bioinformaticians, or experimentalists.\n\nIf the guidelines are intended for experimentalists, the current manuscript may not align with the needs of this non-expert audience. The language and content may need to be adapted to cater to individuals with limited knowledge in data management.\n\nThe phrase \"make future data depositions more useful\" needs clarification. Who benefits from this increased usefulness, and in what way? Is the goal to enhance practicality, efficiency, or accessibility? A more specific explanation would enhance the abstract's clarity.\n\nThe term \"bioimaging community\" is used in the abstract, but its specific meaning in the context of this manuscript is unclear. Defining this community will provide readers with a better understanding of the scope and relevance of the guidelines.\n\nThe abstract mentions that Bandbox is designed \"to facilitate the process of analyzing data organization.\" It would be beneficial to elaborate on how the analyzing functionality of Bandbox directly benefits the bioimaging community. Specific examples or scenarios demonstrating its advantages would enhance the abstract's informativeness.\n\nIntroduction\n\nWhat does data ‘archiving’ means exactly in this specific manuscript?\n\nObjective of the guideline: Harmonising how to organise datasets for maximum usefulness with archival in mind?\n\nWhere this organization should occur in the data life cycle: before/during or after generation? Where this organisation should occur? In which physical storage space?\n\nOrganisation = order of the data. Organisation or order of the data should be implicitly connected to the related metadata and even contained somewhere in the metadata.\n\n‘Good organisation (order) of data improves its usefulness and is the responsibility of the data depositors.’ Do you mean here the data generator or specifically the data depositor? Based on the description it seems like the data depositor is implicitly the data generator. ‘Users can immediately distinguish the various experimental categories’: should you not refer to (p)ISA to clarify what is meant by ‘experimental categories’ (https://doi.org/10.1038/s41597-022-01805-5)?\n\n‘Facet refers to the various attributes germane to the experiment which may be included in the folder and file names’. Should ‘facet’ not be called ‘key’? If not then explain the differences between both terms.\n\nRecommendations:\n\nThe potential users for these recommendations lack clear definition, and depending on the proposed users, the guide should be tailored for optimal understanding. Data depositors and generators often have different levels of familiarity compared to program developers or data stewards, employing distinct languages. Addressing these differences is crucial for ensuring accessibility and effectiveness.\n\nOpen-source command-line interfaces can be intimidating, particularly for experimentalists who serve as the primary data generators and often act as data depositors. As a cell biologist and experimentalist, I find the proposed CLI tool, while impressive and useful, potentially challenging to navigate comfortably. Enhancements in user-friendliness or alternative interfaces might significantly benefit experimentalists who are integral to both data generation and deposition.\n\nGiven the recommendation for data producers to pre-define structures before data collection, it becomes apparent that the target audience of this guide is experimentalists with limited knowledge of data management and programming. Including guidelines or tips on naming conventions would be particularly valuable for such users, enhancing the practicality and applicability of the recommendations.\n\nThe suggestion regarding folder contents description appears somewhat vague and may not be universally suitable for various experiment types. A more nuanced approach that considers the diversity of experiments would enhance the guide's usability.\n\nThe concept of \"meaningful names\" for folders raises questions about subjectivity and human sensitivity, which may not align with the precision required for effective data management structures. Establishing a clear naming convention, is objectively applicable across various contexts, would contribute to the robustness and reliability of the guide.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "10981",
"date": "22 Mar 2024",
"name": "Gerard J Kleywegt",
"role": "Author Response",
"response": "Response to Reviewer #3 (in italics) Specific comments: The guideline presented by Korir and colleagues, who are recognized experts in data structure, data organization, and FAIRification, marks an important step toward fostering a comprehensive discussion on the management of bioimaging data. The authors, primarily developers and bioinformaticians dealing with intricate datasets, have assembled a set of recommendations that, while valuable, may be perceived as overly abstract, potentially posing challenges for experimentalists who serve as the primary data producers. One critical aspect that emerges is the need for greater clarity regarding the intended audience for this guideline. Currently, it appears somewhat ambiguous, leading to potential misalignment with the individuals it should be primarily targeting. It is recommended that the authors explicitly define the community they aim to address at the outset of the manuscript. If, indeed, the target audience is the data producers, particularly experimentalists, then a comprehensive revision of the recommendations may be necessary. Consideration should be given to conveying the guidelines in a more accessible language, ensuring that the practical implications for experimentalists are clearly delineated. Additionally, the authors might explore the possibility of tailoring specific sets of guidelines for distinct roles, such as data managers and data producers, to enhance relevance and utility. Below are listed some specific points of attentions: Abstract: The abstract lacks clarity on the intended audience of these recommendations. It is essential to specify whether the guidelines primarily target core facility managers, data managers/stewards, bioinformaticians, or experimentalists. We welcome the suggestion to clarify the intended audience and have updated the abstract to clarify this. If the guidelines are intended for experimentalists, the current manuscript may not align with the needs of this non-expert audience. The language and content may need to be adapted to cater to individuals with limited knowledge in data management. We aim to address a wide and varied audience, so the language and terminology needs to strike a balance for the content to be accessible and digestible by different groups. We hope we have managed a reasonable balance, especially following the many constructive suggestions of all the reviewers. If this reviewer has specific comments on sections in the revised manuscript that could be improved further in this respect we would be happy to attempt to do so. The phrase \"make future data depositions more useful\" needs clarification. Who benefits from this increased usefulness, and in what way? Is the goal to enhance practicality, efficiency, or accessibility? A more specific explanation would enhance the abstract's clarity. We accept the correction and have spelled out in more precise terms what ‘more useful’ means and to whom this applies. The term \"bioimaging community\" is used in the abstract, but its specific meaning in the context of this manuscript is unclear. Defining this community will provide readers with a better understanding of the scope and relevance of the guidelines. We accept the correction and have amended the text to reflect this. The abstract mentions that Bandbox is designed \"to facilitate the process of analyzing data organization.\" It would be beneficial to elaborate on how the analyzing functionality of Bandbox directly benefits the bioimaging community. Specific examples or scenarios demonstrating its advantages would enhance the abstract's informativeness. We accept the correction and have included, in the text, some examples of what bandbox is capable of doing. Introduction What does data ‘archiving’ means exactly in this specific manuscript? We have included a definition of ‘archiving’ in the opening paragraph of the article. Objective of the guideline: Harmonising how to organise datasets for maximum usefulness with archival in mind? Yes. Where this organization should occur in the data life cycle: before/during or after generation? Where this organisation should occur? In which physical storage space? The earlier the better. Recommendation #1 (Design before data collection) highlights the impact of data planning before collection commences. The remaining recommendations outline various suggestions on how to improve the usability of the data. The organisation typically would happen on the storage device but can be done either through consoles or the appropriate graphical user interfaces. Organisation = order of the data. Organisation or order of the data should be implicitly connected to the related metadata and even contained somewhere in the metadata. We have edited the text for clarity. ‘Good organisation (order) of data improves its usefulness and is the responsibility of the data depositors.’ Do you mean here the data generator or specifically the data depositor? Based on the description it seems like the data depositor is implicitly the data generator. Data depositors’ here refers to the individual(s) responsible for making the submission to the archive (previously defined) and this may or may not be the generator of the data. In many cases, the depositor is familiar with the data because they performed the analyses implying familiarity with handling the data. ‘Users can immediately distinguish the various experimental categories’: should you not refer to (p)ISA to clarify what is meant by ‘experimental categories’ (https://doi.org/10.1038/s41597-022-01805-5)? We are grateful to the reviewer for pointing out this reference which is now referred to in the text. ‘Facet refers to the various attributes germane to the experiment which may be included in the folder and file names’. Should ‘facet’ not be called ‘key’? If not then explain the differences between both terms. We used the term ‘facet’ in the same sense as in multifaceted, implying that a dataset may be viewed from various perspectives to discern distinct properties much in the same way as a gem. The reviewer’s proposal of ‘key’ does not fit this sense. Recommendations: The potential users for these recommendations lack clear definition, and depending on the proposed users, the guide should be tailored for optimal understanding. Data depositors and generators often have different levels of familiarity compared to program developers or data stewards, employing distinct languages. Addressing these differences is crucial for ensuring accessibility and effectiveness. We have addressed the specificity of the audience in the amendments to the abstract (above). Open-source command-line interfaces can be intimidating, particularly for experimentalists who serve as the primary data generators and often act as data depositors. As a cell biologist and experimentalist, I find the proposed CLI tool, while impressive and useful, potentially challenging to navigate comfortably. Enhancements in user-friendliness or alternative interfaces might significantly benefit experimentalists who are integral to both data generation and deposition. We accept this comment and are only constrained by our capacity to extend the CLI tool to achieve the desired usability. Given the recommendation for data producers to pre-define structures before data collection, it becomes apparent that the target audience of this guide is experimentalists with limited knowledge of data management and programming. Including guidelines or tips on naming conventions would be particularly valuable for such users, enhancing the practicality and applicability of the recommendations. Recommendations 5, 6 and 7 go into considerable detail about what names to choose, which symbols to use in names and matters relating to identity. We are willing to revise any of the provided recommendations which remain unclear. The suggestion regarding folder contents description appears somewhat vague and may not be universally suitable for various experiment types. A more nuanced approach that considers the diversity of experiments would enhance the guide's usability. We appreciate that the authorship of this article does not represent the universe of experimental methods in imaging. We do point out various facets that may be relevant but leave it up to depositors (generators) who are in the best position to judge which to use when structuring/naming folders. We also point out in the abstract that we offer these recommendations to start discussions in various data-rich communities. The concept of \"meaningful names\" for folders raises questions about subjectivity and human sensitivity, which may not align with the precision required for effective data management structures. Establishing a clear naming convention, is objectively applicable across various contexts, would contribute to the robustness and reliability of the guide. As stated above, we do not think it necessary to specify exactly how data should be organised given the vast variety of experiments that can be carried out. We do state in the article (Motivation, paragraph 8) that “...our guide is intended to lead towards best practices rather than serve as a framework. …this guide does not aim to achieve standardisation. We believe it is more practical to have a set of best practices and leave it up to the data authors to decide how best to apply them.”"
}
]
},
{
"id": "217552",
"date": "21 Nov 2023",
"name": "William T. Katz",
"expertise": [
"Reviewer Expertise Data engineering",
"biomedical image processing and analysis."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this opinion article, the authors tackle an important but often-overlooked aspect of biomedical data archives: how best to organize data folders and files to maximize ease of use. Ten recommendations are provided as well as a lightweight command-line tool for inspecting datasets. Since there continues to be an acceleration in both the number and size of these datasets accessible through various repositories, both the recommendations and tool from experienced archivists are useful and should be published, though we feel some revision of the document is warranted.\nThe introduction describes the broader context of bioimaging data management before focusing on the contributions of the article. There could be clearer differentiation of efforts to standardize bioimaging metadata (REMBI, QUAREP-LiMi), file formats and associated libraries (OME-TIFF, OME-NGFF, Zarr, n5), and local or cloud-based services that provide Data APIs (DVID, BossDB) with some level of abstraction in how data is actually stored. The recommendations and tool mainly apply to file-based solutions though some of the recommendations, such as naming, would be applicable to other forms of big data repositories. We suggest that the authors clarify the scope of their contributions.\nIt should be noted that some of the efforts to standardize data and its distribution also have recommendations for organization of data. For example, OME-NGFF requires segmentation to be in a directory called “labels/”.\nIn the third paragraph of Motivation, the terms “ways and means” and “organisational resources” are unclear though some of your examples (folder hierarchy, file formats, identifiers) show how data can be organized. We suggest you start with some examples and then introduce “organizational resources” as a term.\nIf standardization is not an aim, can bandbox be configured to remove warnings not agreed upon by a user? In Figure 2, the printing of the word “warning” for datasets with no red flags seems odd. We would suggest using “check” as in “name check” or “structure check” if no warnings exist.\nGiven recommendation (8)b and the article’s bioimaging focus, the bandbox tool should work by default with well-known, large-scale formats like Zarr and N5. In testing, it appears that bandbox doesn’t recognized file extensions used by such formats like .json and .zarr. The configurability of bandbox is a nice feature and should be mentioned in the article. This would allow other tool builders to contribute configurations for validating common formats and it seems like the regex capability could allow folder hierarchy requirements.\nThe command-line bandbox tool should limit warning output to some maximum number of lines by default. This is particularly true for massive, chunked datasets consisting of many files and folders. We would suggest adding a “verbose” flag to allow full results to be output perhaps to a file.\nSome minor points:\nThe description of the bandbox tool could be moved out of the Motivation section and after listing the recommendations.\nFigure 1 has too small font sizes and would not be readable for printed copies as well as expending quite a bit of black ink.\nThe phenomenon described in the first sub-bullet under 'Verbosity' is an interesting point that seems to deserve its own name. Maybe something like, 'redundant nesting' or 'over-nesting'. A name would also make it easier to connect to solution 3A, which is conceptually related. Also, the second half of this bullet point is in monospace font, but it should be Times New Roman or whatever.\nSome recommendations are more universally advisable than others. For those points, we’d recommend dropping “Consider” for stronger language.\nIn (4)b, “Most archives allow multiple separate entries to be linked or grouped,” it’s not clear what qualifies as an archive since data could be made available through cloud providers’ object stores and other facilities.\nIn (5)b, could you clarify in what ways dates and times are “ambiguous attributes”?\nIn the sentence, “bandbox examines the tree associate with the nested hierarchy…” the word bandbox should be in monospace font.\nWhat is the rationale for limiting folder depth to 3 or 4 levels?\nIn (7)b, “Do not include personal identifiers in folder names.” Personal identifiers should be clarified.\nFor (7)e, zero-padding should be considered for any sequentially ordered set of files. A good case is 2D slices of a 3D volume as described.\nFor (8)b, consider citing OME-NGFF and OME-TIFF as recommended community formats.\nFor (9)a, the recommendation for an overview could explicitly suggest listing the facets used to organize the data.\nIn Figure 4, is the single “brief_description” folder at that level recommended instead of adding the descriptive information to a README file? Perhaps a real description should be used in the example to make it clear why recommendation (3)b doesn’t apply.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "10982",
"date": "22 Mar 2024",
"name": "Gerard J Kleywegt",
"role": "Author Response",
"response": "Response to Reviewer #4 (in italics) Specific comments: In this opinion article, the authors tackle an important but often-overlooked aspect of biomedical data archives: how best to organize data folders and files to maximize ease of use. Ten recommendations are provided as well as a lightweight command-line tool for inspecting datasets. Since there continues to be an acceleration in both the number and size of these datasets accessible through various repositories, both the recommendations and tool from experienced archivists are useful and should be published, though we feel some revision of the document is warranted. The introduction describes the broader context of bioimaging data management before focusing on the contributions of the article. There could be clearer differentiation of efforts to standardize bioimaging metadata (REMBI, QUAREP-LiMi), file formats and associated libraries (OME-TIFF, OME-NGFF, Zarr, n5), and local or cloud-based services that provide Data APIs (DVID, BossDB) with some level of abstraction in how data is actually stored. The recommendations and tool mainly apply to file-based solutions though some of the recommendations, such as naming, would be applicable to other forms of big data repositories. We suggest that the authors clarify the scope of their contributions. It should be noted that some of the efforts to standardize data and its distribution also have recommendations for organization of data. For example, OME-NGFF requires segmentation to be in a directory called “labels/”. In the third paragraph of Motivation, the terms “ways and means” and “organisational resources” are unclear though some of your examples (folder hierarchy, file formats, identifiers) show how data can be organized. We suggest you start with some examples and then introduce “organizational resources” as a term. We accept this correction and have updated the text to better reflect this point. If standardization is not an aim, can bandbox be configured to remove warnings not agreed upon by a user? In Figure 2, the printing of the word “warning” for datasets with no red flags seems odd. We would suggest using “check” as in “name check” or “structure check” if no warnings exist. We have released an updated version (bandbox v0.2.2) where these have been amended. Given recommendation (8)b and the article’s bioimaging focus, the bandbox tool should work by default with well-known, large-scale formats like Zarr and N5. In testing, it appears that bandbox doesn’t recognized file extensions used by such formats like .json and .zarr. The configurability of bandbox is a nice feature and should be mentioned in the article. This would allow other tool builders to contribute configurations for validating common formats and it seems like the regex capability could allow folder hierarchy requirements. We have clarified in the text that bandbox is configurable. The command-line bandbox tool should limit warning output to some maximum number of lines by default. This is particularly true for massive, chunked datasets consisting of many files and folders. We would suggest adding a “verbose” flag to allow full results to be output perhaps to a file. This has been updated in bandbox v0.2.2. Instead of printing all results by default, we have substituted the -S/--summarise flag with a -a/--all flag so that by default users don’t get overwhelmed. The instruction to use the new flag is now highlighted in yellow text beneath each section with more than a certain number of results. Some minor points: The description of the bandbox tool could be moved out of the Motivation section and after listing the recommendations. We have now included a detailed description of bandbox in the Software Availability section. Figure 1 has too small font sizes and would not be readable for printed copies as well as expending quite a bit of black ink. We accept the suggestion and have changed all images to have a light background. The phenomenon described in the first sub-bullet under 'Verbosity' is an interesting point that seems to deserve its own name. Maybe something like, 'redundant nesting' or 'over-nesting'. A name would also make it easier to connect to solution 3A, which is conceptually related. Also, the second half of this bullet point is in monospace font, but it should be Times New Roman or whatever. We have given the section the name ‘Verbosity/Redundancy’. The use of monospace font here is intentional to distinguish between literal text and computer text (file/folder names, commands, tools). Some recommendations are more universally advisable than others. For those points, we’d recommend dropping “Consider” for stronger language. In (4)b, “Most archives allow multiple separate entries to be linked or grouped,” it’s not clear what qualifies as an archive since data could be made available through cloud providers’ object stores and other facilities. We have provided a definition of ‘archive’ in the opening paragraph of the article. In (5)b, could you clarify in what ways dates and times are “ambiguous attributes”? We have provided an explanation on this in the text. Dates and times are ambiguous to the extent that they do not provide meaningful attributes associated with the experiment. While it can be assumed that dates on file names refer to the date of collection, this is not instrumental to the actual data i.e. knowing the date of collection adds no scientific value. Furthermore, having every single image file with the same date consumes precious ‘naming space’ of files, which can either be provided once in the name of the parent folder or as part of the metadata, where it would be expected to convey useful information to users. In the sentence, “bandbox examines the tree associate with the nested hierarchy…” the word bandbox should be in monospace font. This has been corrected in the text. What is the rationale for limiting folder depth to 3 or 4 levels? We have argued this point based on the ISA framework. In (7)b, “Do not include personal identifiers in folder names.” Personal identifiers should be clarified. We accept this point and have provided some examples of what is meant by ‘personal identifiers’. For (7)e, zero-padding should be considered for any sequentially ordered set of files. A good case is 2D slices of a 3D volume as described. We have included ‘sequential ordering’ as another example of this phenomenon. For (8)b, consider citing OME-NGFF and OME-TIFF as recommended community formats. We accept the suggestion and have amended the text as requested. For (9)a, the recommendation for an overview could explicitly suggest listing the facets used to organize the data. We have included a sentence outlining what may be included in the README file. In Figure 4, is the single “brief_description” folder at that level recommended instead of adding the descriptive information to a README file? Perhaps a real description should be used in the example to make it clear why recommendation (3)b doesn’t apply. This term is purely illustrative as are the names of the files and folders."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1391
|
https://f1000research.com/articles/10-411/v1
|
21 May 21
|
{
"type": "Method Article",
"title": "Novel Twenty20 batting simulations: a strategy for research and improved practice",
"authors": [
"Tiago Lopes",
"David Goble",
"Benita Olivier",
"Samantha Kerr",
"David Goble",
"Benita Olivier",
"Samantha Kerr"
],
"abstract": "Twenty20 cricket and batting in particular have remained vastly understudied to date. To elucidate the effects of batting on the batter, tools which replicate match play in controlled environments are essential. This study describes the development of two Twenty20 batting simulations, for a high and low strike rate innings, generated from retrospective analysis of international and domestic competition. Per delivery analysis of probabilities of run-type and on/off-strike denomination produce ball-by-ball simulations most congruent with retrospective competitive innings. Furthermore, both simulations are matched for duration and dictated through audio files. The `high' strike rate innings requires a batter to score 88 runs from 51 deliveries, whereby 60 runs are from boundaries. Similarly, the `low' strike rate innings requires a batter to score 61 runs from 51 deliveries, where 27 runs are scored from boundaries. Because batting simulations dictate run scoring outcomes, a method of quantifying a batter's performance from bat-ball contact scores is described. Ten elite batters achieved a mean performance score of 72 (SD = 26) and 88 (21) for the low and high strike rate simulations respectively. This study provides sport practitioners with a training technique to improve specific skill acquisition and enables research in understudied Twenty20 batting.",
"keywords": [
"Cricket",
"batting performance",
"simulation",
"innings"
],
"content": "1 Introduction\n\nBatting in the sport of cricket is an interceptive task which creates a combination of physical (Johnstone & Ford, 2010; Pote & Christie, 2016) and cognitive stress (Goble & Christie, 2017). In a cricket match, runs are scored by sprinting between the wickets or by hitting the ball out of play (boundaries). During an innings, a batter and batting partner will attempt to accumulate runs, while trying to avoid being dismissed. Resultantly, a batter’s innings may be prolonged resulting in fatigue (Christie, Todd, & King, 2008; Johnstone & Ford, 2010) which may adversely affect batting performance. Research has suggested traditional net-practice may be inadequate to replicate the demands of an innings produced in competitive match-play (Goble & Christie, 2017; Vickery et al., 2018) and thus batters may not experience batting under appropriate fatigue, which may limit the effectiveness of training. Woods and colleagues (2019) further highlighted the value of practice which attempts to closely replicate match-play for the development of skill. The availability of reliable match data in cricket enables the development of detailed batting simulations which may be invaluable tools in practice programmes and research investigating the physiology of a batter.\n\nIn previous studies, attempts to replicate a batting innings have taken various forms. Christie and colleagues (2008) replicated the physical demands of batting through shuttle running. Running multiple shuttles, the length of a cricket pitch (17.68m), physically mimics run scoring in cricket. However, shuttle running protocols neglect to account for the energetic cost of ball striking and boundaries where no shuttles are required. As a result, more sophisticated protocols which require batters to intercept deliveries were subsequently developed. The Battlezone protocol mimics a small-sided cricket match reduced to eight players and six repeated bouts, each consisting of eight overs (Vickery, Dascombe, Duffield, Kellett, & Portus, 2013). Batters are required to compete in a bout against two bowlers and four fielders in a 27m ring. However, the limited length (six overs per batting pair) and smaller field may limit the ecological validity of this protocol and therefore its use in fields of research and elite sport. Finally, the BATEX (Houghton, Dawson, Rubenson, & Tobin, 2011) protocol simulates scoring a One Day International (ODI) century (100 runs) with ball-by-ball audio guidance. In this protocol batters are required to complete an innings of two hours and 20 minutes, the typical length of an ODI century (Houghton et al., 2011). Unlike the Battlezone protocol, which provides batters with freedom to score runs at any rate, BATEX instructs batters on the denomination of runs required – singles, doubles or boundaries - every over. Thus, BATEX mimics the amount of time spent at the crease and also allows the innings to follow a run scoring progression akin to centuries scored in ODI’s. Further, the BATEX protocol is divided into phases which allows researchers and sport practitioners to manipulate scoring zones and running intensities throughout the innings which adds a form of ecological dynamics and match realism suggested by Woods and colleagues (2020; 2019). However, the BATEX protocol, being a simulation of the ODI format, may not be applicable to the increasingly popular, shorter Twenty20 format where an entire team innings is often completed within two hours.\n\nTo date no batting protocol has specifically aimed to address a Twenty20 innings. Batting may be performed at various run scoring intensities (strike rate) depending on the context of the innings and format of the game. Twenty20 cricket is the shortest format of the game (20 overs per side) resulting in higher run scoring intensities as batters attempt to score more runs from fewer available deliveries. Thus, batting simulations which are unique to Twenty20 cricket are required. Further, the BATEX protocol places minimal emphasis on the role of the batter’s partner. As batting is performed in pairs, consideration for how runs are scored while the batter in question is off-strike is necessary as this increases the workload placed on the batter.\n\nThis study aimed to develop two Twenty20 batting simulations which mimic the demands of competitive match play. To further highlight the impact of strike-rate, both simulations possess an equal number of deliveries, resulting in varying run scoring intensities throughout the innings.\n\n\n2 Methods\n\nTwo Twenty20 simulations were developed to simulate match play for an individual achieving a 1) ‘high’ and 2) ‘low’ strike rate innings. Both high and low strike rate simulations are equal in duration, achieved by standardizing the number of deliveries in both simulations. However, the strike rate and mode of run scoring in either innings varies in accordance with data obtained from selected innings. Relevant retrospective innings selection procedures and accessed databases are outlined in Figure 1.\n\nTable 1 provides innings summaries of specialist batters within each ‘low’ and ‘high’ scoring subcategory. Table 2 provides refined innings summaries from each ‘low’ and ‘high’ subcategory with an equal number of on-strike deliveries. Table 3 and Table 4 represent the developed ball-by-ball simulations.\n\nMatch data from previous Twenty20 internationals (2006–2019) and the domestic Vivo Indian Premier League (IPL) competition (2008–2019) were exported from ESPNcricinfo (ESPN Sports Media Ltd, n.d.) using an Excel macro. ESPN’s statistical database ‘Statsguru’ provided match summaries and run tallies of individual innings produced in international competition. An advanced filter was applied to query an innings by innings list of top order batters (top seven) from all available seasons and competitions. To obtain innings summaries from the IPL, match scorecards were opened manually to import summaries produced the by top seven batters from both teams. This process was repeated for every fixture within a season and from all available seasons at the time of analysis. Thus, a total sample of 12,990 individual innings were selected. These innings represented 5906 different batters, runs mean = 19.9 (SD = 21.2).\n\nTwo batting milestones, a half-century (50 runs) and century (100 runs), were selected to represent a ‘low’ and ‘high’ strike rate threshold. These milestones were selected as they represent meaningful team contributions and, secondly, are likely to be of a duration which warrants physiological study. From the 12,990 innings, 87 innings produced exactly 50 runs scored and only nine innings matched the 100 run criteria. Therefore, to increase the sample sizes around the chosen milestones, a range of ±1 standard deviation of runs scored (SD = 21.2 runs) was applied. Thus, the half century (low strike rate) sample size increased to n = 3210 and included innings of 29-71 runs scored. Likewise, the century (high strike rate) sample size increased to include innings ranging from 79-121 runs scored, producing an n = 287. The innings summaries for these adjusted milestones are presented in Table 1.\n\nData represent competitive individual innings produced in Twenty20 internationals and the Vivo Indian Premier League between 2006–2019. Innings milestones are broadened to categorize a range of ± 1SD (21 runs) around the given milestone, increasing the number of innings within each category. ‘low’ strike rate n = 3210 individual innings, ‘high’ strike rate n = 287.\n\na Intercepted delivery which leaves the field of play with a minimum of one bounce, batter credited four runs.\n\nb Intercepted delivery which leaves the field of play without a bounce, batter credited 6 runs.\n\nc Run scoring intensity - fraction of runs scored and on-strike deliveries.\n\nThe number of on-strike deliveries was selected as a robust measure of innings length. To standardize the duration of both batting simulations, frequency distributions of deliveries faced within each innings subset were drawn and the point of intersection with the largest sample size between the ‘high’ and ‘low’ strike rate innings was identified. The resultant overlap occurred at 51 deliveries faced, with a total of 27 half-centuries (‘low’) and 18 centuries (‘high’). While these innings were of equal duration, it is important to note that fundamental differences in runs scored, strike rate, number of boundaries and ratio of boundaries to runs accumulated by running - define the intensity of each simulation. Therefore, to account for each of these factors and to develop accurate simulations, ball-by-ball match data was needed to provide records of how each individual innings (‘low’, n = 27 and ‘high’, n = 18) progressed and how runs were accumulated throughout the innings.\n\nBall-by-ball data was obtained from a second online database (Rushe, 2009). However, at the time of analysis, existing ball-by-ball match data from the online database reduced our sample to 22 ‘low’ and 17 ‘high’ strike rate innings - presented in Table 2.\n\nData represent competitive individual innings produced in Twenty20 internationals and the Vivo Indian Premier League between 2006–2019 with a standardized workload of 51 on-strike deliveries.\n\na Intercepted delivery which leaves the field of play with a minimum of one bounce, batter credited four runs.\n\nb Intercepted delivery which leaves the field of play without a bounce, batter credited 6 runs.\n\nc Run scoring intensity - fraction of runs scored and on-strike deliveries.\n\nMatch data was downloaded as comma separated variables (CSV’s) and reduced to isolate the relevant innings within the match (Lopes, 2021). These CSV’s were imported into an R script for analysis. The purpose of analysing ball-by-ball innings data was to determine; i) the deliveries with the highest frequency of dot balls, singles, twos, threes, fours and sixes, ii) how runs were accumulated, and iii) the scoring rates of each individual innings. Furthermore, because batting is performed in pairs, each innings was analysed for its respective partnership data to determine; i) the average partnership deliveries faced and hence the overall duration of the simulation, ii) the number of deliveries which the batter is most likely on-/off-strike, and iii) the proportion of runs scored by the batter’s partner. By analysing ball-by-ball data, the average number of dot balls, singles, twos, threes, fours and sixes were calculated for both the ‘low’ and ‘high’ strike rate innings.\n\nFor each individual innings, the role of the batter’s partner was determined using a second R script. Ball-by-ball partnership data was extracted from the match data for every delivery faced by the batter’s partner/s (Lopes, 2021). This provided the number of deliveries faced during the innings as well as the sequence of runs scored by the batter’s partner/s. Like the development of the high and low scoring innings, the length of the overall partnership (deliveries faced by both batter and partner/s) was determined by the point of greatest overlap in overall partnership length from the representative high and low scoring innings. However, three overlaps were identified each with a sample size of one. As a result, the overlap which was nearest to the median of deliveries faced for the overall partnership was chosen as the best representative of the partner’s role in both high and low strike rate simulations. This overlap was identified as 43 deliveries resulting in a total simulation length of 94 deliveries. To determine which of the total 94 deliveries the batter is on strike for, a strike score was calculated for every delivery by assigning a ‘1’ if the batter was on-strike and ‘0’ if the batter was off-strike for every innings. Thereafter, each delivery was scored using Equation 1.\n\nWhereby, ‘Ball No.’ is the sequenced number of the delivery in question (e.g. one, two,… 94), ‘P. Length’ denotes the partnership length or number of deliveries within the given partnership and ‘Strike Score’ denotes the assigned binary score given to the delivery whether the batter was on-strike (1) or off-strike (0). The median was calculated for each delivery and rounded up to identify each ball number (of all 94 deliveries) the batter will be on strike for. This procedure was completed for both simulations.\n\nOnce on-/off-strike deliveries were determined, assigning runs to deliveries completed the development of the simulations. For on-strike deliveries, the number of dot balls, singles, twos, threes, fours and sixes were tallied for every delivery (independently for high scoring and low scoring simulations) to determine which deliveries produce the highest frequency/probability of each possible score. From these probabilities run types (dot ball, one, two… etc.) were assigned in descending order of probability. In the case where deliveries produced identical probabilities for two or more run types, priority was given to the run type with the least overall frequency in the innings (for example, sixes were prioritized over dot balls). Lastly, because dictating the exact outcome of each delivery is not representative of match play, every six deliveries (one over) required run types were grouped, giving batters freedom to decide which on-strike delivery, within an over, will produce a given run type according to the stroke played. As studying effects of batting partner/s is not a primary outcome of the batting simulations, required runs from off-strike deliveries were made identical for both high and low scoring simulations. Using the same method described for on-strike deliveries, run type was assigned to each off-strike delivery.\n\nTime motion analysis of Vivo IPL Twenty20 matches was performed and determined the average interval between deliveries to be 35 seconds and 80 seconds between overs, consistent with findings of Houghton and colleagues (2011). An audio recording was created using a written script and computer text-speech function (Supplementary Material A, B) to govern intervals between overs/deliveries. Further, the audio recording describes; i) when the batter is on-/off-strike ii), the run requirements for each over and their denomination (singles, doubles, boundaries etc.), and iii) an indication of the start and end of each over.\n\nDuring each on-strike delivery, the batter is free to select which on-strike deliveries to score from and what run type is achieved from a given delivery. The only constraints placed are that the batter must match the run type with the achieved stroke and that all required shuttles for an over must be achieved. To match run type with achieved stroke for a given delivery, batters are required to penetrate a scoring zone to be awarded ‘four’ and bat-ball contact must be achieved for all other run types. However, if the number of on-strike deliveries remaining in an over are near-depleted, shuttles may be enforced regardless of achieved contact or scoring zone penetration. For a ‘1’ batters should complete a single shuttle (17.68m) likewise, for ‘2’s batters should complete a double shuttle, and three shuttles for a ‘3’. For all shuttles, batters are required to complete a 180º turn at the end of the crease when completing the final shuttle for a given delivery. Boundaries will require one and a half shuttles for a ‘four’ and no shuttles for a ‘six’. When the batter is off-strike, instruction from the audio tape will dictate the required shuttles necessary for each off-strike delivery and the batter will complete these shuttles beginning on the audio cue. After necessary shuttles have been completed the batter will walk back to the striking crease. Shuttles must be run at maximum intensity akin to match play where batters attempt to maximize the number of runs scored from every delivery.\n\nTo improve the ecological validity and dynamics of the simulations, three phases were introduced to represent how an innings would develop under match conditions. These consisted of a ‘PowerPlay’ phase of six overs and two phases of five overs each, and the ’Middle’ and ‘Close Innings’ phases. During these phases, fielding positions or scoring zones can be altered to present varying scoring zones to encourage the batter to manipulate the ball into different areas of the field/arena. In cricket, the Powerplay consists of six overs whereby a maximum of two fielders are placed outside the inner ring while the remaining overs allow a maximum of five fielders outside the inner ring (ICC, n.d.). No more than five fielders may be placed on the ‘leg-side’ throughout the innings (ICC, n.d.). Therefore, we suggest a reduction in the number of available scoring zones following the ‘PowerPlay’ phase and discretion in the remaining number and placement of zones depending on the desired objectives of the simulation and skill of the batter.\n\nTo incentivise the batter and provide a form of match pressure, an overall batting performance score can be obtained according to the method of Muller and Abernethy (2008). Briefly, the method entails tallying bat-ball contacts according to three criteria. Good ball contact requires contact on the face of the bat and the ball deflecting in the intended direction (2 points). Bad ball contact entails contact with the bat and the ball deflects into an unintended direction (1 point). One point is deducted for an unsuccessful attempt at contact (-1 point) and a `leave' entails an intentional lack of contact with the ball (1 point). The achieved score for a given delivery is doubled if the stroke penetrates a scoring zone. If a batter is dismissed, the final achieved batting score is halved, with further deduction factors applied for multiple dismissals (i.e. two dismissals; performance score divided by three). Batters are instructed to bat for a maximized performance score by ensuring optimal bat-ball contacts, manipulating deliveries into pre-assigned scoring zones as often as possible and avoiding a loss of wicket. Attempting to achieve a maximal performance score in the simulation places a form of pressure on the batter improving match realism. According to the batting performance score criteria, a maximum score of 4 points may be achieved per on-strike delivery resulting in a maximum simulation score of 204 points from 51 on-strike deliveries.\n\nThe method was piloted in a controlled study and recruited 10 experienced (competitive playing experience >6 years) batters who bat in the top seven of their respective teams. Participants were required to be currently competing in amateur cricket leagues and free from injury (age: 22.3 (SD = 3.4) years, stature: 178 (8) centimetres, mass: 80.9 (9.0) kilograms). Procedures were reviewed by the Human Research Ethics Committee (clearance no: M180872) and participants signed informed consent. An arena schematic and procedural outlines are provided in Figure 2. Participants completed both batting simulations, in a randomised order, separated by a minimum of 48 hours. A regulation size indoor/action cricket arena with artificial playing surface was used and deliveries projected from an electric bowling machine Figure 2. In the PowerPlay phase, four scoring zones (2.5 meters wide) were placed in positions to mimic fielding gaps at third-man, extra cover, mid-wicket and long-on. Scoring zones were demarcated with coloured cones and batters were informed to their placement and changes throughout the simulation. Once the PowerPlay phase was concluded, one scoring zone (third-man) was removed to increase the difficulty of achieving boundaries in the ‘Middle’ and ‘Close Innings’ phase.\n\n\n3 Results\n\nThe developed simulations are 1 hr 2 min in duration and provided in audio format for ease of accessibility (Lopes, 2021). Ball-by-ball run requirements and on-strike delivery numbers, within an over, are presented in Table 3 (‘low’ strike rate innings) and Table 4 (‘high’ strike rate innings). The low strike rate simulation requires a batter to score 61 runs at a strike rate of 120, whereby 27 runs are scored through boundaries. The ‘high’ strike rate simulation requires a batter to score 88 runs at a strike rate of 173, whereby 60 runs are scored through boundaries.\n\nBall-by-ball audio dictation provided in supplementary material A.\n\nBall-by-ball audio dictation provided in supplementary material B.\n\n* Intercepted deliveries which penetrate demarcated scoring zones - bat-ball contact score multiplied by two.\n\n† 1 point deducted for every failed attempt at ball contact.\n\n§ Bat-ball contact scores tallied and adjusted for maximum available points (4 points per on-strike delivery).\n\nIn the half-century innings, batters achieved a batting performance score mean (SD): 72 (26) points, while the century produced a mean (SD): 88 (21). Table 5 presents by-phase summaries of both simulations and achieved performance scores adjusted to percent scores with associated point multipliers (scoring zone placement) and deductions (play-and-miss).\n\n\n4 Discussion\n\nThis study has developed two comprehensive batting simulations which are unique to Twenty20 cricket. Descriptions of high and low strike rate individual innings which vary in strike rate and requirement of boundaries are detailed ball-by-ball. Additionally, we suggest a method of improving the ecological dynamics and validity of batting simulations. These considerations improve match realism allowing researchers to produce match representative data and are a tool for sport practitioners to bolster training programmes.\n\nPrevious studies have investigated the physiological costs of scoring an ODI century (Goble & Christie, 2017; Houghton et al., 2011; Pote & Christie) or the effect of shuttle running volume (Christie et al., 2008) on a batter’s physiology. However, the simulations developed in this study provide researchers with the necessary tools to investigate Twenty20 batting in a more comprehensive manner. Namely, the simulations developed in this study may highlight the impact of run scoring intensity (strike rate) on the batters’ physiology which previously was not possible. Additionally, compared to shuttle running protocols and net practice, batting simulations as described in this study provide a more accurate representation of the stressors imposed on a batter during match play (Goble & Christie, 2017; Vickery et al., 2018).\n\nCurrent theories of skill acquisition also attest to the benefit of utilizing realistic game scenarios in training. Reilly and colleagues (2009) pioneered the Specific Adaptation to Imposed Demands (SAID) principle, which suggests adaptations are specific to the stressors/demands placed on the athlete. Therefore, sport practitioners should prioritize training scenarios where the replication of match stressors is at the forefront. Recently, ecological dynamics frameworks have been described to guide practitioners in constructing highly specific game scenarios for high-level sport development (Woods et al., 2020). In cricket, batting sessions which utilize SAID and ecological dynamics principles, like the batting simulations described in this study, may provide an ecologically valid tool to improve skill acquisition. Batters can routinely experience match-like fatigue and run scoring pressures which in turn may improve the athletes’ ability to cope once similar stressors arise during match play.\n\nBatting simulations dictate run requirements thus, losing the metric of runs scored as a valuable measure of performance and incentive. To account for this, we implemented a method which objectively quantifies the batter’s performance from bat-ball contacts, stroke placement and dismissals. Batters achieved similar scores in both simulations (Table 5) which may indicate a ceiling of skill set for our sample at the time of investigating or a lack of sensitivity in our scoring method. Future research should identify additional variables which may contribute to batting performance scores that are representative of skill. Further developing a dependable method of scoring batting performance will benefit both researchers and coaches. Sport practitioners can also adjust details of the Twenty20 simulations such as, the number and placement of scoring zones or setting batting performance score targets to create varying demands of difficulty for different athletes. Innings simulations, like BATEX (Houghton et al., 2011) and those described in our study are naturally limited in flexibility. As a result, effectiveness for skill acquisition and the batter’s interest may reduce with repetition. To alleviate this, additional simulations which highlight unique game dynamics namely, recovering from a sudden loss of multiple wickets or catering to specific batting order positions could be developed.\n\n\nConclusion\n\nBatting research in cricket requires intricate methods of replicating the stressors and demands of an individual innings. By doing so, the physiological effects of batting on the batter may be investigated while also providing a tool for specific skill acquisition. The simulations developed in this study replicate an hour-long partnership consisting of 51 on-strike deliveries and played at either a high or low strike rate. Batters produced similar scores in both the high and low strike rate innings when quantifying their performance based on bat-ball contacts and stroke placement. Utilizing these simulations should provide an enhanced training stimulus to traditional net-based practice while future research investigates other factors that contribute to a batters performance.\n\n\nData availability\n\nZenodo: Cricket-Research: Developing Twenty20 batting simulations. http://doi.org/10.5281/zenodo.4740316 (Lopes, 2021)\n\nThis project contains the following underlying data:\n\n• Supp.Material.A.m4a (audio description used to implement the low strike rate innings)\n\n• Supp.Material.B.m4a (audio description used to implement the high strike rate innings)\n\n• T20Simulation.R (Code to reduce ball-by-ball match data for development of additional batting simulations)\n\n• T20TOP7.csv (Innings summaries produced by specialist batters in the Indian Premier League and international competition between 2006-2018)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nChristie CJ, Todd AI, King GA: Selected physiological responses during batting in a simulated cricket work bout: A pilot study. J Sci Med Sport. 2008; 11(6): 581–584. PubMed Abstract | Publisher Full Text\n\nESPN Sports Media Ltd: Cricket Records - Find ICC Cricket Stats Online — ESPNcricinfo.com. n.d. Retrieved 2019-05-10 Reference Source\n\nGoble D, Christie CJ-A: Cognitive, physical and physiological responses of school boy cricketers to a 30-over batting simulation. J Sports Sci. 2017: 35(12): 1148–1154. PubMed Abstract | Publisher Full Text\n\nHoughton L, Dawson B, Rubenson J, et al.: Movement patterns and physical strain during a novel, simulated cricket batting innings (batex). J Sports Sci. 2011; 29(8): 801–809. PubMed Abstract | Publisher Full Text\n\nICC: Cricket Rules and Regulations — ICC Rules of Cricket. n.d.Retrieved 2020-09-20 Reference Source\n\nJohnstone JA, Ford PA: Physiologic profile of professional cricketers. J Strength Cond Res. 2010; 24(11): 2900–2907. PubMed Abstract | Publisher Full Text\n\nMüller S, Abernethy B: Validity and reliability of a simple categorical tool for the assessment of interceptive skill. J Sci Med Sport. 2008; 11(6): 549–552. PubMed Abstract | Publisher Full Text\n\nPote L, Christie CJ: Selected physiological and perceptual responses during a simulated limited overs century in non-elite batsmen. Eur J Sport Sci. 2016; 16(6): 654–660. PubMed Abstract | Publisher Full Text\n\nReilly T, Morris T, Whyte G: The specificity of training prescription and physiological assessment: a review. J Sports Sci. 2009; 27(6): 575–589. PubMed Abstract | Publisher Full Text\n\nRushe S: Cricsheet. 2009. Retrieved 2019-10-04 Reference Source\n\nVickery W, Dascombe B, Duffield R, et al.: Battlezone: An examination of the physiological responses, movement demands and reproducibility of small-sided cricket games. J Sports Sci. 2013; 31(1): 77–86. PubMed Abstract | Publisher Full Text\n\nVickery W, Duffield R, Crowther R, et al.: Comparison of the physical and technical demands of cricket players during training and match-play. J Strength Cond Res. 2018; 32(3): 821–829. PubMed Abstract | Publisher Full Text\n\nWoods CT, McKeown I, O’Sullivan M, et al.: Theory to practice: performance preparation models in contemporary high-level sport guided by an ecological dynamics framework. Sports Med Open. 2020; 6(1): 1–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWoods CT, McKeown I, Shuttleworth RJ, et al.: Training programme designs in professional team sport: An ecological dynamics exemplar. Hum Mov Sci. 2019; 66: 318–326. PubMed Abstract | Publisher Full Text\n\nLopes T: MrTLopes94/Cricket-Research: DOI badge (Version v1.0.3). Zenodo. 2021, May 6. Publisher Full Text"
}
|
[
{
"id": "85928",
"date": "09 Jun 2021",
"name": "Sean Muller",
"expertise": [
"Reviewer Expertise Expertise and motor skill 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\nThanks for the opportunity to review an interesting study. Well done to the authors for going to great effort to design and test the simulated batting task. I only have a few points to make, which the authors should consider and revise the manuscript. First, I understand the reasoning for using a bowling machine, but it does not present important bowler kinematic cues. Contextual (field-placing) information is also important particularly for T20 cricket. Was the complete field placing presented to batsmen throughout phases of the test? These cues are important to load the cognition of batters like occurs in competition (noting the authors have mentioned “…to closely replicate match-play….”). Presenting these sources of information is important for future design of simulators. Please discuss this as a limitation and how it might be improved upon in future research. Second, the correct terminology is representative task design, not ecological validity (see Araújo & Davids, 20151). Third, introduction and discussion sections; ecological-dynamics theory is not the only framework that guides “….constructing highly-specific game scenarios….”. The specificity of practice hypothesis (see Magill & Anderson, 20172; Thorndike, 19063) provides the same guidance. Please revise this in the manuscript to provide a more balanced discussion of the literature.\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? No source data required\n\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? Yes",
"responses": [
{
"c_id": "11124",
"date": "10 Apr 2024",
"name": "Tiago Lopes",
"role": "Author Response",
"response": "Thank you for your valuable input and fair critique to this version of the manuscript. Following your comments the manuscript has been revised to include; a more balanced discussion of representative task design with updated references, critique around the use of bowling machines in future studies and simulators which will disregard kinematic cues of the bowling action, clarification on the presentation and instruction provided to batters for fielding positions."
}
]
},
{
"id": "85930",
"date": "15 Jun 2021",
"name": "Habib Noorbhai",
"expertise": [
"Reviewer Expertise Cricket Sciences and Sports Biomechanics."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 the opportunity to review this interesting study, which would be a valuable contribution to the cricket sciences literature.\nBelow, I have suggested a few points that will assist in improving the standard of the paper:\nIt is not clear why a bowling machine was utilised? Bowling / real-life kinematics are key, especially for high strike rate scoring. This needs to be listed as a limitation.\n\nWere the deliveries bowled permutated?\n\nThe discussion requires a well-rounded discussion including aspects of task and temporal constrains of batting, motor control, performance analysis and batting kinetics/kinematics (even though this study is based on simulation and research strategy).\nYou may also want to consider other T20 studies your paper:\nDavis, J., Perera, H. and Swartz, T.B., 2015. A simulator for Twenty20 cricket 1\n\nSholto-Douglas, R., Cook, R., Wilkie, M. and Christie, C.J.A., 2020. Movement demands of an elite cricket team during the big bash league in Australia2\n\nNoorbhai, H. (2020). The backlift techniques of cricketers in the Indian Premier League: batting implications for the shorter format. International Sports Studies3\n\nIrvine, S. and Kennedy, R., 2017. Analysis of performance indicators that most significantly affect International Twenty20 cricket4\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? No source data required\n\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? Yes",
"responses": [
{
"c_id": "11125",
"date": "10 Apr 2024",
"name": "Tiago Lopes",
"role": "Author Response",
"response": "Thank you providing input to improve the quality of this work. Following your comments, the manuscript has been adjusted to discuss the limitations of using a bowling machine in research and batting simulations. A clarification on the set-up of the bowling machine and permutation of deliveries is provided. Reviewed literature has also been updated from your input. For brevity, some information has remained omitted including the T20 simulator by Davis, Perera & Swartz which addresses a different objective to that presented in this study."
}
]
}
] | 1
|
https://f1000research.com/articles/10-411
|
https://f1000research.com/articles/11-996/v1
|
05 Sep 22
|
{
"type": "Research Article",
"title": "Factors associated with the intention of telehealth service utilization among Bangladeshi people: a cross-sectional study",
"authors": [
"Humayun Kabir",
"Md. Kamrul Hasan",
"Nahida Akter",
"U Swai Ching Marma",
"Tohidul Alam",
"Ariful Haque Tutul",
"Lila Biswas",
"Rawshan Ara",
"Dipak Kumar Mitra",
"Nahida Akter",
"U Swai Ching Marma",
"Tohidul Alam",
"Ariful Haque Tutul",
"Lila Biswas",
"Rawshan Ara",
"Dipak Kumar Mitra"
],
"abstract": "Background: Telehealth is comprised of telecommunications and electronic information systems to support and maintain long-distance healthcare services. Although it has not been thoroughly explored, the intention of using the service among the general public is critical to its success. We investigated the factors associated with the intention to utilize telehealth services among the general population of Bangladesh. Methods: This cross-sectional study was conducted between May 22, 2021 and June 15, 2021 in Bangladesh, where the total number of participants was 1038. The Pearson chi-square test and Kruskal-Wallis H tests were used to examine the unadjusted relationship between the explanatory variables and the intention to use telehealth services. A multinomial logistic regression model was fitted to determine the adjusted association. Shapiro-Wilk tests were used to check the normality of continuous data. Data were processed and analyzed by software STATA-16. Results: The probability of utilizing the service increased significantly with increasing knowledge, perceived benefit, and predisposition levels among respondents. However, when perceived concern increased, the likelihood of utilizing the service dropped significantly. Age, marital status, educational status, profession, residence, and perceived health status were significantly associated with the participants’ intention to utilize the telehealth service. Conclusions: The influencing aspects of telehealth service utilization should be recognized by the respective authorities. Possible activities to enhance usability among people are also recommended.",
"keywords": [
"Telehealth",
"telemedicine",
"knowledge",
"benefit",
"concern",
"predisposition",
"Bangladesh"
],
"content": "Introduction\n\nOver the last few decades, Bangladesh’s healthcare system has made significant advancements; in particular, made tremendous progress in public health while focused on meeting the Millennium Development Goal.1 It has also had considerable success in lowering maternal and newborn mortality and morbidity rates, as well as diarrheal illnesses, malaria, and tuberculosis.2 However, challenges still exist, such as Bangladesh is staying a long way from obtaining universal health care for all from vulnerable groups, e.g., low socio-economic status and people from remote locations.3 The shortages of skilled healthcare personnel, climate-induced environmental changes,4 and transportation constraints are the most pressing issues in accessing the healthcare system.5 Telehealth, in which people have benefited from recent technological advancements, has the potential to overcome many of these health care system-related constraints.3\n\nTelehealth uses telecommunications and electronic information to support and continue long-distance clinical health service, healthcare management, and patient-focused health education.6 This term also refers to a wide range of remote healthcare service delivery strategies. Telehealth is recommended as one of the most essential and promising technology-based services for addressing many challenges the Bangladeshi healthcare system usually faces.7 Nevertheless, the effectiveness of the telehealth service is contingent on healthcare professionals’ and the general public’s acceptance and willingness to utilize it.8 As individuals can be benefited from how telehealth services are offered,9 it is crucial to understand their intentions and the significance of other elements in their decision to utilize telehealth to build services that people will embrace.9\n\nHowever, the intention of the general population to utilize telehealth services was not widely documented; the literature generally focuses on physicians’ and clients’ impressions of telehealth services. There were a few reports on peoples’ attitudes, but they did not focus on the elements that can influence their decision to adopt telehealth. Jennett et al. (2003) conducted a study in Canada to assess the preparation of rural people to utilize telehealth,10 and Schwarz et al. (2014) conducted a study in New South Wales, Australia, to investigate the preparedness of Australia’s distant population.11 However, both studies drew their samples from key informants or persons who had already used telehealth services rather than the general population. Likewise, several studies conducted in different places in the world emphasized the physician’s views toward telehealth, but general people’s perceptions or intentions toward telehealth service utilization were merely investigated.12–14\n\nIn Bangladesh, the majority of telehealth research has focused on the role and importance of telehealth service,15,16 how it may be used in disease or outbreak management,17 and methods to promote the telehealth sector.18 Furthermore, few pieces of research focused on healthcare providers’ perceptions of telemedicine and potential hurdles in Bangladesh.19,20 Those studies only included specific samples yet focused on the general people’s intentions. Despite the fact that a study described the people’s economic view7 and the perception of people with chronic diseases, they have yet to examine the influence of demographic or health-related factors on intention to utilize the telehealth service.7,21 Therefore, this research investigated the factors associated with the intention to utilize telehealth services among the general population of Bangladesh.\n\n\nMethods\n\nThis cross-sectional study was conducted during the coronavirus disease 2019 (COVID-19) pandemic between May 22, 2021, and June 15, 2021. In this study, 1038 Bangladeshi population participated. The inclusion criteria for the study participants was at least 18 years old and willing to participate by ensuring consent. Those who failed to provide the completed responses to the questionnaire were excluded from this study.\n\nThe outcome variable of the study was the intention of utilizing telehealth services. The respondents’ were asked to respond to an item; “Do you have any plan to utilize telehealth service in the future?” The responses were considered into three categories such as “they will not utilize,” “they may utilize” and “they will utilize”. The exploratory variables included participants’ knowledge, perceived benefit, perceived concern, and predisposition to telehealth, demographic variables (age, sex, marital status, educational status, profession, residence, and division), and perceived health status.\n\nThe knowledge, perceived benefit, perceived concern, and predisposing were measured by adopting a questionnaire by Gagnon et al. (2004), who conducted a study in Quebec, Canada.8 The questionnaire was developed based on the telehealth applications such as telediagnosis, telemonitoring, teletriage, teleintervention, remote access, continuing education for health care professionals, cost savings, quality, safety, and confidentiality. The item of telehealth knowledge was a response to a three-point scale. All the responses to the items related to perceived benefit, perceived concern, and predisposition was obtained via a five-point scale. The details of the questionnaire are provided in the extended data.49\n\nTo evaluate perceived health status, we implemented a single-item measure suggested by the World Health Organization (WHO) (\"In general, how would you rate your current health status?\").22,23 The scale featured five options for replies; “very good”, “good”, “fair”, “bad”, or “very bad”. For statistical purposes, “very good” and “good” were considered “good”, while “fair” was regarded as “as usual”.23 Similarly, “poor” was regarded to be “bad” and “very bad”. A similar scale was used to measure the Bangladeshi healthcare workers’ perceived health status.24\n\nFor this study, a structured questionnaire was developed. Two experts reviewed the questionnaire, and required changes were performed based on their recommendations. The completed questionnaire was transferred to “Google Form” in terms of creating an online version. By utilizing an online questionnaire, data were acquired, and a convenient sampling procedure was followed. The questionnaire was distributed via social media platform (Facebook and WhatsApp) with the request that respondents participate voluntarily. By using these strategies, after receiving 1130 responses, 1038 completed responses were accepted for data analysis.\n\nOur estimated sample size was 784 at 80% power, 95 % CI of 0.05 to 1.96, and 3.5% margin of error, with the assumption that 50% of study participants were knowledgeable about telehealth.25 The authors aimed to reduce the margin of error by collecting a larger sample size than was required, and an additional 254 responses (32% of the estimated sample size) were included. As a result, a total of 1038 samples were included in the final analysis.\n\nData were automatically entered into an online Excel spreadsheet considering the nature of data collection. Only completed responses were collected and processed into the data analysis software STATA-16. The Pearson chi-square test was used to examine the unadjusted relationship of demographic and perceived health status with the intention to utilize telehealth services. Furthermore, Shapiro-Wilk tests were used to check the normality of knowledge, perceived benefit, perceived concern, and predisposition score and found that the scores were non-normally distributed. Kruskal-Wallis H test is usually used to assess more than two independent subgroups with non-normally distributed data. As a result, the Kruskal-Wallis H test was used to determine the unadjusted association between the scores and the intention to utilize telehealth services. Finally, a multinomial logistic regression model was fitted to determine the adjusted association between the explanatory variables and the intention to utilize telehealth services. The p-value of 0.05 was considered statistically significant at the 95% confidence interval.\n\nOn the top of the page of the questionnaires, the study aims and objectives were specifically outlined. The authors secured the privacy of the acquired data and the respondents’ flexibility to exit from the study at any moment. This study’s subjects were all Bangladeshi, and none were under the age of 18 years. Besides, the respondents were asked for electronic signatures; after that, they were asked to respond and submit the answers to the items. Moreover, the Ethical Review Committee of Tejgoan College, Dhaka-1215, Bangladesh, reviewed and approved the study on April 25, 2021 (reference number 2021/OR-TGC/0202). The research was carried out in line with the Helsinki Declaration.26\n\n\nResults\n\nA flow diagram of the sample recruitment procedure in detail is presented in Figure 1. In total, 1038 responses were analysed.\n\nIn Table 1, the distributions of demographic and perceived health status by intention to utilize telehealth services are presented.48 In the age group of 30-39 years, 40.83% intended to utilize (will utilize) the telehealth service. The number of unmarried participants intended to utilize the telehealth service was 37.72%, whereas the intention of utilizing the service among graduates was 44.00%. The urban residence’ intention to utilize the service was 38.57%. Of those who perceived poor health status, their intention to utilize the service was 38.35%.\n\nIn Table 2, the distributions of knowledge, perceived benefit, perceived concern, and predisposition by intention to utilize telehealth services are presented. The knowledge, perceived benefit, and predisposition scores were significantly highest (p<0.001) among those who will utilize the telehealth service. Albeit, the perceived concern score was found to be significantly highest (p<0.001) among those who will not utilize the telehealth service.\n\nTable 3 presented a multinomial logistic regression that was used to determine the factors (sociodemographic factors and perceived health status) associated with the intention of utilizing telehealth services. The reference category of the outcome variable was “they will not utilize,” and each of the other two (“they may utilize” and “they will utilize”) was compared to this reference group. The probability of utilizing the service increased significantly with increasing knowledge level among respondents who ‘may utilize’ (RRR= 1.24, 95% CI: 1.16-1.32) and ‘will utilize’ (RRR= 1.64, 95% CI: 1.50-1.80). Similarly, as the perceived benefit score climbed significantly, so did the likelihood of utilizing the service among those who ‘may utilize’ (RRR= 1.22, 95% CI: 1.15-1.30) and those who ‘will utilize’ (RRR= 1.62, 95% CI: 1.50-1.75). However, when perceived concern increased, the likelihood of utilizing the service dropped significantly among respondents who ‘may utilize’ (RRR= 0.67, 95% CI: 0.57-0.79) and ‘will utilize’ (RRR= 0.53, 95% CI: 0.45-0.63). Albeit, the chance of utilizing service increased with the increased level of predisposition among respondents who ‘may utilize’ (RRR= 1.47, 95% CI: 1.33-1.63) and ‘will utilize’ (RRR=2.30, 95% CI: 2.02-2.61). In comparison to the oldest age group (≥40 years), the chance of utilizing the service was 3.02 (RRR=3.02, 95% CI: 1.29-7.03) times significantly higher among the youngest (<20 years). Furthermore, the likelihood of ‘may utilize’ and ‘will utilize’ the service were 2.11 (RRR=2.11, 95% CI: 1.13-3.35) times and 3.17 (RRR=3.17, 95% CI: 1.91-5.26) times among the participants with age of 20-29 years. Compared to the married, the unmarried participants were significantly 72% (RRR=1.72, 95% CI: 1.17-2.54) and 71% (RRR=1.71, 95% CI: 1.14-2.56) more likely to ‘may utilize’ and ‘will utilize’ the service, respectively. The graduate participants were 4.28 (RRR=4.28, 95% CI: 2.52-7.27) times and 5.22 (RRR=5.22, 95% CI: 3.02-9.02) times more likely to ‘may utilize’ and ‘will utilize’ the service, compared to the education level up to SSC. Similarly, HSC completed respondents’ intention to utilize service in the category of ‘may utilize’ and ‘will utilize’ was 3.26 (RRR=3.26, 95% CI: 2.04-5.51) times and 2.56 (RRR=2.56, 95% CI: 1.56-4.22) times higher than the up to SSC level educated. Among the students’ the possibility of ‘may utilize’ and ‘will utilize’ the service was 85% (RRR=1.85, 95% CI: 1.24-2.75) and 86% (RRR=1.86, 95% CI: 1.23-2.80) higher compared to the employed respondents. The urban residence was 2.42 (RRR=2.42, 95% CI: 1.41-4.16) times more likely to ‘will utilize’ service than the rural.\n\n\nDiscussion\n\nSeveral pieces of research around the world have already shown how people’s and health care providers’ views and intentions influence their usage of telehealth services.12–14,19,20 Meanwhile, few pieces of research in Canada looked at the impact of social, cultural, economic, and environmental factors on people’s decisions to utilize telehealth-care services.27,28 In Bangladesh, the intention of telehealth service utilization of the general population was yet to be investigated. Therefore, in this study, we examined the associated factors such as sociodemographic factors, perceived health status, knowledge, perceived benefit, perceived concern, and predisposition with the intention to utilize telehealth services.\n\nOur study found a significant association between telehealth of knowledge and the intention to utilize the service. We found that as the knowledge score improved, the level of intention to utilize the telehealth service increased. Albarrak et al. (2021) reported that Saudi Arabian participants had an average level of understanding were more intended to utilize the telehealth service.29 Albarrak et al. (2021) believed that training on telehealth could improve understanding, and this was expected to influence people’s intention to utilize the telehealth service.29 Malhotra et al. (2020) in India and Woo & Dowding (2019) in the United States also drew a similar conclusion as our study findings.30,31\n\nIn our study, participants were more intent to utilize the telehealth services if they perceived a high level of benefit. Similarly, Alaboudi et al. (2016) and El-Mahalli et al. (2012) in Saudi Arabia found the same result that the participants who perceived the benefit of the service were more intended to utilize the service.32,33 When participants had a high level of perceived concern, their intention to utilize this service was found low. Numerous studies around the world found that worried and particularly privacy issues were connected to the intention of technology-based health service utilization.34,35 Furthermore, Bangladeshis who had a favorable predisposition were more interested in the telehealth service. In order to determine whether socio-demographics and technology-enabling factors may influence how telehealth is utilized, a study was carried out in the United States in 2021.36 The researchers revealed that individuals with favorable predispositions toward ICT devices and internet access exhibited more enthusiasm for using telehealth.36\n\nWe found that several demographic factors were significantly associated with the intention to utilize telehealth services. Age influenced people’s intention to adopt telehealth services. The intention to utilize the service in the near future was 3.02 times higher among the youngest (<20 years) than it was among the oldest (≥40 years). Numerous studies also supported the findings of our research. Lee et al. (2019) and Raghunathan et al. (2018) found that younger participants had a stronger intention to utilize telemedicine or internet adaptive equipment, which could be due to their competence and past familiarity with the advanced technology.37,38 However, Jenkins et al. (2016) reported that older stroke patients were more eager to employ telehealth observation with ongoing technical assistance than younger patients were.39\n\nOur research focused on education status and found that those with better education were more likely to be utilizing telehealth services. More specifically, we found that graduate participants were 4.28 and 5.22 times more likely to “may utilize” and “will utilize” the service, respectively, than those with an education level up to SSC. Schulz et al. (2013) found that persons with higher levels of education were more likely to pay for and use technology-based health monitoring systems.40 Another study found that cancer patients with higher education were more likely to use mobile devices to utilize their health care services.38 Education may frequently be mentioned as a component that influences people’s thoughts and actions, but few researchers have looked at this factor in the interaction between the fundamental indicators and people’s willingness to adopt technology-based health monitoring systems.41\n\nOur study revealed that unmarried participants were much more intent to utilize telehealth than married people were; 72% and 71% ‘may utilize’ and ‘will utilize’ the service, respectively. According to Choi et al. (2021) telehealth users were more likely to be married or in a relationship than non-users.36 Additionally, they demonstrated in their research that during the COVID-19 outbreak, a more significant percentage of users than non-users either joined in with others or somebody came in with them.36\n\nThe intention was also found higher among students than among other employed individuals. The possible reason could be as they were more likely to expose to distance learning and technology based service usability.42–45 A similar study measuring nursing students’ readiness to use telenursing was carried out in Poland.46 Amazingly, 69.49% of the students reported that they would be very likely to include telenursing in their course curriculum.46 Additionally, students from a selected number of colleges demonstrated a noticeably greater desire to integrate telenursing courses into the nursing curriculum and a willingness to utilize telenursing services in their future professional practice.46\n\nFurthermore, we found that urban people were more intent on utilizing this service compared to rural individuals. However, according to Lin et al. (2004) the people of rural areas had a higher likelihood of adopting telehealth services.47 Moreover, in Canada, Gagnon et al. (2004) did not find any influence of residential status on participants’ intention of telehealth service utilization.8\n\nAn association between perceived health status and the intention to utilize the telehealth service was found in our study. Our findings revealed that those with a low health status were more intended to utilize telehealth services than those with normal or good health status. Similarly, Ghaddar et al., (2020) conducted a study in the United States and found that participants with chronic diseases were more interested in utilizing the telehealth service than those with good perceived health status.3\n\n\nConclusions and recommendations\n\nThe healthcare system seems successful when there is equal participation in services. However, there are many constraints that may hinder people from getting access to the universal health system. Therefore, several initiatives can be considered to reach the health service to the people’s door, including the technology-based digital health system telehealth. Without addressing the digital constrain of accessing the existing healthcare system, the disparities at the community level may be unprivileged. Numerous factors were identified to be connected with people’s intention to utilize the telehealth service in this study. The appropriate authorities can consider the factors and conduct studies more broadly to investigate more containment of telehealth implementation. Moreover, we advocated for policy actions to make the telehealth system more accessible to the community and to enhance the understanding and awareness of the benefits of utilizing digital health to improve usability among the underprivileged.\n\nTelehealth is an emerging healthcare platform that allows patients to access healthcare services effortlessly. Public intent to utilize the platform is also deemed significant when encountering an expansion of this service widely. However, no study had yet investigated the intention of telehealth among Bangladeshi adults, which is one of the strengths of this study. The large sample size in this study provides substantial support for the accuracy of the results. However, selection bias was inescapable due to the convenient nature of data collection method. Because of the cross-sectional study design, causality between variables could not be established. Moreover, more rigorous research is recommended in Bangladesh by utilizing a random sampling approach.\n\n\nData availability\n\nZenodo: Intention to utilize telehealth service in Bangladesh, https://doi.org/10.5281/zenodo.6862986.48\n\nThis project contains the following underlying data:\n\n• Intention_utilize_telehealth_bd.xls (raw data). Data set of the study.\n\nZenodo: Telehealth research questionnaire in detail, https://doi.org/10.5281/zenodo.6953539.49\n\nThis project contains the following extended data:\n\n• Telehealth_research_questionnaire.docx (in English). Copy of the research questionnaire.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
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}
|
[
{
"id": "149710",
"date": "21 Oct 2022",
"name": "Victoria Ramos",
"expertise": [
"Reviewer Expertise Telemedicine and Digital 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\nGood and innovative work in Bangladesh where the intention of telehealth among Bangladeshi adults had not been studied before and is important to improve usability among the underprivileged.\nSome contrariety in the expression. For instance, this work revealed that unmarried participants were much more intent on utilizing telehealth than married people were, but it does not take into account another work that presents that telehealth users were more likely to be married or in a relationship than non-users. Could there be a relationship between the intent to use telehealth services and the need for socialization or loneliness?\nUnexpected result about urban people being more intent on utilizing this service compared to rural individuals when it is taken into account that it is probable that, in urban environments, there is more access to healthcare service than in rural environments.\nA review of the discussion of the results is recommended. Their findings revealed that those with a low health status had more intention to utilize telehealth services than those with normal or good health status, without any reason. On the contrary, the authors believe that severe cases prefer face-to-face care over telecare.\nThere are a number of issues with the methods and analysis that are not clear enough. Below are some comments:\nI have indicated that there is some contradiction between the intention of the married and the unmarried. In the second paragraph on page 9, there seems to be a contradiction and it would be interesting if they give some explanation about it.\nIt would also improve the work to have some indications on how to improve the intention to use among those less favorable to telecare. The young and digitally born are already immersed in these tools and have no problem using them. Is there any explanation for that perceived concern? When concern increases, the likelihood of utilizing the service dropped significantly.\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": []
},
{
"id": "222057",
"date": "22 Jan 2024",
"name": "Michelle Lozada-Urbano",
"expertise": [
"Reviewer Expertise Nutrition",
"Public Health and Health economic"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 is important, as it can help understand how to improve access to care for patients who are not close to health services. It is necessary to modernize the health system. The use of telehealth has shown to be efficient in patient care, knowing the intention of use and the associated factors, which is the objective of this study, is key to understanding where the best application could be, together to other studies such as satisfaction and evaluation.\n\nWhen mentions the use of a questionnaire by Gagnon et al. It is better to place if you have internal and external validation. In table 1, the columns express the number (percentage), you can enter n(%). I would like to know that they only have 3 categories of educational level. In the case of graduates, it would have been important to know if they are from the health area or from other careers. This can help to better understand the behavior of these variables, as mentioned in the discussion. about nursing students. They mention cancer patients as being more predisposed to using virtual care; other studies during the COVID-19 pandemic have demonstrated optimal care for overweight and obese patients, with anthropometric and nutritional changes. Students today are familiar with these new technologies or telehealth. This comment may help improve the limitations. I think the conclusions and recommendations could be improved. There is an understudied population that is older adults who have movement restrictions and have caregivers in their care.\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? Partly",
"responses": [
{
"c_id": "11091",
"date": "13 Apr 2024",
"name": "Humayun Kabir",
"role": "Author Response",
"response": "Comment-1: This study is important, as it can help understand how to improve access to care for patients who are not close to health services. It is necessary to modernize the health system. The use of telehealth has shown to be efficient in patient care, knowing the intention of use and the associated factors, which is the objective of this study, is key to understanding where the best application could be, together to other studies such as satisfaction and evaluation. Response-1: Thank you. Comment-2: When mentions the use of a questionnaire by Gagnon et al. It is better to place if you have internal and external validation. Response-2: Thank you for the query on the validity of the tool. We addressed your comment and added, “For face and content validity, the questionnaire was reviewed by two experts in this area. The reliability of the questionnaire was found 0.86 in our study, representing an excellent internal consistency” in the method section of the revised version. Comment-3: In table 1, the columns express the number (percentage), you can enter n (%). Response-3: Thank you. We addressed your suggestion. Comment-4: I would like to know that they only have 3 categories of educational level. In the case of graduates, it would have been important to know if they are from the health area or from other careers. This can help to better understand the behavior of these variables, as mentioned in the discussion. about nursing students. Response-4: Thank you. According to the literature, Bangladeshi education levels are commonly classified as SSC (Secondary School Certificate), HSC (Higher Secondary Certificate), and graduate (Bachelor or honours, master's degree). As a result, we conducted our research using identical educational level groups. However, if we could categorize education according to subject areas such as health, nursing, engineering, social science, etc., we would understand the influence of education on telehealth. We considered this issue in our study's limitations section. Comment-5: They mention cancer patients as being more predisposed to using virtual care; other studies during the COVID-19 pandemic have demonstrated optimal care for overweight and obese patients, with anthropometric and nutritional changes. Response-5: Thank you. We included this evidence in the revised manuscript. Comment-6: Students today are familiar with these new technologies or telehealth. This comment may help improve the limitations. Response-6: We addressed your concern and mentioned this issue in the limitations section. Comment-7: There is an understudied population that is older adults who have movement restrictions and have caregivers in their care. Response-7: Thank you. We addressed your concern and mentioned this issue in the limitations section. Comment-8: I think the conclusions and recommendations could be improved. Response-8: Thank you. We revised and improved the conclusions and recommendations sections."
}
]
}
] | 1
|
https://f1000research.com/articles/11-996
|
https://f1000research.com/articles/11-319/v1
|
17 Mar 22
|
{
"type": "Research Article",
"title": "Typhoid diagnosis and associated prevailing drug resistance in Mbale city, Uganda",
"authors": [
"SAMUEL GIDUDU",
"Jesca Nakavuma",
"Dennis Muhanguzi",
"Francis Mutebi",
"Herbert Itabangi",
"Jacob Iramiot",
"Jesca Nakavuma",
"Dennis Muhanguzi",
"Francis Mutebi",
"Herbert Itabangi",
"Jacob Iramiot"
],
"abstract": "Background: The study aimed at determining the predictive values of Widal’s test against culture and the antimicrobial sensitivity profile of Salmonella typhi (S. typhi) isolates from patients attending private health facilities in Mbale city, Uganda. Methods: This was a quantitative cross-sectional study in which 172 participants were recruited. Blood and stool samples collected were cultured; and to each stool sample the following tests were done; Xylose Lysine Deoxycholate (XLD), Salmonella Shigella agar (SSA), and MacConkey. Isolates suggestive for S. typhi were examined with triple sugar iron (TSI) and SIM (Sulphur, indole, and motile) and antibiotic sensitivity test (Ciprofloxacin, Imipenem, Ceftriaxone, Chloramphenicol and Augmentin for sensitivity testing) conducted with Mueller Hinton respectively. Generated data was entered into the Epidemiological information (Epi Info) software (version 7) and analyzed using the contingency table to determine the sensitivity, specificity, positive predictive value and the negative predictive value. The analysis was then presented in form of graphs and tables. Results: The positive predictive value (PPV) for Widal’s test was 6.8% while the negative predictive value (NPV) was 100%. Three isolates were sensitive to Ciprofloxacin (3, 100%) and Imipenem (3, 100%), intermediate to Ceftriaxone (2, 67%) and resistant to Chloramphenicol (2, 67%) and Augmentin (2, 67%). Conclusion: In comparison with culture, Widal’s test is highly sensitive (100%) with a low specificity of 76% and PPV (6.8%) and NPV (100%). It should therefore be followed up with a more specific confirmatory test. S. typhi was highly sensitive to both Ciprofloxacin and Imipenem; and resistant Chloramphenicol and Augmentin.",
"keywords": [
"Typhoid fever",
"Widal's test"
],
"content": "Introduction\n\nThe global burden of typhoid fever was estimated at 17 million cases with 178,000 deaths in 2015 with more cases being reported in South Asia, South East Asia, and Sub-Saharan Africa.1 Whereas typhoid fever appears to be less common or under ascertained in Africa compared to Asia, more recent studies confirm that typhoid fever incidence is high in some parts of Africa.2\n\nThe prevalence of the fever in Uganda was reported to be 7.6% during the February, 2015 disease outbreak that started from Kampala City3 and by the month of December 2015, the cases were reported by nearly all districts in Uganda with central region reporting the highest numbers followed by Northern, Western and Eastern respectively. In Mbale specifically, the prevalence of typhoid fever was reported at 1.3%.4\n\nThe recommended diagnosis for typhoid fever in Uganda is by use of culture, rapid antibody tests, Polymerase Chain Reaction (PCR) and relative leukopenia tests and not Widal’s test5; and the antibiotics used for treatment include Ciprofloxacin, Chloramphenicol, Ceftriaxone, and or Amoxicillin depending on the fever’s severity.5 Private health facilities in Mbale city are still depending on the Widal’s test that is no longer recommended to diagnose typhoid fever which isn’t the case in public health facilities. The test is not recommended because of its low positive predictive value (60%) and low negative predictive value (75.2%).6 The non-compliance to the diagnostic guidelines of diagnosing typhoid fever is causing inappropriate drug prescription and multidrug resistance development against antibiotics like ampicillin, chloramphenicol and ciprofloxacin.7\n\nSince accurate diagnosis is crucial to the management of typhoid fever,7 the research aimed at determining the predictive values of Widal’s test against culture and the antimicrobial sensitivity profile of S. typhi isolates from patients attending private health facilities in Mbale city, Uganda; and give information about how typhoid fever is being managed in private health facilities, act as a basis for developing or re-enforcing policies on typhoid fever management, and also act as a reference to other researchers adventuring in the same field of study.\n\n\nMethods\n\nThis study was approval by the Mbale regional referral hospital research ethical committee (MRRH REC) with a reference of MRRH-REC IN-COM 006/2018 before data collection. MRRH REC is accredited by UNST with a registration number of UG-REC-011. Permission was sought from Mbale city authorities and private health facility authorities before conducting the study. A written consent was sought from the participants prior to recruitment into the study. Codes instead of names were used as sample identification numbers for confidentiality purposes. Results obtained were availed to the clinicians and the research participants for health management purposes. The S. typhi isolates and the data summary was kept safely in the Mbale regional referral hospital microbiology laboratory.\n\nThis was a quantitative cross-sectional study that recruited 172 patients clinically suspected for typhoid fever and seeking treatment from private clinics in Mbale city between December, 2017 to January, 2018. A systematic sampling technique was used to identify and enroll four participants (every 1st, 3rd, 5th and 7th) from each private health facility into the study. The sample size was used to obtain the number of private facilities to be enrolled into the study (i.e., sample size/number of expected participants per facility). The study included typhoid suspects seeking diagnosis and treatment in private health facilities during the period of study and consented in writing to participate in the study. Those who were on antibiotics within one month of the study were excluded. Both blood samples (10 ml and 2 ml) and stool samples (2 g) were collected from the research participants for study and treatment purposes.\n\nUsing a vacuum extraction blood-sampling system, 10 mls of blood was aseptically collected from the research participants and dispensed directly into the BD blood culture bottles. 2 ml syringes were used to aseptically collect 2 ml of blood from the research participants, discard the needle, open the plan vacutainer tube to dispense the 2 ml volume of collected blood into the plan vacutainer; this was used for Widal’s test by the laboratory staff at the private health facility as routine. Following orientation, research participants scooped 2 g of fresh stool samples using the spoon in the clean leak-proof containers that were free from disinfectant or detergent residue and recapped with tight-fitting, leak-proof lids; and delivered to the private health facility laboratory where it was inoculated into a Cary Blair media for transportation to the microbiology laboratory for culture. Both blood and stool samples including the request form were triple packaged and transported to the microbiology Laboratory Unit at Microbiology Department in Mbale regional referral hospital. Other information collected from the research participants included demographic data such age and gender and the Widal’s test result at the private health facility.\n\nBD blood culture bottles inoculated with blood samples were inserted into the Bactec machine for incubation set at 37°C for up to seven days. While, Stool samples were inoculated on XLD, SS agar (placed in the incubator set at 37°C for 24 hours) and MacConkey was first placed into anerobic gar before placing it in the incubator in order to limit the background of environmental flora and allow only S. typhi to grow. Gram reaction testing, triple iron sugar (TSI), and SIM biochemical testing were performed on isolates for identification purposes. The susceptibility of each bacteria to each antibiotic disk (Ciprofloxacin, Ceftriaxone, Azithromycin, Amoxiclave, Imipenem and Chloramphenicol) was done using the disc diffusion method and results recorded as resistant (R), Intermediate (I) and Sensitive (S).\n\nData generated from the study was entered into the Epidemiological information (Epi Info) software (version 7) and analyzed using the contingency table to determine the sensitivity, specificity, positive predictive value and the negative predictive value. The analysis was then presented in form of graphs and tables.\n\nThe personal protective equipment (examination gloves, lab coats and closed shoes) was put on during sample collection and sample processing procedures. The media (except blood culture broth) were prepared aseptically, and incubated to rule out contamination. All Laboratory procedures were done following the standard operation procedures (SOPs) guide lines of the Mbale regional referral hospital microbiology laboratory.\n\n\nResults\n\nA total of 172 participants, 55% female and 45% male, aged between 17 to 50 years were enrolled for the study. Majority of the participants were aged between 18 and 34 years and few were those above 50 years of age (Figure 1).\n\nOccurrence of S. typhi positive participants\n\nOut of the 172 Widal’s tests that were done in the private health facility, 44 (25.6%) were reactive and 128 (74.4%) were non-reactive. When compared to the gold standard, culture had 3 (1.7%) S. typhi isolates and 169 (98.3%) did not have any significant growth (Table 2).\n\nThe samples were drawn from 43 private health facilities of which only three (7%) had S. typhi isolated from their referred samples (Figure 2).\n\nS. typhi was isolated more from the male participants (67%, 2/3) as compared to the female counterparts (33%, 1/3). These isolates were mainly obtained from two age groups namely 18-34 years and 35-49 years with more amongst the 18-34 years age group (67%, 2/3). The S. typhi was isolated from three (03) stool samples and none from blood samples.\n\nDiagnostic accuracy study\n\nThis study showed the Widal’s test diagnostic accuracy to be as follows: sensitivity (100%), specificity (76%), positive predictive value (6.8%) and negative predictive value (100%) (Table 2).\n\nDrug sensitivity patterns\n\nThis study showed that the drugs i.e., Chloramphenicol and Augmentin demonstrated resistance each at 67% (2/3). Those that were highly sensitive included Ciprofloxacin and Imipenem each at 100% (3/3). Ceftriaxone 67% (2/3) was intermediate (Table 1).\n\n\nDiscussion\n\nThis study revealed the Widal’s test had a positive predictive value (PPV) of 6.8% implying that, there was a 6.8% probability that the participant with a positive Widal’s test result truly had typhoid fever.8,9 This finding was similar to most of the studies reviewed whose PPV was below 60% with exception of Minjibir (2020) whose PPV was 68.2%.6,10–15 Therefore, the Widal’s test is not dependable for the diagnosis of typhoid fever.14 This study revealed that the Widal’s test had a negative predictive value (NPV) of 100%. This implied that, there was a likelihood that the participant with negative Widal’s test results truly didn’t have typhoid fever.8,9 This finding was similar to most of the studies reviewed whose NPV was above 90% with exception of Mengist (2017) and Mawazo (2019) who obtained 75.2% and 89.7% respectively.6,10–15 Therefore, the Widal’s test result can serve as a good indicator of the absence of typhoid fever.11 This study revealed that the Widal’s test had a sensitivity of 100%. This indicated that, the Widal’s test has the ability to rule out the presence of typhoid fever and this surpasses that of Widal’s test acceptable of 70%.16 This finding was similar to most of studies with exception of Yousif (2018) whose value was 26.5%.6,10–15 This study also revealed that the Widal’s test has a specificity of 76%. This indicated that Widal’s test has the ability to identify positive cases although with a high false positive rate of 93.2% (41/44). This was so probably because typhoid fever is uncommon among the participants hence giving a large proportion of false positive test results and this explains partly why this study’s positive predictive value was low (6.8%).17 This finding was similar to most of the studies reviewed whose value was above 70% specificity with exception of Deksissa and Gebremedhin (2019), Mawazo (2019) and Muthoni (2016) whose values were 44.4%, 18.3% and 47.7% respectively.6,10–15 As described by many scholars, false diagnosis of typhoid fever can lead to an inappropriate treatment which eventually leads to antibiotic resistance development, a serious threat to the global public health which if not addressed in time, may lead to mortality.18,19 This study described the antibiotic sensitivity profile of S. typhi. Chloramphenicol was 67% (2/3) resistant, a finding was similar to Wasihum et al (2015) and Deksissa and Gebremedhi (2019) who reported 76.1% and 20% resistance respectively.11,20 Augmentin was 67% (2/3) resistant, a finding similar to Wasihum et al (2015) and; Deksissa and Gebremedhi (2019) also reported 2.6% and 100% resistance.11,21 This study’s finding was however contrary to Chaudhary et al (2016) who reported Augmentin as 94.3% sensitive.10 This study also revealed that Ciprofloxacin was 100% (3/3) sensitive which finding was contrary to Wasihum et al (2015) who reported (76.1%).21 This study’s finding of Ceftriaxone being 67% (2/3) intermediate was contrary to Deksissa and Gebremedhi (2019) who reported 100% sensitivity.11\n\nThe limitation of this study was the very few S. typhi isolates since this did not provide adequate information on the antibiotic resistance profile of Mbale city. Future studies would increase the scope and study in order to obtain more S. typhi isolates such that adequate information on the antibiotic profile is obtained.\n\n\nConclusion\n\nIn comparison with culture, the gold standard, Widal’s test is highly sensitive (100%) with a low specificity of 76% and PPV (6.8%) and NPV (100%). It should therefore be followed up with a more specific confirmatory test. S. typhi was highly sensitive to both Ciprofloxacin and Imipenem; and resistant Chloramphenicol and Augmentin.\n\nThis study is significant in that, it gives information about how typhoid fever is being managed in private health facilities, act as a basis to develop or re-enforce policies on typhoid fever management, and also act as a reference to other researchers adventuring in the same field of study. Inappropriate typhoid diagnosis in Mbale city private health facilities could lead to inappropriate antibiotic prescription, antibiotic resistance development and death. Conducting this comparative study and determining the antimicrobial sensitivity profile will provide information on typhoid fever management in private health facilities in Mbale city.\n\n\nData availability\n\nThe data that support the findings of this study are available on request from the corresponding author, [SG]. The data are not publicly available because they contain information that could compromise the privacy of research participants. In the event that the reader needs access to the said data, they could do so by writing an email to the corresponding author, [SG] detailing justification for the primary data source request.",
"appendix": "Acknowledgements\n\nThe author(s) would like to thank Makerere University for technical support while conducting the study; and with permission, the author(s) acknowledges the administrative support from Rt. Rev. Patrick Gidudu, DR. Can. Hannah Gidudu, Rev. Prof. Dr. Jeanette Meadway and Mr. John Meadway that facilitated the study. The views expressed in the submitted article are author(s) own and not an official position of the institution.\n\n\nReferences\n\nRadhakrishnan A, Als D, Mintz ED, et al.: Introductory article on global burden and epidemiology of typhoid fever. Vol. 99, American Journal of Tropical Medicine and Hygiene. American Society of Tropical Medicine and Hygiene. 2018 [cited 2021 Feb 23]; p. 4–9. PubMed Abstract | Publisher Full Text Reference Source\n\nCrump JA: Progress in Typhoid Fever Epidemiology. Clin. Infect. Dis. 2019 Feb 15 [cited 2021 Feb 23]; 68(Supplement_1): S4–S9. PubMed Abstract | Publisher Full Text Reference Source\n\nAinebyoona E: Uganda: Why Typhoid Is Still a Problem in Kampala - allAfrica.com. The Monitor news paper.2015 [cited 2017 Mar 12]. Reference Source\n\nWHO Uganda: WHO Uganda Bulletin.2016 [cited 2017 Mar 14]. Reference Source\n\nMinistry of health Uganda: Uganda Clinical Guidelines. Ministry of health Uganda; 2016 [cited 2017 Mar 10]; 1142. Reference Source\n\nMengist HM, Tilahun K, Mihiretie H: Diagnostic Value of Widal Test in the Diagnosis of Typhoid Fever: A Systematic Review. J. Med. Microb. Diagn. 2017 Feb 6 [cited 2018 May 11]; 06(01). Reference Source\n\nKabwama SN, Bulage L, Nsubuga F, et al.: A large and persistent outbreak of typhoid fever caused by consuming contaminated water and street-vended beverages: Kampala, Uganda, January - June 2015. BMC Public Health. 2017; 17(1): 241–320. Publisher Full Text Reference Source\n\nAttia J: Moving beyond sensitivity and specificity: Using likelihood ratios to help interpret diagnostic tests. Vol. 26, Australian Prescriber. NPS MedicineWise. 2003 [cited 2018 May 11]; p. 111–113. Publisher Full Text Reference Source\n\nBentley ERLO: Positive and Negative Predictive Value of Diagnostic Tests: Introduction. Graduate Entry Medical School, University of Nottingham.2014 [cited 2018 May 11]. Reference Source\n\nChaudhary P, Sharma V, Chaudhary A, et al.: Comparative Study of Blood Culture and Widal Agglutination Test from the Patients Suspected of Enteric Fever. Br. Microbiol. Res. J. 2016 Jan 10 [cited 2021 Feb 24]; 16(5): 1–9. Publisher Full Text Reference Source\n\nDeksissa T, Gebremedhin EZ: A cross-sectional study of enteric fever among febrile patients at Ambo hospital: Prevalence, risk factors, comparison of Widal test and stool culture and antimicrobials susceptibility pattern of isolates. BMC Infect. Dis. 2019 Mar 27 [cited 2021 Feb 24]; 19(1): 288. PubMed Abstract | Publisher Full Text\n\nMinjibir AA, Diso SU, Ibrahim IS, et al.: Comparative Study of Widal test Against Stool Culture in Diagnosis of Typhoid Fever Suspected Cases in Kano, Northern Nigeria. South Asian Res. J. Eng. Tech. 2020 [cited 2021 Feb 24]; 2(5): 39–44. Publisher Full Text Reference Source\n\nMawazo A, Bwire GM, Matee MIN: Performance of Widal test and stool culture in the diagnosis of typhoid fever among suspected patients in Dar es Salaam, Tanzania. BMC. Res. Notes. 2019 Jun 5 [cited 2021 Feb 24]; 12(1): 316. PubMed Abstract | Publisher Full Text\n\nMuthoni GC: Performance of Widal’s test and Stool culture as diagnostic methods for Salmonella typhi infectionin Chuka General Hospital, Tharaka Nithi County.2016 [cited 2021 Feb 24]. Reference Source\n\nYousif TAT: Comparison of Widal Test In Diagnosis of Typhoid Fever with Blood Culture and Immuno chromatographic Test among Patients in Wad Medani Teaching Hospital, Gezira State, Sudan (2012-2017).2018 Feb 13 [cited 2021 Feb 24]. Reference Source\n\nTULIP diagnostics: Widal Antigen Set/Antigens for Slide and Tube Tests.2012 [cited 2021 Feb 25]; 1–2. Reference Source\n\nMcNamara LA, Martin SW: Principles of Epidemiology and Public Health. Principles and Practice of Pediatric Infectious Diseases. Elsevier Inc.; 2018; p. 1–9.e1.\n\nEng SK, Pusparajah P, Ab Mutalib NS, et al.: Salmonella: A review on pathogenesis, epidemiology and antibiotic resistance. Frontiers in Life Science. 2015 Jul 3 [cited 2018 Sep 20]; 8(3): 284–293. Publisher Full Text\n\nWatkins RR, Bonomo RA: Overview: Global and Local Impact of Antibiotic Resistance. Vol. 30, Infectious Disease Clinics of North America. Elsevier.2016 [cited 2018 Sep 20]; p. 313–322. Reference Source\n\nElexson N, Rukayadi Y, Nakaguchi Y, et al.: Evaluation of cloves (Syzygium aromaticum) against antibiotics resistant Vibrio parahaemolyticus on seafood. Int. Food Res. J. 2016 Aug 1 [cited 2018 Sep 21]; 23(5): 2229–2233. Reference Source\n\nWasihun AG, Wlekidan LN, Gebremariam SA, et al.: Diagnosis and Treatment of Typhoid Fever and Associated Prevailing Drug Resistance in Northern Ethiopia. Int. J. Infect. Dis. 2015 Jun 1; 35: 96–102. Publisher Full Text"
}
|
[
{
"id": "204934",
"date": "03 Oct 2023",
"name": "Letemichael Negash Welekidan",
"expertise": [
"Reviewer Expertise Microbiologist"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 paper:\nThe article tried to evaluate widal test as a diagnostic test for typhoid fever in private clinics in Mbale, Uganda. The paper mentioned that widal test is not recommended in Uganda for diagnosing typhoid fever due to low positive and negative predictive values but the private clinic in Uganda still uses it. This paper aimed at evaluating widal test and antimicrobial susceptibility test for Salmonella typhi (S.typhi), the causative agent of typhoid fever.\nThe result showed the the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of widal test and the antimicrobial susceptibility pattern of S.typhi.\nQuestions:\nIf widal test is not recommended by the ministry of health of Uganda due to its low PPV and NPV, so what gap are you going to fill from this paper's finding?\n\nWhat technique and what sample have you used for the widal test and how you performed? I could not find it in the paper.\n\nYou have cultured both blood and stool samples, what was the purpose to culture both the samples and how did you present the results for both samples is not clear?\n\nWhat software do you used for analysis of drug susceptibility profile (DST) and participant's data?\n\nIn the result part, it is written that participant age range is 17-50 but figure-1 shows also <17 years. Make a correction or justify it why you put it like that\n\nHow did you calculate the sensitivity, specificity, PPV and NPV?\n\nI suggest reorder the table numbers and correct its citation on the text, and text should be before the table and correct the table for antimicrobial susceptibility profile\n\nFigure captions should be at the bottom of the figure, make corrections to your figure captions.\n\nUse one suitable subtitle under the result part; e.g you used: Comparison of widal test with bacterial culture and under it Occurrence of S.typhi positive participants and same comment for the antimicrobial sensitivity profile\n\nIn the discussion part you did not justify or reason out for the disagreement between your study and other studies when applicable.\n\nIn your introduction it is written that widal test is not recommended by the ministry of health of Uganda but you concluded that widal test should be followed by specific confirmatory test. As the ministry of health is recommended already these specific tests that you are referring for as primary diagnostics, so are you recommending to the policy makers to use widal test or recommending for what they have already recommend? Make it clear.\n\nThere are spelling errors\n\nOver all the paper looks shallow so try to enrich it to make it a good 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? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "11129",
"date": "13 Apr 2024",
"name": "Samuel GIDUDU",
"role": "Author Response",
"response": "If widal test is not recommended by the ministry of health of Uganda due to its low PPV and NPV, so what gap are you going to fill from this paper's finding? The gap to be filled is providing evidence-based information to the policy implementer in order to enforce appropriate diagnostic technique for Typhoid fever in Mbale city What technique and what sample have you used for the widal test and how you performed? I could not find it in the paper. This been made clearer in the newer vision of the article. As quick response, we only retrieved Widal test results from the private health facility. and collected samples for Culture and Sensitivity. Also to mention. We did not interfere with the procedure used at the private health facility but rather requested them to also collect blood for culture in addition to their routine method of Widal testing. You have cultured both blood and stool samples, what was the purpose to culture both the samples and how did you present the results for both samples is not clear? This been made clearer in the newer vision of the article. As quick response, We cultured both blood and stool to widen the scope of investigation of typhoid fever. What software do you used for analysis of drug susceptibility profile (DST) and participant's data? We did not use a software to do the analysis but rather a contingency table that was generated from Epidemiological information (Epi Info) software (version 7). In the result part, it is written that participant age range is 17-50 but figure-1 shows also <17 years. Make a correction or justify it why you put it like that: This has been corrected to read <17 to >50. all persons below 17 years were summed up How did you calculate the sensitivity, specificity, PPV and NPV? We used stardard formulas to calculate these. The formulas have been included in the newer version of the manuscript I suggest reorder the table numbers and correct its citation on the text, and text should be before the table and correct the table for antimicrobial susceptibility profile: This have been addressed in the newer version of the manuscript Figure captions should be at the bottom of the figure, make corrections to your figure captions. This have been addressed in the newer version of the manuscript Use one suitable subtitle under the result part; e.g you used: Comparison of widal test with bacterial culture and under it Occurrence of S.typhi positive participants and same comment for the antimicrobial sensitivity profile This have been addressed in the newer version of the manuscript In the discussion part you did not justify or reason out for the disagreement between your study and other studies when applicable.This have been addressed in the newer version of the manuscript In your introduction it is written that widal test is not recommended by the ministry of health of Uganda but you concluded that widal test should be followed by specific confirmatory test. As the ministry of health is recommended already these specific tests that you are referring for as primary diagnostics, so are you recommending to the policy makers to use widal test or recommending for what they have already recommend? Make it clear. This have been addressed in the newer version of the manuscript There are spelling errors. This have been addressed in the newer version of the manuscript Over all the paper looks shallow so try to enrich it to make it a good paper. This have been addressed in the newer version of the manuscript"
}
]
}
] | 1
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https://f1000research.com/articles/11-319
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https://f1000research.com/articles/13-146/v1
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26 Feb 24
|
{
"type": "Systematic Review",
"title": "Association between angiotensin-converting enzyme (ACE) gene I/D polymorphism with the risk of knee OA: A systematic review, meta-analysis, and meta-regression",
"authors": [
"M. Nasser Mustari",
"Muh. Nasrum Massi",
"Muh. Andry Usman",
"Agussalim Bukhari",
"Irfan Idris",
"Alfian Zainuddin",
"Endy Adnan",
"Syakib Bakri",
"Mizwar Hatta",
"Haerani Rasyid",
"Achmad Fikry",
"Audrey Suryani Soetjipto",
"M. Nasser Mustari",
"Muh. Nasrum Massi",
"Muh. Andry Usman",
"Agussalim Bukhari",
"Irfan Idris",
"Alfian Zainuddin",
"Endy Adnan",
"Syakib Bakri",
"Mizwar Hatta",
"Achmad Fikry",
"Audrey Suryani Soetjipto"
],
"abstract": "Background Previous studies have linked genetics to knee osteoarthritis. Angiotensin-converting enzyme (ACE) gene I/D polymorphism may cause OA. However, evidence remains inconsistent. This study examines knee OA risk and ACE gene I/D polymorphism.\n\nMethods We explored Europe PMC, Medline, Scopus, and Cochrane Library using keywords. Three assessment bias factors were assessed using the Newcastle-Ottawa Scale (NOS). Criteria for inclusion: (1) Split the study population into knee OA patients and healthy controls; (2) Analysed the ACE gene I/D polymorphism; (3) Case-control or cross-sectional surveys. Studies with non-knee OA, incomplete data, and no full-text were excluded. The odds ratio (OR) and 95% confidence intervals (95% CI) were calculated using random-effect models.\n\nResults A total of 6 case-control studies consist of 1,226 patients with knee OA and 1,145 healthy subjects as controls were included. Our pooled analysis revealed that a significant association between ACE gene I/D polymorphism and risk of knee OA was only seen in the dominant (DD + ID vs. II) [OR 1.69 (95% CI 1.14 – 2.50), p = 0.009, I2 = 72%], and ID vs. II [OR 1.37 (95% CI 1.01– 1.86), p = 0.04, I2 = 43%] genotype models. Other genotype models, including recessive (DD vs. ID + II), alleles (D vs. I), DD vs. ID, and DD vs. II models did not show a significant association with knee OA risk. Further regression analysis revealed that ethnicity and sex may influence those relationships in several genotype models.\n\nConclusions Dominant and ID vs. II ACE gene I/D polymorphism models increased knee OA risk significantly. More research with larger samples and different ethnic groups is needed to confirm our findings. After ethnicity subgroup analysis, some genetic models in our study showed significant heterogeneities, and most studies are from Asian countries with Asian populations, with little evidence on Arabs.",
"keywords": [
"ACE",
"genetic models",
"polymorphism",
"osteoarthritis",
"knee"
],
"content": "Introduction\n\nOsteoarthritis (OA) of the knee is the most common type of arthritis involving the knee joint (besides rheumatoid arthritis, post-traumatic arthritis, etc).1 This disease is well-recognized as a major public health problem.1 Epidemiologically, it is estimated that there were around 654.1 million people in the world who experience knee OA in 2020 with a global prevalence of 22.9% in individuals aged 40 years and over.2 Knee OA is also one of the main causes of individual dysfunction/disability which may reduce the quality of life.2 It is estimated that the burden of knee OA will continue to increase, along with increasing age and people with obesity.2\n\nIn knee OA, there is a disintegration of the cartilage structure of the knee joint, which becomes softer and damaged, accompanied by imperfect growth of new cartilage and the formation of osteophytes around the joint.1,3 Apart from increasing age and obesity, joint trauma and excessive workload on the joints are also risk factors for knee OA.2,3 Researchers also found that genetic factors in the form of polymorphism in several genes also play an important role in increasing the risk of knee OA in certain individuals.2,3 Previous research has shown that genetic factors contribute to 35-65% of a person’s overall risk of developing knee OA.4\n\nAngiotensin-converting enzyme (ACE) is a membrane-bound enzyme that catalyzes the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor.5 ACE also metabolizes bradykinin, a strong vasodilator, to its inactive form, namely bradykinin 1-5.5 As an inflammatory vasodilator, bradykinin has an important role in the generation of pain, swelling, and inflammation through its receptors, mainly bradykinin receptor B1 (BKB1).6,7 Bradykinin can promote cartilage degradation and inhibit the synthesis of cartilage proteoglycans and type II collagen which is the main components of the extra-cellular matrix (ECM) in articular cartilage.6,7 Considering the important role of ACE in the renin-angiotensin system (RAS) and inactivation of bradykinin, some evidence suggests the possibility of ACE polymorphism in causing OA.8 The ACE gene is located on chromosome 17 and contains a polymorphism based on the presence (insertion, I) or absence (deletion, D) of intron 16, of a 287 bp ALU repeat sequence; resulting in three genotypes: DD and II homozygotes and ID heterozygotes.9,10 ACE levels in plasma were found to be highest in individuals with the DD genotype and lowest in individuals with the II genotype.9,10\n\nUnfortunately, previous studies still showed conflicting results on the relationship between ACE gene I/D polymorphism and the risk of knee OA. In their study of the Korean population, Hong SJ et al.11 demonstrated that ACE gene I/D polymorphism, especially the I allele, is associated with early onset and radiographically severe knee OA. On the other hand, Shehab DK et al.12 found no association between ACE gene I/D polymorphism genotype and primary knee OA in Kuwaiti patients. Therefore, this systematic review and meta-analysis aims to summarize evidence regarding the relationship between ACE gene I/D polymorphism and the risk of knee OA.\n\n\nMethods\n\nThis review was written based on the guidelines from the PRISMA statement.13 We selected the literature for inclusion in this review if it met the following inclusion criteria: (1) The population of the study was divided into two groups, namely those with knee OA and healthy controls (without knee OA); (2) Analysed the ACE gene I/D polymorphism, which may be in the form of major (I) and minor (D) alleles as well as the distribution of genotype variations (DD, ID, and II) in both groups of patients; (3) Case-control studies or cross-sectional surveys. Meanwhile, literature in which one or more of the following exclusion criteria were fulfilled were removed from this review: (1) Studies involving OA other than knee; (2) Incomplete data; (3) Not available in the full-text form; (4) Studies beside case-control and cross-sectional.\n\nA systematic literature search on 4 databases: Europe PMC, Medline, Scopus, and the Cochrane Library was conducted by two independent authors from the date of inception until January 12th, 2023. The search was limited to English-language literature only. We used the following keyword combinations to elicit relevant literature: “(knee osteoarthritis OR OA knee OR gonarthrosis OR osteoarthritis genu OR OA genu) AND (Angiotensin Converting Enzyme OR Angiotensin I-Converting Enzyme OR ACE OR Peptidyl-Dipeptidase A OR Dipeptidyl Peptidase A OR Kininase A OR Kininase II) AND (polymorphism OR insertion/deletion OR I/D)”. The process of identifying relevant literature through titles/abstract screening and duplicate removal was carried out by the same two authors. If the articles passed the screening process, they were evaluated in full-text format to match the eligibility criteria. All discrepancies in this review were resolved through discussion.\n\nThe data extraction and tabulation into Microsoft Excel 2019 were carried out by two independent authors. The data extracted were as follows: author’s name, year of publication, country, number of samples, baseline characteristics of study participants, and distribution of ACE genotype variations or alleles in each patient group.\n\nThe same two authors also performed a risk of bias assessment of the included case-control studies using the appropriate tool. We used the Newcastle-Ottawa Scale (NOS) which covers three aspects of assessment: (1) selection of cases and appropriate controls; (2) comparability between two groups of participants; (3) measurement of the exposure.14 The results of the evaluation using this tool were in the form of numbers from 0 to 9 where studies with a total score of ≥7 were categorized as “good” quality.14\n\nDichotomous variable outcomes were computed in the form of odds ratio (OR) along with 95% confidence intervals (95% CI) using the Mantel-Haenszel formula to compare the ACE gene I/D polymorphism between the two groups of patients. Random-effect models were chosen in this review because of the consideration that significant heterogeneity was expected due to differences in the population characteristics. Three common genetic models (dominant, recessive, and allele type) and three additional genotype models comparison (DD vs. DI, DD vs. II, and DI vs. II) were chosen to comprehensively assess the relationship between ACE gene I/D polymorphism and risk of knee OA. In this review, we used the I-squared (I2) statistic to assess the heterogeneity between studies where I2 values of ≤25%, 26 – 50%, and >50% were categorized as low, moderate, and high heterogeneity, respectively.15 Meta-regression with a random-effects model was performed using a restricted-maximum likelihood for pre-specified variables including ethnicity, sample size, age, sex, BMI, Kellgren-Lawrence grade, and duration of OA to see the interaction effect between ACE gene I/D polymorphism, and these variables in influencing the risk of knee OA. A publication bias analysis was performed when there were more than 10 studies on each outcome of interest. All of these statistical analyses were carried out using an application from the Cochrane Collaboration, namely Review Manager 5.4 and Comprehensive Meta-Analysis version 3.\n\n\nResults\n\nA literature search of the four databases yielded a total of 372 studies. After eliminating duplicates and screening articles based on their titles/abstracts, 359 studies were excluded and 13 were left for full-text assessment. Of these 13 studies, 7 studies were further excluded for the following reasons: 3 studies did not have the suitable outcome of interest data, 1 study involved a mixed OA population, 1 study conducted an assessment on different alleles of ACE, 1 study was a literature review, and 1 study was only available in abstract form. Ultimately, there were 6 studies11,12,16–19 included in the final analysis with 1,226 patients with knee OA and 1,145 healthy subjects as controls (Figure 1). All included studies had a case-control design. The countries of origin of each included study were China, Taiwan, South Korea, India, Turkey, and Kuwait. For analysis purposes, studies originating from China, Taiwan, South Korea, and India were grouped into the Asian ethnicity group while studies originating from Turkey and Kuwait were grouped into the Arab ethnicity group. Further details regarding the baseline characteristics of the included studies were summarized in Table 1.\n\nBased on the results of the study quality assessment using the NOS tool, it was found that all included case-control studies had “good quality” so they were deemed worthy of being included in the meta-analysis. A summary of the assessment of study quality is presented in Table 2.\n\na (1) representativeness of the exposed cohort; (2) selection of the non-exposed cohort; (3) ascertainment of exposure; (4) demonstration that outcome of interest was not present at start of study.\n\nb (1) comparability of cohorts on the basis of design or analysis, (maximum two stars).\n\nc (1) assessment of outcome; (2) was follow-up long enough for outcomes to occur; (3) adequacy of follow up of cohorts.\n\nDominant (DD + ID vs. II)\n\nBased on our pooled analysis of 6 studies (n = 2,367), it has been shown that the dominant model of ACE gene I/D polymorphism (DD + ID vs. II) was associated with a higher risk of developing knee OA [OR 1.69 (95% CI 1.14 – 2.50), p = 0.009, I2 = 72%, random-effect models] (Figure 2A). However, subgroup analysis based on ethnicity revealed that a statistically significant association was only observed in the Arab ethnicity subgroup (p = 0.03), but not in the Asian ethnicity subgroup (p = 0.08) (Figure 2A).\n\nRecessive (DD vs. ID + II)\n\nBased on our pooled analysis of 6 studies (n = 2,269), it has been shown that the recessive model of ACE gene I/D polymorphism (DD vs. ID + II) was not associated with knee OA risk [OR 1.26 (95% CI 0.82 – 1.94), p = 0.30, I2 = 78%, random-effect models] (Figure 2B). A non-significant association was also observed both in the Asian ethnicity (p = 0.41) and Arab ethnicity subgroups (p = 0.64) (Figure 2B).\n\nAlleles (D vs. I)\n\nOur meta-analysis from a total of 6 studies (n = 4,328) showed that neither alleles of ACE gene I/D polymorphism (D vs. I) was associated with the risk of knee OA [OR 1.25 (95% CI 0.95 – 1.65), p = 0.11, I2 = 75%, random-effect models] (Figure 2C). A non-significant association was also observed both in the Asian ethnicity (p = 0.12) and Arab ethnicity subgroups (p = 0.67) (Figure 2C).\n\nDD vs. ID\n\nOur meta-analysis from a total of 6 studies (n = 1,690) showed that the genetic model comparing DD with ID genotypes of ACE gene I/D polymorphism was not associated with the risk of knee OA [OR 1.12 (95% CI 0.76 – 1.64), p = 0.57, I2 = 65%, random-effect models], and the results remained consistent for both subgroups of ethnicity (p for Asian = 0.58; p for Arab = 0.95) (Figure 3A).\n\nDD vs. II\n\nOur meta-analysis from a total of 6 studies (n = 1,349) showed that the genetic model comparing DD with II genotypes of ACE gene I/D polymorphism was not associated with the risk of knee OA [OR 1.63 (95% CI 0.87 – 3.03), p = 0.12, I2 = 83%, random-effect models], and the results remained consistent for both subgroups of ethnicity (p for Asian = 0.27; p for Arab = 0.46) (Figure 3B).\n\nID vs. II\n\nOur meta-analysis from a total of 6 studies (n = 1,349) showed that the genetic model involving ID and II genotypes of ACE gene I/D polymorphism was associated with a higher risk of knee OA [OR 1.37 (95% CI 1.01 – 1.86), p = 0.04, I2 = 43%, random-effect models], but the results remained significant only for Asian ethnicity subgroup (p = 0.03), and not for Arab ethnicity subgroups (p = 0.32) (Figure 3C).\n\nThe summary of the results from the meta-regression analysis of several factors that may influence the relationship between ACE gene I/D polymorphism and knee OA is summarized in Table 3. From the results of the meta-regression analysis, it was found that ethnicity (Asian as reference) (p = 0.0461) has a significant effect on the relationship between ACE gene I/D polymorphism and knee OA risk in the dominant model (DD + ID vs. II). In addition, our regression analysis also showed that sex is an important variable that significantly influences the risk of knee OA in 3 genetic models of ACE gene I/D polymorphism, namely recessive (DD vs. ID + II) (p = 0.0378), alleles (D vs. I) (p = 0.0060), and DD vs. DI models (p = 0.0332). Other factors, such as sample size from included studies, age, and BMI did not significantly influence the relationship between ACE gene I/D polymorphism and the risk of knee OA.\n\nThe number of studies for each outcome of interest in this review is less than 10 studies where funnel plots and statistical tests to detect publication bias are less reliable,20,21 so publication bias analysis was not performed in this study.\n\n\nDiscussion\n\nBased on the results of our meta-analysis, it has been shown that the genetic models of ACE gene I/D polymorphism that play a significant role in the risk of knee OA were only seen in the dominant (DD + ID vs. II) model for Arab ethnicity population and ID vs. II models for Asian ethnicity population. Other genetic models of ACE gene I/D polymorphism, such as recessive (DD vs. ID + II), alleles (D vs. I), DD vs. ID, and DD vs. II models did not show a significant relationship with the risk of knee OA, both in Asian ethnicity and Arab ethnicity subgroups. Further regression analysis also showed that ethnicity and sex were variables that significantly influenced the risk of knee OA in several genetic models.\n\nThe results of our meta-analysis are similar to the previous meta-analysis written by Lin C et al.18 In their meta-analysis of 6 studies, Lin C et al.18 showed that the relationship between ACE gene I/D polymorphism and knee OA were only seen in the dominant (DD + ID vs. II) and ID vs. II genetic models. Other genetic models did not show a significant relationship with knee OA risk. Nonetheless, there are some differences between the meta-analyses by Lin C et al.18 with our current meta-analysis.\n\nFirst, although the total number of included studies is the same (6 studies), Lin C et al.18 have mistakenly included the study by Inanir A et al.22 which includes not only the population of patients with knee OA but also patients with hip and hand OA. This of course contradicts the title and eligibility criteria of the study by Lin C et al.18 which stated that only knee OA studies would be included in the analysis. In addition, including studies with different populations of patients (patients with osteoarthritis other than knee) is inappropriate according to the Cochrane Handbook for Systematic Review because it will also have an impact on the increased heterogeneity between studies.23 On the other hand, we fully adhere to the Cochrane guidelines where only studies with knee OA population were included in the analysis and discarded the study by Inanir A et al.22 Instead, we included 1 additional study by Chen G et al.17 published in 2019 which was not included in the previous meta-analysis by Lin C et al.18\n\nSecond, the previous meta-analysis by Lin C et al.18 involved 4 variables namely ethnicity, sex, age, and BMI in the meta-regression analysis. However, the sex variable was only analyzed as a categorical moderator (female or male) and the age and BMI variables were only calculated based on a certain number of multiplications (every 10 years for age and every 5 kg/m2 for BMI).18 This certainly can have an impact on the lack of accuracy within the results from the meta-regression analysis of this variable. In contrast, in our meta-regression analysis, the variable sex was calculated as male sex prevalence and the variable age and BMI were not calculated based on multiples of certain numbers but based on their true values so that any addition or reduction in the value of the variable, even it is small, is still meaningful. By doing this, we have found that sex influenced the relationship between ACE gene I/D polymorphism and knee OA risk in recessive (DD vs. ID + II), alleles (D vs. I), and DD vs. ID genetic models, a result not found in the previous meta-analysis. Our study also added the sample size variable to the regression analysis so that a total of 5 variables were analyzed further.\n\nOur study is certainly not without some limitations. Notable heterogeneities were identified in some of the genetic models in our study, even after subgroup analysis based on ethnicity, which is difficult to explain. The total number of studies included in our analysis is also relatively small due to limited evidence regarding ACE gene I/D polymorphism on knee OA risk. The majority of the included studies also come from Asian countries with populations of Asian ethnicity and only a portion of the studies involve populations of Arab ethnicity. Data regarding other ethnicities, such as Caucasian, Hispanic, and Black so far cannot be found so they cannot be analyzed further, and thus, the results from this study are also not necessarily applicable to those ethnicities.\n\n\nConclusion\n\nOur systematic review and meta-analysis suggest that only the dominant (DD + ID vs. II) model of ACE gene I/D polymorphism in Arab populations and the ID vs. II models of ACE gene I/D polymorphism in Asian populations have a significant association with a higher risk of knee OA. Other genetic models of ACE gene I/D polymorphism, including recessive (DD vs. ID + II), alleles (D vs. I), DD vs. ID, and DD vs. II were not associated with the risk of knee OA. Further studies with larger sample sizes and involving different ethnic groups are still needed to confirm the results of our study.\n\nThis review was registered on PROSPERO ID CRD42023398472 (Association between Angiotensin-Converting Enzyme (ACE) gene I/D polymorphism with the risk of knee OA).",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required. Data analyzed in this study were a re-analysis of existing data, which are openly available at locations cited in the reference section.\n\nFigshare: PRISMA_2020_abstract_checklist.pdf, https://doi.org/10.6084/m9.figshare.25019756.v2. 24\n\nThis project contains the following extended data:\n\n• repository.xlsx (characteristics of all articles included in the research; forest plot data for Figures 2 and 3).\n\nFigshare: PRISMA checklist for ‘Association between angiotensin-converting enzyme (ACE) gene I/D polymorphism with the risk of knee OA: A systematic review, meta-analysis, and meta-regression’, https://doi.org/10.6084/m9.figshare.25019756.v2. 24\n\n\nReferences\n\nSharma L: Osteoarthritis of the Knee. N. Engl. J. Med. 2021 Jan 7; 384(1): 51–59. Publisher Full Text\n\nCui A, Li H, Wang D, et al.: Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020 Nov 26; 29-30: 100587. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSilverwood V, Blagojevic-Bucknall M, Jinks C, et al.: Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthr. Cartil. 2015 Apr; 23(4): 507–515. PubMed Abstract | Publisher Full Text\n\nFernández-Moreno M, Rego I, Carreira-Garcia V, et al.: Genetics in osteoarthritis. Curr. Genomics. 2008 Dec; 9(8): 542–547. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChang Y, Wei W: Angiotensin II in inflammation, immunity and rheumatoid arthritis. Clin. Exp. Immunol. 2015 Feb; 179(2): 137–145. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDe Falco L, Fioravanti A, Galeazzi M, et al.: Bradykinin and its role in osteoarthritis. Reumatismo. 2013 Jul 23; 65(3): 97–104. PubMed Abstract | Publisher Full Text\n\nMeini S, Maggi CA: Knee osteoarthritis: a role for bradykinin? Inflamm. Res. 2008 Aug; 57(8): 351–361. PubMed Abstract | Publisher Full Text\n\nWu Y, Lu X, Li M, et al.: Renin-angiotensin system in osteoarthritis: A new potential therapy. Int. Immunopharmacol. 2019 Oct; 75: 105796. PubMed Abstract | Publisher Full Text\n\nYigit S, Inanir A, Tural S, et al.: Association of angiotensin converting enzyme (ACE) gene I/D polymorphism and rheumatoid arthritis. Gene. 2012 Dec 10; 511(1): 106–108. PubMed Abstract | Publisher Full Text\n\nUppal SS, Haider MZ, Hayat SJ, et al.: Significant association of insertion/deletion polymorphism of the angiotensin-converting enzyme gene with rheumatoid arthritis. J. Rheumatol. 2007 Dec; 34(12): 2395–2399. PubMed Abstract\n\nHong SJ, Yang HI, Yoo MC, et al.: Angiotensin converting enzyme gene polymorphism in Korean patients with primary knee osteoarthritis. Exp. Mol. Med. 2003 Jun 30; 35(3): 189–195. PubMed Abstract | Publisher Full Text\n\nShehab DK, Al-Jarallah KF, Alawadhi AM, et al.: Prevalence of angiotensin-converting enzyme gene insertion-deletion polymorphism in patients with primary knee osteoarthritis. Clin. Exp. Rheumatol. 2008 Mar-Apr; 26(2): 305–310. PubMed Abstract\n\nPage MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29; 372: n71. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStang A: Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur. J. Epidemiol. 2010 Sep; 25(9): 603–605. PubMed Abstract | Publisher Full Text\n\nHiggins JP, 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\nBayram B, Sayın E, Güneş HV, et al.: DD genotype of ace gene I/D polymorphism is associated in a Turkish study population with osteoarthritis. Mol. Biol. Rep. 2011 Mar; 38(3): 1713–1716. PubMed Abstract | Publisher Full Text\n\nChen G, Hu S, Lai Z, et al.: Association between ACE gene I/D polymorphism and knee osteoarthritis in a Chinese population. Biosci. Rep. 2019 Feb 26; 39(2): BSR20181713. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLin C, Chen HC, Fang WH, et al.: Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis. PLoS One. 2016 Sep 22; 11(9): e0161754. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPoornima S, Subramanyam K, Khan IA, et al.: The insertion and deletion (I28005D) polymorphism of the angiotensin I converting enzyme gene is a risk factor for osteoarthritis in an Asian Indian population. J. Renin-Angiotensin-Aldosterone Syst. 2015 Dec; 16(4): 1281–1287. PubMed Abstract | Publisher Full Text\n\nThornton A, Lee P: Publication bias in meta-analysis: its causes and consequences. J. Clin. Epidemiol. 2000 Feb; 53(2): 207–216. Publisher Full Text\n\nTerrin N, Schmid CH, Lau J, et al.: Adjusting for publication bias in the presence of heterogeneity. Stat. Med. 2003 Jul 15; 22(13): 2113–2126. Publisher Full Text\n\nInanir A, Yigit S, Tural S, et al.: MTHFR gene C677T mutation and ACE gene I/D polymorphism in Turkish patients with osteoarthritis. Dis. Markers. 2013; 34(1): 17–22. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHiggins JPT, Thomas J, Chandler J, et al.: Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane; 2022. Reference Source\n\nRasyid H: PRISMA_2020_abstract_checklist.pdf. [Dataset]. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "252578",
"date": "29 Apr 2024",
"name": "Nata Pratama Hardjo Lugito",
"expertise": [
"Reviewer Expertise Internal medicine",
"clinical epidemiology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe systematic review, meta-analysis, and meta-regression manuscript was well written according to the PRISMA guidelines. There are some data that need clarification.\nThe total number of sample. In the result section, study selection and characteristics subsection it was written that the sample was 1,226 patients with knee OA and 1,145 healthy subjects as controls, making a total of 2,371. In the result section, classical model subsection, Dominant (DD + ID vs. II) it was written that the total number of sample was 2,367. Which one is the correct number? In the figure 2B, the Arab ethnicity was written as Non-Asian ethnicity. Please correct\nIn the discussion, the authors mentioned that their study’s results was similar to the previous meta-analysis written by Lin C et al. Yet the authors, explained the difference between their study compared to Lin’s study. The authors should explain how the differences could still resulted in similar results. The authors should put more emphasise on their results and discuss the impact of ACE gene I/D polymorphism on the pathogenesis, therapy, and prognosis of knee OA, rather than making critical analysis on Lin’s study. The authors should also try to explain how ethnicity, age, sex, BMI, Kellgren-Lawrence grade, and duration of OA interact with the ACE gene I/D polymorphism.\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",
"responses": []
},
{
"id": "252579",
"date": "10 May 2024",
"name": "Yoyos Dias Ismiarto",
"expertise": [
"Reviewer Expertise Orthopedics",
"Arthritis",
"Degenerative Disease",
"Osteoarthritis",
"Traumatology"
],
"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\nMajor comment: The study's results are significant in that they contribute to the understanding of the genetic factors involved in the development of knee OA and may have implications for the prevention and treatment of the disease. However, there are some data that need clarification: 1. **Sample Size Discrepancy**: The total number of samples is reported as 2,371 in the study selection and characteristics subsection, but as 2,367 in the classical model subsection.\n\n2. **Focus on Results and Implications**: The authors should also explore how factors interact with the ACE gene I/D polymorphism to influence the outcomes of knee OA. This would provide a more comprehensive understanding of the genetic and environmental factors involved in the disease.\n\nMinor comment: This manuscript presents a comprehensive analysis of the relationship between the angiotensin-converting enzyme (ACE) gene I/D polymorphism and the risk of knee osteoarthritis (OA). The meta-analysis was well written according to the PRISMA guidelines. The authors also provide a comprehensive summary of the existing literature on the topic, highlighting the strengths and limitations of previous studies\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-146
|
https://f1000research.com/articles/13-145/v1
|
23 Feb 24
|
{
"type": "Study Protocol",
"title": "A study on awareness of breast cancer and breast self-examination practices among women above 35 years of age in rural areas of Wardha District, Maharashtra: a protocol",
"authors": [
"Mithila Koreti",
"Pramita Muntode",
"Pramita Muntode"
],
"abstract": "Background Breast cancer is a major cause of morbidity and mortality in women and a global health issue. Breast self-examination (BSE) is a recommended breast cancer screening technique that a woman can use on her own, in the privacy of her home. Hence, awareness regarding it and knowledge to identify any changes will be a boon to the early identification and promotion of treatment. This study aimed to increase awareness and educate women about breast self-examination (BSE) to facilitate the early detection of breast cancer in rural areas of Wardha District.\n\nMethods A community-based cross-sectional study was conducted on rural women in Wardha district. Women older than 35 years of age will be included in the study and assessed using a ‘pre-designed’ and ‘pre-structured’ questionnaire inquiring about their socio-demographic profile, awareness of breast cancer, and breast self-examination.\n\nResearch implications Most studies show how to self-examine breasts, but awareness and knowledge regarding the subject are not well demonstrated and applied in many studies. Although we now understand that women do not always need to use a specific BSE technique, they should still be taught and encouraged to recognize breast changes. BSE for early detection of breast cancer has undergone a paradigm change or development into breast awareness. The progression towards breast awareness is a concept where a woman is familiar with her breasts so that she detects any change that might emerge and brings this to the attention of her healthcare practitioner right away, whereas BSE is monthly palpation of the breasts in a specific manner in which women are professionally taught. Early detection of breast cancer relies heavily on breast awareness, which is why it should be covered in general breast health education.",
"keywords": [
"Breast self-examination",
"Knowledge",
"Practice",
"Awareness",
"adult women",
"breast cancer",
"breast health."
],
"content": "Introduction\n\nCancer is a disease that causes the majority of fatalities worldwide.1 Among women, breast cancer is a leading cause of death and a major health concern worldwide.2 2.1 million women globally are affected by this, the most prevalent cancer among women annually, and is expected to affect over 3.2 million new cases annually by 2050. Breast cancer is a disorder in which cells in the breast start locally and then spread, resulting in the development of a malignant tumor.3,4 Self-examination of the breasts and research indicate that breast cancer is a widespread health issue and prevalent in all types of cancer and tumors in women worldwide, even in developed and undeveloped nations.5,6\n\nAccording to estimates, 8.3% of all fatalities in India are caused by cancer, which affects an estimated 2.25 million people. Between 1990 and 2016, the incidence and mortality of cancer more than doubled in India, significantly increasing the number of deaths and disability-adjusted life-years (DALYs).7\n\nBreast cancer is the uncontrolled growth of unfavourable cells in the glands that produce milk in the breast or milk ducts, leading to the nipples.8 Breast self-examination (BSE), clinical breast examination, and physical examination of the breasts by a doctor or other licensed health care practitioners are some of the most important ways to detect breast cancer early. Mammography is one of the most important tools for this purpose. Breast self-examination is advised by the American College of Obstetricians and Gynaecologists (ACOG) for females, to report any changes and educate themselves on the benefits and limitations of breast self-examination (BSE). They also advised women to be conscious of their breasts.9 BSE is one of numerous screening techniques for the detection of breast cancer. Breast self-examination (BSE) can aid in the detection of lumps, tumours, cysts, and other abnormalities. Two or more are clinical evaluations and radiological analyses.10 is to reduce women’s breast cancer morbidity and mortality.11 The most recent nationally available data indicate that breast cancer affects 100,000 women on average around the age of 33.21. If a woman lacks access to another screening technique such as mammography, it is helpful for her to self-examine her breasts before having a doctor look at them.12 Women should begin self-examination of their breasts at the age of 20, even during pregnancy and beyond menopause.13\n\nWomen can use the BSE, a screening method at home. It is an easy, inexpensive, and straightforward technique. BSE enhances the likelihood that women will receive treatment, increasing their chance of survival for any physical or obvious changes, and allows women to examine their breast tissue using this simple, affordable, and simple procedure. Women may have received health information regarding the causes, prevention, and appropriate BSE treatment through hands-on seminars and handouts.14 Breast cancer at younger ages may be symptomatic of genetic abnormalities such as BRCA1/2. According to recent studies, BRCA mutations are more common than expected among African American 45 age group women, who are diagnosed with breast cancer. Women who seek genetic counseling can better understand their hereditary risk for breast cancer and decide whether genetic testing is necessary to identify hereditary linked genetic abnormalities.15\n\nThe breast self-examination gives each woman control over her health and awareness of how her breasts feel. BSE benefits women in two ways: first, it helps them become accustomed to how their breasts feel and appear, and second, it helps them identify any breast changes as soon as they can. According to research, 90% of the time, people learn that they have breast cancer. According to numerous studies, it is also possible to circumvent barriers to detection and treatment by taking advantage of and decreasing the awareness of breast cancer.16\n\nPremenopausal women are frequently told to associate their “BSE day” with the beginning of their menstrual cycle. The only instruction given to postmenopausal women was to perform a self-examination on a specific date each month. The rules of the technique were established without considering the ideal.17 Therefore, increasing breast cancer awareness and breast self-examination (BSE) techniques can be effectively achieved in females through educational programs.18\n\nBreast self-examination and the causes of breast cancer are issues that have received less attention and affect women’s health. The study has taken place to find knowledge regarding their consequences on health around rural women and the impact of the structure and to spread the word about BSE. Monthly breast self-examination is a crucial step in the early diagnosis of breast cancer. Additionally, treatment is typically more effective if the cancer is found early.\n\nAdditionally, breast self-examinations are a cost-free procedure used by each woman, regardless of age, to learn more about the normal feel and appearance of your breasts. It is also possible to discover what women in the community know, think, and do about BSE.\n\nThis study aims to evaluate the awareness and practice of breast self-examination for the early detection of breast cancer in adult women of Wardha District.\n\n\n\n1. To record the sociodemographic profile of adult women above 35 years of age in a selected rural area of Wardha District.\n\n2. To find more about women’s knowledge, attitudes, and practices regarding breast self-examination (BSE).\n\n3. To determine awareness about breast cancer in rural women.\n\n\nMethods\n\nThis study will be performed as a cross-sectional study of women aged over 35 years in a rural area in the Wardha district of Maharashtra.\n\nA study will be conducted in the Community Medicine Department of the field practice region. under the auspices of Datta Meghe Institute of Higher Education and Research.\n\nThe study participants will be adult women aged 35 years and above who live in the rural areas of Wardha Maharashtra. We will provide them a thorough explanation of the research and goals of the study, as well as information on how they will profit from it and what they will learn in the end. And we will ensure them that your responses were remain anonymous and kept confidential throughout the research.\n\nInclusion criteria\n\nThe study will include all women over 35 years of age who are willing to participate. and the residents of the village.\n\nExclusion criteria\n\n1. Those women below 35 years of age are not a part of this study.\n\n2. Migratory populations are excluded.\n\n3. Suffering from any chronic psychosocial illness patients are also excluded from the study.\n\n4. Who are hesitant and Unwilling participate to take part in the study will be excluded.\n\nAs shown in Table 1, the variables assessed will be:\n\n1. Sociodemographic profile.\n\n2. Knowledge about breast cancer.\n\n3. Knowledge and practice about breast cancer Screening.\n\n\n\n• Age\n\n• Education\n\n• Type of family\n\n• Economic Status\n\n• Marital status\n\n• Married\n\n• Signal/unmarred\n\n• Widower\n\n\n\n• Selected Village area in Wardha district. (Study participant are women above 35 years of age)\n\n\n\n• Knowledge about breast cancer\n\nLine listing of all the adult women in the selected village will be done with the assistance of the local ASHA and Anganwadi workers.\n\nThe residential area nearest Anganwadi was the starting point. A house-to-house survey using a pre designed and pre-structured questionnaire was conducted.19,24 The questionnaire will be administered in a local language to facilitate the participants.\n\nCollected data will be put into an MS Excel sheet and analyzed using statistical production and service solution (SPSS) version 25 statistical software. Standard deviation and mean were used to summarize the descriptive statistics for continuous variables, while frequency and percentage were used to describe the descriptive statistics for categorical data. The Chi-square test was used to compare categorical data.\n\nSocial desirability as Breast examination is a very intimate matter.\n\nAll research volunteers will get assistance and have their privacy protected during the BSE, which will take place in a private room.\n\nThe sample size was calculated by using this formula:\n\nAlpha (α) = 0.05\n\nEstimated proportion (p) = 0.1054\n\nEstimation error (d) = 0.05\n\nMinimum sample size needed = 145\n\nThe collected data were transferred to an MS Excel sheet and analyzed using statistical production and service solution (SSPS) version 25 statistical software. Mean and standard deviation were used to summarize the descriptive statistics for continuous variables, while frequencies and percentages were used to describe the descriptive statistics for categorical data. Categorical data were compared using the chi-squared test.\n\nThis study will help to understand the awareness of BSE women in the community. In this study, we can help women through BSE prevention and protection, which is an affordable, easy, and noninvasive method for the early detection of breast tumours in women. Thus, knowledge of the procedure and consistent practice could protect women from severe morbidity and mortality due to breast cancer. and improves quality of life.\n\nWe are currently in the process of tool making, and Kobo Tool Box (ver. 2020.4.4.9/3/2023) is being used to complete the questionnaire.\n\n\nDiscussion\n\nIn 2015, Gangane et al. conducted a cross-sectional study on “Women’s Knowledge, Attitudes, and Practises about Breast Cancer in a Rural District of Central India” located in the Wardha district of Central India Maharashtra. The sample comprised 1000 women aged 13 to 50 years, and urban and rural women made up less than 7% of those who had heard about breast self-examination, according to the statistics, yet nearly two-thirds of these women knew about breast cancer. Women in both rural and urban areas have little understanding of breast cancer. Compared to their counterparts in rural areas, urban women exhibited more positive attitudes toward breast cancer screening treatments. Self-examination of the breasts is rarely done, although there is a lot of openness to learning. Positive screening attitudes offer the opportunity to encourage breast self-examination.20\n\nAkanksha Pal et al. Through their review-based study titled (2021) “Knowledge, Attitude, and Practise Towards Breast Cancer and Its Screening Among Women in India: A Systematic Review to learn how Indian women feel about breast cancer screening. Fifteen studies that included observational data were chosen, totaling 7545 women between the ages of 14 and 75 years. The study participants included medical professionals, women from rural and urban areas, and members of the public. The range of illiteracy among women was 5.6%–42.8%, and the majority of them were married. The estimated awareness of breast cancer is 62.99%. In the majority of studies under consideration, a connection was found between participants’ educational level, marital status, age, and knowledge of breast cancer.21\n\nDadzi R, Adam A (2019), A cross-sectional study on “Assessment of knowledge and practice of breast self-examination among reproductive age women in the Ghanaian Volta region’s Akatsi South area” 385 women between the ages of 15 and 49 made up the sample. Only 94 (37.2%) of the respondents practiced BSE and only 64.9% of those surveyed reported having adequate awareness of breast cancer, even though 88.3% of respondents knew about breast cancer. Over half of the interviewees were unable to execute the BSE.22\n\nRumpa Sarker et al. (2022), “Effectiveness of educational intervention on breast cancer knowledge and breast self-examination among female university students in pre-post experimental research in Bangladesh,” This study evaluated the experiences of Bangladeshi young female students in the university. An educational intervention strategy was favorably received by people who were aware of breast cancer and had completed breast self-examinations. People who have conducted breast self-examinations and are aware of breast cancer react favorably to an educational intervention plan. After the educational intervention, there were discernible increases in the awareness and comprehension of BSE practices and breast cancer. The study’s results demonstrated that the study participants’ baseline knowledge and awareness were low; however, after receiving instruction, they significantly improved.18 Shubhangini Sachdeva et al. (2021). “Breast Self-Examination Knowledge, Attitude, and Practises Among Indian Women: A Pan-India Study” Despite becoming proficient with BSE, the respondents had a bad opinion of it and were reluctant to utilize it. In total, 54.4%, 15.1%, 21.3%, and 9.2% of respondents were from India’s north, south, west, and east regions, respectively.23\n\nKumarasamy et al. (2017), The sample for the study, “Determinants of Awareness and Practice of Breast Self-Examination Among Rural Women in Trichy, Tamil Nadu,” consisted of 200 women. The study sample had a mean age of 36.9 ± 8.8 years. Literate individuals accounted for 80% of the total population. Of 178 women, 89% were aware of them knew about breast cancer.5\n\nBreast cancer is the most common malignancy in women in India. Early diagnosis of breast cancer is facilitated by regular BSE, which improves health results and chances of survival. The purpose of this study was to determine the association between sociodemographic trials, breast cancer awareness, and the behavioral stage of BSE adoption.\n\nThis study demonstrates that women in rural Wardha District have less knowledge of BSE practices. The factors that predicted whether women would use BSE were their knowledge of how to execute it when and where to perform it, and their perception of its importance and value in detecting breast cancer. Health professionals and other interested parties should create educational initiatives that can improve young females’ understanding and familiarity with BSE.\n\nThe limitation of the study is that this study will be conducted in only a few villages of wardha District Maharashtra that comes under the filed practice area of community department of DMIHER. As a result, the study’s findings wil not be comparable to findings from a region with a higher population, and its external validity is constrained. And we cannot take it as a whole District result. It is unclear whether they will actually perform the right procedure or whether they will do so regularly, which will elicit honest responses from the people and help them self-examine their breasts.\n\nThis study will raise awareness of breast cancer among rural women. Although we now understand that women do not always need to use a specific BSE technique, they should still be taught and encouraged to recognize breast changes. BSE for early detection of breast cancer has undergone a paradigm change or development into breast awareness. The progression toward breast awareness is a concept where a woman is familiar with her breast so that she detects any change that might emerge and brings this to the attention of her healthcare practitioner right away, whereas BSE is monthly palpation of the breasts in a specific manner in which women are professionally taught. Early detection of breast cancer relies heavily on breast awareness, which is why it should be covered in general breast health education. Additional studies are required to determine the efficacy of breast self-examination in lowering breast cancer mortality, and the various programmatic ways that could be used if it is found to be so.\n\nThe Datta Meghe Institute of Higher Education and Research’s institutional committee approved the study protocol (Reference Number: DMIHER (DU)/IEC/2023/642) on 2nd November 2023.\n\nAdditionally, prior to starting the study, we will obtain written informed consent that expressly assures them that this research is being conducted so that they can assess the level of awareness among women over 35 years of breast cancer and breast self-examination in order to take the necessary action in this regard.\n\nInformation regarding the participants will be kept private. Throughout the interview, we ensured that the subjects were comfortable and had privacy.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nZENODO questionnaire about the self-breast examination. 10.5281/zenodo.10212705. 24\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nEsfahani MS, Taleghani F, Noroozi M, et al.: An educational intervention on based information, motivation and behavior skills model and predicting breast self-examination. J. Prev. Med. Hyg. 2018 Dec 15 [cited 2022 Dec 16]; 59(4): E277–E281. PubMed Abstract | Publisher Full Text Reference Source\n\nMihret MS, Gudayu TW, Abebe AS, et al.: Knowledge and Practice on Breast Self-Examination and Associated Factors among Summer Class Social Science Undergraduate Female Students in the University of Gondar, Northwest Ethiopia. Antwi S, editor. J. Cancer Epidemiol. 2021 Apr 10; 2021: 8162047. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSarker R, Islam MS, Moonajilin MS, et al.: Knowledge of breast cancer and breast self-examination practices and its barriers among university female students in Bangladesh: Findings from a cross-sectional study. PLoS One. 2022; 17(6): e0270417. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVinod: Diagnostic utility of imprint cytology for assessment of breast lumps.[cited 2023 May 18]. Reference Source\n\nKalliguddi S, Sharma S, Gore CA: Knowledge, attitude, and practice of breast self-examination amongst female IT professionals in Silicon Valley of India. J. Fam. Med. Prim. Care. 2019 Feb; 8(2): 568–572. Publisher Full Text\n\nDash: p53 Expression in Breast Carcinoma and Its Association with Tumor Aggressiveness.[cited 2023 May 18]. Reference Source\n\nAmin MN, Uddin MG, Uddin MN, et al.: A hospital based survey to evaluate knowledge, awareness and perceived barriers regarding breast cancer screening among females in Bangladesh. Heliyon. 2020 Apr 10 [cited 2023 Jul 14]; 6(4): e03753. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSamad SA, Phatak SV: Bilateral axillary accessory breast with ductal ectasia: Ultrasonography and elastographic appearance. J. Datta Meghe Inst. Med. Sci. Univ. [cited 2023 May 18]. Reference Source\n\nBirhane K, Alemayehu M, Anawte B, et al.: Practices of Breast Self-Examination and Associated Factors among Female Debre Berhan University Students. Int. J. Breast Cancer. 2017; 2017: 1–6. Publisher Full Text\n\nNanda: A cytohistologic correlation study of breast carcinoma with reference to robinson’s cytologic grading system.[cited 2023 May 18]. Reference Source\n\nJanaki KL, Kannan NS, Palaniappan M, et al.: Profile of Breast Diseases in Post Pubertal Women Assessed By Clinical Breast Examination - A Community Based Study in Rural Pondicherry. J. Clin. Diagn. Res. JCDR. 2016 Feb [cited 2023 Jul 12]; 10(2). Publisher Full Text Reference Source\n\nMadurwar: Benign fibrous histiocytoma of male breast: Ultrasonography, doppler, and elastography imaging with pathological correlation.[cited 2023 May 18]. Reference Source\n\nInvestigating the predictors of breast cancer screening behaviors (breast self-examination, clinical examination or examination by physician/midwife and mammography) based on protection motivation theory (PMT) in women - PMC.[cited 2023 Jul 14]. Reference Source\n\nKalliguddi S, Sharma S, Gore CA: Knowledge, attitude, and practice of breast self-examination amongst female IT professionals in Silicon Valley of India. J. Fam. Med. Prim. Care. 2019 Feb; 8(2): 568–572. Publisher Full Text\n\nLunsford NB, Sapsis KF, Smither B, et al.: Young Women’s Perceptions Regarding Communication with Healthcare Providers About Breast Cancer, Risk, and Prevention. J. Women’s Health. 2002. 2018 Feb; 27(2): 162–170. Publisher Full Text\n\nDoshi D, Reddy BS, Kulkarni S, et al.: Breast Self-examination: Knowledge, Attitude, and Practice among Female Dental Students in Hyderabad City, India. Indian. J. Palliat. Care. 2012 [cited 2022 Nov 27]; 18(1): 68–73. Publisher Full Text Reference Source\n\nSelf-examination in the early detection of breast cancer: memorandum from a WHO meeting. Bull. World Health Organ. 1984; 62(6): 861–869. PubMed Abstract\n\nSarker R, Islam MS, Moonajilin MS, et al.: Effectiveness of educational intervention on breast cancer knowledge and breast self-examination among female university students in Bangladesh: a pre-post quasi-experimental study. BMC Cancer. 2022 Feb 22; 22(1): 199. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSarker R, Islam MS, Moonajilin MS, et al.: Effectiveness of educational intervention on breast cancer knowledge and breast self-examination among female university students in Bangladesh: a pre-post quasi-experimental study. BMC Cancer. 2022 Feb 22 [cited 2023 Nov 23]; 22(1): 199. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGangane N, Ng N, Sebastian MS: Women’s Knowledge, Attitudes, and Practices about Breast Cancer in a Rural District of Central India. Asian Pac. J. Cancer Prev. APJCP. 2015; 16(16): 6863–6870. PubMed Abstract | Publisher Full Text\n\nPal A, Taneja N, Malhotra N, et al.: Knowledge, attitude, and practice towards breast cancer and its screening among women in India: A systematic review. J. Cancer Res. Ther. 2021 [cited 2022 Dec 31]; 17(6): 1314–1321. PubMed Abstract | Publisher Full Text Reference Source\n\nDadzi R, Adam A: Assessment of knowledge and practice of breast self-examination among reproductive age women in Akatsi South district of Volta region of Ghana. PLoS One. 2019 Dec 30 [cited 2022 Nov 29]; 14(12): e0226925. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSachdeva S, Mangalesh S, Dudani S: Knowledge, Attitude and Practices of Breast Self-Examination Amongst Indian Women: A Pan-India Study. Asian Pac. J. Cancer Care. 2021 May 6; 6: 141–147. Publisher Full Text\n\nQuestionnaire and Consent Form for study A study on awareness of breast cancer and breast self-examination practices among women above 35 years of age in rural areas of Wardha District, Maharashtra: a protocol.[cited 2023 Nov 28]. Reference Source"
}
|
[
{
"id": "274240",
"date": "16 May 2024",
"name": "Freda Halim",
"expertise": [
"Reviewer Expertise General surgery",
"Biology molecular of Breast cancer"
],
"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. Although the authors are delivering an interesting background of this study, unfortunately it is not followed with interesting research question. BSE practices and awareness is thoroughly studied in India community, and the authors already mentioned those studies in Background as well as Discussion. Therefore this study (in this current format), in my opinion, will not provide any interesting point in BSE practices and awareness. There has to be more to be studies or asked to the participants.\n2. To deal with obstacles in Breast Self Examination(BSE) practice, the authors aimed to evaluate the awareness and practice of BSE. However it is not clearly stated how they would evaluate the awareness and practice in their study design and the table 1. In simple example, how they would ask the participants about their awareness? Is it simply just asking yes or no? How they will access the knowledge of the participants breast cancer? Will they used standardized questionnaire in accessing the knowledge? Will they conduct deep interview with the participants regarding the knowledge and awareness? If yes, what are the items being asked/discussed? 3. In conjunction with item 2, there are no sufficient details of how the researchers want to do the research, therefore it is not replicable. 4. There are no information why this area/location is in particular chosen to be the research location. Is it the highest population with Breast cancer cases in India? The authors themselves stated in the limitation that it is only conducted in a few villages of Wardha District Maharashtra, therefore the external validity is not applicable. I suggest to provide epidemiologic explanation for answering this question, to justify the location of this study. 5. The study protocol overall is not concise, and I strongly suggest the authors to refer to STROBE protocol in https://www.strobe-statement.org/ to understand how observational study should be reported. 6. Last but not least, this protocol definitely needs language editing for grammar. The current format also comprised of repeatedly themes and phrases in Background as well as in discussion. Please fix the matter as it is confusing to understand the authors' point.\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? No\n\nAre the datasets clearly presented in a useable and accessible format? No",
"responses": []
},
{
"id": "287930",
"date": "04 Jul 2024",
"name": "Armel Herve Nwabo Kamdje",
"expertise": [
"Reviewer Expertise 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\nRegarding this manuscript, authors have worked on awareness of breast cancer and breast self-examination practices among women above 35 years of age in rural areas of Wardha District, Maharashtra: a protocol. I read carefully and I found it interesting. However some aspects of this work have to be improved before we can make the final decision.\nMajor points: 1- Authors have to increase the size of participants and have to be more to be studies or asked to the participants. 2- Authors aimed to evaluate the awareness and practice of BSE. However it is not clearly stated how they would evaluate the awareness and practice in their study design and the (table 1). They have to conduct deep interview with the participants regarding the knowledge and awareness. 3- I suggest to provide epidemiologic explanation and to justify the location of this study.\nMinor Points: In this manuscript, authors have to improve grammar and typos. There are some repeatedly themes and phrases in background and in discussion. I suggest major revision. Authors have to address all questions raised by all reviewers before the final decision can be made. Many thanks in advance for your understanding.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Partly",
"responses": []
},
{
"id": "274256",
"date": "11 Sep 2024",
"name": "Rajiv Janardhanan",
"expertise": [
"Reviewer Expertise Public Health",
"AI",
"Vascular Biology",
"Bioprospecting"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript under review does not add any value to the existing body of literature although it is a unique attempt at evaluating along with the provisioning of health literacy modules to curb the menace of Breast Cancer among the women residing in the rural milieus of the Wardha District, Maharashtra, There are approximately 40 Primary Healthcare Centres in Wardha district and authors have not clearly mentioned the details of the PHCs liaised with in the current along with epidemiological as well as the demographic attributes of the subjects evaluated in the study. This in itself makes the observations made in this study redundant . The authors need to ascribe the observations made in the current study to the specific village from which the participants were enrolled in the study. The reviewer is also of the opinion that the authors should astutely characterize the subjects evaluated in the current study to understand the patterns of variability with respect to their ethnicity, socio-cultural norms as well as lifestyle choices. Perhaps a detailed evaluation of the familial cladistics may provide a striking clue as to whether consanguinity exists in the population surveyed as a part of the current study. This could indeed be a game changer as it would skew the susceptibility patterns to Breast Cancer. Use of Artificial Intelligence–enabled softwares to evaluate the women would also help towards the creation of a unique triage to prioritize the allocation of clinical to intervention to women at high risk of getting afflicted with Breast Cancer. The sample size for the subjects evaluated in the current study is very low to draw a conclusion for the entire district of Wardha, Maharashtra. The manuscript is ridden with grammatical errors which need to be corrected in the revised version of the manuscript. The authors need to also provide a future scope of this study along with the integration of other modalities including molecular attributes and Artificial Intelligence to provide more value to the long term outcomes envisaged in the study.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? No\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-145
|
https://f1000research.com/articles/13-144/v1
|
23 Feb 24
|
{
"type": "Study Protocol",
"title": "Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease: a study protocol",
"authors": [
"Sudheeshreddy Naramreddy",
"Ashish Varma",
"Amar Taksande",
"Ashish Varma",
"Amar Taksande"
],
"abstract": "Background Sickle cell disease, a hereditary hemoglobinopathy, presents complex clinical challenges including increased susceptibility to iron deficiency anemia (IDA). However, the clinical profile of IDA in pediatric patients with sickle cell disease still needs to be adequately characterized. This study aims to comprehensively investigate the prevalence, severity, associated risk factors, and potential impact of IDA on morbidity and mortality in this vulnerable population.\n\nMethods A prospective observational study will be conducted on 303 children from January 2024 to December 2024 at the Department of Pediatrics, Jawaharlal Nehru Medical College and AVBR Hospital, Sawangi, Wardha. Participants will include pediatric patients diagnosed with sickle cell disease, with informed consent from their parents or legal guardians. Data will be collected through clinical assessments, blood sample analyses for hematological parameters, and systematic recording of relevant clinical information. Statistical analyses, including Fisher’s exact test, Chi-square test, and Student’s t-test, will be used to assess the data, with a significance level set at p < 0.05.\n\nExpected outcomes This study aims to provide critical insights into the prevalence and clinical profile of IDA in children with sickle cell disease, shedding light on potential risk factors and correlations with comorbid conditions. Furthermore, it seeks to explore the relationship between IDA and disease-related morbidity and mortality.",
"keywords": [
"Sickle cell disease",
"Iron deficiency anemia",
"Pediatric patients",
"Clinical profile",
"Prevalence",
"Morbidity"
],
"content": "Introduction\n\nSickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by abnormal hemoglobin levels, leading to chronic hemolytic anemia, vaso-occlusive events, and organ damage.1 It is a significant global health concern, particularly prevalent in regions with a high malaria prevalence. While much research has been dedicated to understanding the pathophysiology and management of SCD, one aspect that continues to challenge clinicians and researchers is the co-occurrence of iron deficiency anemia (IDA) in pediatric patients with SCD.2\n\nIron deficiency anemia represents a distinct clinical entity marked by iron deficiency, which is necessary for red blood cell production and other critical cellular processes.3 In the context of SCD, the interplay between these two hematological conditions is complex and needs to be fully elucidated. The prevalence, severity, and clinical implications of IDA in children with SCD need to be further characterized to represent a critical gap in our understanding of the disease.4\n\nUnderstanding the clinical profile of IDA in children with SCD is essential for several reasons. First, IDA can exacerbate the pre-existing anemia in SCD, potentially increasing the disease burden and complicating its management. Second, iron deficiency may result from SCD-related factors such as chronic hemolysis, making it a unique challenge to address. Furthermore, the presence of IDA may be associated with specific clinical outcomes, including an increased risk of infections, pain crises, and organ damage.5\n\nThis study adopts a prospective observational approach to address the knowledge gaps and clinical challenges. This study aims to investigate the prevalence of IDA in pediatric patients with SCD, assess the severity of anemia, identify potential risk factors contributing to IDA, explore correlations with comorbid conditions, and examine whether IDA plays a role in SCD-related morbidity and mortality. By shedding light on the intricate relationship between SCD and IDA, we hope to provide valuable insights that can inform improved clinical management and ultimately enhance the quality of life of children living with these conditions.\n\nThis study aims to investigate the prevalence of IDA in children diagnosed with SCD and to gain insights into the clinical profile of this patient population.\n\n\n\n1. To determine the prevalence of IDA among children diagnosed with SCD in the study population.\n\n2. To assess the severity of anemia in these children by evaluating key hematological parameters, primarily focusing on hemoglobin (Hb) levels.\n\n3. To identify and analyze potential risk factors associated with the development of IDA in pediatric patients with SCD, including factors such as age, sex, dietary habits, and disease severity.\n\n4. To investigate the correlations between iron deficiency anemia and other comorbid conditions commonly observed in sickle cell disease, such as vaso-occlusive pain crises, infections, organ damage, and growth impairment.\n\n5. To assess the impact of iron deficiency anemia on the overall morbidity of children with sickle cell disease, aiming to determine whether IDA exacerbates or is associated with increased disease-related complications.\n\n6. To explore any potential relationship between iron deficiency anemia and mortality rates in the study population, focusing on understanding whether IDA contributes to a higher mortality risk in children with SCD.\n\n\nMethods\n\nThe study has been structured as a prospective observational investigation, characterized by systematically gathering participant data over a specified duration from January 2024 to December 2024. Proforma for data collection can be found as Extended data.11\n\nThis study will focus on pediatric patients diagnosed with SCD receiving care at the Department of Pediatrics, Jawaharlal Nehru Medical College, and AVBR Hospital, Sawangi, Wardha.\n\nThis research will be conducted at the Department of Pediatrics, Jawaharlal Nehru Medical College, and AVBR Hospital, Sawangi, Wardha.\n\n\n\n1. Pediatric age group: Children within a specified age range, typically aged between 1 to 16 years diagnosed with sickle cell disease.\n\n2. Diagnostic confirmation: Pediatric patients with a confirmed diagnosis of sickle cell disease based on High Performance Liquid Chromatography (HPLC).\n\n3. Informed consent: Written informed consent must be obtained from parents or legal guardians for the participation of their children in the study. The consent process will involve a detailed explanation of the study’s objectives, procedures, and potential risks and benefits.\n\n\n\n1. Iron supplementation status: Patients currently receiving iron supplementation will be excluded from the study. This criterion aims to focus on individuals with no ongoing iron intervention, ensuring a clearer understanding of natural iron deficiency anemia in the study population.\n\n2. Consent willingness: Patients or parents/legal guardians unwilling to provide informed consent for participation in the study will be excluded. The consent process is integral to ethical considerations and ensures voluntary participation.\n\nParticipants who meet the inclusion criteria and provide informed consent will be enrolled in this study. Recruitment will be conducted by the research team at the Department of Pediatrics.\n\nFormula\n\nPrevalence of patients who underwent echocardiographic evaluation = 27% (As per reference article6)\n\nMinimum sample size required = 303\n\nThe data collection process for our prospective observational study on the clinical profile of IDA in children with SCD involves several structured steps to ensure the systematic and accurate gathering of pertinent information. First, we enroll eligible pediatric patients diagnosed with SCD under the Department of Pediatrics at Jawaharlal Nehru Medical College & AVBR Hospital, Sawangi, Wardha. During this enrollment phase, we will comprehensively explain the study’s objectives and procedures to the parents or legal guardians and obtain informed consent for their children’s participation.\n\nBlood samples of 2 ml will be collected from the arms and drawn into plain Vacutainer tubes, ensuring the precise preservation of sample integrity. This vital procedure will be carried out by proficient healthcare professionals to maintain uniformity. Subsequently, the samples will be promptly conveyed to the laboratory within a 30-minute timeframe, thereby minimizing the risk of any potential degradation. The storage of biological samples will adhere to established guidelines to safeguard the quality of the samples. Collected blood samples will be immediately centrifuged to obtain plasma, which will then be aliquoted and stored at the recommended temperature and conditions. Detailed records of the storage process will be meticulously maintained, ensuring the traceability and reliability of the stored samples.\n\nOnce participants are enrolled, we will collect baseline data, including demographic details such as age, sex, and relevant medical history, using the proforma uploaded as Extended data. A clinical assessment involves a thorough physical examination to evaluate overall health and identify any signs or symptoms of iron deficiency anemia. A crucial aspect of our data collection process is the collection of blood samples using strict aseptic techniques. We will ensure proper labeling and documentation of each sample to maintain traceability and accuracy.\n\nSubsequently, these blood samples will be subjected to laboratory analysis to measure key hematological parameters. This includes assessing the High Performance Liquid Chromatography7 to determine the presence and severity of anemia and determine serum iron levels to gauge iron status and serum ferritin levels to evaluate iron stores within the body. All collected data will be meticulously recorded in structured forms or electronic databases tailored for the study. These records will be subjected to rigorous quality control measures to ensure data accuracy and consistency.\n\nData validation procedures will be rigorously implemented throughout the study to ensure the completeness and accuracy of all recorded information. A systematic approach will be adopted to scrutinize data entries, promptly identifying and addressing any discrepancies or missing information. To achieve this, a dedicated data validation team will be assigned the responsibility of regularly reviewing all collected data. This team will employ a thorough process, which includes cross-checking entered information against source documents, verifying the accuracy of data points, and ensuring that all required fields are appropriately completed. Any inconsistencies or missing data will be flagged for immediate attention.\n\nFurthermore, periodic data audits will be conducted to assess the overall quality of the dataset. This involves a comprehensive review of a random subset of collected data to validate its accuracy and consistency. Any discrepancies discovered during these audits will be thoroughly investigated, and corrective actions will be promptly taken. To maintain transparency and accountability, a detailed log of all data validation activities will be maintained. This log will document the date, nature of validation checks performed, any issues identified, and the corrective actions taken. This systematic approach to data validation aims to enhance the reliability and integrity of the dataset, ultimately ensuring the robustness of our study findings.\n\nThroughout this process, we are committed to maintaining the utmost privacy and confidentiality of participants’ personal and medical information, adhering to ethical standards and regulations. Throughout this process, we are committed to safeguarding the privacy and confidentiality of participants’ personal and medical information, aligning with stringent ethical standards and regulations. To uphold this commitment, we will implement robust measures, including secure data storage, restricted access, and de-identification practices. Only authorized personnel directly involved in the study will have access to identifiable participant information, ensuring the utmost confidentiality. Any shared or published results will strictly maintain anonymity, protecting the privacy of the individuals who have contributed to this research. Our approach complies with the ethical guidelines set forth by the Institutional Ethics Committee of the Datta Meghe Institute of Higher Education and Research (DU) and prioritizes the well-being and privacy of our study participants. Finally, using the collected data, we will utilize appropriate statistical software, such as SPSS version 23, to perform the detailed analysis outlined in our study protocol. The results will provide valuable insights into the prevalence, risk factors, correlations, and potential associations between iron deficiency anemia and sickle cell disease outcomes. This comprehensive data collection process will ensure the reliability and robustness of our study findings, while upholding ethical considerations and participant welfare.\n\nThe Institutional Ethics Committee of the Datta Meghe Institute of Higher Education and Research (DU) has granted its approval to the study protocol (Reference number: DMIHER (DU)/IEC/2022/1074; Date: 21/07/22). Prior to commencing the study, we will obtain written informed consent from all participants, providing them with a comprehensive explanation of the study’s objectives.\n\nStatistical methods: Data analysis will be conducted with meticulous attention to detail, employing a combination of software tools and specific statistical tests tailored to address the study’s objectives. After the initial organization of collected data using Microsoft Excel, in-depth statistical analyses will be executed using the Statistical Package for the Social Sciences (SPSS) version 23.\n\nCategorical variables: For categorical variables, such as those related to prevalence rates and risk factors, statistical tests including Fisher’s exact and Chi-square tests will be applied. These tests are chosen for their suitability in assessing associations and differences within qualitative data.\n\nQuantitative variables: For quantitative variables, particularly continuous data such as hematological parameters, the analysis will involve the application of the student’s t-test. This test is chosen for its appropriateness in comparing means between two groups, providing insights into the severity of anemia in pediatric patients with sickle cell disease.\n\nCorrelation analysis: In addition to the specified tests, correlation analyses will be performed to explore relationships between variables, particularly focusing on correlations between iron deficiency anemia and comorbid conditions in sickle cell disease. The choice of correlation analysis will be based on the nature of the variables involved, with Pearson correlation for linear relationships and Spearman correlation for non-linear relationships.\n\nSignificance level: A significance level of p < 0.05 will be employed for all statistical tests, ensuring the robustness and reliability of the results. This stringent threshold is set to ascertain the validity of observed associations and differences in the study population.\n\nAfter completion of the study, we will publish it in an indexed journal or conference.\n\nThis study is yet to be conducted. After publication of the protocol, we will begin recruitment for the study.\n\n\nDiscussion\n\nIn a study conducted by Anwesha Singh,8 a cohort of 100 children who have SCD exhibiting the SS hemoglobin pattern, aged between six months and 12 years, were enrolled. Among these participants, sex distribution revealed that 52% were male and 48% were female, portraying a nearly balanced male-to-female ratio of 1.08:1.\n\nMoreover, a study by Salman9 demonstrated a similar pattern, in which 91 individuals (56.88%) were male and 69 (43.12%) were female, with ages ranging from 0 to 14 years. Notably, these sex distributions echo the findings of other studies conducted.10\n\nThese findings have a substantial clinical significance. They underscore the importance of routine monitoring of iron status in pediatric patients with SCD, particularly emphasizing the early detection and effective management of IDA. Tailored interventions, including judicious iron supplementation and targeted dietary counseling, may prove essential in addressing IDA in this vulnerable patient population.10\n\nAdditionally, these observations emphasize the indispensability of adopting a multidisciplinary approach to patient care and fostering collaboration between hematologists, nutritionists, and other specialized healthcare professionals. Such an integrated approach can potentially optimize the overall well-being and health outcomes of pediatric individuals grappling with the complexities of SCD.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nZenodo: Proforma for the data collections ‘Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease’. https://zenodo.org/doi/10.5281/zenodo.10360381. 11\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nMangla A, Ehsan M, Agarwal N, et al.: Sickle Cell Anemia. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.\n\nChao DL, Oron AP, Chabot-Couture G, et al.: Contribution of malaria and sickle cell disease to anaemia among children aged 6–59 months in Nigeria: a cross-sectional study using data from the 2018 Demographic and Health Survey. BMJ Open. 2022; 12: e063369. Publisher Full Text\n\nBermejo F, García-López S: A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World J. Gastroenterol. 2009; 15: 4638–4643. Publisher Full Text\n\nMohanty D, Mukherjee MB, Colah RB, et al.: Iron deficiency anaemia in sickle cell disorders in India. Indian J. Med. Res. 2008; 127: 366–369.\n\nOdunlade O, Adeodu O, Owa J, et al.: Iron deficiency, still a rarity in children with sickle cell anemia in Ile-Ife, Nigeria. Hematol. Transfus. Cell Ther. 2019; 41: 216–221. Publisher Full Text\n\nMadoori S, Ramya C, Valugula S, et al.: Clinico hematological profile and outcome of anemia in children at tertiary care hospital, Karimnagar, Telangana, India. Int. J. Res. Med. Sci. 2015; 3: 3567–3571. Publisher Full Text\n\nHigh Performance Liquid Chromatography (HPLC)|ELGA LabWater. Accessed: December 12, 2023. Reference Source\n\nSingh A, Bokade C, Tirpude B, et al.: Clinical Profiles of Children With Sickle Cell Anaemia Presenting With Acute Clinical Events: A Single-Center Study. Cureus. 15: e39008. Publisher Full Text\n\nSalman ZA, Hassan MK: Hospitalization Events among Children and Adolescents with Sickle Cell Disease in Basra, Iraq. Anemia. 2015; 2015: 195469. Publisher Full Text\n\nÖzdemir N: Iron deficiency anemia from diagnosis to treatment in children. Turk. Pediatri. Ars. 2015; 50: 11–19. Publisher Full Text\n\nSudheeshreddy N: Proforma for the data collections ‘Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease’. [Dataset]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "262395",
"date": "28 Jun 2024",
"name": "Yaddanapudi Ravindranath",
"expertise": [
"Reviewer Expertise Red cell disorders"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is research proposal and therefore no data available for review. The proposal aims to assess the frequency of concurrent iron deficiency in children with Sickle cell anemia- the authors wish to focus on cases with homozygous Sickle cell disease. The disease status will be established by HPLC and iron status will be assessed by iron profile including serum ferritin. I recommend adding soluble transferrin receptor measurement as well as serum ferritin levels are influenced by concurrent infections - serum ferritin is an acute phase reactant. Also standard blood counts should be done in real time on EDTA containing vaccutainer tubes. In general the incidence of Iron Deficiency in SCD is low in the US given the high meat containing diets. The situation could be vastly different in India considering the varied dietary habits and as well the risk for hookworm infestation.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
},
{
"id": "287988",
"date": "03 Jul 2024",
"name": "Berengere Koehl",
"expertise": [
"Reviewer Expertise red cells disorders",
"haemoglobinopathy",
"transfusion",
"pediatrics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 protocol of Naramreddy aim to explore the interesting question of iron deficiency in children with SCD. The challenge is both to describe the prevalence of iron deficiency in this population, and to investigate the impact of IDA on the severity of SCD. To answer these questions, the authors propose to collect biological and clinical data from patients with SCD, age 1 to 16 yo. 1/Concerning the evaluation of iron deficiency, the authors propose to measure serum iron levels and serum ferritin levels. Since these parameters could be impacted by the chronic inflammation status in patients with SCD, the mesure of transferrin and the transferrin saturation levels should probably be added to fully explore the iron status. 2/The second objective of the study is to correlate the iron deficiency with the severity of the disease, and to look for risk factors associated with IDA. Nevertheless, the detail of the clinical /biological parameters that will be recorder remains elusive and should definitely be precised. For exemple, the authors propose to include “factors of disease severity”. Which parameters will precisely be assessed? History of acute chest syndrome? Number of vaso-occlusive event? Same question about several items: “dietary habits”: what will precisely be evaluated? “Organ damage”= which organ? With which criteria? “growth impairment” = BMI? or a inflection/ break in the growth curve 3/ No mention is made about the transfusion history for the patients. However, since red blood cell transfusion has a strong impact on iron status, these information seem important to collect in order to interpret the results (for exemple the volume/kg of packed red blood cells transfused in the past 12 months before the inclusion?) 4/ One of the objective is to “determine whether IDA exacerbates or is associated with increased disease-related complications”. Which clinical/biological criteria will be used to evaluate this correlation? 5/ Idem for the objective “explore any potential relationship between iron deficiency anemia and mortality rates in the study population, focusing on understanding whether IDA contributes to a higher mortality risk in children with SCD”. How will the authors answer this question? How will be explored the relationship between IDA and mortality rate?\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? No\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-144
|
https://f1000research.com/articles/13-142/v1
|
23 Feb 24
|
{
"type": "Research Article",
"title": "Impact of hemB mutations on 5-aminolevulinic acid production in Escherichia coli",
"authors": [
"Koki Ninomiya",
"Kohei Yoneda",
"Yoshiaki Maeda",
"Yasushi Iwata",
"Iwane Suzuki",
"Koki Ninomiya",
"Kohei Yoneda",
"Yoshiaki Maeda",
"Yasushi Iwata"
],
"abstract": "Background Microbial production of 5-aminolevulinic acid (ALA) attracts attention due to a wide range of biotechnological and medical applications of ALA, including cancer treatment and diagnosis. Various genetic engineering approaches have been employed to improve ALA production in bacterial hosts such as Escherichia coli possessing the C5 pathway. Glutamyl-tRNA reductase (GluTR) encoded by hemA, glutamate-1-semialdehyde aminotransferase (GSA-AT) encoded by hemL, and ALA dehydratase (ALAD) encoded by hemB play important roles in ALA metabolism including the C5 pathway. Attenuation of the intercellular ALAD activity, which condensates 2 molecules of ALA to synthesize porphobilinogen (PBG), has been employed by various measures. However, a mutation approach by substituting catalytically important residues in ALAD encoded by hemB has never been attempted. The aim of this study is to assess the impact of hemB mutations on the ALA production in E. coli.\n\nMethods In this study, the authors mutated the amino acid residues potentially related to the enzymatic activity of E. coli ALAD by referring to a mutation experiment of human ALAD. The authors created five types of mutated hemB genes, introduced these genes to the hemB-deleted mutant strain of E. coli, and assessed the impact of the ALAD mutations on ALA production. In addition, hemA, hemL, and rhtA encoding an ALA exporter were introduced to the E. coli possessing a mutated hemB.\n\nResults The authors revealed that the mutations of ALAD employed in this study did not significantly enhance ALA production. Overexpression of hemA, hemL, and rhtA substantially increased ALA production in any E. coli strain possessing mutated hemB, while a difference in ALA production of the strain could be rather attributed to its growth behaviour than ALAD inactivation.\n\nConclusions This study provides an important piece of information to design the bioprocess of ALA production using E. coli engineered through the C5 pathway.",
"keywords": [
"5-aminolevulinic acid",
"5-aminolevulinic acid dehydratase",
"hemB",
"hemA",
"hemL",
"rhtA"
],
"content": "Introduction\n\n5-aminolevulinic acid (ALA) is an intermediate in the synthetic pathway of porphyrin derivatives indispensable to life such as heme, vitamin B12 and chlorophyll, and thus found in a wide range of prokaryotic and eukaryotic organisms.1 ALA has been useful compounds or agents of very considerable interest because it is applicable to various biotechnologies including diagnosis and treatment of cancer, biodegradable herbicide, and growth promotion factor for plants.2\n\nIndustrial production of ALA was conventionally performed using a photosynthetic bacterium Rhodobacter sphaeroides possessing the C4 pathway in which ALA synthase (EC 2.3.1.37) produces ALA from glycine and succinyl-CoA.3 The mutation and metabolic engineering approaches of R. sphaeroides have successfully demonstrated a significant improvement in ALA productivity.4 Another option is to use bacteria (including Escherichia coli) that possess another pathway of ALA-synthesis referred to as the C5 pathway, which originates with glutamate (Glu) and subsequently glutamyl-tRNA, glutamate-1-semialdehyde leading to ALA (Figure 1).5–7 The enzymes that specify the C5 pathway to produce the precursors of ALA accumulation are glutamyl-tRNA reductase (GluTR, EC 1.2.1.70) encoded by hemA and glutamate-1-semialdehyde aminotransferase (GSA-AT, EC 5.4.3.8) encoded by hemL. In the downstream pathway of the C5 pathway, ALA dehydratase (ALAD, EC 4.2.1.24) encoded by hemB condensates two molecules of ALA to synthesize porphobilinogen (PBG), which is converted to various types of tetrapyrrole including heme. Membrane transporter RhtA encoded by rhtA serves as an exporter of ALA.\n\nThe genes hemA encoding glutamyl-tRNA reductase (GluTR), hemL encoding glutamate-1-semialdehyde aminotransferase (GSA-AT), hemB encoding ALA dehydratase (ALAD), and RhtA-encoding gene were engineered in this study.\n\nVarious types of genetic engineering approaches have been examined to enhance ALA production through the C5 pathway. Kang et al., obtained a high ALA accumulation in E. coli through the synergetic effect of the endogenous hemL and heterologous hemAM that was mutated to stabilize the encoding GluTR structurally.8 They also found that overexpression of rhtA increased ALA production. Inhibiting the conversion of ALA to porphyrin derivatives is also a well-known strategy to improve ALA production. Since the ALDA encoded by the hemB gene plays a crucial role in synthesizing porphyrin derivatives essential to the cellular growth, an efficient inhibitory node can be arranged on the downstream metabolic pathways not by completely knocking-out hemB but by lowering the ALAD enzyme activity (Figure 1). Zhang et al., verified inactivation of the ALAD enzyme activity in Corynebacterium glutamicum as reduced to 47% and 69% in contrast with the enhancement of ALA accumulation as 1.34 and 1.19 times, respectively, by replacing the intrinsic ribosome-binding site (RBS) of hemB to relatively weak RBS along with overexpression of hemA, hemL and rhtA.9 Attenuation of the hemB expression was also achieved by some other approaches such as promoter exchanging,10 CRISPRi,11 and antisense RNA expression.12 Although researchers have examined various approaches to downregulation of the transcriptional or translational levels of hemB for enhancement of ALA production, the authors have first attempted the mutation approach to lower the enzymatic activity of ALAD.\n\nIt has been known that the human ALAD forms quaternary homo-oligomers (four types of morpheein forms) of high-activity octamer, transient hugging dimer, transient detached dimer, and low-activity hexamer.13 In rare cases, heteromeric oligomers were found in the human ALAD of patients with ALAD porphyria with more than one genetic aberration.13 The heteromeric oligomers comprise the wild-type K59 or N59 and the mutant F12L. The F12L variant forms a stable homohexamer and possesses a significantly low enzymatic activity, whereas the wild type K59 and N59 variants form a stable homooctamer (hexameric morpheein concentration is 0% and 3%, respectively) and possess a high enzymatic activity. Jaffe and Stith demonstrated that porphyria-associated mutation in the human ALAD causes the morpheein equilibrium to be shifted toward the inactive hexamer.13 Inspired by the study, the authors considered that some mutations in the E. coli ALAD also have a certain possibility of the morpheein shift toward the hexameric assembly for leading to enzymatic inactivation and an increase in ALA accumulation of the genetically engineered E. coli.\n\nIn the present study, the specific amino acid residues on E. coli ALAD was first identified to correspond to the enzymatically important residues on the human ALAD, and then inactive residues were substituted for the specific residues. Subsequently, the impacts of these mutations on ALA accumulation in the E. coli cells were analysed. Furthermore, the synergetic effects of these ALAD mutations and overexpression of RhtA, GluTR (encoded by hemA) and GSA-AT (encoded by hemL) were also examined.\n\n\nMethods\n\nE. coli strain W3110 hemB (mutant with hemB deletion, kanamycin resistance) was obtained from National BioResource Project (National Institute of Genetics (NIG), Shizuoka, Japan). Molecular cloning was performed using E. coli strain JM109. E. coli was cultured at 37°C in the lysogeny broth (LB) medium containing appropriate combinations of 50 μg/mL kanamycin sulphate (FUJIFILM Wako Pure Chemical Co., Catalogue number: 113-00343), 50 μg/mL chloramphenicol (FUJIFILM Wako Pure Chemical Co., Catalogue number: 034-10572), 100 μg/mL spectinomycin dihydrochloride pentahydrate (FUJIFILM Wako Pure Chemical Co., Catalogue number: 152067) or 150 μg/mL ampicillin sodium (FUJIFILM Wako Pure Chemical Co., Catalogue number: 012-23303) for selection. Isopropyl-β-D-thiogalactopyranoside (IPTG, final concentration: 0.1 mM, TaKaRa Bio Inc., Catalogue number: 9030) was added to induce the expression of the genes under the control of the lac promoter.\n\nProtein structures of ALAD derived from Homo sapience (PDB 1E51) and E. coli (PDB 1B4E) were obtained from the Protein Data Bank (PDB). Alignment of the protein structures was carried out using PyMoL (RRID:SCR_000305) (The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC.).\n\nPrimers, plasmids, and E. coli strains used in this study are listed in Tables 1, 2, and 3, respectively. pACYCDuet-1 (carrying the P15A replicon origin, ~10 copies/cell) was purchased from Sigma-Aldrich Co. (Catalogue number: 71147, St. Louis, MO, USA). A partial fragment of pACYCDuet-1 without lac-promoter was amplified by PCR using primers of pACYCDuet_F and pACYCDuet_R and PrimeSTAR Max DNA polymerase (TaKaRa Bio Inc., Shiga, Japan, Catalogue number: R045A). PCR amplification experiments were performed using the PCR machines (Takara Bio Inc., model TP350 and Blue-Ray Biotech Co., TurboCycler, model TCST-9612) with the thermal cycling condition unless otherwise noted; after the initial denaturation step at 98°C for 1 min, 30 cycles of the denaturation step at 98°C for 10 sec, annealing step at 50~68°C for 5 or 15 sec, and extension step at 72°C for 1 min/kbp, followed by an additional extension step at 72°C for 4 min. The hemB along with native hemB promoter was amplified by PCR using primers of hemB promoter+hemB_F and hemB promoter+hemB_R with the extracted E. coli genome as a template. DNA concentrations were measured using NanoDrop 1000 (Thermo Fisher Scientific, Waltham, MA, USA). These fragments were assembled by In-Fusion HD Cloning Kit (TaKaRa Bio Inc., Catalogue number: 639634) at 50°C for 15 min. The assembled samples were introduced into E. coli strain JM109 by heat shock method (42°C, 45 sec). The colonies were cultivated in LB agar (1.5%) medium containing 50 μg/mL chloramphenicol. The assembly of the plasmid was confirmed by restriction enzyme treatment, followed by Sanger sequencing. The resulting plasmid were designed as pACYC-hemB. Additionally, five types of plasmids containing mutated hemB (namely hemB’[K13L], hemB’[E87K], hemB’[G131R], hemB’[G268T], hemB’[A269M]) were constructed by inverse PCR using pACYC-hemB as a template and one of the following primer sets, hemB_K13L_F and hemB_K13L_R, hemB_E87K_F and hemB_E87K_R, hemB_G131R_F and hemB_G131R_R, hemB_G268T_F and hemB_G268T_R, and hemB_A269M_F and hemB_A269M_R. The amplified fragments were assembled as described above. The resulting plasmids were designed as pACYC-hemB’[K13L], pACYC-hemB’[E87K], pACYC-hemB’[G131R], pACYC-hemB’[G268T], and pACYC-hemB’[A269M], respectively.\n\nF, forward; R, reverse.\n\npCL1920 (carrying the pSC101 replicon origin, ~5 copies/cell) was purchased from National BioResource Project (NIG). A partial fragment of pCL1920 by PCR using a primer sent of pCL1920_F and pCL1920_R. The rhtA was amplified by PCR using primers of rhtA_In_pCL1920_F and rhtA_In_pCL1920_R with the extracted E. coli genomic DNA as a template. The amplified fragments were assembled as described above. The colonies were cultivated in LB agar medium containing 100 μg/mL spectinomycin. The resulting plasmid was designed as pCLS-rhtA.\n\npMD19 (derived from pUC19 with ~500 copies/cell) was purchased from TaKaRa Bio (Catalogue number: 3271). A partial fragment of pMD19 was amplified by PCR using primers of pMD19_In_hemL_F and pMD19_In_hemL_R. The hemA and hemL, both derived from E. coli, were amplified using primers of hemA_In_pMD19_F and hemA_In_hemL_R, and hemL_In_hemA_F and hemL_In_pMD19_R, respectively. Subsequently, the amplified fragments of hemA and hemL were together assembled with the partial fragment of pMD19 by the method described above using LB agar medium containing 150 μg/mL ampicillin. The resulting plasmid was designed as pMD-hemA-hemL.\n\nPartial fragments of pCLS-rhtA and pMD-hemA-hemL were amplified by PCR using primer sets of pCLS-rhtA_F and pCLS-rhtA_R, and hemA-hemL_F and hemA-hemL_R, respectively. These fragments were assembled by the method described above. The resulting plasmid was designed as pCLS-rhtA-hemA-hemL containing rhtA, hemA and hemL.\n\nThe amount of ALA production was measured by colorimetric quantification using a modified Ehrlich’s reagent prepared by mixing 1 g of dimethylaminobenzaldehyde (DMAB, FUJIFILM Wako Pure Chemical Co., Catalogue number: 047-18042), 30 mL of acetic acid (FUJIFILM Wako Pure Chemical Co., Catalogue number: 017-00256), 8 ml of 60% (v/v) perchloric acid (Kanto Chemical Co. Inc., Catalogue number: 32059-1B), followed by addition of acetic acid to make the total volume 50 mL.14 The supernatant of culture (100 μL) was added to 100 μL of the mixture (1:99 vol. ratio) of acetylacetone and acetate buffer (prepared by mixing 91 mL of 0.1 M acetic acid and 109 mL of 0.1 M sodium acetate solution, pH 4.7), and incubated at 100°C for 15 min. The mixture was then cooled down on ice. The modified Ehrlich’s reagent (200 μL) was added to the mixtures and incubated at room temperature for 15 min. Ultrapure water (600 μL) was added, and absorbance at 553 nm was measured using a spectrophotometer UV-1900 (Shimadzu Co., Kyoto, Japan).\n\n\nResults and Discussion\n\nFigure 2 illustrates both the structures of the E. coli ALAD (in orange) and human ALAD (in blue) resemble each other. Figure 2 also demonstrates that the K13, E87, G131, G268 and A269 residues on the E. coli ALAD occupy the positions corresponding to the F12, E89, G133, A274 and V275 residues on the human ALAD. The conformational characteristics of these residues guided us to design mutations of the K13L, E87K, G131R, G268T and A269M variants in the E. coli ALAD following the inactive F12L, E89K, G133R, A274T and V275M variants in the human ALAD.13 The authors applied an inverse PCR method to introduce mutations to hemB on the pACYC-based plasmids (pACYC-hemB’[K13L], pACYC-hemB’[E87K], pACYC-hemB’[G131R], pACYC-hemB’[G268T] and pACYC-hemB’[A269M] listed in Table 2) to express these mutated E. coli ALAD. Successful mutations of hemB were confirmed by Sanger sequencing (Figure 3).\n\nK13, E87, G131, G268, and A269 on the E. coli ALAD structurally correspond to F12, E89, G133, A274, and AV275 on the H. sapience ALAD, respectively. Porphobilinogen (PGB) products are shown in green wire forms. The figure was prepared using PyMoL (The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC.).\n\nIn the present study, the mutant E. coli strain W3110 hemB with hemB deletion (hereinafter referred to as strain ∆B, Table 3) was used as a basic strain to assess the impacts of ALAD mutations. The strain ∆B with a lack of ALAD activity can grow only in the LB medium containing supplementation of 0.2% glucose as well (Figure 4A).15 The strain ∆B_B was established by introducing the intrinsic hemB in the strain ∆B and can grow without supplementation of 0.2% glucose (Figure 4), suggesting that ALAD activity was essential to support the E. coli growth in the absence of glucose. When one of the five types of mutated hemB was introduced to the strain ∆B, every strain (namely, the strains ∆B_B’[K13L], ∆B_B’[E87K], ∆B_B’[G131R], ∆B_B’[G268T], or ∆B_B’[A269M], Table 3) showed steady growth even in the LB medium without supplementation of glucose (Figure 4). This result indicates that the above-mentioned five types of the mutated hemB expressed the enzymatically active ALAD in E. coli. Figure 4B showed the comparison of the growth of these strains. The mutant strain harbouring pACYC-hemB’[G131R] exhibited an obviously low growth rate, while the molecular mechanism underlying the growth inhibition remains unclear.\n\n(A) Culture of E. coli strains ∆B, ∆B_B, and ∆B_B’[K13L] in the lysogeny broth (LB) medium after overnight incubation. (B) Growth curves of E. coli strains ∆B_B, ∆B_B’[K13L], ∆B_B’[E87K], ∆B_B’[G131R], ∆B_B’[G268T], and ∆B_B’[A269M] (inset: specific growth rates of each strain).\n\nFurther engineering of the strains expressing mutated ALAD was performed by introducing the ALA-exporter gene rhtA. We successfully obtained the transformant strains designated as ∆B_B’[K13L]&R, ∆B_B’[E87K]&R, ∆B_B’[G131R]&R, ∆B_B’[G268T]&R and ∆B_B’[A269M]&R (Table 3). The restriction enzyme assay confirmed that the transformed pACYC-based plasmid with mutated hemB and pCLS-rhtA plasmid were maintained in the transformant strains (Figure 5). Moreover, along with the pACYC-based plasmid with mutated hemB and pCLS-rhtA plasmid, the pMD-hemA-hemL plasmid with an ability of highly copying was also introduced to overexpress GluTR and GSA-AT. However, unfortunately, mature colonies did not grow on the LB-agar plates containing antibiotics for selection. Although tiny colonies were observed on the plates (Figure 6A), the cells forming tiny colonies did not grow in the liquid LB medium containing the antibiotics. The introduction of the empty vector pMD19 leaded to the results of the formation of mature colonies (Figure 6B), indicating that the backbone vector pMD19 did not cause the formation of tiny colonies. These results suggest that excess GluTR and GSA-AT expressed from a high copy number of plasmid pMD-hemA-hemL might negatively affect the E. coli growth. To avoid the problem, we replaced the backbone vector pMD19 with pCL1920 having an ability to copy a relatively low number of plasmids for expressing GluTR and GSA-AT. The hemA and hemL encoding GluTR and GSA-AT, respectively, were inserted to the expression cassette of rhtA in pCLS-rhtA. Resultantly, the mature colony of E. coli transformed with the pCLS-rhtA-hemA-hemL plasmid was successfully obtained. The results indicates that the transformant of E. coli was able to harbour mutated hemB (∆B_B’[K13L]&R-A-L, ∆B_B’[E87K]&R-A-L, ∆B_B’[G131R]&R-A-L, ∆B_B’[G268T]&R-A-L and ∆B_B’[A269M]&R-A-L, Table 3). Maintenance of both the pCLS-rhtA-hemA-hemL and pACYC-based plasmid carrying mutated hemB in each transformant clone was confirmed with the restriction enzyme assay (Figure 7). We should emphasize that overexpression of GluTR and GSA-AT in E. coli is a technical challenge involving a risk of their toxic effects on the host cells. As far as we found out, the present study has first achieved to solve the problem by fine-tuning their expression levels with reducing the number of plasmid copies.\n\nLane M represents the DNA ladder.\n\nLane M represent the DNA ladder.\n\nTaking the results mentioned above, the authors constructed three kinds of the series of E. coli transformant strains harbouring the mutated hemB; namely (1) the primary hemB mutation (strains ∆B_B’[mutation]) that simply express the mutated hemB alone, (2) the intermediate hemB mutation (strains ∆B_B’[mutation]&R) that express the mutated hemB along with recombinant rhtA, (3) the triplet hemB mutation (strains ∆B_B’[mutation]&R-A-L) that express the mutated hemB along with recombinant rhtA, hemA and hemL. The ALA production of these transformants were evaluated by the colorimetric measurement. The ALA production of the primary hemB mutation strains was almost uniform under the mutational variation, even though the values were slightly lower than that of the wild type hemB strains (Figure 8A and Table 4). The primary mutation strains did not show any improvement in ALA production of E. coli, suggesting that the primary hemB mutations only slightly decreased the enzymatic activity of ALAD in E. coli, and those impacts on ALA accumulation were hindered by the effects of multiplication of the mutated hemB genes on pACYC-based plasmids (~10 copies/cell). The intermediate hemB mutation strains with overexpression of RhtA from low copy number plasmid marginally improved the ALA production by actively exporting ALA to the supernatant of the culture (Figure 8B and Table 4).\n\nNumeric data of Figure 8 is shown in the Table 4.\n\nThe same data are represented in the form of bar-graph in Figure 4. The unit of the data is mg/L. Data represent the average values of two replicated experiments.\n\n1 OX: over-expression.\n\n2 ND: no data.\n\nThe triplet hemB mutation strains with further overexpression of GluTR and GSA-AT from low copy number of plasmid carrying hemA and hemL drastically increased the ALA production (Figure 8C and Table 4). The overexpression of GluTR could be expected to lead an enhancement in ALA production because the reaction catalysed by GluTR encoded by hemA is a rate-limiting step for ALA production in the C5-pathway8 and GSA-AT encoded by hemL tightly forms a complex with GluTR.8,16 Clear difference also appeared in ALA production of the transformants with the aid of overexpression of GluTR and GSA-AT depending on the five types of mutated hemB variation. The transformant strains with hemB’[K13L] showed the highest ALA production of 368.1 mg/L, followed those with hemB’[G268T] (354.6 mg/L), hemB’[E87K] (309.7 mg/L), hemB’[A269M] (288.7 mg/L) and hemB’[G131R] (262.4 mg/L). However, we have not been able to attribute the difference appeared in ALA production rigorously to the declining variation in the levels of the ALAD activity caused by the individual mutation because the ALA production depends on both the ALA contents in a unit cell and the biomass production (in other word, growth of cells) of E. coli. The ALA production order of the transformants (hemB’[K13L] was highest, followed by hemB’[G268T], hemB’[E87K], hemB’[A269M] and hemB’[G131R] in Figure 8C and Table 4) is the exact same as the order in the specific growth rates of the corresponding platform strains with mutated hemB (inset figure of Figure 4B). Given these two results; (1) the authors have not discriminated any significant difference of ALA production in the five types of hemB in the platform strains without overexpression of RhtA, GluTR and GSA-AT, (2) the difference of ALA production of the transformant strains with overexpression of RhtA, GluTR and GSA-AT was consistent with the growth behaviour of the platform strains, difference of ALA production shown in Figure 8C could be most likely attributed to not the declining variation of ALAD activity encoded by the mutated hemB, but the different growth of E. coli strains.\n\n\nConclusions\n\nFive types of mutations have been introduced on the E. coli ALAD encoded by hemB to induce the accumulation of ALA in E. coli. However, any mutation examined in the present study has not increased ALA production significantly. As far as we found out, the present study has been first performed to assess the impact of mutations of ALAD on ALA production in E. coli. Tuning of the copy number of the plasmid containing hemA and hemL allowed us to obtain the transformant strains expressing rhtA, hemA, hemL, and mutated hemB. Overexpression of RhtA, GluTR (encoded by hemA) and GSA-AT (encoded by hemL) substantially improved ALA production as previously reported. These transformant strains expressing each type of mutated ALAD showed different ALA production, while their different ALA production was most likely attributed to not the declining variation of ALAD activity but the difference in the growth rate of E. coli strains.",
"appendix": "Data availability\n\nFigshare: Gene sequence file (fasta). https://doi.org/10.6084/m9.figshare.24557605.v1. 17\n\nFigshare: Uncropped raw gel images for diagnostic restriction digestion analyses 1. https://doi.org/10.6084/m9.figshare.24556849.v1. 18\n\nFigshare: Uncropped raw gel images for diagnostic restriction digestion analyses 2. https://doi.org/10.6084/m9.figshare.24557308.v1. 19\n\nFigshare: Numeric data for E. coli growth curve. https://doi.org/10.6084/m9.figshare.24556828.v1. 20\n\nFigshare: Output files from PyMoL. https://doi.org/10.6084/m9.figshare.24556768.v1. 21\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nShemin D, Russell CS: δ-Aminolevulinic acid, its role in the biosynthesis of porphyrins and purines 1. J. Am. Chem. Soc. 1953 Oct 1; 75(19): 4873–4874. Publisher Full Text\n\nSasaki K, Watanabe M, Tanaka T, et al.: Biosynthesis, biotechnological production and applications of 5-aminolevulinic acid. Appl. Microbiol. Biotechnol. 2002; 58: 23–29. Publisher Full Text\n\nKikuchi G, Kumar A, Talmage P, et al.: The enzymatic synthesis of δ-aminolevulinic acid. J. Biol. Chem. 1958 Nov; 233(5): 1214–1219. Publisher Full Text\n\nNishikawa S, Watanabe K, Tanaka T, et al.: Rhodobacter sphaeroides mutants which accumulate 5-aminolevulinic acid under aerobic and dark conditions. J. Biosci. Bioeng. 1999 Jun; 87(6): 798–804. PubMed Abstract | Publisher Full Text\n\nOh-hama T, Stolowich NJ, Scott AI: 5-Aminolevulinic acid formation from glutamate via the C 5 pathway in Clostridium thermoaceticum. FEBS Lett. 1988 Feb 8; 228(1): 89–93. PubMed Abstract | Publisher Full Text\n\nLi JM, Brathwaite O, Cosloy SD, et al.: 5-Aminolevulinic acid synthesis in Escherichia coli. J. Bacteriol. 1989 May; 171(5): 2547–2552. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIkemi M, Murakami K, Hashimoto M, et al.: Cloning and characterization of genes involved in the biosynthesis of δ-aminolevulinic acid in Escherichia coli. Gene. 1992 Nov; 121(1): 127–132. PubMed Abstract | Publisher Full Text\n\nKang Z, Wang Y, Gu P, et al.: Engineering Escherichia coli for efficient production of 5-aminolevulinic acid from glucose. Metab. Eng. 2011 Sep; 13(5): 492–498. PubMed Abstract | Publisher Full Text\n\nZhang B, Ye BC: Pathway engineering in Corynebacterium glutamicum S9114 for 5-aminolevulinic acid production. 3 Biotech. 2018 May 1; 8(5): 247. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang J, Weng H, Zhou Z, et al.: Engineering of multiple modular pathways for high-yield production of 5-aminolevulinic acid in Escherichia coli. Bioresour. Technol. 2019 Feb 1; 274: 353–360. PubMed Abstract | Publisher Full Text\n\nSu T, Guo Q, Zheng Y, et al.: Fine-tuning of hemB using CRISPRi for increasing 5-aminolevulinic acid production in Escherichia coli. Front. Microbiol. 2019; 10(JULY). PubMed Abstract | Publisher Full Text | Free Full Text\n\nLuo Z, Pan F, Zhu Y, et al.: Synergistic Improvement of 5-Aminolevulinic Acid Production with Synthetic Scaffolds and System Pathway Engineering. ACS Synth. Biol. 2022 Aug 19; 11(8): 2766–2778. PubMed Abstract | Publisher Full Text\n\nJaffe EK, Stith L: ALAD porphyria is a conformational disease. Am. J. Hum. Genet. 2007; 80: 329–337. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nMauzerall D, Granick S: The occurrence and determination of saminolevulinic acid and porphobilinogen in urine. J. Biol. Chem. 1956 Mar; 219(1): 435–446. Publisher Full Text\n\nNational BioResource Project-NBRP E.coli Strain. http\n\nLüer C, Schauer S, Möbius K, et al.: Complex formation between glutamyl-tRNA reductase and glutamate-1- semialdehyde 2,1-aminomutase in Escherichia coli during the initial reactions of porphyrin biosynthesis. J. Biol. Chem. 2005 May 13; 280(19): 18568–18572. PubMed Abstract | Publisher Full Text\n\nNinomiya K, Yoneda K, Maeda Y, et al.: Gene sequence file (fasta). [Dataset]. figshare. 2023. Publisher Full Text\n\nNinomiya K, Yoneda K, Maeda Y, et al.: Uncropped raw gel images for diagnostic restriction digestion analyses 1. [Dataset]. figshare. 2023. Publisher Full Text\n\nNinomiya K, Yoneda K, Maeda Y, et al.: Uncropped raw gel images for diagnostic restriction digestion analyses 2. [Dataset]. figshare. 2023. Publisher Full Text\n\nNinomiya K, Yoneda K, Maeda Y, et al.: Numeric data for E. coli growth curve. [Dataset]. figshare. 2023. Publisher Full Text\n\nNinomiya K, Yoneda K, Maeda Y, et al.: Output files from PyMoL. [Dataset]. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "258981",
"date": "13 May 2024",
"name": "Nguyen Quoc Khuong",
"expertise": [
"Reviewer Expertise soil and environmental 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\nThe title should be rewritten to suit the work of the study. The abstract is well written. The introduction is also well prepared. However, it lacks a sufficient number of literatures. Thus, many statements are not cited, such as “The enzymes that … an exporter of ALA.”, “ Inhibiting the …enzyme activity (Figure 1).”, etc. Lacking of literature review could make the study less persuasive. Moreover, in this section, the sentences are too wordy. These run-on sentences should be separated into more concise ones. Should the Figure 1 be cited? Last but not least, at the end of the introduction, objectives or hypotheses should be clearly stated, instead of the methods used in the study. Are there any studies investigating the properties of E. coli strain W3110? How long has the strain incubated before the ALA quantification? Are there any chances to improve the quality of Figure 5? The gel image is blur and probably contains bubbles. The discussion in the Results and Discussion section is not adequate. The section lacks comparisons and interpretations of the results based on previous studies. The conclusion should deliver what the study can be used and its further investigation.\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": []
},
{
"id": "254155",
"date": "13 May 2024",
"name": "Nabil I. Elsheery",
"expertise": [
"Reviewer Expertise plant physiology"
],
"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 work about Five types of mutations have been introduced on the E. coli ALAD encoded by hemB to induce the accumulation of ALA in E. coli. However, any mutation examined in the present study has not increased ALA production significantly. As far as we found out, the present study has been first performed to assess the impact of mutations of ALAD on ALA production in E. coli. Tuning of the copy number of the plasmid containing hemA and hemL allowed us to obtain the transformant strains expressing rhtA, hemA, hemL, and mutated hemB. Overexpression of RhtA, GluTR (encoded by hemA) and GSA-AT (encoded by hemL) substantially improved ALA production as previously reported. These transformant strains expressing each type of mutated ALAD showed different ALA production, while their different ALA production was most likely attributed to not the declining variation of ALAD activity but the difference in the growth rate of E. coli strains.\nthe idea is good but i still have some comments where is Statistic? improve your discussion added paragraph about the importance of ALA in geeneral\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/13-142
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https://f1000research.com/articles/11-1392/v1
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28 Nov 22
|
{
"type": "Study Protocol",
"title": "The dynamics and determinants of specific systemic and mucosal antibody responses to SARS-CoV-2 in three adult cohorts in the Ecuadorian Andes: a study protocol",
"authors": [
"Jose E. Leon-Rojas",
"Tatiana Veloz",
"Jair Teran",
"Monica Perez",
"Fernanda Arias-Erazo",
"Lizet Villacis",
"Jorge Velez",
"Ricardo Recalde",
"Patricia Jiménez",
"Miguel Martin",
"Irina Chis Ster",
"Philip Cooper",
"Natalia Romero",
"Tatiana Veloz",
"Jair Teran",
"Monica Perez",
"Fernanda Arias-Erazo",
"Lizet Villacis",
"Jorge Velez",
"Ricardo Recalde",
"Patricia Jiménez",
"Miguel Martin",
"Irina Chis Ster",
"Philip Cooper",
"Natalia Romero"
],
"abstract": "Introduction: There are limited longitudinal data on the systemic and mucosal antibody responses to SARS-CoV-2 from Latin America, a region severely affected by COVID-19, and where vaccine strategies have been implemented during the evolving pandemic. Objective: To evaluate determinants of seroprevalence and changes in levels of anti-SARS-CoV-2 antibodies longitudinally in adults with different levels of exposure to SARS-CoV-2 (defined a priori as low, medium, and high based on presumed occupational risk), in two Andean cities in Ecuador. Methods: Longitudinal cohort study of 1,000 adults aged 18 years and older with questionnaire data and sample collection done at 0, 3, 6, and 12 months during the period 2020-2023. Observations collected included WHO-ISARIC questionnaire and peripheral blood and saliva samples for measurement of IgG and IgA antibodies, respectively. Planned analyses are tailored to the longitudinal nature of the outcomes defined by participants’ antibody levels and aim at estimating their average trends with time since infection in each of the occupational groups, adjusted for demographics and calendar-time levels of SARS-CoV-2 infection in the general population. The latter reflect the impact of the national control measures such as vaccinations and movement restrictions. Importance: Understanding the duration and the dynamics of waning immunity to SARS-CoV-2, in the context of exposures to emerging virus variants and immunization, will inform the implementation of targeted public health strategies in the Latin American region. Ethics and Dissemination: This study will observe the bioethical principles of the Declaration of Helsinki. Informed written consent will be obtained. Samples from participants will be stored for up to three years after which they will be destroyed. The study protocol was approved by the Ecuadorian Ministry of Public Health Ethics Committee for COVID-19 Research. Antibody results will be provided to participants and participating institutions and to the national health authorities.",
"keywords": [
"COVID-19",
"SARS-CoV-2",
"Seroprevalence",
"Antibody levels",
"risk factors",
"Ecuador"
],
"content": "Introduction\n\nThe pandemic caused by the new coronavirus, SARS-CoV-2, the etiological agent of COVID-19, has caused 612 million confirmed cases and approximately 6.5 million deaths worldwide since December 2019 when the virus first emerged (Johns Hopkins Coronavirus Resource Center). In Ecuador, the first confirmed case of COVID-19 was reported on 29th February 2020 and as of 19th September 2022, one million confirmed cases have been reported with 35,885 deaths. The highest burden of infection is among those aged 20 to 55 years age group, while death rates are greatest among those aged over 65 years (Daily Report of the Ecuadorian Ministry of Public Health).\n\nThe presence of specific IgG antibodies to SARS-COV-2 indicates past exposure to SARS-COV-2 and vaccination, given that most serological assays using the spike protein cannot distinguish between these two forms of exposure. Additionally, since the virus invades the body through the mucosal surfaces, the role of mucosal immune responses measured by specific IgA, has been neglected compared to the measurement of systemic IgG responses.1 Timely seroprevalence studies in the population are useful in monitoring rates of exposure to natural infections (prior to vaccination programs), and vaccine coverage and immunogenicity following the implementation of vaccination programs.2 Measuring the waning immunity across different groups in the population will add to our understanding of the epidemiology of the infection and will help identify population groups with increased infection susceptibility.1–3\n\nNumerous seroprevalence studies have been conducted in the Latin American region, both population-based studies and studies focusing on specific populations (healthcare (HCW) or first-line workers, prison workers, indigenous populations, elderly populations, etc).4–15 The reported seroprevalence is highly heterogenous between studies (10,4% – 68,1 %), varying by study population, characteristics of the COVID-19 epidemic at the time of sampling, and differences in sociodemographic factors.4–15 Factors associated with increasing risk of seropositivity include ethnicity (indigenous or Afro-descent), presence of COVID-19 symptoms, past history of COVID-19 or close contacts, lower educational level, and working night shifts (for HCW) or in a prison.4–15\n\nAmong these studies, a cross-sectional study in 2020 of 3,124 children aged 5 to 17 years in 10 Colombian cities reported highly variable seroprevalence ranging from 25.0% in Medellin to 63.9% in Guapi, the latter a coastal city with a high proportion of Afro-Colombians with the poorest living conditions.10 Further, a cross-sectional study in 2021 from Brazil of six indigenous groups in the Amazon region showed a high average seroprevalence for anti-SARS-CoV-2 IgG (68.1%).11 Finally, a systematic review analysing 15 seroprevalence studies from Latin America and the Caribbean reported a highly variable seroprevalence between indigenous populations ranging 4.2% to 81.7%.13\n\nThere are nine published studies estimating seroprevalence rates for IgM/IgG antibodies to SARS-CoV-2 from different regions of Ecuador (Table 1) covering the period from April 2020 to April 2021 with seroprevalence estimates ranging 7.7% to 64%.16–24 Six of these studies are derived from samples nested within the same observational adult cohort from Atahualpa, a coastal community in Santa Elena Province and it is uncertain the degree of overlap between samples.16–21 Two of four longitudinal studies using the Atahualpa cohort with follow-up of 116 and 1218 months, estimated seroincidence (i.e., incidence rate ratio for seroconversion) of 7.416 to 9.918 per 100 person years, respectively.\n\nIn most regions, vaccination has been a major component of national mitigation strategies for COVID-19 resulting in marked reductions in hospitalizations and deaths worldwide.25 In Ecuador, vaccination was initiated on 21st January 2021 as part of the national vaccination strategy “Plan Vacunarse”, consisting of four phases: Phase 0, a pilot phase, started in January 2021 and targeted first line workers and very high-risk individuals; Phase 1 started in March 2021 and included individuals with risk of severe disease such as the elderly; Phase 2 started in June 2021 and included the adult populations living in provinces with a high incidence of COVID-19; and Phase 3 started in September 2021 including adult populations in the other provinces.26 Booster doses (third and fourth doses) started in October 2021 and April 2022, respectively (Vaccination Report Ministry of Public Health). As of May 2022, 83% of the population had received a complete 2-dose vaccination schedule (with one of CoronaVac, Pfizer-BioNTech, AstraZeneca, and Cansino), and 35.6 % has received at least one booster shot (Vaccination Report Ministry of Public Health). Figure 1 shows confirmed cumulative SARS-COV-2 infections and monthly incidence per 1000 population over the period February 2020 through May 2022.\n\nLegend: Arrows indicate the initiation of different phases in the national vaccination programme. Data from: https://www.salud.gob.ec/coronavirus-covid19-ecuador/.\n\nHere, we present the protocol for a longitudinal study of seroprevalence and changes in systemic (plasma IgG) and mucosal (salivary IgA) antibodies being done in three adult cohorts of different infection risk justified by presumed different infection patterns, in two Andean cities. In addition, we will explore the effects of natural infections and vaccinations, as well as other relevant determinants (e.g. age, sex, and occupation), on seroprevalence and time trends since infection on antibody levels.\n\n\nProtocol\n\nTo estimate changes in and determinants of seroprevalence and levels of anti-SARS-CoV-2 antibodies over 12 months of follow-up in adults aged 18 years and older, with varying levels of exposure (defined a priori as low, medium, and high based on presumed occupational risk) and associated factors, in two Ecuadorian Andean cities.\n\n\n\n1. Identify risk factors (including cohort membership) associated with baseline seroprevalence and IgG antibody levels in the three cohorts (pre-vaccination)\n\n2. Evaluate changes in seroprevalence and IgG antibody levels over at least 12 months of follow-up.\n\n3. Identify effects of determinants on longitudinal changes in specific IgG antibody levels over at least 12 months of follow-up. Potential determinants will include cohort membership, sociodemographic factors, vaccination, number of vaccine doses, natural (past exposures) infections, and their timing.\n\n4. Estimate the pattern of decline in anti-SARS-CoV-2 IgG antibodies among seropositives and impact of vaccinations and other relevant determinants on this decline.\n\n5. To estimate the development and longevity of the mucosal immune response through the measurement of levels of anti-SARS-CoV-2 IgA in saliva and the impact of relevant determinants on changes in antibody levels.\n\nStudy design\n\nProspective longitudinal cohort (Figure 2).\n\nLegend: Syringes show introduction of COVID-19 vaccine doses, red drops show sample collections, and dotted red drops show timings of future sample collections.\n\nThree cohorts from two Ecuadorian Andean cities, based on assumed risk of occupational exposure to SARS-CoV-2, are being recruited in two Andean cities, Quito, and Ambato. These three cohorts are presumed to differ in the probability of exposure to SARS-CoV-2. Eligibility criteria for entry into the 3 cohorts are provided in Table 2.\n\n1. High Risk (HR): Defined as being of high exposure risk through an occupational setting of health care workers and support personnel working in the emergency service, ICUs and hospitalization areas at a major public hospital (Hospital Eugenio Espejo) in Quito, at altitude of 2,800 m in northern Andean region, with 2.9 million inhabitants.\n\n2. Medium Risk (MR): Population whose occupation puts them at a considerable risk of contracting SARS-CoV-2 (merchants, farmers or those that do not self-isolate due to the nature of their work). The population selected was Huachi Grande parish in the city of Ambato, at altitude of 2,600 m, in central Andean region, with 500,000 inhabitants.\n\n3. Low Risk (LR): Population with a presumed low risk of SARS-CoV-2 infection due to the characteristics of their occupation (staff and students at a private university, with the means to self-isolate) and living within the metropolitan district of Quito. This cohort is composed of teachers, administrative staff, and the student community of Universidad Internacional del Ecuador (UIDE), Quito.\n\n\n\n1. Adults aged 18 years or older\n\n2. Healthcare workers\n\n3. Hospital workers\n\n\n\n1. Adults aged 18 years or older\n\n2. Inhabitant of Huachi Grande\n\n\n\n1. Adults aged 18 years or older\n\n\n\n1. Age <18 years\n\n2. Pregnancy or breastfeeding\n\n3. Religious beliefs that prevent participation\n\n4. Unable to provide informed consent\n\nQuestionnaires\n\nData are being collected digitally by trained interviewers using a standardised tool developed specifically for the COVID-19 pandemic (ISARIC-WHO Global COVID-19 Clinical Platform “Rapid core case report form (CRF)” questionnaire, subsections 1b, 1f, and 3a) at baseline (month 0) and every three months either via telephone or face-to-face interviews. This tool collects data on socio-demographics, history of signs and symptoms related to COVID-19, and previous diagnoses and treatments.\n\nSaliva and blood are being collected at baseline and 3-monthly intervals (0, 3, 6, and 12 months). Blood samples are being collected into 5 ml Vacutainer tubes with EDTA as anticoagulant (Vacutainer, BD Biosciences), and plasma separated by centrifugation and stored in 0.5 mL aliquots at -20 °C. Saliva sample (0.5-1 mL) are being collected directly into 2 ml microtubes after asking the participant to think of food, centrifuged to remove residual food debris, and stored in 0.5 mL aliquots at -20 °C.\n\nPresence and levels of IgG antibodies directed against the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein will be measured in stored plasma using an ELISA essay adapted from Guevara et al., 2021.27 Specific IgA antibodies against SARS-CoV-2 RBD will be measured in saliva samples using an ELISA-based assay modified from Costantini et al., 2022.28 Specific IgG and IgA quantitation will use standard curves of serum pools of positive samples calibrated against an WHO international standard (National Institute for Biological Standards and Control, Potters Bar, United Kingdom).\n\nThe initial sample was collected before vaccination in all cohorts; after baseline evaluation subsequent sampling was done as follows:\n\na. at 3 months after baseline if the participant had not been vaccinated.\n\nb. at 30-45 days after receiving the two-dose vaccine schedule or boosters’ doses.\n\nFollow-up was done on site (university, hospital, or parish administrative building) or through home visits at the sampling follow-up times (0, 3, 6, and 12 months depending on vaccine dose timings). Subjects were contacted also by phone at monthly intervals to collect data on new infections and vaccinations and to provide antibody results, as well as address any doubts or concerns about the study. All evaluations were done by a dedicated and trained study team.\n\nAt the time of study planning, there were no reliable longitudinal data to estimate minimum sample size needed to understand the dynamics of waning immunity in different risk populations. Given the rapid dynamics of unfolding events, convenience sampling will be done in each of the three occupational risk cohorts with the aim of recruiting a total of 1,000 adults. Our data are exploratory in nature and the estimates will serve as input for planning future prospective comparative studies.\n\nCross sectional variables will be summarized according to their nature, i.e. means, standard deviations, medians, inter-quartiles, ranges and frequencies and proportions for categorical variables. Data summaries will be done for each risk group to understand the characteristics of each risk group.\n\nPresence and levels of IgG/IgA antibodies will define binary and continuous longitudinal outcomes, respectively. Generalized estimation equations (GEEs) will be used to fit population averaged models under the most general assumptions of unstructured variance covariance matrix. It is likely that the distributions IgG/IgA antibody levels will be highly skewed and logarithmic transformation will be required to satisfy such models’ assumptions. The continuous longitudinal outcome will quantify patterns in trends in the monthly average waning immunity across groups and their characteristics – trends are expected to be nonlinear. The binary outcomes will evaluate the associations between presence/absence of antibodies and epidemiologically plausible independent variables through odds ratios. Mixed models will also be done and the estimates will be compared with those obtained by the GEEs fit. All analyses will be adjusted for levels of the infection in the general populations by calendar time, and by associated periods of interventions. Time-varying covariates are expected to be defined based on these later interventions. P-values less than 0.05 will indicate statistically significant (potentially adjusted) associations and 95% confidence intervals will assess the uncertainty of the estimates.\n\nMultivariable models will be built for each risk group accounting for all potential explanatory variables and their interactions - particularly with time at follow-up. The most parsimonious model will be constructed based on the largest complete observations dataset using likelihood criteria such as quasi-likelihood value under the independence model criterion (QIC) for GEEs or likelihood-ratio type criteria for mixed models. GEE estimation is based on completely at random missing observations assumption whilst mixed models are based on missing at random assumption. The attrition patterns will be investigated, and sensitivity analyses to the estimates obtained on complete datasets using the two estimation techniques will be performed and discussed.\n\nThe study protocol was approved by the Ecuadorian Ministry of Public Health Ethics Committee for COVID-19 Research (approval ID 020-2020- MSP-CGDES-2020-0172-O). The study results will be disseminated through presentations at conferences and to key stakeholder groups including policy makers, and through postgraduate theses and peer-review publications. All participants were required to accept participation by reading and signing an informed consent at the time of the first sampling.\n\n\nDiscussion\n\nWe are following up three adult longitudinal cohorts with presumed distinct exposure risks to SARS-CoV-2 based on occupation, in two Andean cities of Ecuador, to study determinants of seroprevalence and changes in systemic and mucosal antibody levels against SARS-CoV-2.\n\nSeroprevalence testing can be done using the detection of specific IgG and or IgM antibodies. IgM antibodies are detectable first from day 5-7 days post-infection with a peak at day 28 while IgG become detectable after 5-10 days and peak at 49 days.1,29,30 In contrast, specific IgG antibodies following vaccination against SARS-CoV-2 are detectable from about a week following the first dose and peak at approximately 30 days after the second dose, remaining detectable for 3-6 months.31,32 For example, a cross-sectional study in 56,261 Chilean individuals reported an IgG seroprevalence of 28.1% three weeks after the first dose and 77.4% four weeks after the second dose of the CoronaVac vaccine; and a prevalence of 79.4% three weeks after the first dose and 96.5% four weeks after the second dose of the BNT162b2 Pfizer vaccine.7 In healthcare workers (HCW) receiving the BNT162b2 Pfizer vaccine, a study showed that median serum levels of antibodies reached a peak 1 month after the second dose and were 37% and 57% lower at 3 and 6 months, respectively.33 Finally, a study, also in HCW, showed that antibodies remained high at three months after the third vaccination dose and that antibodies were quantitatively higher in those HCWs that had a history of COVID-19 infection and a third vaccine dose.34\n\nOur study aims to measure changes in antibody levels in the context of continuous (documented) exposures to natural infection and widespread vaccination with blood collections done as follows: 1) before the first vaccine dose; 2) at 30-60 days after the second dose; 3) 30-60 days after the third dose (when possible); and 4) 30-60 days after the fourth dose (where possible). These sampling times will allow us to measure effects of COVID-19 vaccination and booster doses with the three vaccines licensed for use in Ecuador (CoronaVac, Pfizer and AstraZeneca) on seroprevalence and antibody levels.\n\nOther than vaccination or natural infection, additional factors have been reported to have significant effects on anti-SARS-Cov-2 antibodies. Front-line professionals such as doctors, nurses, hospital workers, police officers, among others, are more likely to acquire COVID-19 and therefore, would be expected to have higher seroprevalence rates than the general population.35–37 A study involving 569 Canadian HCWs reported an IgG seropositivity duration of 415 days and 213 days for symptomatic and asymptomatic individuals, respectively; with obesity, age (over 55 years), and non-Caucasian ethnicity associated with longer seropositivity.38 Finally, ethnicity is also a factor affecting seroprevalence with indigenous populations having the highest reported seroprevalence (ranging from 4.2 – 81.65%) and populations of African descent having 68% prevalence.35–37 These differences might be explained by greater levels of migration (particularly in seeking work) and more menial work opportunities that don’t allow self-isolation, and a consequently greater risk of exposure to SARS-CoV-2. This is exemplified by a study done in Colombia where the global prevalence in the populations studied was 32.25%, while in Pacific coastal city of Guapi (where a high proportion of the population is of African descent with high rates of temporary migration), the IgG seroprevalence was 68%.10\n\nThere are relatively few longitudinal data on mucosal antibody (IgA) response to SARS-CoV-2 from settings in low and middle-income countries. A systematic review of 38 original studies measuring specific IgA reported a seroprevalence of 86.5% among PCR positive SARS-CoV-2 patients and that the production of specific IgA was detectable during the first 10 days following infection, and remained detectable for prolonged periods (e.g. 75 days after symptom onset).39 Finally, a study that analysed 100 communities in Wuhan, China showed that the presence of specific IgA antibodies decreased rapidly over time, as for IgM, especially those infected but who were asymptomatic.40\n\nOur study will evaluate differences in seroprevalence between cohorts with different occupational exposures (HCWs, highly mobile workers, and university staff and students) believed to have differing a priori risks of exposure to SARS-CoV-2. To our knowledge, there are no published longitudinal studies analysing cohorts with differing occupational risks for changes in systemic and mucosal antibodies to SARS-CoV-2. We hope to identify relevant factors related to changes in antibody levels including the effect of vaccination (including vaccine type and dose), occupation, and natural infections (and re-infections) with SARs-CoV-2.\n\nThe study is subject to several potential limitations. Significant losses to follow-up can lead to selection bias and these are being minimized by close coordination of project activities with community leaders and institutional authorities, and regular contacts with study participants (at 3-monthly intervals). Recall bias is being minimized through these regular follow-ups to collect information on potential infections with SARS-CoV-2 and vaccination dates. Misclassification of data collection is being minimized by using a widely used standardized instrument (ISARIC WHO), and of antibody measurements by the use of validated detection assays blind to potential exposures. Because of high expected seroprevalence through vaccination, we are measuring antibody levels, thus maximizing the potential power of the study. Misclassification of exposure to SARS-CoV-2 is unavoidable and may be systematic because of limited access to PCR-based assays – underreporting of confirmed infections will likely be least in the hospital-based cohort. Similarly, the use of different vaccines of differing immunogenicity likely will influence maximal antibody levels: vaccine type and dose will be considered as a potential confounder or determinant in different longitudinal analyses. The receipt of multiple vaccine doses at regular intervals (up to 3 doses during 12 months or so of follow-up) may limit the ability to measure rates of decline in antibody levels.\n\n\nConclusions\n\nWe are undertaking a prospective longitudinal cohort study to evaluate the effects of SARS-CoV-2 and vaccine exposures on longitudinal changes in systemic (plasma IgG) and mucosal (salivary IgA) antibodies to SARS-CoV-2. To our knowledge, this is one of very few such longitudinal studies being done in a low-middle income country setting and will contribute to our understanding of the impact of natural infectious exposures versus vaccination on population immunity, and the need for further booster vaccinations in different population groups.\n\n\nData availability\n\nNo data are associated with this article.",
"appendix": "Acknowledgements\n\nThe authors would like to thank Corporación Ecuatoriana para el Desarrollo de la Investigación y Academia - CEDIA for the financial support given to the present research, development, and innovation work through its CEPRA program, especially for the CEPRA XVI-2022-17 ANTICUERPOS IGG IGA fund.\n\n\nReferences\n\nHuang AT, Garcia-Carreras B, Hitchings MDT, et al.: A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity. Nat. Commun. 2020; 11(1): 4704. PubMed Abstract | Publisher Full Text\n\nHoffman T, Nissen K, Krambrich J, et al.: Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2. Infect. Ecol. Epidemiol. 2020; 10(1). PubMed Abstract | Publisher Full Text\n\nBryant JE, Azman AS, Ferrari MJ, et al.: Serology for SARS-CoV-2: Apprehensions, opportunities, and the path forward. Sci Immunol. 2020; 5(47). 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PubMed Abstract | Publisher Full Text"
}
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[
{
"id": "191772",
"date": "01 Aug 2023",
"name": "Chun-Yang Lin",
"expertise": [
"Reviewer Expertise Mucosal immunology",
"virology",
"host-pathogen interactions",
"B cell",
"transcriptome analysis",
"influenza virus",
"SARS-CoV-2"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 study protocol, Leon-Rojas et al. proposed a longitudinal cohort study to follow 1000 adults with varying SARS-CoV-2 exposure and to monitor the change in antibody levels against SARS-CoV-2 spike. Participant demographic information and baseline samples are collected at month 0. The clinical samples and relative information will be collected over the following 3, 6 and 12 months or when the participant receive the booster dose after 30-45 days. The antibody level in the samples is measured by ELISA and calibrated to NIBSC positive samples. With the study they want to understand 1) whether there are risk factors related to the level of SARS-CoV-2 exposure. 2) the change in SARS-CoV-2 spike antibody levels over a period of at least 12 months. 3) whether there are determinants that can affect antibody levels; 4) whether vaccination or other determinants affect antibody regression. 5) whether the relevant determinant also influences the SARS-CoV-2 IgA level in saliva. The results are analyzed by generalized estimating equations to construct a multivariable model for determinant identification.\nMajor points:\nThe introduction provides a comprehensive overview of the seroprevalence studies that have been conducted in Latin America. However, the rationale for the study is not explicitly stated until the discussion section. It would be helpful to emphasize the unique aspects of this study, such as the fact that it is a longitudinal study being conducted in a low-middle income country, in the introduction. This would help to make the study more relevant to the target audience.\n\nThe authors propose to use SARS-CoV-2 RBD ELISA to determine the determinants of antibody levels. However, it is important to note that the antibody levels to SARS-CoV-2 RBD can be influenced by both natural infection and vaccination. If the authors do not closely monitor the participants, such as by conducting routine nasal swabs for PCR detection, the effect of vaccination or asymptomatic infection on the change in antibody levels could be confounded. It is therefore recommended that the authors include the detection of antibody to viral internal proteins, such as N, ORF8, or M proteins in the ELISA (1-2), in order to distinguish between the effects of infection and vaccination.\n\nThe authors describe the methods of ELISA measurement using two reference papers. However, it would be helpful to provide more detail about the procedure, such as whether the serum will be serially diluted for the measurement and what TMB substrate will be used. Additionally, the authors should consider the huge different antibody levels that could be observed between vaccination and natural infection, which might out of ELISA detection range. If all samples are diluted to the same extent, the differences between the antibody levels in the vaccinated individuals may be limited because of saturating antibody binding.\n\nThe authors mention that demographic and related information will be collected using WHO CRF Questionnaires. However, they do not specify which determinants they plan to include in the analysis. It would be helpful to provide more detail about the specific determinants that the authors plan to investigate, as this information would be relevant to the target audience. \nOverall, the study protocol is well-designed and has the potential to provide valuable insights into the determinants of antibody levels against SARS-CoV-2 in a low-middle income country. The suggestions that I have made are intended to improve the clarity and relevance of the study.\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": "11119",
"date": "13 Apr 2024",
"name": "Jose Leon-Rojas",
"role": "Author Response",
"response": "Comment 1: The introduction provides a comprehensive overview of the seroprevalence studies that have been conducted in Latin America. However, the rationale for the study is not explicitly stated until the discussion section. It would be helpful to emphasize the unique aspects of this study, such as the fact that it is a longitudinal study being conducted in a low-middle income country, in the introduction. This would help to make the study more relevant to the target audience. Response 1: Thank you for your recommendation, we have added a highlighted sentence in the introduction section. Comment 2: The authors propose to use SARS-CoV-2 RBD ELISA to determine the determinants of antibody levels. However, it is important to note that the antibody levels to SARS-CoV-2 RBD can be influenced by both natural infection and vaccination. If the authors do not closely monitor the participants, such as by conducting routine nasal swabs for PCR detection, the effect of vaccination or asymptomatic infection on the change in antibody levels could be confounded. It is therefore recommended that the authors include the detection of antibody to viral internal proteins, such as N, ORF8, or M proteins in the ELISA (1-2), in order to distinguish between the effects of infection and vaccination. Reponse 2: We appreciate the recommendation of including antibody detection against internal viral proteins; we agree that measuring RBD IgG can result in confounding in antibody levels between naturally-acquired and vaccine-induced immunity. However, our study was performed at the early stages of the pandemic in Ecuador with limited access to COVID-19 testing. In order to try to mitigate this, we have conducted a strict follow-up of participants and recorded the reported PCR results or clinical diagnosis of COVID-19 at each new sample that will be considered in the analysis. Comment 3: The authors describe the methods of ELISA measurement using two reference papers. However, it would be helpful to provide more detail about the procedure, such as whether the serum will be serially diluted for the measurement and what TMB substrate will be used. Additionally, the authors should consider the huge different antibody levels that could be observed between vaccination and natural infection, which might out of ELISA detection range. If all samples are diluted to the same extent, the differences between the antibody levels in the vaccinated individuals may be limited because of saturating antibody binding. Response 3: Additional information on the procedure is now provided in the text: Flat bottom 96-well microtiter plates (Nunc Maxisorp™, Thermo Fisher Scientific, USA) were coated overnight at room temperature with recombinant RBD (50 ng/well) in phosphate-buffered saline solution (PBS pH 7.2). Wells content was discarded and washed with PBS containing 0.1% Tween-20 (PBST) and wells blocked with 100 µL of blocking buffer (PBS-0.1% Tween 20 and 4% bovine serum albumin) to each well and incubated for 30 minutes at 37°C. After blocking, the plates were washed and 100 µL of serum samples diluted with 5% non-fat milk in PBST was added to each well for reaction at 37°C for 1 hour. Dilutions from 1:200 to 1:1000 were used to capture a broad range of antibody levels and achieve optimal measurement of antibody levels. After washing, 100 μL of horseradish peroxidase (HRP)-labelled goat anti-human IgG (Invitrogen, USA) antibody diluted 8000-fold with 5% non-fat milk in PBST was added to each well and incubated at 37°C for 30 minutes. Post-wash, 100 μL of SIGMAFAST o-phenylenediamine dihydrochloride substrate solution (Sigma-Aldrich, USA) was added to each well for reaction at room temperature (RT) for 10 minutes in the dark. The reaction was stopped by the addition of 100 μL of 3M HCl. Optical density (OD) at 490 nm was measured. To assay saliva samples, the same procedure as mentioned above was followed, with the exception that the saliva samples were centrifuged at 14,000 rpm for 8 minutes at 4°C and supernatants were diluted 1:1 to 1:4. As secondary antibody, 50 μl of Goat Anti-Human IgA alpha chain (HRP) (Abcam, United Kingdom) antibodies were added at dilution of 1:2000 with 5% non-fat milk in PBST and incubated for 30 minutes at 37°C. The development procedure was the same as for IgG. Comment 4: The authors mention that demographic and related information will be collected using WHO CRF Questionnaires. However, they do not specify which determinants they plan to include in the analysis. It would be helpful to provide more detail about the specific determinants that the authors plan to investigate, as this information would be relevant to the target audience. We have included a sentence in the Questionnaires section explaining the main determinants to be considered. We would like to point out that, as specified in the text, we’re using subsections 1b, 1f, and 3a of the WHO CRF. Overall, the study protocol is well-designed and has the potential to provide valuable insights into the determinants of antibody levels against SARS-CoV-2 in a low-middle income country. The suggestions that I have made are intended to improve the clarity and relevance of the study. Thank you for your kind remarks, we have included your suggestions."
}
]
},
{
"id": "216384",
"date": "15 Nov 2023",
"name": "Ria Lassaunière",
"expertise": [
"Reviewer Expertise Infectious diseases",
"Virology",
"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\nThe well-written protocol addresses relevant questions regarding antibody dynamics, factors associated with seroconversion, longitudinal changes in IgG and IgA levels, and the effect of vaccination on waning antibody levels. A strength of the study is the longitudinal design, inclusion of participants residing in different regions of Ecuador and of various occupations, and assessment of mucosal antibody responses. The authors address the limitations in the study including recall bias using interviews to collect data on a 3-monthly basis; however, it may be difficult to overcome this bias for exposures before enrolment. Furthermore, studying anti-spike antibodies only will not be sufficient to distinguish between infection and vaccination.\nSpecific comments:\nSpecific objective 3 – in addition to the factors listed, vaccine modality is also an important factor to consider. The authors list different vaccines administered to the Ecuadorian population including a whole inactivated vaccine (CoronaVac), mRNA vaccine (Pfizer-BioNTech), and adenoviral-vectored vaccines (AstraZeneca and Cansino), that could be considered.\nAs the authors mention, it will not be possible to differentiate between infection-induced and vaccination-induced antibodies using anti-spike antibodies. With the exception of whole inactivated vaccines, approved COVID-19 vaccines do not include the nucleocapsid protein, a viral protein that induces antibody responses in those who become infected. Did the authors consider using an anti-nucleocapsid ELISA in addition to distinguish vaccine-induced responses from infection-induced responses?\nThe risk of SARS-CoV-2 infection for farmers/merchants and university students/staff may be quite difficult to segregate considering the multitude of other factors contributing to transmission/acquisition of SARS-CoV-2, beyond the possibility to self-isolate. For example, farmers and merchants likely spend more time outdoors, with short interactions with other people in well-ventilated areas, unlike students who are much more social and aggregate in environments with a large number of people for longer periods of time, likely poorly ventilated environments. Since the authors will consider cohort membership for identifying risk factors for baseline seroprevalence, is it necessary to categorize the cohorts according to exposure risk?\nDo the authors anticipate a confounding effect of the antigen used in the ELISA after individuals may have been infected with Omicron that contains >12 amino acid changes in the RBD?\nIt is unclear if this study protocol is written for a prospective study with planned recruitment and sampling, a retrospective study with planned antibody analyses on samples already collected, or an ongoing study. At the time of writing, were the cohorts being recruited (page 6), or were recruited and sample collection done and subjects contacted (page 8)?\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": [
{
"c_id": "11120",
"date": "10 Apr 2024",
"name": "Jose Leon-Rojas",
"role": "Author Response",
"response": "Comment 1: The well-written protocol addresses relevant questions regarding antibody dynamics, factors associated with seroconversion, longitudinal changes in IgG and IgA levels, and the effect of vaccination on waning antibody levels. A strength of the study is the longitudinal design, inclusion of participants residing in different regions of Ecuador and of various occupations, and assessment of mucosal antibody responses. The authors address the limitations in the study including recall bias using interviews to collect data on a 3-monthly basis; however, it may be difficult to overcome this bias for exposures before enrolment. Furthermore, studying anti-spike antibodies only will not be sufficient to distinguish between infection and vaccination. Response 1: Thank you for your comments, we agree that some recall bias will be present in exposure before the enrolment, although given that COVID-19 created significant distress in the country, we believe that participants were likely to have good recall of pre-study COVID-19-related illnesses. We agree that measuring RBD IgG can result in confounding of the antibody levels between infection or vaccination. Comment 2: Specific objective 3 – in addition to the factors listed, vaccine modality is also an important factor to consider. The authors list different vaccines administered to the Ecuadorian population including a whole inactivated vaccine (CoronaVac), mRNA vaccine (Pfizer-BioNTech), and adenoviral-vectored vaccines (AstraZeneca and Cansino), that could be considered. Response 2: The vaccine received will be considered in the analysis and we have made this clearer in the text. Comment 3: As the authors mention, it will not be possible to differentiate between infection-induced and vaccination-induced antibodies using anti-spike antibodies. With the exception of whole inactivated vaccines, approved COVID-19 vaccines do not include the nucleocapsid protein, a viral protein that induces antibody responses in those who become infected. Did the authors consider using an anti-nucleocapsid ELISA in addition to distinguish vaccine-induced responses from infection-induced responses? Response 3: We agree that recent studies indicate that assays to measure levels of IgG nucleocapsid antibodies may not be as robust and replicable as those used to measure spike protein and might wane faster which is a limitation in a longitudinal analysis 1-4. Our study protocol, which was written early in the epidemic and approved by the emergency bioethics committee of the Ecuadorian Ministry of Health, only allowed us to measure spike protein antibodies. In retrospect, we agree that the ability to measure antibodies against other SARS-CoV-2 antigens would have allowed us to distinguish natural immunity from that acquired after vaccination. This limitation has been added to our manuscript. Additionally, the ethics committee that approved our protocol was disbanded soon after the emergency had been resolved and we were therefore unable to modify the protocol to allow us to measure these antibodies. Further, the measurement of IgG specific for spike protein and not for other SARS-CoV-2 antigens will limit our ability to distinguish vaccine-induced antibodies from those induced by natural infection. References: Santosh Dhakal, Tong Yu, Anna Yin, Nora Pisanic, Zoe O Demko, Annukka A R Antar, Andrea L Cox, Christopher D Heaney, Yukari C Manabe, Sabra L Klein, Reconsideration of Antinucleocapsid IgG Antibody as a Marker of SARS-CoV-2 Infection Postvaccination for Mild COVID-19 Patients, Open Forum Infectious Diseases, Volume 10, Issue 1, January 2023, ofac677, https://doi.org/10.1093/ofid/ofac677 Van Elslande J, Oyaert M, Ailliet S, et al. Longitudinal follow-up of IgG anti-nucleocapsid antibodies in SARS-CoV-2 infected patients up to eight months after infection. J Clin Virol 2021; 136:104765. Karger AB, Brien JD, Christen JM, et al. The serological sciences network (SeroNet) for COVID-19: depth and breadth of serology assays and plans for assay harmonization. mSphere 2022; 7:e0019322. Owusu-Boaitey N, Russell TW, Meyerowitz-Katz G, Levin AT, Herrera-Esposito D. Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modelling study. medRxiv 2022.09.08.22279731 [Preprint]. September 9, 2022. Available at: https://doi.org/10.1101/2022.09.08.22279731. Comment 4: The risk of SARS-CoV-2 infection for farmers/merchants and university students/staff may be quite difficult to segregate considering the multitude of other factors contributing to transmission/acquisition of SARS-CoV-2, beyond the possibility to self-isolate. For example, farmers and merchants likely spend more time outdoors, with short interactions with other people in well-ventilated areas, unlike students who are much more social and aggregate in environments with a large number of people for longer periods of time, likely poorly ventilated environments. Since the authors will consider cohort membership for identifying risk factors for baseline seroprevalence, is it necessary to categorize the cohorts according to exposure risk? Response 4: Thank you for your insightful comments. We have categorized the cohorts according to perceived exposure risk. For example, university students during sampling time were self-isolating in their homes with strict curfews mandated by the Ecuadorian government while the merchant/farmer group, rather than working on the fields, depended on face-to-face selling in markets and cattle fairs, places characterized by the agglomeration of people. Comment 5: Do the authors anticipate a confounding effect of the antigen used in the ELISA after individuals may have been infected with Omicron that contains >12 amino acid changes in the RBD? Response 5: We do expect that the Omicron variant will result in cofounding; however, its important to note that in Ecuador, the Omicron variant was starting to become dominant on the 7th of January of 2022, reaching its peak at the end of the month. Until then, all groups had at least two follow-up samples collected. Comment 6: It is unclear if this study protocol is written for a prospective study with planned recruitment and sampling, a retrospective study with planned antibody analyses on samples already collected, or an ongoing study. At the time of writing, were the cohorts being recruited (page 6), or were recruited and sample collection done and subjects contacted (page 8)? Response 6: At the time of writing, all participants had been recruited and were being followed-up. As you can see in figure 2, in the HR cohort sample collection was finalized, whereas in the MR and LR cohorts, 3 of 4 samples were finalized and the final one was ongoing."
}
]
}
] | 1
|
https://f1000research.com/articles/11-1392
|
https://f1000research.com/articles/12-760/v1
|
28 Jun 23
|
{
"type": "Research Article",
"title": "PKD1 gene mutation and ultrasonographic characterization in cats with renal cysts",
"authors": [
"Kotchapol Jaturanratsamee",
"Palin Jiwaganont",
"Pratch Sukumolanan",
"Soontaree Petchdee",
"Kotchapol Jaturanratsamee",
"Palin Jiwaganont",
"Pratch Sukumolanan"
],
"abstract": "Background: Polycystic kidney disease (PKD) has a complex phenotype partly explained by genetic variants related to this disease. Ultrasonography is a promising approach for defining clinical signs. This study aimed to assess kidney characteristics in cats with Polycystin-1 (PKD1) gene mutations and wild-type cats. Kidney characteristics were identified by ultrasonography. Methods: A total of 108 cats of variable breeds aged an average of 37.01±3.50 months were included. Blood examination and biochemical tests were evaluated. For cystic formation, renal ultrasound was performed. The PKD1 gene mutation was identified via polymerase chain reaction (PCR) and DNA sequencing. Matrix correlation and effectiveness of ultrasound for PKD1 mutation detection were determined. Results: The results showed that 19.44% of cats had PKD1 mutations, a high prevalence in Persian and Persian-related breed cats. Our results demonstrated the characteristics of kidneys in wild-type cats and cats with gene mutations. Based on ultrasonography results, there was an association between cats with gene mutations and cyst formation. The findings indicated that ultrasound did not detect cysts in cats aged 4-36 months, supporting the evidence that PKD1 gene mutations may not be present. This study found high sensitivity and renal specificity ultrasound for PKD1 heterozygous mutation. Moreover, cystic formation via renal ultrasound showed an increased risk for PKD1 mutation 2,623 times compared to normal kidneys. Conclusions: Ultrasonographic examination, coupled with genetic investigations, may help to clarify the phenotypic variability of PKD1. The phenotypic profile of PKD1 will guide therapeutic outcomes and reduce the prevalence of PKD morbidity and mortality in cats.",
"keywords": [
"Gene",
"kidney disease",
"mutation",
"polycystic",
"ultrasonography"
],
"content": "Introduction\n\nThe most common hereditary disease in cats is feline polycystic kidney disease (PKD). A previous study reported that the genetic condition of the PKD gene affects Persian and Persian-related cats.1 Renal, hepatic, and pancreatic cysts are the common symptoms of feline PKD, inherited in an autosomal dominant manner.2 This disease is frequently detected in the Persian breed. It is one of this breed’s most common feline genetic diseases, other than diabetes and feline lower urinary tract disease.3 This disease not only impacts the Persian breed but other breeds, including the Exotic Shorthair, British Shorthair, American Shorthair, Himalayan, Scottish fold, Ragdoll, Chartreaux, and Maine Coon breeds, may also be affected by this disease.4–6 The feline Polycystin-1 (PKD1) gene was examined for the point of 85% of causal mutations, and the cats carried heterozygous CA transversion at c.10063 in exon 29, resulting in impaired renal function.1,7\n\nPolycystin-1 upregulation was reported in the renal tissue from a mouse model with a PKD1 mutation. The increased expression of the mammalian target of rapamycin (mTOR) affected autophagy and apoptosis signaling in cells with a PKD1 gene mutation.1,7–9 In addition, many studies have shown the mechanisms by which cyclic adenosine monophosphate (cAMP) levels influence PKD.10–13 Oral administration of antioxidant agents such as DHA-enriched fish oils showed potential renoprotective effects in cats with chronic kidney disease related to PKD gene mutation.14\n\nUltrasonography is a useful diagnostic tool for evaluating the renal structure and renal parenchyma that cannot be evaluated through radiography.15,16 This technique is a useful diagnostic tool for assessing and revealing renal parenchyma alteration, as that occurs when the disease progresses.17 This technique is a practical and accurate approach to diagnosing PKD. Cats with PKD have multiple hypoechoic to anechoic cysts that are round or oval in shape and clearly distinguished from the renal parenchyma.18 In a previous study, ultrasound had a sensitivity of 75% when performed at 16 weeks of age and 91% when performed at 36 weeks of age.19\n\nThis study aims to investigate the association between clinical presentations and the ultrasonography of the kidneys in wild-type cats and cats with gene mutations to provide the guide treatment and aid prevalence estimates of PKD in cats.\n\n\nMethods\n\nThe Ethics Committee of Kasetsart University, Bangkok, Thailand, approved this research on September 12, 2022 (ACKU-65-VET-077). In addition, all cat owners in this study signed an informed consent agreement.38 A total of 108 cats, including 18 Persian cats, 49 Persian-related breed cats, 22 domestic shorthair cats, and 19 Bengal cats, were enrolled in this study at the Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Kasetsart University, from September 2022 to April 2023, as shown in Figure 1. The cat underwent a complete physical examination to evaluate the general condition. All procedures were refined as much as possible to minimize suffering to alleviate the harm to the cats in this study with a high standard that is internationally accepted (‘Best Practice Guidelines’) of veterinary clinical care for individual cats and following the ethical approvals. This study adhered to the ARRIVE guidelines.39\n\n(A) Various breeds of enrolled cats. (B) Age in the different groups, including 4-12 months, 13-24 months, 25-36 months, 37-48 months, and more than 48 months. (C) Weight comprising 2.0-3.0, 3.1-4.0, 4.1-5.0, and more than 5.0 kg.\n\nA complete blood count and serum biochemistry profile were performed for each cat. Kidney characterization was assessed by ultrasonography analysis in all cats using only gentle restraint and no sedation. The non-invasive two-dimensional (2D)-mode ultrasonography was used to define the kidney structure and size. The ultrasonography images have demonstrated that multiple cysts are a common finding in PKD1 heterozygous mutation cats, as shown in Figure 2.\n\n(A) Normal kidney appearance without cystic formation. (B) Multiple cyst formation in renal parenchyma. In (A) and (B), the ultrasonography image was cropped for the proper size.\n\nDNA amplification with polymerase chain reaction (PCR) was performed to detect PKD1 gene mutation. PCR protocol obtained the specific forward and reversed primers from Lee et al.18 The PCR primers were PKD-forward 5′-CAGGTAGAC GGGATAGACGA-3′ and PKD-reverse 5′-TTCTTCCTGGTCAACGACTG-3′. In brief, DNA was extracted from the blood using FavorPrep Blood Genomic DNA Extraction Mini Kit (Farvogen, Taiwan). Then, 2 μl of extracted DNA from blood (Farvogen, Taiwan) was mixed with 2.5 μl of 10X Taq buffer, 0.2 μl of dNTPs (25 mM each dNTP) (Thermo Fisher Scientific, USA), 1.5 μl of MgCl2 (25 mM), 1 μl of each custom forward and reverse primer from the manufacturer (Integrated DNA Technologies, USA) (10 μM each primer), 1 unit of Taq DNA polymerase (Thermo Fisher Scientific, USA), and 16.7 μl of nuclease-free water. The final volume of the PCR reaction was 25 μl per reaction. The PCR condition was as follows: heat-activation at 94°C for 3 minutes, 35 cycles of denaturation for 1 minute, annealing at 58°C for 1 minute, and extension at 72°C for 1 minute. Finally, the final extension was performed at 72°C for 10 minutes via Biometra Thermocycler T-Gradient ThermoBlock (Thermo Fisher Scientific, USA). The PCR product was detected with 1.5% agarose gel electrophoresis. The PCR product was visualized under gel documentation (Bio-rad, USA) at 559 bp. The PCR product was stored at -20°C until sequencing. The Barcode-tagged (BT) sequencing method was performed to detect the PCR product’s nucleotide. According to BT sequencing, the PCR product was analyzed by Celemics, Inc. (Seoul, Korea). Single nucleotide polymorphism of the PKD1 gene was detected using the BioEdit version 7.2 (RRID:SCR_007361) program and A plasmid Editor (ApE) version 2.0.60 (RRID:SCR_014266) program.\n\nThe procedure for ultrasound examination of the kidneys followed that of a previous report.4,20 Briefly, ultrasonography was performed using a Mindray real-time ultrasound machine (model DC-7, Shenzhen Mindray Bio-medical Electronics, Nanshan, Shenzhen, China) with a linear transducer (frequency 7.5-12.0 MHz). The kidneys were examined in the longitudinal and transverse planes. Results were recorded for each cat. The three separated regions, the renal cortex, the renal medulla, and the renal sinus, were identified. The renal sinus is the most hyperechoic component of the kidney and is surrounded by the renal pelvis and vascular branches. In the renal pelvis, ultrasonography images can be assessed using the renal crest as a landmark. The renal size can be measured by measuring from the long axis view. The renal lengths of the right and left kidneys were measured to identify the renal structure, as shown in Figure 2.\n\nDescriptive statistics were determined as mean ± standard error of the mean (SEM). An evaluation of the effectiveness of diagnostic tests was performed. The datasets were analyzed using a paired Student’s- t-test. An odds ratio (OD) was performed to measure the association between cysts in renal parenchyma and PKD1 mutation. A correlation matrix was used to represent the correlation coefficients for different variables. Pearson’s correlation coefficient was used to determine the correlation between variables and to analyze the multiple linear regression models that contained several independent variables (GraphPad Prism (RRID: SCR_002798) Software version 9.0, USA). A P-value of 0.05 or less was indicated for statistical significance.\n\n\nResults\n\nThe number of cats in the PKD1 mutation group was 21 (19.44 %) from an overall population of 108 cats. The cats in the PKD1 mutation group were older than those in the wild-type group (50.89 ± 9.19 vs. 33.93 ± 3.59 months, P = 0.051). However, there were no significant differences in weight between cats in the wild-type group and the PKD1 mutation group. General characteristics and ultrasonographic parameters for the cats are reported in Table 1.36,37 The size of the left kidney was significantly larger in the PKD1 mutation group than in the wild-type group. Blood profiles and serum biochemistry results are reported in Table 2. The levels of other biochemical profiles, such as symmetric dimethyl arginine creatinine (SDMA), significantly differed between groups. However, the blood profile parameters of red blood cell count, hematocrit, and plasma protein were not different between the groups.\n\n* P < 0.05.\n\n*** P < 0.001.\n\nThe association between ultrasonography findings and the genotypes of PKD1 mutations was analyzed for 108 cats. PKD1 heterozygous mutations were identified in 21 cats, and the results showed significant differences between C/C and C/A genotypes for the homozygous wild-type and heterozygous mutation (Figure 3). In the present study, gene mutation cats were associated with cyst formation in cats. The ultrasonographic analysis showed renal cysts in 19 cats, and all of these cats harbored PKD1 heterozygous mutations.\n\n(A) Gel electrophoresis represented 559 bp of target DNA of the PKD1 gene. Lane 1 represents DNA marker (M), while Lane 2 and Lane 3 show DNA products from cats with homozygous wild-type and heterozygous mutation, respectively. Lane 4 indicates negative control. (B) The barcode-tagged (BT) sequencing result of PKD1 was shown in two groups, including homozygous wildtype (C/C) and heterozygous mutation (C/A). The green arrow pointed to two peaks of cytosine and alanine, while the blue arrow represented one peak of cytosine. In (A), the gel electrophoresis image was adjusted to the darkness of the background and cropped for the proper size. In (B), the chromatogram results were cropped from BT sequencing in the Bioedit program and the arrow cursors (green and blue) were added, pointing to the mutation area for clarity and easy understanding. The text of the chromatogram nucleotide above the sequencing picture was edited in another font with bold letters.\n\nRegarding renal ultrasonography, the effectiveness of this method was evaluated for detecting the variation of PKD1 gene polymorphism (Table 3). The sensitivity and specificity of renal ultrasound accounted for 100.00% (95% CI, 84.54 to 100.00) and 98.91% (95% CI, 94.10 to 99.94), respectively. In addition, positive predictive value (PPV) and negative predictive value (NPV) were indicated at 95.45% (95% CI, 78.20 to 99.77) and 100.00% (95% CI, 95.95 to 100.00), respectively. On top of that, according to the OD, presenting renal cysts from renal ultrasonography increased the possibility for PKD1 heterozygous mutation 2,623.00 times (95% CI, 103.2465 to 66637.8792, P < 0.0001).\n\nAge, body weight, right kidney size, left kidney size, and the number of cysts were analyzed using correlation matrix analysis (Figure 4). The results showed that age and weight were negatively related to the number of cysts. However, the weight was related to kidney size. There is likely no gene mutation if the cyst is not found at less than 36 months of age. Cysts are usually found in small cats weighing between 2 and 4 kg (Figure 5).\n\n(A) PKD1 wild-type, (B) PKD1 heterozygous mutation, (C) no renal cyst and (D) renal cysts.\n\n\nDiscussion\n\nThis study’s differential ultrasonographic profiles between cats with PKD1 mutations and wild-type cats may provide complementary tools for detecting and evaluating polycystic kidney disease. The findings in our study are consistent with previously reported findings that the formation of the cysts is closely related to PKD1 gene mutations with high sensitivity and specificity.18 As well as that, reports from Italy and Taiwan revealed that the sensitivity of ultrasonography was approximately 78.6 to 92.6%, and the specificity was 91 to 100%.18,20 However, a previous study reported that pure-breed Maine Coon cats developed cystic formation in renal parenchyma without PKD1 gene mutation.21 Therefore, the gold-standard technique of PKD1 gene mutation, PCR, and DNA sequencing is still recommended for confirming the genotype and further breeding selection consideration.\n\nOf the total 108 cats examined by ultrasound, 19 were confirmed to have renal cysts, and in every cat with cysts found, a PKD1 mutation was present. Previous studies have indicated age-related cyst numbers for an ultrasound to diagnose PKD1 mutations. The cysts detected are sufficient for a positive diagnosis in young cats up to 12 months of age. In addition, these criteria will help to determine a positive result for PKD1 mutations if multiple bilateral cysts are detected (>10 per kidney) or if cysts are not detected in older cats. The results from this study are similar to a previous study that reported a positive correlation between the detection of renal cysts and age, as cyst detection was increased in older animals.22\n\nThe apoptosis pathway is associated with inflammation in PKD in humans and mouse models.23–26 Bcl-2 and Erb-b2 may be related to the pathway of PKD in cats with sarcomeric protein mutations. Inhibition of the apoptosis pathway might be associated with renal fibrosis and cyst expansion in cats with PKD.27,28\n\nCaspases are another essential target in the apoptosis mechanism.29,30 Caspases are involved in preserving kidney function, suggesting caspases as a potential new target for the treatment of PKD.25\n\nPKD1 mutation is caused by disrupting the mechanism that controls the tubular diameter. The cyst characteristics were reported to be involved in cAMP signal transduction. The vasopressin that acts on the V2 receptor is the most potent catalyst for cAMP formation. Vasopressin 2 receptors are located in the collecting ducts, connecting ducts, and thickened limbs of Henle, which is the area of cyst formation. Tolvaptan has been used in treating PKD because the anti-vasopressin 2 receptor plays an important role in cyst growth.31–33 Other medications, such as metformin, which targets AMPK and cAMP signaling, have shown great promise in reducing cyst formation and cellular proliferation.34,35 However, reports linking these novel therapeutic drugs with PKD in cats still require further confirmation. Future clinical trials of potential signaling pathways are crucial in PKD diagnosis and treatment in feline patients.\n\n\nConclusions\n\nThe frequency of PKD1 mutations was high in Persian and Persian-related breed cats. Such modifications were associated with the polycystic kidney phenotype. Ultrasonographic examination of cats will be a helpful tool for the routine identification of carriers of the mutated gene for polycystic kidney disease in cats. The results from this study may provide important information on clinical presentation and a gene associated with feline PKD. Genetic insights from genes may enable a more precise diagnosis of the type of renal cyst, which allows treatment or prevention strategies. Furthermore, knowing a genetic susceptibility to kidney cysts early may help to more accurately predict those most at risk of chronic kidney disease in the future.\n\n\nEthical approval\n\nThe work described in this manuscript involved using non-experimental (owned) animals. Established internationally recognized high standards (‘best practice’) of veterinary clinical care for the individual patient always followed ethical approval, and written informed consent for publication of the participants was obtained from the owners.",
"appendix": "Data availability\n\nFigshare: Raw data PKD1 in cats. https://doi.org/10.6084/m9.figshare.22957526.v1. 36\n\nFigshare: Figures. https://doi.org/10.6084/m9.figshare.22957715.v1. 37\n\nFigshare: consent form. https://doi.org/10.6084/m9.figshare.22958243.v1. 38\n\nRepository: ARRIVE checklist for ‘PKD1 gene mutation and ultrasonographic characterizations in cats with renal cysts’. https://doi.org/10.6084/m9.figshare.23123414.v1. 39\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 are grateful to Kasetsart University Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Kasetsart University, for providing facilities for the study.\n\n\nReferences\n\nLyons LA, Biller DS, Erdman CA, et al.: Feline polycystic kidney disease mutation identified in PKD1. J. Am. Soc. Nephrol. 2004; 15: 2548–2555. PubMed Abstract | Publisher Full Text\n\nEaton KA, Biller DS, DiBartola SP, et al.: Autosomal dominant polycystic kidney disease in Persian and Persian-cross cats. Vet. Pathol. 1997; 34: 117–126. PubMed Abstract | Publisher Full Text\n\nSchirrer L, Marín-García PJ, Llobat L: Feline polycystic kidney disease: an update. Vet. Sci. 2021; 8: 269. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBeck C, Lavelle RB: Feline polycystic kidney disease in Persian and other cats: a prospective study using ultrasonography. Aust. Vet. J. 2001; 79: 181–184. PubMed Abstract | Publisher Full Text\n\nBarrs VR, Gunew M, Foster SF, et al.: Prevalence of autosomal dominant polycystic kidney disease in Persian cats and related-breeds in Sydney and Brisbane. Aust. Vet. J. 2001; 79: 257–259. PubMed Abstract | Publisher Full Text\n\nBarthez PY, Rivier P, Begon D: Prevalence of polycystic kidney disease in Persian and Persian related cats in France. J. Feline Med. Surg. 2003; 5: 345–347. PubMed Abstract | Publisher Full Text\n\nGrahn R, Biller D, Young AE, et al.: Genetic testing for feline polycystic kidney disease. Anim. Genet. 2004; 35: 503–504. PubMed Abstract | Publisher Full Text\n\nNivy R, Lyons L, Aroch I, et al.: Polycystic kidney disease in four British shorthair cats with successful treatment of bacterial cyst infection. J. Small Anim. Pract. 2015; 56: 585–589. PubMed Abstract | Publisher Full Text\n\nCornec-Le Gall E, Torres VE, Harris PC: Genetic complexity of autosomal dominant polycystic kidney and liver diseases. J. Am. Soc. Nephrol. 2018; 29: 13–23. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTorres VE, Chapman AB, Devuyst O, et al.: Tolvaptan in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med. 2012; 367: 2407–2418. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRinschen MM, Schermer B, Benzing T: Vasopressin-2 receptor signaling and autosomal dominant polycystic kidney disease: from bench to bedside and back again. J. Am. Soc. Nephrol. 2014; 25: 1140–1147. PubMed Abstract | Publisher Full Text\n\nTorres VE, Chapman AB, Devuyst O, et al.: Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N. Engl. J. Med. 2017; 377: 1930–1942. PubMed Abstract | Publisher Full Text\n\nRowe I, Chiaravalli M, Mannella V, et al.: Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy. Nat. Med. 2013; 19: 488–493. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKobayashi S, Kawarasaki M, Aono A, et al.: Renoprotective effects of docosahexaenoic acid in cats with early chronic kidney disease due to polycystic kidney disease: a pilot study. J. Feline Med. Surg. 2022; 24: e505–e512. PubMed Abstract | Publisher Full Text\n\nDomanjko-Petrič A, Černec D, Cotman M: Polycystic kidney disease: a review and occurrence in Slovenia with comparison between ultrasound and genetic testing. J. Feline Med. Surg. 2008; 10: 115–119. PubMed Abstract | Publisher Full Text\n\nWills SJ, Barrett EL, Barr FJ, et al.: Evaluation of the repeatability of ultrasound scanning for detection of feline polycystic kidney disease. J. Feline Med. Surg. 2009; 11: 993–996. PubMed Abstract | Publisher Full Text\n\nBartges JW: Chronic kidney disease in dogs and cats. Vet. Clin. Small Anim. Pract. 2012; 42: 669–692. Publisher Full Text\n\nLee YJ, Chen HY, Hsu WL, et al.: Diagnosis of feline polycystic kidney disease by combining ultrasonographic examination and PKD1 gene analysis. Vet. Rec. 2010; 167: 614–618. PubMed Abstract | Publisher Full Text\n\nBiller DS, DiBartola S, Eaton KA, et al.: Inheritance of polycystic kidney disease in Persian cats. J. Hered. 1996; 87: 1–5. Publisher Full Text\n\nBonazzi M, Volta A, Gnudi G, et al.: Comparison between ultrasound and genetic testing for the early diagnosis of polycystic kidney disease in Persian and Exotic Shorthair cats. J. Feline Med. Surg. 2009; 11: 430–434. Publisher Full Text\n\nGendron K, Owczarek-Lipska M, Lang J, et al.: Maine Coon renal screening: ultrasonographical characterization and preliminary genetic analysis for common genes in cats with renal cysts. J. Feline Med. Surg. 2013; 15: 1079–1085. PubMed Abstract | Publisher Full Text\n\nNoori Z, Moosavian HR, Esmaeilzadeh H, et al.: Prevalence of polycystic kidney disease in Persian and Persian related-cats referred to Small Animal Hospital, University of Tehran, Iran. Iranian J. Vet. Res. 2019; 20: 151.\n\nEcder T, Melnikov VY, Stanley M, et al.: Caspases, Bcl-2 proteins and apoptosis in autosomal-dominant polycystic kidney disease. Kidney Int. 2002; 61: 1220–1230. PubMed Abstract | Publisher Full Text\n\nZeng F, Miyazawa T, Kloepfer LA, et al.: Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice. Kidney Int. 2014; 86: 538–547.\n\nNowak KL, Edelstein CL: Apoptosis and autophagy in polycystic kidney disease (PKD). Cell. Signal. 2020; 68: 109518. Publisher Full Text\n\nRichards T, Modarage K, Malik SA, et al.: The cellular pathways and potential therapeutics of Polycystic Kidney Disease. Biochem. Soc. Trans. 2021; 49: 1171–1188. Publisher Full Text\n\nBilgen N, Bişkin Türkmen MB, Çınar Kul B, et al.: Prevalence of PKD1 gene mutation in cats in Turkey and pathogenesis of feline polycystic kidney disease. J. Vet. Diagn. Investig. 2020; 32: 549–555. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXue C, Mei C-L: Polycystic kidney disease and renal fibrosis. Renal fibrosis: mechanisms and therapies.2019; pp. 81–100.\n\nSwenson-Fields KI, Ward CJ, Lopez ME, et al.: Caspase-1 and the inflammasome promote polycystic kidney disease progression. Front. Mol. Biosci. 2022; 9: 1300. Publisher Full Text\n\nTao Y, Kim J, Faubel S, et al.: Caspase inhibition reduces tubular apoptosis and proliferation, slowing disease progression in polycystic kidney disease. Proc. Natl. Acad. Sci. 2005; 102: 6954–6959.\n\nPatel V, Chowdhury R, Igarashi P: Advances in the pathogenesis and treatment of polycystic kidney disease. Curr. Opin. Nephrol. Hypertens. 2009; 18: 99–106. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBlair HA: Tolvaptan: a review in autosomal dominant polycystic kidney disease. Drugs. 2019; 79: 303–313. Publisher Full Text\n\nBellos I: Safety profile of Tolvaptan in the treatment of autosomal dominant polycystic kidney disease. Ther. Clin. Risk Manag. 2021; 649–656.\n\nLian X, Wu X, Li Z, et al.: The combination of metformin and 2-deoxyglucose significantly inhibits cyst formation in miniature pigs with polycystic kidney disease. Br. J. Pharmacol. 2019; 176: 711–724. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGattone VH, Wang X, Harris PC, et al.: Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat. Med. 2003; 9: 1323–1326. PubMed Abstract | Publisher Full Text\n\nPetchdee S: Raw data PKD1 in cats. [Dataset]. figshare. 2023. Publisher Full Text\n\nPetchdee S: Figures. [Dataset]. figshare. 2023. Publisher Full Text\n\nPetchdee S: consent form. [Dataset]. figshare. 2023. Publisher Full Text\n\nPetchdee S: ARRIVE checklist_edited. [Dataset]. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "183547",
"date": "16 Oct 2023",
"name": "Leslie A. Lyons",
"expertise": [
"Reviewer Expertise Genetics PKD feline diseases"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript by Jaturanratsamee et al., entitled “PKD1 gene mutation and ultrasonographic characterization in cats with renal cysts” describes the evaluation of 108 cats of variable breeds. Blood examination and biochemical tests were evaluated. For cyst detection, renal ultrasound was performed. The PKD1 gene mutation was identified via polymerase chain reaction (PCR) and DNA sequencing. 19.44% (21 of 108) of cats had PKD1 mutations, a high prevalence in Persian and Persian-related breed cats.\nThe authors present a dataset including 108 cats in which 21 had the variant for PKD1. The dataset is important however the authors need to do some different presentations that would be of more significant value to the veterinary and PKD research communities. Hence. “partly” for the interpretation of data. Partly for data presentation as all US images are not available.\nThe authors should note 87 cats had no cysts at all. What is the frequency of singular cysts in humans, I think this supports cats rarely have singular cysts, or at least less commonly than humans.\n18 Persian cats, 49 Persian-related breed cats, 22 domestic shorthair cats, and 19 Bengal cats – need table with age at US for each cat – the figures are less useful. Produce a summary table that summarizes groups, per breed, the cats without the PKD1 variant and then provides each breed cat that had PKD individually. Which cat had PKD1 variant but no cysts – what was the cat’s age? Mention this in the text.\nScottish Folds are popular in eastern countries, however, the rate of PKD is high – contrast to other, recent population data suggesting PKD1 is a very low rate in Persians and other breeds.\nBUN high for both populations – age correlation is important – please comment.\nPKD is one of the most common hereditary disease – actually simple Mendelian diseases in cats. HCM may be more common but has a complex inheritance.\nWas the hair clipped for the US evaluations or alcohol or gel applied for US?\nOverall creatinine for overall population was 2.21 _ 0.19 – odd not intermediate – correct?\nWhich was most predictive of PKD – renal failure, number of cysts, age, BUN, SDMA?\n\nAny cats in renal failure?\nWas left to right kidney size significantly different in PKD1 cats?\nFigure 4 would be better with biochemistries and cysts, kidney size, in affected cats versus normal. More figures like this, less pie charts.\nThe results showed that age and weight were negatively related to the number of cysts? I think this is misstated in results.\n\"The feline Polycystin-1 (PKD1) gene was examined for the point of 85% of causal mutations\" – not sure what this 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? 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? Partly",
"responses": [
{
"c_id": "10416",
"date": "30 Nov 2023",
"name": "Soontaree Petchdee",
"role": "Author Response",
"response": "Reviewer1: The authors present a dataset including 108 cats in which 21 had the variant for PKD1. The dataset is important however the authors need to do some different presentations that would be of more significant value to the veterinary and PKD research communities. Hence. “partly” for the interpretation of data. Partly for data presentation as all US images are not available. The authors should note 87 cats had no cysts at all. What is the frequency of singular cysts in humans, I think this supports cats rarely have singular cysts, or at least less commonly than humans. Answer to the reviewer: We apologize for this point. We have edited this point in the revised manuscript in the discussion section. Of the total 108 cats examined by ultrasound, no cyst was found in 87 cats of the wild-type group. However,19 cats were confirmed to have renal cysts, and in every cat with cysts found, a PKD1 mutation was presented. 18 Persian cats, 49 Persian-related breed cats, 22 domestic shorthair cats, and 19 Bengal cats – need a table with age at US for each cat – the figures are less useful. Produce a summary table that summarizes groups, per breed, the cats without the PKD1 variant and then provide each breed cat that had PKD individually. Which cat had PKD1 variant but no cysts – what was the cat’s age? Mention this in the text. Answer to the reviewer: We appreciate the helpful comment. We have edited this point in the revised manuscript in Table 3 and mentioned more information in the results part. We apologize for this point. However, there was a 51-month-old domestic shorthair cat without the PKD1 gene mutation developing the cysts in renal parenchyma. Table 3 demonstrates the number of cats in various breeds with PKD1 gene mutation and renal cyst development. Scottish Folds are popular in eastern countries, however, the rate of PKD is high – contrast to other, recent population data suggesting PKD1 is a very low rate in Persians and other breeds. Answer to the reviewer: We appreciate the helpful comment. We have edited this point in the revised manuscript in the discussion section. This study found that the rate of PKD1 gene mutation was high in Persian and Persian-related breed cats including Scottish Folds cats, Previous reports has been suggested that PKD1 mutation was found at very low rates in Persians and other breeds which is contrary to our results. The high number of PKD1 mutations that had been reported may be due to the Persian and Persian-related breed cats being a popular cat breed in eastern countries and Thailand. BUN is high for both populations – age correlation is important – please comment. Answer to the reviewer: We apologize for this point. We have edited this point in the revised manuscript in the results and discussion part. As indicated in Table 2, the levels of BUN were mildly elevated than the normal reference value. However, Pearson’s correlation results revealed that there was no correlation between age and BUN levels in WT (r=0.1436 P = 0.62) and PKD1 mutation group (r=0.3234 P = 0.099). PKD is one of the most common hereditary diseases – actually simple Mendelian diseases in cats. HCM may be more common but has a complex inheritance. Answer to the reviewer: We apologize for this point. We have edited this point in the revised manuscript in the introduction part. Feline polycystic kidney disease (PKD) is an inherited disorder that develops cysts in the renal parenchyma. Was the hair clipped for the US evaluations or alcohol or gel applied for US? Answer to the reviewer: We apologize for this point. We have edited this point in the revised manuscript in the materials and methods part. In our ultrasonographic examination, all cats were clipped the hair in the abdominal area and the ultrasonographic gel was used in all cats. Overall creatinine for overall population was 2.21 _ 0.19 – odd not intermediate – correct? Answer to the reviewer: We apologize for this point. We have edited this point in the revised manuscript in the results part. Additionally, the results of average creatinine levels in overall cats were elevated. Nonetheless, our results demonstrated that increasing creatinine exceeding 2.0 mg% may slightly increase the possibility for renal cyst formation by 1.41 times (95% CI, 0.3827 to 5.1764, P = 0.6070). Which was most predictive of PKD – renal failure, number of cysts, age, BUN, SDMA? Any cats in renal failure? Answer to the reviewer: We apologize for this point. We have edited this point in the revised manuscript in the results part. The enrolled cats in this study are represented with either renal failure or non-renal failure. Therefore, cats with increasing SDMA, an age exceeding 36 months, body weight between 2-4 kg, and renal cyst formation from ultrasonographic examination are a high possibility of PKD1 gene mutation with PKD disorder. According to the elevated BUN in our study, the enrolled cats in this study are represented with either renal failure or non-renal failure. The high levels of BUN and increasing age were not related in contrast with the prior study from humans at that age and BUN indicated a positive correlation. Was left to right kidney size significantly different in PKD1 cats? Answer to the reviewer: We apologize for this point. We have edited this point in the revised manuscript in the results part. However, there was no statistically significant difference between right and left kidney size in cats affected with PKD1 mutation (P=0.9980). Figure 4 would be better with biochemistries and cysts, kidney size, in affected cats versus normal. More figures like this, less pie charts. Answer to the reviewer: We apologize for this point. We have edited this point in the revised manuscript and added Figure 4. The results showed that age and weight were negatively related to the number of cysts? I think this is misstated in results. Answer to the reviewer: We apologize for this point. We have edited this point in the revised manuscript in the discussion part. As in Figure 4, the results of matrix correlation show a negative correlation between the number of cysts and body weight (r=0.08) and age (r=0.44). Nevertheless, our study indicated a negative correlation between the age and the number of cysts in recruited cats. Moreover, the cats in this study have a negative correlation between cyst number and body weight. This could potentially result from the manifestation of PKD symptoms in cats with PKD1 mutation. \"The feline Polycystin-1 (PKD1) gene was examined for the point of 85% of causal mutations\" – not sure what this means. Answer to the reviewer: We apologize for this point. We have edited this point in the revised manuscript in the introduction part. The polycystin-1 (PKD1) gene mutation was indicated for 85% of human autosomal dominant polycystic kidney disease (ADPKD). The mutation of the PKD1 gene in cats carried heterozygous CA transversion at c.10063 in exon 29, resulting in impaired renal function. Best regards Soontaree Petchdee Corresponding author"
}
]
}
] | 1
|
https://f1000research.com/articles/12-760
|
https://f1000research.com/articles/13-140/v1
|
23 Feb 24
|
{
"type": "Case Report",
"title": "Case Report: Granulocytic Sarcoma of the Parotid in Chronic Myeloid Leukemia: A Case Report and Literature review",
"authors": [
"Priya Chatterjee",
"Kishor Hiwale",
"Sunita Vagha",
"Kishor Hiwale",
"Sunita Vagha"
],
"abstract": "Granulocytic sarcomas are infrequent, extramedullary malignant occurrences, generally seen with or secondary to acute myeloid leukemia (AML). Their association with chronic myeloid leukemia (CML) is rare and their appearance in parotid gland is sparsely reported in the literature, as per our literature search. In this report, we present an unusual and rare case of imatinib resistant BCR-ABL1 positive secondary granulocytic sarcoma to CML in chronic phase. The rarity of this clinical presentation presents a diagnostic dilemma, which required the pathologist and the clinician to combine a strong clinical suspicion with cytopathological features to diagnose this case, in order to ensure timely therapeutic modifications (shift from imatinib to second-generation tyrosine kinase inhibitor), considering the improvements in prognosis of imatinib resistant granulocytic sarcomas.",
"keywords": [
"Granulocytic sarcoma",
"Chronic myeloid leukemia",
"parotid swelling"
],
"content": "Introduction\n\nGranulocytic sarcomas (GS) are a rare build-up of the malignant myeloid progenitor cells at an extramedullary location, often leading to an architectural distortion of the affected areas. These tumors typically accompany acute myeloid leukemia (AML) (3–8%), myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN) or chronic myeloid leukemia (CML) only during the blast crisis.1 Further, GS has a predilection towards young and male patients and most common sites include lymph nodes, paraspinal area, dura, orbit, skin, soft tissues, bone, mediastinum, lungs, peritoneum, and the gastrointestinal tract.1 Salivary gland involvement of GS is very rare, more so in case of a CML patient in chronic phase.2 Here, we present an extremely rare case of GS involving the parotid gland in a previously diagnosed elderly female patient of CML in chronic phase.\n\n\nCase report\n\nA 74-year-old female of Indian ethnicity presented to the outpatient department of a tertiary care hospital in Maharashtra in January 2023, with an insidious onset swelling on the right sided angle of the mandible since the past 1 month (Figure 1). She had been diagnosed in 2020 with CML (chronic phase) and BCR-ABL1 positive, confirmed by flow cytometry and cytogenetics, for which she was initiated on oral imatinib therapy 400 mg daily (tyrosine kinase inhibitor). Otherwise, she had no known co-morbidities. The patient was a farmer, however, currently unable to work on health grounds. Further, the patient did not provide any relevant family history. Examination revealed a 2.5×2.5 cm solitary nodular mass, non-tender, firm to the touch and not fixed to underlying tissues. Her laboratory parameters, traced back from diagnosis till present episode are as mentioned in Table 1. The peripheral smear picture from the present episode is reflected in Figure 2. The fine needle aspiration cytology (FNAC) of the right parotid swelling performed under aseptic conditions revealed a microscopic picture of neoplastic population consisting of myeloblast, myelocytes, metamyelocytes, promyelocytes and polymorphs arranged diffusely (Figure 3). Thus, combined with the past history and the present episode’s peripheral smear and FNAC findings, a diagnosis of extra medullary relapse involving parotid gland in a known case of CML (chronic phase) on therapy was arrived upon for this patient. Post diagnosis, due to development of imatinib resistance, it was discontinued, and the treatment modality was changed to dasatinib 100 mg daily. On her subsequent routine follow-up, the patient has been responding well to her treatment, with the resolution of the right parotid swelling and no evidence of relapse observed, with her blood investigations near normal almost 6 months post the current visit.\n\n\n\n1. Hb – 7.2 g/dL\n\n2. TLC – 2.25 lac cells/mm3\n\n3. DLC –\n\na. Myeloblasts – 5%\n\nb. Promyelocytes – 30%\n\nc. Myelocytes – 10%\n\nd. Metamyelocytes – 6%\n\ne. Bands + neutrophils – 30%\n\nf. Lymphocytes – 10%\n\ng. Monocytes – 4%\n\nh. Eosinophils – 2%\n\ni. Basophils – 3%\n\n4. RBC – Predominantly normocytic with mild hypochromic RBCs, showing anisopoikilocytosis, with few macrocytes, microcytes and pencil cells\n\n5. nRBCs – 5.4 nRBCs/100 WBCs\n\n6. Platelets – adequate smear, with absolute platelet count – 2.2 lac cells/cu. Mm\n\n7. No hemoparasites seen\n\n8. WBCs – Total counts increased on smear with shift to left up to blasts\n\n\n\n1. Hb – 10.5 g/dL\n\n2. TLC – 1.82 lac cells/mm3\n\n3. DLC –\n\na. Myeloblasts – 3%\n\nb. Promyelocytes – 27%\n\nc. Myelocytes – 5%\n\nd. Metamyelocytes – 5%\n\ne. Bands + neutrophils – 40%\n\nf. Lymphocytes – 10%\n\ng. Monocytes – 4%\n\nh. Eosinophils – 2%\n\ni. Basophils – 4%\n\n4. RBC – Mild anisopoikilocytosis with normocytic normochromic RBCs along with few microcytes, pencil cells and occasional macrocytes\n\n5. nRBCs – 2-3 nRBCs/100 WBCs\n\n6. Platelets – adequate smear, with absolute platelet count – 2.2 lac cells/cu. Mm\n\n7. No hemoparasites seen\n\n8. WBCs – Total counts increased on smear with shift to left upto blasts\n\n\n\n1. Hb – 10.2g/dl\n\n2. TLC – 3,200 cells/mm3\n\n3. DLC –\n\na. Myelocytes – 02%\n\nb. Metamyelocytes – 08%\n\nc. Neutrophils – 70%\n\nd. Lymphocytes – 15%\n\ne. Monocytes – 03%\n\nf. Eosinophils – 02%\n\ng. Basophils – 00%\n\n4. RBCs – Normocytic normochromic RBCs with occasional normoblasts seen\n\n5. Platelets – adequate on smear\n\n6. Absolute platelet count – 1,88,000/cumm as per cell counter\n\n7. No haemoparasites seen.\n\n8. WBCs – Total count reduced on smear\n\n\n\n1. Adequate, hypercellular with replacement of fat by hyperplastic hemopoietic cells with marked myeloid hyperplasia\n\n2. M:E ratio – increased\n\n3. Few megakaryocytes seen with normal morphology\n\n\nDiscussion\n\nThe salivary gland involvement of GS is an extremely rare phenomenon, especially in a patient diagnosed with CML in chronic phase.2 Our literature search on PubMed with the following key-words “myeloid sarcoma,” “granulocytic sarcoma,” “chloroma,” “extramedullary myeloid tumor,” “salivary gland,” and “parotid gland,” revealed only 18 cases mentioned in 11 case reports and three retrospective reviews (Table 2).2–15 Our search was limited to English language reports. Any report of GS originating from a lymph node without salivary gland involvement was excluded. The novelty of our case was that our patient is an elderly person with parotid involvement alone. Pertinently, she was diagnosed with CML BCR-ABL1 positive, which presents an overall clinical presentation not reported in the literature, since GS accompanies AML or CML in the blast phase. Hence, in the background of this clinical presentation, the ultrasound-guided FNAC was performed which revealed a cellular picture comprising of all myeloid lineages, different from the usual picture comprising of myeloblasts/AML-like picture seen in GS. Despite the rarity of this presentation, it was the prior and recent diagnosis of CML as well as the rapid development of the nodular parotid lesion, which raised a clinical suspicion of imatinib resistant secondary GS to BCR-ABL1 positive CML in chronic phase. Though imatinib has emerged as the front-line therapy for BCR-ABL1 positive CML, its resistance is on the rise.16 In such cases, if patient remains in chronic phase, second-generation tyrosine kinase inhibitors (TKIs) are advised17; thereby our patient was switched to dasatinib and responded well to the change in therapy.\n\nThrough this case, we wanted to highlight the need for combining strong clinical suspicion with cytological evaluation for the timely diagnosis of such rare secondary GS cases, so that appropriate treatment decisions can be undertaken, considering the improvement in prognosis with the advent of second-generation TKIs.\n\n\nConsent\n\nWritten informed consent has been taken from the patient’s family for the use and publication of the patient’s data in this manuscript. As the patient found it difficult to comprehend the discussion around the consent for use of her data for scientific publication, hence she delegated her family to understand and provide consent on her behalf.",
"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\nRakesh M, Mohamed Kunhi NM, Vijayaraghavan NS, et al.: Granulocytic sarcoma: A case series and review. J. Appl. Hematol. 2021; 12: 51–54. Publisher Full Text\n\nDagna F, Giordano P, Boggio V, et al.: Myeloid sarcoma of submandibular salivary gland. SAGE Open Med. Case Rep. 2016; 4: 2050313X1562501. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDufour C, Garaventa A, Brisigotti M, et al.: Massively diffuse multifocal granulocytic sarcoma in a child with acute myeloid leukemia. Tumori. 1995; 81(3): 222–224. PubMed Abstract | Publisher Full Text\n\nÇankaya H, Ugras S, Dilek I: Head and neck granulocytic sarcoma with acute myeloid leukemia: three rare cases. Ear Nose Throat J. 2001; 80(4): 224–229. Publisher Full Text\n\nNayak DR, Balakrishnan R, Raj G, et al.: Granulocytic sarcoma of the head and neck: a case report. Am. J. Otolaryngol. 2001; 22(1): 80–83. Publisher Full Text\n\nSood BR, Sharma B, Kumar S, et al.: Facial palsy as first presentation of acute myeloid leukemia. Am. J. Hematol. 2003; 74(3): 200–201. PubMed Abstract | Publisher Full Text\n\nLee Y-H, Lee N-J, Choi E-J, et al.: Granulocytic sarcoma (chloroma) presenting as a lateral neck mass: initial manifestation of leukemia: a case report. Eur. Arch. Otorhinolaryngol. 2006; 263(1): 16–18. PubMed Abstract | Publisher Full Text\n\nJo S, Shim HK, Kim JY, et al.: Myeloid Sarcoma That Infiltrated a Preexisting Sebaceous Lymphadenoma in the Parotid Gland: Diagnostic Challenges and Literature Review. Biomed. Res. Int. 2019 Nov 22; 2019: 1–11. Publisher Full Text\n\nLai Y-H, Chang C-S, Liu Y-C, et al.: Postallogeneic hematopoietic stem cell transplantation relapse of acute myeloid leukemia presenting with salivary gland myelosarcoma. Ann. Hematol. 2010; 89(6): 631–633.\n\nAhmad J, Zafar L, Hussain G, et al.: Myeloid sarcoma in a child with acute myeloblastic leukaemia. J. Coll. Physicians Surg. Pak. 2011; 21(6): 369–370. PubMed Abstract\n\nJung D, Hasserjian RP, Faquin WC, et al.: Pathology quiz case 2. Myeloid sarcoma (MS) of the submandibular gland. Arch. Otolaryngol. Head Neck Surg. 2011; 137(4): 414–415.\n\nIngale Y, Patil T, Chaudhari P, et al.: Granulocytic sarcoma of parotid gland in a 4-year-old child with subleukemic AML: a diagnostic challenge! Case Reports in Otolaryngology. 2013; 2013: 3.\n\nCai G, Levine P, Şen F: Diagnosis of myeloid sarcoma involving salivary glands by fine-needle aspiration cytology and flow cytometry: report of four cases. Diagn. Cytopathol. 2008; 36(2): 124–127. PubMed Abstract | Publisher Full Text\n\nZhou J, Bell D, Medeiros LJ: Myeloid sarcoma of the head and neck region. Arch. Pathol. Lab. Med. 2013; 137(11): 1560–1568. PubMed Abstract | Publisher Full Text\n\nLee JY, Chung H, Cho H, et al.: Clinical characteristics and treatment outcomes of isolated myeloid sarcoma without bone marrow involvement: a single-institution experience. Blood Res. 2017; 52(3): 184–192.\n\nBhattacharyya D, Ghosh R, Gupta P, et al.: 1098-P. Incidence of imatinib resistance in chronic myeloid leukemia (CML) patients: Experience from resource poor center of eastern India. Ann. Oncol. 2019; 30(5): v445. Publisher Full Text\n\nKantarjian H, Cortes JE: Chronic Myeloid Leukemia. Abeloff’s Clinical Oncology. Elsevier; 2019; pp. 1836–1849.e2. Publisher Full Text"
}
|
[
{
"id": "270221",
"date": "10 May 2024",
"name": "Claudio Sorio",
"expertise": [
"Reviewer Expertise Cell biology and pathology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 report of a rare and interesting case of CML-related granulocytic sarcoma of the parotid gland.\nThe case is well described, I only have a minor request for clarification regarding Table 1:\nWhy do you indicate TLC as lac cells in the first two columns of Table 1 and refer to a much larger number for TLC in the third one without mentioning lac? First of all, do you mean LUC (large unstained cells)? Otherwise, what does lac stand for? I might understand that LUC cells disappear upon treatment, but I suggest indicating true TLC in all columns and separately the LUC number. TLC is an interesting parameter to describe.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": [
{
"c_id": "11547",
"date": "24 Jun 2024",
"name": "Priya Chatterjee",
"role": "Author Response",
"response": "Dear Reviewer, Thank you for your valuable comment. \"Lac\" is another terminology for \"lakhs\" used in India to represent the numbers. The Complete blood count report at the time of diagnosis tells us about the Total Leucocyte count as 2,25,000cells/mm3, during the present episode of Right parotid gland swelling the Total leucocyte counts came to be as 1,82,000cells/mm3 and on follow-up visit the Total leucocyte count came down to 3,200cells/mm3."
}
]
}
] | 1
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https://f1000research.com/articles/13-140
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https://f1000research.com/articles/13-139/v1
|
22 Feb 24
|
{
"type": "Study Protocol",
"title": "Assessment of quality of life (QoL) in patients with chronic skin diseases: an observational study",
"authors": [
"Shrutika Thakare",
"Dr. Bhushan Madke",
"Dr. Bhushan Madke"
],
"abstract": "Background Chronic skin diseases such as psoriasis, scleroderma, and vitiligo adversely affect a patients health and well-being. The evaluation of quality of life (QoL) is a crucial part of the overall care of patients with chronic skin diseases. Identification and dealing with multidimensional aspects such as physical, social, psychological, and emotional features of these diseases are important to enhance their quality of life and to obtain a better response to treatment.\n\nMethods This is a prospective, observational, cross-sectional, questionnaire-based study to evaluate the impact of chronic skin diseases (i.e. psoriasis, vitiligo, and scleroderma) on the quality of life of patients. The primary objective of this study is to measure the effect of chronic skin diseases and their treatment on patients quality of life using the Skindex-29 questionnaire. The secondary objectives are to determine the relationship between quality of life and sociodemographic variables and the relationship between quality of life and disease variables. Patients diagnosed with psoriasis, vitiligo, and scleroderma will be recruited for the study after signing a voluntary informed consent form. A validated Skindex-29 questionnaire will be used to record the emotions, symptoms, and functioning domains of the patients. Approximately 100 patients will be recruited for the study. Data analysis will be done at the end of patient recruitment.\n\nConclusion Dermatologists can aid their patients QoL by using the Skindex-29 questionnaire score to better understand the impact of psoriasis, vitiligo, and scleroderma. Furthermore, they can aid in estimating the disease burden as well as help direct interventions to avoid further complications.",
"keywords": [
"Quality of Life (QoL)",
"Chronic Skin Diseases",
"Psoriasis",
"Vitiligo",
"Scleroderma",
"Skindex-29"
],
"content": "Introduction\n\nPsoriasis, vitiligo, and scleroderma are chronic skin conditions that negatively affect patients quality of life (QoL). It has been observed that patients with chronic skin diseases have a lower quality of life than people in the general population.1–4\n\nPsoriasis is an autoimmune skin disease that causes rashes with itchy and scaly patches on the skin. Psoriasis can range in severity from small localized patches to total body coverage. It is common, chronic, and has no known cure.5,6 Men and women both experience it equally, and 2–4% of the population is affected by this disease.7 Many treatment options are available to manage symptoms.8 Patients with psoriasis frequently express feelings of insecurity, helplessness, embarrassment, anger and frustration. Patients with psoriasis tend to avoid or stay away from social gatherings and public areas where rejection may occur. Decreased work productivity and becoming too physically disabled to work have also been reported.9–11\n\nPatchy skin depigmentation, which can appear on any portion of the body, is a hallmark of vitiligo.12 It is an autoimmune skin disease, initially the patches are small but they will enlarge over time. The face, hands, and wrists are the most common locations of skin lesions. All skin tones are affected by vitiligo; however, those with dark or black skin may notice it more.13,14 Worldwide the prevalence is about 2%.15 Vitiligo lowers self-esteem and causes severe psychological anguish in patients, both of which have a detrimental impact on their quality of life. Skin lesions associated with vitiligo can be observed and cause shame, anxiety and depression.16–19\n\nScleroderma is an autoimmune disease that results in hardening and tightening of the skin. Although there is no known cure, available therapies may lessen symptoms.20 Typically, the fingers, hands, feet, and face are the first body areas to be affected. The two warning indications are swelling and itching. Affected skin may become lighter or deeper in colour and appear shiny as a result of tightness.21,22 Men are less often affected than women and the prevalence of disease is about less than 1% worldwide.23 It restrict the physical and mental well-being of the patient and contributing to deterioration of quality of life over time.24–26\n\nDue to the lack of a permanent cure, several treatment methods and unrecognition without appropriate assessment of these chronic skin diseases have profoundly detrimental effects on the health, functioning, and quality of life of those who are affected on all fronts, thus leading to lower quality of life. Additionally, chronic skin diseases are a substantial burden for patients, caretakers, and society.27–29 It is essential to understand the factors that affect the quality of life of patients with psoriasis, vitiligo, and scleroderma. The prevalence of these chronic skin diseases is coming up to 7%, and the same has been utilized for the calculation of sample size.\n\nThe aim of this study is to address issues related to patients quality of life. Assessment of the severity of chronic skin conditions and its effects on the patients quality of life is not easy. The Skindex-29 questionnaire, a skin-specific instrument, will be used to assess the quality of life of patients diagnosed with chronic skin diseases, such as psoriasis, vitiligo, and scleroderma. The Skindex-29 is a more comprehensive, validated, and reliable instrument for investigating and understanding the effects of chronic skin diseases on patients quality of life. Skindex-29 captures the lived experiences of patients through its items on symptoms, emotions, and functioning. It has a longer recall period of 4 weeks and is easy to understand.30–35\n\nThe Skindex-29 has 30 items divided into three categories: symptoms, emotions, and functioning. Each item is rated on a Likert scale ranging from 1 to 5. The following items will be measured in 3 domains:, in symptoms – itching, burning, pain, irritation, bleeding etc.; in emotions – worried, embarrassed, ashamed, frustrated, depressed, etc.; and in functioning – affect, relationships, stay at home, hard to work, sleepless, well-being, etc. Early diagnosis and initiation of a proper course of treatment can significantly enhance the results. QoL instruments such as Skindex-29 provide important information for healthcare professionals, which aids in avoiding the neglect of chronic skin illness. Using the results of Skindex-29, dermatologists can better understand and treat chronic skin diseases, such as psoriasis, vitiligo, and scleroderma.\n\n\nProtocol\n\nNumerous people worldwide suffer from chronic skin disorders, such as psoriasis, vitiligo, and scleroderma. These illnesses have a substantial impact on a person's emotional and psychological health, in addition to the physical discomfort and agony they produce. Low self-esteem, despair, and anxiety are common among patients with chronic skin illnesses and can have a detrimental effect on their general quality of life. Healthcare professionals can better understand the psychological and social effects of chronic skin problems on patients by researching how these ailments affect their quality of life. This information can be utilized to design interventions to enhance the quality of life of patients with psoriasis, vitiligo, and scleroderma as well as to better manage chronic skin illnesses.\n\nWhat factors affect the QoL of patients diagnosed with chronic skin diseases (i.e. psoriasis, vitiligo, and scleroderma)?\n\nTo assess the impact of chronic skin diseases (i.e. psoriasis, vitiligo, and scleroderma) on the QoL of patients.\n\nPrimary objective\n\n1. To measure the effect of chronic skin diseases (i.e. psoriasis, vitiligo, and scleroderma) and their treatment on patients QoL using the Skindex-29 questionnaire.\n\nSecondary objectives\n\n1. To determine the relationship between QoL and socio-demographics variables.\n\n2. To determine the relationship between QoL and disease variables.\n\n\nMethods\n\nProspective, observational, cross-sectional, questionnaire based study.\n\nNon-probability: consecutive sampling method.\n\nDepartment of Dermatology, Venerology & Leprosy, Acharya Vinoba Bhave Rural Hospital, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha, Maharashtra, India.\n\nApproximately 6 months.\n\nPatients diagnosed with chronic skin diseases (i.e., psoriasis, vitiligo, and scleroderma) attending the dermatology outpatient department (OPD) for treatment.\n\nMinimum 100 patients will be enrolled.\n\nInclusion criteria:\n\n1. Either sex (male and female)\n\n2. Age ≥ 18 years and ≤ 65 years.\n\n3. Patients diagnosed with psoriasis, vitiligo and scleroderma.\n\n4. Patients who are willing to comply with the study protocol and complete study assessment tools, such as questionnaires or interviews.\n\n5. Willing to give voluntarily informed consent.\n\n6. Patients who know English or Hindi or Marathi.\n\nExclusion criteria:\n\n1. Patients who are illiterate.\n\n2. Unable to communicate properly.\n\n3. Cognitive impairment (having a history of prior or current psychiatric or neuropsychological disorders) which would limit their ability to complete the questionnaires.\n\n4. Physically handicapped.\n\n5. Pregnant women.\n\nStudy procedure & data collection\n\nThis is an observational, cross-sectional, questionnaire-based study and will be conducted at the Dermatology Department, Acharya Vinoba Bhave Rural Hospital (AVBRH), Wardha, Maharashtra, after obtaining an approval from the Institutional Ethics Committee (IEC) of the Datta Meghe Institute of Higher Education and Research (DMIHER), Wardha, Maharashtra, India. The study will be conducted in compliance with all regulatory and ethical requirements, and patients details will be kept confidential throughout the study duration.\n\nThe duration for enrollment of study patients will be 6 months (26 weeks), and the patients will be enrolled from the Dermatology OPD. Once a suitable patient is found for the study, details about the study and its importance will be explained. The Participant Information Sheet (PIS) will then be given to them to read and understand.\n\nAfter this, if the patient shows interest in participating in the study, then the Informed Consent Form (ICF) will be given for signature. Once consent is signed, the patient will be screened according to inclusion and exclusion criteria using the Participant Screening Form (PSF) for eligibility.\n\nAfter screening, if a patient is found to be eligible, he/she will be enrolled in the study and a patient code will be assigned. Approximately 100 patients will be enrolled in this study. Their demographics and other details will be recorded in a Case Report Form (CRF).\n\nA validated questionnaire (i.e. Skindex-29) will be administered through a formal interview to measure the quality of life (QoL) of the patient. Once the interview is completed, the patient will be free to perform routine activities.\n\nAll patient data and other study related documents will be stored in the Study Master File (SMF). After total data collection, the data will be analyzed using simple descriptive statistics and other applicable statistical tests. The formulation of the results and conclusion will be drawn on completion of patients recruitment. Refer Figure 1 for study flow chart.\n\nData assessment & statistical analysis\n\nData will be assessed:\n\n1. To measure the effect of chronic skin diseases (i.e. psoriasis, vitiligo, and scleroderma) and their treatment on patients quality of life (QoL) using the Skindex-29 questionnaire.\n\n2. To determine the relationship between QoL and socio-demographics variables.\n\n3. To determine the relationship between QoL and disease variables.\n\nData will be analyzed for emotions, symptoms, and functioning domains using the Skindex-29 questionnaire scaling and scoring guidelines.\n\nSimple descriptive statistics will be applied, such as sum, min, max, average, frequency distribution, and percentage distribution. Graphical representation of data in the form of tabulation, bar charts, and pie charts will be performed using microsoft excel software etc.\n\nPatient enrollment criteria\n\nPatients will be recruited from the Dermatology OPD of Acharya Vinoba Bhave Rural Hospital (AVBRH) according to the inclusion criteria.\n\nIt is a patients decision to be part of the study and they will be given a written informed consent document (ICD) to understand. All the details about the study and enough time will be given to decide whether or not to take part in the study.\n\nPatient withdrawal criteria\n\nThe Principal Investigator (PI) /Co-Principal investigator may withdraw a patient from the study if the patient:\n\n• Is in violation of the protocol.\n\n• Requires early discontinuation for any reason.\n\n• The investigators will also withdraw all patients if the study is terminated.\n\n• The patients are free to withdraw from the study at any time upon request.\n\nSample size calculation\n\nFormula for qualitative variable7,15,23\n\nZ1-α/22 = Standard normal variate (at 5% type 1 error (P < 0.05) it is 1.96.\n\np = Expected proportion in population based on previous or pilot studies i.e. 7% (0.07).\n\nd = Absolute error or precision i.e. 5% (0.05).\n\nCalculation:\n\nHence, the minimum sample size required for the study is 100 patients.\n\nStudy flow chart\n\nDissemination\n\nIt will be published in an indexed journal.\n\nStudy status\n\nThe study is yet to begin.\n\n\nDiscussion\n\nIn this prospective, cross-sectional study, we are focusing on measuring the effect of chronic skin diseases (i.e. psoriasis, vitiligo, and scleroderma) on patients QoL by using the Skindex-29 questionnaire. Psoriasis, vitiligo, and scleroderma are chronic skin diseases affecting hundreds of people worldwide. According to recent studies, the quality of life of patients suffering from these diseases is impaired. Higher rates of depression, anxiety, psychological well-being, limitations in roles and activities, and poor physical health were observed, which negatively affected overall quality of life.\n\nA study carried out by Sendrasoa et al. on psoriasis reported that symptoms, feelings, and psychological well-being were the most altered dimensions. Disease duration also contributes to poor quality of life.36 Another study by Milcic et al. concluded that stress, disease severity, and a lower level of education are important determinants of poor quality of life in patients with psoriasis.37\n\nIn Vora et al.’s study, vitiligo patients' quality of life was evaluated and it was discovered that young patients with the condition had higher levels of depression as well as higher levels of quality of life impairment. The study recommends including mental health consultation and counselling in addition to disease-specific treatment.38 According to a vitiligo study by Bae et al., the participation of visible body parts and a larger afflicted body surface area were consistently linked to a lower quality of life. Additionally, individuals between the ages of 20 and 59 had reduced functioning, and a higher level of education was linked to unfavorable emotional features.39\n\nA study by Lopez-Bastida et al. on scleroderma concluded that patients experience a significant decline in quality of life and significant social expenses.40 Muller et al. conducted a cross-sectional study and observed high psychosomatic morbidity and impaired quality of life in patients diagnosed with scleroderma.41\n\nBased on the results and conclusions of the above studies, we expect similar results in our study population. This study aims to identify the domains in which patients are affected and to find solutions for better management and improvement of patients QoL suffering from psoriasis, vitiligo, and scleroderma.\n\nThe study protocol is approved by the Institutional Ethics Committee (IEC) of Datta Meghe Institute of Higher Education and Research (DMIHER), Sawangi (Meghe), Wardha, Maharashtra, India. Pin Code: 442001.\n\nRef. No.: DMIHER (DU)/IEC/2023/815\n\nThis study will be conducted in compliance with the Study Protocol, ICH-GCP, Declaration of Helsinki, ICMR Guidelines, NDCT-2019 and its amendments. In addition, the study will be conducted in compliance with local regulations and ethical requirements. Patients details will be kept confidential.",
"appendix": "Data availability\n\nNo underlying data are associated with this article.\n\n\nAcknowledgements\n\nWe are grateful to all patients who will participate in this study.\n\n\nReferences\n\nEvers AWM, Lu Y, Duller P, et al.: Common burden of chronic skin diseases? Contributors to psychological distress in adults with psoriasis and atopic dermatitis. Br. J. Dermatol. 2005; 152(6): 1275–1281. Publisher Full Text\n\nHong J, Koo B, Koo J: The psychosocial and occupational impact of chronic skin disease. Dermatol. Ther. 2008; 21(1): 54–59. PubMed Abstract | Publisher Full Text\n\nBasra MK, Shahrukh M: Burden of skin diseases. Expert Rev. Pharmacoecon. Outcomes Res. 2009; 9(3): 271–283. PubMed Abstract | Publisher Full Text\n\nGreen L: The effect of skin conditions on patients’ quality of life. Nurs. Stand. 2010; 25(9): 48–56. PubMed Abstract | Publisher Full Text\n\nLangley RG: Psoriasis: epidemiology, clinical features, and quality of life. Ann. Rheum. Dis. 2005; 64(suppl_2): ii18–ii23. Publisher Full Text\n\nGriffiths CE, Barker JN: Pathogenesis and clinical features of psoriasis. Lancet. 2007; 370(9583): 263–271. Publisher Full Text\n\nKamiya K, Kishimoto M, Sugai J, et al.: Risk Factors for the Development of Psoriasis. Int. J. Mol. Sci. 2019; 20(18): 4347. Publisher Full Text\n\nRendon A, Schäkel K: Psoriasis Pathogenesis and Treatment. Int. J. Mol. Sci. 2019; 20(6): 1475. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVoorhees AS, Fried R: Depression and Quality of Life in Psoriasis. Postgrad. Med. 2009; 121(4): 154–161. Publisher Full Text\n\nBasavaraj KH, Navya MA, Rashmi R: Stress and quality of life in psoriasis: an update. Int. J. Dermatol. 2011; 50(7): 783–792. PubMed Abstract | Publisher Full Text\n\nAugustin M, Radtke MA: Quality of life in psoriasis patients. Expert Rev. Pharmacoecon. Outcomes Res. 2014; 14(4): 559–568. Publisher Full Text\n\nEzzedine K, Eleftheriadou V, Whitton M, et al.: Vitiligo. Lancet. 2015; 386(9988): 74–84. Publisher Full Text\n\nBergqvist C, Ezzedine K: Vitiligo: A Review. Dermatology. 2020; 236(6): 571–592. Publisher Full Text\n\nGhafourian E, Ghafourian S, Sadeghifard N, et al.: Vitiligo: Symptoms, Pathogenesis and Treatment. Int. J. Immunopathol. Pharmacol. 2014; 27(4): 485–489. Publisher Full Text\n\nBergqvist C, Ezzedine K: Vitiligo: A focus on pathogenesis and its therapeutic implications. J. Dermatol. 2021; 48(3): 252–270. PubMed Abstract | Publisher Full Text\n\nTeovska Mitrevska N, Eleftheriadou V, Guarneri F: Quality of life in vitiligo patients. Dermatol. Ther. 2012; 25: S28–S31. Publisher Full Text\n\nRamakrishna P, Rajni T: Psychiatric Morbidity and Quality of Life in Vitiligo Patients. Indian J. Psychol. Med. 2014; 36(3): 302–303. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmer AA, Gao X-H: Quality of life in patients with vitiligo: an analysis of the dermatology life quality index outcome over the past two decades. Int. J. Dermatol. 2016; 55(6): 608–614. PubMed Abstract | Publisher Full Text\n\nElbuluk N, Ezzedine K: Quality of Life, Burden of Disease, Co-morbidities, and Systemic Effects in Vitiligo Patients. Dermatol. Clin. 2017; 35(2): 117–128. PubMed Abstract | Publisher Full Text\n\nFett N: Scleroderma: Nomenclature, etiology, pathogenesis, prognosis, and treatments: Facts and controversies. Clin. Dermatol. 2013; 31(4): 432–437. Publisher Full Text\n\nChung L, Lin J, Furst DE, et al.: Systemic and localized scleroderma. Clin. Dermatol. 2006; 24(5): 374–392. Publisher Full Text\n\nChen K, See A, Shumack S: Epidemiology and pathogenesis of scleroderma. Australas. J. Dermatol. 2003; 44(1): 1–7. Publisher Full Text\n\nRongioletti F, Ferreli C, Atzori L, et al.: Scleroderma with an update about clinico-pathological correlation. G Ital. Dermatol. Venereol. 2018; 153(2): 208–215. PubMed Abstract | Publisher Full Text\n\nLis-Święty A, Skrzypek-Salamon A, Ranosz-Janicka I, et al.: Health-related quality of life and its influencing factors in adult patients with localized scleroderma - a cross-sectional study. Health Qual. Life Outcomes. 2020; 18(1): 110–133. PubMed Abstract | Publisher Full Text | Free Full Text\n\nvan Leeuwen NM , Ciaffi J, Liem SI, et al.: Health-related quality of life in patients with systemic sclerosis: evolution over time and main determinants. Rheumatology. 2021; 60: 3646–3655. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSierakowska M, Doroszkiewicz H, Sierakowska J, et al.: Factors associated with quality of life in systemic sclerosis: a cross-sectional study. Qual. Life Res. 2019; 28(12): 3347–3354. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPärna E, Aluoja A, Kingo K: Quality of life and emotional state in chronic skin disease. Acta Derm. Venereol. 2015; 95(3): 312–316. PubMed Abstract | Publisher Full Text\n\nBehera PR, Palepu S, Sirka C, et al.: Psychosocial distress and quality of life among patients with a chronic skin disorder at a tertiary care hospital in Eastern India: A hospital-based case-control study. Cureus. 2022; 14(10): e29830. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBes J, Legierse C, Prinsen C, et al.: Patient education in Chronic skin diseases: A systematic review. Acta Derm. Venereol. 2011; 91(1): 12–17. PubMed Abstract | Publisher Full Text\n\nChren M-M, Lasek RJ, Quinn LM, et al.: Skindex, a quality-of-life measure for patients with skin disease: Reliability, validity, and responsiveness. J. Investig. Dermatol. 1996; 107(5): 707–713. Publisher Full Text\n\nChren M-M, Lasek RJ, Quinn LM, et al.: Convergent and discriminant validity of a generic and a disease-specific instrument to measure quality of life in patients with skin disease. J. Investig. Dermatol. 1997; 108(1): 103–107. PubMed Abstract | Publisher Full Text\n\nChren M-M: Improved discriminative and evaluative capability of a refined version of Skindex, a quality-of-life instrument for patients with skin diseases. Arch. Dermatol. 1997; 133(11): 1433–1440. PubMed Abstract | Publisher Full Text\n\nChren M-M, Lasek RJ, Sahay AP, et al.: Measurement properties of skindex-16: A brief quality-of-life measure for patients with skin diseases. J. Cutan. Med. Surg. 2001; 5(2): 105–110. PubMed Abstract | Publisher Full Text\n\nSaimbi D, Raju M, Dubey V, et al.: Skindex-29 to Determine Quality of Life and Emotional Factors in Dermatological Conditions. Ann. Natl. Acad. Med. Sci. (India). 2017; 53(01): 041–050. Publisher Full Text\n\nChren M-M: The skindex instruments to measure the effects of skin disease on quality of life. Dermatol. Clin. 2012; 30(2): 231–236. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSendrasoa FA, Razanakoto NH, Ratovonjanahary V, et al.: Quality of life in patients with psoriasis seen in the Department of Dermatology, Antananarivo, Madagascar. Biomed. Res. Int. 2020; 2020: 1–5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMilčić D, Janković S, Vesić S, et al.: Assessment of quality of life in patients with psoriasis: A study from Serbia. Int. J. Dermatol. 2014; 54(5): 523–528. PubMed Abstract | Publisher Full Text\n\nVora R, Kota R, Varma J, et al.: Study on assessment of quality of life and depression in patients of Vitiligo. Indian Dermatol. Online J. 2019; 10(2): 153–157. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBae JM, Lee SC, Kim TH, et al.: Factors affecting quality of life in patients with Vitiligo: A nationwide study. Br. J. Dermatol. 2017; 178(1): 238–244. PubMed Abstract | Publisher Full Text\n\nLópez-Bastida J, Linertová R, Oliva-Moreno J, et al.: Social/economic costs and health-related quality of life in patients with scleroderma in Europe. Eur. J. Health Econ. 2016; 17(S1): 109–117. PubMed Abstract | Publisher Full Text\n\nMüller H, Rehberger P, Günther C, et al.: Determinants of disability, quality of life and depression in dermatological patients with systemic scleroderma. Br. J. Dermatol. 2011; 166(2): 343–353. Publisher Full Text"
}
|
[
{
"id": "249592",
"date": "25 May 2024",
"name": "Andrea Gibbons",
"expertise": [
"Reviewer Expertise Health psychology",
"specifically in the impact of diagnosis of and management of chronic and long-term conditions."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study aims to explore the impact of skin disease on individuals quality life. Quality of life will be measured using the Skindex-29 questionnaire. Participants will be recruited via skin clinics in a hospital setting.\nAlthough the study is well-designed, there is some information that could be included that would clarify the study.\nFor example, although one of the objectives is to determine the relationship between QoL and disease variables, it is not clear what disease variables will be assessed. Is it disease severity? If so how will this be measured? Will disease duration be recorded? What about medication and treatments? Will participants be informed in the information sheet that participation involves their medical information being accessed by the researchers? Justification is needed for some of the inclusion/exclusion criteria. For example, why is there a cut-off for age of 65 years or older? Why are pregnant women excluded? Considering the condition, age and pregnancy status doesn’t negate someone’s experience of their skin condition, if anything, they may exacerbate it. A rationale for why these have been included as criteria needs to be provided. The specific analyses that will be conducted should be included in the report. It is not enough to say that you will conduct simple descriptive statistics and will use graphs to represent the data. If you aim to explore the effects of chronic skin disease on QoL, then you will at least have to conduct correlations, and most likely, regression to explore the impact of disease and demographic variables on QoL. I appreciate that you may not have a clearly defined analysis plan, but you should have some idea based on your hypotheses. You include a sample size calculation, but you need to link this to your planned analyses. Additionally, in the sample size calculation, you refer to a ‘formula for qualitative variable’. Please be mindful of the terminology you use. You are administering a quantitative questionnaire within an ‘interview’. Ensure that you make it clear that this is not a qualitative interview. If there is any qualitative data collection element in this study, it is not clear and you need to address this.\n\nIf each of these four points are addressed, then this will greatly improve the strength of this report. It will aid clarity in the methodology, and will allow for replicability for others.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": [
{
"c_id": "11736",
"date": "14 Jun 2024",
"name": "Shrutika Thakare",
"role": "Author Response",
"response": "Response to Query 1 Disease variables that will be assessed in the study are Type of disease will be categorised into Psoriasis or Vitiligo or Scleroderma, Duration of Disease will be measured in Days or Months or Years, Disease Level by New or Recurrence, Disease Severity by Mild or Moderate or Severe, Type of Treatment Details such as Drug/Therapy/Procedure Name, Drug From, Drug Dose, Route of Administration and Frequency will be assessed and recorded. Participants will be informed in the ICD (Informed Consent Document) that their medical records will be accessed for recording the clinical data. Thank you Response to Query 2 I agree with the statement, but this study will be conducted in rural area of India, where the literacy rate is poor, and we are focusing on recruiting subjects who are literate. So, the subject should understand the questionnaire very well and respond to it correctly, and credible information must be generated. When it comes to pregnant women, they fall under the vulnerable population, so we need an LAR / Impartial Witness for consent. By considering both conditions, we decide to exclude subjects with an age above 65 and pregnant women. Thank you Response to Query 3 Agreed, we will initially represent the data with descriptive statistics and graphs so we can get a basic understanding of the data collected. The statistical measures, like correlation and regression analysis, etc., will be used to explore the impact of disease and demographic variables on quality of life. Statistician and guide help will be taken to analyse the data and form the results after the entire data collection. Thank you Response to Query 4 In this study, we are recording the responses in never, rarely, sometimes, often, and all the time. This is a qualitative form of data. Then, with the help of the user guide that came with the questionnaire, it will be used to analyse the data. Thank you"
}
]
},
{
"id": "309661",
"date": "22 Aug 2024",
"name": "Yen T Chen",
"expertise": [
"Reviewer Expertise Symptom experience and symptom management in people with scleroderma"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 protocol focuses on an important research area: examining the impact of chronic skin diseases on quality of life (QoL) using the Skindex-29 among 100 patients. While the protocol shows promise, several areas require further clarification and additional details to enhance the study’s robustness and feasibility:\nPlease clarify why three different patient populations are included. Scleroderma, in particular, is complex and heterogeneous, which may influence the overall results. If scleroderma patients are included, consider including covariates specific to this population, such as gastrointestinal involvement, digital ulcers, and PAH, as these factors could significantly impact QoL. Also, the role of disease duration, especially since patients with diffuse cutaneous scleroderma often experience more severe symptoms within the first five years following diagnosis. The current minimum sample size of 100 may be insufficient due to potential missing data. Consider increasing the sample size by 5-10% to ensure the final analytic sample is adequately powered. Provide a detailed list of the sociodemographic and disease variables that will be collected. Explain how diagnoses will be confirmed. Will they be self-reported, or will there be verification through medical records? Elaborate on the recruitment plan. Will study staff approach potential participants directly, or will referrals from healthcare providers be used? Additionally, will participants be able to contact the study team through hospital flyers or other methods? Clarify if participants will receive any compensation, as this can impact recruitment and participation rates. Provide specifics on how the Skindex-29 will be administered. Indicate who will conduct the interviews, where they will occur (e.g., hospital private rooms), and whether interviews will be recorded for accuracy. Include a detailed statistical analysis plan. Examining the relationship between QoL and study variables will require more than simple descriptive statistics.\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Partly\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
},
{
"id": "274467",
"date": "10 Sep 2024",
"name": "Zachary Hopkins",
"expertise": [
"Reviewer Expertise I am a board-certified dermatologist",
"have completed a one-year fellowship in autoimmune and complex medical dermatology",
"and am an expert in autoimmune skin disease. I am a clinician-scientist focused on improving the care of patients with autoimmune and complex medical dermatologic conditions by leveraging patient-reported outcomes to better guide patient-centered decision-making. My research expertise includes dermatoepidemiology",
"psychometrics",
"and health-services research focused on utilization of patietn-reported outcomes."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn general, the authors propose an interesting study to investigate the impact of chronic skin diseases on health-related quality of life (HRQL). The study is interesting and holds important merit, but some details need to be better delineated to meet the needs of protocol pre-submission and assure high-quality study execution. Introduction:\n\nIt may be helpful to briefly outline why psoriasis, scleroderma and vitiligo were chosen to study? Is there any unifying reason for this mix of diagnoses? The aim of this study is to address issues related to patients quality of life. Assessment of the severity of chronic skin conditions and its effects on the patient's quality of life is not easy. This statement deserves some more delineation. What about it is not easy? I think one of the things that deserves some discussion here is the differences between quality of life, health-related quality of life, disease indices, etc. For example, Skindex-29 really doesn't measure quality of life so much as health-related quality of life. It may also be worth discussing some different approaches/models for quality of life (i.e. see Wilson and Cleary's model, etc.) The Skindex-29 is a more comprehensive, validated, and reliable instrument for investigating and understanding the effects of chronic skin diseases on patients quality of life. It is more comprehensive/validated/reliable than what? I agree that it is a good candidate measure, however it does have key holes in its validation that should at least be acknowledged (Pérez-Chada LM.et.al., 2024 [Ref 1]) for a review of measurement properties of health-related quality of life instruments in psoriasis. This is a good extrapolation as psoriasis probably has the most data in this area). It may be worth a small discussion here of types of HRQL measures in dermatology (i.e. general, skin-specific, and disease-specific, and why the Skindex-29 was used in lieu of DLQI, Skindex-16, etc.). The following items will be measured in 3 domains:, in symptoms itching, burning, pain, irritation, bleeding etc.; in emotions worried, embarrassed, ashamed, frustrated, depressed, etc.; and in functioning affect, relationships, stay at home, hard to work, sleepless, well-being, etc. Would be more clear to discuss this as: Items are categorized into the following domains Instruments such as Skindex-29 provide important information for healthcare professionals, which aids in avoiding the neglect of chronic skin illness. Using the results of Skindex-29, dermatologists can better understand and treat chronic skin diseases, such as psoriasis, vitiligo, and scleroderma. Rewording/reworking of these last two sentences could be done to better set up the purpose of this study.\nProtocol\nLow self-esteem, despair, and anxiety are common among patients with chronic skin illnesses and can have a detrimental effect on their general quality of life. Citation should be provided Prospective, observational, cross-sectional, questionnaire-based study. This is not entirely clear. I.e. both cross-sectional and prospective is mentioned. Is it both? Is it serially cross-sectional, or true prospective? It would be helpful to place the later sample size calculation in the same section as the initial sample size description. Why were patients not included? This seems unfortunate as the survey is validated for this population and HRQL in the elderly is a highly important issue, especially with these chronic diseases where treatment decisions must especially be weighed with comorbidities, HRQL, and management risks. Also curious why those with physical handicaps or pregnant women would be excluded? There is no ostensible risk with surveys to this population and the understanding of how their HRQL is impacted seems important? This is an observational, cross-sectional, questionnaire-based study. This contradicts the previous mentions of a prospective study Data will be analyzed for emotions, symptoms, and functioning domains using the Skindex-29 questionnaire scaling and scoring guidelines. It is helpful to give readers an idea of this, i.e. Each Skindex-29 domain (emotions, symptoms, and functioning) is converted to a 0-100 scale with 0 signifying no impact on HRQL and 100 signifying maximum impact/worst HRQL). The statistical protocol needs further delineation. This needs to occur in the following ways It needs to be clarified what the study design is, if truly longitudinal/prospective, then appropriate models (i.e. linear mixed models, etc.) that can handle repeated measures should be utilized It is noted that associations between disease severities, sociodemographic variables, etc. will be drawn, but how these factors will be measured, nor how those relationships will be assessed was described. The study flow chart needs better delineation, namely of how data is collected over time and what is entailed in the interview which is first mentioned in the flow chart.\n\nDiscussion\nIn the psoriasis discussion, (Hopkins ZH. et.al., 2023 [Ref 2] ) as this also demonstrates the importance of the emotional domain of Skindex and demonstrates that worsening psoriasis severity is associated with worsening HRQL.\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Partly\n\nAre sufficient details of the methods provided to allow replication by others? No\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-139
|
https://f1000research.com/articles/12-1002/v1
|
18 Aug 23
|
{
"type": "Research Article",
"title": "Prevalence of Panton-Valentine leucocidin (pvl) and exfoliative toxin A (eta) gene within methicillin resistant and sensitive Staphylococcus aureus in an urban tertiary referral hospital: A molecular epidemiology pilot study",
"authors": [
"Sri Amelia",
"R. Lia Kusumawati",
"Mirzan Hasibuan",
"Lavarina Winda",
"Ridwan Balatif",
"Alvin Ivander",
"R. Lia Kusumawati",
"Mirzan Hasibuan",
"Lavarina Winda",
"Ridwan Balatif",
"Alvin Ivander"
],
"abstract": "Background: Staphylococcus aureus is well known to cause a multitude of clinical manifestations, from mild to severe bloodstream infections that could lead to death. Infections are common, either in community-acquired or hospital-acquired settings, and treatment remains a challenge due to methicillin-resistant Staphylococcus aureus (MRSA). The pathogenesis of S. aureus is mediated by several cell-surface and secreted virulence factors. The virulence factors discussed in this study are Panton-Valentine leucocidin (pvl) and exfoliative toxin A (eta). Our pilot study aimed to observe pvl and eta as virulence gene prevalence in a North Sumatera tertiary referral health center. Methods: Our study was a descriptive-analytical observational study with a cross-sectional design in which we collected isolates over a single time period. The frequency of genes is reported as a percentage comparison between MRSA and methicillin-sensitive S. aureus (MSSA). Qualitative gene prevalence analysis was carried out using the polymerase chain reaction (PCR). Results: Our results showed that from 38 MRSA sample isolates, six samples were found to be pvl-negative, or 15.7% of the total samples. From 40 MSSA sample isolates, one sample was found to be pvl-negative MSSA, or 0.025%. Regarding eta, from 38 MRSA sample isolates, 18.4% of the total sample did not have eta, while from 40 MSSA sample isolates, all samples were found to be positive for eta. We found that both pvl and eta were significantly more likely to be expressed in the MSSA strain. Conclusions: Our study shows that pvl and eta are more likely expressed in MSSA strains than in MRSA strains in Indonesia.",
"keywords": [
"Staphylococcus aureus",
"Virulence factor",
"pvl",
"eta"
],
"content": "Introduction\n\nStaphylococcus aureus are Gram-positive spherical bacteria, usually arranged in a grape-like manner. This bacterium is well known to cause a multitude of clinical manifestations, from mild to severe bloodstream infections that could lead to death. Infections are common, either in community-acquired or hospital-acquired settings, and treatment remains a challenge due to multi-drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA).1 S. aureus, including MRSA, is commonly found on the skin and mucous membranes as part of the normal flora of human bodies.2 While usually known as a commensal bacterium, research has shown that S. aureus infection is one of the most prevalent in the world. In the industrialized world, Tong et al.’s review showed a 10 to 30 per 100,000 person-year incidence of bacteremia caused by S. aureus. While overall rates may have stabilized due to the rise of antibiotics, the contribution of MRSA has fluctuated.3 However, while it is well observed that staphylococcal infections caused by MRSA remain varying, in which at a specific time and location MRSA prevalence might be higher while in other time and location MRSA prevalence could be lower than predicted, studies have shown an increasing amount of MRSA infections in each decade. Hasanpour et al.’s research showed that before 2000, only 441 elderlies were infected with MRSA; however, this number skyrocketed to 4,365 in the 2001–2010 period and 11,987 in 2011–2022.4 As such, it can be said that MRSA creates a new challenge for healthcare workers and researchers to identify its pathogenesis and thus create a sound and reliable solution.\n\nThe pathogenesis of S. aureus is mediated by several cell-surface and secreted virulence factors. One such virulence factor is Panton-Valentine leucocidin (pvl).5 pvl is a toxin comprising two components, LukS-PV and LukF-PV. After their secretion, both components assemble into a pore-forming heptamer on neutrophil membranes, causing neutrophil lysis. There is a significant amount of research that shows the role of pvl in pathogenesis; however, it remains unclear what the trends are for pvl-positive methicillin- sensitive S. aureus (MSSA) or MRSA. The molecular epidemiology and burden of pvl-positive MSSA or MRSA are highly variable within studies, with the US dominated by pvl-positive MRSA, while such bacteria have been found to be rare in Australia, which has a predominance of both pvl-positive MRSA and MSSA.6 Prudent research toward pvl molecular epidemiology is vital because it is well known that pvl is associated with invasive disease and thus could be used as a gene marker for severe infection. In industrialized countries, such epidemiological studies have led to public health measures aimed at individuals infected with the pvl-producing strain.7\n\nAnother such virulence factor was identified as exfoliative toxin A (eta). Exfoliative toxins (ETs), also known as epidermolytic toxins, are serine proteases secreted by S. aureus that recognize and hydrolyze desmosome proteins in the skin. ETs have been associated with the loss of keratinocytes and cell-cell adhesion, inducing peeling of the skin and blister formation. One of the principal isoforms of exotoxins implicated in human skin damage is eta. Recognizing eta prevalence could help distinguish the extent of the damage caused by S. aureus.8 Research has shown that eta is a prevalent toxin. A study done by Mohseni et al. revealed that 76.7% of isolates were positive for eta in S. aureus isolates.9 However, research is limited toward MSSA, and there is a lack of research assessing eta prevalence in MRSA strains.\n\nDue to the need for molecular epidemiological study in defining public health measures and mapping molecular profiles, especially in Indonesia and possibly in Southeast Asia, our study aimed to measure pvl and eta gene molecular prevalence at the Adam Malik General Hospital, one of Indonesia’s main tertiary referral health centers.\n\n\nMethods\n\nOur study was a descriptive-analytical observational study with a cross-sectional design, in which we collected isolates from the North Sumatera Tertiary Referral Center over a single time point which was in January 2022. Our study was carried out after it had been approved by the ethical medical research committee of the Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia through letter no. 540/KEPK/USU/2022. Isolates were collected in a blind manner. This method was used to prevent bias in clinical correlation due to our specific study to identify molecular epidemiology at a specific time point, not to explain a phenomenon caused by a toxin or virulence factor specifically. We determined the sample size needed using the following descriptive sample formula:\n\nTo obtain 95% confidence interval, Za was pre-determined with 1.96 while d was 0.1. According to Mohseni’s study,8 which found P (proportion of eta positive sample in population) to be 0.767, we found that our study needed at least a total sample of 68 isolates to obtain statistical power. Our study included samples that were as evenly divided into MRSA and MSSA as possible.\n\nAfter we obtained the minimal sample needed, we collected isolates from the Adam Malik General Hospital Microbiology Installation using cluster random sampling. Sample lab numbers with MRSA and MSSA results were obtained with consecutive sampling; thus we obtained 38 MRSA samples and 40 MSSA samples without information regarding sample clinical history to prevent bias. The samples were then cultured on blood agar medium, and colonies suspected of being Staphylococcus aureus were tested using Gram staining, catalase, oxidase, and coagulase tests. Colonies suspected to be S. aureus were cultured in mannitol salt agar (MSA) medium, while antibiotic susceptibility tests were performed on Muller-Hinton agar (MHA). Antibiotic discs were placed inside MHA. after 24 hours of incubation. Suspension was transferred to the Eppendorf and stored at -80°C.\n\nDNA extraction was done from bacterial cells using Presto Mini gDNA Bacteria (Geneaid). 1 × 109 colonies of bacterial cells were inserted in a 1.5 mL sterile tube and centrifuged at 13.000 rpm for 1 minute; afterwards, the supernatant was removed. Inside the tube, 200 μL of buffer (including 0.8 mL/200μL lysozyme) were vortexed. Incubation was then performed at 20°C for 5 minutes, and then 20μL of proteinase K was added and vortexed. Incubations were then performed at 70°C for 10 minutes, then added to 200 μL of absolute ethanol and vortexed. GD columns were then arranged inside the collection tube, and 400 μL of buffer W1 were centrifuged at 13,000 rpm for about 30 seconds. Then, liquids were extracted, and centrifugation was re-done with 600 μL wash buffer. After 100 μL of elution buffer were added and maintained at room temperature for 3 minutes, the tubes were filled with pure DNA. Tubes were saved in a freezer at -20°C. Our protocol was in accordance with GeneAid protocol specified inside the product kit.\n\nIn the PCR detection of the pvl and eta genes, specific primers were used after searching through the NCBI search engine to ensure their specificity. Table 1 lists the specifications for the primers used, and Table 2 describes our temperature program and volume.\n\nAfterward, we began PCR mastermix preparation by liquefying GoTaq Green Master Mix 2×, primers (forward and reverse), nuclease-free water and DNA template. Our primer was obtained from Integrated DNA Technologies. These were then vortexed and spun down for 10 seconds, and a PCR mix was then prepared with the materials specified below (Table 2) to get one sample. Afterward, vortexing was done to ensure suspension homogeneity. DNA templates were then added, and the thermal cycling was carried out with the parameters listed in Table 2. In summary, for most steps, 30 seconds are sufficient, while in the first step, a 5-minute hot start at 94°C would be necessary. To detect pvl, 35 cycles consisting of 94, 52, and 72°C of denaturation, annealing, and extension were performed for 30 seconds. eta followed a similar step.\n\nPCR products were electrophoresed using 2% agarose gel (Merck, Germany). A mixture of 1 λ DNA loading dye and 5 λ PCR product was loaded in the gel. Electrophoresis was performed at a voltage of 80 V.\n\nThe electrophoresis results were obtained and visualized through a UV transilluminator. PCR results were defined as positive when a contrast streak was within the primer base pair or negative when the chamber was found to be empty after visualization. As the aim of the study was to identify specific virulence gene prevalences, quantitative PCR or RNA sampling were not performed.\n\nSPSS version 25 and Microsoft Office Excel were used to analyze the data. The frequency of genes was reported as a percentage frequency, and a descriptive comparison was made between MRSA strain gene prevalence and that of MSSA. A bivariate analysis was performed to determine the statistical difference between groups. Due to the categorical nature of our data data, the Chi-square test was chosen. Significance was proven with a p-value below 0.05 in the 95% confidence interval.\n\n\nResults\n\nThe results of our PCR tests showed that from 38 MRSA sample isolates, six samples were found to be pvl-negative, or 15.7% of total samples. From 40 MSSA sample isolates, one sample was found to be pvl-negative MSSA, or 0.025%. Regarding eta, of 38 MRSA sample isolates, 18.4% of the total sample did not have eta, while from 40 MSSA sample isolates, all samples were found to be positive. Afterwards, we analyzed our data with the Chi-square test to determine whether significant differences existed between pvl and eta prevalence. We found that both pvl and eta were significantly more likely to be present in the MSSA strain, with p ≤ 0.05, respectively. The results can be seen in Table 3.\n\n* Chi-square test.\n\nElectrophoresis visualisation for each group can be seen in Figure 1 below.\n\n\nDiscussion\n\nOur research was performed to identify the molecular epidemiology of pvl-positive MRSA, pvl-positive MSSA, and eta prevalence in either MRSA or MSSA, thus supporting local public health authorities in creating a sound public health measure and fulfilling data needs regarding S. aureus molecular epidemiology, especially in Southeast Asia. According to our results, most MRSA and MSSA were found positive for pvl and eta expression. We also found that MSSA was significantly more likely to encode both pvl and eta.\n\nOur research shows very concerning new updates. In a study performed by Boan et al. in Australia during the 2007–2009 period, pvl-negative and positive samples were still equally dominating, with 141 pvl-positive S. aureus and 148 pvl-negative strains. The Boan study did find that PVL didn’t significantly affect methicillin resistance, with 56% of pvl-positive strains found to be MRSA. However, it is interesting to note that in the Boan study, which reflects Australia’s S. aureus molecular epidemiology, it was shown that pvl-positive MRSA had begun to dominate in Western Australia.11 These results concur with our study, and by reflecting its close geographical distance, our result creates a new concern that pvl-positive MRSA and MSSA dominate most S. aureus specimens.\n\nRecent research performed in Gambia by Darboe et al. in 2019 revealed a somewhat different result at several time points, while at the same time reflecting the similar results found in our study in another time points. While it is correct to assume that the pvl-positive samples have increased from 2005 levels to 2015 levels, their numbers has been fluctuating at best. However, it is interesting to note that in one period of the study, the pvl-positive strain was as high as 90%. Darboe’s study didn’t elaborate on whether there is methicillin resistance in pvl-positive or pvl-negative strains; however, Darboe did conclude that there was no association between pvl and antimicrobial resistance, while emphasizing the still-low antimicrobial resistance in Gambia.12 This result brought a new perspective to our study as it showed a fluctuating trend. It might be possible that some measures were taken during the lower pvl-positive strain infection period, and it has been found that while our results show unusually high pvl-positive MRSA and MSSA, this result was not irreversible.\n\nJaiswal’s report in 2022 revealed another different result. Their study results were not consistent with ours, whereby Jaiswal revealed only 49 out of 162 positive pvl strains within MRSA.13 We noted that the Jaiswal study was not consistent with our study or with other studies performed in India. A study by Kaur from India reported 85.1% pvl-positive MRSA prevalence within the country,14 similarly to D’Souza’s study in Mumbai which revealed 64% pvl-positive MRSA.15 This doesn’t necessarily mean that the Jaiswal study was incorrect, as it emphasized the dynamic change in MRSA genetic epidemiology. In a very large country like India, even molecular epidemiology could differ between regions and provinces.\n\nLocal studies at Andalas University performed by Linosefa et al. revealed a more balanced number. Linosefa found only two out of 19 samples to be positive for pvl.16 While this result was encouraging, it should be noted that this research was performed nearly a decade ago, and this research recommends the importance of surveillance, as was done in our study. This result also strengthened our hypothesis regarding how varying pvl prevalence could be.\n\nAnother interesting is the research done by Bhatta et al. in 2016 in Nepal. In his study, Bhatta observed that 90.4% of MRSA acquired in the community was pvl-positive, while pvl detected in nosocomial infections was only 7.1% positive. It was also found that pvls were not associated with bloodstream infections.17 While the number of samples makes it hard to draw any definitive scientific conclusion, there is a high possibility that Indonesian S. aureus-infected patients mostly acquire their infection from the community. Interventions toward personal hygiene or public health measures might indeed lower pvl-positive prevalence.\n\nWith regards to eta, our results also show a disturbing new discovery in which most MRSA and MSSA were positive for the eta gene, with MSSA being significantly more likely to have eta. However, this has actually been predicted by several studies. Mohseni, in his study conducted in Iraq, found that 87.3% of isolates, or 131 samples, were positive for at least ET genes, with eta being dominant. eta was found in 76.7% of the samples obtained by Mehsani. In the conclusion, Mehsani deemed the finding a serious problem as it may spread through gene transfer between strains.9\n\nA study performed by Koosha et al. in 2013 is, however, quite consistent with our study. In the Kooesha study, lack of both eta and etb genes was only detected in eight (4%) isolates, and eta dominated ET prevalence. ETs play a role in colonization and invasion of injured mucosa and skin. Koosha also found that the distribution of ETs was largely similar between the MRSA and MSSA groups. Finally, drug resistance was abundant in the analyzed population.18 However, a study performed by Montazeri et al. in 2021 revealed that eta expression was only 23.7%. It must be emphasized that the Montazeri study was limited to cancer patients, who may have immunological disorders that could affect staphylococcal infection prevalence.19 This result might also emphasize regional fluctuations in molecular epidemiology. The study from the Middle East showed an even more surprising result: none of the MRSA isolates expressed the eta gene, out of 76 Iraqi isolates and 49 refugee isolates.20\n\nThe study conducted in the People’s Republic of China by Li et al. showed much more consistent results compared with our study. Li found that most MRSA and MSSA contained eta genes at rates of 61.8% and 55%, respectively. Li’s research compared the prevalence from year to year, and there was indeed an increasing prevalence of eta gene prevalence, which was 23.1% in the 2013–2014 period and increased to 80.1% in the 2018–2019 period.21 Our results revealed that Li’s increasing trend is persisting even in Indonesia.\n\nA systematic review was conducted regarding eta-positive S. aureus in Iran alone. It showed quite variable results. Fooladi’s study showed 92.7% Staphylococcus aureus were positive for eta.22 On the other side of the spectrum, eta detection could be as low as 0%, as shown in the Rahimi study in 2018.23 This systematic review showed that even between regions, the variability of the S. aureus virulence gene is quite large.24\n\nLastly, a study in Indonesia done by Santosaningsih et al. in 2017 showed that only 11.3% of patients encoded eta gene.25 This result shows the importance of our study due to the very variable and volatile molecular epidemiology of S. aureus. Modifiable factors can help reduce the burden of disease.\n\nThe limitation of our study was the blind setting. While blind research might be ideal to recognize molecular epidemiology while preventing specific clinical bias (e.g., lower pvl prevalence in bloodstream infection),17 a clinical-to-molecular genetics relationship study could show the magnitude of this effect. Other limitations include our single-center study. However, our hospital is the main tertiary referral center in Sumatera Island, so it could reflect Staphylococcal molecular epidemiology in all of Sumatera. It still must be emphasized that most infections occur in the acute phase, and milder strains of S. aureus might have been treated in a primary health center.\n\n\nConclusions\n\nOur study shows that pvl and eta are more likely expressed in MSSA strains than in MRSA strains in Indonesia. This is a relatively new finding and could have significant implications for treating MSSA, as pvl and eta have been deemed virulence factors that could worsen disease progression. Public health measures are necessary, and continued surveillance is important to ensure that pvl or eta prevalence as a virulence factor decreases with time and effort.",
"appendix": "Data availability\n\nFigshare: Electrophoresis result of Staphylococcus aureus clinical isolates from Adam Malik General Hospital, https://doi.org/10.6084/m9.figshare.22796012.v1. 26\n\nFigshare: Result of ETA and PVL PCR and Cefoxitime Screening of Clinical Isolates, https://doi.org/10.6084/m9.figshare.22849361.v1. 27\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nRiedel S, Morse SA, Mietzner T, et al.: Jawetz, Melnick & Adelberg’s Medical Microbiology. LANGE McGrawHill; 2019.\n\nTaylor TA, Unakal CG: Staphylococcus Aureus. [Updated 2022 Jul 18]. StatPearls. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Reference Source\n\nTong SY, Davis JS, Eichenberger E, et al.: Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin. Microbiol. Rev. 2015 Jul; 28(3): 603–661. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHasanpour AH, Sepidarkish M, Mollalo A, et al.: The global prevalence of methicillin-resistant Staphylococcus aureus colonization in residents of elderly care centers: a systematic review and meta-analysis. Antimicrob. Resist. Infect. Control. 2023 Jan 29; 12(1): 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDarboe S, Dobreniecki S, Jarju S, et al.: Prevalence of Panton-Valentine leukocidin (PVL) and antimicrobial resistance in community-acquired clinical Staphylococcus aureus in an urban Gambian hospital: a 11-year period retrospective pilot study. Front. Cell. Infect. Microbiol. 2019 May 22; 9: 170. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHealth Protection Agency Guidance on the diagnosis and management of PVL-associated Staphylococcus aureus infections (PVL-SA) in England: 2008. (accessed July 17, 2012). Reference Source\n\nShallcross LJ, Fragaszy E, Johnson AM, et al.: The role of the Panton-Valentine leucocidin toxin in staphylococcal disease: a systematic review and meta-analysis. Lancet Infect. Dis. 2013 Jan; 13(1): 43–54. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMariutti RB, Tartaglia NR, Seyffert N, et al.: Exfoliative Toxins of Staphylococcus aureus. The Rise of Virulence and Antibiotic Resistance in Staphylococcus aureus.2017 Mar 8. Publisher Full Text\n\nMohseni M, Rafiei F, Ghaemi EA: High frequency of exfoliative toxin genes among Staphylococcus aureus isolated from clinical specimens in the north of Iran: Alarm for the health of individuals under risk. Iran J. Microbiol. 2018 Jun; 10(3): 158–165. PubMed Abstract | Free Full Text\n\nHesari MR, Salehzadeh A, Darsanaki RK: Prevalence and molecular typing of methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin gene. Acta Microbiol. Immunol. Hung. 2018 Mar 1; 65(1): 93–106. PubMed Abstract | Publisher Full Text\n\nBoan P, Tan HL, Pearson J, et al.: Epidemiological, clinical, outcome and antibiotic susceptibility differences between PVL positive and PVL negative Staphylococcus aureus infections in Western Australia: a case control study. BMC Infect. Dis. 2015 Dec; 15(1): 1–6. Publisher Full Text\n\nDarboe S, Dobreniecki S, Jarju S, et al.: Prevalence of Panton-Valentine leukocidin (PVL) and antimicrobial resistance in community-acquired clinical Staphylococcus aureus in an urban Gambian hospital: a 11-year period retrospective pilot study. Front. Cell. Infect. Microbiol. 2019 May 22; 9: 170. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJaiswal R, Garg A, Tripathi P, et al.: Epidemiology of Panton Valentine Leukocidin in clinical Staphylococcus aureus isolates-A prospective study at a tertiary care centre in North India. Clinical Epidemiology and Global Health. 2022 May 1; 15: 101006. Publisher Full Text\n\nKaur H: Clindamycin resistance in PVL positive isolates of Staphylococcus aureus, Belgaum, North Karnataka (India). IOSR J. Eng. 2014; 4(3): 31–37. Publisher Full Text\n\nD’Souza N, Rodrigues C, Mehta A: Molecular characterization of methicillin-resistant Staphylococcus aureus with Emergence of epidemic clones of sequence type (ST) 22 and ST 772 in Mumbai, India. J. Clin. Microbiol. 2010; 48(5): 1806–1811. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLinosefa L, Lestari DC, Kusumaningrum A, et al.: Prevalensi Isolat MRSA Penghasil Panton-Valentine Leukocidin Pada Pasien Icu Rumah Sakit Tersier. Majalah Kedokteran Andalas. 2016; 39(1): 1–10. Publisher Full Text\n\nBhatta DR, Cavaco LM, Nath G, et al.: Association of Panton Valentine Leukocidin (PVL) genes with methicillin resistant Staphylococcus aureus (MRSA) in Western Nepal: a matter of concern for community infections (a hospital based prospective study). BMC Infect. Dis. 2016 May 15; 16: 199. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKoosha RZ, Fooladi AA, Hosseini HM, et al.: Prevalence of exfoliative toxin A and B genes in Staphylococcus aureus isolated from clinical specimens. J. Infect. Public Health. 2014 May 1; 7(3): 177–185. PubMed Abstract | Publisher Full Text\n\nAbbasi Montazeri E, Khosravi AD, Khazaei S, et al.: Prevalence of methicillin resistance and superantigenic toxins in Staphylococcus aureus strains isolated from patients with cancer. BMC Microbiol. 2021 Dec; 21: 1–9. Publisher Full Text\n\nRasheed NA, Hussein NR: Characterization of different virulent factors in methicillin-resistant Staphylococcus aureus isolates recovered from Iraqis and Syrian refugees in Duhok city, Iraq. PLoS One. 2020 Aug 17; 15(8): e0237714. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi X, Huang T, Xu K, et al.: Molecular characteristics and virulence gene profiles of Staphylococcus aureus isolates in Hainan, China. BMC Infect. Dis. 2019 Dec; 19(1): 1–2. Publisher Full Text\n\nImani Fooladi AA, Ashrafi E, Tazandareh SG, et al.: The distribution of pathogenic and toxigenic genes among MRSA and MSSA clinical isolates. Microb. Pathog. 2015; 81: 60–66. PubMed Abstract | Publisher Full Text\n\nRahimi F, Shokoohizadeh L: Characterization of virulence factors and prophage profiles of methicillin-resistant Staphylococcus aureus strains isolated from a referral hospital in Tehran, Iran. Jundishapur J. Microbiol. 2018; 13: e59385. Publisher Full Text\n\nMemariani M, Memariani H, Shahidi-Dadras M, et al.: Contemporary systematic review and meta-analysis of exfoliative toxin-producing Staphylococcus aureus strains isolated from patients in Iran. Reviews and Research in Medical Microbiology. 2020 Jan 1; 31(1): 1–10. Publisher Full Text\n\nSantosaningsih D, Santoso S, Setijowati N, et al.: Prevalence and characterisation of Staphylococcus aureus causing community-acquired skin and soft tissue infections on Java and Bali, Indonesia. Trop. Med. Int. Health. 2018 Jan; 23(1): 34–44. PubMed Abstract | Publisher Full Text\n\nAmelia S: Electrophoresis result of Staphylococcus aureus clinical isolates from Adam Malik General Hospital.2023. Publisher Full Text\n\nAmelia S: Result of ETA and PVL PCR and Cefoxitime Screening of Clinical Isolates. Dataset. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "221584",
"date": "24 Nov 2023",
"name": "Dewi Santosaningsih",
"expertise": [
"Reviewer Expertise Antimicrobial resistance",
"infection control",
"Staphylococcus aureus"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 Manuscript title: Prevalence of Panton-Valentine leucocidin (pvl) and exfoliative toxin A (eta) gene within methicillin resistant and sensitive Staphylococcus aureus in an urban tertiary referral hospital: A molecular epidemiology pilot study\nAim: to observe pvl and eta as virulence gene prevalence in a North Sumatera tertiary referral health center.\nGeneral comments: This study is important to predict the clinical manifestation of Staphylococcus aureus infection based on the properties of virulence genes including pvl and eta.\nAccording to the previous studies, pvl and eta genes were more likely found among Staphylococcus aureus isolated from community setting. In this study, the authors have evaluated the prevalence of the pvl and eta genes among clinical Staphylococcus aureus isolated from a tertiary care hospital in Indonesia. The reasons or background for evaluating the prevalence of pvl and eta genes in the hospital setting have not been described yet (both in the abstract and body text).\n\nThe academic merit of this study have not been explained yet.\n\nEnglish grammar issue should be improved.\n\nTitle:\nThe genes should be written in italic (e.g pvl, eta)\n\nPlease use methicillin-susceptible Staphylococcus aureus instead of methicillin-sensitiveStaphylococcus aureus\n\nA tertiary care hospital in Indonesia indicates a referral hospital, therefore the title contains redundancy.\n\nAbstract: The abstract was not described the study clearly, it should be re-arranged. The abstract would be better after the authors revised the body text (introduction, materials and methods, results, and discussion)\nIntroduction: The authors should be described the purpose of the study clearly. The urgency of the study was not described in the background yet.\nMaterials and methods: The type of specimens of clinical isolates Staphylococcus aureus collected in this study were not mentioned yet. The method of identification and antibiotic susceptibility test of the clinical isolates Staphylococcus aureus were not described clearly yet.\nResults: The description of results section should be re-arranged to be clearer and more understandable. The authors can start by explaining the prevalence of Staphylococcus aureus (overall) and then divide it into MRSA (%) and MSSA (%). Furthermore, the authors could describe the prevalence of pvl and eta genes among either MSSA or MRSA clinical isolates based on the type of specimen. How many pvl gene was positive among either MSSA or MRSA isolates from blood, sputum, and wound? Then, the severity of disease could be predicted.\nDiscussion: The authors should elaborate the discussion section based on the results section, therefore the conclusion will be drawn adequately 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? 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": "10840",
"date": "16 Jan 2024",
"name": "Sri Amelia",
"role": "Author Response",
"response": "General comments: This study is important to predict the clinical manifestation of Staphylococcus aureus infection based on the properties of virulence genes including pvl and eta. According to the previous studies, pvl and eta genes were more likely found among Staphylococcus aureus isolated from community setting. In this study, the authors have evaluated the prevalence of the pvl and eta genes among clinical Staphylococcus aureus isolated from a tertiary care hospital in Indonesia. The reasons or background for evaluating the prevalence of pvl and eta genes in the hospital setting have not been described yet (both in the abstract and body text). The academic merit of this study have not been explained yet. English grammar issue should be improved. We had attempted to fix this issue, hopefully while minor, this could improve our manuscript. Title: The genes should be written in italic (e.g pvl, eta) Please use methicillin-susceptible Staphylococcus aureus instead of methicillin-sensitiveStaphylococcus aureus A tertiary care hospital in Indonesia indicates a referral hospital, therefore the title contains redundancy. Thank you for the correction. We had fixed the issue. Abstract: The abstract was not described the study clearly, it should be re-arranged. The abstract would be better after the authors revised the body text (introduction, materials and methods, results, and discussion) Thank you for the correction. We had fixed the issue. Introduction: The authors should be described the purpose of the study clearly. The urgency of the study was not described in the background yet. Thank you for the correction. We had fixed the issue. Materials and methods: The type of specimens of clinical isolates Staphylococcus aureus collected in this study were not mentioned yet. The method of identification and antibiotic susceptibility test of the clinical isolates Staphylococcus aureus were not described clearly yet. Thank you for the correction. We had fixed the issue. Results: The description of results section should be re-arranged to be clearer and more understandable. The authors can start by explaining the prevalence of Staphylococcus aureus (overall) and then divide it into MRSA (%) and MSSA (%). Furthermore, the authors could describe the prevalence of pvl and eta genes among either MSSA or MRSA clinical isolates based on the type of specimen. How many pvl gene was positive among either MSSA or MRSA isolates from blood, sputum, and wound? Then, the severity of disease could be predicted. We couldn't fix this issue, all samples were obtained from bacteremia patient through blood collection. No other samples were obtained through other methods. However this may be the limitation of our studies thus we had described this in limitation. Discussion: The authors should elaborate the discussion section based on the results section, therefore the conclusion will be drawn adequately supported by the results. We had attempted to fix this issue."
}
]
},
{
"id": "202379",
"date": "24 Nov 2023",
"name": "Amin Soebandrio",
"expertise": [
"Reviewer Expertise Clinical Microbiology",
"Immunology",
"Molecular 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\nMethodology:\nPlease clarify the followings:\n\nAntibiotic discs were placed inside or on MHA?\n\nWhat does it mean \"after 24 hours of incubation\"?\n\nWhat suspension was transferred?\n\nDNA extraction\nBacterial cells should be first suspended before centrifugation. In what solution or buffer the bacteria was suspended.\n\nBuffer contained Lysozyme was then added and vortexed. What buffer?\n\n200uL of absolute ethanol was then added and vortexed.\n\nSentences in this paragraph should be rewritten to improve clarity or the procedures.\nDiscussion. The percentage of PVL gene in community-acquired and hospital-acquired MRSA and MSSA should be described and discussed. More references should be included in the discussion and conclusion development. Among others, Melles DC, van Leeuwen WB, Boelens H, Peeters JK, Verbrugh HA, van Belkum A. Panton-Valentine Leukocidin Genes in Staphylococcus aureus. Emerg Infect Dis. 2006;12(7):1174-1175. https://doi.org/10.3201/eid1207.050865.\nOthers. Any abbreviation should be described when it appears for the first time. Example: ET.\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?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "10839",
"date": "16 Jan 2024",
"name": "Sri Amelia",
"role": "Author Response",
"response": "Methodology: Please clarify the followings: Antibiotic discs were placed inside or on MHA? What does it mean \"after 24 hours of incubation\"? What suspension was transferred? Thank you for the correction all unclear parts in methodology has been corrected. DNA extraction Bacterial cells should be first suspended before centrifugation. In what solution or buffer the bacteria was suspended. Buffer contained Lysozyme was then added and vortexed. What buffer? 200uL of absolute ethanol was then added and vortexed. Sentences in this paragraph should be rewritten to improve clarity or the procedures. Thank you for the correction all unclear parts in methodology has been corrected. Discussion. The percentage of PVL gene in community-acquired and hospital-acquired MRSA and MSSA should be described and discussed. More references should be included in the discussion and conclusion development. Among others, Melles DC, van Leeuwen WB, Boelens H, Peeters JK, Verbrugh HA, van Belkum A. Panton-Valentine Leukocidin Genes in Staphylococcus aureus. Emerg Infect Dis. 2006;12(7):1174-1175. https://doi.org/10.3201/eid1207.050865. We found this research interesting and we had added this research in our discussion. Thank you Others. Any abbreviation should be described when it appears for the first time. Example: ET. Thank you for the correction. We had followed the review as best as we could."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1002
|
https://f1000research.com/articles/13-138/v1
|
22 Feb 24
|
{
"type": "Research Article",
"title": "Fabrication and in vitro characterization of curcumin film-forming topical spray: An integrated approach for enhanced patient comfort and efficacy",
"authors": [
"Amitha Shetty",
"Akhilesh Dubey",
"Jeshma Chrystle",
"Manohar M",
"Anish John",
"Amitha N",
"Paramita Das",
"Srinivas Hebbar",
"Amitha Shetty",
"Akhilesh Dubey",
"Jeshma Chrystle",
"Manohar M",
"Anish John",
"Amitha N",
"Paramita Das"
],
"abstract": "Background Curcumin, known for its anti-inflammatory properties, was selected for the developing consumer friendly film forming spray that offers precise delivery of curcumin and and improves patient adherence.\n\nMethods An optimized film-forming solution was prepared by dissolving curcumin (1%), Eudragit RLPO (5%), propylene glycol (1%), and camphor (0.5%) in ethanol: acetone (20:80) as the solvent. The solution was filled in a spray container which contained 70% solutions and 30% petroleum gas. In-vitro characterization was performed.\n\nResults Potential anti-inflammatory phytoconstituents were extracted from the PubChem database and prepared as ligands, along with receptor molecules (nsp10-nsp16), for molecular docking using Autodock Vina. The docking study showed the lowest binding energy of -8.2 kcal/mol indicates better binding affinities. The optimized formulation consisted of ethanol:acetone (20:80) as the solvent, Eudragit RLPO (5%) as the polymer, propylene glycol (1%) as the plasticizer, and camphor oil (0.5%) as the penetration enhancer. The optimized formulation exhibited pH of 5.8 ± 0.01, low viscosity, low film formation time (19.54 ± 0.78 sec), high drug content (8.243 ± 0.43 mg/mL), and extended ex vivo drug permeation (85.08 ± 0.09%) for nine hours. Consequently, the formulation was incorporated into a container using 30% liquefied petroleum gas, delivering 0.293 ± 0.08 mL per actuation, containing 1.53 ± 0.07 mg of the drug. The film-forming spray exhibited higher cumulative drug permeation (83.94 ± 0.34%) than the marketed cream formulation and pure drug solution after 9 h, with an enhancement ratio of 14. Notably, the film-forming spray exhibited no skin irritation and remained stable for over three months.\n\nConclusions The developed curcumin film-forming system is promising as a carrier for wound management because of its convenient administration and transport attributes. Further in vivo studies are required to validate its efficacy in wound management.",
"keywords": [
"film-forming spray",
"curcumin",
"design of experiment",
"docking study",
"permeation",
"stability study"
],
"content": "Introduction\n\nA wound is an abrupt or gradual loss of skin or tissue integrity that causes inflammation and the entry of pathogens into the body. Wounds must heal rapidly to reduce the risk of infection and restore the functional status of the skin. In general, the healing process of a wound lasts from 8 to 12 weeks; however, for chronic wounds, it may take years. The natural wound healing process has four distinct phases: hemostasis followed by inflammatory phases. Within a few hours of injury, a new epithelium begins to develop, including the growth of new blood vessels, collagen fiber implantation, and granulation tissue production. The production of collagen is stimulated, as well as collagen reassembly and the development of scar tissue, in the final stage of wound healing.1 The currently available products function in wound healing in terms of antimicrobial agents, anti-inflammatory agents, and certain drugs that promote cell proliferation to repair damaged cells.\n\nThe importance of herbal-based drug delivery systems has significantly increased in recent years. World Health Organization (WHO) estimates that more than 80% of people worldwide depend on traditional medical practices for primary healthcare. The use of phytoconstituents such as curcumin, silymarin, and quercetin has expanded over the years because of the escalating cost of drugs and the side effects of synthetic agents.2 Curcumin is a polyphenolic constituent obtained from the rhizomes of Curcuma longa (turmeric) belonging to the family Zingiberaceae. As per the Indian Ayurvedic medicinal system, Curcuma longa and its constituents are widely used in several dosage forms for various disease conditions. According to other studies, polyphenol curcumin possesses potent antioxidant, antimicrobial and anti-inflammatory properties, and it is involved in re-epithelization by enhancing fibroblast proliferation.3 The anti-inflammatory properties of curcumin inhibited the production of two significant cytokines, tumor necrosis alpha and interleukin -1. Upon topical administration, the antioxidant property of curcumin has been shown to drastically reduce wound healing time by scavenging free reactive oxygen molecules such as hydrogen peroxide (H202) and superoxide (O2-).4 Additionally, Mohanty et al. demonstrated that a transdermal patch with curcumin-loaded oleic acid promoted granulation of new tissue and fibroblast infiltration within a week of application compared to the control group of animals.5 Despite these benefits, curcumin has significant limitations, such as poor aqueous solubility, a higher rate of elimination, and faster degradation. Therefore, topical product formulations aim to solubilize curcumin while protecting it from hydrolysis and ensuring its prolonged release into the target location. One disadvantage of topical curcumin is that toxicity at the wound site can occur at high concentrations. Therefore, the optimal concentration of the formulation was selected.6\n\nSuperficial and shallow wounds were effectively treated with polymeric films composed of transparent polyurethanes. Transparent films enable the exchange of carbon dioxide and oxygen between the wound and the environment, while protecting the site from microbial contamination.7 The film can be developed by spraying drug-polymer mixtures onto the skin as a patient-friendly method compared to gels and ointments. The advantages of film-forming spray over conventional topical formulations are a uniform distribution of the drug, lower irritation, improved wound healing by controlling moisture, and continuous spraying, which enhances the mechanical properties of the polymeric film.8 The nature of the polymer, nozzle type, spray pressure, and other variables can affect the spray pattern. Various film-forming sprays are available, such as ordinal spray, metered-dose spray, electrostatic spray, and ultrasonic spray.\n\nIn recent years, the discovery of new therapeutic agents has become simpler through the application of computer-assisted approaches. Determining the possible molecular interactions for selective binding between a drug and protein receptors is made easier using molecular docking techniques. These prospective approaches provide promising results at shorter intervals.9 In the present study, curcumin compounds were analysed using in silico methods to assess their possible inhibitory activities against the nsp10-nsp16 receptor. However, in vitro in vivo methodologies are required to authenticate drug properties. The objective of this in vitro study was to develop and assess a polyphenol curcumin-based film-forming spray intended to efficiently treat wounds.\n\n\nMethods\n\nCurcumin was acquired from Sigma-Aldrich Chemicals Pvt. Ltd. (>94% purity) (Bangalore, India). Eudrgait S100, Eudrgait RS100, Eudrgait E100, PVP K30, Carbopol 934-P, PEG 400, propylene glycol, camphor oil, dibutyl phthalate, menthol, ethanol, and acetone were purchased from Loba Chemie Pvt. Ltd. (Mumbai, India). Transcutol P was obtained from Nice Chemical Pvt. Ltd. (Kerala, India). All other chemicals and reagents used were of analytical grades.\n\nThe NGSM Institute of Pharmaceutical Sciences Institutional Animal Ethics Committee (IAEC) approved the purchase of adult male Wistar rats weighing approximately 200–250 g from the Nitte University-affiliated Centre for Animal Research and Experimentation (NUCARE) (Approval No. NGSM/IAEC/2021-22/240 dated 28th June 2021). Experiments were conducted in accordance with the Committee for Control and Supervision Experiments on Animals (CPCSEA) rules, experiments were conducted. All efforts were made to ameliorate any suffering of animals by the application of methylated spirit as an antiseptic to prevent infection and careful, gentle handling to minimize distress. The nine animals allocated to three groups of three animals each were maintained in a cage, with the optimum conditions of 25 ± 2°C, 50 ± 1% relative humidity (RH), and 12-hour light/dark intervals with regular feeding, including water and pellet food (Krishna valley Aggrotech, Sangli, Maharashtra, India).\n\nLigand preparation and molecular docking from PubChem database chemical structures of potential phytoconstituents with anti-inflammatory properties, namely both ligand and receptor molecules (nsp10–nsp16), were prepared in Autodock software (version number 4.2.0) to predict the target receptor by performing blind docking. A grid of 60 points each in the X, Y, and Z directions was chosen to accommodate any possible ligand-receptor complex using a blind docking approach. The graphical user interface of the PyMOL tool (version number 2.5) was used to visualize the structure files, and the protein-ligand interaction was prepared in Biovia Discovery Studio (2021).10\n\nSolvents such as ethanol, isopropyl myristate, ethyl acetate, propylene glycol, oleic acid, and acetone were used to determine the solubility of curcumin in these solvents. Excess curcumin was dissolved in 100 mL of each solvent and kept in a shaking water bath for 48 h. After 48 h, the solvents were centrifuged for 15 mins at 3000 rpm. From the centrifuged sample, 1 mL was taken, diluted to 10 mL with the respective solvents, and spectrophotometrically determined at 426 nm.11\n\nPolymers such as Eudragit RS100, Eudragit RLPO, Eudragit S100, Eudragit E100, PVP K-30, Carbopol 934-P, and PEG 400 were selected for the study. A film-forming solution was prepared using 1% curcumin and 5% polymer in ethanol: acetone (20:80), respectively, and was evaluated for viscosity, drying time, and stickiness.12\n\nPlasticizers, such as PEG 400, propylene glycol, and dibutyl phthalate, were selected for this study. The polymeric solvent system was prepared by dissolving 1% curcumin and 5% Eudragit RLPO in ethanol:acetone (20:80), respectively. Subsequently, plasticizers (0.75%) were added to the previously prepared polymeric solvent system and further evaluated for flexibility.13\n\nPenetration enhancers, such as camphor, menthol, and Transcutol P, were selected for this study. The polymeric solvent system was prepared to comprise 1% curcumin, 5% Eudragit RLPO, and 0.75% propylene glycol in ethanol:acetone (20:80), and 0.75% of each penetration enhancer, which was then evaluated for ex vivo permeation studies, flux, and enhancement ratio.14\n\nThe impact of selected independent variables including concentration of polymer (A), concentration of plasticizers (B), and concentration of penetration enhancers (C), and the dependent variables included film formation time (s) and ex vivo permeation studies (%). The experimental conditions were optimized using Design Expert software (Version 13.0.3.0, Stat-Ease, Minneapolis, MN 55413, USA) employing central composite design (CCD). An open-access alternative that can perform an equivalent function is R commander. The levels at which the independent variables were selected are listed in Table 1.15 The variable levels were optimized based on the desirability function approach. As shown in Table 2, appropriate constraint (target) levels were chosen to achieve the desired responses of the formulation.\n\nAs per the optimized formula obtained after optimization, the optimized film-forming solution was prepared by dissolving curcumin (1%), Eudragit RLPO (5%), propylene glycol (1%), and camphor (0.5%) in ethanol:acetone (20:80) as the solvent.\n\nViscosity\n\nViscosity assessment of the film-forming solution was assessed at a controlled temperature of 25 ± 1°C using a Brookfield viscometer (DV-11 +pro). A specific spindle (S 63) was used, and measurements were taken at different rotational speeds (10, 50, and 100 rpm) for 10 min. This systematic evaluation aimed to determine the viscosity limits suitable for the sprayability of a solution, which is an essential characteristic for its practical application. Each viscosity measurement was performed in triplicates.16\n\nFilm formation time\n\nThe film formation time, a critical parameter for ensuring patient compliance, was assessed by placing a minute quantity of the film-forming solution onto a petri dish. The time taken for the solution to transform into a fully formed dry film was carefully observed and recorded. This evaluation aimed to determine the time required for the film-forming process, which is a crucial factor for the convenience and usability of the formulation for patients. Among the various formulations, preference was given to those that exhibited shorter drying times, as they offered quicker film development, potentially enhancing patient comfort and adherence.17 Each measurement was performed thrice.\n\nStickiness\n\nThe stickiness evaluation involved gently placing a piece of cotton onto each dried film without applying any pressure. The degree of stickiness was determined based on the extent of cotton fibre retention on the film’s surface: films with a greater amount of retained cotton fibers were categorized as “very sticky,” films with a moderate level of retained fibers were classified as “medium sticky,” and films with no adherence of cotton fibers were considered “non-sticky.” This approach provides a practical and visual means of distinguishing between different levels of stickiness, systematically facilitating characterization of the adhesive properties of the films.18\n\npH determination\n\nThe pH of the film-forming solution was determined using a digital pH meter (Systronics, Ahmedabad, India). The pH meter electrode was submerged in the film-forming solution, and the pH value was directly recorded from the meter’s display.19\n\nDrug content studies\n\nThe drug content was carried out to determine the distribution of the drug in the film-forming patch. A 2 cm patch was cut, dissolved in 5 mL methanol, and made up to a volume of 10 mL using phosphate buffer (pH 7.4) (1st dilution). From this dilution, 1 mL was pipetted into another 10 mL volumetric flask, and the volume was made using phosphate buffer (pH 7.4). Drug content was estimated spectrophotometrically using a UV-visible spectrophotometer at 426 nm.20\n\nEx vivo permeation study\n\nDrug permeation from the subcutaneous layer of the skin was assessed using porcine ear pinna skin, because the porcine ear skin membrane morphology is similar to that of human skin using Franz diffusion cells. Skin was bought from the slaughterhouse and preserved in phosphate-buffered saline (pH 7.4) at room temperature. The hair present in the skin was gently removed and dipped in hot water for 15 min to remove any subcutaneous fatty layer. The excised skin was mounted between the donor and receptor compartments of the diffusion cell apparatus with effective permeation area of 3.14 cm2 and the formulation being applied on the stratum corneum facing outward of the donor compartment and the Phosphate buffer with pH 7.4 as receptor medium. A weighed amount of the formulation equivalent to 20 mg of the drug was placed on the surface of the skin. The dissolution medium was mixed using a magnetic stirrer at 50 rpm, and the temperature was maintained at 37 ± 0.5°C to simulate external skin conditions using a water bath. A sample of 1 mL was withdrawn at predetermined time intervals (0, 1, 2, 3, 4, 5, 6, 7, 8, and 9 h). The sink condition was maintained by replacing the sink with the same amount of saline buffer. One millilitre of the withdrawn sample was dissolved in 10 mL of phosphate-buffered saline (pH 7.4) in a volumetric flask. Absorbance was measured using a UV-visible spectrophotometer at 426 nm. The cumulative amount of drug that permeated (%) through the skin was plotted versus time (h). Data are expressed as the mean ± standard deviation (SD) of three determinations. This study assessed and compared the transdermal permeation capabilities of an in-house pure curcumin drug solution, film-forming spray formulation, and commercially available cream.21\n\nPermeation data analysis\n\nThe experimental determination of permeation parameters involved calculating the skin flux (J) in μg/cm2/h using Equation (1), derived from the slope of the linear segment in the plot of cumulative amount permeated per unit area against time. The skin flux (J) can be experimentally determined using the formula\n\nVerification of optimization\n\nThe predicted results from the optimization were compared with the experimental values were compared and the relative percentage error was determined.\n\nThe process of filling the container with film-forming solutions involved the application of a pressure-filling method. This procedure employed 70% of the film-forming solution and 30% of liquefied petroleum gas as the propellant. This precise mixture was introduced into the container to ensure controlled and efficient filling. The developed formulation is illustrated in Figure 1.\n\nThe delivery volume per actuation\n\nThe formulation delivered per actuation was measured using the following formula:\n\nWhere AL represents the volume of the solution delivered per actuation, Wo and Wt is the weight of the formulation before and after actuation, and Dn is the density of the formulation. The measurements were made in triplicates and the results were expressed as mean ± SD.23\n\nSpray pattern\n\nThe formulation was sprayed onto Whattmann paper positioned at a predetermined distance. This paper was securely fastened to a board to create a stable platform for the experiment. The spray formulations were discharged from the container at a distance of 15 cm from the paper surface. This standardized procedure allowed for the observation and assessment of the resultant spray pattern on paper. By conducting this test, the uniformity and spread of the spray could be visually examined and analysed for consistency and effectiveness.24\n\nSpray angle\n\nThe sprays were actuated horizontally on white paper mounted 15 cm from the nozzle. The radius of the circle formed on the paper was recorded in triplicate from different directions. The spray angle (θ) is calculated using the following equation:\n\nThe protocol for the present study (Ref: NGSM/IAEC/2021-22/240) was approved by the Institutional Animal Ethics Committee (IAEC). A skin irritation study was conducted in male Wistar rats to ensure product safety. Inclusion and exclusion criteria for animals included factors such as the health status, age, weight, of either sex were considered. Nine healthy male Wistar rats weighing between 200–250 gm were included based on a thorough literature survey, aligning with ethical guidelines to use the minimum animals necessary while ensuring statistical robustness. The sample size was determined according to the available literature, as the study did not consider a specific primary outcome measure for hypothesis testing, and therefore no a priori sample size calculation was conducted. Nine Wistar rats were divided into three groups, with three rats in each group: Group I (control, placebo spray), Group II (standard, drug in solvent), and Group III (film-forming formulation). They were caged separately according to their groups and provided with food, water, and proper environmental conditions. Twenty-four hours before the application, the hair on the dorsal side (3 × 3 cm) of the male Wistar rats was removed using an electric clipper in the direction of the tail to the head without damaging the skin, and the methylated spirit was then applied as an antiseptic to the shaved region with the aid of cotton wool to prevent infection caused by bacteria. As only skin irritation studies were carried out on the dorsal surface, animals were not euthanised. The formulations were applied to the depilated areas of the animals in each group. Exclusion criteria included any signs of pre-existing skin conditions or illness. For data points, criteria for inclusion or exclusion involved the presence of observable skin irritation reactions. Humane endpoints were based on the observations such as presence of severe irritation, ulceration, and significant behavioural changes. If these conditions transpired, the animals were excluded from the study with immediate implementation to minimize suffering. Skin irritation was observed according to the OECD guidelines at predetermined intervals three times daily. At the end of 24 h, the skin surface was rinsed with distilled water and graded if edema was observed. Wistar rats were re-caged, and post-procedure observation (i.e., scoring) was repeated for seven days. Based on the scoring, the formulated films were graded as non-irritant, irritant, or highly irritant.26,27\n\nThe formulated film-forming spray was kept for stability investigation according to International Council for Harmonisation (ICH) guidelines [Q1A, R2] for six months at 40°C ± 2 and relative humidity of 75 ± 2%. The study conditions were maintained in a stability chamber (Photostability Chamber, Rotek). At three months, samples were taken to determine the film-formation time, pH, volume delivered upon each actuation, and drug content per actuation. The samples were assessed in triplicate [n = 3].28\n\nThe results are presented as mean ± SD. The experiments were performed in triplicate. A t-test and one-way ANOVA were used for statistical analysis to determine significant differences between the means tested (p <0.05), applying Sidak’s multiple comparisons test to assess the differences between groups. All calculations were completed using Graphpad Prism 10 (GraphPad Inc., La Jolla, CA, USA). An open-access alternative that can perform an equivalent function is JASP.\n\n\nResults\n\nIn this study, in-silico docking tools were employed to validate the viability of selected curcumin molecules with respect to their interactions with the target protein (nsp10-nsp16), considering a variety of conformations and binding energies. A comprehensive understanding of binding dynamics was obtained by scrutinizing multiple conformations, shown in Figure 2. This multifaceted approach revealed a spectrum of binding energies, providing insights into the strength of the interactions between the curcumin molecules and the receptor. Curcuminoids in turmeric exhibited the most favorable binding energy among the studied molecules, with a remarkable value of -8.2 kcal/mol. This outcome underscores the potential of curcumin as a potent ligand for target proteins. Through its interactions with the receptor, curcumin establishes hydrogen bonds with key residues, including ASP:135, GLN:327, CYS:47, LEU:152, and ARG:469, contributing to its robust binding affinity. A crucial indicator of the efficacy of the ligand-receptor interaction is the calculated change in Gibbs free energy (ΔG). In the context of this study, the lower value of ΔG associated with curcumin underscores its enhanced binding affinity to the target protein. This implies a more stable and robust interaction, reinforcing the potential therapeutic relevance of curcumin.29 Thus, the computational docking study offers valuable insights into the molecular-level interactions between curcumin and the nsp10-nsp16 receptor.\n\nThe solvent used to suspend a drug has the potential to exert a significant impact on the thermodynamic activity of the drug itself. This can lead to increased drug penetration into the subcutaneous layer, subsequently facilitating the achievement of a more substantial concentration of the drug at the topical application site.30 Hence, various solvents, including ethanol, isopropyl alcohol, ethyl acetate, propylene glycol, oleic acid, and acetone, were systematically assessed for compatibility with curcumin. Notably, among the solvents tested, ethanol and acetone demonstrated the highest solubility for curcumin. Owing to the lone pair of oxygen atom electrons in its molecular structure, curcumin forms hydrogen bonds that allow it to dissolve in organic solvents.31 Therefore, different ethanol/acetone ratios (20:80, 50:50, and 80:20) were used to determine the concentration. The solvent with the highest concentration was ethanol: acetone, taken in a ratio of 20:80, and thus was selected as the best solvent for further studies (Figure 3).\n\nIn the current study, the screening process for polymers revolved around critical attributes, including viscosity, drying time, and stickiness, as listed in Table 3. Often regarded as a crucial determinant, viscosity leans towards lower values for spray-based film formation, enabling accurate and adaptable dosing strategies. In this context, the formulations were thoroughly evaluated to assess viscosity, yielding a spectrum ranging from 0.21 to 2.9 cps. Consequently, solutions with lower viscosities were developed for further consideration. Drying time, another parameter, underpins the efficacy of film-forming solutions. Swift drying times, typically within the range 3–4 minutes, are preferred to prevent extended waiting periods for patients. To ascertain this, the formulations were subjected to drying time evaluations spanning from 10 s to 10 min. Subsequent analysis led to the selection of solutions with the shortest drying times, effectively avoiding prolonged patient waiting intervals.32 Moreover, an imperative criterion involves the adherence potential of the prepared film-forming solutions, which necessitates minimal stickiness to avert undesired interactions with clothing or surfaces. The assessment of stickiness rendered a diverse spectrum, encompassing solutions ranging from least sticky to markedly adhesive solutions. Consequently, solutions characterized by reduced stickiness were identified as successful candidates, warranting further investigation.33 An intriguing observation was made within the conducted investigations regarding Carbopol 934-P, which displayed an exceptionally rapid drying time of 10 ± 0.31s owing to its inherent hydrophilic nature. However, this was accompanied by a moderate level of stickiness. In contrast, Eudragit RLPO exhibited a marginally extended drying time of 11 ± 0.03s while remaining non-sticky, which rendered it particularly favorable. As a result, Eudragit RLPO emerged as the preferred polymer for film-forming spray formulation.\n\nPlasticizers contribute to improved film-forming solution flexibility, and thus reduce the brittleness, cracking, and flaking of the film. The plasticizers selected were PEG 400, propylene glycol, and dibutyl phthalate. Dibutyl phthalate was not considered because it was not sufficiently flexible, was very sticky, and did not form an even patch. PEG 400 and propylene glycol (0.75%) were evaluated based on flexibilities. The propylene glycol films were found to be more flexible than PEG 400.\n\nThe complex arrangement of the intercellular lipid layers is a major barrier to transdermal drug penetration. The drug diffusion process begins, and the interaction between the permeation enhancer and skin lipids influences its solubility.34 The stratum corneum, sweat glands, or hair follicles are all involved in the process used by penetration enhancers to allow drugs to get through. The penetration enhancers selected were camphor, menthol, and Transcutol P at a concentration of 0.75% each. They were evaluated based on the ex vivo drug permeation, flux, permeability coefficient, and enhancement ratio. The addition of Transcutol P to the solution resulted in turbidity and increased viscosity; thus, it was not considered for further studies. Camphor 0.75% demonstrated statistically significant maximum drug permeation of 85.60 ± 0.32% after nine hours, with a flux value of 7.41 ± 0.17 μg/cm2/hr and a permeability coefficient of 0.37 ± 0.05 cm2/hr, compared to menthol (p < 0.05) with an enhancement ratio of 18.5 as depicted in Figure 4 and Table 4. Therefore, camphor was selected as the best penetration enhancer in this study.\n\nThe data presented are the mean ± standard deviation (n = 3). Significance was measured by One-way ANOVA. ** indicates the significance between camphor and without penetration enhancer (p < 0.005), and *indicates the significance between camphor and menthol (p < 0.05).\n\nThe formulation was optimized using 23 levels of factorial randomized central composite design using the Design Expert software. Seventeen trial batches were prepared and evaluated for film formation time and ex vivo drug permeation. The film formation time and ex vivo drug permeation studies were 18.20–49.73 secs and 65.08–89.64%, respectively (Table 5).\n\nImpact of selected variables on film formation time\n\nThe p-value <0.0001 and an F-value of 69.71 indicated that the quadratic model for film formation time was significant. The non-significant lack of fit, (p = 0.5471), suggested the appropriateness of the model for predicting film formation time. the contour plot and response surface plot (Figure 5), indicated that the film formation time was substantially increased with increase in the concentrations of polymer, plasticizer, and permeation enhancer from -1 to +1 levels.\n\nThe impact of selected factors on the film formation time is shown in the following equation:\n\nA, B, and C represent the coded values for the polymer, plasticizer, and penetration enhancer concentrations, respectively.\n\nImpact of selected variables on ex vivo drug permeation studies\n\nThe p-value of 0.0036 and an F-value of 9.53 indicated that the quadratic model for ex-vivo drug permeation studies was significant. The non-significant lack of fit, (p=0.1455), indicated that the appropriateness of the model for ex-vivo drug permeation studies. The contour plot and response surface plot (Figure 6) indicated significant increase in ex-vivo drug permeation with an increase in both polymer and plasticizer concentrations from -1 to +1 level. However, as the penetration enhancer increased from 0.5% to 1%, the ex vivo drug permeation studies decreased. These factors significantly affected ex vivo drug permeation studies, as shown in the following equation:\n\nA, B, and C represent the coded values for the polymer, plasticizer, and penetration enhancer concentrations, respectively.\n\nThe criteria for numerical optimization and the optimized formulation based on Design Expert software are presented in Table 2.\n\nThe pH, viscosity, film formation time, drug content, and ex-vivo permeation studies were performed as described in the methods section. The results are shown in Table 6. The colour and appearance of the optimized film-forming solutions were then evaluated. The physical appearance of the film-forming solution was dark yellow and transparent. The evaluation of pH is a crucial parameter for topical formulations, as it can cause skin irritation if it differs from standard skin pH conditions (i.e., 4 to 6). The pH was 5.8 ± 0.01, closer to the skin pH. Therefore, the curcumin film-forming solution may not irritate the skin while administered topically and also helps in the ionization of the drug into the permeation process. The viscosity of the optimized film-forming solution was 2.268 cps, which ensured accurate and flexible dosing because viscosity is inversely proportional to the number of polymers utilized; a higher viscosity results in less spray coverage.\n\nThe mechanism of film formation is the evaporation of the solvent base. Solvent drying at room temperature is essential to obtain a film-forming solution that promotes patient compliance. The test revealed the time required for solvent evaporation and production of skin-contacting films. The total drying time of the optimized film-forming solution was 19.54 ± 0.78 s, indicating an ideal value compared to the standard film-forming spray, that is, less than 3 min.35\n\nThe drug content in the optimized film-forming solution was 8.243 ± 0.43 mg\\mL. Drug content assessment suggested that the drug was uniformly distributed. Uniformity of the drug content is necessary to ensure the homogeneity of the dispersed drug in the entire formulation.\n\nThe cumulative drug permeation of the optimized film-forming solution ranged from 21.01 ± 0.06% after 1 hr to 85.08 ± 0.09% after 9 h. Hence, the optimized film-forming curcumin solution containing 5% RLPO, 1% propylene glycol, and 0.5% v/v camphor showed prolonged drug permeation.\n\nTable 7 lists the predicted and experimental values of all response variables and the percentage error. The mean percentage error was 1.04 after comparing the observed and predicted responses. Thus, a low magnitude of error indicated an excellent fit of the model.\n\nThe volume delivered upon each actuation\n\nIn this study, assessing the volume delivered per actuation emerged as a pivotal consideration for ensuring the reliability and uniformity of dosing across applications. The experimental findings unveiled a delivered volume of 0.293 ± 0.08 mL for each spray actuation.\n\nSpray pattern\n\nEvaluation of the spray pattern is an integral aspect in assessing the functionality and performance of the optimized film-forming solution. A visual representation of the spray pattern in Figure 7 empirically confirms the performance of the formulation. This illustration provides tangible insight into the dispersion dynamics of the solution, reaffirming its potential for successful application.\n\nSpray angle\n\nThe spray angle was found to be 72.59° ± 1.43, which was optimal. The actuation amount and spray angle are influenced by the nature of the polymer and its concentration, as well as the viscosity of the formulation.\n\nDrug content\n\nDetermining the amount of curcumin delivered per actuation is a pivotal parameter for assessing the reliability and consistency of drug delivery systems. The findings revealed a consistent delivery of curcumin, with 1.53 ± 0.07 mg delivered per actuation.\n\nAn ex vivo animal skin model is the most realistic method for evaluating transdermal formulations and understanding drug permeation through the subcutaneous skin layer. Porcine ear skin shows the most relevant histological structure as human skin, with a subcutaneous thickness of 21–26 μm and hair follicle density of 20/cm2.36 The Figure 8 results indicated that the film-forming spray exhibited the highest drug permeation, showing a significant difference compared to the pure drug solution (p < 0.005), with an exceptional 83.94 ± 0.34% permeation after 9 h. This was accompanied by a flux value of 8.47 ± 0.13 μg/cm2/hr and a permeability coefficient of 0.42 ± 0.35 cm2/hr. In contrast, owing to its physicochemical properties, the pure drug solution displayed the lowest permeability at 20.23±0.16%. The formulation of curcumin as a film-forming spray significantly elevated drug permeation compared to that of the pure drug solution, demonstrating an enhancement ratio of 14 (Table 8). This enhancement can be attributed to a natural permeation enhancer, 0.5% camphor, which interacts with subcutaneous intracellular lipids, augments the partition coefficient of curcumin. Notably, the permeability of the film-forming spray was slightly superior (enhancement of 1.4) to that of the marketed cream formulation.\n\nThe data represent the mean ± SD. n = 3. The data presented are the mean ± standard deviation (n = 3). Significance was measured by One-way ANOVA. ** indicate the significance between film-forming spray and pure drug (p < 0.005), and * indicate the significance between film-forming spray and marketed formulation (p < 0.05).\n\nSkin irritation is a sign that the skin is exposed to various external stimuli that cause inflammation, without triggering the production of specific antibodies.37 In the transdermal formulation, skin irritation may be caused by the chemical nature of the API and other excipients. The concentration of the permeability enhancers and the formulation’s contact time duration may be contributory variables. This study was conducted using healthy Wistar rats. Group I was used as the control, Group II was the standard drug group, and Group III was used for the film-forming spray. After visual inspection, the film-forming spray was compatible with rat skin and showed no irritation. The rats were observed after 0 h, 1 d, and 7 d, and readings were recorded. There were no signs of erythema or edema over the entire period of seven days. From the results tabulated in Table 9 and Figure 9, it can be concluded that the curcumin film-forming spray is irritation-free.\n\nThe formulation was assessed according to the ICH regulatory authority [Q1, R2] accelerated stability conditions and observed changes in the formulation for its film formation capacity in terms of pH, volume delivered, and drug content per actuation using a UV spectrometer. No statistically significant difference (p ≤ 0.05) in the intermediate and the final testing point of the study (three and six months) was observed in the film formation time, pH, actuation volume, and drug content per actuation values compared to the initial formulation.\n\nFurthermore, drug content appears to decrease non-significantly from 1.53 ± 0.07 mg/actuation to 1.50 ± 0.27 mg/actuation to 1.49 ± 0.57 mg/actuation to 1.43 ± 0.01 mg/actuation. According to the ICH Q1 R2 guidelines, these minimal changes are acceptable to pass the stability study. The formulated product maintained its quality with respect to its physical and chemical stability over six months at 40 ± 2°C and 75 ± 2% RH. The results of this study are presented in Table 10.38\n\n\nDiscussion\n\nComputational docking techniques hold immense promise for predicting the potential applicability of a drug by elucidating its interactions with a specific receptor.39,40 The outcomes of the docking investigations shed light on the distinctive properties of different curcumin molecules in their interactions with the target protein. Identifying the optimal binding energy of curcumin and its specific interactions with key residues furthers our understanding of its ligand potential. These findings provide a theoretical foundation for the efficacy of curcumin and pave the way for future experimental validation and potential applications in drug development or therapeutic interventions targeting the nsp10-nsp16 protein complex.\n\nThe exploration of solvent solubility is inherently tied to supersaturation, a principle pivotal to solvent evaporation from the surface of the skin post-application. The fact that drugs remain soluble in the non-volatile component prevents drug precipitation. The combined mixture of acetone and ethanol increased the vapor pressure compared with the use of a single solvent.41\n\nThe selection of appropriate polymers is a pivotal factor that influences the successful formation of film-forming sprays.42 The reasonable drying time and non-sticky behavior positioned Eudragit RLPO as the optimal choice for further development and evaluation within the context of this study.\n\nA flexible wound film can bend, stretch, and adapt to body movements and changes in the wound area. This is crucial for patient comfort and effective wound healing. When plasticizer molecules are coupled with long polymeric chains, the film functionality is altered. This combination decreases the intermolecular forces and increases the flexibility of the films.43 The propylene glycol structure has less polarity than PEG 400; therefore, it has a lower ability to bind water. The lower hydrophilicity of propylene glycol leads to greater flexibility of the film.44\n\nCamphor is a promising natural penetration enhancer because according to a study by Feng Xie et al., it exhibits a safer and more effective increase in penetration, improving the transdermal permeation of medications with various lipophilicities.45\n\nThe accurate and consistent delivery of a specific volume with each actuation of a spray is a critical parameter that directly influences dosing precision within the application context. The close approximation in volume with minimal variance signifies meticulous design and engineering of the spray mechanism, resulting in a nearly consistent volume of liquid dispensed during each spray. Such a consistent volume is of paramount importance because it plays a dual role in ensuring accurate dosing and forming an effective film over the target area.46\n\nThe spray pattern, denoting the spray’s geometric shape in the cross section, is a defining attribute that characterizes the behavior of the delivered substance upon actuation.47 The favorable spray pattern, indicative of the optimized solution’s ability to achieve a desirable and uniform cross-sectional shape, further contributes to the formulation’s potential for wound treatment.\n\nSpray angles are essential to prevent over-spraying of the film-forming solution onto the skin. It also provides adequate coverage for product application. Gohel et al. stated that the suitable angle for spray determination was less than 85° for easy operation and covering the total surface area.48\n\nThe amount of curcumin delivered with each actuation is of substantial importance, as it directly influences the uniformity of drug distribution and subsequently affects the therapeutic effectiveness of the formulation. The closely aligned quantity, accompanied by minimal variance, signifies meticulous engineering of the delivery mechanism and precise calibration.\n\nThe enhanced drug permeation observed with the film-forming spray formulation emphasizes its compatibility with the permeation characteristics of curcumin and its potential to enhance patient compliance owing to its convenient administration and transport attributes. This investigation underscores the superiority of the film-forming spray over liquid and semi-solid preparations, establishing its efficacy in terms of permeability.\n\n\nConclusions\n\nThe formulation and evaluation of a curcumin film-forming spray for wound healing has shown promising results. Film-forming sprays offer several advantages over traditional topical formulations, including improved absorption, reduced skin irritation, and a consistent dose distribution. A molecular docking study augmented the anti-inflammatory properties of curcumin. The drug was successfully incorporated into a film-forming solution and sprayed with a propellant. The formulated solution exhibited favorable pH and viscosity and demonstrated prolonged permeation of curcumin with high ex vivo drug permeation. Notably, the formulation was found to be a non-irritant, ensuring its suitability for topical applications. This study presents a novel approach to effectively deliver curcumin locally for wound healing, while enhancing patient compliance using a film-forming spray. Further extensive research and clinical studies are warranted to explore the full potential of curcumin-based film formation in wounds and pain management.\n\n\nAuthors contributions\n\nAS, JC, and AJ conceptualized this study. AS and JC strategized the methods and AS supervised the work. JC and AN conducted the experiments and analyzed the data. AS, MM, PD, AD, and SH interpreted data. PD conceptualized the docking study. MM, AD, AN, and SH designed the figure and performed statistical analysis. All authors aided in drafting the manuscript. All the authors critically reviewed, edited, and approved the final manuscript.",
"appendix": "Data availability\n\nFigshare: Underlying data for ‘Fabrication and in vitro characterization of curcumin film-forming topical spray: An integrated approach for enhanced patient comfort and efficacy’, https://www.doi.org/10.6084/m9.figshare.24191067. 27\n\nFigshare: ARRIVE checklist for ‘Fabrication and in vitro characterization of curcumin film-forming topical spray: An integrated approach for enhanced patient comfort and efficacy’, https://www.doi.org/10.6084/m9.figshare.24191067. 27\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nAcknowledgements\n\nThe authors would like to acknowledge “Vaidyaratnam Ayurveda Research Institute,” Thrissur, Kerala, for assisting with the development of the spray product.\n\n\nReferences\n\nBarchitta M, Maugeri A, Favara G, et al.: Nutrition and Wound Healing: An Overview Focusing on the Beneficial Effects of Curcumin. Int. J. Mol. Sci. 2019 Jan; 20(5): 1119. 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Rochester, NY: 2020 [cited 2023 Aug 20].\n\nGupta V, Trivedi P: Ex vivo localization and permeation of cisplatin from novel topical formulations through excised pig, goat, and mice skin and in vitro characterization for effective management of skin-cited malignancies. Artif Cells Nanomed Biotechnol. 2015; 43(6): 373–382. PubMed Abstract | Publisher Full Text\n\nSintov AC, Botner S: Transdermal drug delivery using microemulsion and aqueous systems: Influence of skin storage conditions on the in vitro permeability of diclofenac from aqueous vehicle systems. Int. J. Pharm. 2006 Mar 27; 311(1): 55–62. PubMed Abstract | Publisher Full Text\n\nResponse Surface Optimization and In-vitro Evaluation of Sustained Release Topical Insulin Liposomal Spray for Wound Healing. J. App. Pharm. Sci. 2018; 8(6): 22–29. Publisher Full Text\n\nIgnjatović J, Šušteršič T, Bodić A, et al.: Comparative Assessment of in vitro and In Silico Methods for Aerodynamic Characterization of Powders for Inhalation. Pharmaceutics. 2021 Nov; 13(11): 1831. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSmyth H, Hickey AJ, Brace G, et al.: Spray pattern analysis for metered dose inhalers I: Orifice size, particle size, and droplet motion correlations. Drug Dev. Ind. Pharm. 2006 Oct; 32(9): 1033–1041. PubMed Abstract | Publisher Full Text\n\nWang J, Li Z, Sun F, et al.: Evaluation of dermal irritation and skin sensitization due to vitacoxib. Toxicol. Rep. 2017; 4: 287–290. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHebbar S, Shetty A: Curcumin film forming topical spray Figshare. [Dataset]. 2023. Publisher Full Text\n\nSritharadol R, Nakpheng T, Wan Sia Heng P, et al.: Development of a topical mupirocin spray for antibacterial and wound-healing applications. Drug Dev. Ind. Pharm. 2017 Oct; 43(10): 1715–1728. PubMed Abstract | Publisher Full Text\n\nDu X, Li Y, Xia YL, et al.: Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods. Int. J. Mol. Sci. 2016 Jan 26; 17(2): 144. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJagannathan R, Abraham PM, Poddar P: Temperature-dependent spectroscopic evidences of curcumin in aqueous medium: a mechanistic study of its solubility and stability. J. Phys. Chem. B. 2012 Dec 20; 116(50): 14533–14540. PubMed Abstract | Publisher Full Text\n\nGhavami R, Biazar E, Taleghani AS, et al.: Design of Curcumin-Loaded Electrospun Polyhydroxybutyrate Mat as a Wound Healing Material. Nano Biomed. Eng. 2020 Mar 31; 12(1): 14–20. Publisher Full Text\n\nLiew KB, Tan YTF, Peh KK: Effect of polymer, plasticizer and filler on orally disintegrating film. Drug Dev. Ind. Pharm. 2014 Jan; 40(1): 110–119. PubMed Abstract | Publisher Full Text\n\nNoebels M, Cross RE, Evans DA, et al.: Characterization of spray-coating methods for conjugated polymer blend thin films. J. Mater. Sci. 2014 Jun 1; 49(12): 4279–4287. Publisher Full Text\n\nHagen M, Baker M: Skin penetration and tissue permeation after topical administration of diclofenac. Curr. Med. Res. Opin. 2017 Sep; 33(9): 1623–1634. PubMed Abstract | Publisher Full Text\n\nShababdoust A, Zandi M, Ehsani M, et al.: Controlled curcumin release from nanofibers based on amphiphilic-block segmented polyurethanes. Int. J. Pharm. 2020 Feb 15; 575: 118947. PubMed Abstract | Publisher Full Text\n\nAbd E, Yousef SA, Pastore MN, et al.: Skin models for the testing of transdermal drugs. Clin. Pharmacol. 2016 Oct 19; 8: 163–176. PubMed Abstract | Publisher Full Text\n\nAhn JH, Eum KH, Lee M: Assessment of the Dermal and Ocular Irritation Potential of Lomefloxacin by Using in vitro Methods. Toxicol. Res. 2010 Mar; 26(1): 9–14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJyothi VGSS, Pawar J, Fernandes V, et al.: Film forming topical dermal spray of meloxicam attenuated pain and inflammation in carrageenan-induced paw oedema in Sprague Dawley rats. J. Drug Deliv. Sci. Technol. 2022 Apr 1; 70: 103195. Publisher Full Text\n\nMeng XY, Zhang HX, Mezei M, et al.: Molecular docking: a powerful approach for structure-based drug discovery. Curr. Comput. Aided Drug Des. 2011 Jun; 7(2): 146–157. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPinzi L, Rastelli G: Molecular Docking: Shifting Paradigms in Drug Discovery. Int. J. Mol. Sci. 2019 Sep 4; 20(18): 4331. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee S, Kang T, Lee JY, et al.: Thin-Film Composite Nanofiltration Membranes for Non-Polar Solvents. Membranes (Basel). 2021 Mar 9; 11(3): 184. PubMed Abstract | Publisher Full Text | Free Full Text\n\nŠveikauskaitė I, Briedis V: Effect of Film-Forming Polymers on Release of Naftifine Hydrochloride from Nail Lacquers. Int. J. Polym. Sci. 2017; 2017: 1–7. Publisher Full Text\n\nZhong Y, Zhuang C, Gu W, et al.: Effect of molecular weight on the properties of chitosan films prepared using electrostatic spraying technique. Carbohydr. Polym. 2019 May 15; 212: 197–205. PubMed Abstract | Publisher Full Text\n\nHong SH, Cho Y, Kang SW: Formation of Water-Channel by Propylene Glycol into Polymer for Porous Materials. Membranes (Basel). 2021 Nov 16; 11(11): 881. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXie F, Chai JK, Hu Q, et al.: Transdermal permeation of drugs with differing lipophilicity: Effect of penetration enhancer camphor. Int. J. Pharm. 2016 Jun 30; 507(1–2): 90–101. PubMed Abstract | Publisher Full Text\n\nNaidu H, Kahraman O, Feng H: Novel applications of ultrasonic atomization in the manufacturing of fine chemicals, pharmaceuticals, and medical devices. Ultrason. Sonochem. 2022 May 1; 86: 105984. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSuhag R, Kumar N, Petkoska AT, et al.: Film formation and deposition methods of edible coating on food products: A review. Food Res. Int. 2020 Oct 1; 136: 109582. PubMed Abstract | Publisher Full Text\n\nGohel MC, Nagori SA: Fabrication of Modified Transport Fluconazole Transdermal Spray Containing Ethyl Cellulose and Eudragit® RS100 as Film Formers. AAPS PharmSciTech. 2009 May 22; 10(2): 684–691. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "259329",
"date": "18 Apr 2024",
"name": "Minakshi Nitin Nehete",
"expertise": [
"Reviewer Expertise phytochemical analysis",
"phytochemistry",
"pharmacology",
"molecular docking study"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article titled \"Fabrication and In vitro Characterization of Curcumin Film-Forming Topical Spray: An Integrated Approach for Enhanced Patient Comfort and Efficacy\" presents a well-written account with sufficient detail regarding methods and analysis. It serves as a valuable resource for researchers looking to undertake similar research endeavors. The introduction provides comprehensive details regarding the study, including background, rationale, and the selection of curcumin and film-forming spray. However, it fails to specify the types of wounds for which the developed curcumin film-forming spray is intended, such as acute, diabetic, etc. In the methods section, it is noted that each group of laboratory animals only consists of three rats. According to ICH guidelines, a treatment group should ideally contain six animals per group. Additionally, the name of the standard used in the skin irritation study is not mentioned. The article meticulously outlines the formulation and evaluation processes of the curcumin film-forming topical spray. The results section is detailed and informative. In the discussion section, formulation-related aspects are discussed thoroughly. However, the mechanism of action of the curcumin film-forming spray is not addressed in relation to wound healing activity, particularly concerning molecular docking study results. While the article does address some aspects of current literature, it falls short in fully addressing others. Furthermore, in the references section, while most references are from current literature, a few are not up-to-date.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "249576",
"date": "14 May 2024",
"name": "Tejal Mehta",
"expertise": [
"Reviewer Expertise Novel drug delivery systems and Pharmaceutical 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 work done systematically using experimental design. Results are justified with suitable cases. Following are the suggestions: 1. Include units in Table 2 2. Add the reason to choose particular grade of Eudragit in present study. 3. How the organic solvent residue is checked in final product?\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": "249577",
"date": "30 May 2024",
"name": "Ruchi Tiwari",
"expertise": [
"Reviewer Expertise Pharmaceutical sciences including all aspects of nano drug delivery systems."
],
"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\nStrength\nThe article “Fabrication and in vitro characterization of curcumin film-forming topical spray: An integrated approach for enhanced patient comfort and efficacy” is well within the journal’s scope. The paper introduces a novel method for delivering curcumin utilizing a film-forming spray, offering a convenient and precise means of administration. The study extensively characterizes the developed formulation, including its pH, viscosity, film formation time, drug content, and permeation properties, providing a thorough understanding of its characteristics. The study demonstrates superior drug permeation compared to traditional cream formulations and pure drug solutions, indicating the effectiveness of the developed film-forming spray in facilitating drug delivery.\nOpportunity\nAvoid typographical errors such as and 2 times in the abstract. Inconsistency in the usage of time units; it alternates between “h” and “hr” and “sec” and “s.” Kindly maintain uniformity by choosing one format throughout the manuscript. Include information on the temperature and agitation speed of the shaking water bath during the solubility testing of curcumin in various solvents, as these factors can influence solubility, ensuring the experiment's reproducibility. Specify whether the stickiness evaluation and pH determination were conducted in triplicates, similar to the film formation time assessment, to provide information on the reproducibility and reliability of the experimental findings. Table 5 in the text says optimization results, whereas the skin irritation tests table has been given. Kindly rectify it.\nWeaknesses:\nWhile the study demonstrates promising results in vitro, the absence of in vivo experimentation limits the ability to fully assess the efficacy and safety of the formulated spray in real physiological conditions. However, the authors acknowledge this limitation in the conclusion and suggest further extensive research and clinical studies to address this gap, indicating awareness of the need for further validation.\nOverall, the topic is relevant. The manuscript is recommended for indexing with the changes to the above-mentioned comments.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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/13-138
|
https://f1000research.com/articles/13-137/v1
|
22 Feb 24
|
{
"type": "Research Article",
"title": "Evaluation of accuracy and potential harm of ChatGPT in medical nutrition therapy - a case-based approach",
"authors": [
"Vinaytosh Mishra",
"Fahmida Jafri",
"Nafeesa Abdul Kareem",
"Raseena Aboobacker",
"Fatma Noora",
"Fahmida Jafri",
"Nafeesa Abdul Kareem",
"Raseena Aboobacker",
"Fatma Noora"
],
"abstract": "Background ChatGPT is a conversational large language model (LLM) based on artificial intelligence (AI). LLMs may be applied in health care education, research, and practice if relevant valid concerns are proactively addressed. The current study aimed to investigate ChatGPT’s ability to generate accurate and comprehensive responses to nutritional queries created by nutritionists/dieticians.\n\nMethods An in-depth case study approach was used to accomplish the research objectives. Functional testing was performed, creating test cases based on the functional requirement of the software application. ChatGPT responses were evaluated and analyzed using various scenarios requiring medical nutritional therapy, which were created with varied complexity. Based on the accuracy of the generated data, which were evaluated by a registered nutritionist, a potential harm score for the responses from Chat GPT was used as evaluation.\n\nResults Eight case scenarios with varied complexity when evaluated revealed that, as the complexity of the scenario increased, it led to an increase in the risk potential. Although the accuracy of the generated response does not change much with the complexity of the case scenarios, the study suggests that ChatGPT should be avoided for generating responses for complex medical nutritional conditions or scenarios.\n\nConclusions The need for an initiative that engages all stakeholders involved in healthcare education, research, and practice is urgently needed to set up guidelines for the responsible use of ChatGPT by healthcare educators, researchers, and practitioners. The findings of the study are useful for healthcare professionals and health technology regulators.",
"keywords": [
"Medical Nutrition Therapy",
"Generative AI",
"Large Language Models",
"ChatGPT"
],
"content": "Introduction\n\nNoncommunicable diseases (NCDs), which are also called chronic diseases, are long-lasting and occur because of a combination of factors including genetics, physiology, environment, and behavior.1 The major categories of NCDs are known as chronic diseases, and they include cardiovascular diseases, which cause 17.9 million deaths every year across the globe. Cancers also contribute significantly to chronic disease, causing 9 million deaths annually. Additionally, chronic respiratory diseases result in 3.9 million deaths each year, and diabetes causes 1.6 million deaths per year.1\n\nThe rising incidence of chronic illnesses is having a significant financial impact on healthcare systems worldwide, and it has attracted the interest and attention of policymakers and researchers at all levels of government.2 Typically, the methods employed to manage chronic illnesses are multifaceted, and they revolve around dietary or nutritional interventions, consistent physical exercise, and lifestyle adjustments at their core.3\n\nStudies have demonstrated that low-glycemic index (GI) and low-carbohydrate diets are successful in treating type 2 diabetes, and there has been extensive research into the use of unsaturated fatty acids, vitamins, and bioactive compounds in the management of chronic diseases. Although multidimensional approaches are crucial in managing these chronic illnesses, dietary interventions are of paramount importance and occupy a significant role in these strategies.2\n\nA chatbot powered by artificial intelligence (AI), ChatGPT (Chat Generative Pre-Trained Transformer), was launched by OpenAI in November 2022. With both supervised and reinforcement learning techniques, it is built on top of OpenAI’s GPT-3.5 and GPT-4 large language models (LLMs).4 By using a two-stage training process, large language models learn from data more efficiently than traditional deep learning models, as they begin self-supervised learning on huge amounts of unannotated data, then fine-tune their performance on smaller, task-specific, annotated datasets based on user specifications.5\n\nThe original ChatGPT release was based on GPT-3.5 as the foundation, an LLM (Large Language Model) with over 175 billion parameters.6 The newest OpenAI model, GPT-4 was released on March 14, 2023. It is important to note that ChatGPT’s training data is derived from a wide range of online sources, including books, articles, and websites. Utilizing reinforcement learning from human feedback in conversational tasks,7 ChatGPT can consider the complexity of users’ intentions to respond effectively to a variety of end-user tasks, such as medical queries.\n\nA growing amount of medical data and the complexity of clinical decision-making could theoretically benefit clinicians through NLP tools, allowing doctors to make timely, informed decisions. In addition, technological advancements have democratized knowledge, enabling patients to access medical information without relying solely on healthcare professionals. Instead, they are increasingly using search engines, and now artificial intelligence chatbots, to find medical information.8\n\nBy engaging in conversational interactions, Chat GPT and other recent chatbots provide authoritative-sounding responses to complicated medical queries. Even though ChatGPT is a promising technology, it often produces inaccurate results, meaning caution is warranted when applying it to medical practice and research.9–13 These engines have not been evaluated for accuracy and reliability, especially in terms of open-ended medical questions that doctors and patients might ask.10–12\n\nOur study aims to assess ChatGPT’s ability to generate accurate and comprehensive responses to nutritional queries created by Nutritionist/Dietician. In addition, this will provide an early indication of ChatGPT’s reliability as a provider of accurate and complete information. Furthermore, this study will highlight limitations and propose an approach for addressing those.\n\n\nMethods\n\nAll participants gave written informed consent. Ethical approval was not required as the study had low risk to participants.\n\nThe study uses a case study approach to achieve the research objectives stated in the earlier section. It provides rich and detailed data that can be used to gain a deep understanding of a particular case. It allows for the exploration of complex phenomena that cannot be easily studied through other research methods.14 Although there are limitations to the case study method it is one of the most useful tools in the exploratory study of abstract and evolving phenomena. The type of case study method utilized in this study is Illustrative case studies.15 The approach used in this study is borrowed from functional testing and quality Assurance practices in software development. Functional testing involves creating test cases based on the functional requirements of the software application. These test cases are designed to evaluate whether the software performs as expected. Functional testing is typically performed using black box testing techniques, which means that the tester does not have access to the source code of the software application. In this case, ChatGPT acts as a black box for the researchers involved in this study.\n\nTo evaluate the performance of ChatGPT in medical nutrition therapy a well-defined Study Protocol was used. The steps followed in the study as follows:\n\nStep 1: Creation of questions (scenarios) of varied complexity by public health professionals. The questions were selected by the licensed medial nutrition therapist working in UAE. The selected scenario was simple diet consultation to patient with comorbid conditions.\n\nStep 2: The response of ChatGPT was taken and recorded for further analysis.\n\nStep 3: The responses from Step 2 were evaluated by a registered nutritionist for accuracy.\n\nStep 4: Based on the accuracy the potential of harm score for the response was created.\n\nStep 5: Data was summarized and analyzed by the expert group used in Step 1.\n\nThe expert group for deciding complexity contained five public health professionals working in the United Arab Emirates. The experts were selected from Gulf Medical University, UAE and method of selection was nonrandom purposive sampling. The inclusion criteria for the expert were master’s degree and clinical experience greater than five years. The researchers involved in this study approached 7 healthcare professionals out of which five agreed to be part of the expert group. The researchers wanted to recruit five to nine experts as a number greater than that if difficult to handle and a number less than that may result in bias.\n\nFor accuracy, one registered nutritionist’s response was taken for step 3. The nutritionist gave a score on a ordinal scale of one to ten where one being least and ten being most accurate.\n\nTo ascertain the potential of harm in Step 4 all five experts discussed earlier worked together.\n\nThe method utilized for reaching consensus was the Delphi method depicted in Figure 1.16 Using the steps mentioned above and data provided in the support material the reproducibility of the research can be established. Again, a scale of one to ten was used to ascertain the potential to harm where one being least and ten being highest.\n\nSource: Author’s Compilation.\n\nThe Delphi method is a structured communication technique originally developed as a systematic, interactive forecasting method that relies on a panel of experts. The experts answered questionnaires in three rounds. After each round, a researcher VM provides an anonymous summary of the from the previous round as well as the reasons they provided for their judgments. Thus, the experts are encouraged to revise their earlier answers considering the replies of other members of their panel. It was observed that the range of the answers decreased, and the group converged. Finally, the process is stopped after a predefined stop and the median scores of the final rounds determined the results (Figure 1).\n\nThe conceptual definitions of the terms used in the study are as follows:\n\nClinical Accuracy: “A clinical accuracy is a qualitative approach that describes the clinical outcome of basing a treatment decision on the result of a measurement method being evaluated”.17\n\nComplexity of the Clinical Problem: “Clinical complexity is a protean term encompassing multiple levels and domains. Illustratively, a prominent concern in health care involves a multiplicity of disorders and conditions experienced by a person along with their cross-sectional and longitudinal contexts”.18\n\nPotential for Harm: “Harm means an injury to the rights, safety or welfare of a research participant that may include physical, psychological, social, financial or economic factors”.19\n\n\nResults & discussion\n\nThis section discusses the results obtained from the illustrative case study method described in the earlier section.\n\nThe question is simple, with age, gender, and a weight loss goal provided. The statement emphasizes the importance of sustainable weight loss and the potential risks of rapid weight loss. The provided diet chart is low carb, high fiber/protein, suitable for the given condition. There is a negligible risk for a user following this diet unless they have comorbid conditions. The statement that a diet chart need not contain caloric information is not true, as it serves as a guideline for achieving a caloric deficit to aid in weight loss. In terms of the evaluation criteria, the statement receives a complexity score of 2, an accuracy score of 8, and a potential risk score of 1. This result suggests that in case of lower complexity the accuracy of the information is higher and potential risk is lower.\n\nThe question is slightly more complex than the previous one, with the addition of BMI information. For a person with a BMI of 34, a calorie-deficit diet is required for weight loss. The diet, however, does not specify the amount of oil to be consumed, which can significantly increase the calorie count. The diet is not specific, and portions are assumed, which may result in a diet of around 1400-1500 calories, which may not be enough to achieve the target weight loss. A layperson following this guide may not achieve their weight loss target as the diet provided is not guided. In terms of the evaluation criteria, the statement receives a complexity score of 3, an accuracy score of 7, and a potential risk score of 3. This result again supports the finding of the case 1 as increase in the complexity score reduces the accuracy while increasing the potential to harm.\n\nThe complexity of the question increases with the addition of the condition of PCOS. The diet provided is like the previous question with the addition of extra guidelines for PCOS, which is general information. However, the diet provided is not specific to the condition, and a user following it may not achieve their weight loss target, but they are not at potential risk for harm. In terms of the evaluation criteria, the statement receives a complexity score of 4, an accuracy score of 6, and a potential risk score of 4. The result of this case is also concurring the hypothesis complexity to question asked results in less accuracy and higher risk to harm.\n\nThe question is complex due to the mention of diabetes, which requires consideration of many factors before preparing a diet chart. A simple statement of diabetes does not provide enough information, and the patient should be asked about the type of diabetes, medications, and recent blood reports. Calories, BMI, and current physical activity are critical considerations for a diabetic diet. The patient is at risk of developing hypoglycemia if they are on insulin and have a low BMI or high activity levels. A dietitian would consider all these factors while preparing a plan for a diabetic patient. In terms of the evaluation criteria, the statement receives a complexity score of 4, an accuracy score of 5, and a potential risk score of 6. The complexity score of four for an older patient has less accuracy and high potential of harm. Does age contribute to potential to harm? This question needs to be further tested empirically.\n\nThe complexity of the question increases with the addition of chronic kidney disease (CKD), which requires consideration of several factors while preparing a diet chart, such as the stage of CKD and the current level of potassium and sodium in the blood. However, the statement receives a low accuracy score of 4 as the diet generated does not mention limiting the sodium intake to at least 1.5 g/day, which is essential for CKD patients. Additionally, the diet contains high sources of protein, 75-80 g, which is much higher than what is recommended for a CKD patient and not calculated as per patient weight and CKD level. As a result, a layperson following this diet may be at a high potential for risk, indicating a high potential for risk score of 8. In terms of the evaluation criteria, the statement receives a complexity score of 5, an accuracy score of 4, and a potential risk score of 8. Increasing complexity of the query from 4 to 5 increases the potential of risk from 6 to 8. This makes us conclude that with increasing complexity the increase in potential harm increases exponentially after a point. This phenomenon needs to be further tested empirically.\n\nThe complexity of the question increases with the addition of hypertension as a comorbidity. However, the diet chart provided is the same as the previous question, which does not pose much risk for diabetes and hypertension but poses all the risks previously mentioned for CKD. Therefore, the statement receives a low accuracy score of 4. Additionally, patients need to be educated about sugar and salt sources, and general guidelines are not enough. Measurements should be incorporated into the diet plan itself to avoid potential risks. As a result, the statement receives a high potential for risk score of 8. In terms of the evaluation criteria, the statement receives a complexity score of 6, an accuracy score of 4, and a potential risk score of 8. The finding of this study doesn’t concurs the finding of the case 5 that increase in potential harm with increase in exponential as increasing complexity potential risk remains same.\n\nThe complexity of the question increases with the addition of gluten sensitivity. As a result, a proper dietitian is required to prepare a diet plan that takes into consideration the patient’s multiple comorbidities and dietary restrictions. However, the statement is lacking in accuracy as it does not provide any specific information on how to prepare a diet plan for a person with these conditions. Therefore, the accuracy score is low at 4. Additionally, without a specific diet plan, there is potential for risk for the patient with so many comorbidities and dietary restrictions. As a result, the statement receives a high potential for risk score of 8. In terms of the evaluation criteria, the statement receives a complexity score of 7, an accuracy score of 4, and a potential risk score of 8. The findings from this case also concurs the finding from the earlier cases. The increase in complexity is inversely proportional to accuracy while directly proportional to the potential risk.\n\nThis question is extraordinarily complex with multiple parameters given, including the condition of hypothyroidism. The ideal diet for this patient is a low-carb, high-protein, anti-inflammatory diet, with the need to avoid goitrogenic foods like soy products. However, the accuracy of the given information is relatively low, and there is still a potential risk for the patient if not properly guided by a qualified dietitian. Overall scores are as follows: Complexity - 8, Accuracy - 3, Potential for Risk - 6. This study examines the case of highest complexity and hence minimum accuracy. The risk score for this study was expected to be highest but that is not the case. This finding does not concur the findings from the earlier seven cases.\n\nThe summary of the analysis of eight cases is listed in Table 1.\n\nAs depicted in Figure 2, the complexity of the scenario increases risk potential also increases. That suggests that ChatGPT should be avoided for complex medical conditions/scenarios. Researchers believe accuracy does not change much with an increase in complexity and needs to be further evaluated empirically.\n\nThe findings of the study are supported by the researcher Johnson et al. (2023). They observed that ChatGPT can produce accurate information to diverse medical queries as judged by academic physician specialists although with important limitations. Further research and model development are needed to correct inaccuracies and for validation.20 Another group of researchers found that ChatGPT provides medical information of comparable quality to available static internet information.21 Another recent study suggests cautious approach against use of the ChatGPT in clinical practice. They lament that it doesn’t provide references for the information hence is not reliable for clinical use. Thus, the findings of this study also suggest the cautious use of ChatGPT in medical nutrition therapy as irresponsible use has potential harm for the user. The study assessing the accuracy and potential risks of using nutrition therapy information provided by ChatGPT, evaluated by nutritionists and a group of experts, has several limitations that must be considered when interpreting its results. ChatGPT’s responses are based on the information available up to its last training data, which might not include the latest research or updated guidelines in nutrition therapy. This time-lag in information can introduce a bias towards outdated practices or missing new evidence-based approaches. The accuracy and risk assessments made by the nutritionists and experts are subjective and can vary based on their individual experiences, knowledge, and biases. This variability can introduce both direction and magnitude biases in the evaluation process. The experts and nutritionists might have preconceived notions about the reliability of AI-generated information, which could influence their assessment of ChatGPT’s responses, either positively or negatively. The range and type of nutrition therapy questions asked may not comprehensively cover the vast field of nutrition. Thus, the study’s findings might not be generalizable across all areas of nutrition therapy.\n\n\nConclusion\n\nThe primary objective of the present study was to assess the accuracy and comprehensiveness of ChatGPT’s responses to nutritional queries generated by nutritionists/dieticians. To achieve this, an in-depth case study approach was employed. Functional testing was conducted by creating test cases that aligned with the functional requirements of the software application. ChatGPT’s responses were evaluated and analyzed in different scenarios that involved medical nutritional therapy, varying in complexity. The accuracy of the generated data was assessed by a registered nutritionist, and a potential harm score was used to evaluate the responses provided by ChatGPT.\n\nWhen several case scenarios with varying levels of complexity were evaluated for their risk potential, it was demonstrated that as the complexity increased, so did the potential risk. The study suggests that the ChatGPT should not be used for complex medical nutrition situations and conditions, even though the accuracy of the generated response does not change much with the complexity of the case scenario.\n\nThe study’s findings have important clinical implications for practitioners, particularly nutritionists, and dieticians, who may use ChatGPT or similar AI-powered tools in their practice. Practitioners should exercise caution and avoid relying solely on ChatGPT for complex cases that require specialized knowledge and expertise.\n\nThe study’s findings underscore the importance of using ChatGPT or similar AI-powered tools appropriately in clinical practice. It should not be used as a replacement for professional judgment or clinical decision-making, particularly in complex medical nutrition situations. Practitioners, especially nutritionists and dietitians, should consider ChatGPT as a complementary tool to support their clinical practice, and not solely rely on it for making critical nutrition-related decisions. This study emphasizes the importance of human verification and not solely relying on AI-generated information.\n\nThe findings of the study have important implications for policymakers. One key recommendation is to exercise caution when implementing generative AI, such as ChatGPT, in clinical practice. Rushing to adopt such tools without thorough evaluation and validation may not be advisable. While generative AI has the potential to improve efficiency in healthcare operations, it should be considered as a decision support system for registered practitioners, rather than a standalone tool for making clinical decisions.\n\nIt is important to note that patients should not rely solely on generative AI for self-medication or medical nutrition therapy, especially in situations where multiple health conditions (comorbidities) are involved. This is because generative AI tools like ChatGPT may not have the ability to fully assess and address the complexities of comorbid conditions, which could potentially result in harm to patients.22\n\nIn conclusion, a collaborative effort involving all stakeholders in healthcare education, research, and practice is urgently needed to establish guidelines for the responsible use of ChatGPT by educators, researchers, and practitioners.\n\nThe study used a small sample size which could affect the accuracy of the results. Another limitation is the dynamic nature of technology. Since technology is constantly evolving and improving, the results of the study may need to be reevaluated after a few days or weeks to account for any changes or updates. Additionally, the study’s reliance on only one nutritionist to assess accuracy introduces the possibility of bias and human errors.",
"appendix": "Data availability\n\nFigshare: Evaluation of accuracy and potential harm of ChatGPT in medical nutrition therapy – a case-based approach. https://dx.doi.org/10.6084/m9.figshare.24547276.\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 of this study are grateful to Datta Meghe Institute of Higher Education & Research, Gulf Medical University, and Thumbay University Hospital for the infrastructural support provided for completion of this research work.\n\n\nReferences\n\nDrozd M, Pujades-Rodriguez M, Lillie PJ, et al.: Non-communicable disease, sociodemographic factors, and risk of death from infection: a UK Biobank observational cohort study. Lancet Infect. Dis. 2021; 21(8): 1184–1191. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStefano M, Marco S, Daniela C, et al.: Nutritional knowledge of nursing students: A systematic literature review. Nurse Educ. Today. 2023; 105826.\n\nMagliano DJ, Boyko EJ: IDF diabetes atlas.2022.\n\nBiswas SS: Role of ChatGPT in public health. Ann. Biomed. Eng. 2023; 51(5): 868–869. PubMed Abstract | Publisher Full Text\n\nShen Y, Heacock L, Elias J, et al.: ChatGPT and other large language models are double-edged swords. Radiology. 2023; 307(2): e230163. PubMed Abstract | Publisher Full Text\n\nShen Y, Heacock L, Elias J, et al.: ChatGPT and other large language models are double-edged swords. Radiology. 2023; 307(2): e230163. PubMed Abstract | Publisher Full Text\n\nJaques N, Ghandeharioun A, Shen JH, et al.: Way off-policy batch deep reinforcement learning of implicit human preferences in dialog. arXiv preprint arXiv:1907.00456. 2019.\n\nVaira LA, Lechien JR, Abbate V, et al.: Accuracy of ChatGPT-Generated Information on Head and Neck and Oromaxillofacial Surgery: A Multicenter Collaborative Analysis. Otolaryngol. Head Neck Surg. 2023. PubMed Abstract | Publisher Full Text\n\nHosseini M, Rasmussen LM, Resnik DB: Using AI to write scholarly publications. Account. Res. 2023; 1–9. Publisher Full Text\n\nThorp HH: ChatGPT is fun, but not an author. Science. 2023; 379(6630): 313–313. PubMed Abstract | Publisher Full Text\n\nShah FA: IS Chat-GPT A Silver Bullet for Scientific Manuscript Writing? J. Postgrad. Med. Inst. 2023; 37(1): 1–2.\n\nFlanagin A, Bibbins-Domingo K, Berkwits M, et al.: Nonhuman “authors” and implications for the integrity of scientific publication and medical knowledge. JAMA. 2023; 329(8): 637–639. PubMed Abstract | Publisher Full Text\n\nGoodman RS, Patrinely JR, Osterman T, et al.: On the cusp: Considering the impact of artificial intelligence language models in healthcare. Med. 2023; 4(3): 139–140. PubMed Abstract | Publisher Full Text\n\nYin RK: The case study method as a tool for doing evaluation. Curr. Sociol. 1992; 40(1): 121–137. Publisher Full Text\n\nHeaton J, Day J, Britten N: Collaborative research and the co-production of knowledge for practice: an illustrative case study. Implement. Sci. 2015; 11: 1–10. Publisher Full Text\n\nChapman B, MacLaurin T, Powell D: Food safety info sheets: Design and refinement of a narrative-based training intervention. Br. Food J. 2011; 113(2): 160–186. Publisher Full Text\n\nBoren SA, Clarke WL: Analytical and clinical performance of blood glucose monitors. J. Diabetes Sci. Technol. 2010; 4(1): 84–97. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMezzich JE, Salloum IM: Clinical complexity and person-centered integrative diagnosis. World Psychiatry. 2008; 7(1): 1–2. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGuideline: Harm and risk in research - University College Dublin.[cited 2023Apr25]. Reference Source\n\nJohnson D, Goodman R, Patrinely J, et al.: Assessing the accuracy and reliability of AI-generated medical responses: an evaluation of the Chat-GPT model. Research Square. 2023.\n\nWalker HL, Ghani S, Kuemmerli C, et al.: Reliability of medical information provided by ChatGPT: assessment against clinical guidelines and patient information quality instrument. J. Med. Internet Res. 2023; 25: e47479. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWhiles BB, Bird VG, Canales BK, et al.: Caution! AI bot has entered the patient chat: ChatGPT has limitations in providing accurate urologic healthcare advice. Urology. 2023; 180: 278–284. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "265582",
"date": "25 Apr 2024",
"name": "Daniel Kirk",
"expertise": [
"Reviewer Expertise nutrition",
"machine learning",
"biochemistry"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAs more people rely on ChatGPT as a source of information, the authors aim to evaluate the competency of ChatGPT at answering nutrition questions asked by a nutritionist using a case-study approach. The approach is interesting and the topic of chatbots for managing chronic diseases is important and highly relevant.\n\n“The major categories of NCDs are known as chronic diseases,” this is repetitive and unnecessary given the first sentence. I would just say “The major categorised of NCDs are….”\n\n“Chat GPT” should be corrected to ChatGPT (without a space between)\n\nWe have previously published an article that compared the quality of answers to nutrition questions between ChatGPT and human dietitians (Ref [1]). In our study, we found ChatGPT performed well on all metrics but, importantly, we excluded medical questions. Given that the authors’ find that accuracy was not compromised but risk potential was higher with increasing complexity, this is interesting. Discussing these findings in the context of their own would enrich the author’s article. At the end of the intro, the authors state that the questions were asked by “Nutritionist/Dietician”. First, “a” is missing before this (or the noun should be pluralized). Second, nutritionists and dietitians are similar but different, with the conditions for naming oneself a dietitian being more stringent. The authors should specify which the chose here.\n\n“The approach used in this study is borrowed from functional testing and quality Assurance practices in software development.” There should be citations here for those that are not from a software development background.\n\n“The researchers wanted to recruit five to nine experts as a number greater than that if difficult to handle and a number less than that may result in bias.” We chose a similar number of experts for similar reasons. This may be used in support of the authors’ approach.\n\n“Step 3: The responses from Step 2 were evaluated by a registered nutritionist for accuracy.” This represents one of the most vulnerable points of the authors’ study. What constitutes as a “good”/correct answer in the field of nutrition can be (unfortunately) quite subjective. Topics in nutrition can be polarized and a nutritionist’s interpretation of the science can be disproportionately influenced by their own experience. Since the scoring of ChatGPT’s answers was only performed by only one individual, the author’s results become subject to the knowledge and belief’s of only one single individual. How do the author’s justify their methodology in spite of this?\n\nThe prompts given to, and responses from, ChatGPT should be made available.\n\nI think the research would benefit from having some type of a control group (i.e., scores of answers from human experts). At present, it cannot be discounted that questions of increasing complexity naturally lead to higher potential of harm. In this case, this would not be a limitation of ChatGPT but rather a function of complicated questions. However, since there is no control group, this cannot be known.\n\nThere is insufficient detail in the discussion of the results. The authors mention the results of similar studies but do not contextualise these their own findings in these others.\n\nThe authors do well in the introduction to set the scene for the motivation of research on chatbots for managing chronic diseases but then do not elaborate further on this when discussing their own results. The authors mention what the findings mean for policymakers and practitioners but it would be worth discussing what these findings mean for individuals with chronic diseases who might wish to use ChatGPT for obtaining information and what they mean for the future of chatbots in a medical 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? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "258226",
"date": "06 May 2024",
"name": "Maren C. Podszun",
"expertise": [
"Reviewer Expertise Nutrition Science",
"MASLD",
"AI in nutrition"
],
"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 have investigated the accuracy of ChatGPT for medical nutrition therapy. They selected a case study-based approach with queries increasing in complexity and then a nutritionist evaluated the given output for accuracy. The output was furthermore scaled for potential of harm. While the topic is certainly a hot one and very important there are some shortcomings in the current version that need to be addressed.\n\nOne diet plan per condition is too little to make any inference about the accuracy, please consult a statistician to calculate the number of plans needed for a sound statistical analysis. Assessment for accuracy by one nutritionist is too little, I would suggest to at least add two others that are blinded to the previous answers. The rational for the number of experts is week. It’s further confusing why public health professionals were chosen and not nutritionists Please indicate the version of ChatGPT. It is a tremendous difference whether ChatGPT-3.5 or 4 was used, as ChatGPT4 is connected to the internet and will have different output. Please also indicate the time (date) of data collection The exact prompts used for the cases need to be given in the method section and not just the supplementary data The manuscript would benefit from English language/ grammar service to improve clarity\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?\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": []
}
] | 1
|
https://f1000research.com/articles/13-137
|
https://f1000research.com/articles/13-135/v1
|
22 Feb 24
|
{
"type": "Study Protocol",
"title": "Single-centre, randomised clinical trial of the immunomodulatory mechanisms of daily supplementation of palm tocotrienol-rich fraction in healthy human volunteers following influenza vaccination",
"authors": [
"Ammu Kutty Radhakrishnan",
"Badariah Ahmad",
"Kanga Rani Selvaduray",
"Sitti Rahma Abdul Hafid",
"Uma Devi Palanisamy",
"Cheng Zsien Zhin",
"Badariah Ahmad",
"Kanga Rani Selvaduray",
"Sitti Rahma Abdul Hafid",
"Uma Devi Palanisamy",
"Cheng Zsien Zhin"
],
"abstract": "Background Vitamin E from palm oil, known as the tocotrienol-rich fraction (TRF), has been shown to have immune-enhancing activity. To date, only one dose of TRF (400 mg daily) has been tested in a clinical trial. The proposed study will evaluate the immune-enhancing activity effects of lower doses (200, 100 and 50 mg) in a clinical trial using an influenza vaccine as the immunological challenge.\n\nMethods A single-centre, randomised, parallel, double-blinded, placebo-controlled clinical trial with balance allocation involving five arms will be conducted. The healthy volunteers recruited will be randomly assigned to one of the arms, and they will be asked to take the respective supplements (400 mg, 200 mg, 100 mg, 50 mg of TRF or placebo) daily with their dinner. The volunteers will receive the influenza vaccine after four weeks. They will be asked to return to the study site four weeks later. A blood sample will be taken for the study at baseline, four and eight weeks. Primary outcome measures will be antibody levels to influenza, blood leucocyte profile and cytokine production. Secondary outcomes will be correlating plasma vitamin E levels with immune responses, plasma proteins and gene expression patterns. The findings from this study will be published in relevant peer-reviewed journals and presented at relevant national and international scientific meetings.\n\nConclusions The recent world events have created the awareness of having a healthy and functional immune system. Nutrition plays an important role in helping the immune system to function optimally. This study will show the effects of lower doses of TRF in boosting the immune response of healthy individuals and also elucidate the mechanisms through which TRF exerts its immune-enhancing effects.\n\nClinical trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) [ACTRN12622000844741] dated 15 June 2022.\n\nProtocol version 2",
"keywords": [
"tocotrienols",
"tocotrienol-rich fraction (TRF)",
"influenza vaccine",
"immune response"
],
"content": "Introduction\n\nThe host immune system plays a pivotal role in protecting the body from infectious agents and cancers.1–4 Appropriate and effective immune responses are essential to distinguish foreign antigens, such as infectious agents (e.g. viruses, bacteria, parasites and fungi) and abnormal or malignant cells from normal “self” antigens to prevent unwanted immune responses. The immune system is characterised by two mechanisms, the innate and the adaptive immune systems. The innate immune system comprising monocytes, macrophages, neutrophils, natural killer cells, dendritic cells, and granulocytes serves as the first line of defence against foreign antigens, directly targeting and facilitating the activation of the adaptive immune system.5–7 The T- and B-lymphocytes are the key players of the adaptive immune system. The lymphocytes are not the first line of defence against foreign antigens as these cells need to be appropriately activated upon antigen recognition. Once activated, the lymphocytes elicit a more efficient and specific immune response as well as develop immunological memory.6,8,9\n\nA well-balanced nutritional status is essential for maintaining normal immune function. Deficiencies in nutrients often lead to impaired immune system function; on the contrary, intake at suggested levels can lead to normal or enhanced immune function.2,3,10 Nutritional interventions have powerful effects on activating the host immune system.10–12 One compound is vitamin E, which consists of tocopherols and tocotrienols. The vitamin E from palm oil, known as the tocotrienol-rich fraction (TRF), is a mixture of tocotrienols (70%) and tocopherols (30%).13,14 Several clinical and experimental model-based studies have shown that tocotrienols have several biological activities such as antioxidant,15,16 lipid-lowering,17,18 immune-enhancing,19–21 anticancer,22–24 neuroprotective,25–27 and anti-diabetic.28,29 Tocotrienols may cause these effects by acting at the epigenome, genome or protein levels.30 Recently, it was reported that consuming TRF can also cause changes to the gut microbiome.31,32\n\nIn an earlier study, we reported that daily supplementation of 200 mg TRF or α-tocopherol (α Toc) did not induce significant immunomodulatory changes in healthy human volunteers in the absence of any immunological challenge.33 In a subsequent study, we included an immunological challenge in the form of tetanus toxoid (TT) vaccination in healthy individuals supplemented daily with 400 mg TRF. Daily supplementation of 400 mg TRF produced a significantly higher immune response to the TT vaccine.19 A recent report showed that daily supplementation of 150 mg TRF for six months modulated some genes related to the immune system in healthy older adults.34 In the literature, most studies have used a single dose of TRF to report their findings. To date, no studies have evaluated the dose-response effects of TRF supplementation on the host immune system. So, there is a need to evaluate the effectiveness of supplementing daily with lower doses of TRF (200, 100, or 50 mg) to boost immune response following an immunological challenge such as a vaccine. The influenza vaccine was chosen in this study as the vaccine model, as flu is a major problem faced by individuals worldwide.\n\n\nObjectives\n\nThis study aims to investigate the effects of different concentrations of TRF (400, 200, 100 or 50 mg) on the immune response to an influenza vaccine in healthy individuals and to elucidate the mechanism of action. Using high and low dosages is important to understand what may happen following TRF supplementation. This information can be used to develop this in a range of functionality. The specific objectives are (i) to compare antibody responses to influenza antigen following daily supplementation with TRF (400, 200, 100 or 50 mg) with placebo; (ii) to compare leucocyte profiles and cytokine levels in response to influenza antigen following daily supplementation with TRF (400, 200, 100 or 50 mg) with placebo; (iii) to identify differentially expressed plasma proteins following daily supplementation with TRF (400, 200, 100 or 50 mg) with placebo in the presence or absence of vaccination; and (iv) to correlate plasma vitamin E levels with antibody levels in volunteers with and without daily supplementation with TRF.\n\nWill daily supplementation of lower doses of TRF (400, 200, 100 or 50 mg) enhance the immune response to an immunological challenge such as the influenza vaccine?\n\nThe research hypothesis of this study is that daily supplementation of lower doses of TRF will enhance the host’s immune response to an influenza vaccine.\n\nThe primary outcomes of this trial will be comparing the antibody levels to influenza, the blood leucocyte profile, plasma vitamin E and cytokine production between the different groups. Secondary outcomes will be correlating plasma vitamin E levels with immune responses, plasma proteins and gene expression patterns.\n\n\nProtocol\n\nThe Monash University Human Ethics Committee (MUHREC) have reviewed and approved the study protocol [MUHREC 30401] (27 January 2022). In addition, the study will be conducted in accordance with the principles of the Declaration of Helsinki 2013 and the Malaysian laws on medical research involving human subjects. All changes to changes to the protocol will require approval from MUHREC before they are applied. All data, including personal information about potential and enrolled participants for this study, will be stored in a file kept in a locked cabinet in a locked room in Monash facilities. The digital data will be stored on a secure shared drive behind the Monash firewall. Only the chief investigator will have access to these files. Upon completion of the study, all data will be stored and handled by Monash University Malaysia for at least 15 years after the study has ended. Only researchers listed in the ethics approval will have access to the research data.\n\nThis protocol has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) [ACTRN12622000844741] on 15 June 2022.\n\nA single-centre, parallel, double-blinded, placebo-controlled with balanced randomisation into five arms (Table 1).\n\nThe sample size was calculated using G*Power version 3.1.9.4. With the power set at 80% and a 5% level of significance, the analysis showed that 26 subjects per arm were required to detect a large difference between groups. The effect size (d) was assumed to be 0.7, based on a previous study.19 Assuming a 15% dropout rate in two months, 30 subjects per arm (150 subjects) will be enrolled.\n\nThis study will be conducted at the Thomson Hospital, Kota Damansara, Malaysia. Thomson Hospital is a private tertiary-level health facility in Kota Damansara in Selangor, Malaysia. Participants will be invited to join this study by way of placing posters around the hospital’s primary care clinics and through social media. Hence, some of the volunteers recruited will include healthy hospital employees and their relatives, who became aware of the study through the posters placed in the hospital. Volunteers will also recruited using social media (Facebook, Instagram and WhatsApp).\n\nHealthy subjects (n = 200-250) aged between 25 to 60 years old will be invited to participate in this study. At the time of screening, the purpose of the study and what the study entails will be explained to all volunteers who express an interest in joining the study. Before recruiting a subject for this study, a blood sample (12 mL) will be taken from all interested volunteers, where 10 mL of the blood will be sent to the Thomson Hospital medical diagnostic laboratory for various biochemical tests to establish baseline parameters to assist in the selection of healthy volunteers. The remaining 2 mL of blood will be used to quantify baseline plasma levels of vitamin E and anti-influenza antibodies. Then, 150 healthy volunteers who meet the inclusion and exclusion criteria (Table 2) of this study, with the lowest level of anti-flu antibody and low plasma vitamin E, will be recruited for the study. Once a volunteer is selected for the study, a physician will explain the study protocol to the volunteer and ask the volunteer to provide a signed written informed consent to participate in this study.\n\n\n\n• 18–60 years-old\n\n• Healthy and free of diseases (biochemical tests)\n\n\n\n• Have some health-related problems\n\n• On treatment or medication\n\n• Currently taking vitamin E supplements\n\n• Smoker\n\n• Received influenza A and B vaccination in the last 12 months\n\n• Obese (BMI > 35 kg/m2)\n\n• Pregnant and/or breast-feeding\n\nThe study is expected to screen around 200–250 volunteers to recruit 150 volunteers required for this study. During the screening step, the volunteers will be subjected to a routine simple medical history and health screening to collect some data [age, gender, eating habits, occupation, lifestyle (smoking, alcohol, exercise), height, weight] as well as biochemical blood [full blood count (FBC), glucose, HBA1c, lipid profile, estimated glomerular filtration rate (EGFR), liver function tests (LFT)] and urine [full examination microscopy examination (FEME)] tests. Once the healthy volunteers are selected, they will be randomly assigned to one of the five study groups (Table 1). The volunteers will be asked to attend three clinic sessions (days 0, 28 and 56) (Figure 1). A trained phlebotomist will take blood via venepuncture, as shown in Figure 1. After the blood-taking on day 0, the volunteers will be given a bottle containing sufficient test supplements for 28 days. The volunteers will be asked to take the supplement after dinner every day for 28 days.\n\nThe volunteers will be asked to return to the study site on day 28 for blood-taking (5 mL) and to receive an influenza vaccine. The volunteers will be given a second bottle containing sufficient supplements for another 28 days. The volunteers will return to the study site on day 56 for blood-taking (15 mL) (Figure 1). Of the 15 mL of blood taken on Day 56, 10 mL will be sent to the Thomson Hospital medical diagnostic laboratory for various biochemical tests to establish the end-study parameters. At the second (day 28) and third (day 56) clinic visits, the volunteers will be asked to return the bottle with their supplement. The pill count will check compliance at each visit. In addition, the volunteers will be asked to maintain a normal balanced diet and exercise/activity regimen during the study period. They will be asked to keep a diary to record major deviations from their diet. The diary will be checked at each visit for any unusual entries.\n\nThe TRF used in this study will be Tocovid SuprabioTM, manufactured by HOVID Ltd in Malaysia, and is a registered supplement in Malaysia that is sold as an over the counter (OTC) supplement in major pharmacies in Malaysia. The active ingredient of the Tocovid SupraBioTM, called EVNolTM was manufactured by ExcelVite Sdn. Bhd., Malaysia. The TRF has received the generally regarded as safe (GRAS) status by the USA Food Development Authority (FDA).35\n\nThe influenza vaccine used in this study will be the VaxigripTetra Influenza vaccine type A and B as per the WHO recommendations, which will be obtained from the Thomson Hospital’s pharmacy.\n\nThe supplements will be packed in identical bottles and packaging. Each package will be labelled anonymously with a running number. The supplements in the first four weeks will be labelled with a number and an additional label, “FIRST”, while supplements in the second four weeks will have the same number, but the additional label will be “SECOND”. All investigators and volunteers will be blinded to the intervention. Then, a simple randomisation process allocated the intervention package to the volunteers, where the first volunteer recruited will receive the first anonymous number with the label, “FIRST” while the second volunteer recruited will receive the second anonymous number with the label, “FIRST” and so on for their first four weeks of supplementation. When they return to the study site after four weeks, they will receive a supplement package having the same number as their first package but with the label, “SECOND”. Each subject will receive the package with the supplement having a number from the study nurse. The number on each bottle will correspond to a supplement listed in Table 1, which only the principal investigator of the study will know. All other investigators in the study will be blinded to this information.\n\nUnblinding will only occur at the end of the study after all data have been collected for analysis. However, if any of the subjects in the study were to experience any adverse effects, then unblinding will be permitted for the said volunteer for further action.\n\nTRF has received the GRAS status from the US FDA.35 Hence, severe adverse effects following the consumption of TRF are not expected. However, volunteers can drop out of the study at any time if they experience any side effects or do not want to continue with the study.\n\nAntibodies to human influenza viruses\n\nThe level of antibodies to influenza antigen in the plasma taken on days 0, 28 and 56 will be determined using an enzyme-linked immunosorbent assay (ELISA). Briefly, 100 μL of the flu vaccine (1 μg/mL) in coating buffer (Thermo Fischer Scientific, USA) will be added to 96-well ELISA plates (Corning C62-9018 plate) and incubated at 4°C for 24 hours. The plate will be washed thrice with 250 μL of ELISA wash buffer (Thermo Fischer Scientific, USA). Then, the plate will be blocked with 250 μL of ELISA diluent (Thermo Fischer Scientifc, USA) at room temperature for 2 hours. The plate will be washed thrice with 250 μL of ELISA wash buffer (Thermo Fischer Scientific, USA). The plate will be dried by gently tapping on absorbent paper. Then, 100 μL of diluted human serum (baseline, Day 28 and Day 56) will be added to each well in duplicates. A standard curve of anti-influenza A (Santa Cruz, USA) and anti-influenza B (Santa Cruz, USA) antibodies will be used to quantify anti-influenza A and anti-influenza B levels in the serum of healthy volunteers at different time points. Blank wells will contain 100 μL of ELISA diluent (Thermo Fischer Scientific, USA). After 2 hours at room temperature, the plate will be washed five times with 250 μL of ELISA wash buffer (Thermo Fischer Scientific, USA). Then, 100 μL of anti-human Ig (IgG, IgM and IgA) or anti-human IgG conjugated with horseradish peroxidase (HRP) (Abcam, USA) will be added to all wells. After one hour at room temperature, the plate will be washed five times with 250 μL of ELISA wash buffer (Thermo Fischer Scientific, USA), and 100 μL of TMB ELISA substrate (Abcam, UK) will be added to all wells. The enzymic reaction will be stopped after 10-20 mins by adding 100 μL Stop solution for TMB substrate (Abcam, UK). Absorbance at 450 nm will be read using a microplate reader (Tecan, Switzerland).\n\nAntigen-specific proliferation\n\nThe buffy coat will be isolated from peripheral blood and cultured in the presence of the influenza vaccine for 72 hours. The antigen-specific proliferation will be measured using a commercial cell proliferation kit. The culture supernatant will be harvested and stored at -80°C until used for cytokine analysis.\n\nPlasma levels of vitamin E\n\nPlasma levels of vitamin E will be quantified from samples taken on days 0, 28 and 56 using the high-performance liquid chromatography (HPLC) [Agilent HPLC 1200 with fluorescence detector, Agilent, USA] as desbribed previously.36 Briefly, 1.0 mL of 0.9% sodium chloride (NaCl) will be added to 1.0 mL of human plasma in a glass test tube and vortexed for 30 seconds. Then, 1.0 mL ethanol-BHT (0.625 mg/mL) will be added, and the mixture will be vortexed for 30 seconds. Following this, 5.0 mL of n-hexane-BHT (0.05 mg/mL) will be added, and the mixture will be shaken overnight for 16 hours at 250 rpm, at 10°C using a shaking incubator (WIS-20, Witeg, Germany). After centrifugation (2500 rpm for 15 minutes at 4°C), the upper organic layer will be carefully extracted and transferred to a sterile tube. The tubes will be evaporated to dryness using a speed vacuum concentrator with CoolSafe -110°C cold trap (MaxiVac, LaboGene, Denmark). To obtain a standard curve for quantification, standard tocopherols (Toc) and tocotrienols (T3) (Hovid, Malaysia) will be separated on a Phenomenex KinetexTM PFP column (5.0 μm, 150 × 4.6 mm; Phenomenex) with a guard column using MeOH/H2O (87:13) as an eluent at a flow rate of 0.9 mL/min. The dried samples will be reconstituted with 0.3 mL of mobile phase [methanol (MeOH) + butylated hydroxytoluene (BHT) (0.625 mg/mL)] and filtered using a nylon syringe fitted with a 0.45 μm, 4 mm filter (Chrominex, Singapore) prior to HPLC analysis. Then, 10 μL of the preparation will be injected into the HPLC (Agilent HPLC 1200, USA). The fluorescence detector will be set an excitation wavelength of 296 nm and emission wavelength of 325 nm and photomultiplier tube (PMT) gain will be set at 10.\n\nCytokines\n\nPlasma and culture supernatant stored at -80°C will be thawed and used to quantify plasma levels of cytokines [e.g. interferon-gamma (IFN-γ) (MABtech, USA), tumour necrosis factor-alpha (TNFα) (MABtech, USA), interleukin-12 (IL-12) (MABtech, USA), and interleukin-17A (IL-17A) (MABtech, USA)] using commercial ELISA kits.\n\nProtein expression\n\nThe plasma protein concentrations will be determined using a commercial Bradford test. The plasma will be subjected to albumin and immunoglobulin elimination steps using the Pierce albumin/IgG removal kit (ThermoScientific, USA). Then, the protein will be processed using the EasyPep™ Mini MS Sample Prep Kit (ThermoScientific, USA) before being analysed with liquid chromatography-mass spectrometry/mass spectrometry (LCMS/MS) (Agilent, USA) to identify differentially expressed proteins (DEP). The expression of the selected DEP will be verified using ELISA or Western blotting.\n\nGene expression studies\n\nTotal RNA will be extracted from 1.5 mL of freshly drawn blood using a commercial ribonucleic acid (RNA) extraction kit (QIAGEN® RNA Blood Mini kit, QIAGEN GmBH, Hilden, Germany). Briefly, the red blood cells (RBC) will be lysed by adding 7.5 mL RBC lysis buffer (provided with RNA extraction kit, (QIAGEN, Germany). The mixture will be incubated on ice for 15 min, and the buffy coat will be recovered by centrifugation (10 min at 4°C). The supernatant will be discarded, and the pellet will be washed twice with 3 mL of the RBC lysis buffer and recovered by centrifugation (10 min at 4°C). Then, RNA will be extracted using RNA extraction, as recommended by the manufacturer (QIAGEN, Germany). The extracted RNA’s purity, quality, and integrity will be assessed using NanoDrop® ND-1000 (NanoDrop Technologies Wilmington, DE, USA) and Agilent 2100 Bioanalyzer (Agilent Technologies Santa Clara, CA, USA). The primers related to various genes associated with T-helper (Th) and T-regulatory (Treg) cells (Hoxa10, GATA3, RORα, CCR5, CXCR3 CCR7, IL-24, IL-12β2R, FoxP3; CD49b, folate receptor-4) will be synthesised commercially (IDT Integrated DNA Technologies, Singapore). Quantitative PCR (QPCR) will be performed to compare mRNA expression between the groups and within the group (day 0 and day 56). The purified RNA will be processed using qPCRBIO SyGreen 1-Step Detect LOW-ROX kit (CAT#PB25.11-01), (QIAGEN, Hilden, Germany) for complementary DNA (cDNA) synthesis according to the manufacturer’s instruction. The total reaction volume per sample will be 20 μL with 10 ng of RNA template, 2 ng/μl of forward and reverse primers. Each sample will be analysed using commercial primer sets various genes associated with T-helper (Th) and T-regulatory (Treg) cells (Hoxa10, GATA3, RORα, CCR5, CXCR3 CCR7, IL-24, IL-12β2R, FoxP3; CD49b, folate receptor-4), which will be synthesized commercially (IDT Integrated DNA Technologies, Singapore). The GAPDH gene will be used as the housekeeping gene to normalize the quantitative polymerase chain reaction (QPCR) data. The cycling protocol will consist of 40 cycles involving denaturation at 95° for 5 seconds, followed by annealing and extension- steps, each at 60°C for 30 seconds. All samples will be run in triplicates. At the end of the 40 cycles, a dissociation curve analysis will be performed to confirm amplification specificity using the optical module PCR detection system available in the thermocycler (QuantStudio™ 5 Real-Time PCR System, Applied Biosystem, Thermo Scientific, USA). The ratio of gene expression of the target gene was compared between undifferentiated and differentiated cells using the formulae: 2-(ΔCt (test gene) – ΔCt (GAPDH)), where ΔCt represents the difference of threshold cycle (Ct) for each target gene.\n\nStatistical Package for the Social Sciences (SPSS) version 18 will be used for the statistical analysis. The mean and standard deviation values will be calculated for each parameter and compared with the baseline and/or placebo. Differences between the baseline and/or placebo will be tested using a paired-t-test when data are normally distributed or Wilcoxon signed-rank when the data are skewed. The significance level will be set as a P value of ≤ 0.05.\n\nThe findings from this clinical trial will be published in suitable peer-reviewed journals.\n\nThis study is at the screening of volunteers’ stage to identify suitable subjects to be included in the study as per the inclusion and exclusion criteria (Table 2) of this study.\n\n\nDiscussion\n\nAt the start of 2020, a global public health challenge was caused by a novel coronavirus known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).37 This virus was named the novel coronavirus 2019 or COVID-19. COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2021. The pandemic has increased awareness of the need for a well-functioning immune system.38,39 Nutritional interventions can potentially affect the host immune systems.9–10 One such compound is vitamin E from palm oil. The vitamin E from palm oil is known as the tocotrienol-rich fraction (TRF), which contains tocotrienols (70%) and tocopherols (30%).13,14 Several researchers have reported on the ability of TRF to modulate the host immune system. To the best of our knowledge, no studies investigated a dose-response curve using TRF supplementation and its impact on the host immune system. Previous studies have used high TRF concentrations, which may not be necessary to achieve the immune-enhancing effects in healthy individuals.\n\nFurthermore, not many people may be able to afford a high dose of TRF. For any supplement, it is crucial to know what is happening biochemically at different dosages to understand the targeted effects as well as any side effects. It is important to use both high and low dosages in a study to fully understand what is happening in response to the intervention and develop this in a range of functionality. The influenza vaccine was chosen in this study as the vaccine model, as flu is a major problem faced by individuals worldwide.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nWe would like to thank the Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia and Thomson Hospital, Kota Damansara, Malaysia, for supporting this study.\n\n\nReferences\n\nKoelman L, Egea Rodrigues C, Aleksandrova K: Effects of dietary patterns on biomarkers of inflammation and immune responses: a systematic review and meta-analysis of randomized controlled trials. Adv. Nutr. 2022; 13(1): 101–115. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi P, Wu G: Important roles of amino acids in immune responses. Brit J of Nutri. 2022; 127(3): 398–402. Publisher Full Text\n\nCalder PC: Foods to deliver immune-supporting nutrients. Curr. Opin. Food Sci. 2022; 43: 136–145. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSaeed F, Nadeem M, Ahmed RS, et al.: Studying the impact of nutritional immunology underlying the modulation of immune responses by nutritional compounds–a review. Food Agric. Immunol. 2016; 27(2): 205–229. Publisher Full Text\n\nPadariya M, Kalathiya U, Mikac S, et al.: Viruses, cancer and non-self recognition. Open Biol. 2021; 11(3): 200348. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIwasaki A, Medzhitov R: Regulation of adaptive immunity by the innate immune system. Science. 2010; 327(5963): 291–295. PubMed Abstract | Publisher Full Text | Free Full Text\n\nForsdyke DR: Positive selection of immune repertoires: a short further history. Scand. J. Immunol. 2022; 95(4): e13144. PubMed Abstract | Publisher Full Text\n\nDeets KA, Vance RE: Inflammasomes and adaptive immune responses. Nature Immunol. 2021; 22(4): 412–422. Publisher Full Text\n\nSette A, Crotty S: Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021; 184(4): 861–880. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWu D, Lewis ED, Pae M, et al.: Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Front. Immunol. 2019; 9: 3160. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPae M, Wu D: Nutritional modulation of age-related changes in the immune system and risk of infection. Nutr. Res. 2017; 41: 14–35. PubMed Abstract | Publisher Full Text\n\nKim KS, Hong SW, Han D, et al.: Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science. 2016; 351(6275): 858–863. PubMed Abstract | Publisher Full Text\n\nRizki IF, Panjaitan FR, Mulyono ME, et al.: The utilization of natural deep eutectic solvent composition in tocotrienol and tocopherol extraction from crude palm oil and its acylglycerol products. J. Food Compos. Anal. 2022; 114: 104818. Publisher Full Text\n\nChong WT, Tan CP, Cheah YK, et al.: In-vitro and in-vivo evaluations of tocotrienol-rich nanoemulsified system on skin wound healing. PLoS One. 2022; 17(5): e0267381. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSadikan MZ, Nasir NA, Iezhitsa I, et al.: Antioxidant and anti-apoptotic effects of tocotrienol-rich fraction against streptozotocin-induced diabetic retinopathy in rats. Biomed. Pharmacother. 2022; 153: 113533. Publisher Full Text\n\nSzewczyk K, Daniluk P, Górnicka M: Assessment of Tocotrienols Intake in Adults—A Pilot Study. Biol. Life Sci. Forum. 2022; 12(1): 16.\n\nZuo S, Wang G, Han Q, et al.: The effects of tocotrienol supplementation on lipid profile: A meta-analysis of randomized controlled trials. Compl. Ther. Med. 2020; 52: 102450. PubMed Abstract | Publisher Full Text\n\nWong RS, Radhakrishnan AK: Tocotrienol research: past into present. Nutr. Rev. 2012; 70(9): 483–490. PubMed Abstract | Publisher Full Text\n\nMahalingam D, Radhakrishnan AK, Amom Z, et al.: Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers. Eur. J. Clin. Nutr. 2011; 65(1): 63–69. Publisher Full Text\n\nSubramaniam S, Anandha Rao JS, Ramdas P, et al.: Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation. Clin. Exp. Immunol. 2021; 206(2): 161–172. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPae M, Meydani SN, Wu D: The role of nutrition in enhancing immunity in aging. Aging Dis. 2012; 3(1): 91–129. PubMed Abstract\n\nAbdul-Hafid SR, Chakravarthi S, Nesaretnam K, et al.: Tocotrienol-adjuvanted dendritic cells inhibit tumor growth and metastasis: a murine model of breast cancer. PLoS One. 2013; 8(9): e74753. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSelvaduray KR, Radhakrishnan AK, Kutty MK, et al.: Palm tocotrienols inhibit proliferation of murine mammary cancer cells and induce expression of interleukin-24 mRNA. J. Interf. Cytokine Res. 2010; 30(12): 909–916. PubMed Abstract | Publisher Full Text\n\nPierpaoli E, Viola V, Pilolli F, et al.: γ-and δ-tocotrienols exert a more potent anticancer effect than α-tocopheryl succinate on breast cancer cell lines irrespective of HER-2/neu expression. Life Sci. 2010; 86(17-18): 668–675. PubMed Abstract | Publisher Full Text\n\nRanasinghe R, Mathai M, Zulli A: Revisiting the therapeutic potential of tocotrienol. Biofactors. 2022; 48(4): 813–856. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMagalingam KB, Somanath SD, Md S, et al.: Tocotrienols protect differentiated SH-SY5Y human neuroblastoma cells against 6-hydroxydopamine-induced cytotoxicity by ameliorating dopamine biosynthesis and dopamine receptor D2 gene expression. Nutr. Res. 2022; 98: 27–40. PubMed Abstract | Publisher Full Text\n\nTrela-Makowej A, Leśkiewicz M, Kruk J, et al.: Antioxidant and Neuroprotective Activity of Vitamin E Homologues. In Vitro Study. Metabol. 2022; 12(7): 608. Publisher Full Text\n\nPang KL, Chin KY: The role of tocotrienol in protecting against metabolic diseases. Molecules. 2019; 24(5): 923. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHor CP, Fung WY, Ang HA, et al.: Efficacy of oral mixed tocotrienols in diabetic peripheral neuropathy: a randomized clinical trial. JAMA. Neurology. 2018; 75(4): 444–452. Publisher Full Text\n\nRadhakrishnan AK, Rao JS, Subramaniam S, et al.: Gamma-tocotrienol modifies methylation of HOXA10, IRF4 and RORα genes in CD4+ T-lymphocytes: Evidence from a syngeneic mouse model of breast cancer. Curr. Res. Immunol. 2021; 2: 169–174. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCossiga V, Lembo V, Nigro C, et al.: The combination of berberine, tocotrienols and coffee extracts improves metabolic profile and liver steatosis by the modulation of gut microbiota and hepatic miR-122 and miR-34a expression in mice. Nutrients. 2021; 13(4): 1281. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang C, Zhao Y, Im S, et al.: Vitamin E delta-tocotrienol and metabolite 13’-carboxychromanol inhibit colitis-associated colon tumorigenesis and modulate gut microbiota in mice. J. Nutr. Biochem. 2021; 89: 108567. PubMed Abstract | Publisher Full Text\n\nRadhakrishnan AK, Lee AL, Wong PF, et al.: Daily supplementation of tocotrienol-rich fraction or α-tocopherol did not induce immunomodulatory changes in healthy human volunteers. Brit. J. Nutri. 2009; 101(6): 810–815. Publisher Full Text\n\nGhani SM, Goon JA, Azman NH, et al.: Comparing the effects of vitamin E tocotrienol-rich fraction supplementation and α-tocopherol supplementation on gene expression in healthy older adults. Clinics. 2019; 74: e688. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUS FDA GRAS Notice No:307: Reference Source\n\nChe HL, Tan DM, Meganathan P, et al.: Validation of a HPLC/FLD method for quantification of tocotrienols in human plasma. Int. J. Anal. Chem. 2015; 2015: 1–7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWu Y, Ho W, Huang Y, et al.: SARS-CoV-2 is an appropriate name for the new coronavirus. Lancet. 2020; 395(10228): 949–950. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAltmann DM, Boyton RJ: SARS-CoV-2 T cell immunity: Specificity, function, durability, and role in protection. Sci. Immunol. 2020; 5(49): eabd6160. PubMed Abstract | Publisher Full Text\n\nAmanat F, Krammer F: SARS-CoV-2 Vaccines: Status Report. Immunity. 2020; 52(4): 583–589. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLewis ED, Meydani SN, Wu D: Regulatory role of vitamin E in the immune system and inflammation. IUBMB Life. 2019; 71(4): 487–494. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "282394",
"date": "30 May 2024",
"name": "Sonia Chew Wen Phang",
"expertise": [
"Reviewer Expertise Biochemistry",
"diabetes"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study aims to investigate the effect of different concentrations (50, 100, 200, 400 mg) of tocotrienol-rich fraction (TRF) on the immune response to an influenza vaccine in healthy participants. Given the heightened awareness of immune health due to the recent pandemic, understanding how nutritional interventions like TRF can enhance immunity is timely and relevant. By utilising both low and high dosages of TRF, the findings of this study may offer a more complete understanding of the biochemical impacts of TRF on the host immune system.\nOverall, the study protocol is concise and clear in its research objectives and study design. The methodology of each approach is explained thoroughly in detail, allowing replication by others.\nOnly one point that needs to be addressed as well as a suggestion on terminology:-\n1) Clarification is needed on the age criterion of the participants. In the study plan, it is stated that participants aged between 25 to 60 years old will be invited, while in Table 2, the age range stated in the inclusion criteria is 18 to 60 years old.\n2) The terminology used to refer to the individuals taking part of the study could be standardized for clarity and consistency. I recommend the use of either 'volunteers', 'participants', or 'subjects' consistently throughout the protocol.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
},
{
"id": "282388",
"date": "10 Jun 2024",
"name": "Philip C Calder",
"expertise": [
"Reviewer Expertise Nutritional immunology",
"human 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\nThis manuscript describes the protocol for a human RCT testing 4 doses of tocotrienol rich fraction of palm kernel oil vs placebo using response to influenza vaccination as the main outcome. Other outcomes include some other immune measures and plasma \"vitamin E\" concentrations. The experimental design is appropriate to test the hypothesis. There is sufficient detail in the protocol. The power calculation is rather unspecific. The trial has been ethically approved and is registered.\nSpecific comments: 1. In section Research question I think \"lower dose\" should read \"different doses\" 2. In section Study hypothesis, again you refer to \"low dose\", but compared to what? Isn't your hypothesis that \"different doses of TRF will have different effects ..\". 3. Ethics considerations, 3rd sentence. You write \"changes to\" twice. 4. Sample size. What does \"a large difference\" mean. To do a sample size calculation you need to define what the \"difference\" (effect size) will be. 5. It is not exactly clear how you will randomly assign participants to groups. In an RCT each person should have an equal chance to be allocated to each group. 6. Discussion, 2nd sentence. COVID-19 is the disease caused by SARS-CoV-2, it is not the name of the virus, although during the pandemic the two terms unfortunately were often used interchangeably. COVID-19 is coronavirus disease discovered in 2019.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
},
{
"id": "274149",
"date": "11 Sep 2024",
"name": "Pablo Cañete",
"expertise": [
"Reviewer Expertise Humoral Immunity",
"Antibody Responses",
"Follicular T cells"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nRadhakrishnan and colleagues have designed a clinical study to interrogate the effects of tocotrienol-rich fraction (TRF) supplementation on influenza vaccine outcomes. Their protocol’s rationale is grounded on previous research that showed elevated antibody production in a tetanus toxoid immunisation study. The research is significant and timely, given the growing interest in nutritional interventions to boost immunity and particularly due to the ease of an oral administration treatment in the context of recent global health challenges like the COVID-19 pandemic. The study protocol has a strong design methodology as a randomized, double-blinded, placebo-controlled trial. The primary aim is to evaluate the immune-enhancing effects of different doses of TRF (50, 100, 200, and 400 mg) compared to a placebo, using an influenza vaccine as the immunological challenge, and by measuring several parameters indicative of immune function (antibody production, cytokine release upon rechallenge and soluble factors in the serum). While the study is interesting and will generate much-needed knowledge to mitigate poor vaccine outcomes, there are few concerns that need attention. Major concerns The authors plan to gauge vaccine efficacy on the basis of, i) antigen specific antibodies, ii) soluble factors in the serum indicative of immune activity, and iii) cytokines produced by antigen-activated peripheral leukocytes. While all these metrics are indicative of immune activity, and thus suggestive of potential changes in vaccine efficacy, they are insufficient to definitively determine whether FRT enhances influenza vaccine outcomes for the following reasons:\nHigh affinity antibodies are crucial for generating long-lived humoral memory in the form of a continuous secretion by long-lived plasma cells in the bone marrow. These antibodies have undergone affinity maturation in germinal centres, are mutated, and have such remarkable affinity that only minute amounts of it are needed to prevent re-infection. They form the foundation of most successful vaccines. Therefore, the authors need to measure antibody affinity to substantiate their conclusions regarding whether TRF enhances the quality of the immune response. The ultimate metric for vaccine efficacy is protection: the proportion of individuals who are protected, develop mild disease, or remain asymptomatic upon re-exposure. I understand these exercises are difficult with, i) such low sample sizes, and ii) the likely budgetary and time constrains. However, the authors should at least try to address the previous point. The sample size calculation accounts for a 15% dropout rate. However, there seems to be a discrepancy in the final number. If 26 subjects per arm are needed and the expected dropout rate is 15%, the correct sample size per arm should be:\n\nRequired per arm = 26 / (1-0.15) ≈30.6. The result 30.6 should be rounded up to 31, not rounded down to 30. Sample size calculations should always be rounded up, not down, to ensure that the sample size is large enough. The reason for this is that the result represents the smallest sample size needed to produce the desired error. Thus, the total should be 31 subjects per arm for a total of 155 subjects (not 150). I recommend that the protocol manuscript is amended to increase the sample size to 155.\nMinor concerns\nReadability is a minor issue for some sections of the manuscript. For example, the second paragraph of the blinding section is a bit confusing. There is also some repetition of the same sentences within the manuscript, for example the last paragraph of the introduction and the last paragraph of the discussion end with exactly the same sentence: “The influenza vaccine was chosen in this study as the vaccine model, as flu is a major problem faced by individuals worldwide”. I recommend that all sections are reviewed for readability and consistence within the manuscript. FBC is not generally considered a biochemical test and should be classified as a haematological test (study approach section). Inconsistencies between information shown in protocol and in study registration website regarding data sharing:\nThe study registration entry in ANZCTR states that “De-identified raw data for each participant outside of the investigator team for the purposes of IPD meta-analyses, upon request” while the protocol says that “Only researchers listed in the ethics approval will have access to the research data.” The manuscript should specify the potential for data to be shared and the procedures for de-identification in the protocol.\nBlinding methodology:\nThe blinding methodology seems appropriate; however, the manuscript would benefit from some clarifications:\n\nRandomization Process: The phrase \"a simple randomisation process\" is vague. I recommend for the manuscript to describe the exact method used for randomization (e.g., computer-generated random numbers, block randomization, stratified randomization).\n\nAllocation Concealment: The manuscript should state how the randomization list is generated and how allocation concealment is maintained. This section should include information specifying who generates the list and how it is kept from investigators and participants.\n\nBlinding of Study Nurse: The manuscript should explicitly state if the study nurse is being blinded.\n\nRecommendation Should the authors be willing to address the concerns outlined above, the article can be indexed.\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/13-135
|
https://f1000research.com/articles/13-134/v1
|
22 Feb 24
|
{
"type": "Opinion Article",
"title": "Generative AI, UK Copyright and Open Licences: considerations for UK HEI copyright advice services",
"authors": [
"Andrew Johnson"
],
"abstract": "With the enormous growth in interest and use of generative artificial intelligence (AI) systems seen since the launch of ChatGPT in autumn 2022 have come questions both about the legal status of AI outputs, and of using protected works as training inputs. It is inevitable that UK higher education institution (HEI) library copyright advice services will see an increase in questions around use of works with AI as a result. Staff working in such library services are not lawyers or able to offer legal advice to their academic researchers. Nonetheless, they must look at the issues raised, consider how to advise in analogous situations of using copyright material, and offer opinion to researchers accordingly. While the legal questions remain to be answered definitively, copyright librarians can still offer advice on both open licences and use of copyright material under permitted exceptions. We look here at how library services can address questions on copyright and open licences for generative AI for researchers in UK HEIs.",
"keywords": [
"copyright",
"artificial intelligence",
"AI",
"generative AI systems",
"open access",
"open licences"
],
"content": "1. Introduction\n\nThis article was prompted in part by an audience question at a recent library presentation, asking how open licences fit with artificial intelligence (AI). To answer the question of how library advice services in UK higher education institution (HEIs) can advise researchers to assess any copyright risks in their use of, or creation of their own, generative AI systems, we will look at the following research questions:\n\n• Does the AI make copies of any copyright works used to train it?\n\n• Does the AI create outputs that are copies of one or more copyright works used to train it?\n\n• Does the AI further communicate any copies of copyright works online?\n\n• Does the AI attribute the works used to train it?\n\nTo begin, we must define what we mean by open licences, copyright, and AI.\n\nWith regard to AI, we mean the text, image, music and video generative software that has seen a huge increase in attention of late. This includes products such as OpenAI’s ChatGPT and DALL-E2, Stable Diffusion, Google Bard, Adobe Firefly, and others. AI systems might be Large Language Models (LLMs, e.g., ChatGPT), or may rely on diffusion image generating technology (e.g., DALL-E, Stable Diffusion). We are specifically concerned with any generative AI software trained from a corpus of copyright protected works.\n\nTurning to open licences, the presentation at which the AI query arose concerned Creative Commons (CC) licences, perhaps the most frequently encountered open licences for academic authors. They are the staple licences under which many of the research outputs from UK HEIs are published, due to the combination of Research Excellence Framework (REF) requirements and funder open access mandates (e.g., The Wellcome Trust1 and UK Research and Innovation (UKRI)2). The six main licences allow reuse under clearly defined terms, ranging from the most open Attribution (CC BY) to the most restrictive Attribution NonCommercial NoDerivatives (CC BY-NC-ND).\n\nIn addition to the above licences, we will consider works available under the CC0 Public Domain Dedication. CC0 waives all copyright and related rights in a work to the greatest extent permitted by law, and allows the work to be treated as public domain i.e., no restrictions on use or requirement to attribute3 (though to avoid allegations of plagiarism, public domain works should still be cited in line with usual academic norms). There are also numerous open software licences,4 the main principles of which apply in a similar way to those of the CC licences under discussion. Key questions for any open licence are:\n\n• Does the licence permit:\n\n○ Copying?\n\n○ Distribution in any or all formats?\n\n○ Communication online?\n\n• Does the licence require attribution?\n\n○ If yes, how must it (and/or the creator) be attributed?\n\n• Does the licence allow commercial (i.e., profit-making) use?\n\n• Does the licence allow derivatives (adaptations) of the licensed work to be made?\n\n○ If yes, are there restrictions on how derivatives must be licensed and/or attributed?\n\nIn terms of copyright, we limit ourselves to the current situation as we see it in the UK. Copyright as an intellectual property (IP) right, and how the right may be infringed, is set out in the Copyright, Designs and Patents Act 1988 (CDPA) and the numerous amendments made since it came into force. The owner of copyright in a qualifying work has the right to prevent others doing any of the restricted acts – copying, publishing and distributing copies, playing, performing, renting or lending, adapting and communicating online. Set against these are certain permitted exceptions, under which others can use copyright works provided they adhere to the terms of the exception, do not prevent the rights owner exploiting their work in the usual manner, and do not compete economically with the original work.\n\nWe should also note the Copyright and Rights in Databases Regulations 1997. At s.6 this defines a database as ‘a collection of independent works, data or other materials which – (a) are arranged in a systematic or methodical way, and (b) are individually accessible by electronic or other means.’ The important points are that while individual copyright works might be included in a database, the whole collection may have protection under database right if there was, as defined at s.13(1) ‘a substantial investment in obtaining, verifying or presenting the contents of the database’. If a person, without the database owner’s consent, ‘extracts or re-utilises all or a substantial part of the contents of the database’, including by ‘the repeated and systematic extraction or re-utilisation of insubstantial parts of the contents’, this infringes the database right. Furthermore, the database can, in theory, qualify as a copyright literary work if the selection and arrangement of the contents represents the author’s own intellectual creation.\n\nHaving established the terms and definitions to be used we will now address the four research questions and how the answers to these inform what advice should be given.\n\n\n2. Does the AI make copies of any copyright works used to train it?\n\nIf an AI, or anyone, reproduces a copyright protected work beyond what is permitted under legal exception this can infringe the reproduction right. The exception to which we might turn when looking at AI training is s.29A CDPA, the exception for text and data mining (TDM). The conditions of that exception are that it is limited to non-commercial use, requires lawful access to the work, and any copies made cannot be transferred onward or be further used for any new purpose. Setting aside concerns TDM can facilitate academic data laundering5 that bypasses non-commercial restrictions, we must look at another aspect of the AI training process which may affect what is permissible. That is whether the training involves multiple copying. For clarity, we should note we are not claiming all, or any specific, AI systems make such copies. Rather, we are considering what copyright issues researchers might conceivably encounter in using or creating generative AI systems, and how relevant library services should advise accordingly.\n\nA corpus of online copyright works may be web-scraped and analysed for non-commercial scientific research. Any data generated may be shared openly and either have no copyright or be open access. If a commercial actor then uses that data, this in itself may not be creating further copies of the originally scraped works, so is not infringement of copyright. However, if the commercial actor makes any further copies of the works in training their AI, this is not covered by the TDM exception that allowed the initial research and is potentially infringing. For example, re-scraping or copying works to match this to metadata in a public domain database could prove infringing as it would not be covered by s.29A. So academic-commercial partnerships, or research activities making profit – directly or indirectly – from an AI system, cannot rely on the UK TDM exception to make copies as part of the system’s training. A suitable licence is required in such cases where copyright works form the training corpus.\n\nIn addition, the provisions of CDPA s.28A appear to offer little protection for copying of input training works. This permits transient or incidental copying as an essential part of a technical process, so may at first seem ideal for covering AI training. This exception only applies where all these conditions apply:\n\n(it enables)…’a transmission of the work in a network between third parties by an intermediary; or … a lawful use of the work; and which has no independent economic significance.’ (CDPA s.28A)\n\nThis is intended to allow transient copying as must occur, for example, to allow the web to function. Where an AI system uses copyright material “in-house” as part of what is ultimately a for-profit business model this would not meet all the requirements above. This exception supports transient copying for non-commercial research use under s.29A, but only insofar as the reproduction is limited to that purpose - not for any further copying, training or communication.\n\nSo, what can be relied upon? Material licensed under the six main CC licences could be used for AI training. If the licence is a non-commercial one, then material could only be used if the AI system usage is not profit-making. However, problems of scale would be encountered if copies are shared, as the individual attribution requirements of CC licences might reasonably simply be met for a small number of works, but not for a large training corpus (see also Section 5 below). Avoiding onward distribution requiring attribution is important if using works available under Creative Commons licences. Anything available under CC0, or already in the public domain in the territory where the copying is taking place, can be freely copied and used to train – with one final caveat to consider.\n\nThat caveat is database right. A database may consist of uncopyrightable data, or copyrightable works, or a combination of both. While you might copy a database whose individual constituent works are open licensed or public domain without infringing copyright in the works themselves, you could still infringe database right. If the database represents a substantial investment on the part of the creator, then irrespective of the copyright status, or licence, of the individually searchable parts, repeated extraction of small parts can still infringe without the owner’s consent. A website collating a large body of images and associated metadata could qualify as a database. Repeatedly accessing and copying excerpts of the database – i.e., the web archive – could therefore be extraction or re-utilisation of a substantial part.\n\nDatabases can be openly licensed, much as their constituent parts can be, so if using a database for AI training it would be wise to choose one available under a permissive licence, or one available in a territory where no legal database right subsists – the UK and Europe have had database protection since 1996,6 however many other territories do not.\n\n\n3. Does the AI create outputs that are copies of one or more copyright works used to train it?\n\nHere the waters are somewhat murkier. There are articles providing in-depth legal analysis (see for example Guadamuz, 20237). Here we will limit our analysis to the more straightforward issues of UK copyright as we would expect a HEI copyright service to address them.\n\nDue to the way AI systems generate outputs it is extremely rare for training inputs to be reproduced exactly (see for example Somepalli et al., 20228 for diffusion image models, or Liang et al., 20229 for LLM text regurgitation), however a work does not need to be reproduced in its entirety for there to be infringement. The CDPA only requires copying a substantial part (CDPA s.16(3a)) for infringement to occur. While some may believe Temple Island Collections Ltd v New English Teas Ltd & another [2012] EWPCC 110 takes the protection of ideas or “style” too far, it stands as an example of how partial copying can be infringing in the UK. A user asking a generative AI to create an image in a particular artists’ style may not lead to an output that infringes any copyright, however if the prompt leads to close fitting to an existing work, or clearly reproduces a substantial part of an existing input too closely, this might infringe. It should be noted Temple Island is a very narrow decision, due to the judge basing his decision in part on the causal link, as he saw it, between the two works.11 Whether a causal link would be found between an output substantially similar to a training input, and what effect – if any – the prompt used would have, remains to be determined.\n\nOpen licences are more helpful in the case of outputs. Reproduction of a substantial part of a work available under open licence is unlikely to be problematic and should be covered by the licence terms. Similarly, public domain or CC0 works may be freely reproduced. Care must be taken with some licences (e.g., non-commercial or share-alike). Any terms and conditions applied to the AI end-user’s reuse of the work their prompt generates should, if it substantially copies an input work, be compatible with the licence applying to that input. For example – and exceptionally unlikely this may be – if an output copies a substantial part of an input that is licensed non-commercially, that non-commercial licence might apply to the end-user’s reuse of the parts of their output that are a reproduction of the original.\n\nAll this immediately raises the objection that the AI is not copying as such, but rather only adding data in minimum amounts to create a new output, via an as-yet imperfectly understood process.12 Building pixels into a representation of a dog chewing on a hat, in response to a prompt of ‘picture of a dog eating a hat’, that by chance matches closely or exactly to an original copyright work, can only infringe if that work was part of the training data, as the AI would have to have access to the allegedly infringed work to have copied it. However, if it is in the training data, then regardless of how the system generates outputs it may be difficult to argue against a challenge of copyright infringement if a substantial part of a trained work is reproduced.\n\nConsequently, training on works that are public domain, openly licensed or under compatible reuse permissions must be the recommendation. This avoids any potential issues of infringing copying by commercial TDM in training inputs and negates any issues of infringement by outputs recreating a work in the training dataset too closely. This will, presumably, be the route chosen by Adobe with Firefly, for which they have offered their business users indemnity against copyright challenges.13\n\nFrom the observations above, we might conclude originality appears the important consideration in determining the potential for infringement – but possibly not so in determining copyright subsistence in outputs. We will briefly address the question of copyright ownership of outputs, and where this might subsist the further question of how such right is assigned and licensed.\n\nThe CDPA at s.9(3) allows for the possibility of copyright in computer-generated works in the UK, where such a work is, by virtue of the author, in theory qualifying for UK copyright. Computer generated is helpfully defined at CDPA s.178 as meaning a work with no human author. The copyright owner – author – is taken as being “the person by whom the arrangements necessary for the creation of the work are undertaken”.14 This seems ideally suited to allowing copyright in AI generated works. Duration of copyright in such works is fifty years from the end of the year the work was made. This shorter duration could reflect the reduced human skill and labour, or intellectual creation, required in the making of the work. It may also reflect that such literary, dramatic, musical or artistic works do not require the same originality to qualify for copyright.15\n\nMore attention has been directed to analysing the question of whether AI generated works might qualify for copyright subsistence in the USA,16 and how this should be registered,17 than on the issue of who should own that right in the UK. For now, some commercial AI system owners seem confident that if outputs qualify for UK copyright then the system owner can choose how to licence such outputs. Copyright in prompts – so-called prompt engineering – is seemingly enjoying a moment of popularity despite some doubts about its future.18 Court of Justice of the European Union (CJEU) precedent from Infopaq19 allows even short combinations of words to qualify for copyright if they represent the author’s own intellectual creation. Despite this, ownership of any possible copyright in a prompt does not necessarily entail ownership of the output work. It is debatable whether the prompter contributed the correct intellectual creativity, or labour skill and judgment, to have made the arrangements necessary for the creation of the work, or whether they have in effect only “played the game”.20 Until greater clarity arises on this point, whether by guidance from the UK Intellectual Property Office, statutory amendment or judicial interpretation, this seems open to interpretation depending on how the system concerned is owned and operated.\n\nEven if all input into the system’s training is public domain, new works created may qualify for copyright. The terms and conditions of any existing system researchers use should be noted carefully – for example, Midjourney21 images created under the free trial terms are licensed CC BY-NC, with copyright owned by the company.\n\n\n4. Does the AI further communicate any copies of copyright works online?\n\nFor outputs shared online by an end-user, who entered the prompt(s) to cause generation of the output, the licence terms applied to that output work will govern how they can use it. An output that (by virtue of s.9(3) and the qualifying status of the creator) has its own copyright and does not, in whole or substantial part, reproduce any input, can be communicated in accordance with the rights owner’s licence, and the terms and conditions of the AI system.\n\nFurther communication is unlikely to present a problem where the output is not a (substantial) copy of any copyright-restricted input, and both the owner of rights in the output (if any) and the terms of use of the system permit it. It is difficult to think of a situation where an AI might communicate inputs onward online other than as a substantially similar output. Communicating inputs directly would almost certainly infringe unless those inputs were public domain or (openly or otherwise compatibly) licensed.\n\n\n5. Does the AI attribute the works used to train it?\n\nWe have already touched on the issue of attribution, so there is little to add beyond a brief look at outputs that recreate a substantial part of an input. As noted, this appears very unlikely, but theoretically possible. This raises the issue of how such a reproduction should attribute the original.\n\nCC0 and the public domain are certainly the AI trainer’s friend once again, with no attribution required. What, though, of a work openly licensed under CC BY 4.0? Any onward sharing, or sharing of an adaptation, should include attribution. For AI systems to identify outputs that reproduce a substantial part of a protected input, and add suitable attribution at the point of generation, is surely impracticable. Breach of licence terms through failure to attribute is, at least in theory, possible. For version 4.0 CC licences this could be remedied by adding suitable attribution on demand from the licensor. Earlier CC licences could result in a permanent breach of the licence terms. Any possible risk from this is difficult to quantify, however the history of so-called copyright “trolls” exploiting22 this seeming loophole in early CC licences is real and has led to many infringement actions.\n\n\n6. Summary\n\nThe clear conclusion is that to be free of any concerns about copyright (or database right) infringement in the UK, researchers should use (or if training their own, create) an AI system trained entirely on public domain or suitably open-licensed works and databases. One possibility would be to use bespoke licensing covering use under predefined conditions. A body of works with clear licence terms allowing non-commercial educational use, with only blanket attribution of the corpus being required, would be a perfectly sensible option. A body of student coursework or dissertations, stored in a non-public intranet, could conceivably be such a corpus if the terms under which the students licence their IP to the institution as part of their enrolment are compatible.\n\nWhere either input works or the data source used for training is copyright protected, risk must creep in until the current situation is made clearer. The resolution of the existing legal challenges23 may provide greater clarity.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nThe author gratefully acknowledges the assistance of two colleagues in commenting on an early draft of this article. Open access funding for this paper was provided by the University of Sheffield Institutional Open Access Fund. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.\n\n\nReferences\n\nOpen access policy: Wellcome. accessed June 22, 2023. Reference Source\n\nUKRI open access policy: UK Research and Innovation.August 6, 2021. Reference Source\n\nFrequently Asked Questions: Attribution: Creative Commons. accessed August 25, 2023. Reference Source\n\nOSI Approved Licences: Open Source Initiative. accessed August 22, 2023. Reference Source\n\nBaio A: AI Data Laundering: How Academic and Nonprofit Researchers Shield Tech Companies from Accountability, (blog).2022. Reference SourceReference Source\n\nDirective 96/9/EC of the European Parliament and of the Council of 11 March 1996 on the legal protection of databases. http\n\nGuadamuz A: A Scanner Darkly: Copyright Liability and Exceptions in Artificial Intelligence Inputs and Outputs. SSRN. 2023. Publisher Full Text\n\nSomepalli, et al.: Diffusion Art or Digital Forgery? Investigating Data Replication in Diffusion Models. arXiv (preprint). 2022. Publisher Full Text\n\nLiang, et al.: Holistic Evaluation of Language Models. arXiv (preprint). 2022. Publisher Full Text\n\nTemple Island Collections Ltd v New English Teas Ltd & Anor [2012] EWPCC 1. http\n\nTemple Island Collections Ltd v New English Teas Ltd & Anor [2012] EWPCC 1 [55]-[67].\n\nLee TB, Trott S: A jargon-free explanation of how AI large language models work. ars technica. 2023. Reference Source\n\nNellis S: Adobe pushes Firefly AI into big business, with financial cover.2023. Reference SourceReference Source\n\nCopyright Designs and Patents Act 1988, s.9(3). http\n\nGuadamuz A: Do Androids Dream of Electric Copyright? Comparative Analysis of Originality in Artificial Intelligence Generated Works. Intellect. Prop. Q. 2017; 2.\n\nZirpoli CT: Generative Artificial Intelligence and Copyright Law. Copyright, Fair Use, Scholarly Communication, etc. Libraries at University of Nebraska-Lincoln; 2023; 243. .\n\nUnited States Copyright Office: Copyright Registration Guidance: Works Containing Material Generated by Artificial Intelligence.March 16, 2023. Reference Source\n\nAcar OA: AI Prompt Engineering Isn’t the Future. Harv. Bus. Rev. 2023. Reference Source\n\nInfopaq International A/S v Danske Dagblades Forening: 2009. Reference Source\n\nKitchin J: Nova Productions Ltd v Mazooma Games Ltd [2006] EWHC 24 (Ch) [106].\n\nTerms of Service. Midjourney. July 21, 2023. Reference Source\n\nDoctorow C: A Bug in Early Creative Commons Licenses Has Enabled a New Breed of Superpredator: Copyleft trolls, robosigning, and Pixsy. Medium (blog). 2022. Reference Source\n\nChatGPT and Deepfake-Creating Apps: A Running List of Key AI-Lawsuits. The Fashion Law. June 5, 2023. Reference Source"
}
|
[
{
"id": "254872",
"date": "26 Mar 2024",
"name": "Jane Secker",
"expertise": [
"Reviewer Expertise Copyright and new technologies",
"information and digital literacy",
"copyright literacy"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThere is a huge amount of interest in copyright and AI - and copyright advisors in UK universities are getting a lot of questions - so this article is extremely timely and I suspect it's going to be of interest.\nIt is not a legal analysis but it does point to case law and others who undertake legal analysis. It also looks in some detail at the text and data mining exception and whether this can be relied on by those who are using or creating Generative AI.\nThe starting premise of the four questions that arose at a library event are all helpful. While I don't want to expand on the remit of the paper - I wonder if it needs to be clear that much of what it is discussing is relevant if an academic wants to build a GenAI - so encouraging them to rely on CC Licensed content or content in the public domain. I think it is worth acknowledging that the concerns extend beyond these questions, particularly when academics might be using a host of GenAI tools that are not transparent about the sources they are trained on - in light of cases such as the New York Times case - we could see some of these tools having to be more transparent. However there are also questions about whether you can protect works created by an AI with no human creator. And what to advise academics who might be tempted to feed their own research data into an AI to help analyse it (that is likely to contravene the ethical approval they have for a project aside from any copyright concerns.). While I don't want the author to widen the scope, it might be worth just flagging up there are increasing numbers of copyright issues that are arising and that copyright advisors are going to need to try and stay up to date with the case law and evolving landscape - which is a real challenge. I wonder if it might end with some practical - where to go to keep up to date. LIS-Copyseek (the Jiscmail list for copyright queries) remains very lively and many AI related issues are being discussed. There are of course various briefings and Jisc are keeping the sector up to date on AI. But I welcome this publication, with just a few amendments to the introduction and conclusion just to flag up some of the wider issues and to point people to sources of advice.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": []
},
{
"id": "274058",
"date": "10 May 2024",
"name": "Nicola Lucchi",
"expertise": [
"Reviewer Expertise Comparative law",
"Intellectual property law",
"Law & Technology",
"Media Law"
],
"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 discusses the implications of using copyrighted materials in generative AI systems within UK Higher Education Institutions (HEIs). It provides a detailed analysis of the legal frameworks governing copyright in the UK, particularly as they apply to AI-generated content and the use of such content in academic settings. The article is structured around key legal questions that arise in the context of AI and copyright, including whether AI makes unauthorized copies of copyrighted works, whether AI outputs might themselves be copyright infringements, and the licensing implications of using copyrighted material to train AI.\nAlthough the article is rather short, it is well-researched and presents a thorough analysis of the copyright issues associated with the use of AI in academic environments. It effectively uses legal statutes and case law to discuss potential legal outcomes and the responsibilities of copyright advisors in HEIs. The originality of the article is evident in its specific focus on the role of HEI copyright advisors, providing nuanced insights into how these professionals can manage legal risks associated with AI technologies.\nThe factual statements in the article are accurate and well-supported by citations. The author refers to relevant legal documents, case law, and current scholarly work to back up claims, providing an appropriate evidential base for the discussion.\nThe conclusions drawn in the article are mostly balanced and justified based on the presented arguments. They provide practical, actionable advice for HEI copyright advisors based on a thorough analysis of the legal issues discussed. However, as noted by the other peer reviewer, the article could benefit from a broader discussion of non-transparent AI tools and the evolving legal landscape.\nRecommendations for Improvement: Given the rapid development in the field of AI and copyright, the article could be strengthened by referencing additional current literature. This would ensure that the article remains relevant and provides the most up-to-date advice possible.\nThat said, the article is certainly a valuable contribution to the literature on copyright and AI, especially in the academic context, with some minor improvements.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-134
|
https://f1000research.com/articles/13-131/v1
|
22 Feb 24
|
{
"type": "Opinion Article",
"title": "Geophysics for the environment in Indonesia",
"authors": [
"Achmad Darul",
"Dasapta Erwin Irawan",
"Eleonora Agustine",
"Achmad Darul",
"Eleonora Agustine"
],
"abstract": "This paper explores the hidden potential of geophysics for the environment, focusing on subsurface mapping activities in Indonesia. Geophysics plays a crucial role in understanding the Earth’s physical characteristics and addressing environmental challenges. It is particularly relevant in water-related environmental problems, such as groundwater contamination and infiltration monitoring. Geophysics is also used to detect metals in fertile soils and plants, providing insights into agricultural practices and potential health risks. However, applying geophysics in urban areas poses challenges due to physical obstructions, cultural noise, limited workspace, permits, and safety concerns. This article emphasizes the integration of geophysics with environmental studies, the need for further research on water-related environmental problems and metal detection, and the development of techniques tailored for urban environments. It suggests focusing on understanding the specific environmental challenges in Indonesia and leveraging advancements in technology for more accurate and efficient geophysical investigations. In the Indonesian context, geophysics has diverse applications, including energy exploration, seismology, and oceanography. However, it has not been properly utilized in the field of environmental studies, particularly in urban areas.",
"keywords": [
"geophysics",
"environmental problems",
"urban areas",
"urban hydrogeology",
"subsurface analyses",
"geology",
"aquifers",
"groundwater"
],
"content": "Introduction\n\nGeophysics plays a crucial role in environmental studies by providing valuable insights into the Earth’s physical characteristics and the living environment of mankind. Environmental geophysics, also known as near-surface geophysics, integrates environmental science and geophysics to study the relationship between geophysical fields and the Earth’s physical characteristics, including natural and artificial environments.1 Geophysical techniques are pivotal tools for detecting and studying various environmental problems caused by drinking and wastewater, as well as delineating contaminated, partly affected, and virgin areas.2\n\nThese applications demonstrate the importance of geophysics in environmental studies, emphasizing its role in understanding environmental anomalies. The objective of this paper is to highlight the crucial role of geophysics in environmental studies and showcase its applications for addressing environmental problems in Indonesia. This will be based on a small bibliometric dataset from the Scopus database.3\n\n\nThe general applications of geophysics\n\nGeophysics has played a crucial role in addressing various water-related environmental challenges, as demonstrated the improved extraction of hydrologic information from geophysical data through coupled hydrogeophysical inversion, allowing for the monitoring of infiltration and redistribution of water using surface-based electrical conductivity surveys.4 Another work highlighted the integration of geophysical techniques with hydrological investigation for identifying groundwater contamination, emphasizing its frequent use in solving geological and environmental problems related to groundwater quality and exploration.2 Additionally, we found a successful application of geophysical methods in investigating aquifer contamination by various sources such as graveyards, highlighting the versatility of geophysics in addressing environmental problems related to groundwater pollution.5 These examples underscore the pivotal role of geophysics in understanding and mitigating water-related environmental issues, ranging from groundwater contamination to the study of aquifer pollution by diverse sources.\n\nThe application of geophysics in detecting metals from fertile soil and plants has been demonstrated in various studies, including those conducted in Indonesia by several researchers from Institut Teknologi Bandung.6 Another instance from North China Plain, researchers have utilized geophysical methods to investigate the accumulation of heavy metals in agricultural soil and products, highlighting the relationship between the application of organic and phosphate fertilizers and the accumulation of cadmium, lead, copper, and zinc in the soil and agricultural products.7 This study underscores the significance of geophysics in understanding the factors contributing to metal accumulation in agricultural areas.\n\nFurthermore, this work has also shed light on the influence of soil heterogeneity on plant development and crop yield, as evaluated using time-series of UAV and ground-based geophysical imagery.8 This research emphasized the integration of multiscale and multitype soil and plant datasets to identify the spatiotemporal co-variance between soil properties and plant development and yield, showcasing the utility of geophysics in understanding the complex interactions between soil and plants.\n\nMoreover, several studies have contributed to the widespread applications of geophysical methods for environmental problems. For example, we found two researchers have investigated the resistance properties of different soil types to heavy metals, particularly in agricultural soils. Their research highlights the role of geophysics in assessing the impact of agricultural practices on soil properties and metal content. It provides valuable insights into the potential effects of long-term fertilization on the accumulation of heavy metals in soil, even in cemetery areas.9,10\n\nAdditionally, geophysics have been used to assess heavy metal accumulation in agricultural soil, understanding soil-plant interactions, evaluating the impact of agricultural practices on metal content in soil and plants, and studying the hyper-accumulation of metal content by certain plants.6\n\n\nThe applications of geophysics in Indonesia\n\nThis section explains the applications of various geophysical methods in Indonesia. To gather scientific articles on this topic, we conducted a search using the Scopus database with the keywords “geophysics” AND “Indonesia”. The search yielded 582 articles. To provide a visual representation of the corpus, we utilized Vosviewer11 and obtained the following result (see Figure 1).\n\nIn the diagram below, we present an overview of the applications of geophysics based on a search of the Scopus database. The applications of geophysics in the Scopus database can be categorized into the following areas:\n\n1. Engineering, constructions, and disaster management: Geophysics plays a crucial role in engineering and construction projects by providing insights into subsurface conditions, detecting potential hazards, and assessing the structural integrity of buildings and infrastructure. It also aids in the management and mitigation of natural disasters such as earthquakes and landslides.\n\n2. Climate, meteorology, infectious diseases, public health, agriculture: Geophysics contributes to understanding climate patterns, meteorological phenomena, and their impact on public health and agriculture. It helps monitor environmental factors, such as air quality, temperature, and rainfall, that influence the spread of infectious diseases and the productivity of agricultural systems.\n\n3. Oceanography, physical and chemical analyses: Geophysics is essential for studying the oceans, including their physical and chemical properties. It aids in understanding sea wave behavior, coastal erosion, and the design of offshore structures. Geophysical techniques also contribute to the analysis of water column properties, such as salinity, temperature, and currents, which are crucial for oceanographic research.\n\n4. Energy exploration, hydrocarbon, geothermal, volcanoes, structural geology, groundwater: Geophysics plays a vital role in energy exploration, including the identification of hydrocarbon reservoirs, assessment of geothermal resources, and monitoring of volcanic activity. It also aids in studying structural geology and understanding groundwater systems, including their availability and quality.\n\n5. Seismology, earthquake, earth interior, geodynamics: Geophysics is fundamental to seismology, the study of earthquakes and the Earth’s interior. It helps detect and monitor seismic activity, analyze earthquake sources, and investigate the dynamics of the Earth’s tectonic plates. Geophysical methods provide valuable insights into the structure and composition of the Earth’s interior.\n\nThese categories highlight the broad range of applications of geophysics, demonstrating its significance in various scientific disciplines and practical fields. Geophysics plays a vital role in understanding the Earth’s physical characteristics and addressing environmental challenges.\n\nFor a more detailed search focusing on the intersection of geophysics, Indonesia, and the environment, we used the keywords “geophysics” AND “Indonesia” AND “environment”. This search yielded 40 articles, providing a more focused collection of research on these specific topics. The visualization in Figure 2 showcases the breadth and depth of geophysics research conducted in Indonesia, specifically related to environmental studies.\n\nIn addition to the applications mentioned in the paper, geophysics is widely used in energy exploration and seismology to identify the structure of the Earth’s interior. By analyzing seismic waves and conducting geophysical surveys, scientists can gain insights into underground formations, including potential energy resources such as oil, gas, and minerals.12 This information is crucial for the exploration and extraction of these resources.\n\nFurthermore, airborne geophysical mapping has proven to be a valuable tool in various applications. The use of aerial platforms equipped with geophysical sensors allows for the rapid and efficient collection of data over large areas.13 This technique has been applied in geological mapping, mineral exploration, and environmental studies. It enables researchers to obtain high-resolution data, which is particularly useful for identifying subsurface structures and mapping geological features.\n\nGeophysics also plays a significant role in oceanography, which is particularly relevant in Indonesia. As an archipelago nation, Indonesia has a vast expanse of ocean, covering approximately 62% of its total area. Geophysics aids researchers in understanding the behavior of sea waves, including their propagation, energy dissipation, and interaction with coastal areas. By studying these processes, scientists can better predict and manage coastal erosion, as well as improve the design and safety of offshore structures.14 Additionally, geophysics contributes to the study of coral reefs in Indonesia by providing insights into their growth patterns, health, and vulnerability to environmental changes.\n\nSurprisingly, geophysics also finds applications in climate properties and predictions related to human health. By monitoring changes in the Earth’s magnetic field and studying atmospheric conditions, scientists can investigate the effects of climate change on human well-being. Geophysical techniques, such as magnetometry and atmospheric measurements, contribute to understanding the links between climate patterns, air quality, and human health outcomes.15 These applications highlight the interdisciplinary nature of geophysics and its potential impact on various aspects of our lives.\n\nGeophysics is a valuable tool for environmental investigations and remediation. However, it is important to be aware of the limitations and use it in conjunction with other techniques.\n\nGeophysical methods allow for the quick and efficient mapping of large land areas, which is crucial for identifying and characterizing potential contamination sites.16 Despite being costly, they provide significant advantages by efficiently assessing contamination extent and identifying potential sources. These non-invasive methods minimize disturbance to the environment and save time and resources.\n\nGeophysics offers a non-destructive approach to investigating the Earth’s physical characteristics. Electrical resistivity tomography (ERT) can map groundwater contamination plumes by imaging subsurface resistivity distribution. Ground penetrating radar (GPR) detects buried objects and structures, aiding in environmental site assessments and remediation. Electromagnetic induction (EMI) maps salt distribution in soil, indicating potential groundwater contamination areas.17\n\nIt’s important to note that geophysical methods may not detect all types of contamination, such as volatile organic compounds (VOCs), and interpreting data in complex geological settings can be challenging.18 Nonetheless, they provide valuable insights into subsurface geology, helping assess groundwater contamination potential and guide well and sampling point placement.\n\nHowever, despite its advantages, applying geophysics in dense urban areas can be challenging due to several factors. Here are some of the key challenges:\n\n• Physical obstructions: Urban environments are characterized by a dense network of infrastructure, including buildings, roads, bridges, and underground utilities. These structures can obstruct access to the subsurface, making it difficult to deploy geophysical equipment and collect data.\n\n• Cultural noise: Urban areas generate significant cultural noise, including traffic vibrations, electromagnetic interference from electronic devices, and human activity. This noise can mask the subtle geophysical signals that geophysicists are trying to measure.\n\n• Limited workspace: Urban areas often have limited open space, making it challenging to set up and operate geophysical equipment. This can be particularly problematic for methods that require large arrays of sensors or long survey lines.\n\n• Permits and regulations: Urban environments are often subject to strict regulations and permit requirements, which can add time and complexity to geophysical surveys.\n\n• Safety concerns: Working in urban areas can pose safety risks, including exposure to traffic, hazardous materials, and confined spaces. Geophysicists must carefully plan and execute their surveys to minimize these risks.\n\nDespite these challenges, geophysics can still be a valuable tool for urban applications. Geophysicists have developed a variety of techniques that can be adapted to urban environments, and new technologies are being developed all the time.\n\n\nRemarks\n\nThe document discusses the hidden potential of geophysics for the environment, with a focus on Indonesia. It highlights the role of geophysics in understanding the Earth’s physical characteristics and its applications in addressing environmental challenges. The paper explores the use of geophysics in solving water-related environmental problems, detecting metals in fertile soils and plants, and its relevance in the Indonesian context. It also provides an overview of the broad applications of geophysics in the world, including engineering, climate, oceanography, energy exploration, and seismology. The limitations and challenges of applying geophysics in urban areas are also discussed.\n\nBelow are some important remarks that should be noted and developed by future earth scientists, particularly Indonesian earth scientists. These remarks provide directions for future research and highlight the potential for further development and collaboration in the field of geophysics for environmental studies, particularly in the Indonesian context.\n\n1. Integration of geophysics and environmental studies: The document emphasizes the importance of integrating geophysics with environmental studies to address environmental challenges effectively. Future researchers should continue exploring the interdisciplinary nature of geophysics and its applications in various environmental contexts.\n\n2. Water-related environmental problems: Geophysics plays a crucial role in addressing water-related environmental problems, such as groundwater contamination and infiltration monitoring. Researchers should further investigate the potential of geophysics in assessing water quality and exploring innovative techniques for sustainable water management.\n\n3. Metal detection in soils and plants: The use of geophysics for detecting metals in fertile soils and plants provides valuable insights into agricultural practices and potential health risks. Further research is needed to expand this application and explore its implications for food security and environmental sustainability.\n\n4. Urban applications of geophysics: Applying geophysics in dense urban areas presents unique challenges due to physical obstructions, cultural noise, limited workspace, permits, and safety concerns. Researchers should focus on developing techniques and methodologies specifically tailored for urban environments to overcome these challenges and unlock the full potential of geophysics in urban applications.\n\n5. Indonesian context: Geophysics plays a significant role in Indonesia due to its diverse geological and environmental characteristics. Future research should concentrate on understanding the specific environmental challenges faced by Indonesia and developing innovative geophysical approaches to address these issues effectively.\n\n6. Advancements in technology: Continued advancements in geophysical technology, such as aerial platforms, improved sensors, and data analysis techniques, offer promising opportunities for expanding the applications of geophysics. Researchers should stay updated with emerging technologies and incorporate them into their studies to enhance the accuracy and efficiency of geophysical investigations.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nFigshare: Extended data for ‘Geophysics for the environment in Indonesia’, https://doi.org/10.6084/m9.figshare.24759996.v2. 3\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgments\n\nThe authors would like to express their sincere gratitude to the following individuals for their invaluable support and contributions to this research. 1) From Faculty of Earth Sciences and Technology, Institut Teknologi Bandung: Prof. Deny Juanda Puradimaja, Prof. Lambok Hutasoit, Prof. Prihadi Sumintadireja, Prof. Agus M. Ramdhan, Dr. Rusmawan Suwarman, and Dr. Edi Riawan. 2) From Faculty of Geology, Universitas Padjadjaran: Prof. Hendarmawan. Their guidance, expertise, and support were instrumental in the successful completion of this research. We are truly grateful for their time and dedication. We also extend our heartfelt thanks to the invited and public reviewers who provided insightful and constructive feedback that significantly improved the quality of this manuscript. Their contributions are greatly appreciated.\n\n\nReferences\n\nSun L, Ding Y, You J, et al.: Introduction and Analysis of Environmental Geophysics. The Netherlands: Atlantis Press; 2015.\n\nRehman F, Harbi HM, Azeem T, et al.: Shallow geophysical and hydrological investigations to identify groundwater contamination in Wadi Bani Malik dam area Jeddah, Saudi Arabia. Open Geosci. 2021 Jan; 13(1): 272–279. Publisher Full Text\n\nIrawan DE, Darul A, Agustine E: Datasets - Geophysics for the Environment in Indonesia. Dataset. figshare. 2023. Publisher Full Text\n\nHinnell AC, Ferré TPA, Vrugt JA, et al.: Improved extraction of hydrologic information from geophysical data through coupled hydrogeophysical inversion. Water Resour. Res. 2010 Apr; 46(4). Publisher Full Text\n\nMatias MJS, da Silva MM , Goncalves L, et al.: An investigation into the use of geophysical methods in the study of aquifer contamination by graveyards. Near Surf. Geophys. 2004 Aug; 2(3): 131–136. Publisher Full Text\n\nHamdan AM, Bijaksana S, Tjoa A, et al.: Magnetic characterizations of nickel hyperaccumulating plants (Planchonella oxyhedra and Rinorea bengalensis) from Halmahera, Indonesia. Int. J. Phytoremediation. 2019 Jan; 21: 364–371. PubMed Abstract | Publisher Full Text\n\nLiu Z, Bai Y, Gao J, et al.: Driving factors on accumulation of cadmium, lead, copper, zinc in agricultural soil and products of the North China Plain. Sci. Rep. 2023 May; 13(7429): 1–13. Publisher Full Text\n\nFalco N, Wainwright HM, Dafflon B, et al.: Influence of soil heterogeneity on soybean plant development and crop yield evaluated using time-series of UAV and ground-based geophysical imagery. Sci. Rep. 2021 Mar; 11(7046): 1–17. Publisher Full Text\n\nAddisu MT, Bikila AM: Heavy metal resistance properties of bacteria from different soil types in Horo Guduru Wollega, Ethiopia. Int. J. Sci. Rep. 2019 Oct; 5(11): 320–323. Publisher Full Text\n\nda Silva FC , de Assis CF , Aquino WF, et al.: USE OF GEOPHYSICAL TECHNIQUES FOR ANALYSIS OF TRACE METALS IN A CEMETERY UNSATURATED SOIL ZONE. Geosciences = Geociências. 2022 Oct; 41(2): 517–525. Publisher Full Text\n\nVOSviewer - Visualizing scientific landscapes. VOSviewer; 2023. Reference Source\n\nBruno PPG: Seismic Exploration Methods for Structural Studies and for Active Fault Characterization: A Review. Appl. Sci. 2023 Aug; 13(16): 9473. Publisher Full Text\n\nLiao J, Wu K, Xiong L, et al.: Dissolution mechanism of a deep-buried sandstone reservoir in a deep water area: A case study from Baiyun Sag, Zhujiang River (Pearl River) Mouth Basin. Acta Oceanol. Sin. 2023; 42(3): 151–166. Publisher Full Text\n\nPasseri DL, Hagen SC, Medeiros SC, et al.: The dynamic effects of sea level rise on low-gradient coastal landscapes: A review. Earth’s Future. 2015 Jun; 3(6): 159–181. Publisher Full Text\n\nKapper KL, Bautista F, Goguitchaishvili A, et al.: The use and misuse of magnetic methods to monitor environmental pollution in urban areas. Bol. Soc. Geol. Mex. 2020; 72(1). Publisher Full Text\n\nDay-Lewis FD, Slater LD, Robinson J, et al.: An overview of geophysical technologies appropriate for characterization and monitoring at fractured-rock sites. J. Environ. Manag. 2017 Dec; 204: 709–720. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVaudelet P, Schmutz M, Pessel M, et al.: Mapping of contaminant plumes with geoelectrical methods. A case study in urban context. J. Appl. Geophys. 2011 Dec; 75(4): 738–751. Publisher Full Text\n\nGuireli Netto L, Barbosa AM, Galli VL, et al.: Application of invasive and non-invasive methods of geo-environmental investigation for determination of the contamination behavior by organic compounds. J. Appl. Geophys. 2020 Jul; 178: 104049. Publisher Full Text"
}
|
[
{
"id": "263217",
"date": "07 May 2024",
"name": "Joseph Omeiza Alao",
"expertise": [
"Reviewer Expertise Applied GeophysicsGephysics specialize in environmental and geotechnical geophysics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Editor, I have completed reviewing the manuscript. I am sorry for doing this later. The paper by Darul et al., titled “Geophysics for the environment in Indonesia” contains two basic approaches to modelling surface and groundwater. The paper is an OPINION ARTICLE that provides an important topic bordering society. However, the work requires more generation information in the introductory part, especially the application of Geophysics in engineering and also discusses the importance of geophysics as a professional course and education to widen the global scientific interest. So, the author should strive to improve on that. In addition, the work is good for publication as an opinion article.\n\nIntroduction: the introduction is not rich enough and needs more relevant information, especially the general part. The author can read the following articles to improve the manuscript quality if he/she finds them relevant [https://doi.org/10.1007/s11600-023-01096-3; https://doi.org/10.1007/s10064-023-03076-9; https://doi.org/10.1007/s40328-022-00398-0; https://doi.org/10.1016/j.scitotenv.2023.165469; DOI: 10.26855/oajrcap.2021.12.001]. Please, note that you are not in any way compelled or forced to cite these articles. Figure: figures 1 and 2 are blunt, please provide a better figure with high resolution. Under “Limitations of geophysical approaches at a practical level in Indonesia” provide more information on funding, inadequate experts, and lack of poor geophysical experimental sites like Geophysical Test Site (GTS) to train young geophysicists in the country. You can obtain information in the suggested articles above. Conclusion: please, present a more accurate, sharp, and pointed conclusion. Refinances: the reference styles are good but not consistent.\n\nBest wishes Thank.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": []
},
{
"id": "263222",
"date": "07 May 2024",
"name": "Pradeep Naik",
"expertise": [
"Reviewer Expertise Hydrogeology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 virtues of geophysics with a focus on potential environmental applications in Indonesia. The paper is written well, but is too repetitive, meaning the same matters are being conveyed in different ways.\nFew specific observations are as follows:\nAbstract: Too long; may be substantially reduced. Only one paragraph. Keywords: Words mentioned in the title may be avoided. Introduction: May include the next section, i.e. the general applications, as well.\n\nThe general applications of geophysics: May be merged into the Intro. The first sentence is too long. Does not match with the sentences authors have generally framed. May be broken into pieces for clarity. The first para has tense problem. Please use present tense as used elsewhere for coherence purposes. The applications of geophysics in Indonesia: The colour shades and sizes in Fig. 1 may be explained in the legend. The captions ‘geophysics methods’ may be stated as ‘geophysical methods'. Abbreviations may be expanded in the legend. Exploring the potential of geophysics in solving environmental challenges: Are these 40 articles included the 582 articles of the previous section? Same observations in Fig. 2 as well. Limitations: Only limitations may be described in this section. Solutions, if any, to overcome these challenges may be described, if authors desire to. In fact, how these challenges were overcome by the workers in different parts of the world would really be an interesting thing to read about. The advantages of geophysical techniques mentioned in the initial portion of this section may be included in the Intro or the previous sections. Remarks: This section may be termed as ‘Conclusions’ or ‘Concluding Remarks’. But it again repeats the same matters stated in the Intro. Are the listed issues not addressed presently by the geophysical workers world-wide? Or, the authors limit their remarks to Indonesia only – may be clarified.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-131
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https://f1000research.com/articles/13-130/v1
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22 Feb 24
|
{
"type": "Case Study",
"title": "Exploring secondary school learners' perceptions of the effectiveness of SOLEs pedagogy in physical sciences as a component of STEM",
"authors": [
"Hodi Tsamago",
"Anass Bayaga",
"Hodi Tsamago"
],
"abstract": "The exploratory case study design investigated learners’ perceptions of the effectiveness of self-organized learning environments (SOLEs) pedagogy in physical sciences. Fifteen Grade 11 learners were selected using a purposive sampling method and underwent SOLEs pedagogy instruction for four weeks before they were interviewed through focus group interviews (FGIs). Data were analyzed thematically using the coding method, which was conducted on a sentence-by-sentence basis. The results indicated that learners have a positive perception towards SOLEs pedagogy, because they believe that SOLEs pedagogy enables them to link their classroom experiences with their real-life experiences; it provides them (learners) with an opportunity to simulate practical experiments in the physical sciences; it provides them with multiple channels for receiving information; it enables them to learn collaboratively and limits their reliance on the teacher. Consequently, this study’s findings justify the implementation of SOLEs pedagogy in science education at the secondary school level.",
"keywords": [
"SOLEs pedagogy",
"metacognitive skills",
"attitude",
"technology integration",
"collaborative learning"
],
"content": "Introduction\n\nThe South African government regards the studying of physical sciences, which is part of science, technology, engineering, and mathematics (STEM), as paramount because it fosters scientific literacy, which allows learners to gain the necessary 21st-century skills that will enable them to be part of the broader economy. The government has been encouraging more learners to enroll in physical sciences and other STEM subjects that will assist them in gaining the necessary expertise and being part of the ever-changing world of technology. Unfortunately, the situation in many physical science classrooms is two-pronged. On the one hand, learners have difficulties learning physical science concepts, as indicated by their underperformance in tests and examinations (DBE, 2020; HSRC, 2020; Mullis et al., 2020). On the other hand, teachers are facing problems in making physical sciences and thus STEM content accessible to most learners, as they continue to employ futile teacher-centered pedagogies in the teaching of physical sciences, which do not yield positive outcomes (Geduld, 2019; Kibirige et al., 2014). The reasons for teachers to continue using teacher-centered pedagogies include lack of appropriate learner-centered pedagogy, limited pedagogical strategies, lack of training in the use of new innovative teaching strategies, and the belief that learners are incapable of learning on their own (Alami, 2016; Ben-David & Orion, 2012; Chilanda, 2020; Geduld, 2019; Organization for Economic Co-operation and Development (OECD), 2017). For example, Geduld (2019) found that although teachers believe that metacognitive skills are important for the successful learning of physical sciences, they fail to integrate metacognitive skills in their teaching because of a lack of the requisite skills to employ them. Similarly, Kibirige et al. (2014) found that teachers who lack expertise in employing learner-centered pedagogies resort to the use of futile teacher-centered pedagogies that do not yield positive results.\n\nEvidently, how learners perceive a pedagogy employed in the physical sciences classroom affects their acquisition of a conceptual understanding of physical sciences (Dulosa et al., 2019; Mitra et al., 2016). Karuru et al. (2021) further asserted that learners’ perceptions of their learning affect their performance on the subject. This implies that if learners perceive the way they are taught physical sciences as understandable, they will perform well. For example, Kihwele (2014) postulates that learners perceive STEM, and thus physical sciences, as only meant for those with a high level of understanding and who are part of a particular category of people. However, UNICEF (2020) found that every learner has the potential to learn STEM.\n\nHowever, the problem is the lack of suitable pedagogies that teachers can employ in the teaching of STEM. For example, National Senior Certificate (NSC) examination results show that learners continue to perform poorly in physical sciences, which indicates that the pedagogies teachers continue to employ do not assist learners. Instead, these pedagogical strategies make learners run away from the subject and cause the number of those who enroll to study this subject to decrease. Hence, teachers need to employ innovative pedagogical strategies that put learners at the center of the learning process (Department of Basic Education (DBE), 2020; Kibirige & Lehong, 2016; McLoughlin & Loch, 2012). Finally, literature prescribes 21st-century technology-based pedagogical strategies as an effective way of improving learners’ perception of science learning (Al Zakwani & Walker-Gleaves, 2019; Bleeker, 2019). For example, Bleeker (2019) recommends that no child should be left behind in terms of technology integration in the learning of physical sciences, thus STEM, including learners with special educational needs (LSENS). Additionally, Al Zakwani and Walker-Gleaves (2019) found that technology-based pedagogies such as self-organized learning environments (SOLEs) have the potential to improve the learning outcomes as they optimize learner autonomy and motivation to learn.\n\nSOLEs pedagogy (teaching approach) is a technology-based model of learning in which learners self-organize themselves in groups and search for information using any technological device that can connect to the Internet with little teacher (Dolan et al., 2013). SOLEs can take the form of project-based or problem-based learning; however, SOLEs pedagogy as implemented in this study took the form of problem-based learning, as was the case with the original “hole in the wall” experiment. The difference is that this study used cellphones instead of desktops as technological devices to connect to the Internet. The original “hole-in-the-wall” experiment performed in India, by Seguta Mitra in 1999, used computers connected to the internet put in the hole and allowed children to demonstrate their ability to learn with computers without the assistance of the teacher (Dolan et al., 2013), discovered that learners can learn ahead of time.\n\nFor example, studies on the effectiveness of SOLEs pedagogy have found that it has the potential to improve learners’ performance in the classroom (Ghavifekr & Rosdy, 2015; Mitra & Dangwal, 2010; Mitra & Crawley, 2014). However, there is little information in the literature on how learners perceive SOLEs pedagogy (Al Zakwani and Walker-Gleaves 2019). It is essential to uncover learners’ perception of SOLEs pedagogy, as the perception of pedagogy affects learners’ attitudes towards the subject and, as a result, their performance. Hence, the current study explores learners’ perceptions of using (SOLEs) pedagogy as a technology-based pedagogy in teaching physical sciences. It is noteworthy that the perception of pedagogy is directly linked to learners’ satisfaction with pedagogy, which influences their learning outcomes (Acharya et al., 2019; Patandean & Baharuddin, 2017).\n\nTechnology integration in the teaching of physical sciences can improve educational outcomes (Fernández-Batanero et al., 2021). However, Akcil et al. (2021) found that technology integration is not easily implementable because of available pedagogies. For example, Bayaga (2021) stated that teacher-training institutions prepare teachers inadequately to use Information Communication Technology (ICT) in teaching and learning. Bayaga’s (2021) outcry is echoed by Mathevula and Uwizeyimana (2014), who discovered that available technology integration training (inset and pre-service) does not affect teachers’ classroom practice. In addition, Harrell and Bynum (2018) linked inadequate teacher training to technology integration, with their (teachers) low self-efficacy and negative attitudes towards the use of technology in the classroom. Combining these ideas, it can be argued that SOLEs pedagogy can bring relief to teachers by assisting them in integrating technology into their physical sciences classrooms. According to Mitra and Crawley (2014), SOLEs pedagogy can be defined as a pedagogy that allows learners to independently find solutions to problems and acquire new information on the subject matter using the Internet. Mitra and Crawley found that working in groups during SOLEs interventions improves learners’ conceptual understanding more than working individually. In addition, secondary school learners’ motivation to learn physical sciences is affected by their level of participation in their learning (Tasgin & Tunc, 2018). Thus, SOLEs pedagogy, when correctly employed, can reaffirm Vygotsky’s view that effective science learning occurs when learners construct meaning by socially interacting with their peers (Bruner, 1998; Vygotsky, 1969). SOLEs pedagogy works because it complies with all the requirements of constructivist learning and uses technology to bring the world into science classrooms. The model initially used a personal computer (PC) as a technological resource that learners could access the Internet. Currently, technological devices such as smartphones, computers, tablets, and laptops that can be connected to the Internet can be used as the primary learner-teacher support material (LTSM) to facilitate SOLEs pedagogy.\n\nDevices such as smartphones are now accessible to most learners in South Africa, including those from rural and disadvantaged backgrounds in South Africa (Ngesi et al., 2018). SOLEs pedagogy requires that learners be given questions/problems on the content they have not yet dealt with in the classroom, and devices they can use to access the Internet to investigate solutions to the problems. Using a literature review, Heslup (2018) argued that SOLEs pedagogy minimizes learners’ dependence on their teacher, which improves their ability to learn beyond their typical classroom. Minimizing learners’ dependence on their teachers also improves their autonomy in learning, which is imperative in physical sciences teaching and learning (Lai, 2011). This is why the SOLEs pedagogy is effective across all demographic groups (Mitra & Dangwal, 2017).\n\nTherefore, it is imperative to investigate learners’ perceptions of pedagogical strategy before it can be implemented in the classroom for two reasons. The first reason is that learners’ perceptions of teachers’ pedagogical strategies have a dire effect on the (learners) achievement of their learning goals (Susanto et al., 2019; Tudor et al., 2010). The second reason is based on Rogers’ (2003) theory of the diffusion of innovation, which indicates that it is vital to investigate learners’ perceptions of pedagogy in order to understand their attitudes, which can affect their learning outcomes. Hence, the current study employed an exploratory qualitative method to investigate physical sciences learners’ perception of SOLEs pedagogy after they were exposed to it for four weeks.\n\nThe current study aimed to investigate the perceptions and views of physical sciences learners on the effectiveness of pedagogy of self-organized learning environments (SOLEs) in the classroom. To achieve this objective, the following question was formulated.\n\n• What are learners’ views on the effectiveness of SOLEs pedagogy in physical sciences?\n\nThe current study is underpinned by two metacognitive skills development theories, which assert that learning occurs during social interaction with others and when learners learn collaboratively, and sociological theory, which explains how people receive innovative programs or strategies such as SOLEs pedagogy. Metacognitive skills development theories are Zimmerman’s (2000) self-regulated learning theory and Hadwin et al.’s (2011) socially shared regulated learning model. Zimmerman’s theory postulates that for metacognitive skills to develop, learners need to be allowed to plan, choose the strategy for implementing their plans, put the plan into action, evaluate the plan, and start over again. The development of metacognitive skills is directly linked to the development of conceptual understanding (Panchu et al., 2016). The current study argues that SOLEs pedagogy can develop learners’ metacognitive skills and, as a result, learners’ conceptual understanding, as it affords learners the opportunity to learn independently and collaboratively. Similarly, socially shared regulated learning (SSRL) helps develop learners’ metacognitive skills. SSRL explains the regulation of learning in social and interactive environments, such as ICT and computer-based learning environments (Winne & Hadwin, 1998). SSRL fits well with models that integrate self-regulated learning (SRL) and metacognition in a collaborative learning environment that integrates technology. Studies have found that technology can positively affect learners’ attitudes towards science education, as it improves their problem-solving abilities (Andrew et al., 2018; Baglama & Yucesoy, 2019; Tatlı et al., 2019). For example, Andrew et al. (2018) found that pedagogy incorporating traditional teaching and technology integration is useful in improving learners’ metacognitive knowledge, which is important for self-regulation and problem-solving. Pedagogy that allows learners to self-regulate their learning and share their innovations through social interaction can affect learners’ perceptions. As a result, pedagogy that can encourage socially shared regulated learning can develop learners’ perceptions towards learning physical sciences and, as such, can improve their conceptual understanding. This is best explained by the following diagram.\n\nThe model indicates that, for any new innovation, the perceptions of the affected people need to be investigated to determine whether the program is well received. If it is not well received, there needs to be some modification; thereafter, the perceptions of the participants on the modified program should be investigated until the program is positively received. SOLEs pedagogy is a program based on Zimmerman and Hardwin’s metacognitive development theories, which were investigated to determine how it was perceived. This is in line with the theory of diffusion of innovation, which can be defined as the processes by which communication of innovation among participants in a social system occurs through certain channels (Rogers, 2003), as the study investigated the perception of stakeholders (learners) on a new program or strategy (SOLEs pedagogy). The theory underscores the importance of investigating stakeholders’ views, as they adversely affect a program’s success. Hence, the current study investigated learners’ perceptions of the effectiveness of SOLEs pedagogy in physical sciences, so that if learners have unfavorable attitudes towards the pedagogy, they can be reconstructed until they receive a positive perception.\n\n\nMethods\n\nThe current study employed qualitative methods to investigate learners’ perceptions of the effectiveness of SOLEs pedagogy in physical sciences. Qualitative research methods were chosen because they allow researchers to deeply explore the matter by interviewing participants (Boyce & Neale, 2006). In addition, qualitative study methods allowed the researcher to acquire a deeper understanding of the learners’ perceptions of SOLEs pedagogy, which would be impossible through statistical analysis as in quantitative study methods. The main research question was: What are physical sciences learners’ perceptions of the effectiveness of SOLEs pedagogy in their learning of the subject? Responding to the research question required learners to be initially exposed to SOLEs pedagogy instruction (program) and later interviewed to capture their views about the effects of the pedagogy and how it assisted them.\n\nAs a case study, the current study population was all Grade 11 enrolled to study physical sciences in Capricorn district (South Africa, Limpopo province) in 2019. There were 120 (69 urban and 51 rural) participants selected through a purposive sampling method, considering whether they studied physical sciences and are in Grade 11 class. All 120 participants were exposed to SOLEs pedagogy instructions for four weeks, and only 15 were subjected to focus group interviews. The researcher purposively selected participants for the focus group interviews, considering their capabilities to provide valuable information.\n\nThis study investigated learners’ perceptions of the effectiveness of SOLEs pedagogy in the physical sciences classroom. This study employed focus group interviews (FGIs) to gather data from 15 participants. FGIs were used because they allow the collection of richer data, as it facilitates robust discussions where participants are free to express themselves, as opposed to individual interviews where the participant may feel intimidated (Then, Rankin, & Ali, 2014). Data collection commenced after the learners were exposed to SOLEs pedagogy instruction for four weeks.\n\nData were analyzed thematically using coding methods. Thematic analysis was chosen because it allows the researcher to analyze qualitative data without pre-determined criteria and allows the researcher to generate real codes (Cohen et al., 2007). The coding methods included open, axial, and selective coding. Open coding (on a sentence-by-sentence basis) involves reading the transcripts to identify the main themes and give them codes. Open coding was followed by axial coding, in which connections between discrete excerpts were drawn (Yin, 2014) . Finally, axial coding was followed by selective coding, where codes were grouped under themes.\n\n\nResults\n\nThe following table indicates the demographical information of the participants.\n\nAs shown in Table 1, 15 public school students were interviewed. Of the 15 participants, 5 (2 boys and 3 girls) were from rural schools and 10 (4 boys and 6 girls) were from urban schools (Tsamago & Bayaga, 2023). There were no learners with special educational needs, and they were all from the same ethnic group.\n\nDuring data analysis, three themes emerged:\n\nThe data from the FGIs revealed that learners opined that SOLEs pedagogy assists them in linking what they learn in the physical sciences classroom to their outside classroom experience. This view was expressed by participant Speaker (SP) 3, who, when asked, “How did the use of technology during lessons assist you in learning physical sciences?” responded by indicating the following.\n\nI realised that, technology nehh … e kgona go dira gore re bone gore seo re ithutang sona ka phaphušing se sepelelana le bophelo ka kakaretšo, se se ra gore thuto ga e felele ka phaphušing feela. I love how technology gives us the information beyond classroom.\n\nThis can be translated to: “I realised that technology shows us that whatever we learn in the classroom is related to life in general. This means education is not confined to the classroom only. I love how technology gives us the information beyond the classroom.” The main objective of education is to empower learners to develop problem-solving skills for solving real-life problems. However, learners struggle to relate what they learn in the classroom to what they are confronted with outside the classroom. The quote by participant SP3 validates the use of SOLEs pedagogy, as learners are of the view that it enables them to relate what they learn in the classroom to what they are confronted with outside the classroom environment. Participant SP3 has said that it resonates well with what has been reported by Bransford et al. (2001) that learners come to class with preconceptions about how the world works, and the new information learned may become superficial if their initial understanding is not reinforced.\n\nConsequently, they are likely to revert to their preconceptions when tackling real-life problems. Therefore, SOLEs pedagogy can assist learners in improving their metacognitive skills and mold their views to align with those of scientists, as it minimizes the prevalence of cognitive dissonance by linking learners’ classroom experiences with their out-of-the-classroom experiences. This was also echoed by participant SP5, who responded:\n\nI never thought … nna gore … that frictional force in class is the same frictional force that stops me from slipping when I walk (laughs), ja … I mean … neither did I know gore a car can roll over because of inertia; this is so…so … so amazing. When we searched the information from the internet I realised that everything we learn in class does exist even outside of classroom, ja … I’m fascinated.\n\nThis can be translated to: \"I never thought that frictional force in class is the same frictional force that stops me from slipping when I walk. Neither did I know that a car can roll over because of inertia; this is so amazing. When we searched the information from the internet I realised that, everything we learn in class exists outside of the classroom. So, yes, I am fascinated.\" Accordingly, participant SP5 was of the view that SOLEs pedagogy allows the learning of physical sciences to continue beyond the usual science classroom. SOLEs pedagogy enables learners to continue learning even when not in the classroom. The findings indicate that participants are of the view that SOLEs pedagogy can arouse learners’ curiosity and improve their focus on learning the physical sciences.\n\nIn essence, SOLEs pedagogy fosters self-regulated learning, as it encourages learners to learn “anywhere and anytime,” according to participant SP5. If learners can relate what they learn in the classroom to their outside classroom experiences, their motivation to learn, attitude towards the subject, and interest in learning the subject will improve. This was pointed out by SP10, who stated:\n\nI enjoyed using technology because it made me realise what real science is all about, and it helped me relate what I read in the textbook with what I saw outside, and ja … it saves a lot of time, you know …\n\nIn many cases, learners spend a lot of time trying to learn concepts that do not make sense to them, and as a result, they give up, lose interest, and become demotivated. Participant SP5 validates the use of the SOLEs pedagogy as it motivates learners to learn and improve their interest in the subject; it further allows them to understand concepts quicker, saving them much time when learning. This participant (SP10) attested to having enjoyed learning physical sciences through the SOLEs pedagogy as it allowed them to link what they learned in the classroom with their day-to-day experiences outside the classroom. It also helped them make sense of what was written in their textbook rather than having to memorize the facts directly without proper understanding. In essence, the use of SOLEs pedagogy is well received by learners, as it allows them to explore the applications of scientific knowledge in real life through access to the Internet.\n\nThe current study’s findings show that learners are of the view that SOLEs pedagogy is effective in assisting them in their learning of physical sciences because the technology usage that goes with the pedagogy enables them (learners) to perform practical work (experiments), even if schools do not have adequate physical sciences resources. It emerged from the data that learners think that SOLEs pedagogy provides them with an opportunity to simulate physical sciences practical experiments and processes, as indicated by participants (SP3), who stated that:\n\nNtwe re trying go e bolela like ke gore technology gives us an idea ya dilo tšeo e leng gore like ge e le gore ke tlo dira experiment a ke nore yona yela re e dirileng, e kgona go refa idea ya gore ehh okay smell sebile so o wa kwišiša and le nna ge e dira mo ka humana smell e se sona ke tla tseba gore there is something wrong yeo eleng gore ke edirile which means I have to back again ke e dire gape ke e dire correctly gore ke kgone go humana exactly what diresults tša ntwela di mpoditšeng tšona. In our activity we could understand the concepts of forces easily because of the use of internet. This is the most effective way of learning physical sciences and I can still remember most of the things.\n\nThis can be translated to: \"What we are trying to indicate is that technology gives us an idea of what to expect if we experiment physically. It gives us an idea if our experiment is working because we would have seen that on the internet and would know our expectations. We would know what kind of smell must come out; if it does not become as expected, we will know that something was wrong, and we will have to go back and re-do the experiment correctly to get the expected results. In our activity we could understand the concepts of forces easily because of the use of internet. This is the most effective way of learning physical sciences and I can still remember most of the things.” The evidence emerging from the current study indicates that learners are of the view that SOLEs pedagogy can enhance the reflective aspect of metacognitive skills, as they attested that it enabled them to self-check their mistakes when performing an experiment that they first watched on the internet. According to participant SP3, the SOLEs pedagogy enabled them to develop implicit ways of self-checking, as using the Internet helped them anticipate the results of the experiment, and if they did not go according to the plan, what they had watched on the Internet would enable them to self-check and conduct error analysis. Since SOLEs pedagogy requires the use of the Internet, learners can see experiments performed on the Internet before they physically perform them to verify their findings. If there are mistakes, they will be able to correct themselves. In such instances, simulations provide an alternative way to help learners learn about the experiment by watching demonstrations on the Internet, which is better than not having any experiment at all, as participant SP3 attests.\n\nTechnology helps where there is no equipment … You can watch the demonstration [simulation] from the screen … we can’t wait for the government to bring us equipment, … We need to have alternatives that we can use to perform experiments instead of having to wait for the department. If they do not give us equipment what is going to happen? Are we going to wait and say we don’t have equipment … to use? This indicates that participant SP3 is of the view that SOLEs pedagogy allows learners to continue with their learning, even when the government has not supplied the school with equipment. The study’s findings show that simulating experiments is better than having no experiments.\n\nAgain, learners think that SOLEs pedagogy is effective in assisting them in the learning of physical sciences because it can enable them to select materials relevant to their learning style, which in turn assists them in becoming aware of their effective learning style. The finding was supported by participant SP5 who stated that: “Technology (internet) helps us if our lab does not have apparatus we can download videos and watch to improve our understanding. This is what we have done and I found it to be more effective.” Furthermore, SOLEs pedagogy can close the gap caused by the lack of standard science equipment in South African schools, as participant SP5 believed that it enabled them to perform physical science experiments on the Internet, supported by participant SP3, who stated that:\n\nTechnology e tsena mo eleng gore ga gona di equipment like safety gloves or maybe digoggles technology e a thuša. O kgona go bona ge batho ba le ba di dira. Nagana ge nke re re re a e dira mo sekolong re sena dilo tšeoweng, so se se ka ba dangerous. So we can’t wait for the government gore e tla re tlišetša equipment, you can’t wait for that period. Are you going to leave out that experiment? No! Re lebelela di alternatives tšeo eleng gore re ka di usa gore re dire like those experiments instead of having to wait ra re hehe department ga se e refe di apparatus re tlano ema re ka se dire experiment because of ga rena those other things to use.\n\nThis can be translated to: \"Technology proves to be more important where there is no equipment like safety gloves or maybe goggles. You can watch the demonstration on the screen. Imagine if we were forced to perform other experiments without equipment, this could be dangerous. So we can’t wait for the government to bring us equipment; you can’t wait for that period. Are you going to leave out that experiment? No! We need to have alternatives that we can use to perform experiments instead of having to wait for the department; if they do not give us equipment what is going to happen? Are we going to wait and say we don’t have the equipment because we don’t have those other things to use?\"\n\nParticipants acknowledged that practical work (experiments) is important when studying the physical sciences. Learners agreed that practical work is essential for understanding physical sciences, but the evidence from the current study indicates that most schools in South Africa (including those in the current study) lack adequate equipment for practical work. This leads to science teaching focusing more on theory, which is not good for understanding physical science concepts. However, using SOLEs pedagogy can provide learners with an opportunity to experience practical work in physical sciences online, which can address the lack of proper physical science equipment.\n\nThe participants of the current study believed that SOLEs pedagogy could provide multiple channels for receiving information, accelerating the cognitive process. For example, participant SP8 was of the view that it is easier to remember things that you see on video than to read about them in the textbook. When asked, ‘How did the use of technology during lessons assist you in learning physical sciences?’ Participant (SP8) responded by stating that:\n\nEng because bana ba kgona go gopola le dilo tše ba di boning ka pela than theory like gore motho a dule fase a bale ke ntwengwe mara ge a kgonne go e bona o tlo gopola ka pela and o tlo improva mo go learning science. Le rena after seeing how forces work by using our cellphones re kgonne go di kwišiša. Technology e ya thuša.\n\nThis can be translated as: \"Yes, learners can easily remember things they saw rather than relying on theory. Sometimes to sit down and read about things you did not see is a problem than what you saw. If you have seen it, you will remember it quickly, and you will be able to improve in learning science. Even in our case, after seeing how forces work by using our cell phones, we were able to understand. Technology helps a lot.\" This participant believed that it is easy to remember what you have seen, and if the method used to teach physical sciences allows learners to see what they are learning, it will likely positively impact their learning. As a result, the participants believed that SOLEs pedagogy could assist learners in learning through multiple channels.\n\nIt emerged from the data that the use of technology in SOLEs pedagogy assists learners in gathering information quicker and saving time. Moreover, by simply using a small technological device, SOLEs pedagogy expands learners’ sources of information and allows easy access. This was revealed by Participant SP7:\n\nYes, cause of ge re dira di ehh di practicals ehh re di bona thwii go di cell phones tša rena ka di videos and re ba le idea ya gore go nyakega eng so e dira dilo dibe symbol there is no need ya gore re hlwe re nyakana le di resource yes.\n\nThis can be translated to: \"Yes, when we perform practical work, we can do it live on our cell phone screens through videos, and we develop an idea of what is happening, and it makes things easy, and there will be no need to look for resources.\" For example, SOLEs pedagogy can allow learners to explore any physical science experiment or phenomenon through online simulations and videos, which assist learners in learning through multiple senses. This implies that SOLEs pedagogy improved learners’ metacognitive skills and enabled them to learn independently by accessing information from the Internet, which developed conceptual understanding.\n\n\nDiscussion\n\nThe current study’s findings indicate that participants believe that SOLEs pedagogy enables them to link what they learn in the classroom to their real-life experiences. This finding resonates well with Shunk (1996) and Hadzigeorgiou and Schulz (2017), who deduced an interplay between learners’ ability to relate what they learn in the classroom to their real-life experiences and the development of metacognitive skills and conceptual understanding. The researcher of the current study argues that SOLEs pedagogy can improve learners’ metacognitive skills because it enables them to relate what they have learned in their physical sciences classroom to their real-life experiences and further enhance their conceptual understanding. Furthermore, the current study’s findings indicate that learners enjoyed being taught through SOLEs pedagogy, as it enabled them to relate what they learned in the physical sciences classroom to their real-life experiences. It appears that learning through SOLEs pedagogy improves learners’ learning motivation and interest.\n\nOn the other hand, Hadwin et al.’s (2011) socially shared regulated learning (SSRL) model et al. directly links motivation and interest in learning the physical sciences with the development of metacognitive skills. This assertion is in line with Wang et al. (2021), who found a positive correlation between metacognition and interest in learning. It can, therefore, be argued that SOLEs pedagogy improved learners’ metacognitive skills because it motivated them to learn.\n\nIn addition, it was found that participants were of the view that SOLEs pedagogy provides them with multiple channels for receiving information. According to constructivism, if learners receive information through multiple channels, the cognition rate improves as cognition overload (experienced if only one channel is used) is reduced (Dagar & Yadav, 2016). Mthethwa et al. (2020) made a similar inference by deducing that the use of technology-enhanced pedagogy in the teaching of science and mathematics can improve learners’ conceptual understanding because it engages learners’ visual and auditory channels, which in turn improves the rate at which the comprehension process (conversion of information from short-to long-term memory) occurs. Finally, the researcher of the current study argues that SOLEs pedagogy can improve learners’ metacognitive skills and conceptual understanding of physical sciences because it accelerates their cognition process, as reported by the participants in the current study.\n\nFurthermore, the findings of this study indicate that SOLEs pedagogy accustomed learners to cooperative learning, which is one of the grounds for metacognitive development, according to Hadwin et al.’s (2011) SSRL model. Group work allowed learners to verbalize and share their thinking processes with their peers. This is consistent with White’s (2017) view that learning in groups forces learners to think about their thinking process when performing a learning task. Learners had the opportunity to express different views on the learning task, and by referring to additional information on the internet, they eventually reached a common ground. This provides evidence that supports the SSRL model proposed by Hadwin et al. (2011). According to White (2017), verbalizing thinking in a group setting provides opportunities for learners to learn metacognitive skills. In addition, it allows learners to learn about their peers’ weaknesses and robust points, which contributes to developing the empathy aspect of metacognitive skills.\n\nA review of the literature on the state of physical sciences education in South African schools points to a severe shortage of textbooks, leading to more learners relying on their teachers for information (Du Plessis & Mestry, 2019; John, 2019). This shortage limits the learners’ access to learning opportunities. The current study’s findings are significant because they revealed that SOLEs pedagogy limits learners’ reliance on the teacher while maximizing their autonomy as it expands their sources of information. Access to the Internet allows learners to search for and download various digital learning resources (such as audio and video clips, textbooks, worksheets, and images) and access up-to-date information beyond the textbook (OECD, 2017). This promotes self-regulated learning (SRL), as learners no longer rely on their teachers to learn physical sciences; however, teachers should supervise learners to ensure that Internet access is used for academic purposes only.\n\nThe findings of the current study indicate that SOLEs pedagogy is effective in assisting them in effectively acquiring physical science knowledge because it enables them to find a connection between their classroom experiences and real-life experiences and improves their learning motivation, interest, and attitude. Furthermore, SOLEs pedagogy limits learners’ reliance on teachers, which fosters learner autonomy. This inference is in line with constructivist and self-regulated learning theories, which assert that the learning process must be autonomous and learners must work in groups during the learning process. Thus, it can be concluded that learners have a favorable attitude towards SOLEs pedagogy.\n\n\nConclusions\n\nThe study concludes that learners perceive SOLEs pedagogy as effective in physical sciences learning, as a component of STEM, because it enables them to link their classroom experiences with their real-life experiences; it provides them (learners) with an opportunity to simulate practical experiments in the physical sciences; it provides them with multiple channels for receiving information; it enables them to learn collaboratively, which limits their reliance on the teacher. Hence, this conclusion justifies the use of SOLEs pedagogy in STEM education at the secondary school level.\n\nThe current study revealed that learners have a positive attitude towards SOLEs pedagogy, which could result in the development of their metacognitive skills and conceptual understanding, which was previously poorly understood. This revelation indicates that the current study has significantly contributed to understanding the impact that SOLEs pedagogy can have on science education, if implemented. Regarding contributions to practice, the current study has proven that SOLEs pedagogy can be employed in the physical sciences classroom at the secondary school level because learners have a positive attitude towards it (SOLEs pedagogy). The current study adds to previous studies that used SOLEs pedagogy because they (previous studies) did not investigate learners’ perceptions of the effectiveness of SOLEs pedagogy in the classroom. The current study found that learners have a positive attitude towards SOLEs pedagogy, which implies that it can yield positive results if implemented in the physical sciences classroom. In addition, the current study recommends further investigation of how teachers perceive SOLEs pedagogy in the teaching of physical sciences and other related subjects.",
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Publisher Full Text\n\nThen KL, Rankin JA, Ali E: Focus group research: What is it and how can it be used? The Canadian Journal of Cardiovascular Nursing. 2014; 24(1): 16–22. PubMed Abstract\n\nTsamago H, Bayaga A: Exploring secondary school learners’ perceptions of the effectiveness of SOLEs pedagogy in Physical sciences as component of STEM [version 1; peer review 1 approved]. [Dataset]. F1000Research 20223.docx. figshare. 2023. Publisher Full Text\n\nTudor J, Penlington R, McDowell PL: Perceptions and their influences on approaches to learning. Engineering Education. 2010; 5(2): 69–79. Publisher Full Text\n\nUNICEF: Goal area 2: Every child learns. International Journal of Humanities and Social Sciences. 2020; 2(15): 123–129.\n\nVygotsky L: Thought and language. MIT Press; 1969.\n\nWang M-T, Binning KR, Toro JD, et al.: Skill, thrill, and will: The role of metacognition, interest, and self-control in predicting student engagement in mathematics learning over time. Child Development. 2021; 92: 1369–1387. Publisher Full Text\n\nWhite JP: The impact of graphic organizer use on the metacognitive skills of ten senior high school students in an English IV British literature class at Seaside High School (Doctoral dissertation). Scribbr.2017. Reference Source\n\nWinne PH, Hadwin AF: Studying as self-regulated learning.Hacker DJ, Dunlosky J, Graesser AC, editors. Metacognition in educational theory and practice.Lawrence Erlbaum; 1998; pp. 277–304.\n\nYin RK: Case study research: Design and methods. 5th ed.Sage Publications; 2014.\n\nZimmerman C: The development of scientific reasoning skills. Dev. Rev. 2000; 20: 99–149. Publisher Full Text"
}
|
[
{
"id": "277288",
"date": "12 Jun 2024",
"name": "Sugata Mitra",
"expertise": [
"Reviewer Expertise Children's education",
"Minimally Invasive Education",
"Self-Organised Learning Environments."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper addresses learner's perception of Self-Organised Learning Environments (SOLEs). This work is important as such perception of pedagogy has not, to my knowledge, been attempted before. There are a few points in the manuscript that need attention: 1. The work of CSIR (Gush, Cambridge and Smith), South Africa, on the original hole in the wall experiments need a mention. See, for example K gush,et.al.,2004 Ref 1 2. \"Sugata\" has been misspelled as \"Seguta\" in the introduction. 3. Figure 1 needs more explanation. This is provided in the text but should be included in very brief in the diagram. \"Rogers\" does not mean anything unless there is some explanation of what part of his work is being referred to. 4. The actual method used in the SOLEs needs more elaboration. Particularly, how do learners using mobile phones share what they are seeing with others? This collaborative viewing is crucial for SOLEs.\nThe paper is considered suitable for indexing, subject to the above points being addressed. Further review is not required.\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? 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? Partly",
"responses": []
},
{
"id": "303478",
"date": "24 Jul 2024",
"name": "Anggi Datiatur Rahmat",
"expertise": [
"Reviewer Expertise TPACK Framework",
"Science Education (Physics)",
"Integrated Science",
"Technology in 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\nThis article explores secondary school learners' perceptions of the effectiveness of Self-Organized Learning Environments (SOLEs) pedagogy in teaching physical sciences within STEM education. It addresses an important aspect of STEM education by exploring innovative pedagogical approaches, uses qualitative methodology effectively to understand learner perceptions, and provides rich data. The manuscript is well-written and structured, with a clear presentation and logical flow. However, there are a few points that need attention: 1. Expand Background Section: Include more detailed historical context and examples of past studies on SOLEs. 2. Enhance Practical Utility: Add practical implementation details and guidelines to make the findings more actionable for educators. By addressing these points, the article will be more scientifically sound and useful for a broader audience, including researchers, educators, and practitioners in STEM education.\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? 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? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-130
|
https://f1000research.com/articles/12-981/v1
|
15 Aug 23
|
{
"type": "Research Article",
"title": "Vietnam national competency standards for midwifery: A Delphi study",
"authors": [
"Tung Thanh Le",
"Anh Tuan Truong",
"Thanh Van Vu",
"Ha Thi Viet Tran",
"Huong Thi Thanh Pham",
"Huong Thi Thanh Nguyen",
"Anh Thi Lan Mai",
"Tung Thanh Le",
"Anh Tuan Truong",
"Thanh Van Vu",
"Ha Thi Viet Tran",
"Huong Thi Thanh Pham",
"Huong Thi Thanh Nguyen"
],
"abstract": "Background: After nearly a decade, Vietnam’s basic midwifery competency standards need to be updated to effectively implement midwives, enhance the quality of midwifery human resources to meet the requirements of integration of countries in the region and around the world. This study aims to develop the competency standards for midwifery in Vietnam by using a Delphi process. Methods: The draft midwifery competency standard was initially developed based on a literature review. Midwives and professionals working with midwives completed a two-round Delphi survey to evaluate the relevance of standards of competence on a four-point Likert scale. The criteria with consensus of under 80% were revised and included in the second round. 75 participants were in the first round and 72 participants were in the second round. Phase 3 was led by the Ministry of Health to finalize the consensus on the midwifery competency standards in Vietnam. Results: The research results indicated that midwifery competency was mostly rated as quite relevant or higher (over 80%). Some standards were removed, and some were included in the second round of the Delphi process. The final competency standards were issued with 4 areas (midwifery professional practice; care management; midwifery management; professional development), 11 standards and 44 criteria; along with the general skills of midwifery. Conclusions: The study developed a midwifery competency standard in Vietnam. These competency standards are consistent with the perceptions of the International Confederation of Midwives and the domestic midwifery context. The higher education institutions, employers, policy makers and midwives themselves benefit from this developed midwifery competency standards. Future research needs to be conducted to validate midwifery competency standards in clinical settings for further responses.",
"keywords": [
"Vietnam",
"national competency",
"midwives",
"midwifery competency",
"midwifery management"
],
"content": "Introduction\n\nIn 2014, with the support of the United Nations Population Fund (UNFPA), the Ministry of Health, in collaboration with the Vietnam Midwives Association, developed the National Competency Standard for Midwives in Vietnam to meet the country’s maternal and child health care requirements (Vietnam Ministry of Health, 2015). Through the competency standards, training institutions have developed midwifery training programs, contributing to enhancing the quality of midwifery human resources. However, after nearly a decade, the National Competency Standard for Midwives in Vietnam needs to be reviewed and supplemented to effectively enhance the quality of midwifery and meet the needs of midwives requirements for the integration of countries in the region and around the world. In addition, the International Confederation of Midwives (ICM) has recommended that competencies need to be updated continuously and in a timely manner as the evidence on health and clinical practice has evolved rapidly and health care needs to change (ICM, 2018).\n\nIn Vietnam, Midwifery is a profession with a long history of development with the first training institution being the Indochina Midwifery School. Then, there were many other institutions across Vietnam training midwifery, including intermediate and college levels. In 2013, there were some universities that started training midwives at university level. Since then, most of the trainers involved in the training are university level midwifery lecturers and a part of the specialties are obstetrics and paediatrics. In 2014, the Vietnam Midwifery Association released a set of National Competency Standards for Midwives in Vietnam, marking an important milestone in the practice and training of midwifery in Vietnam.\n\nThe ICM has a mission to support the Association of Midwives and develop the midwifery profession globally by supporting midwives to work independently to give the best care to pregnant women and their families. They support safe childbirth and improve the reproductive health of women, babies and families. ICM has worked closely with other international organizations to develop and continuously update the international midwifery competency standards, in which the latest competency standards were updated in 2019 (ICM, 2019).\n\nThe ICM defines competence as the knowledge, skills and behaviors required by midwives to practice safely in any setting (ICM, 2013, 2017, 2018a, 2018b, 2023). Some other countries have defined the concept of midwifery competence as representing the quality of practice, moderate knowledge, skills and attitudes in midwifery practice (Yin et al., 2018; The Midwives Council of Hong Kong, 2010; Midwifery Council of New Zealand, 2016). The process of developing competency standards for Vietnamese midwives in 2014 is also based on these definitions of competence, to describe the professional standards set by the profession for members and society.\n\nThe National Midwifery Competency Standards has been reviewed and supplemented for a variety of purposes including disseminating to clients, professions and others the competency standards they can expect from a bachelor or midwife. At the same time, competency standards also serve to inform the approval or recognition process of midwifery training programs; Determining the conditions for midwifery practice for people who have graduated from midwifery in Vietnam; Evaluation of qualified midwives who need to demonstrate their continuing qualifications for their current position; Allowing midwives to define their continuing professional development plan; creating conditions for Vietnam and the world to recognize each other in the midwifery discipline (Vietnam Ministry of Health, 2015).\n\nMidwifery national competency standards include the core competencies required to fulfill the role of a midwife. Therefore, it is important to clearly define midwifery professional competence in order to develop training programs for midwifery qualifications and ultimately to improve midwifery quality. In fact, there are still challenges in implementing the basic competency standards of midwives in 2014, as well as difficulties in developing training programs based on the competency standards. Vietnam’s midwifery industry currently has two main levels of univeristy and college midwifery. Although, there is still a large number of intermediate level midwives in lower-level midwifery care facilities, according to Circular No. 26/2015/TTLT-BYT-BNV stipulating codes and standards of professional titles of nursing, midwifery and medical technicians. The document will lead to gradually eliminate midwifery titles at intermediate level by 2025 (ACNM, 2014). In addition, the national exam for certification of midwifery practice has been included in the law draft on Medical Examination and Treatment. Accordingly, all midwives after graduating from training institutions who want to practice their profession at medical facilities must pass a national exam to be granted a practicing certificate. In order to be able to have an accurate assessment tool for midwifery practice competency, the midwifery professional competencies need to be standardized and legally recognized (UNFPA, 2014).\n\nTherefore, it is very important to review and supplement Vietnam’s midwifery national competency standards. Firstly, midwifery competency standards were reviewed and supplemented after nearly a decade of application to training management agencies to develop training competencies for midwifery in Vietnam. The training institutions develop appropriate graduate outcomes, curriculum, methods and teaching contents. Second, this is the basis for managers to develop competencies for certification, recruitment, appointment, promotion of midwives, planning and creating opportunities for midwives to be trained continuously or self-trained while working in medical facilities. Consequently, the quality of health care for women and children in Vietnam will be improved. Third, midwifery national competency standards are the basis for midwives at each level to develop their competency in the working process. This study aimed to develop the national competency standards for midwifery in Vietnam.\n\n\nMethods\n\nThe study used a multi-stage modified Delphi process (de Loë et al., 2016) to reach a national agreement on competency standards for midwives in Vietnam. The study was managed by Vietnam Ministry of Health and the Nam Dinh University of Nursing and in constant consultation with the Steering Committee and the Professional Committee. The research was conducted at Nam Dinh University of Nursing, which is the first institution providing the bachelor of midwifery program in Vietnam. The Ministry of Health convened Nam Dinh University of Nursing and representatives from regulatory agencies, the healthcare universities/colleges, obstetrics and gynecology hospitals, departments, Midwifery Association and the other professional associations in Vietnam. The research was conducted from October 2020 to December 2021.\n\nPhase 1: phase 1 consisted of a systematic review to synthesize the initial set of competency standards. A literature review was conducted to identify the Vietnamese and international literature on midwifery competency standards. The review included material from established databases such as the Ministry of Health, ICM, CINAHL, Sciencedirect and Medline as well as conference presentations, national and international publications and reports from regulatory and professional bodies. Keywords included in the literature were “midwifery competency standards”; “bachelor of midwifery”; “professional competency standards”. The literature resources were identified according to the following criteria: (1) midwifery population; (2) the competency standards and the elements were examined. The PRISMA Flow Diagram was used to guide the search (Thanh Le et al., 2023).\n\nInitial searches captured 275 records across all databases. Duplicated references were removed, and 105 citations remained for screening. Finally, 15 documents that met the inclusion criteria were included, in which there were 7 research studies and 8 midwifery competency standards. The most relevant literature found are listed as Basic competency standards of Vietnamese midwives (2014); Vietnam Nursing Basic Competency Standard (2012); Basic midwifery competency standards (ICM, 2019); Singapore Midwifery Core Competency Standards (2018); Australian Midwifery Competency Standards (Australia, 2007). Based on the systematic review results, the research team proposed the first draft of Vietnamese midwifery competency. This draft of competency with 110 statements were included in the survey of phase 2. The process was presented in Figure 1.\n\nPhase 2: A modified Delphi survey with 2 rounds was conducted to reach a consensus on proposed Vietnam Midwifery Competencies. The purposive sampling method was widely used to collect data through official correspondence to hospitals, universities/college training midwives, and Vietnamese midwifery associations. The university coordinated with the Ministry of Health to send dispatches to hospitals, universities, colleges and associations related to midwifery. The dispatches asked each institution to appoint a leader to participate in the survey. There were 75 managers, policy makers, presidents of midwifery associations, head midwives and midwives in obstetric departments and hospitals. This data collection process was carried out in different settings representing different regions of Vietnam. Using this approach, midwives from urban, regional and rural settings, as well as from public and private institutions, were included in the survey. This shows the diversity of the participants. Participants rated importance of each competency statement using a four-point Likert scale (1 = not relevant at all; 4 = relevant) and gave feedback/suggestions in text. The participants were asked to rate the questionnaires and send back to Nam Dinh University of Nursing by the dispatches. The round 1 survey was conducted from October to December, 2020. At the end of the first round of the surveys, the research team met to review the data and revise the statements. The round 1 results provided the competency set with 75 statements, which were included in round 2. The round 2 survey was from February to April 2021 providing the set of competencies with 72 statements. For each round, the team retained the midwifery competencies that reached a consensus level of 80% or more of the participants.\n\nStep 3: the phase to finalize the consensus on the competency standards. The Ministry of Health sent an invitation to attend the workshop on assessment of midwifery competency standards, attached with the expected midwifery competency standards to relevant institutions. The “Developing Midwifery Competency Standards in Vietnam” workshop was conducted within four hours at Nam Dinh University of Nursing under the chairmanship of MOH in June 2021. Participants were representatives from associations related to midwives such as Vietnam Midwifery Association; managers of midwifery training units, hospitals and policy makers. Each institution appointed a representative to attend the workshop and give feedback on the expected midwifery competency standards. The workshop was organized with different representatives from different regions of Vietnam. In particular, the input of regulatory agencies was essential for the common goal of ensuring the consistency of national midwifery competency standards. At the workshop, the Ministry of Health and the manager boards of Nam Dinh University of Nursing presented on importance of midwifery competency standards, the results of Delphi phase and proposed midwifery competency standards. Representatives of the institutions gave feedback and discussed on each criteria in the proposed midwifery competency standards. The Steering Committee and the Professional Committee followed the minutes of the workshop on comments and suggestions of the participants to propose the final version of the national midwifery competency standards. The workshop was a strategy for consultation and feedback on the draft text and for informing the various authorities of the process and results.\n\nThe research proposal was approved by the Ethical Board of Nam Dinh University of Nursing (#2539/GCN-HĐĐĐ). All study participants were clearly informed about the purpose of the study, the data collection procedure, possible inconveniences, and the right to participate in the study. The research team respects the participants’ decisions, ensuring anonymity and confidentiality of information. This study was conducted without physical assessment or intervention.\n\nQualitative and quantitative data analysis methods were used to analyze the data obtained from the survey and workshop consultation. Quantitative data were analyzed using a statistical software program. Statistical significance level was set at p < 0.05. Descriptive statistics will include frequencies, percentages, mean for categorical variables, and standard deviation for continuous variables. The comments/suggestions about the competency statements were converted into a single report by the research assistant for the study team members to review and discuss.\n\n\nResults\n\nThe study participants in Rounds I and II had similar characteristics in terms of their years of work, education, current position, and workplace. The majority of participants in both rounds had worked for 10-19 years, followed by those who had worked for 1-9 years and those who had worked for 20-29 years. In terms of education, most participants had an undergraduate degree, followed by those with a master’s degree and then those with a diploma/certificate or doctorate. Most of the participants in both rounds worked as midwives, followed by doctors and managers. The most common workplace was an obstetrics and gynecology hospital, followed by an obstetrics and gynecology department and a midwifery education institution. The participants’ characteristics were presented in Table 1. The full dataset can be found under Underlying data (Thanh Le et al., 2023).\n\nThe research results indicated that midwifery competency was mostly rated as quite relevant or higher (over 80%). The statements in competency standards on effective communication competency, comprehensive, consistent and continuous quality of care and maintaining a safe environment through the use of quality assurance and risk management strategies were the highest rating (97.8%). Some participants rated disagree and quite disagree, in which the criterion related to the midwife’s communication competency was rated at only 70.5%. Participants provided comments on the text that it is necessary to adjust some criteria of the competency for future feasibility of evaluating these competencies for the midwife. At the same time, the criteria should ensure vertical and horizontal connectivity. Some participants said that the criteria should only be given as a guideline framework to ensure feasibility and relevance in case there are changes to other related guiding documents.\n\nThe final set of competency standards for Vietnamese midwifery was structured into 4 areas, 11 standards and 43 criteria; along with the general skills of midwifery. Each area represents a basic role of the midwifery. The competency standards was divided into 4 areas of (1) Midwifery Professional Practice; (2) Care management; (3) Midwifery management; (4) Professional development. Each standard represents a section of the field and covers a task for the midwifery. Furthermore, the midwifery competency benchmark provides a set of general skills that midwives should be able to perform.\n\nBased on the results shown in Table 2, midwives are expected to have a thorough understanding of their positions, roles, functions, and duties. They were able to perform midwifery interventions according to standards and guidelines while practicing within laws, policies, and regulations. Midwives maintained complete and clear care documentation and records and ensured their physical, cognitive, psychological, and emotional well-being.\n\nMidwives also demonstrated obligation and responsibility for care within the scope of practice and level of competence, following the required competency of midwives while respecting the values, customs, beliefs, and spiritual practices of the individual, family, and community of customers.\n\nCare management is also an essential aspect of midwifery competency standards. Midwives could communicate clearly through verbal/nonverbal means in writing and other means of communication. They developed a midwifery care plan in collaboration with the healthcare team, client, and family while conducting a comprehensive, systematic assessment. Midwives also implemented and documented planned midwifery care, evaluated and adjusted the plan of care, and demonstrated critical thinking, problem-solving, and clinical reasoning in decision-making.\n\nMidwives were efficient in applying evidence-based practice, participating in care decision-making and coordination, collaborating with clients, families, and colleagues to provide a continuum of healthcare services, and creating a safe care environment. The results demonstrated that they also engaged in continuous quality assurance and improvement activities; assigned, monitored, and supervised the work of other supportive care workers; and implemented continuous quality improvement in care delivery.\n\nMidwifery management is an important aspect of the midwifery competency standards. Midwives demonstrated the ability to make appropriate management decisions; apply positive thinking skills to problem-solving; implement and critique new initiatives and changing processes; seek help and advice to manage tasks effectively; collect, analyze, and use incident data and trends to improve care and service strategies; and effectively use and manage resources. They also applied measures and guidelines in safe midwifery practice, participated in projects and initiatives to improve quality and ensure safety, analyzed possible risks in the working environment, and supported and cooperated with care team members in risk management. They maintained and enhanced their professional roles; participated in projects and research; applied evidence-based midwifery practice; corrected deficiencies in knowledge, skills, and continuous learning; contributed to policy development; demonstrated an understanding of the basic knowledge of scientific research processes; and participated in research and innovative technical improvement.\n\n\nDiscussion\n\nThis study develops a set of midwifery competency standards in Vietnam. The basic midwifery competency standards issued by MOH in 2014 were developed based on the ICM’s midwifery competency standards updated in 2013 while this competency benchmark is constantly updated and verified by practice. Moreover, the Vietnamese midwifery competency standards are structured according to the common template of the Singapore midwifery core competency standards and the International Basic Midwifery Competency Standard (ICM) to meet the requirements of regional and international integration (ICM, 2018; Singapore Nursing Board, 2018). Research results showed that the midwifery competency standards, after being developed through the Delphi process changed significantly. Most of the participants found this competency standard to be relevant and important for Vietnamese midwives.\n\nResearch results indicated that the set of midwifery national competency standards was built to reflect the up-to-date criteria and competency standards, which presented the characteristics of midwifery care according to the reproductive process of a person’s life cycle. That is, midwives in midwifery care serve individuals of all ages and form long-term, ongoing relationships with clients. This element of continuity of midwifery care is reflected throughout the competency statements and helps define the scope of midwifery practice in this particular role. In addition, the areas of competence and statements identified in this study may serve as a framework to guide midwifery roles and responsibilities. Bäck et al. (2017) developed a Swedish midwifery competency standards that described the competence and role of midwives, not limited to, care for the reproductive periods of the clients, vaccinations and immunizations, care for prenatal women, during labor and postpartum, infant development, breastfeeding, medications, reproductive health education and, follow-up on admission, PAP smear, maintainance of health policies and procedures (Bäck, Hildingsson, Sjöqvist, Karlström, 2017). The competency standards covers four key areas of care including midwifery practice in compliance with regulations and professional ethics, care management, midwifery management and career development in which there are 11 standards and 43 criteria. Moreover, the competency standards also reflect general skills, which is a set of skills that midwives perform in their career. Along with midwifery professional competencies, general skills define the requirements for applying for a midwifery license in Vietnam. Included in this document are 112 skills common to midwives covering seven key skill groups in the care of women through the reproductive and neonatal periods.\n\nThe competency standards identified may serve as a guiding framework for assessing midwifery performance and contributions and assist researchers and other stakeholders (e.g. employers) to generate evidence on the effectiveness of midwives’ contribution to the prevention and reduction of maternal and child mortality and the broader reproductive health care system. To date, there is still limited research to support the assessment of midwives’ contributions to the reproductive health care system, particularly regarding the impact of midwives on clients, providers system-level results. Nove et al. (2021) performed a study on low- and middle-income populations estimating the potential impact of midwives in reducing maternal and neonatal mortality.\n\nDue to the growing number of midwives in the reproductive health care workforce, recent research in this area suggested a need for undergraduate programs that specifically target this role (Gavine et al., 2019). The role of competency standards is to establish minimum requirements for training and to assess midwifery skills during midwifery training. These competency-based training institutions are the basis for developing specific curricula to enhance the readiness of midwifery students before entering the clinical practice environment. This set of competency standards also supports policy makers; provides a list of essential skills that a bachelor of midwifery needs to perform when practicing midwifery; provides guidelines for developing an assessment plan for the midwifery practice certification exam. Well-defined national competencies may also aid in this role integration by assisting with staff recruitment through the development of job descriptions, interview guides, and the use of identification tools, guidelines as well as other relevant literature (Mharapara et al., 2022). A standardized set of competencies may serve as a framework for developing a well-defined scope of practice (Hastings-Tolsma et al., 2018). This may enable midwives to practice to the best of their abilities in a reproductive healthcare environment, optimize the performance of their interdisciplinary team, and deliver high-quality midwifery care services to their clients throughout their life (Chakraborty et al., 2023).\n\nThis study has several limitations. The views of all midwives and those involved in midwives in Vietnam cannot be fully expressed during the review and supplementation process, only designated units will be selected to participate. Recognizing this limitation, the research team made every effort to ensure that the most representative midwifery units were selected to participate. The consultation team will also select those that will make an important contribution related to midwifery such as midwifery unit leaders in educational and practice roles nationally and in policy and expertise. The time frame of the study is limited so the stage of confirming the competency standards by observation of midwifery practice will not be carried out which also means that the competency standards cannot be verified in practice settings. However, the participants in the survey and consultation process are those who work in a range of units closely related to midwives such as the midwifery association, the ministry of health, midwifery training schools and state and private maternity hospitals.\n\nThe additional review also resulted in participant reports on the applicability of the competency benchmarks that helped policymakers recognize the importance of next steps to further strengthen the applicability of competency standards and to ensure that they are relevant to midwives working in different settings across the country. For example, some participants responded that it was not possible to use or meet all competency standards due to organizational and systemic barriers. Incorporation of competency standards into employment contracts, position description and evaluating the results of the job performance will support the acquisition of more competency standards, and at the same time provide a toolkit to assess midwifery clinical practice. Developing a framework of midwifery training program based on competency standards is urgent after the promulgation of this competency standard.",
"appendix": "Data availability\n\nFigshare: Vietnam National Competency Standards for Midwifery: A Delphi Study. https://doi.org/10.6084/m9.figshare.23502300.v2 (Thanh Le et al., 2023).\n\nThis project contains the following underlying data:\n\n- Underlying Data.xlsx\n\n\n\n- PRISMA 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\nACNM: Core competencies for basic midwifery practice 2012.2014.\n\nBäck L, Hildingsson I, Sjöqvist C, et al.: Developing competence and confidence in midwifery-focus groups with Swedish midwives. Women Birth. 2017 Feb; 30(1): e32–e38. Epub 2016 Aug 22. PubMed Abstract | Publisher Full Text\n\nChakraborty S, Saggurti N, Adanu R, et al.: Validating midwifery professionals’ scope of practice and competency: A multi-country study comparing national data to international standards. PLoS One. 2023 May 25; 18(5): e0286310. Publisher Full Text\n\nde Loë RC , Melnychuk N, Murray D, et al.: Advancing the state of policy Delphi practice: A systematic review evaluating methodological evolution, innovation, and opportunities. Technol. Forecast. Soc. Change. 2016; 104: 78–88. Publisher Full Text\n\nGavine A, MacGillivray S, McConville F, et al.: Pre-service and in-service education and training for maternal and newborn care providers in low- and middle-income countries: an evidence review and gap analysis. Midwifery. 2019; 78: 104–113. Publisher Full Text\n\nHastings-Tolsma M, Foster SW, Brucker MC, et al.: Nature and scope of certified nurse-midwifery practice: A workforce study. J. Clin. Nurs. 2018 Nov; 27(21-22): 4000–4017. PubMed Abstract | Publisher Full Text | Free Full Text\n\nICM: Essential competencies for basic midwifery practice 2010 revised 2013.2013.\n\nThe Midwives Council of Hong Kong: Core competencies for registered midwives. Hong Kong.2010.\n\nInternational Confederation of Midwives: ICM Position Statements. [accessed 24 March 2023]. Reference Source\n\nInternational Confederation of Midwives: ICM International Definition of the Midwife.2017. [accessed 24 March 2023]. Reference Source\n\nInternational Confederation of Midwives: ICM Definitions. [accessed 20 December 2018a]. Reference Source\n\nInternational Confederation of Midwives: ICM Policy and Practice. [accessed 20 December 2018b]. Reference Source\n\nInternational Confederation of Midwives: Essential Competencies for Midwifery Practice.2019. Reference Source\n\nMharapara TL, Staniland N, Stadler M, et al.: Drivers of job satisfaction in midwifery-A work design approach. Women Birth. 2022 Jul; 35(4): e348–e355. Epub 2021 Jul 24. PubMed Abstract | Publisher Full Text\n\nMidwifery Council of New Zealand: The Association; Wellington.2016. [cited 2018 Jan 15]. Maintaining Competence. Reference Source\n\nNove A, Friberg IK, de Bernis L , et al.: Potential impact of midwives in preventing and reducing maternal and neonatal mortality and stillbirths: a Lives Saved Tool modelling study. Lancet Glob. Health. 2021 Jan; 9(1): e24–e32. Epub 2020 Dec 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSingapore Nursing Board: Core competencies of registered midwife.2018. [accessed from December 2021]. Reference Source\n\nThanh Le T, Tuan Truong A, Van Vu T, et al.: Vietnam National Competency Standards for Midwifery: A Delphi Study. Dataset. figshare. 2023. Publisher Full Text\n\nVietnam Ministry of Health: Basic Competency Standards of Vietnamese Nurses.2015. [accessed 24 March 2023]. Reference Source\n\nYin Y, Li J, Lu H, et al.: Essential competencies for three grades of midwives in China. Int. J. Nurs. Sci. 2018 Jan 11; 5(1): 18–23. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUNFPA: The state of the World’s midwifery 2014.2014; pp. 22–35."
}
|
[
{
"id": "199885",
"date": "07 Sep 2023",
"name": "Christine Catling",
"expertise": [
"Reviewer Expertise Midwifery"
],
"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 review this paper.\nThere are a few queries and suggestions for improvement – mostly to enhance clarity. Overall the paper could do with an English-language edit.\np. 3, second paragraph – consider using ‘education’ instead of ‘training’ – as midwives are highly educated, and we have moved away from ‘training’. Its unclear as to why, if there were national standards released in 2014, why do there appear to be two levels of midwifery education in Vietnam? Could you add a paragraph to explain the current education pathways for midwives in Vietnam – to make this clearer for the reader?\nThird paragraph – the sentence ‘They support safe childbirth and improve the reproductive health of women, babies and families’ – this reads as though babies and families have ‘reproductive health’ so I suggest deleting ‘reproductive’.\nFourth paragraph – its unclear why you allude to ‘moderate knowledge’ in the second sentence?\nFifth paragraph – the first sentence is unclear – please rewrite.\nSixth paragraph – typo for the word ‘university’. The last sentence states that midwifery professional competencies need to be standardized and legally recognised – but it appears there were national competency standards released in 2014 – were these not legally recognised? If not – please make this clearer.\nPage 4, top of page – it is stated that midwives can be ‘self-trained’ – please elaborate – perhaps you mean that they are educated within the workplace (as opposed to a university/college)?\nMethods – first paragraph. Could it be made clearer that the organisations listed were selected to participate in the Delphi process? How/why were these organisations selected? What are the ‘other professional organisations’ that are alluded to here?\nSecond paragraph – last sentence – could you check that you have the correct reference for the PRISMA diagram? This appears wrong. See here PRISMA (prisma-statement.org)\nThird paragraph – this explains the search process but the inclusion and exclusion criteria have not been stated clearly, please do this. The second half of this paragraph states the relevant literature that was found which informed the second survey to progress the Delphi process. There is a jump from identifying the literature to the creation of the survey – how were the 110 competency statements chosen from the literature by the research team? That process needs more depth of reporting here.\nFourth paragraph. It is stated that round 1 resulted in 75 statements and round 2 resulted in 72 statements – which 3 statements were deleted and why? Did they not reach the 80% consensus?\nAlso – in the abstract it is mentioned that there were 75 participants in round 1 and 72 in round 2 – are these similarity in numbers (to your numbers of statements) just a coincidence – or has there been a mis-reporting here?\nFig 1 – there are two asterisks in one of the boxes but no legend included that explain them. Why are the ‘Reports assessed for eligibility recorded as ‘7+8’? Also the boxes to the right of the first column of boxes appears to report a higher number of articles than the box on the left – this is not the usual way of reporting included/excluded papers in a PRISMA. Similarly – there is repetition in the way the duplicates are reported in this figure (repeated three times), and usually the boxes just contain numbers and concise reasons why articles are excluded, but do not include the article in-text citations themselves. Please look at examples from other authors to gain clarity on the best way to use PRISMA diagrams and re-write.\nEthical considerations paragraph. It is unclear why the last sentence is there – regarding physical assessment or intervention.\nResults – can it be made clearer that the participants had worked in midwifery/reproductive health? At the moment it reads that they had just ‘worked’ for a certain length of time – but unclear in what capacity.\np. 7 first paragraph – there are many sentences in this paragraph that are unclear, eg ‘..ensure vertical and horizontal connectivity’ – this is unclear. The sentence about participants providing comments – can you give an example?\nThird paragraph – last sentence – did the midwives ensure their own physical etc. wellbeing or do you mean that of the women they care for? Please re-write for clarity.\nPage 7 needs to be clearer in general – as many small paragraphs could be amalgamated.\np. 9 second from last paragraph – the second from last sentence here needs qualifying and a reference given. The last sentence mentions a study by Nove et al – more information about this study is necessary for clarity here.\nIn the middle of the last paragraph on p. 9 – you mention a ‘bachelor of midwifery’ – do you mean a ‘bachelor of midwifery graduate’?\nP. 10 – the first paragraph needs to be changed to the past tense.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-981
|
https://f1000research.com/articles/11-961/v1
|
19 Aug 22
|
{
"type": "Opinion Article",
"title": "‘Science by consensus’ impedes scientific creativity and progress: An alternative to funding biomedical research",
"authors": [
"Nejat Düzgüneş"
],
"abstract": "The very low success rates of grant applications to the National Institutes of Health (NIH) and the National Science Foundation (NSF) are highly detrimental to the progress of science and the careers of scientists. The peer review process that evaluates proposals has been claimed arbitrarily to be the best there is. This consensus system, however, has never been evaluated scientifically against an alternative. Here we delineate the 15 major problems with the peer review process, and challenge the Science Advisor to the President, and the leadership of NIH, NSF, and the U.S. Academy of Sciences to refute each of these criticisms. We call for the implementation of more equitable alternatives that will not constrain the progress of science. We propose a system that will fund 80,000 principal investigators, including young scientists, with just half the current NIH budget, three-fold more than the current number of grants, and that will forego the cumbersome, expensive, and counterproductive peer review stage. Further, we propose that the success of the two methods over 5–10 years be compared scientifically.",
"keywords": [
"Peer review",
"grant applications",
"NIH",
"NSF",
"granting agency"
],
"content": "Introduction\n\nThe success rate for National Institutes of Health (NIH) grants is currently 20% (NIH Report, 2022). The funding rate at the National Science Foundation (NSF) was 26% in 2021 (National Science Foundation, 2022). The Gates Foundation does not even release its grant success rate information. In 2009 and 2010, NIH received more than 20,000 applications for its Challenge Grants funded through the American Recovery and Reinvestment Act; the success rate was only 4% (NIH Report, 2011). The ‘successful’ projects are those that have been deemed by the consensus of peers to be worthwhile pursuing. Despite these very low percentages that afflict the careers of the great majority of scientists, the peer review system has been claimed to be the best system there is to allocate funding for biomedical research. This consensus system, however, has never been evaluated scientifically against an alternative (Düzgüneş, 1999).\n\nPerhaps the earliest challenge to this system at NIH was made by John McGowan (1992), who was at the time the Director of Extramural Research at the National Institute of Allergy and Infectious Diseases (NIAID). He revealed that proposals to investigate human immunodeficiency virus (HIV) infections of macrophages had been rejected by a study section because “the literature does not support the hypothesis that HIV can grow in macrophages” (McGowan, 1992). And this is untrue! Regrettably, study sections have had too much power over what projects should proceed and which ones should be scrapped. As we have stated before, “such ‘science by consensus’ is unhealthy for the unfettered and productive pursuit of biomedical science” (Düzgüneş, 1999).\n\nWe challenge the Science Advisor to the President, and the leadership of NIH, NSF, and the U.S. National Academy of Sciences to refute each of the following 15 major problems with the current NIH and NSF grant systems. If they cannot, however, and we believe they cannot, we ask these institutions to implement more equitable alternatives that will not constrain the progress of science.\n\nThe NIH Peer Review document describes the mission of NIH to be seeking ‘fundamental knowledge about the nature and behavior of living systems and to apply that knowledge to enhance health, lengthen life, and reduce illness and disability.’ The document claims that the “NIH has a longstanding and time-tested system of peer review to identify the most promising biomedical research” (NIH Peer Review, 2019). During the initial peer review, the scientific merit of a grant application is evaluated by the Scientific Review Group that comprises scientists with relevant expertise in the area. The second review is the responsibility of the National Advisory Councils or Boards that decide on funding a proposal as well as on research priorities. Despite the claims of NIH that this is a longstanding and time-tested review process, it has never been compared scientifically to an alternative system, with respect to scientific productivity and breakthroughs, new therapeutic modalities, patents and its psychological, personal and scientific impact on grant applicants who do not ‘succeed.’\n\nFurthermore, NIH has to process over 80,000 applications a year, utilizing over 25,000 reviewers (NIH Peer Review, 2019).\n\nWe have identified 15 major shortcomings and problems of peer review, which we delineate below.\n\nSome major breakthroughs in biomedical sciences have not been funded by NIH or NSF. There have been several publicized cases of highly important research not being given grant support that have later gone on to be recognized as significant scientific discoveries. Nobel Prize winner Stan Prusiner was not able to obtain NIH funding for studying prions early on in his research. Craig Venter’s proposal to apply his whole-genome sequencing method to sequence a bacterial genome was not funded by NIH, and Nobel Prize winner Leon Cooper’s work on neural networks was not supported by either the NIH or NSF (Bendiscioli, 2019). These examples should have been a history lesson for funding organizations like NIH and NSF (Düzgüneş, 1998).\n\nGrant reviewers are competitors of applicants. If they are truly ‘peers’, grant review panel members are very likely to be competitors of the grant applicant, even if not directly on the subject of the proposal. Thus, they will not be inclined to give the benefit of the doubt to an innovative research proposal that has not already been substantially carried out, particularly when they are struggling to procure funding themselves.\n\nDiscoveries are made before grant awards. The requirement for preliminary data in most grant applications indicates that a scientific discovery is expected to have already been made. Thus, the NIH and NSF may not be funding discoveries, but merely funding “mopping up operations,” in the words of Thomas Kuhn (1962), unless the preliminary data have been generated by a previous grant.\n\nReviewer critiques may be inaccurate, but without the responsibility of making inaccurate statements. Reviewers appear to have a mission to severely criticize applications to be able to weed them out, usually without the requirement to provide a published reference for any criticism. The reviewers are never accountable for their false statements or their scores (Swift, 1996), even though they can derail scientific careers and the advancement of a field of science.\n\nCriticism never ends. Grant applicants may re-apply after revising their proposal to respond to the written critique of the review panel. However, the panel may have new members at this later time and may then have entirely new criticisms. In essence, if the review panel does not want to fund an application it will not fund the application, revealing the whims of the individual reviewers.\n\nEarly career reviewers trained in a narrow area of science often think that valid science is what they are trained in. Thus, they prevent the progress of science that may otherwise produce significant insights or therapeutic approaches to treat diseases. This problem was emphasized by Costello (2010): “… the new generation of grant reviewers judge grant proposals through the myopic lenses of their specialties …. Important ideas and proposals that lie outside the current interest in molecular biology are unlikely to get a credible and knowledgeable review …”\n\nNonscientific, unpublished review criteria. Reviewers tend to use nonscientific criteria when making funding decisions. These include: (i) ‘probability of success’ which would favor projects proposing only incremental advances and no risk-taking; (ii) ‘level of enthusiasm’ which is highly subjective and depends on the reviewer’s mood at the time; and (iii) ‘grantsmanship’ which is essentially rendering grant-writing a game, expecting particular approaches to the project. Implying the nonscientific nature of the evaluation process, the study by Pier et al., (2018) has shown that there is very little agreement between reviewers evaluating the same NIH grant applications.\n\nTranslational projects may require long-term funding. Projects that need additional time and experimentation to translate basic findings and initial discoveries into therapeutics or diagnostics may be considered by reviewers not to be innovative, thereby precluding the rapid development of a product that could diagnose or treat diseases. An example of this problem with NIH peer review is our inability to obtain grant funding since the mid-2000s for our research to develop gene therapy for oral cancer based on our initial discoveries (Neves et al., 2009), despite many applications.\n\nRobbing Peter to pay Paul. Principal investigators may need to channel the funds of an existing grant to produce preliminary data for a new application in a new research area, instead of performing the funded experiments. Thus, experiments described in detail in applications may never be carried out and may essentially have been written only to convince reviewers to fund the grant application. In our view, this practice is unethical. It also demonstrates the absurdity of requiring preliminary data.\n\nPrecious scientist time is wasted on grant applications. Investigators spend a large proportion of their time on grant applications, which necessarily takes them away from their currently funded projects, if they are indeed grant recipients. This is not only counter-productive but may also be time paid by salary support from the granting agency, time that should have been spent on the funded project. A study by Kulage et al. (2015) calculated the cost of preparing a grant application. Principal investigators in this particular field spent between 70 to 162 hours per grant, and research administrators spent 34 to 66 hours, at a cost of USD $4,784 to $13,512. They estimated that, because funding rates are in the range 5–15%, a grant that is eventually funded would cost $72,460–$270,240. They concluded that “less costly and more efficient models of research funding are needed for the sustainability of the nursing profession” (Kulage et al., 2015). Scientists who have spent years in training and in research should be spending their time on scientific research, not on bureaucracy.\n\nDescribing experiments to be performed in five years is unrealistic. The elaborate description of experiments that will be performed three or five years in the future in a grant application contradicts the true nature of scientific research. Thus, for reviewers to expect meticulous descriptions, as if this is how science advances, goes against the true nature of science. Science is driven by the insights of scientists and new discoveries, and often requires immediate changes in approach or direction.\n\nWaiting for grant funding hinders scientific progress. Many fields advance rapidly while investigators are waiting for their grant applications to be evaluated and funded. If the investigator is not funded independently, the project barely moves forward. We cannot afford science to progress at this slow and saltatory rate with the uncertainty in grant funding.\n\nThe human and material cost of NIH peer review. The administration of approximately 80,000 applications and 25,000 reviewers per year (NIH Peer Review, 2019) costs NIH and the research community both money and time that could have been used for actual research. For reviewers, evaluating grant applications is a chore performed for the sake of recognition and prestige, and perhaps to increase their own chances of obtaining funding. This can result in the compromise of objectivity by the reviewers, and even resentment, because of the inordinate amount of time required to complete a review. NIH officials conducting sessions at scientific meetings on how to write grants admit that reviewers may not be able to spend quality time on reviewing applications. Of course, this is never admitted in print, since peer review is supposed to be unquestionably the ideal system for funding science.\n\nNIH scientists do not compete for grant funding. Although NIH provides extramural funds following grueling peer review of grant applications, its own scientists do not have to compete for this type of funding. Thus, NIH itself appears to have recognized the extreme drawbacks of the peer review system, enabling its intramural community to undertake long-term projects with stable funding and large laboratory groups. If peer review is such an indispensable system for funding science, why does NIH not implement this system for its own scientists? Why is the extramural scientific community considered second-rate citizens who must clamor for funding all their lives?\n\nReview panel scores do not predict success. An analysis of 102,740 funded grants has shown that percentile scores generated by NIH review panels for the applications are poor predictors of publication and citation productivity (Fang et al., 2016). Thus, the meticulous scoring process is essentially useless. Arturo Casadevall of Johns Hopkins University and the senior author of this study is quoted as saying “A negative word at the table can often swing the debate. And this is how we allocate research funding in this country” (Johns Hopkins Bloomberg School of Public Health, 2016).\n\nWe have previously proposed simple alternatives to the current peer review system (Düzgüneş, 1999, 2007). This new system would provide continuous and stable funding for 10-year periods to scientists with a track record of solid publications (Düzgüneş, 1999) and to young scientists starting their first independent positions in a university or a research institute (Düzgüneş, 2007). Scientists opting for this mode of funding would merely submit a letter of intent with a one-page broad outline of their research direction. They could be chosen based on criteria including publications, citations and potential impact of their research field, by an international group of both established and young scientists who are not in a position to receive funding from NIH or NSF and are thus not competitors. About half of the NIH extramural funds could still be allocated to the current system of review, especially for projects requiring much larger budgets than what we are proposing below.\n\nUnder this new system, NIH grants to established scientists would be limited to $400,000 per year, and they would be phased in over several years, up to possibly 40,000 grantees. With indirect costs limited to 30%, these grants would cost $20.8 billion per year. Grants to young investigators would be set at $150,000 per year, with the same indirect cost rate. 40,000 such grants would cost NIH $7.8 billion. Thus, at a total cost of $28.6 billion the NIH could fund 80,000 such grants, with minuscule expenses for scientific review. Since the sum is only slightly more than half of the current NIH budget of $52 billion, the rest of the NIH budget could be allocated to about half (about 13,000) the current number of grants. Since this system will be phased in, and the NIH budget is likely to increase within the next five years, there will be no undue burden on the traditional grants and intramural funding. This system will result in the funding of 93,000 principal investigators, instead of the current approximately 26,000.\n\nIt is instructive to note the findings of Azoulay et al. (2011) in comparing Howard Hughes Medical Institute awardees and NIH grant recipients. They reported that “selection into the HHMI investigator program—which rewards long-term success, encourages intellectual experimentation, and provides rich feedback to its appointees—leads to higher levels of breakthrough innovation, compared with NIH funding—which is characterized by short grant cycles, predefined deliverables, and unforgiving renewal policies. Moreover, the magnitudes of these effects are quite large.”\n\nVaesen and Katzav (2017) analyzed the proposal to “distribute available funds equally among all qualified researchers, with no interference from peer review.” Their analysis indicated that “researchers could, on average, maintain current PhD student and Postdoc employment levels, and still have at their disposal a moderate (the U.K.) to considerable (the Netherlands, U.S.) budget for travel and equipment.” Our proposal combines this equitable distribution of funds with the option for scientists undertaking very expensive projects to apply for the remaining highly competitive funds.\n\nThe paradigm shift we are proposing does not end here. The scientific productivity of scientists in these two categories over a five-year and 10-year period will be analyzed, in terms of citations, significant discoveries, and development of therapeutics, per dollar amount spent. As we have indicated previously (Düzgüneş, 1999), “The United States has expended enormous capital in the training of its scientists. The scientific potential of the more than 80 percent of biomedical scientists who are unable to procure grants is too precious a resource to waste.”\n\n\nConclusions\n\nWhile contemplating writing this section, we came across an e-mail sent to potential NIH grant applicants and a separate website aimed at academics and including advice on grant applications as part of an industry aimed at grant applicants for ‘winning’ reviews. The e-mail advertised that their program enabled the participants to ‘successfully write for reviewers’. If an applicant is writing to impress a particular reviewer, the detailed norms, supposed objectivity, and scoring system of NIH peer review becomes questionable. Another website gave the advice to involve the reviewers’ ‘reptilian brain’ and went on to say that the written review of a grant application may come from the rational, cerebral layer of the brain, but the decision on whether the grant is awarded or not actually comes from the most instinctual layer. What has become of the best method to review grant applications?\n\nWith all the problems of peer review of grant applications, we ask the Science Advisor to the President, and the leadership of NIH, NSF, and the U.S. National Academy of Sciences to implement more equitable alternatives that will not constrain the progress of science. A staring point is the very simple and highly cost-effective alternative we have proposed here.\n\n\nData availability\n\nNo data are associated with this article.",
"appendix": "References\n\nAzoulay P, Graff Zivin JS, Manso G: Incentives and creativity: evidence from the academic life sciences. RAND J Economics. 2011; 42(3): 527–554. Publisher Full Text\n\nBendiscioli S: The troubles with peer review for allocating research funding: Funders need to experiment with versions of peer review and decision-making. EMBO Rep. 2019 Dec 5; 20(12): e49472. PubMed Abstract | Publisher Full Text\n\nCostello LC: Perspective: is NIH funding the “best science by the best scientists”? A critique of the NIH R01 research grant review policies. Acad. Med. 2010 May; 85(5): 775–779. Publisher Full Text\n\nDüzgüneş N: History lesson. The Scientist. 1998; 12(6): 8.\n\nDüzgüneş N: Science by consensus: why the NIH grant review system must be changed. The Scientist. 1999; 13(8): 13.\n\nDüzgüneş N: A new paradigm for NIH grants. The Scientist. 2007; 21(8): 24.\n\nFang FC, Bowen A, Casadevall A: NIH peer review percentile scores are poorly predictive of grant productivity. elife. 2016 Feb 16; 5: e13323. PubMed Abstract | Publisher Full Text\n\nJohns Hopkins Bloomberg School of Public Health: Researchers: Peer Review System for Awarding NIH Grants Is Flawed.2016.(accessed August 2, 2022).Reference Source\n\nKuhn TS: The Structure of Scientific Revolutions. Chicago:University of Chicago Press;1962; 264 pp.\n\nKulage KM, Schnall R, Hickey KT, et al.: Time and costs of preparing and submitting an NIH grant application at a school of nursing. Nurs. Outlook. 2015 Nov-Dec; 63(6): 639–649. PubMed Abstract | Publisher Full Text\n\nMcGowan JJ: NIH peer review must change. J. NIH Res. 1992; 4(8).\n\nNational Science Foundation: Funding and support descriptions.2022. (accessed July 4, 2022).Reference Source\n\nNeves S, Faneca H, Bertin S, et al.: Transferrin lipoplex-mediated suicide gene therapy of oral squamous cell carcinoma in an immunocompetent murine model and mechanisms involved in the antitumoral response. Cancer Gene Ther. 2009 Jan; 16(1): 91–101. PubMed Abstract | Publisher Full Text\n\nNIH Peer Review: grants and cooperative agreements:2019. (accessed July 30, 2022).Reference Source\n\nNIH Report: NIH ARRA funding.2010. (accessed July 29, 2022).Reference Source\n\nNIH Report: Success rates: R01-equivalent and research project grants.2022. (accessed July 4, 2022).Reference Source\n\nPier EL, Brauer M, Filut A, et al.: Low agreement among reviewers evaluating the same NIH grant applications. Proc. Natl. Acad. Sci. U. S. A. 2018 Mar 20; 115(12): 2952–2957. PubMed Abstract | Publisher Full Text\n\nSwift M: Innovative research and NIH grant review. J. NIH Res. 1996; 8(12): 18.\n\nVaesen K, Katzav J: How much would each researcher receive if competitive government research funding were distributed equally among researchers? PLoS One. 2017; 12(9): e0183967. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "149008",
"date": "12 Sep 2022",
"name": "Ferric Fang",
"expertise": [
"Reviewer Expertise microbiology",
"molecular biology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis commentary is a critique of the approaches used by the U.S. National Institutes of Health and National Science Foundation to allocate research funding. The commentary lists what it describes as 15 “major problems with the peer review process.” In place of the current system, the commentary suggests awarding funds at fixed levels based on level of applicant experience, a one-page summary of research plans, and publication record. This would reduce administrative costs and substantially increase the number of funded researchers. Few of the issues with grant peer review or the solutions proposed in this commentary are new1,2,3. Nevertheless, the topic remains timely, as low success rates for grant applications persist.\n1. The 20% success rate for NIH grants is a misleading indicator of the current difficulty in obtaining research funding, as success rates count original and resubmitted grants that are received during the same fiscal year as a single submission and combine different types of grants that have variable success rates. A better indicator would be paylines, which are at 10-12% for R01 applications from established investigators at many institutes. Thus, the situation is even more dire than the commentary suggests.\n2. There is some redundancy in the list of “major problems,” which essentially boil down to: (a) peer review is biased and unreliable; (b) the current funding system discourages innovation and long-term projects; (c) too much time is wasted on seeking funding or peer review instead of on research. Another concern, which is not mentioned, is that insufficient levels of public funding for research and development can have a disproportionate impact on female and underrepresented minority researchers4,5,6.\n3. The commentary fails to consider potential disadvantages of the proposed funding strategy. For example, dramatically lowering the bar for research funding might result in an increase in lower quality research, because many labs whose work was not previously found to be sufficiently meritorious to warrant support would now be funded. Some institutions might be tempted to expand the size of their faculties in order to exploit the system, which would increase pressure on the research budget. Half of the extramural budget would be retained for competitive applications involving projects that require larger budgets, but this would essentially intensify competition among larger laboratories, which include some of the most productive research groups. The $400,000 per year budget falls far short of the $750,000 direct funding level that was found to be associated with peak measures of productivity in a 2006 NIH study7, and research costs have only risen since that time, suggesting that most labs would be underfunded under the new scheme.\n4. The comparison of recipients of support from the NIH and Howard Hughes Medical Institute is invalid, because HHMI investigators represent a more highly selected subset of scientists with demonstrated high levels of productivity.\n5. The proposed funding approach shares some features with the approach proposed by Pagano1, which should be cited.\n6. A single paragraph suggests performing a 5- and 10-year formal study to compare the productivity resulting from the current and alternative funding approaches but fails to consider the many methodological challenges in performing such a study.\n7. The commentary repeatedly refers to “we,” but only a single author is listed.\nAlthough I share many of the frustrations expressed in this commentary, I have concerns about the practicality of the proposed solution. Nevertheless, a dialogue on possible ways to address the inadequate current levels of research funding and the shortcomings of grant peer review should continue. This commentary may help to further that dialogue.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": [
{
"c_id": "10593",
"date": "04 Dec 2023",
"name": "Nejat Düzgüneş",
"role": "Author Response",
"response": "Response to Dr. Ferric Fang We thank Dr. Ferric Fang for his thorough review of our paper. We greatly appreciate his conclusion that “Nevertheless, a dialogue on possible ways to address the inadequate current levels of research funding and the shortcomings of grant peer review should continue. This commentary may help to further that dialogue.” Our response to the Reviewer’s individual comments are given below. The changes in the manuscript are indicated by Track Changes. 1. The 20% success rate for NIH grants is a misleading indicator of the current difficulty in obtaining research funding, as success rates count original and resubmitted grants that are received during the same fiscal year as a single submission and combine different types of grants that have variable success rates. A better indicator would be paylines, which are at 10-12% for R01 applications from established investigators at many institutes. Thus, the situation is even more dire than the commentary suggests. We have modified the Introduction to indicate this important point. 2. There is some redundancy in the list of “major problems,” which essentially boil down to: (a) peer review is biased and unreliable; (b) the current funding system discourages innovation and long-term projects; (c) too much time is wasted on seeking funding or peer review instead of on research. Another concern, which is not mentioned, is that insufficient levels of public funding for research and development can have a disproportionate impact on female and underrepresented minority researchers We agree with the reviewer’s summary of the major problems with peer review; but we would prefer to retain the detailed exposé of peer review in our article. Regarding the disproportionate impact on female and minority resesarchers, we believe that our proposed system of grant allocation will alleviate the problem of recognition of the names of applicants by review panelists and the consequent bias against female and minority scientists. We have added a statement to this effect in the revised manuscript. 3. The commentary fails to consider potential disadvantages of the proposed funding strategy. For example, dramatically lowering the bar for research funding might result in an increase in lower quality research, because many labs whose work was not previously found to be sufficiently meritorious to warrant support would now be funded. Some institutions might be tempted to expand the size of their faculties in order to exploit the system, which would increase pressure on the research budget. Half of the extramural budget would be retained for competitive applications involving projects that require larger budgets, but this would essentially intensify competition among larger laboratories, which include some of the most productive research groups. The $400,000 per year budget falls far short of the $750,000 direct funding level that was found to be associated with peak measures of productivity in a 2006 NIH study7, and research costs have only risen since that time, suggesting that most labs would be underfunded under the new scheme. We have added a section in the manuscript that discusses the unintended consequences of the proposed funding strategy, as also requested by Reviewer 2. Lowering the bar for research funding is highly unlikely to result in lower quality research, considering that a project that, for example, scores 10 points lower than the score of the funded grants is not expected to be of that much lower scientific quality. In support of this contention is the current inclination of some funding agencies to use a lottery to fund the grant applications in the top tiers. The reviewer in essence admits that large laboratories obtain the large grants, leaving individual, creative scientists (who may not be good academic politicians), without funds. In the revised manuscript, we have cited the recent case of Nobel Laureate Dr. Katalin Karikó, who could not obtain funding during the period of her groundbreaking work on modified mRNA. The alternative system we are proposing would enable scientists like Dr. Karikó to do their work without having to become a junior member of a large lab. The study reported in Wadman (2010), cited by the reviewer, regarding the high productivity of a lab with funding of $750,000 in direct costs is very misleading. The data presented in the article indicate that the productivity index of a lab with $400,000 is 6, whereas that of a lab with $750,000 is about 7.5. When expressed in terms of productivity per 1000 dollars, however, the $400,000 lab has a productivity index/1000 dollars of 0.015, compared to 0.01 for the lab with higher funding. This is 50% higher productivity per dollar! 4. The comparison of recipients of support from the NIH and Howard Hughes Medical Institute is invalid, because HHMI investigators represent a more highly selected subset of scientists with demonstrated high levels of productivity. We cite this example only to illustrate the advantages of long-term funding, which allows for long-term and risky projects that may not produce results in a 3-year cycle. It is essential for policy-makers to implement such alternatives that will potentially produce results with high impact on understanding and curing diseases. 5. The proposed funding approach shares some features with the approach proposed by Pagano1, which should be cited. We have cited Pagano (2006) regarding the impracticality of describing experiments to be done in 5 years, and the estimated total cost of writing and reviewing grant applications. 6. A single paragraph suggests performing a 5- and 10-year formal study to compare the productivity resulting from the current and alternative funding approaches but fails to consider the many methodological challenges in performing such a study. The reviewer mentions the many methodological challenges in comparing the current and alternative funding approaches, but does not provide any examples. We propose that the international panel that sets the criteria for funding in the alternative system would use similar criteria, but weighted differently to also include patents, significant discoveries with high impact and developed therapeutics. We have also indicated provisions for center grants focusing on a particular disease. 7. The commentary repeatedly refers to “we,” but only a single author is listed. The use of “we” is common practice in scientific writing. We have also cleared this with the Editorial Team at F1000."
}
]
},
{
"id": "200648",
"date": "22 Sep 2023",
"name": "Alejandra Recio-Saucedo",
"expertise": [
"Reviewer Expertise I am Senior Research Fellow at the National Institute for Health and Care Research within the Research on Research group and have conducted research on peer review."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe author presents an interesting and important reflection on a debate that has been going on for quite some time: Is peer review the best mechanism (e.g., in terms of efficiency, fairness, ability to detect ground-breaking ideas, resistance to bias) to make research funding decisions? Given the worldwide use of this mechanism for a number of activities within the research landscape (research funding, academic promotions, publications), peer review has been extensively studied many times with the aim of finding alternative mechanisms to fund research, some of them having been more or less successful than others.\nIn the article the author describes an alternative mechanism to distribute funds which would be relevant to US funding agencies. The potential impact of an efficient alternative to the use of peer review in funding decisions to the research practice is significant. Some of the key points in the article indicate:\nThe author summarises peer review in research funding as ‘cumbersome, expensive, and counterproductive’\n\nThe author presents 15 issues with the current peer review system (science by consensus), including: missing major scientific breakthroughs, unfair/unbiased process driven by competition from researchers working in fields similar/the same to that of the applicant, requirements for preliminary data, lack of accountability for reviewers, poor understanding of the value of trans-disciplinary proposals, poor reviewer agreement, lack of long-term funding, and others.\n\nThe author proposes the alternative to be implemented with a view to evaluate its effect compared to the current peer review system in 5-10 years, also raising a challenge to senior management of major US research funders and leaders.\n\nOverall strengths The article is well structured, interesting, and contributes to the literature on how to increase research efficiencies, decision-making transparency, and impact, which keeps large funding organisations across the world preoccupied and involved in constant efforts for improvement. Reading this led me to think about how I am indeed putting peer review into practice by writing my reflection on this article. At the same time I couldn’t avoid thinking that for all its challenges, peer review is a mechanism that encourages conversation, debate, and advances in scholarship, and how open peer review offers avenues to address some of the challenges associated with peer review discussed by the author.\nAreas for improvement The literature used to illustrate some of the research in peer review is not particularly the most recent. Comprehensive analysis of alternatives to peer review, which covers issues associated to peer review at all stages of funding processes, are available (see for example Peter Kolarz, Anete Vingre, Aaron Vinnik, Antonio Neto, Carlos Vergara, Claudia Obando, Rodriguez, Kalle Nielsen, Laura Sutinen, Review of peer review. Online report. June 2023, https://www.ukri.org/wp-content/uploads/2023/07/UKRI-060723-Review-of-peer-review-Final-report-revs-v2.pdf). Alternatives that substitute peer review at the funding decision stage have been published (e.g., the use of random allocation mechanisms to allocate research funds: Avin S: Mavericks and lotteries. Stud Hist Philos Sci. 2019; 76: 13-23) as well as researchers’ views of some of these approaches (see for example: Liu M, Choy V, Clarke P, Barnett A, et al.: The acceptability of using a lottery to allocate research funding: a survey of applicants.Res Integr Peer Rev. 2020; 5: 3).\nThe description of the alternative is summarised since it refers to previous publications, but the summary misses the key challenges and unintended consequences of implementing the proposed alternative. Identification of unintended consequences will allow for the development of relevant indicators that would generate data/evidence to evaluate the efficiency of the alternative in comparison to the traditional use of peer review. In addition, the alternative proposed does not seem to offer a new way of allocation research funds, as it includes the use of peer review in the way that is currently used (i.e., a panel of peers selects applications based on given criteria).\nI appreciate that the author is not bringing in the positives of peer review to this article and that this strategy adds emphasis to the argument presented, however the narrative highlights the inefficiencies and issues surrounding peer review without acknowledging that no system is likely to be a one-size-fits-all solution to all the challenges surrounding allocation of research funds. Recognising unintended consequences of alternatives is key and recognising the pros of peer review would actually support the alternative proposed (since it utilises peer review).\nIn terms of the alternative proposed, there are some points that would benefit from clarification:\nThe author writes: “Review panel scores do not predict success. An analysis of 102,740 funded grants has shown that percentile scores generated by NIH review panels for the applications are poor predictors of publication and citation productivity (Fang et. al., 2016). Thus, the meticulous scoring process is essentially useless.”\nGiven the broad range of impacts that result from research, and the efforts on responsible use of metrics that are addressing known issues with research culture, the conclusion that a scoring system is not useful based on its ability to predict publication and citation productivity is to some extent reductive. I understand that the author is presenting more issues around peer review, but the emphasis on publication and citation is running counter intuitively to how research culture is evolving.\nThe proposed alternative reads: “They [applicants] could be chosen based on criteria including publications, citations and potential impact of their research field, by an international group of both established and young scientists who are not in a position to receive funding from NIH or NSF and are thus not competitors”\nThe alternative offered here is a variation of peer review, but does not offer a different method to assess funding applications that decreases potential bias in decisions or increase inter-rater agreement of scorers. As written earlier, some aspects of the alternative are not different from the current way of selecting applications based on given criteria. The author suggests that funding decisions be made by “established and young scientists who are not in a position to receive funding”. Finding established and young scientists who cannot receive funding by the selected organisations to conduct the review and/or make funding decisions decreases the pool of potential reviewers. Thus the workload on eligible individuals can become unmanageable very rapidly. Another aspect is training those young scientists in assessing applications for awards/grants that they do not know in depth. There seems to be underlying risks to the proposed alternative that run the risk of affecting Early Career Researchers (ECRs) disproportionately. In addition, the author suggests that funding panels consider potential impact of their research field. How can potential impact be objectively assessed by reviewers/funding panels? How would criteria that takes into account publications and citations be supportive of ECRs whose list of publications would not be competitive compared to senior researchers? Are ECRs inadvertently ineligible to the alternative?\n“Thus, at a total cost of $28.6 billion the NIH could fund 80,000 such grants, with minuscule expenses for scientific review.”\nIf the process to identify reviewers and go through the peer review process for the other half of the NIHR extramural funds remain in place, how will costs decrease to the point that they become negligible?\nOverall, this is a good paper that will benefit from including additional information on key challenges of a large-scale implementation of an alternative to the de facto mechanism used in the distribution/allocation of research funds, which currently also regulates all research and scientific activity (from funding to publication; recruitment and career progression).\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": [
{
"c_id": "10594",
"date": "04 Dec 2023",
"name": "Nejat Düzgüneş",
"role": "Author Response",
"response": "Response to Dr. Recio-Saucedo We thank Dr. Recio-Saucedo for her insightful review of our paper. “At the same time I couldn’t avoid thinking that for all its challenges, peer review is a mechanism that encourages conversation, debate, and advances in scholarship, and how open peer review offers avenues to address some of the challenges associated with peer review discussed by the author.” We agree that “open peer review” has its advantages in encouraging debate on peer review and on advances in research. When individuals are willing to be identified in open peer review, they are less likely to be harshly critical of a scientific proposal. When “peer review” is anonymous, and it does not present published evidence to support the “review”, it can become irresponsible and vicious. “The literature used to illustrate some of the research in peer review is not particularly the most recent. Comprehensive analysis of alternatives to peer review, which covers issues associated to peer review at all stages of funding processes, are available (see for example Peter Kolarz…June 2023,…” We hope it is appreciated that our original article was submitted in August 2022, about 10 months earlier than the analysis mentioned by the Reviewer. Nevertheless, in the revised article, we cite and discuss this paper as well as some of the other publications the Reviewer has suggested. All the revisions in the manuscript are indicated with Track Changes. “The description of the alternative is summarised since it refers to previous publications, but the summary misses the key challenges and unintended consequences of implementing the proposed alternative. Identification of unintended consequences will allow for the development of relevant indicators that would generate data/evidence to evaluate the efficiency of the alternative in comparison to the traditional use of peer review.” The reviewer refers to “the key challenges and unintended consequences of implementing the proposed alternative;” but does not give any examples. Nevertheless, this is an important point. As an unintended consequence, we may think of cases where the track records of a few awardees were misidentified, and they do not generate any significant publications during the 10 years of funding. We would argue, however, that the loss of scientific progress in these circumstances should be compared to the loss of productivity by a laboratory when it cannot renew a 3-year grant and all the trained personnel have to leave the laboratory. By contrast, we could envision a scientist who opted for the novel funding mechanism, but did not make the cutoff of scientific measures used to establish the track record. In this case, the scientist always has the option to apply for the competitive grants. This is the situation with the current peer review system in which about 80% of biomedical scientists find themselves. The frequency of such incidences could be quantified by the granting agency. Whether this analysis could be translated into the “efficiency of the alternate in comparison to the traditional use of peer review” begs the question, “is there any efficiency in the current peer review system?” Our answer would be “no.” We have added a section in the revised paper discussing the possible, but in our view minimal, unintended consequences of our alternative method of funding. “In addition, the alternative proposed does not seem to offer a new way of allocation research funds, as it includes the use of peer review in the way that is currently used (i.e., a panel of peers selects applications based on given criteria).” We stated in our paper that the alternative method of funding scientists would be based on the track record of solid publications of the scientists, a system which we had first proposed in 1999 (Düzgünes ̧, 1999). In 2007, we added the mechanism to provide funding to young scientists starting their first independent positions in a university or a research institute (Düzgünes ̧, 2007). The reviewer interprets the work of the “international group of both established and young scientists who are not in a position to receive funding from NIH or NSF and are thus not competitors” as a form of peer review, possibly because of our use of the word “chosen.” We should have given more details of what determines a “track record of solid publications” We did not intend this group of scientists to be involved in the choice of the scientists to receive funding, but merely to establish the track record criteria. Examples of such criteria are citations, publications, the h-index and the d-index (Di Caro et al., 2012). The international panel of scientists would only be involved in establishing the overall weight of such criteria. We have modified the manuscript to clarify this aspect of our proposed system. “…however the narrative highlights the inefficiencies and issues surrounding peer review without acknowledging that no system is likely to be a one-size-fits-all solution to all the challenges surrounding allocation of research funds. Recognising unintended consequences of alternatives is key and recognising the pros of peer review would actually support the alternative proposed (since it utilises peer review). One of our main contentions here is that a system that has been acclaimed for decades as being the best method to allocate research funding, has not even been tested side-by-side against an alternative, unbiased, and more rational system. As we have delineated above, we have recognized the positive aspect of peer review by proposing that the unequivocally objective criteria for the new system would be discussed and established by an international panel of junior and established scientists. Further pros of peer review may be seen in the review of manuscripts submitted to journals, where errors in the research or in the analysis of data may be identified. Even so, the rejection of breakthrough articles by Karikó and Weissman on mRNA by reputable journals, as reported in the NY Times, is not a plus for the reputation of peer review even for journal articles. In terms of the alternative proposed, there are some points that would benefit from clarification: The author writes: “Review panel scores do not predict success. An analysis of 102,740 funded grants has shown that percentile scores generated by NIH review panels for the applications are poor predictors of publication and citation productivity (Fang et. al., 2016). Thus, the meticulous scoring process is essentially useless.” Given the broad range of impacts that result from research, and the efforts on responsible use of metrics that are addressing known issues with research culture, the conclusion that a scoring system is not useful based on its ability to predict publication and citation productivity is to some extent reductive. I understand that the author is presenting more issues around peer review, but the emphasis on publication and citation is running counter intuitively to how research culture is evolving. We are merely stating the conclusions of Fang et al. (2016), which may be reductive, but they provide strong support for our contention that the supposedly objective scoring system of grant peer review (which, by the way, has not been tested against an alternative system) does not lead to success in terms of measurable quantities, such as publications and citations. The Reviewer has not explained what she means by the thesis that these metrics are “running counter intuitively to how research culture is evolving.” Nevertheless, we believe this issue is outside the scope of our article. The alternative offered here is a variation of peer review, but does not offer a different method to assess funding applications that decreases potential bias in decisions or increase inter-rater agreement of scorers. As written earlier, some aspects of the alternative are not different from the current way of selecting applications based on given criteria. In the revised manuscript, we have clarified the involvement of the international panel of scientists. They do not act as peer reviewers of any grant applicant or application. They merely set the objective criteria by which scientists applying for the new system are ranked, without knowing anything about the scientist, their field of research or the general topic of the research the scientist wishes to pursue. “Finding established and young scientists who cannot receive funding by the selected organisations to conduct the review and/or make funding decisions decreases the pool of potential reviewers.” The majority of scientists live in countries outside of the United States. Although some non-U.S. scientists receive funding from NIH or NSF, their number is extremely limited, and they would not be permitted to participate in the international panel. “Thus the workload on eligible individuals can become unmanageable very rapidly” As we have clarified above and in the revised manuscript, the work of the international panel is minuscule compared to that of the NIH study sections or NSF reviewers. The panel merely determines the criteria of acceptance, such as the percentage weight of the d-index, the number of citations, the number of publications, and other criteria (e.g. the h-index) they may consider to be useful. If such ranking is too rigorous and eliminates too many of the applicants (which would be calculated almost instantaneously), the panel would relax the criteria. “Another aspect is training those young scientists in assessing applications for awards/grants that they do not know in depth.” As we have explained above, no such training would be required of any scientist. Nevertheless, the members of the review panel would have to become familiar with the d-index and the h-index, and perhaps other criteria. “There seems to be underlying risks to the proposed alternative that run the risk of affecting Early Career Researchers (ECRs) disproportionately.” On the contrary, in the scheme we have proposed, early career researchers beyond their post-doctoral training would be given 5-year grants to establish their own researach programs, without spending most of their time applying for grants, and most likely failing. This would help young scientists in obtaining tenure and keeping their laboratories and trained personnel. By contrast, in the current system, the fierce competition with established scientists puts early career researchers at a perilous disadvantage, and force a majority of them to close their labs and move to other universities, research institutions or industry. In addition, the author suggests that funding panels consider potential impact of their research field. How can potential impact be objectively assessed by reviewers/funding panels? How would criteria that takes into account publications and citations be supportive of ECRs whose list of publications would not be competitive compared to senior researchers? Are ECRs inadvertently ineligible to the alternative? We agree that considering the potential impact of the research field would be difficult; thus, we have deleted this expectation of the international panel. Regarding the ECRs, we have addressed this concern in the previous point above. In contrast to the Reviewer’s contention, ECRs are currently at an enormous disadvantage, because they are expected to compete with all the established investigators. In the system we are proposing, ECRs have the opportunity to set up their independent research with the help of the 5-year grant they will be given when they start their first independent position. Depending on the NIH and NSF budgets, the period and the amount of funding to the ECRs could be increased from those we are proposing here. If the process to identify reviewers and go through the peer review process for the other half of the NIH extramural funds remain in place, how will costs decrease to the point that they become negligible? The system we are proposing here would enable investigators whose research needs are much greater than the $400,000 per year, to compete for funds just like they have been doing for decades. The advantage of the split system we are proposing is that these investigators would not have to also compete with the 80,000 other applicants. We proposed the split system of funding with the expectation that the two segments could be compared at the end of a 5- or 10-year period, in terms of research productivity, breakthroughs and patents (Düzgüneş, 1999). The burden of peer review in study sections at NIH would be lowered, because there would be 80,000 fewer applications."
}
]
}
] | 1
|
https://f1000research.com/articles/11-961
|
https://f1000research.com/articles/12-757/v1
|
28 Jun 23
|
{
"type": "Research Article",
"title": "Optimization of binding affinities in chemical space with generative pre-trained transformer and deep reinforcement learning",
"authors": [
"Xiaopeng Xu",
"Juexiao Zhou",
"Chen Zhu",
"Qing Zhan",
"Zhongxiao Li",
"Ruochi Zhang",
"Yu Wang",
"Xingyu Liao",
"Xin Gao",
"Xiaopeng Xu",
"Juexiao Zhou",
"Chen Zhu",
"Qing Zhan",
"Zhongxiao Li",
"Ruochi Zhang",
"Yu Wang",
"Xingyu Liao"
],
"abstract": "Background: The key challenge in drug discovery is to discover novel compounds with desirable properties. Among the properties, binding affinity to a target is one of the prerequisites and usually evaluated by molecular docking or quantitative structure activity relationship (QSAR) models. Methods: In this study, we developed Simplified molecular input line entry system Generative Pre-trained Transformer with Reinforcement Learning (SGPT-RL), which uses a transformer decoder as the policy network of the reinforcement learning agent to optimize the binding affinity to a target. SGPT-RL was evaluated on the Moses distribution learning benchmark and two goal-directed generation tasks, with Dopamine Receptor D2 (DRD2) and Angiotensin-Converting Enzyme 2 (ACE2) as the targets. Both QSAR model and molecular docking were implemented as the optimization goals in the tasks. The popular Reinvent method was used as the baseline for comparison. Results: The results on Moses benchmark showed that SGPT-RL learned good property distributions and generated molecules with high validity and novelty. On the two goal-directed generation tasks, both SGPT-RL and Reinvent were able to generate valid molecules with improved target scores. The SGPT-RL method achieved better results than Reinvent on the ACE2 task, where molecular docking was used as the optimization goal. Further analysis shows that SGPT-RL learned conserved scaffold patterns during exploration. Conclusions: The superior performance of SGPT-RL in the ACE2 task indicates that it can be applied to the virtual screening process where molecular docking is widely used as the criteria. Besides, the scaffold patterns learned by SGPT-RL during the exploration process can assist chemists to better design and discover novel lead candidates.",
"keywords": [
"Drug design",
"transformers",
"reinforcement learning",
"molecular docking",
"hit discovery"
],
"content": "Introduction\n\nThe key challenge in drug discovery is to discover new molecules with desirable properties.1 In traditional drug discovery campaigns, high-throughput virtual screening, biochemical assays, physicochemical assays, and in vitro profiling of absorption, distribution, metabolism, and excretion (ADME) properties of chemicals are usually conducted.2 However, the chemical space of possible molecules is enormous, with 1023 to 1060 potential drug-like molecules and the number of synthesized molecules in the order of 108.3 It is infeasible to screen all the molecules to select the desirable ones. Many machine learning tools to predict molecular properties, including binding affinity, drug-likeness, synthetic accessibility, and ADME properties have been integrated into the screening pipelines as key components,4 as they are much faster than traditional computational methods and yield rapid and accurate property predictions.3,5 Employing these tools has improved the efficiency to virtually screen the chemical libraries, which are generated from available chemical reagents.6,7 However, the search is still limited to molecules in the chemical libraries.\n\nIn recent years, de novo molecular design, especially deep generative models, has witnessed rapid progress, which can efficiently explore the chemical space and optimize the molecular generation towards desired properties.3,8,9 A pioneer work was published in 2018, which employed variational autoencoder (VAE) to learn a continuous representation of the chemical space and used gradient-based optimization to search for functional molecules.10 After that, many methods were developed and the most representative classes include recurrent neural networks, autoencoders, generative adversarial networks, and reinforcement learning (RL).3,4 Among them, RL methods were shown to be able to optimize the generation of molecules towards desirable properties, including target activity, drug-likeness, molecular weight, synthetic accessibility (SA), and similarity to given molecules.4,6,11,12\n\nTransformer13 is a prominent deep learning method that was first proposed for natural language translation and has made tremendous impact in many fields, such as language modeling, speech processing, and computer vision.14 A decoder-only variant of the transformer, Generative Pretrained Transformer (GPT), stands out among the many transformer variants. It was trained on a large corpus of unlabeled text and able to generate news articles difficult for human evaluators to differentiate from human-written ones.15,16 Besides, a GPT model fine-tuned with reinforcement learning showed better generative results, with reduced toxic outputs and better truthfulness.17\n\nSeveral transformer-based methods have been proposed for molecular generation tasks.4,18–20 A study formulated the protein-specific molecular generation as a machine translation problem and used amino acid sequences as inputs and simplified molecular input line entry system (SMILES) representation of molecules as outputs.18 The model was pretrained on amino acid sequences of targets and the corresponding SMILES of the binding molecules, and able to generate valid molecules with structural novelty and plausible drug-likeness. Another work also formulated molecular generation as a translation problem, but their goal is to optimize the generation of molecules towards desirable properties.20 They added a desirable property together with the starting molecules as the input and the modified molecules fulfilling the desirable property as the output to train their model. Their results showed that transformers can generate molecules with desirable properties through modifications that are intuitive to chemists. A decoder-only transformer model, MolGPT, was also proposed for molecular generation.19 It was trained on molecules with property conditions and able to generate novel molecules fulfilling the corresponding properties. Another work also used a decoder-only transformer model but targeting multiple properties.4 After pretraining a transformer model, a GRU model was used to distill it and initiate an RL agent. This agent was then trained to optimize multiple properties through the Reinvent approach.12 The agent can generate novel molecules satisfying multiple property constraints. In summary, these studies showed the advantages of transformers on molecular generation, especially for constrained generation tasks.4,11\n\nActivity of a compound is the primary consideration for drug discovery, which is induced by binding affinity of a compound to a target. Three approaches are used to estimate binding affinity, including bioassays, quantitative structure activity relationship (QSAR) models and molecular docking.21 In vitro bioassays are reliable but often scarce, and QSAR models and molecular docking are usually used for in silico screening process.21 Because transformers are so good at sequence generation and RL has an advantage on optimization tasks, an intuitive idea is to combine transformer and RL to optimize the binding affinity. However, as far as we know, no such studies have been conducted. Two main obstacles may stop researchers from conducting such studies. First, high-end GPUs with large memories are required to conduct such studies. During the RL process, a transformer decoder has to be used to generate a batch of molecules, however, such generation is very memory expensive. Besides, conducting such studies requires interdisciplinary knowledge, including computational chemistry and machine learning expertise. For example, molecular docking is usually used for virtual screening, but is not easy for machine learning experts to perform and interpret; while transformer and RL are widely used in deep learning society, but are hard for computational chemists to grasp and implement.\n\nIn this study, we proposed the first method that combines a transformer and RL for molecular generation. We developed a tool named SGPT-RL, which uses a transformer decoder as the policy network of RL agents. The workflow is shown in Figure 1. First, GPT was trained on lead-like molecules to obtain a prior model that learns the chemical space. This prior model was used to initiate the agent, which shared the same decoder model as the policy network. Then, the agent was trained in an RL fashion to optimize the generation of molecules towards desirable properties, as shown in Figure 1c. The agent was used to generate a batch of molecules; the molecules were scored by scoring functions to obtain the target scores; the scores were combined with the prior likelihoods to calculate the losses; the losses that contain both the target score and prior likelihood information were used to serve as the feedback to the agent. During training, the likelihood of the agent to generate molecules with good target scores is increased and those with poor scores decreased. We evaluated SGPT-RL on the Moses distribution learning benchmark and two goal-directed generation tasks. Results on the Moses benchmark showed that the SGPT-RL prior model was able to learn good property distributions and generate molecules with high novelty. The two goal-directed generation tasks are a Dopamine Receptor D2 (DRD2) task, with QSAR model-based activity as the scoring function, and an Angiotensin-Converting Enzyme 2 (ACE2) task, with molecular docking affinity as the target score. In both tasks, the SGPT-RL agents were able to generate valid molecules with high target activities. In the DRD2 task, the SGPT-RL agent was able to explore more scaffolds than the popular Reinvent method; in the ACE2 task, the SGPT-RL agent generated molecules with significantly better docking scores than Reinvent. Besides, we found that the Reinvent agents could not learn effectively after around 100 steps, while the SGPT-RL agents were continuous learning and generating molecules with more ring structures. In addition, we found that the SGPT-RL agents were able to learn some generative patterns, while the Reinvent agents were exploring with strong randomness and no clear patterns could be observed.\n\na) The main workflow. Simplified molecular input line entry system (SMILES) from Moses benchmark22 was used to train a prior model. An agent model was then initiated from the prior and trained in a reinforcement learning (RL) fashion to generate molecules with desirable properties. b) The architecture of the prior model. The agent shares the same architecture. c) The pipeline of the RL approach. The prior model was used to initiate the agent model. During each RL step, the agent model was used to generate a batch of SMILES sequences. The generated sequences were evaluated by the prior model and a scoring function to calculate augmented likelihoods, which serve as the feedback to update the agent. In the Dopamine Receptor D2 (DRD2) task, a quantitative structure activity relationship (QSAR) model was used as the scoring function; in the Angiotensin-Converting Enzyme 2 (ACE2) task, ACE2 docking score was used as the scoring function.\n\n\nMethods\n\nThe dataset to train the prior models was obtained from Moses benchmark,22 see also Underlying data.40 This dataset contains 1.9 million lead-like molecules from the Zinc database.23 The train and test dataset in Moses benchmark were used for training and testing, which contain 1,584,664 and 176,075 molecules respectively.\n\nKnown active molecules that bind with DRD2 or ACE2 were obtained from ExCAPE-DB,24 see also Underlying data.40 The 8,036 unique molecules that are known to be active against DRD2 were obtained and 56 unique molecules that are active against ACE2 were retrieved. For these two sets of known active molecules, none of them were found in the Moses training dataset.\n\nPlease note that all code associated with this article is available in the Software availability section.40 A brief overview of the framework is illustrated in Figure 1a. A transformer decoder prior model was trained on the Moses dataset. This pretrained prior model was used to initiate the agent. During the RL process, the agent model was used to generate molecules, which were scored by the prior network and a scoring function to provide feedback to update the agent. The agent model trained after the final step was used to generate molecules for property distribution analysis.\n\nThe prior network\n\nIn SGPT-RL, the transformer decoder model, GPT,25 was used as the prior model to learn the chemical space. Tokenized SMILES sequences were used to train the model on a next token prediction task.\n\nThe GPT model we used is a simplified version of GPT-2, with only ∼6M parameters. The architecture of the model is illustrated in Figure 1b. The model is composed of eight decoder blocks, input and positional embedding before the blocks, a linear layer after the blocks, and a softmax layer before output. Each of the blocks contains a masked multi-head self-attention layer and a fully connected feedforward layer, with residual connections in each of the layers. Layer normalization is conducted in the two layers to normalize the inputs. An embedding size of 256 was used in all layers.\n\nThe core of the GPT model is the masked multi-head self-attention layer. In this layer, eight scaled dot-product attention functions facilitate the model to capture key information in a sequence. In the attention function, a query vector Q is used to calculate a dot product with the key vector K and then divided by the key vector length dk. The resulting product value is passed into a softmax function to get the attention weights, which is dot-producted with a value vector V to get the final attention. The formula is shown in Equation 1.13\n\nThe prior model was trained for ten epochs on the training dataset and evaluated on the testing dataset after each epoch. Cross-entropy loss was used with the AdamW optimizer41 to update the model, with a learning rate of 0.001. A batch size of 1,024 was used to train the model. To generate the SMILES string of a molecule, a start token was fed to the model to predict the next. The generated token was concatenated with previous tokens to predict the next, until an end token was predicted or a maximum sequence length of 140 was reached.\n\nTraining the agent\n\nThe process to generate molecules with desirable properties was framed as a RL problem, and the Reinvent approach was utilized, with the process described below.11 The GPT model described in the previous Subsection was used for the prior and the agent, and customized scoring functions for the target properties were used in each of the two tasks.\n\nThe loss function to update the agent model is defined as in Equations 2 and 3. First, a SMILES sequence A was sampled from the agent model with its log-likelihood logpAagent. Then the SMILES sequence was passed to the prior model to calculate a prior log-likelihood logpAprior, and evaluated with scoring functions of desirable properties to get a score SA. The score was added to the prior log-likelihood with a coefficient σ to get an augmented log-likelihood logpAaug, as shown in Equation 2. The idea behind this equation is that the prior log-likelihood is added to preserve the rules learnt from SMILES sequences of molecules, and the score of desirable properties was used to bias the model to generate SMILES of desirable properties.\n\nFinally, the squared error between the augmented log-likelihood and agent log-likelihood was used as the loss to update the agent model, as shown in Equation 3.\n\nFive metrics from the Moses benchmark were used to evaluate the models, including validity, uniqueness, novelty, Similarity to a nearest neighbor (SNN) and intDiv. The definitions of the metrics are described below. The generated SMILES sequences to be evaluated are denoted by G, the training dataset is denoted by T, and n is the total number of the generated sequences.\n\n• Validity: the fraction of the valid sequences among 10,000 generated sequences.\n\n• Uniqueness: the fraction of the unique sequences among 10,000 valid generated sequences.\n\n• Novelty: the fraction of the unique sequences in G, but not in T.\n\n• Similarity to a nearest neighbor (SNN): evaluates the similarity of the generated molecules to the training molecules. It is the Tanimoto similarity TmGmT between fingerprints of a molecule mG from the generated set G and its nearest neighbor molecule mT in the training dataset.\n\n• Internal diversity (intDiv): assesses the diversity within G. It is defined as one minus the averaged Tanimoto similarity of any pair of molecules m1, m2 in the generated sequences G.\n\nIn our experiments, seven molecular properties were calculated to evaluate the property distributions and used as the optimization goals. All these properties were used to compare the property distributions of molecules. DRD2 activity and ACE2 docking score were used as the scoring functions of the DRD2 and ACE2 tasks, respectively.\n\nDRD2 activity was evaluated with a QSAR model.11 This model is a support vector machine classifier with a Gaussian kernel trained on active and inactive molecules. It predicts a probability score range from zero to one, with the closer to one the higher DRD2 activity.\n\nACE2 affinity was calculated using molecular docking as described in Subsection “Task 2: structure-based generation with ACE2 as the target”.\n\nThe quantitative estimate of drug-likeness (QED) quantifies the drug-likeness of a molecule using molecular properties as inputs.26 It was calculated by RDKit (2017.09.1)27 and ranges from zero to one, with the closer to one the more favorable.\n\nSAscore measures the difficulty of synthesizing a molecule.28 A predictive model built by Blaschke et al.12 was used, where molecular weight was combined with raw score,28 which ranges in,1,10 as features to predict the probability of synthetic accessibility. The model gives a probability score range from zero to one, with the closer to one the better.\n\nMolecular weight and partition coefficient (LogP) were calculated using RDKit.27 Length of the SMILES string was also calculated for the molecules.\n\nThe SGPT-RL model was evaluated on a distribution learning benchmark and two tasks for goal-directed generation. The Moses Benchmark was used for distribution evaluation. DRD2 activity and ACE2 affinity were used as the scoring functions in the two goal-directed generations tasks, respectively.\n\nBenchmarking on distribution learning\n\nTo evaluate on the Moses distribution learning benchmark, the SGPT-RL prior model was trained on Moses training dataset. The model after the final epoch was used to generate 10,000 molecules to evaluate on this benchmark. Five metrics were used for comparison, including validity, uniqueness, novelty, SNN and intDiv. The baseline models from Moses benchmark were run with default parameters for comparison. MCMG (multi-constraints molecular generation) and MolGPT were also run with default parameters to generate 10,000 molecules for comparison.\n\nTask 1: goal-directed generation with DRD2 as the target\n\nIn the DRD2 task, we aimed to generate molecules that are active against DRD2. The DRD2 activity predicted by a QSAR model11 was used as the target. The prior model trained from the Moses dataset was used to initiate the agent on this task. The agent was trained for 2,000 steps and the model after the final step was used to sample 10,000 molecules for property distribution analysis.\n\nThe Reinvent model11 was used as the baseline in comparison. In this agent, a three-layer GRU was used as the policy model. The default hyper-parameters of Reinvent were used. The prior model was trained for five epochs with a batch size of 128. Adam optimizer was used with a learning rate of 0.001. To train this agent, the same scoring function of the SGPT-RL agent was used for a fair comparison. The Reinvent agent was trained with a batch size of 64, a learning rate of 0.0005, a sigma of 60, and 3,000 steps.\n\nTask 2: structure-based generation with ACE2 as the target\n\nIn the ACE2 task, we trained the SGPT-RL agent with ACE2 affinity as the desirable property. ACE2 affinity was evaluated by ligand-receptor docking experiments. The 3D structure of the human ACE2 receptor (PDB ID 1R4L) was downloaded from the Protein Data Bank. It was processed with PyMol (2.5.4)29 to remove water molecules and original ligands. A free, trial version of PyMol is available here. Several open source alternatives (see here) are available that carry out a similar function to PyMol. The structure was also processed with MGLTools (1.5.7)30 to add polar hydrogen and obtain the docking grid. The pocket where XX5 is located was used to dock with generated molecules. The SMILES strings of generated molecules were used to generate 3D structures of ligands using RDKit (2017.09.1).27 The generated 3D ligand structures were processed with OpenBabel (3.0.0)31 to assign Gasteiger partial charges and convert to pdbqt format. The final docking was performed using AutoDock Vina (1.1.2)32 with eight poses for each ligand. The smallest docking score of the eight poses was used as the docking score of a ligand.\n\nTo train the agent, the affinity score was expected to be in a range of zero to one to calculate the augmented log-likelihoods. So the docking score was transformed into a range of zero to one using the reverse sigmoid function as shown in Equation 6, where l, h, and k were constants and set to be -12, -8 and 0.25, respectively.\n\nThe Moses pretrained prior model was also used to initiate the agent on this task. The agent was trained for 1,000 steps and 64 molecules were sampled and scored during each step. 10,000 molecules were sampled from the agent model after the final step for property distribution analysis.\n\nThe Reinvent model11 was also used as the baseline on this task. The default hyper-parameters of Reinvent were used and the same scoring function of the SGPT-RL agent was used for comparison. This model was trained for 1,000 steps with 64 molecules generated during each step.\n\nTo analyze the scaffold overlaps of the prior models, we clustered the scaffolds of generated molecules and training reference using Butina method in RDKit.27,33 The molecules from different sources were merged, with invalid and duplicated molecules removed. Murcko Scaffolds were obtained using RDKit and clustered using Morgan fingerprints as inputs. A minimum distance of 0.2 was used during clustering. Venn diagram was used to visualize the number of overlapping clusters and unique clusters. Examples of molecules were visualized using ChemDraw 20.1.34 Some open source alternatives to ChemDraw are available here.\n\nTo analyze the average number of rings and the number of explored scaffolds in Figures 3 and 4, RDKit27 was used to obtain the Murcko Scaffold and calculate the number of rings for each generated molecule. The duplicated scaffolds were removed before counting the scaffolds.\n\na) The scaffold overlaps between the training reference and molecules generated by the Simplified molecular input line entry system Generative Pretrained Transformer with Reinforcement Learning (SGPT-RL) and Reinvent prior models. Both SGPT-RL and Reinvent were able to generate molecules with novel scaffolds that did not appear in the training reference. b) Representative molecules with unique scaffolds from the three sources. The three rows correspond to training reference only (TR), SGPT-RL prior only (SP), and Reinvent prior only (RP) molecules, respectively.\n\na) and b) SGPT-RL was relatively slower in generating molecules with good validity and DRD2 activity than Reinvent. c) SGPT-RL gradually increased the number of rings in the generated molecules during the reinforcement learning (RL) process. It generated molecules with fewer rings than Reinvent in the beginning, but with more rings in the end. d) SGPT-RL explored more scaffolds than Reinvent during the RL process.\n\n\nResults\n\nThe first step of our workflow is to train a prior model to learn the chemical space. To do that, the dataset from Moses benchmark22 was used to train the prior model. We used Moses dataset because the molecules in this dataset are lead-like molecules and have good chemical properties. A ∼6M GPT model was used as the prior model, details of which are described in Subsection 2.2.1. The Reinvent prior model11 (GRU) was trained on the same dataset for comparison. 10,000 molecules were randomly sampled from the training dataset to be used as the training reference.\n\nA comparison of different models on the Moses distribution learning benchmark22 is shown in Supplementary Table 1 in Extended data.40 Five Moses metrics, including validity, uniqueness, similarity to the nearest neighbor (SNN), internal diversity (IntDiv), and novelty, were selected for comparison. From the table, we found that the SGPT-RL prior model achieved a relatively good validity (0.936), uniqueness (0.997), and novelty (0.946). Though the Reinvent prior model achieved a better validity (0.986) and uniqueness (1.000), it obtained a poor novelty (0.783). The other two transformer-based methods, MCMG and MolGPT, also achieved a good novelty (0.983 and 0.931 respectively).\n\nThe property distributions of the training reference and molecules sampled from the SGPT-RL and Reinvent prior models were visualized as shown in Supplementary Figure 1 in Extended data.40 Six selected properties, including DRD2 activity, ACE2 docking score, QED, synthesize accessibility score (SAscore), length of SMILES strings, and molecular weight were used for comparison. Details on the calculation of these properties are described later. From this figure, we can see that both prior models learned similar property distributions to the training reference. For molecular weight, the distribution curve of SGPT-RL prior is closer to the training reference than that of the Reinvent prior.\n\nTo compare the generative preferences of the SGPT-RL and the Reinvent prior models, we analyzed the scaffolds of the generated molecules. The overlapping scaffolds and unique scaffolds from each source were visualized using a Venn diagram as shown in Figure 2a. From this diagram, we found that both the SGPT-RL and the Reinvent prior models were able to recall scaffolds from the training reference and generate many molecules with novel scaffolds. Several examples of the generated molecules and training samples are shown in Figure 2b.\n\nIn our experiments, we evaluated SGPT-RL for goal-directed generation with two tasks, a DRD2 task, which used a quantitative structure-activity relationship (QSAR) model11 as the scoring function, and an ACE2 task, which used a docking score calculated from AutoDock Vina32 as the scoring function.\n\nDRD2 is one of the most well-studied drug targets, with many chemicals active against it being reported.24,35 A QSAR model was proposed for DRD2 activity prediction.11 In this task, the SGPT-RL prior model pretrained on the Moses dataset was used to initiate the agent, and the agent was trained via RL to optimize the generation of molecules towards good DRD2 activities. The Reinvent model was trained with default hyper-parameters for comparison.11 Details on the training of the agents are shown in Subsection 2.2.2. The hyper-parameter of SGPT-RL was fine-tuned as shown in Supplementary Results in Extended data.40 A sigma value of 60 was chosen for this agent.\n\nThe learning curves of the agent models on the DRD2 task are shown in Figure 3. From Figures 3a and 3b, we see that both agents could learn a good validity and DRD2 activity after 200 steps. The Reinvent agent took fewer steps to obtain good DRD2 activity than the SGPT-RL agent. Figures 3c and 3d show that the SGPT-RL agent gradually increased the number of rings during generation and explored more scaffolds within the first 200 steps. The main difference in scaffold exploration between the two agents is in 100-200 steps. The Reinvent agent was not drastically improving the goal after around 100 steps, while the SGPT-RL agent was continuously learning and improving after that.\n\nThe agent models trained after the final step were also evaluated on the Moses benchmark, as shown in Table 1. The Moses metrics of MCMG was also obtained from the original paper for comparison.4 We found that the SGPT-RL agent achieved better validity and novelty, while the Reinvent model obtained a better internal diversity.\n\nSimplified molecular input line entry system Generative Pretrained Transformer with Reinforcement Learning (SGPT-RL) generated molecules with good validity and novelty. SNN, Similarity to a nearest neighbor; MCMG, multi-constraints molecular generation.\n\nThe property distributions of the training reference and molecules sampled from the final SGPT-RL and Reinvent agents were also compared in this task, as shown in Supplementary Figure 5 in Extended data.40 The properties analyzed include DRD2 activity, QED, SAscore, partition coefficient (LogP), length of SMILES strings, and molecular weight. We found that both SGPT-RL and Reinvent could generate molecules with good DRD2 activities after the final steps, whereas the molecules in training reference have poor DRD2 activities. The property distributions of the molecules generated by the SGPT-RL and Reinvent agents are similar. For SAscore, both agents shifted the distributions to the left, which means generating molecules that are relatively harder to synthesize than the molecules in the training reference.\n\nIn this task, we aimed to generate novel molecules targeting ACE2, a receptor protein which SARS-CoV and SARS-CoV-2 bind to enter a cell.36,37 Only 56 unique molecules were reported to be active against ACE2 in ExCAPE-DB.24 For such targets where few known active molecules are available, it is not possible to build a reliable QSAR model to predict activity. To find binding molecules against targets like ACE2, structure-based docking methods are widely used to evaluate the affinities. In this study, the ACE2 affinity of a molecule was evaluated as the minimum binding free energy calculated by AutoDock Vina.32 Details on the calculation of ACE2 affinity can be found in Subsection 2.4. The pocket, where XX5 is located, in the 3D structure of the human ACE2 receptor (PDB ID 1R4L38) was used to dock with a ligand. The prior model trained on Moses dataset22 was also used to initiate this agent, and the agent was trained for 1,000 steps. The Reinvent model was also trained on this task for a fair comparison.\n\nThe learning curves of the agent models are shown in Figure 4. The SGPT-RL agent was able to generate valid molecules with good ACE2 docking scores after 200 steps. Like the DRD2 task, in the ACE2 task the Reinvent model was not efficiently learning after around 100 steps. The docking scores of the generated molecules were not clearly improving after that. Besides, we also observed that SGPT-RL gradually increased the number of rings in the exploration process, as shown in Subfigure 4c. Examples of molecules generated by SGPT-RL during the initial exploration steps are shown in Figure 5. The SGPT-RL agent generated molecules with few rings in the first step, and gradually increased the number of rings. The Reinvent agent was randomly exploring the molecules, and no clear patterns can be observed, as shown in Supplementary Figure 7 in Extended data.40\n\na) and b) SGPT-RL generated molecules with better validity and ACE2 docking scores than Reinvent after 200 steps. c) SGPT-RL gradually increased the number of chemical rings of the molecules during the Reinforcement Learning (RL) process. The curve difference in c) is highly correlated with the curve difference in b) (Pearson’s r = 0.87). d) Both SGPT-RL and Reinvent generated new scaffolds with increasing steps.\n\nThe SGPT-RL agent generated molecules with few rings in the beginning, and gradually increased the number of rings.\n\nThe final agents were evaluated on the Moses metrics, as shown in Table 2. The SGPT-RL agent achieved good validity (0.990) and novelty (1.000), while Reinvent was better on SNN and internal diversity. The property distributions were plotted for the two agents. Six selected properties, including ACE2 docking score, QED, SAscore, LogP, length of SMILES string, and molecular weight, were analyzed, as shown in Supplementary Figure 8 in Extended data.40 Calculations of these properties are described in Subsection 2.4. From Supplementary Figure 8a in Extended data,40 we see that the SGPT-RL agent was able to generate molecules with good docking scores and clearly shifted the distribution curves to the left. The ACE2 docking scores of SGPT-RL generated molecules were better than the training reference or the Reinvent generated molecules. Supplementary Figure 9 in Extended data40 shows some examples of molecules generated by the agents in the last step. SGPT-RL generated molecules are more similar to each other in comparison with Reinvent generated molecules. From these molecules, we can see that SGPT-RL tends to generate with certain preferences, such as a naphthalene structure in one end in this task.\n\nSGPT-RL, Simplified molecular input line entry system Generative Pretrained Transformer with Reinforcement Learning; SNN, Similarity to a nearest neighbor.\n\nThe top six molecules with the highest docking scores generated by the agents are shown in Figure 6. The SGPT-RL agent was able to generate more molecules with high docking affinities than the Reinvent agent. Besides, five out of the top six molecules generated by SGPT-RL contain a naphthalene structure in one end. Considering the same pattern in the molecules generated by SGPT-RL in the last step, we would guess that the agent had learned such a pattern during the exploration process. However, the top scoring molecules generated by the Reinvent agent have strong randomness and no clear scaffold patterns can be observed.\n\nThe Simplified molecular input line entry system Generative Pretrained Transformer with Reinforcement Learning (SGPT-RL) generated molecules are more similar to each other in comparison with the Reinvent generated molecules.\n\n\nDiscussion\n\nIn this study, we developed a tool named SGPT-RL for de novo molecular generation, which uses a transformer decoder as the policy network of the reinforcement learning (RL) agent. A workstation with two A100 GPUs was used for our experiments. The docking score was used as a scoring function in addition to a QSAR-based scoring function. This enabled us to explore not only a target with many known active molecules but also a new target with few known actives.\n\nWe evaluated SGPT-RL on two goal-directed generation tasks, a DRD2 task and an ACE2 task. As many known DRD2 actives are available, it is possible to build a reliable QSAR model to be used as the scoring function in the DRD2 task. However, few known actives were reported for ACE2, so Vina docking scores had to be used as the optimization goal in the ACE2 task. Our experiments showed that both SGPT-RL (which uses GPT as the policy network) and Reinvent (which uses GRU as the policy network) were able to propose molecules with improved scores on the two tasks. However, the SGPT-RL generated molecules showed significantly better scores on the ACE2 task compared to the Reinvent generated ones (p-value: 0.0). As the molecular docking was widely used for the virtual screening process, we believe that the superior performance of SGPT-RL in the ACE2 task would indicate its wide applicability in the practical molecular design procedure.\n\nBesides, we found three generative differences between the SGPT-RL and Reinvent agents during the exploration steps. First, in the experiments, we found that Reinvent was exploring with strong randomness in the two tasks in general, however, SGPT-RL gradually explored the scaffolds during the generation processes. In the initial steps, SGPT-RL generated molecules with few rings and gradually increased the number of rings during exploration; in the late steps, it generated molecules with some conserved scaffold patterns, such as double ring structures in the ACE2 task. Second, we found that Reinvent was not clearly improving the goal after around 100 steps, while SGPT-RL was continuously optimizing the scores even after 400 steps. We believe that this difference is mainly caused by the difference in policy networks: it is not easy for GRU to learn ring patterns, which are represented as distant numbers in SMILES; however, GPT was able to learn long-range dependencies to remember the ring patterns that had improved scores in previous steps. Thirdly, the SGPT-RL agent could generate molecules with more rings than the Reinvent agent in the ACE2 task (shown in Figure 4c). A diverse number of rings indicates a variety of scaffold structures. Considering the importance of appropriate scaffolds in lead identification,39 we believe that including GPT as the policy network in RL agents might be useful to discover lead candidates of novel scaffolds.\n\nWhile the results of our work are noteworthy, there are two limitations to consider. First, the dataset to train the prior models would be a limit to the generative results. All the prior models were pretrained on the Moses dataset.22 As the Moses dataset was collected from the Zinc database,23 which mainly consists of lead-like molecules, the prior distribution could not represent the entire chemical space. The prior models were used to guide the agents in the two optimization tasks, and the bias in the prior models might contribute to the bias in the agent models. Such bias might be contributive, because it would help to generate molecules with lead-like properties, such as good synthetic accessibility and drug-likeness; however, it might also be undesirable, as it limits the chemical space the agents explored. In tasks which aim to explore out of the space of lead-like molecules, other training data should be utilized to train the prior models. Second, the settings of the docking experiments would also be a limit. We analyzed ACE2 for docking, but docking experiments of additional targets would further confirm the observations in our study.\n\nAs molecular docking was widely used for virtual screening, generative models combined with molecular docking provides another solution for the virtual screening process. The superior performance of SGPT-RL on the ACE2 task indicates that it can be applied to this practical molecular design process and propose novel molecules with good target-binding capabilities. Besides, SGPT-RL explored the chemical space with certain scaffold patterns. The patterns learned by SGPT-RL can provide intuitions for chemists to explore, thus aid the molecular design.",
"appendix": "Data availability\n\nProtein Data Bank: 3D structure of the human ACE2 receptor. Accession number 1R4L; https://www.rcsb.org/structure/1R4L.\n\nThe dataset to train the prior models was obtained from Moses benchmark. 22 This dataset contains 1.9 million lead-like molecules from the Zinc database, and is available to readers here: https://github.com/molecularsets/moses. The train and test dataset in Moses benchmark, used here for training and testing, contains 1,584,664 and 176,075 molecules respectively. Moses is licensed under MIT license (redistribution permitted).\n\nThe 8,036 unique molecules that are known to be active against DRD2 and 56 unique molecules that are active against ACE2 were downloaded from ExCAPE-DB , 24 and which are licensed under Creative Commons Attribution 4.0 International License (redistribution permitted).\n\nThe specific underlying data used in this study been uploaded by the authors to Zenodo (see below).\n\nZenodo: Optimization of binding affinities in chemical space with transformer and deep reinforcement learning -- source code and data. https://doi.org/10.5281/zenodo.7730149. 40\n\nThis project contains the following underlying data:\n\n- Data.zip (the Moses dataset, the DRD2 and ACE2 active molecules, the pretrained models, and the source data underlying Figures 3 and 4).\n\nZenodo: Optimization of binding affinities in chemical space with transformer and deep reinforcement learning -- source code and data. https://doi.org/10.5281/zenodo.7730149. 40\n\nThis project contains the following extended data:\n\n- Chemical_GPT_SI.pdf (supplementary results, tables, and figures).\n\n- Sgpt-rl.png (the workflow of SGPT-RL).\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\nNicolaou CA, Brown N: Multi-objective optimization methods in drug design. Drug Discov. Today Technol. 2013; 10(3): e427–e435. Publisher Full Text\n\nHughes JP, Stephen Rees S, Kalindjian B, et al.: Principles of early drug discovery. Br. J. Pharmacol. 2011; 162(6): 1239–1249. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElton DC, Boukouvalas Z, Fuge MD, et al.: Deep learning for molecular design—a review of the state of the art. Molecular Systems Design & Engineering. 2019; 4(4): 828–849. Publisher Full Text\n\nWang J, Hsieh C-Y, Wang M, et al.: Multi-constraint molecular generation based on conditional transformer, knowledge distillation and reinforcement learning. Nat. Mach. Intell. 2021; 3(10): 914–922. Publisher Full Text\n\nButler KT, Davies DW, Cartwright H, et al.: Machine learning for molecular and materials science. Nature. 2018; 559(7715): 547–555. Publisher Full Text\n\nStåhl N, Falkman G, Karlsson A, et al.: Deep reinforcement learning for multiparameter optimization in de novo drug design. J. Chem. Inf. Model. 2019; 59(7): 3166–3176. Publisher Full Text\n\nHoffmann T, Gastreich M: The next level in chemical space navigation: going far beyond enumerable compound libraries. Drug Discov. Today. 2019; 24(5): 1148–1156. PubMed Abstract | Publisher Full Text\n\nXia X, Jianxing H, Wang Y, et al.: Graph-based generative models for de novo drug design. Drug Discov. Today Technol. 2019; 32: 45–53.\n\nVanhaelen Q, Lin Y-C, Zhavoronkov A: The advent of generative chemistry. ACS Med. Chem. Lett. 2020; 11(8): 1496–1505. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGo´mez-Bombarelli R, Wei JN, Duvenaud D, et al.: Automatic chemical design using a data-driven continuous representation of molecules. ACS central science. 2018; 4(2): 268–276. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOlivecrona M, Blaschke T, Engkvist O, et al.: Molecular de-novo design through deep reinforcement learning. J. Chem. 2017; 9(1): 1–14. Publisher Full Text\n\nBlaschke T, Aru´s-Pous J, Chen H, et al.: Reinvent 2.0: an ai tool for de novo drug design. J. Chem. Inf. Model. 2020; 60(12): 5918–5922. 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\nLin T, Wang Y, Liu X, et al.: A survey of transformers. arXiv preprint arXiv:2106.04554. 2021.\n\nRadford A, Narasimhan K, Salimans T, et al.: Improving language understanding by generative pre-training. arXiv preprint. 2018.\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\nOuyang L, Wu J, Jiang X, et al.: Training language models to follow instructions with human feedback. arXiv preprint arXiv:2203.02155. 2022.\n\nGrechishnikova D: Transformer neural network for protein-specific de novo drug generation as a machine translation problem. Sci. Rep. 2021; 11(1): 1–13. Publisher Full Text\n\nBagal V, Aggarwal R, Vinod PK, et al.: Molgpt: Molecular generation using a transformer-decoder model. J. Chem. Inf. Model. 2021; 62(9): 2064–2076. PubMed Abstract | Publisher Full Text\n\nHe J, You H, Sandstro¨m E, et al.: Molecular optimization by capturing chemist’s intuition using deep neural networks. J. Chem. 2021; 13(1): 1–17. Publisher Full Text\n\nBoitreaud J, Mallet V, Oliver C, et al.: Optimol: optimization of binding affinities in chemical space for drug discovery. J. Chem. Inf. Model. 2020; 60(12): 5658–5666. PubMed Abstract | Publisher Full Text\n\nPolykovskiy D, Zhebrak A, Sanchez-Lengeling B, et al.: Molecular sets (moses): a benchmarking platform for molecular generation models. Front. Pharmacol. 2020; 11: 1931.\n\nIrwin JJ, Shoichet BK: Zinc- a free database of commercially available compounds for virtual screening. J. Chem. Inf. Model. 2005; 45(1): 177–182. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSun J, Jeliazkova N, Chupakhin V, et al.: Excape-db: an integrated large scale dataset facilitating big data analysis in chemogenomics. J. Chem. 2017; 9(1): 1–9.\n\nRadford A, Jeffrey W, Child R, et al.: Language models are unsupervised multitask learners. OpenAI blog. 2019; 1(8): 9.\n\nRichard Bickerton G, Paolini GV, Besnard J, et al.: Quantifying the chemical beauty of drugs. Nat. Chem. 2012; 4(2): 90–98. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLandrum G, et al.: Rdkit: A software suite for cheminformatics, computational chemistry, and predictive modeling.2013.\n\nErtl P, Schuffenhauer A: Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions. J. Chem. 2009; 1(1): 1–11. Publisher Full Text\n\nDeLano WL, et al.: Pymol: An open-source molecular graphics tool. CCP4 Newsl. Protein Crystallogr. 2002; 40(1): 82–92.\n\nMorris GM, Huey R, Lindstrom W, et al.: Autodock4 and autodocktools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 2009; 30(16): 2785–2791. PubMed Abstract | Publisher Full Text | Free Full Text\n\nO’Boyle NM, Banck M, James CA, et al.: Open babel: An open chemical toolbox. J. Chem. 2011; 3(1): 1–14.\n\nTrott O, Olson AJ: Autodock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 2010; 31(2): 455–461.\n\nButina D: Unsupervised data base clustering based on daylight’s fingerprint and tanimoto similarity: A fast and automated way to cluster small and large data sets. J. Chem. Inf. Comput. Sci. 1999; 39(4): 747–750. Publisher Full Text\n\nMills N: Chemdraw ultra 10.0 cambridgesoft, 100 cambridgepark drive, cambridge, ma 02140.2006. commercial price: 1910fordownload, 2150 for cd-rom; academic price: 710fordownload, 800 for cd-rom. Reference Source\n\nGeneCards: DRD2 Gene - Dopamine Receptor D2.2022.\n\nZhou P, Yang X-L, Wang X-G, et al.: A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270–273. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNapolitano F, Xiaopeng X, Gao X: Impact of computational approaches in the fight against covid-19: an ai guided review of 17 000 studies. Brief. Bioinform. 2022; 23(1): bbab456. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTowler P, Staker B, Prasad SG, et al.: Ace2 x-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J. Biol. Chem. 2004; 279(17): 17996–18007. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhao H: Scaffold selection and scaffold hopping in lead generation: a medicinal chemistry perspective. Drug Discov. Today. 2007; 12(3-4): 149–155. PubMed Abstract | Publisher Full Text\n\nXu X, Zhou J, Zhu C, et al.: Optimization of binding affinities in chemical space with generative pre-trained transformer and deep reinforcement learning -- source data (v1.2.3). Zenodo. 2023. Publisher Full Text\n\nLoshchilov I, Hutter F: Decoupled Weight Decay Regularization. International Conference on Learning Representations. 2019.\n\nXu X, Zhou J, Zhu C, et al.: Optimization of binding affinities in chemical space with generative pre-trained transformer and deep reinforcement learning -- source code (v1.2.0). Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "188006",
"date": "20 Jul 2023",
"name": "Ka-Chun Wong",
"expertise": [
"Reviewer Expertise Bioinformatics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors proposed a method, SGPT-RL, to optimize the SMILES sequences to improve binding affinities through incorporating GPT into a reinforcement learning (RL) framework. The authors trained a GPT model as a prior model to learn the chemical space by pretraining on Moses SMILES, and then trained two RL models, one for DRD2 QSAR scores and the other for ACE2 docking scores, to generate SMILES with good binding affinities. The results show that the GPT prior model learned a good distribution of the chemical space. The RL models were able to generate SMILES sequences with binding affinities. In addition, SGPT-RL generated sequences with better docking scores than Reinvent and able to learn certain patterns during the RL process. There are a few considerations that could be addressed:\nMajor issues:\n1. The manuscript includes repetitive explanations of abbreviations, such as SGPT-RL, DRD2, ACE2, and SMILES, throughout the passages and captions. This not only hinders the flow of reading but also makes it tedious to navigate through. To enhance readability, I suggest minimizing the frequency of explanations and providing them only when necessary, particularly upon their initial mention.\n2. GPT is mainly learning distributions, and RL is introducing inductive biases to steer the distributions towards desirable properties. Therefore, I think it is crucial to include a figure that demonstrates how the distribution of these properties evolves. Supplementary Figure 8 addresses this aspect effectively, and I recommend incorporating it into the main context to provide a clear illustration.\n3. The supplementary information should have the same name as the main article, i.e. ‘transformer’ should be ‘generative pre-trained transformer’.\nMinor issues:\n1. In Subsection that explains ”SAscore”, the sentence “which ranges in1, 10” should be “which ranges in [1, 10]”.\n\n2. The authors stated that SGPT-RL outperformed Reinvent on the ACE2 task with a significant p-value. However, the p-value is reported as 0.0, which appears as a numerical zero. To accurately represent this score, it would be preferable to present it in 2-digit scientific notation.\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": "11062",
"date": "13 Apr 2024",
"name": "Xiaopeng Xu",
"role": "Author Response",
"response": "We thank the Reviewer for sharing our aims and appreciating our efforts. Point by point responses to the issues are as follows. Major issues: 1. The manuscript includes repetitive explanations of abbreviations, such as SGPT-RL, DRD2, ACE2, and SMILES, throughout the passages and captions. This not only hinders the flow of reading but also makes it tedious to navigate through. To enhance readability, I suggest minimizing the frequency of explanations and providing them only when necessary, particularly upon their initial mention. We thank the Reviewer for pointing out this issue. We updated the paragraphs and captions and removed the duplicated explanations to make the sentences more fluent to read. 2. GPT is mainly learning distributions, and RL is introducing inductive biases to steer the distributions towards desirable properties. Therefore, I think it is crucial to include a figure that demonstrates how the distribution of these properties evolves. Supplementary Figure 8 addresses this aspect effectively, and I recommend incorporating it into the main context to provide a clear illustration. We thank the Reviewer for the kind advice. We included the main results from Supplementary Figure 8 into our main context to showcase the improvement of the core properties during the optimization process. 3. The supplementary information should have the same name as the main article, i.e. ‘transformer’ should be ‘generative pre-trained transformer’. We thank the Reviewer for pointing out this issue. We updated the title of the supplementary information to fix this issue. Minor issues: 1. In the Subsection that explains ”SAscore”, the sentence “which ranges in1, 10” should be “which ranges in [1, 10]”. We thank the Reviewer for pointing out this typeset issue. The sentence is updated to fix this issue as shown below. \"A predictive model built by Blaschke et al. was used, where molecular weight was combined with raw score, which ranges in from one to 10, as features to predict the probability of synthetic accessibility.\" 2. The authors stated that SGPT-RL outperformed Reinvent on the ACE2 task with a significant p-value. However, the p-value is reported as 0.0, which appears as a numerical zero. To accurately represent this score, it would be preferable to present it in 2-digit scientific notation. We thank the Reviewer for pointing out this issue. Ideally, we also want to have a p-value in 2-digit scientific notation, however, the result from computation is zero with no 2-digits calculated. We think this is due to the nature of distinct distribution. We use “(p-value <0.01)” as a replacement."
}
]
},
{
"id": "188001",
"date": "01 Nov 2023",
"name": "Guohua Wang",
"expertise": [
"Reviewer Expertise Artificial intelligence in bioinformatics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this paper, the authors proposed SGPT-RL, a method that utilizes GPT as the policy network within the Reinvent approach to enhance the optimization of binding affinities, including DRD2 QSAR score and ACE2 docking score. The results of their study demonstrate that GPT effectively learns the chemical space, generating compounds with high novelty and validity, consistent with previous research. Notably, in both optimization tasks, GPT exhibits proficiency in learning ring patterns and successfully explores a wide range of scaffolds during the exploration process. Importantly, SGPT-RL outperforms in the ACE2 task by obtaining superior docking scores and identifying specific patterns, such as the presence of double ring structures.\nOverall, this study is interesting, as GPT is the current hotspot in AI research and de novo drug design is one of the most successful cases in AI for science. The manuscript is also well written and easy to understand. But there are several issues which should be improved.\nFirstly, there are an excessive number of explanations for common abbreviations in this manuscript, which makes it tedious to read. For instance, the abbreviation \"SGPT-RL\" is repeatedly explained in each of the figures. Similarly, abbreviations like \"RL,\" \"DRD2,\" and \"ACE2\" are unnecessarily reiterated many times in the captions. I believe it would be more effective to provide explanations for these abbreviations only during their initial occurrence in the captions, thereby avoiding repetitive explanations.\nSecondly, in this study, the authors compared MCMG in the DRD2 task, but not in the ACE2 task. Wouldn't it be more natural to compare it in both tasks? What is the reason for excluding it from the comparison in the ACE2 task?\nThirdly, while going through the supplementary information, I came across Supplementary Figure 8, which serves as a clear illustration. I believe the author should incorporate it into the main content as it provides a clear explanation of the resulting distributions. Figure 5 should be relocated to the supplementary material instead.\nFurthermore, the author should thoroughly proofread the paper for any typos and formatting errors. For instance, 'the' should be added before 'Moses benchmark'. In the first paragraph of Subsection 'Evaluation metrics', 'Similarity to a nearest neighbor (SNN)' should be corrected to 'similarity to a nearest neighbor (SNN)'.\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": "11064",
"date": "13 Apr 2024",
"name": "Xiaopeng Xu",
"role": "Author Response",
"response": "We thank the Reviewer for the summary, the acknowledgement of our novelty, and for the helpful comments. Point by point responses to the issues are as follows. Firstly, there are an excessive number of explanations for common abbreviations in this manuscript, which makes it tedious to read. For instance, the abbreviation \"SGPT-RL\" is repeatedly explained in each of the figures. Similarly, abbreviations like \"RL,\" \"DRD2,\" and \"ACE2\" are unnecessarily reiterated many times in the captions. I believe it would be more effective to provide explanations for these abbreviations only during their initial occurrence in the captions, thereby avoiding repetitive explanations. We thank the Reviewer for pointing out this issue. We updated the paragraphs and captions and removed the duplicated explanations to make the sentences more fluent to read. Secondly, in this study, the authors compared MCMG in the DRD2 task, but not in the ACE2 task. Wouldn't it be more natural to compare it in both tasks? What is the reason for excluding it from the comparison in the ACE2 task? We thank the Reviewer for pointing out this issue. Initially, we also want to compare MCMG in both tasks. However, after a careful investigation, we found it not doable. MCMG relies on a Transformer decoder, which is trained on known binding molecules, to distill the knowledge to GRU. However, in the ACE2 task, we tackled the task where no sufficient binding molecules exist. MCMG was not designed for such tasks and cannot be applied to tackle this problem. Thirdly, while going through the supplementary information, I came across Supplementary Figure 8, which serves as a clear illustration. I believe the author should incorporate it into the main content as it provides a clear explanation of the resulting distributions. Figure 5 should be relocated to the supplementary material instead. We thank the Reviewer for the kind advice. We included the main subfigures from Supplementary Figure 8 into our main context to showcase the improvement of properties in the optimization process. Figure 5 illustrates the increasing number of rings in the molecules generated in the first several steps. We think it is one of the most important discoveries in the results, so we would like to keep it in the main context. Furthermore, the author should thoroughly proofread the paper for any typos and formatting errors. For instance, 'the' should be added before 'Moses benchmark'. In the first paragraph of Subsection 'Evaluation metrics', 'Similarity to a nearest neighbor (SNN)' should be corrected to 'similarity to a nearest neighbor (SNN)'. We thank the Reviewer for pointing out these typos and errors. We meticulously reviewed this article again, and fixed the errors and typos pointed out."
}
]
},
{
"id": "214547",
"date": "01 Nov 2023",
"name": "Jianmin Wang",
"expertise": [
"Reviewer Expertise drug design",
"deep 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\nThis paper introduces a method called SGPT-RL, which utilizes GPT as the policy network in the Reinvent approach to improve the optimization of binding affinities, such as DRD2 QSAR score and ACE2 docking score. The findings of the study indicate that GPT effectively learns about the chemical space and generates compounds that are both novel and valid, which is consistent with previous research. Furthermore, GPT proves to be proficient in learning ring patterns and successfully explores various scaffolds during the exploration process in both optimization tasks. Particularly in the ACE2 task, SGPT-RL outperforms by achieving superior docking scores and identifying specific patterns, like the presence of double-ring structures.\nThe study shows promise overall, with GPT being a robust generative model and drug design being an important area of application for generative AI. The manuscript is well composed, but certain improvements are necessary to address a few issues.\nMajor issues:\nIn this study, the authors compared MCMG in the DRD2 task but chose not to include it in the ACE2 task. It seems more logical to compare MCMG in both tasks. However, what might be the rationale behind excluding it from the ACE2 task comparison?\n\nThe clarity of the presented results is insufficient. In my opinion, Supplementary Figure 8 effectively demonstrates the distributions and should be included in the main content for clear comprehension. Figure 5, on the other hand, would be more suitable to be relocated to the supplementary material.\nMinor issues:\nThe manuscript is burdened with too many explanations for common abbreviations, making it a tedious read. For example, the abbreviation \"SGPT-RL\" is explained repeatedly in each figure, and abbreviations like \"RL,\" \"DRD2,\" and \"ACE2\" are needlessly reiterated in the captions. It would be more efficient to provide explanations for these abbreviations only when they first appear in the captions, thus avoiding unnecessary repetition.\n\nThe authors should carefully review the paper to avoid any typos and grammatical errors. Specifically, 'the' should be included before 'Moses benchmark'; 'Similarity to the nearest neighbor (SNN)' in the Subsection 'Evaluation metrics', need to be in lower case; “range in1, 10” should be “range in [1, 10]”.\n\nSeveral spots are not fluent to read. For example, the first sentence in the “Model architecture” Subsection does not fit with the context and should be tuned. “see also Underlying data” doesn’t fit with the context as well.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? 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": "11065",
"date": "13 Apr 2024",
"name": "Xiaopeng Xu",
"role": "Author Response",
"response": "We thank the Reviewer for sharing our aims and appreciating our efforts. Point by point responses to the issues are as follows. Major issues: 1. In this study, the authors compared MCMG in the DRD2 task but chose not to include it in the ACE2 task. It seems more logical to compare MCMG in both tasks. However, what might be the rationale behind excluding it from the ACE2 task comparison? We thank the Reviewer for pointing out this issue. Initially, we also want to compare MCMG in both tasks. However, after a careful investigation, we found it not doable. MCMG relies on a Transformer decoder, which is trained on known binding molecules, to distill the knowledge to GRU. However, in the ACE2 task, we tackled the task where no sufficient binding molecules exist. MCMG was not designed for such tasks and cannot be applied to tackle this problem. 2. The clarity of the presented results is insufficient. In my opinion, Supplementary Figure 8 effectively demonstrates the distributions and should be included in the main content for clear comprehension. Figure 5, on the other hand, would be more suitable to be relocated to the supplementary material. We thank the Reviewer for the kind advice. We included the main subfigures from Supplementary Figure 8 into our main context to showcase the improvement of properties in the optimization process. Figure 5 illustrates the increasing number of rings in the molecules generated in the first several steps. We think it is one of the most important discoveries in the results, so we would like to keep it in the main context. Minor issues: 1. The manuscript is burdened with too many explanations for common abbreviations, making it a tedious read. For example, the abbreviation \"SGPT-RL\" is explained repeatedly in each figure, and abbreviations like \"RL,\" \"DRD2,\" and \"ACE2\" are needlessly reiterated in the captions. It would be more efficient to provide explanations for these abbreviations only when they first appear in the captions, thus avoiding unnecessary repetition. We thank the Reviewer for pointing out this issue. We updated the paragraphs and captions and removed the repeated explanations to make the sentences more fluent to read. 2. The authors should carefully review the paper to avoid any typos and grammatical errors. Specifically, 'the' should be included before 'Moses benchmark'; 'Similarity to the nearest neighbor (SNN)' in the Subsection 'Evaluation metrics', need to be in lower case; “range in1, 10” should be “range in [1, 10]”. We thank the Reviewer for pointing out these typos and errors. We meticulously reviewed this article again, and fixed the errors and typos pointed out. 3. Several spots are not fluent to read. For example, the first sentence in the “Model architecture” Subsection does not fit with the context and should be tuned. “see also Underlying data” doesn’t fit with the context as well. We thank the Reviewer for pointing out these spots. We updated the sentences to make them more fluent to read. Specifically, we removed the sentence “Please note that all code associated with this article is available in the Software availability section” and “see also Underlying data” within the paragraphs."
}
]
},
{
"id": "214522",
"date": "12 Dec 2023",
"name": "Qifeng Bai",
"expertise": [
"Reviewer Expertise deep learning",
"binding affinity and drug 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\nIn this study, authors use generative pre-trained transformer and deep reinforcement learning to optimize the binding affinities in chemical space. I have some comments as follows:\n1. I have checked the source codes https://github.com/charlesxu90/sgpt. The authors give a nice description for their models. I have an install question. Why do authors repeat to install “openbabel” by command: “sudo apt-get install -y openbabel” even though Conda can install openbabel?\n2. Please check equation 1. There are some kinds of attention formulas. Do authors describe the correct attention formulas for their used pre-trained models?\n3. To make the affinity introduction richer, authors can add more references about binding affinities with deep learning methods such as “Bai, Q, Liu, S, Tian, Y, Xu, T, Banegas-Luna, AJ, Pérez-Sánchez, H, et al. Application advances of deep learning methods for de novo drug design and molecular dynamics simulation. WIREs Comput Mol Sci. 2022; 12:e1581. https://doi.org/10.1002/wcms.1581 “\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "11066",
"date": "13 Apr 2024",
"name": "Xiaopeng Xu",
"role": "Author Response",
"response": "We thank the Reviewer for the summary and the helpful comments. Point by point responses to the issues are as follows. 1. I have checked the source codes https://github.com/charlesxu90/sgpt. The authors give a nice description for their models. I have an install question. Why do authors repeat to install “openbabel” by command: “sudo apt-get install -y openbabel” even though Conda can install openbabel? We thank the Reviewer for looking into the code and pointing out this issue. We also want to use openbabel in Conda, however, in our experiments, we found that the default openbabel in Conda is not providing the functionality required. The default openbabel installed in our system works well. We believe this is an issue due to the distributed version of openbabel in Conda at the time of our experiments. 2. Please check equation 1. There are some kinds of attention formulas. Do authors describe the correct attention formulas for their used pre-trained models? We thank the Reviewer for pointing out this issue. We trained a generative pre-trained transformer (GPT) from scratch to learn the prior knowledge of molecular distributions. A GPT-2 model with the multi-head self-attention mechanism was used in our model. Equation 1 describes the attention mechanism, which is the core element of it. 3. To make the affinity introduction richer, authors can add more references about binding affinities with deep learning methods such as “Bai, Q, Liu, S, Tian, Y, Xu, T, Banegas-Luna, AJ, Pérez-Sánchez, H, et al. Application advances of deep learning methods for de novo drug design and molecular dynamics simulation. WIREs Comput Mol Sci. 2022; 12:e1581. https://doi.org/10.1002/wcms.1581 “ We added this citation as suggested by the Reviewer."
}
]
},
{
"id": "188009",
"date": "12 Dec 2023",
"name": "Aslıhan Aycan Tanrıverdi",
"expertise": [
"Reviewer Expertise - Polymer Synthesis and Characterization- Monomer Synthesis and Ch.- Quantum Chemistry- Molecular Modelling- Molecular Dynamic- Drug Design- Density Functional Theory- Atom in Molecules Analysis- Film Formation- Gel Formation"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 published the paper entitled \"Optimization of binding affinities in chemical space with generative pre-trained transformer and deep reinforcement learning [version 1; peer review: 1 approved with reservations].\" The work is very comprehensive. An innovative article worth publishing. I want to congratulate the authors. There's just one point where I'm stuck.\n***QSAR processing methodology should be given step by step in the methods section.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? 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": "11067",
"date": "13 Apr 2024",
"name": "Xiaopeng Xu",
"role": "Author Response",
"response": "We thank the Reviewer for sharing our aims and appreciating our efforts. The issue pointed out is responded as below. ***QSAR processing methodology should be given step by step in the methods section. We thank the Reviewer for pointing out this issue. We added descriptions to explain the QSAR processing part, as presented below. \"In the modeling, a SMILES is converted into molecules to obtain the Morgan fingerprints using RDKit. The fingerprints were used as the features to build the SVM classifier. It predicts a probability score range from zero to one, with the closer to one the higher DRD2 activity. A molecule that cannot obtain valid fingerprints was assigned with a score of zero.\""
}
]
}
] | 1
|
https://f1000research.com/articles/12-757
|
https://f1000research.com/articles/11-907/v1
|
08 Aug 22
|
{
"type": "Research Article",
"title": "Determinants of adherence to insulin and blood glucose monitoring among adolescents and young adults with type 1 diabetes in Qatar: a qualitative study",
"authors": [
"Hanan AlBurno",
"Francine Schneider",
"Hein de Vries",
"Dabia Al Mohannadi",
"Liesbeth Mercken",
"Francine Schneider",
"Hein de Vries",
"Dabia Al Mohannadi",
"Liesbeth Mercken"
],
"abstract": "Background: Adherence to insulin and blood glucose monitoring (BGM) is insufficient in adolescents and young adults (AYAs) with type 1 diabetes (T1D) worldwide and in Qatar. Little is known about the factors related to being aware of non-adherence and the beliefs related to non-adherence in this group. This qualitative study investigated factors related to awareness of, and beliefs about non-adherence, as well as the existence of specific action plans to combat non-adherence using the I-Change model.\nMethods: The target group was comprised of 20 Arab AYAs (17–24 years of age) with T1D living in Qatar. Participants were interviewed via semi-structured, face-to-face individual interviews, which were audio-recorded, transcribed verbatim, and analyzed using the Framework Method.\nResults: Suboptimal adherence to insulin, and particularly to BGM, in AYAs with T1D was identified. Some AYAs reported to have little awareness about the consequences of their non-adherence and how this can adversely affect optimal diabetes management. Participants also associated various disadvantages to adherence (e.g., hypoglycemia, pain, among others) and reported low self-efficacy in being adherent (e.g., when outside home, in a bad mood, among others). Additionally, goal setting and action-planning often appeared to be lacking. Factors facilitating adherence were receiving support from family and healthcare providers, being motivated, and high self-efficacy.\n\nConclusions: Interventions that increase awareness concerning the risks of non-adherence of AYAs with T1D are needed, that increase motivation to adhere by stressing the advantages, creating support and increasing self-efficacy, and that address action planning and goal parameters.",
"keywords": [
"type 1 diabetes",
"adolescent",
"young adult",
"insulin",
"blood glucose monitoring",
"adherence",
"qualitative research."
],
"content": "Introduction\n\nType 1 diabetes (T1D) is reaching epidemic proportions1–3 with an annual rise of about 2-5% worldwide.1,4 The exact incidence of T1D in young adults is unknown because reports do not usually distinguish between type 1 and type 2 diabetes in young adults, and available data primarily pertains to children and adolescents.1,2 The Middle East (ME) region, including Qatar, has some of the highest T1D prevalence rates globally,5–7 with significant physical, social, and financial costs.8–10 It is well known in the case of diabetes that T1D in itself constitutes a risk of developing complications, such as nephropathy, retinopathy, neuropathy, and cardiovascular disease.11,12 The focus of the present study was late adolescents and young adults (AYAs), because of their unique developmental, social, mental, and physical characteristics and behaviors.13–15 AYAs with T1D demonstrate a decline in diabetes self-care behaviors and deterioration of glycemic control and therefore are at an increased risk of developing early diabetes complications.14,15\n\nInsulin administration (IA) and blood glucose monitoring (BGM) either by self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM) practices are the key components of the diabetes self-care regimen for T1D. The association between insulin adherence and good metabolic control is well documented.16–18 Large controlled clinical trials have demonstrated that intensive insulin treatment of diabetes can significantly decrease the development and/or progression of the complications of diabetes.12,19,20 Similarly, evidence shows that SMBG21–23 and CGM23–26 can help patients with diabetes detect blood glucose levels and variability, thus adjusting insulin demands. They also provide safety by informing about hypoglycemia. Furthermore, studies have linked regular SMBG27,28 and CGM26,29 to better glycemic control. Schwandt et al. (2017) discovered that patients who self-monitored more than six times daily had lower hemoglobin A1c (HbA1c) than patients who monitored less frequently.28\n\nFindings have shown that insulin adherence among AYAs with T1D is poorer compared to younger children and adults.15,30 AYAs with T1D tend to reduce or omit insulin doses intentionally or unintentionally.31–33 They may also unintentionally increase the dose.34,35 Other insulin adherence-related activities which AYAs with T1D often find to be challenging include carbohydrate (CHO) counting and dose adjustment.36,37 Likewise, studies have demonstrated that regular SMBG38–40 and CGM26,29,38 are underutilized in AYAs. McCarthy and colleagues (2018) reported that emerging adults (age 18–25 years) were performing fewer daily blood glucose checks compared to older age groups (age 25 to ≥65 years).32 Data from the Juvenile Diabetes Research Foundation (JDRF) Continuous Glucose Monitoring (CGM) Study Group revealed that 30% of patients aged 15–24 years used CGM at least six days a week, compared with 50% of patients aged 8–14 years and 86% of patients older than 25 years.16,32\n\nMultiple factors influence adherence and non-adherence to the prescribed recommendations.41,42 However, previous literature has focused predominantly on investigating selected factors, such as socio-demographic (e.g., age, gender, ethnicity, personality) (i.e., Davies et al., 2013; Neylon et al., 2013; Gonzalez et al., 2016; Gloaguen et al., 2018),43–46 socioeconomic (e.g., cost of treatment) (i.e., Davies et al., 2013; Datye et al., 2015; Gonzalez et al., 2016; Gloaguen et al., 2018),43,45–47 and certain aspects of psychosocial factors including affect component (e.g., diabetes emotional distress, depression, anxiety) (i.e., Borus et al., 2010; Davies et al., 2013; Neylon et al., 2013; Datye et al., 2015; Gloaguen et al., 2018; Martinez et al., 2018; Berger et al., 2019; van Duinkerken et al., 2020),16,43,44,46–50 behavior components like eating disorders (Borus et al., 2010; Berger et al., 2019)16,49 and interactions with family (i.e., Borus et al., 2010; Davies et al., 2013; Datye et al., 2015; Gloaguen et al., 2018)16,43,46,47 and healthcare system (i.e., Datye et al., 2015),47 as well as cognition (e.g., knowledge and perception towards diabetes and insulin) (i.e., Gonzalez et al., 2016; Martinez et al., 2018).45,48 Other factors included the complexity of the insulin regimen (i.e., Datye et al., 2015; Jaam et al., 2017)47,51 and type of administration device (i.e., Borus et al., 2010; Gloaguen et al., 2018).16,46\n\nStudies that have used psychological/behavioral models to predict and improve treatment adherence have failed to consider all potentially relevant theory-based socio-cognitive factors in an integrated way.38 Hence, a comprehensive understanding of the socio-cognitive determinants that predict insulin and BGM adherence among AYAs with T1D is needed to develop approaches that integrate these findings into more effective diabetes management programs and services. Within this context, the present study employed an integrative theoretical framework, the I-Change model (ICM),52,53 because it considers numerous and multilevel influences on behavior at three distinct phases: awareness (cognizance, knowledge, risk perception and cues to action), motivational (attitude, social influence, and self-efficacy), and action (action planning and coping planning) (Figure 1). It also considers distal predisposing factors such as information factors (the quality of messages, channels, and sources used). ICM has been successfully used to predict and change treatment adherence behaviors in people with type 2 diabetes (T2D).54–56 The findings from this study are important for tailoring an education programme to improve IA and BGM adherence, and hence diabetes outcomes. They are also useful for diabetes policy strategies aiming to support patients’ needs. Furthermore, few studies have looked at T1D patients in their late adolescence and early adulthood.57,58 T1D studies are limited in the Middle East and North Africa (MENA) region, whereas cultural beliefs and practices are important determinants of diabetes self-management behaviors.59 Therefore, this study aimed to explore adherence determinants to IA and BGM in AYAs, in the age range of 17–24 years within the context of their daily lives, their environment, and cultural and family dynamics in Qatar.\n\nThis figure has been reproduced with permission from de Vries (2017).52\n\n\nMethod\n\nThe Institutional Review Board (IRB), Medical Research Centre Committee-Hamad Medical Corporation approved the study (17017/17).\n\nSemi-structured, face-to-face individual interviews were used. The rationale for using this method was to obtain a detailed description and an in-depth understanding of diverse participants’ perspectives on subjects of interest,60,61 and encourage free discussion, especially when disclosing sensitive issues.62 Data collection started in October 2017 and continued until January 2018, when 20 interviews were deemed sufficient to achieve data saturation,51,63 and no further information could be added. This study was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ).64\n\nArab AYAs with T1D aged 17-24 years old receiving insulin therapy for at least two months prior to the study, and those using SMBG or CGM were eligible. Patients were treated in outpatient diabetic clinics at Hamad General Hospital, the main public hospital in Doha, Qatar. The exclusion criteria were: gestational diabetes, secondary diabetes resulting from medical conditions or certain medications, such as corticosteroids; cognitive impairments, and drug and alcohol dependence. To ensure maximum variation sampling,65 the physicians purposively selected eligible patients who were attending the clinic and had varied experiences across the indicated age group, i.e., patients with optimal, suboptimal and poor metabolic control,66,67 using HbA1c as an index of glycemic control over the previous two-three months.68 The aim was to obtain varied participants’ perceptions of their level of metabolic control and whether they linked this level to their adherence behaviors. Data on HbA1c was collected from patients’ records. HbA1c levels were categorized into three levels of control based on the clinical practice guidelines’ recommendations,23,69–71 with optimal control defined as <7.5% (<58 mmol/mol), suboptimal 7.5-9% (58-75 mmol/mol) and poor >9% (>75 mmol/mol) in adolescents. In young adults, optimal control denoted <7% (<53 mmol/mol), suboptimal 7-7.9% (53-63 mmol/mol) and poor ≥8% (≥ 64 mmol/mol). Purposive sampling continued in parallel during data collection. Patients who agreed to participate were referred to the principal investigator (HB), who explained the study in detail and obtained written informed consent forms from young adults aged 18 to 24 years and assent forms from adolescents under 18 years old, which included their carers’ consents. Two patients declined to participate in the study, citing a busy schedule, but none of those who agreed to participate withdrew from the study.\n\nThe first author (HB), trained in qualitative research and having no prior or post work relationship with the participants, used an open-ended and piloted interview guide during the interviews. ICM was used as the theoretical framework for developing the guide.52 The interview discussion topics are represented in Table 1. Experts in qualitative research methodology, in the area of behavior change theories, and in T1D, guided the development of the guide. The interviews were held in private at the outpatient diabetic clinics and took approximately 60 minutes. Participants were assured that all information would only be used for research purposes. Permission to audio-record and to take notes was granted before starting the interviews, which were then transcribed in Arabic before being translated into English. During the interview sessions, probing questions were used to elicit information extraction, such as (“Can you tell me more? Would you give me an example? Would you explain that further?” among others). To ensure that the participants’ answers were understood, the interviewer repeated the participants’ words and confirmed the summarized main points of their responses with them. Prior to interviewing, we collected information on demographics, diabetes, and insulin history.\n\nDemographic and clinical characteristics\n\nDemographic and clinical characteristics were described using descriptive statistics and frequencies.\n\nResults were expressed as means (standard deviation [SD]) or percentage of total responses, such as the percentages of patients with optimal, suboptimal, or poor metabolic control. Participants were classified as adherents or non-adherents based on their responses during the interviews. Those who reported always or almost always administering insulin or testing blood glucose as recommended were classified as adherents; those who did not were classified as non-adherents.\n\nThematic data analysis\n\nThe framework method was used to analyze the data thematically.72,73 This method was chosen for the following reasons: first, it enables capturing different aspects of behavioral determinants; second, it guides systemic analysis through interrelated stages to describe as well as understanding the behaviors with their corresponding determinants. Third, it ensures transparency of data interpretations.74 The analysis started with the familiarization stage, during which the coder (HB) read through all the transcripts and generated notes about common themes and other concepts from the data by considering each line and phrase. Firstly, a deductive theory-driven analysis was chosen. Based on this approach, a coding book was initially developed using the ICM described previously. The codebook was extensively reviewed by the authors HB, FS, and LM until agreement on the main codes and sub-codes was reached. All transcripts were coded manually in accordance with the coding book. The researchers HB, FS, and LM discussed the coding process to establish reliability.75 The next stage was identifying the thematic framework (coding tree). During this process, codes were organized hierarchically based on how they related to one another, and additional emergent codes from the open discussions were added to the initial codebook and coding tree. An inductive approach was also used to generate meanings and to identify the patterns that could be grouped into themes and categories. During the final interpretation stage, mapping connections between the categories and the main themes aimed to look for similarities, differences, and patterns in the meaning of data. For example, the relationship between self-efficacy and coping plans; comparing participants’ perceptions about their diabetes control and their HbA1c values. Validity and reliability were established through member checking during the coding process and investigator triangulation during data analysis.60\n\n\nResults\n\nOut of the 20 interviewees, 70% were Qatari, 55% were females, and 65% had diabetes for longer than ten years. The mean age was 20.5 ± 2.35. Demographic and medical status information are shown in Table 2.\n\nAYAs with T1D most often asked healthcare professionals (physicians, diabetic educators, and dietitians) about information related to insulin and BGM. Many used general Internet websites as they indicated that diabetes-specialized websites in the Arabic language were deficient (Quote #1). They also sought information from friends without diabetes, parents, relatives, and trainers at the gym. Nearly all participants suggested that the information ideally should be simplified, updated, applicable to daily life, and refreshed. Female subjects wanted more information about pregnancy and child delivery. Others wanted to know more about cases that related to them to help them in the decisions they make on a daily basis (Quote #2). Others wanted more information about counting CHOs and what to do when blood glucose levels are very high.\n\nCognizance\n\nAlmost all participants reported being cognizant about whether they were adherents or not to injecting insulin and BGM as agreed with their HCPs. Quite a few participants indicated being adherent to IA on time. Still, some reported that they sometimes skipped insulin, either intentionally or unintentionally. A few others admitted that they were un-adherent most of the time. Some AYAs, particularly females, deliberately omitted insulin doses to induce hyperglycemia for inpatient admission to avoid school exams or family conflicts (Quote #3). Very few females skipped or reduced insulin doses to control their weight (Quote #4). Irrespective of adherence to insulin, many participants were adherent to carbohydrate counting, apart from a few patients who either needed more education or more motivation to use the required information. Very few participants described themselves as adherent to healthcare providers’ recommendations in terms of the frequency of SMBG and CGM. Two participants said that they would check their blood glucose before doing physical activity. The majority of patients reported testing randomly or rarely (Quotes #5 and #6).\n\nThe awareness of diabetes control level varied between participants. Many of them, irrespective of whether they were adherents or not, believed that their diabetes was uncontrolled. Some reported that their T1D was fairly controlled (Quote #7). Some non-adherent AYAs perceived that their diabetes was controlled, but their perceptions were not consistent with their actual HbA1c levels; thus, they did not feel that they needed to adjust their adherence behaviors (Quotes #8 and #9).\n\nThe main changes few non-adherents wished to make were to manage their time effectively, care more about their health, be able to make diabetes decisions in general and control their HbA1c. Relating to IA, some non-adherents wished not to forget to administer or skip doses. Also, to be competent in counting CHO, while other non-adherents wished to perform BGM more frequently as recommended. A number of poorly adherent patients indicated that there was no need to change their adherence behavior at all. They stated that they did not accept the disease or the treatment; others believed that bringing their glucose levels near normal levels was impossible (Quotes #10 and #11).\n\nKnowledge\n\nRegarding knowledge, all adherents reported knowing how to calculate CHO and use the corrective dose, as well as how to obtain the necessary information from HCPs (Quote #12). However, a few non-adherents stated that they lacked the necessary knowledge to count CHO content, adjust insulin dose accordingly, and base decisions on BGM results (Quote #13), and a couple others reported lacking a certain level of knowledge about long-term complications of diabetes.\n\nRisk perception\n\nNearly all adherents and many non-adherents reported being aware of the risks of developing short- and long-term complications resulting from non-adherence and acknowledged that these complications could have a severe impact on their health, like prolonged hyperglycemia, coma, blindness, and leg amputation (Quote #14). A few adherents, on the other hand, believed that adherence would delay severe long-term complications like renal failure; however, less severe complications like microalbunurea and short-term complications like hypoglycemia are unavoidable (Quote #15). Nonetheless, some non-adherents believed that whatever they did, the complications were unavoidable (Quote #16). Many non-adherents were more likely to be worried about the complications if they avoided thinking about them. Others believed that the complications would not occur as long as they controlled their diabetes (Quotes #17 and 18). Some adolescent non-adherents believed they still had years to develop complications since they were still young, or according to their religious beliefs, everything that happens to them is destined to happen (Quotes #19 and 20).\n\nRegarding BGM, very few adherents thought they were less likely to have complications because of regular testing. They could easily detect and act on hypo-or hyperglycemia (Quote #21). A number of non-adherents, however, did not associate the risks of their non-adherence with a level of diabetes control (e.g., detecting variations in blood glucose levels and linking these to possible causes and acting on them to bring blood glucose levels to a near normal level) or with diabetes-related complications (e.g., detecting unawareness hypoglycemia). These patients checked only when they felt the symptoms of hypo-or hyper-glycemia. Some others lacked the awareness to check even when they were experiencing hypoglycemia (Quotes #22 and 23) (Table 3).\n\nAttitude\n\nParticipants discussed the advantages and disadvantages of adhering to insulin from a physical, practical, and psychological perspective. All interviewees reported similar physical advantages, like controlling, normalizing, or decreasing blood glucose and subsequently avoiding symptoms of hyperglycemia, e.g., fatigue, dizziness, and frequent urination (Quotes #24). The main practical benefit identified by many adherents was improved quality of life for not being hyperglycemic all of the time. Adherents described specific benefits related to the practicality of using injectable devices; while some found injectable pens satisfactory and provided flexibility; others found insulin pumps to be more flexible (Quotes #25 and 26). Nearly all adhering participants agreed on the psychological advantages of adherence, like feeling relieved, not worried, not stressed, under control, and feeling like a normal person (Quote #27).\n\nAll interviewees reported similar physical disadvantages, like skin irritation and discoloration, muscle deformity, and hypoglycemia (Quote #28). Few students talked about the disadvantages of experiencing hypoglycemia the night before or while taking standardized tests, which have adversely affected their exam performances. They requested consideration of options to retake the test and to refund the test fees in case of inability to take the exam due to their diabetes (Quote #29). Weight gain was of particular inconvenience, especially among pump users because of the ease of use of corrective doses and the difficulty of losing weight (Quote #30). Non-adherents talked about the interference of insulin in their daily routine and found the process of injecting and CHO counting as tiring and time-consuming as the main practical disadvantages (Quote #31). Some non-adherents found the pump inconvenient because of life-interference, pain at the injection site, hassle, and the time it takes to prepare the pump (Quotes #32). All non-adherents discussed the psychosocial disadvantages relevant to diabetes care, including negative emotional reactions such as anxiety, depression, among others; ideals for weight; intolerance of regularity; fear of needles and testing, fear of hypoglycemia, which resulted in omitting insulin to avoid hypoglycemia; feeling the burden of counting CHO in their meals and synchronizing insulin dose with CHO content (Quotes # 33). Few female subjects mentioned their concerns about future marital relationships and the side effects of insulin on pregnancy and having babies. One male talked about his concern about erectile dysfunction.\n\nRegarding BGM, very few adherents appreciated the advantages of providing assurance and safety through detecting hypoglycemia/hyperglycemia patterns and blood glucose levels (Quote #34). CGM’s specific practical advantages were the ease and convenience of using sensors (Quote #35). Overall, many non-adherents doubted the role of monitoring in managing diabetes (Quote #36) and described physical, practical, and psychological disadvantages. The physical disadvantages included pain, while skin discoloration, irritation, and callus were particularly relevant among female non-adherents, such that they stopped testing altogether (Quote #37). Some non-Qatari individuals mentioned the cost. Practical disadvantages include frequency of testing, as it needs considerable time management and planning efforts; accuracy and practicality of use through the ability to interpret and act on results; and access to a glucometer. A few non-adherents found CGM inaccurate and described preparing the sensor as disturbing. Non-adherents illustrated psychological disadvantages linked to fear of pricking and negative feelings.\n\nSocial influence\n\nTo many adherents, family social influence was perceived as positive, especially when they were younger. However, as they grew older, they wanted to take more control over their diabetes, IA, and BGM. Many of them also appreciated the support they got from their healthcare team, especially the diabetic educators (Quotes #38 and #39). Several non-adherents accepted advice around diabetes from their close friends but not from their families; they felt family interactions were stressful and conflictual, which elicited guilt and overprotective emotions (Quotes #40 and #41).\n\nWhile some adherents informed their friends about their disease and IA to help them when they were experiencing hypoglycemia events, non-adherents did the opposite because they did not want to be treated differently or with pity. Some felt that the interference of their friends had embarrassed or labelled them. Others justified that their friends were less supportive because they did not know much about diabetes and its complications. To avoid stigma, some skipped insulin or testing in public places (Quotes #42 and #43).\n\nOne of the emerged themes was social modelling, where some adolescents used traditional homeopathic medicines such as ginger, cinnamon, and pomegranate peel drinks or even bee stings to substitute insulin, just as their older relatives with diabetes did (Quote #44).\n\nSelf-efficacy\n\nThe situations which facilitated adherence for some adherents were using the pump and seeing positive results; also, when not surrounded by people and when supported by the healthcare system, when injecting or testing. Unlike non-adherents, the daily IA and BGM of adherents became life routines with the long duration of diabetes (Quotes #45 and #46).\n\nNon-adherents, particularly those using insulin pens and glucometers, highlighted a range of situations in which IA and BGM adherence were perceived to be difficult. These included, first, practical situations in which AYAs found it unpractical to take the insulin pen or the glucometer with them when they are outdoors (Quotes #47 and #48); second, social and cultural situations such as injecting or testing in public places because of people’s curiosity and being judgmental or due to shyness or preference for maintaining a relationship over being adherent (Quotes #49 and #50); third, physical external environmental situations such as traveling, when engaged in social events, being busy. The internal physical situations were related to forgetfulness and sleep issues like feeling sleepy, having a different sleeping pattern, or sleeping (Quotes #51 and #52); fourth, psychological situations, e.g., being in a bad mood, low motivation, feeling restricted and occupied. All non-adherents reported being overwhelmed by their emotions due to the disease’s long duration and the fact that it is incurable, which has negatively impacted their acceptance and adherence (Quotes #53 - #55) (Table 4).\n\nPreparatory, action and coping planning\n\nThe majority of participants, irrespective of adherence, did not report having made preparatory or action plans to control their T1D, adhere to IA and/or BGM, or cope with problems. A few non-adherents considered increasing the frequency of SMBG, decreasing insulin dose, and not using the corrective dose on a regular basis, but they lacked structured plans (Quote # 56). Few others saw planning as an additional emotional strain because they would be preoccupied with their plans (Quote #57).\n\nConcerning coping planning, only one newly diagnosed male used reminders to help him adhere to IA and SMBG (Quote #58). The vast majority of non-adherents did nothing to cope with the difficult situations they encountered in IA, while some used maladaptive coping strategies by drinking herbal tea when they were in a bad mood to use insulin (Quotes #59 and #60). Further, setting goals, maintaining adherence, and the actual skills required (matching insulin dose with CHO content and interpreting BGM results and the ability to act on them) were reported by many non-adherents as areas where they needed improvement in. Routine intolerance and decommitment, having low desire, lack of intention and self-control, distraction, confusion about what to do, not feeling supported as they used to be when they were younger, and not seeing the results, were reported as common barriers to coping with adherence. (Quotes #61- #63). Among the very few facilitating factors reported by adherents were that they kept themselves motivated and had a great deal of self-discipline (Quote #65) (Table 5).\n\n\nDiscussion\n\nThe current study aimed to identify determinants of IA and BGM adherence among AYAs with T1D in Qatar. Our results confirm previous data indicating that IA and BGM adherence continues to be a problem in this age group.\n\nNearly all patients wanted information provided to them to apply to their daily lives, and be refreshed more frequently. Consistent with other results,76 female subjects wanted more information about pregnancy and child delivery. Few non-adherents sought information from older relatives who recommended homeopathic medicines instead of insulin or from generic websites. A previous study among Qatari participants showed that 95% of them used Google as a search engine to look for health information, and the younger adults were using the Internet significantly more than older adults.77 Evidence supports that lack of information78 or irrelevant and false information can negatively impact diabetes management. International guidelines recommend that the information provided to patients should be structured, continuous, and accessible in a language that the patient understands and fulfils his/her needs.79,80 Therefore, it is necessary to focus on improving information-seeking behaviors, understanding how the patient processes information, and translating this understanding into action so as to improve knowledge and facilitate positive self-care behaviors.\n\nConcerning cognizance, this study showed that almost all adherents and non-adherents reported being aware of their behaviors. Yet, a few non-adherents did not have enough awareness that they needed to change their behaviors due to misjudgment about their level of diabetes control, misbelief about achieving target levels, or lack of acceptance of the disease and the treatment. Prior findings support the hypothesis that AYAs who accepted their disease were more adherent than those who did not,81,82 while those who did not achieve their target blood glucose levels felt powerless and under an impossible burden.83 It is documented that knowing how the patient perceives his or her illness improves adherence.84,85 Therefore, increased awareness, monitoring, and support for patients with diabetes, especially those with problems in psychological adaptation, are needed within different T1D care settings.\n\nRegarding knowledge, our study confirms recent findings on the importance of periodically assessing the knowledge and readiness for education of patients with diabetes in clinic visits to meet the demanding nature of diabetes.86 This is necessary because learning is more likely to be achieved when it is presented from the patient’s perspective.\n\nConcerning risk perceptions, our findings showed that few adherents perceived insulin adherence would delay long-term complications (like renal failure) but not short-term complications (like microalbuminuria). Researchers have found contradictory results relating risk perceptions of AYAs with T1D and adherence to DSM activities, emphasizing the need to identify short- and long-term complications when assessing risk perceptions of diabetes in AYAs.87,88 Additionally, in this study, non-adherents indicated that they were not aware of the risks associated with non-adherence. Some groups, reported to deliberately omit insulin doses to induce hyperglycemia to get exam exemptions or avoid family problems. Previous research showed that female adolescents who experienced family problems were more likely to develop psychiatric problems and medication non-adherence.89 Previous cases of deliberate insulin misuse to induce dysglycemia (hypoglycemia or hyperglycemia) have been observed in AYAs with T1D. Patients’ motives varied, such as mental disorders like major depression or factitious disorder (FD) and/or suicidal ideation.31,34,90–92 Induced hypoglycemia was also used to justify eating sweets and carbohydrate-rich meals.31 Factitious dysglycemia should be considered a possible cause of brittle diabetes and requires specialist consultation.90,92 However, the literature on FDs from the Arab region is limited,93,94 with only one report on Iraqi women with type 1 and type 2 diabetes.92 More information is needed from the Arab region to clarify FD’s clinical profile and implications for T1D. Our findings support results from earlier studies95,96 indicating that some AYAs with T1D were not sufficiently aware of the consequences of their illness-specific risk behaviors, which could have a negative impact on optimal management and outcomes, such as severe hyperglycemia, diabetic ketoacidosis, and long-term diabetes complications. Further, similar to previous findings,97 other non-adherents believed that they were less vulnerable to complications because of inherent beliefs that they wouldn’t suffer any negative outcomes or because complications would occur at an older age. Others, and in line with Garrett and colleagues’ study (2014)98 felt that complications were inevitable despite their best efforts. Moreover, a few non-adherents perceived the susceptibility and severity of risks associated with IA non-adherence as ongoing threats that were worrying and depressing, and they avoided thinking about them. These threats have previously been identified to affect AYAs’ emotional well-being and adherence,99–101 and those who perceived their illness to be of greater severity demonstrated poorer glycemic control.102,103 Yet, perceptions of risk and severity may encourage adherence.84,104,105 A meta-analysis has shown that communicating threat messages has an effect on behavior only when efficacy is high.106 Indeed, our results have addressed, similarly to other recommendations,85,107,108 the importance of teaching AYAs about the potential long-term complications in a way that is not depressing or discouraging.\n\nThe findings indicated that the majority of non-adherents did not perceive being at risk because of non-adherence to BGM, and thus they rarely tested themselves. Previously, knowledge gaps regarding SMGB were identified39,.109,110 A prior study found that patients who were less knowledgeable about the importance of glycemic control in developing diabetes vascular complications were less adherent to SMBG.111 In summary, understanding awareness factors is a prerequisite for understanding individuals’ engagement or disengagement in adherence behavior and should be continually evaluated and addressed in every health encounter.\n\nThe majority of non-adherents reported not believing that adhering to the frequency of BGM as recommended would be advantageous. Similar findings are also reported in other studies.112,113 It is also known that the psychological impact of a chronic illness alters an individual’s attitude and affects medication adherence.114 While national and international guidelines recommend that periodic psychological screening should generally be a routine part of diabetes management,115–118 it is clear that these recommendations are not yet being followed up sufficiently. It is important to develop communication strategies to convince non-adherent patients to adhere to the recommended frequency of BGM. This study also highlights AYAs’ concerns about diabetes and its impact on pregnancy, marital life, and sexual dysfunction (SD). Previous research has discovered that AYAs with T1D have more conflicting marital relationships than their non-diabetic counterparts.58,89 Studies from the Arab world119,120 discussed the implications of diabetes on sexual life, usually considering SD in men and patients with T2D. AYAs with T1D have been given less attention, underlining the need for more exploration on this subject and in relation to insulin adherence in order to better understand these factors.\n\nIn our study, AYAs reported hypoglycemia before or during standardized tests to influence their concentration and performance, requesting the option to retake the test or be refunded. A systematic review reported that 23–39% of older children (>11 years) reported that they did not have the opportunity to repeat school exams again when they experienced hypoglycemic events before or during an exam.121 Another systematic meta-review122 has provided evidence that students with chronic illness often demonstrate worse school experiences and outcomes than students without chronic illness. While some countries have expressly defined legislative protections to support students with T1D123–125 other countries have not. Additionally, these specific laws relating to the requested reasonable accommodations during exams vary from country to country. Therefore, international and national policies should provide unified guidance to ensure that AYAs with T1D are not placed at a considerable disadvantage compared to students without diabetes. There is a need for further research into the perceptions and needs of students with T1D relating to exams in the Arab world.\n\nIn this study, adherents indicated that having good support from HCPs had motivated their IA adherence. They added that the availability of social media as a method of communication between the diabetes healthcare team and patients had empowered them in their daily decision-making. Prior findings indicated that the patient-provider relationship strongly impacts treatment adherence in AYAs with T1D.14,126 AYAs with T1D also wanted to become more autonomous in their self-care decisions and behaviors with balanced family interactions, suggesting that the transition of diabetes responsibilities from pediatric to adult should be considered and evaluated for AYAs and their families in order to avoid family conflicts. Previous findings demonstrated that negative family reactions to self-care behaviors were found to be related to poor adherence and glycemic control.102,127 Noser et al. (2017) found that diabetes-specific family conflict negatively influenced SMBG adherence in young adults with T1D even if they possessed high self-efficacy levels.128 The national clinical guidelines116 emphasize the delivery of diabetes self-management education (DSME) at transition points in care. However, more information on the details of the processes involved in the transition preparation period and on how to fully implement these processes is needed to be addressed in further research. Our results revealed that key people in the patient’s life and cultural factors affected the perception of the meaning of illness and its treatment. In a previous study, some adult patients with T1D commented that their family and friends provided incorrect information.129 Hence, the sociocultural environment should be evaluated closely.\n\nOur findings demonstrated that adherents showed higher levels of confidence in their ability to follow medical recommendations and expected more meaningful positive consequences for adherence. On the other hand, difficulty administering insulin and/or performing BGM as recommended has been reported in non-adherents as a result of low self-efficacy. Self-efficacy was previously identified as a significant predictor of relatively high adherence rates.42,130 Therefore, self-efficacy promotion is important to help overcome the various barriers and, in turn, to improve adherence in Arab AYAs with T1D.\n\nOur results revealed that action planning was lacking for nearly all participants, whether adherent or not. Some non-adherents indicated that planning aggravates emotional strains. Previous studies highlighted the action planning construct as a prominent predictor of adherence to asmathtic131 and antiretroviral132 medication in AYAs. Additionally, goal-setting was shown to improve SMBG.38 It is therefore important that health communication programs to foster T1D adherence focus on adequate action planning and goal setting for people with T1D in Qatar.\n\nThe findings from this study can serve to design an educational program in which these psychosocial determinants can be addressed in a patient-centered approach. The strengths of this research are that, firstly, the face-to-face semi-structured approach with a researcher who did not have a relationship before and after the work helped AYAs communicate openly about sensitive issues such as SD, which would be generally difficult to address,133 particularly since it is influenced by different tribal and social attitudes in the Arab region.134 Secondly, while a sample of 12 interviews demonstrated achieving saturation previously with a similar study nature and analytical approach,135–137 we examined the depth and richness of collected information using a saturation grid,138 and interviewing continued until saturation was deemed achieved with a sample of 20 interviews. Therefore, findings from this study may be transferable to similar groups. Thirdly, adopting a framework analysis approach offered a systematic structure to easily manage, analyze, and identify themes.139\n\nThis study also has some limitations. Data collection was self-reported; therefore, reporting bias is possible. Although information about the magnitude of such bias is unavailable in most epidemiologic studies,140 there is a reasonably reliable self-report when questions are asked in a non-judgmental manner.66 Second, although this study has highlighted specific determinants related to the different insulin delivery devices and BGM systems, more research is needed in this area to draw further comparisons and conclusions. Third, the views expressed in the interviews are less representative of the adherents’ sample, particularly for BGM. Therefore, this study may not capture other important facilitators and experiences, highlighting the need for further research among adherents.\n\nFirst, concerning information needs, most respondents reported that they needed more information relevant to their daily lives and more Arabic language websites that provide simple diabetes, insulin, and CHO counting information. Second, concerning awareness, some non-adherents were not optimally aware of the need to change their behaviors, lacked the knowledge required to make decisions on insulin dose adjustments, and underestimated T1D risks. Third, concerning their motivation, many non-adherents reported a negative attitude towards adherence, which resulted from several perceived disadvantages that outweighed the advantages of adherence. They also reported a lack of social support and a low sense of self-efficacy. Fourth, most respondents lacked specific plans to prepare for and cope with adherence. In conclusion, increased efforts are needed for people with T1D in Qatar to strengthen awareness, knowledge, and perceived risks of non-adherence as well as to realize a positive attitude, to strengthen social support and self-efficacy, and to enhance appropriate action planning. A comprehensive approach that takes into account the broader social context in order to minimize conflicts in families and to minimize stigma in the sociocultural environment is needed.\n\n\nData availability\n\nThe qualitative data that support the findings of this research are not publicly available due to concerns that the data could potentially reveal participants’ identities. However, data are available to researchers upon request from the corresponding author (H.Burno@maastrichtuniversity.nl/mailto:hanoneh111@gmail.com) and with permission from the Institutional Review Board-Hamad Medical Cooperation for further academic research.\n\nFigshare: Appendix 1: The interview guide for “Determinants of adherence to insulin and blood glucose monitoring among adolescents and young adults with type 1 diabetes in Qatar: a qualitative study”, https://doi.org/10.6084/m9.figshare.20368068.v2.141\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
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Type 1 diabetes complications, pathogenesis, and alternative treatments. Liu C-P, editor.IntechOpen;2011. Accessed 5 July 2021.Reference Source\n\nJonker D, Deacon E, van Rensburg E , et al.: Illness perception of adolescents with well-controlled type 1 diabetes mellitus. Health Psychol Open. 2018; 5(2): 205510291879996–2055102918799968. Publisher Full Text\n\nAdu MD, Malabu UH, Malau-Aduli AEO, et al.: Enablers and barriers to effective diabetes self-management: a multi-national investigation. PLoS One. 2019; 14(6): e0217771. PubMed Abstract | Publisher Full Text\n\nPeters GJ, Ruiter RAC, Kok G: Threatening communication: a critical re-analysis and a revised meta-analytic test of fear appeal theory. Health. Psychol. Rev. 2013; 7: S8–S31. PubMed Abstract | Publisher Full Text\n\nFreeborn D, Dyches T, Roper SO: Lessons learned from a life with type 1 diabetes: adult perspectives. Diabetes Spectr. 2017; 30(3): 188–194. PubMed Abstract | Publisher Full Text\n\nThe International Diabetes Federation: International curriculum for diabetes health professional education.2008. Accessed 6 July 2021.Reference Source\n\nElhabashy SA, Ezz Elarab HS, Thabet RA, et al.: Assessment of self-monitoring of blood glucose in type 1 diabetic children and adolescents and its influence on quality of life: practice and perspective. Gaz. Egypt. Paediatr. Assoc. 2020; 68: 22.30. Publisher Full Text\n\nWagner J, Malchoff C, Abbott G: Invasiveness as a barrier to self-monitoring of blood glucose in diabetes. Diabetes Technol. Ther. 2005; 7(4): 612–619. Publisher Full Text\n\nHood KK, Hilliard M, Piatt G, et al.: Effective strategies for encouraging behavior change in people with diabetes. Diabetes Manag (Lond). 2015; 5(6): 499–510. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFisher WA, Kohut T, Schachner H, et al.: Understanding self-monitoring of blood glucose among individuals with type 1 and type 2 diabetes: an information-motivation-behavioral skills analysis. Diabetes Educ. 2011; 37(1): 85–94. Publisher Full Text\n\nMesser LH, Cook PF, Tanenbaum ML, et al.: CGM benefits and burdens: two brief measures of continuous glucose monitoring. J. Diabetes Sci. Technol. 2019; 13(6): 1135–1141. PubMed Abstract | Publisher Full Text\n\nMorsa M, Lombrail P, Boudailliez B, et al.: A qualitative study on the educational needs of young people with chronic conditions transitioning from pediatric to adult care. Patient Prefer. Adherence. 2018; 12: 2649–2660. PubMed Abstract | Publisher Full Text\n\nAmerican Diabetes Association: Children and adolescents: standards of medical care in diabetes- 2020. Diabetes Care. 2020; 43(Supplement 1): S163–S182. Publisher Full Text\n\nMinistry of Public Health Qatar: National clinical guideline: the diagnosis and management of diabetes mellitus in children and adolescents.2021. Accessed 8 July 2021.Reference Source\n\nMinistry of Public Health Qatar: National clinical guideline: the diagnosis and management of type 1 diabetes mellitus in adults and the elderly.2021. Accessed 8 July 2021.Reference Source\n\nMinistry of Public Health Qatar: National clinical guidelines. Diabetes mellitus in special situations.2021. Accessed 8 July 2021.Reference Source\n\nAhmed A, Alnaama A, Shams K, et al.: Prevalence and risk factors of erectile dysfunction among patients attending primary health care centres in Qatar. East Mediterr. Health J. 2011; 17(07): 587–592. Publisher Full Text\n\nEl-Sakka AI: Erectile dysfunction in Arab countries. Part I: prevalence and correlates. Arab. J. Urol. 2012; 10(2): 97–103. PubMed Abstract | Publisher Full Text\n\nEdwards D, Noyes J, Lowes L, et al.: An ongoing struggle: a mixed-method systematic review of interventions, barriers and facilitators to achieving optimal self-care by children and young people with type 1 diabetes in educational settings.2014; 14(1): 228–228. PubMed Abstract | Publisher Full Text\n\nLum A, Wakefield CE, Donnan B, et al.: Understanding the school experiences of children and adolescents with serious chronic illness: a systematic meta-review. Child Care Health Dev. 2017; 43(5): 645–662. PubMed Abstract | Publisher Full Text\n\nGordon K, Rapp JA, Dimmick BL, et al.: Going to college with diabetes a self advocacy guide for students.2011. Accessed 14 July 2021.Reference Source\n\nJackson CC, Albanese-O’Neill A, Butler KL, et al.: Diabetes care in the school setting: a position statement of the American Diabetes Association. Diabetes Care. 2015; 38(10): 1958–1963. PubMed Abstract | Publisher Full Text\n\nBratina N, Forsander G, Annan F, et al.: ISPAD clinical practice consensus guidelines 2018: management and support of children and adolescents with type 1 diabetes in school. Pediatr. Diabetes. 2018; 19: 287–301. PubMed Abstract | Publisher Full Text\n\nPatel NJ, Datye KA, Jaser SS: Importance of patient-provider communication to adherence in adolescents with type 1 diabetes. Healthcare (Basel). 2018; 6(2): 30–41. PubMed Abstract | Publisher Full Text\n\nChristie D, Thompson R, Sawtell M, et al.: Structured, intensive education maximising engagement, motivation and long-term change for children and young people with diabetes: a cluster randomised controlled trial with integral process and economic evaluation - the CASCADE study. Health Technol. Assess. 2014; 18(20): 1–202. PubMed Abstract | Publisher Full Text\n\nNoser AE, Huffhines L, Clements MA, et al.: Diabetes conflict outstrips the positive impact of self-efficacy on youth adherence and glycemic control in type 1 diabetes. Pediatr. Diabetes. 2017; 18(7): 614–618. PubMed Abstract | Publisher Full Text\n\nEpp D, Grypma S, Astle B: Living well with type 1 diabetes for 40 years or more. Can. J. Nurs. Res. 2020; 52(1): 54–65. Publisher Full Text\n\nAlvarado-Martel D, Ruiz Fernández MÁ, Cuadrado Vigaray M, et al.: Identification of psychological factors associated with adherence to self-care behaviors amongst patients with type 1 diabetes. J. Diabetes Res. 2019; 2019: 6271591–6271600. PubMed Abstract | Publisher Full Text\n\nSawyer SM: Action plans, self-monitoring and adherence: changing behaviour to promote better self-management. Med. J. Aust. 2002; 177(S6): S72–S74. PubMed Abstract | Publisher Full Text\n\nHawkins A, Evangeli M, Sturgeon K, et al.: AALPHI Steering Committee. Episodic medication adherence in adolescents and young adults with perinatally acquired HIV: a within-participants approach. AIDS Care. 2016; 28 Suppl 1(sup1): 68–75. PubMed Abstract | Publisher Full Text\n\nPopovic D, Majic A, Prodanovic-Simeunovic J: The sexual dysfunction in females with type 1 diabetes: still an underestimated issue? Diabetes Updates. 2019; 5: 1–4. Publisher Full Text\n\nAbu Ali RM, Al Hajeri RM, Khader YS, et al.: Sexual dysfunction in Jordanian diabetic women. Diabetes Care. 2008; 31(8): 1580–1581. PubMed Abstract | Publisher Full Text\n\nAndo H, Cousins R, Young C: Achieving saturation in thematic analysis: development and refinement of a codebook. Comp. Psychol. 2014; 3: 1–7. Publisher Full Text\n\nHennink MM, Kaiser BN, Marconi VC: Code saturation versus meaning saturation: how many interviews are enough? Qual. Health Res. 2017; 27(4): 591–608. PubMed Abstract | Publisher Full Text\n\nVasileiou K, Barnett J, Thorpe S, et al.: Characterising and justifying sample size sufficiency in interview-based studies: systematic analysis of qualitative health research over a 15-year period. BMC Med. Res. Methodol. 2018; 18(1): 148–148. PubMed Abstract | Publisher Full Text\n\nFusch P, Ness L: Are we there yet? Data saturation in qualitative research. Qual. Rep. 2015; 20(9): 1408–1416. Publisher Full Text\n\nHackett A, Strickland K: Using the framework approach to analyse qualitative data: a worked example. Nurse Res. 2019; 26(2): 8–13. PubMed Abstract | Publisher Full Text\n\nMühlhauser I, Overmann H, Bender R, et al.: Social status and the quality of care for adult people with type I (insulin-dependent) diabetes mellitus-a population-based study. Diabetologia. 1998; 41(10): 1139–1150. PubMed Abstract | Publisher Full Text\n\nAlBurno H, Schneider F, de Vries H , et al.: Appendix 1: The interview guide for “Determinants of adherence to insulin and blood glucose monitoring among adolescents and young adults with type 1 diabetes in Qatar: a qualitative study”. figshare. Dataset. 2022; 17. Publisher Full Text"
}
|
[
{
"id": "204927",
"date": "10 Oct 2023",
"name": "Sarah Westen",
"expertise": [
"Reviewer Expertise I am a licensed clinical psychologist with a focus on type 1 diabetes psychosocial research and clinical care."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 entitled “Determinants of adherence to insulin and blood glucose monitoring among adolescents and young adults with type 1 diabetes in Qatar: a qualitative study.” This study investigated factors related to awareness of, and beliefs about suboptimal adherence in a group of 20 Arab adolescents and young adults. The study also investigated the existence of an action plan to address health engagement in this population using the I-Change model. Overall, the manuscript was well-written and provided a detailed rational for the study purpose, qualitative methodology, and findings. Specific comments for improvement are below.\nOverall: It is recommended that the authors pay careful attention to the use of inclusive language throughout the manuscript. The terms “adherence,” “nonadherence,” “adherents and non-adherents”, “poor metabolic control” and “glycemic control” are not recommended. Additionally, consider the use of “suboptimal” rather than “poorer.” Please see the following links for inclusive language guidelines and recommendations:\nhttps://www.dstigmatize.org/resources/language-tools/ https://www.diabeteseducator.org/practice/practice-tools/app-resources/diabetes-language-paper Williford et al. (20231).\n\nIntroduction: Consider the use of “subsequent”, it may be a more appropriate word than “hence” in the last paragraph of the Introduction.\n\nIntroduction: It would be helpful to add specific aims and hypotheses to the end of the Introduction so that the purpose of the manuscript is clear.\n\nResults: When discussing themes identified in participant interviews, it may be helpful to provide specific numbers for how many participants indicated certain feelings, as opposed to subjective terms like “almost all,” “quite a few,” and “some.”\n\nConclusions: It would be helpful for the authors to discuss recommendations and interventions that might be helpful in addressing the themes in comments made by participants noted in the last paragraph. If prior interventions have been done in this sample, they should be noted here. If not, recommendations for interventions should be made.\n\nPlease ensure all source data underlying the results are available to ensure full reproducibility.\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": "11078",
"date": "13 Apr 2024",
"name": "Hanan AlBurno",
"role": "Author Response",
"response": "Dear Dr. Sarah Wetson, Thank you for reviewing our manuscript “Determinants of adherence to insulin and blood glucose monitoring among adolescents and young adults with type 1 diabetes in Qatar: a qualitative study.” We herewith would like to respond to your constructive comments and suggestions raised. Your comments are numbered and depicted first, followed by our responses to these comments. Yours sincerely, Hanan AlBurno Liesbeth Mercken Hein de Vries Dabia Al Mohannadi Francine Schneider General comment Overall, the manuscript was well-written and provided a detailed rational for the study purpose, qualitative methodology, and findings. Response to general comment: Thank you for the compliments. We are glad that the reviewer found the study well written and provided a detailed rational for the study purpose, qualitative methodology, and findings. Comment 1 Overall: It is recommended that the authors pay careful attention to the use of inclusive language throughout the manuscript. The terms “adherence,” “nonadherence,” “adherents and non-adherents”, “poor metabolic control” and “glycemic control” are not recommended. Additionally, consider the use of “suboptimal” rather than “poorer.” Please see the following links for inclusive language guidelines and recommendations: https://www.dstigmatize.org/resources/language-tools/ https://www.diabeteseducator.org/practice/practice-tools/app-resources/diabetes-language-paper Williford et al. (20231). Response to comment 1: We indeed agree and thank the reviewer for this valuable comment and for providing links to the inclusive language guidelines and recommendations. In our definition of adherence we have deliberately highlighted its nature as a mutually agreed upon treatment plan. This emphasis underscores the pivotal role of shared decision-making involving adolescents and young adults, their caregivers, and healthcare providers. After a thorough review of the provided resources, the necessary adjustments were made to align with these recommendations. This involved substituting 'non-adherence' with 'suboptimal adherence,' 'poor diabetes/glycemic control' with 'outside target glucose level,' and 'good diabetes/glycemic control' with 'within target glucose level.\" Comment 2 Introduction: Consider the use of “subsequent”, it may be a more appropriate word than “hence” in the last paragraph of the Introduction. Response to comment 2: Thank you. We replaced hence with subsequent. Comment 3 Introduction: It would be helpful to add specific aims and hypotheses to the end of the Introduction so that the purpose of the manuscript is clear. Response to comment 3: Thank you for your comment. In the introduction section, we have explicitly outlined the specific aim of this study. “Therefore, this study aimed to explore adherence determinants to IA and BGM in AYAs, in the age range of 17–24 years within the context of their daily lives, their environment, and cultural and family dynamics in Qatar.” Additionally, we have highlighted the hypothesis of this study by indicating the problem investigated and contrasting it with prior research. Notably, we have emphasized the novelty of our approach in comprehensively incorporating a theoretical model that encompasses both distal and proximal factors influencing behavior. We also have stressed the pivotal importance of delving into adherence behaviors and their multifaceted determinants within diverse familial, social, and cultural contexts. Please see the below paragraph in the end of the introduction section. “The findings from this study are important for tailoring an education program to improve IA and BGM adherence, and hence diabetes outcomes. They are also useful for diabetes policy strategies aiming to support patients’ needs. Furthermore, few studies have looked at T1D patients in their late adolescence and early adulthood 57,58. T1D studies are limited in the Middle East and North Africa (MENA) region, whereas cultural beliefs and practices are important determinants of diabetes self-management behaviors59.” Comment 4 Results: When discussing themes identified in participant interviews, it may be helpful to provide specific numbers for how many participants indicated certain feelings, as opposed to subjective terms like “almost all,” “quite a few,” and “some.” Response to comment 4: Thank you for your suggestion. The use of quantitative data in qualitative research studies has been controversial. While some researchers prefer using numbers of respondents, others do not. Both approaches are acceptable. However we opted to choose not to report numbers. When numbers and statistical information are used in qualitative research, there is a risk of creating a misleading impression of generalizability. 1, 2 Here are some reasons why this might be the case: In our qualitative study we used purposeful sampling, aiming for in-depth exploration. The use of statistical information might give the false impression that the findings are representative of a larger population when, in fact, they are often not intended to be. Readers may interpret number as indicators of prevalence or frequency, assuming that the findings can be generalized to a broader population. This can lead to misinterpretation of the study's scope and applicability. Because quantitative analysis assumes that variables may be analyzed independently of their environment, it often isolates and examines particular variables. The complex network of linkages and interactions that qualitative research seeks to uncover may be oversimplified by this simplified approach.1 Comment 5: Conclusions: It would be helpful for the authors to discuss recommendations and interventions that might be helpful in addressing the themes in comments made by participants noted in the last paragraph. If prior interventions have been done in this sample, they should be noted here. If not, recommendations for interventions should be made. Response to comment 5: Thank you for suggestion. We have added the below paragraph in the Conclusions and recommendation section in the updated version. Previous systematic reviews and meta-analyses 3,4 on the effectiveness of DSM interventions in young adults with T1D indicated that a limited number of studies have incorporated behavioral theories or outcomes in their research, and there has been a noticeable underutilization of behavioral techniques. Additionally, these interventions were not adequately designed with the active participation of young adults. Consequently, the outcomes of these interventions did not lead to significant improvements in glycemic targets or self-management behaviors. Furthermore, self-management interventions designed for older adults should not be assumed to be equally effective for AYAs. This underscores the immediate demand for the development of more effective interventions tailored to this unique population of AYAs living with diabetes. Therefore, we recommend that for future DSM interventions to be effective, they should integrate the identified socio-cognitive factors throughout the awareness, motivation, and action phases, alongside informational factors. This should be complemented by precise operational measures for these factors. The development of these interventions should be a collaborative effort with AYAs, ensuring alignment with their unique needs and preferences, ultimately enhancing their overall efficacy. Comment 6: Please ensure all source data underlying the results are available to ensure full reproducibility. Response to comment 6: Thank you for your suggestion. We fully recognize the significance of having access to the source data underlying the results to ensure complete reproducibility. Nevertheless, we wish to clarify that our data availability statement explicitly states that the qualitative data supporting the findings of this research cannot be made publicly accessible due to concerns regarding the potential identification of participants. However, we would like to highlight that these data are indeed available to fellow researchers upon request. You may reach out to the corresponding author, Hanan AlBurnor (H.Burno@maastrichtuniversity.nl/mailto:hanoneh111@gmail.com)], to obtain access to the data, subject to approval from the Institutional Review Board-Hamad Medical Cooperation, which is responsible for overseeing data usage for further academic research. We hope that we have adequately addressed all comments. References: Maxwell JA. Using Numbers in Qualitative Research. Qual Inq. 2010;6(6): 475–82. Patton M. Qualitative research and evaluation methods. 4th Edition. Sage Publications: Thousand Oaks; 2015 Wong SKW, Smith HE, Chua JJS, et al. Effectiveness of self-management interventions in young adults with type 1 and 2 diabetes: a systematic review and meta-analysis. Diabet Med. 2020;37(2):229-241. doi: 10.1111/dme.14190 Bassi G, Mancinelli E, Dell'Arciprete G, et al. Efficacy of eHealth interventions for adults with diabetes: a systematic review and meta-analysis. Int J Environ Res Public Health. 2021;26;18(17):8982. doi: 10.3390/ijerph18178982."
}
]
},
{
"id": "220108",
"date": "16 Nov 2023",
"name": "Takahiro Ishikawa",
"expertise": [
"Reviewer Expertise I am a diabetologist and am responsible for the care of numerous type 1 diabetic patients. I also conduct research on diabetes."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for the opportunity to review this manuscript. This study investigated factors associated with perceptions and beliefs of suboptimal adherence in 20 young adults with type 1 diabetes in an interview format. I believe that the records are very detailed and that this is a valuable study that accurately reflects the challenges in young type 1 diabetic patients in actual healthcare settings.\nIf possible, I would like to suggest the following improvements:\nThe authors have summarized the specific comments of the interviewees in Table 3.4. Would it be possible to conduct a qualitative evaluation of these comments? Currently, several text mining software packages are available for free (e.g., KH Coder, etc.). Conducting text mining would allow for a detailed analysis of the trends and characteristics of the interviewee's comments, as well as promote visual understanding. It would be appreciated if this could be considered if possible.\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": "11079",
"date": "13 Apr 2024",
"name": "Hanan AlBurno",
"role": "Author Response",
"response": "Dear Dr. Takahiro Ishikawa, Thank you for reviewing our manuscript “Determinants of adherence to insulin and blood glucose monitoring among adolescents and young adults with type 1 diabetes in Qatar: a qualitative study.” We appreciate your suggestion. However, we do not think that following text mining at this stage would be of added value for the following reasons: First: text mining is a widely employed technique for extracting frequent and significant terms from unstructured data.1 However, our interview data differs in nature as it is semi-structured. Second: while data mining plays a crucial role in identifying valuable patterns from large and complex databases, the computer analysis software relies on syntax (i.e., sentence structure) to locate and highlight common words. This approach may introduce a risk of incorrect coding based solely on syntax.2 Third: one limitation of computerized text analysis lies in the potential oversight of valuable categories and patterns within qualitative data. For instance, computerized text analysis may not uncover relationships or categories based on word usage [2]. In our study, we employed the framework method for analyzing interview data. This method not only describes data but also interprets it through mapping and summarization, facilitating the development of explanations for the studied interviews. During the mapping and interpretation phase of the framework analysis, we made a rigorous effort to not only describe but also provide in-depth interpretations of the interviews we examined. This process involved several key steps, including the identification and categorization of themes and cases (interviews) to create a typology based on the different types of people we had interviewed. We then formed categories based on these themes and proceeded to connect individual cases with specific themes. For instance, we analyzed both commonalities and distinctions in behaviors, such as comparing adherence to suboptimal adherence. We also considered variations related to the characteristics of the interviewees, such as comparing adolescents to young adults. Notably, adolescents reported being more sub-optimal adherents than young adults. Gender differences were also identified revealing that more females reported concerns about weight and body image, leading to insulin skipping. Further comparisons and linkages were identified such as connecting self-efficacy factors with coping planning factors. For example, adolescents and young adults needed to identify challenging situations related to administering insulin or monitoring glucose levels before creating coping plans for those situations. Additionally, we explored the linkage between knowledge factors and information factors, uncovering issues with unreliable/misleading information sources and inaccurate knowledge. Fourth: In an attempt to visualize interviews data, we used the Voyanet tool,3 which facilitated the creation of word clouds and trends. For motivational factors, the most frequently occurring word was \"complications.\" However, we couldn't discern whether the word” complications” was the most frequent word due is related to AYAs' awareness of risks of diabetes complications due to sub-optimal adherence or their level of knowledge about diabetes complications. Which highlights a potential area for further interpretation. Yours sincerely, Hanan AlBurno Liesbeth Mercken Hein de Vries Dabia Al Mohannadi Francine Schneider References: Rasid N, Nohuddin P, Alias H, et al. Using data mining strategy in qualitative research. In: Badioze Zaman H, et al. Advances in Visual Informatics. IVIC 2017. Lecture Notes in Computer Science, vol 10645. Springer, Cham; 2017. doi: 10.1007/978-3-319-70010-6_10 Bright M, O’Connor D. Qualitative data analysis: comparison between traditional and computerized text analysis. Osprey J. Ideas Inquiry. 2007, 21. Voyant see through your text. Available from: https://voyant-tools.org"
}
]
}
] | 1
|
https://f1000research.com/articles/11-907
|
https://f1000research.com/articles/12-1095/v1
|
01 Sep 23
|
{
"type": "Research Article",
"title": "Turmeric extract gel and honey in post-cesarean section wound healing: A preliminary study",
"authors": [
"Andi Nilawati Usman",
"Sartini Sartini",
"Risfah Yulianti",
"Melani Kamsurya",
"Agriyaningsih Oktaviana",
"Zafitri Nulandari",
"Dinah Inrawati Agustin",
"Fendi Fendi",
"Sartini Sartini",
"Risfah Yulianti",
"Melani Kamsurya",
"Agriyaningsih Oktaviana",
"Zafitri Nulandari",
"Dinah Inrawati Agustin",
"Fendi Fendi"
],
"abstract": "Background: Delivery by cesarean section (SC) increases the risk of a surgical site infection (SSI). Therapy from health services and complementary therapy reduce the risk of infection and accelerate the wound-healing process. This study compared wound healing after SC with a turmeric extract gel and original Trigona honey.\nMethods: Female white rats (Rattus novergicus) with pre- and post-testing and a control group were included in this experiment, which was conducted in June-July 2022. The test animals were 56 female white rats, 2-4 months old, weighing 150–350 g. The treatment group was divided into three subgroups with application of 50% and 75% turmeric extract gel and Trigona honey. The turmeric was given twice daily, and the honey was divided into two applications of twice a day and once a day. Wounds were assessed using the Reeda Scale.\nResults: The fastest wound healing occurred in the group given Trigona honey twice daily. Redness, ecchymosis, and edema disappeared in this group on day 9 (score 0), and granulation tissue formed on day 9. The group that was administered 50% and 75% turmeric gel extract and Trigona honey once a day healed by days 12 and 15, respectively; all three of these interventions were better than the control group.\nConclusions: Administering Trigona honey twice daily was more effective for accelerating wound healing than the 50% or 75% turmeric extract gel. Original Trigona honey has the potential to be a post-SC wound healing agent.",
"keywords": [
"Honey Gel",
"Trigona",
"Turmeric Extract Gel",
"and Wound Healing Process"
],
"content": "Introduction\n\nDelivery by Cesarean section (SC) increases the risk of surgical site infection (SSI), which can prolong the hospital stay and increase anxiety. Sepsis can follow if the infection is not resolved. The choice of surgical technique and antibiotic reduces this risk; however, particular risk factors, such as anemia, obesity, hypertension, and parity, continue to make SSI extremely prevalent.1,2\n\nStaphylococcus aureus is the most prevalent pathogenic bacteria in patients with SSI, and 9.8% of these bacteria are resistant to methicillin. Other bacteria include Klebsiella pneumoniae, Escherichia coli, and Enterococcus faecalis.3,4 Antibiotics, such as azithromycin, reduce the risk of SSI, although some studies suggest that the long-term effects of using antibiotics are unclear.5\n\nComplementary therapy based on natural ingredients has received attention because consumers tend to prefer natural ingredients.6,7 The local wisdom of Indonesian people, especially those in South Sulawesi, a province in the eastern part of Indonesia, and various studies have shown that honey and turmeric have anti-inflammatory activities and reduce the expression of proinflammatory cytokines. Treating wounds with honey significantly increases angiogenesis, re-epithelialization, and the formation of granulation tissue. The phenolic and flavonoid compounds in honey and turmeric play a role in wound healing.7–9\n\nTurmeric is a yellow rhizome that is often used as a cooking spice. Turmeric contains active compounds, such as curcuminoids and essential oils. Curcuminoids consist of curcumin, desmethoxycumin, and bisdesmethoxycurcumin.10 The mechanism of action of turmeric extract on wounds is to inhibit cyclooxygenase (COX-2) and lipoxygenase, which play roles in the inflammatory stage to accelerate tissue re-epithelialization, cell proliferation, and collagen synthesis.11\n\nThe antibacterial activity of honey is exhibited by components such as H2O2, glucose, and several polyphenols. The phenolic components inhibit bacterial growth through pro-oxidative activity by increasing H2O2 activity. The acidic pH of honey (3.2–4.5) also functions as an antibacterial due to the presence of gluconate acid from the oxidation of glucose, which creates an acidic environment. The flavonoid and phenolic components are anti-inflammatory and suppress the activity of the proinflammatory cytokines, such as COX-2 and inducible nitric oxide synthase. Proline, arginine, methionine, and glycine contribute to the formation of collagen and fibroblasts during wound healing.8 Honey has been clinically applied successfully to treat elderly wounds that do not heal after homecare services. Scar tissue has also been treated successfully at the preclinical trial stage. Significant changes in angiogenic biomarkers occur, such as hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF), and VEGF receptor-II. Honey is also effective on diabetic wounds, burns, pressure sores, and venous and arterial ulcers.12–14\n\nTurmeric gel and honey have been preclinically tested on post-SC wounds and produced satisfactory results. Researchers tested turmeric gel and applied pure honey to general wounds. We continued this research on more specific wounds, such as postoperative SC wounds in experimental animals. The turmeric was formulated in 50% and 75% gel products, whereas the honey used was 100% pure honey from Apis trigona bees used once or twice a day. Both were made with local ingredients from South Sulawesi Province, Indonesia.\n\nThis study used female Wistar strain Rattus norvegicus rats because they have a gene structure and physiology similar to humans. We compared wound healing, such as redness, swelling, ecchymosis, edema, pus, and tissue granulation, between the turmeric extract gel and pure Trigona honey. This study will hopefully become the basis for clinical trials to prevent SSI in post-SC wounds.\n\n\nMethods\n\nThis research was an experimental pre-post-test laboratory study with female rats (R. novergicus) using a control group. This research received approval from the ethical clearance commission of Hasanuddin University Makassar (number 4883/UN4.14.1/TP.01.02/2022).\n\nThe first stage of the research was carried out at the Hasanuddin University Biopharmaceutical Laboratory to manufacture the turmeric gel extract and the honey. The husbandry and treatment of the experimental animals were carried out at the Animal Laboratory, Faculty of Veterinary Medicine, Hasanuddin University Makassar. This study was conducted during June–July 2022.\n\nThe testing was carried out on 56 female white rats. The inclusion criteria for the study were female Wistar white rats, 2–4 months of age, weighing 150–350 g in good health (actively moving, fur not dull, not shedding, eyes clear, and nimble). The exclusion criteria were illness and inactivity throughout the study.\n\nThirty-one rats did not meet the inclusion criteria (28 rats under 150 g, and three were not active and ill), so 25 rats (n=5/group) were used in the study.\n\nAll efforts were undertaken to minimize the suffering of the animals. Wounds were created after shaving the fur on the part to be cut. The rats were anesthetized intraperitoneally with ketamine (80 mg/kg) before wounding to relieve pain and prevent excessive movement. The area to be cut was marked, and a 2 cm-long incision was made to penetrate the peritoneum. Five groups were prepared:\n\n1. Turmeric gel at 50% and 75% concentrations were applied to the wound using sterile cotton every morning and evening\n\n2. Trigona honey gel was applied twice daily (0.13 mg) (morning and evening) or once daily (0.064 mg) in the morning to the respective subgroups\n\n3. Control, without intervention\n\nThe wound healing was monitored by observing moisture, redness, edema, pus, and granulation tissue in the wound (Reeda Scale). The rats were euthanized after closing the intrathoracic transection of the great vessels and heart.15\n\n\nData analysis\n\nData were grouped according to purpose and type, and descriptive statistical methods were used. The characteristics of the basic data are described to see improvements and no statistics were used. The score entered in the table is the average score (mean) which is calculated by adding up all the female Wistar white rat wound scores in each group, then dividing it by the number of group members. The score was calculated using Microsoft Excel.\n\nTable 1 shows that the groups given the 50% and 75% turmeric extract gel had a redness score of 0 (redness disappeared) on day 12 post-intervention. The groups that were given Trigona honey twice daily and once daily had scores of 0 (redness disappeared) 3 days earlier than the group that was given turmeric, which was on day 9.\n\nRedness score of the wounds in the turmeric extract gel and honey groups.\n\nTable 2 shows that none of the groups administered the 50% or 75% turmeric extract gel scored 0 (ecchymosis disappeared) on day 15 post-intervention. The group given Trigona honey twice daily had a score of 0 (ecchymosis disappeared) on day 9, whereas the group given Trigona honey once daily had a score of 0 (ecchymosis disappeared) on day 15.\n\nEcchymosis scores of the wounds in the turmeric extract gel and honey groups.\n\nTable 3 shows that the groups administered the 50% or 75% turmeric extract gel had scores of 0 (redness disappeared) on day 12 postintervention. The group given Trigona honey twice daily had a score of 0 (redness disappeared) 3 days earlier than the group given turmeric on day 9 (redness disappeared).\n\nEdema score of the wounds in the turmeric extract gel and honey gel groups.\n\nTable 4 shows that the control group displayed pus on day 12 and scored 0 (pus disappeared) on day 15 post-intervention, whereas none of the other groups experienced pus in a wound.\n\nPus score of the wounds in turmeric extract gel and honey gel groups.\n\nTable 5 shows that granulation occurred the quickest (score 2) in the group given Trigona honey twice daily, whereas the group given 50% or 70% turmeric gel extract experienced granulation (score 2.0) on day 15; the longest time to granulation was the control group on day 18.\n\nGranulation tissue score in the wound of the turmeric extract gel and honey groups.\n\n\nDiscussion\n\nDrugs have been used to speed up the wound-healing process. Wound healing is a natural repair process for tissue injury involving inflammatory mediators, blood cells, the extracellular matrix, and parenchymal cells.16 The drugs used in traditional medicines are derived from plants and animals.17 Some of the plants used to treat wounds in mice include turmeric and honey.18\n\nThe present study showed that administering Trigona honey twice daily accelerated wound healing based on redness, moisture, edema, granulation tissue, and scabs in the wound compared with the 50% and 75% turmeric gel extract groups (Tables 2–5). Trigona honey administered twice daily did not result in wound edema (Table 4). Honeys have different chemical compositions, biological properties, and effects depending on the environmental, geographical, and nutritional factors of the plant pollen collected.17 Trigona honey increases angiogenic activity, which is very important during wound healing and accelerates the formation of granulation tissue and re-epithelialization of the skin. Honey has antioxidant, antibacterial, and anti-inflammatory properties.18 The flavonoid content in honey increases angiogenesis; thus, fibrosis and collagen formation increase. Flavonoids also have antibacterial, antioxidant, and anti-inflammatory properties.19\n\nThe results of this study indicate that administering Trigona honey twice daily led to a faster healing process than once daily; this agreed with research conducted by Takzaree et al., who reported that applying honey to wounds twice daily increases healing, shortens the inflammatory process, and increases the granulation rate.20\n\nTurmeric extracts in 50% and 75% gels can be used as an alternative treatment because they accelerate wound healing, although not as quickly as Trigona honey (Tables 2–5). This is due to the curcumin compounds with antimicrobial, antioxidant, and anti-inflammatory properties that accelerate re-epithelialization, proliferation, and collagen synthesis.21–23 Turmeric rhizome extracts have antibacterial activity. Turmeric leaf oil at various concentrations inhibits the mycelial growth of Aspergillus flavus and Aspergillus parasiticus. Turmeric leaf oil is effective against the antibiotic-resistant bacterium Escherichia coli, and the oil from Curcuma longa leaves has antioxidant properties.23–25 The turmeric rhizome is prepared as a gel for topical application. A gel is a semisolid system that provides a cool and soothing feeling to the skin with a high water content so it increases hydration in the stratum corneum and dries easily to form a film layer.11 The results of this study indicate that the turmeric extract gel and Trigona honey can be used as alternative treatments for post-CS wounds. However, further research is needed on humans to determine the appropriate dose.\n\n\nAuthor contributions\n\nANU, SAR, RFY, MNK, AGR, amf ZAN contributed to the literature review, data extraction from various databases, conceptualisation, development of the economic models on Microsoft Excel Software, formal analysis, findings interpretation, and manuscript writing. All authors approved the final version of the paper.",
"appendix": "Data availability\n\nFigshare: MASTER TABLE OF WOUND HEALING OF SECTIO CAESAREA IN RATS.xlsx, https://doi.org/10.6084/m9.figshare.22756712\n\nThis project contains the following underlying data:\n\n- MASTER TABLE OF WOUND HEALING OF SECTIO CAESAREA IN RATS.xlsx\n\n- TURMERIC EXTRACT GEL IN POST SECTIO SECAREA WOUND HEALING.xlsx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nThe authors would like to thank the graduate school of Hasanuddin university for the grant. The author also thanks ENAGO for copyediting our paper.\n\n\nReferences\n\nKaraca SY, Adıyeke M, İleri A, et al.: Identifying the Risk Factors Associated with Surgical Site Infection Following Cesarean Section in Adolescent Mothers. J. Pediatr. Adolesc. Gynecol. 2022; 35: 472–477. Publisher Full Text\n\nSaeed KBM, Corcoran P, O’Riordan M, et al.: Risk factors for surgical site infection after cesarean delivery: A case-control study. Am. J. Infect. Control. 2019; 47(2): 164–169. PubMed Abstract | Publisher Full Text\n\nOnuzo CN, Sefogah PE, Nuamah MA, et al.: SURGICAL SITE INFECTIONS FOLLOWING CAESAREAN SECTIONS IN THE LARGEST TEACHING HOSPITAL IN GHANA. Infect. Prev. Pract. 2022; 4: 100203. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHarzif AK, Wicaksono MD, Kallista A, et al.: Overview of risk factor and bacterial pattern in patient with surgical site infection after caesarean section in Ciptomangunkusumo Hospital from 2016 to 2018. Infect Prev Pract. 2020; 2(4): 100090. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang M, Yuan F, Guo Y, et al.: The efficacy of adding azithromycin to antibiotic prophylaxis in cesarean delivery: A meta-analysis and systematic review. Int. J. Antimicrob. Agents. 2022; 59: 106533. Publisher Full Text\n\nFouelifack FY, Eko FE, Vanessa Ebode Ko’A CO, et al.: Treatment of perineal wounds during the post partum period: evaluation of whether or not antibiotic should be systematically prescribed TT - Prise en charge des plaies du périnée en post partum: faut-il prescrire systématiquement un antibiotique? Pan. Afr. Med. J. 2017 Oct; 28: 144. Publisher Full Text\n\nMutia WON, Usman AN, Jaqin N, et al.: Potency of complemeter therapy to the healing process of perineal wound; turmeric (Curcuma longa Linn) Infusa. Gac. Sanit. 2021; 35: S322–S326. Publisher Full Text Reference Source\n\nNezhad-Mokhtari P, Javanbakht S, Asadi N, et al.: Recent advances in honey-based hydrogels for wound healing applications: Towards natural therapeutics. J. Drug Deliv. Sci. Technol. 2021; 66: 102789. Publisher Full Text\n\nEbadi P, Fazeli M: Evaluation of the potential in vitro effects of propolis and honey on wound healing in human dermal fibroblast cells. South African J. Bot. 2021; 137: 414–422. Publisher Full Text\n\nYati S: Khasiat Ajaib Herbal Daun Umbi Buah Sekitar Kita. 1st ed.Jakarta Barat: Vicosta; 2013.\n\nMilasari M, Jamaluddin AW, Adikurniawan YM: PENGARUH PEMBERIAN SALEP EKSTRAK KUNYIT KUNING (Curcuma longa Linn) TERHADAP PENYEMBUHAN LUKA SAYAT PADA TIKUS PUTIH (Rattus norvegicus) Muthia. J. Ilm Ibnu Sina. 2019; 4(1): 186–202.\n\nZeleníková R, Vyhlídalová D: Applying honey dressings to non-healing wounds in elderly persons receiving home care. J. Tissue Viability. 2019; 28(3): 139–143. PubMed Abstract | Publisher Full Text\n\nSingh S, Gupta A, Gupta B: Scar free healing mediated by the release of aloe vera and manuka honey from dextran bionanocomposite wound dressings. Int. J. Biol. Macromol. 2018; 120: 1581–1590. Publisher Full Text\n\nSalla HR, Al Habsi FS, Al Dholi HM, et al.: A comparative study on the role of Omani honey with various food supplements on diabetes and wound healing. J. King Saud Univ. - Sci. 2020; 32(3): 2122–2128. Publisher Full Text\n\nCorno A, George B, Pearl J, et al.: Surgical options for complex transposition of the great arteries. J. Am. Coll. Cardiol. 1989; 14(3): 742–749. Publisher Full Text Reference Source\n\nNazir F, Zahari A, Anas E: Pengaruh Pemberian Gel Lidah Buaya (Aloe vera) Terhadap Jarak Pinggir Luka pada Tikus Wistar. J. Kesehat Andalas. 2015; 4(3): 827–834. Publisher Full Text\n\nIzzah IN, Wong SK, Mohamed IN, et al.: Wound healing properties of selected natural products. Int. J. Environ. Res. Public Health. 2018; 15(11).\n\nAbd Jalil MA, Kasmuri AR, Hadi H: Stingless bee honey, the natural wound healer: A review. Skin Pharmacol. Physiol. 2017; 30(2): 66–75. PubMed Abstract | Publisher Full Text\n\nAida A, Zhafirah R, Hirawan H, et al.: Wound healing potential of forest honey for increasing TGF-β1 protein expression in palatoplasty: In-vivo and In-silico studies. Sci. Dent. J. 2022; 6(1): 25.\n\nTakzaree N, Hassanzadeh G, Rouini MR, et al.: Evaluation of the effects of local application of thyme honey in open cutaneous wound healing. Iran. J. Public Health. 2017; 46(4): 545–551.\n\nAstuti KEW, Handajani SR: Efektifitas Anti Inflamasi Formulasi Kunyit (Curcuma Longa), Daun Binahong (Anredera Cordifolia) Dan Daun Sambiloto (Andrographis Paniculata) Terhadap Luka Sayat Pada Kelinci. Interes. J. Ilmu Kesehat. 2018; 7(2): 101–221.\n\nNingtyas G: UJI EFEKTIVITAS EKSTRAK RIMPANG KUNYIT (Curcuma domestica Val) DALAM MEMPERCEPAT PROSES PENYEMBUHAN LUKA SAYAT PADA MENCIT (Mus musculus) JANTAN. Universitas Muhammdiyah Surakarta; 2017.\n\nYanti R, Nurdiawati H, Wulandari P, et al.: Chemical composition and antifungal activity of oil extracted from leaves turmeric (Curcuma longa). Canrea J. Food Technol. Nutr. Culin. 2021; 4(2): 123–131. Publisher Full Text Reference Source\n\nKhatun M, Nur MA, Biswas S, et al.: Assessment of the anti-oxidant, anti-inflammatory and anti-bacterial activities of different types of turmeric (Curcuma longa) powder in Bangladesh. J. Agric. Food Res. 2021; 6: 100201. Publisher Full Text Reference Source\n\nKebede BH, Forsido SF, Tola YB, et al.: Free radical scavenging capacity, antibacterial activity and essential oil composition of turmeric (Curcuma domestica) varieties grown in Ethiopia. Heliyon. 2021; 7(2): e06239. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source"
}
|
[
{
"id": "224741",
"date": "27 Nov 2023",
"name": "Maulana Yusuf Alkandahri",
"expertise": [
"Reviewer Expertise Molecular Pharmacology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nPlease complete all your bio-assay with completed validation methods (Please read https://doi.org/10.1016/j.jpba.2022.114735, it maybe can help you to revise your manuscript (at least please calculate Z factor of your methods). Without validation data, the reported results maybe not be replicated by other researchers).\n\nPlease delete all significance tests, and replace it with data of (mean ± Confidence interval) (see Gandevia, S., Cumming, G., Amrhein, F., Butler, A. 2021. Replication: Do not trust your p-value, be it small or large. J. Physiol. 599(11): 2989-2990.\n\nThe study groups, the pattern of using the extract, and administration intervals should be given in a separate section under the title of \"treatment groups\". Also, the protocol and study design should be added as a graphic schematic design to help the author's inference.\n\nThis manuscript needs editing in English language and grammar by a native English speaker. Also, a major spacing problem were noticed all over the text. Please consider thorough editing on that aspect.\n\nOverall scientific term also needs to be edited. They are very informally written, which is not acceptable for publishing in a scientific journal in current format.\n\n80% of the references cited should be between 2018-2023.\n\nThe revised and corrected manuscript should be subjected to plagiarism checker (<10%).\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "232732",
"date": "31 Jan 2024",
"name": "Arfa Nasrine",
"expertise": [
"Reviewer Expertise Pharmaceutical novel formulation development"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nTitle: Review of Manuscript - \"Turmeric extract gel and honey in post-cesarean section wound healing: A preliminary study\"\nOverall Impression: The manuscript presents an interesting study on the use of turmeric extract gel and Trigona honey for wound healing in post-Cesarean section (SC) wounds in rats. The study design, methodology, and results are well-documented, providing valuable insights into the potential benefits of these natural products in wound healing. However, there are a few points that need clarification and improvement.\n1. Title and Keywords: The keywords adequately capture the main topics of the manuscript, but it might be helpful to include terms like \"Cesarean section\" and \"Rattus norvegicus\" for enhanced discoverability.\n2. Introduction: a. The introduction effectively establishes the background and rationale for the study. However, it would be beneficial to provide more recent statistics or studies related to surgical site infections (SSI) and the use of alternative therapies. b. The section on Staphylococcus aureus and antibiotic resistance is well-presented. However, it would be useful to include references to support the mentioned prevalence rates and resistance percentages.\n3. Literature Review: a. The literature review provides a comprehensive overview of the anti-inflammatory properties of honey and turmeric. However, including recent references and studies, especially those related to wound healing, would strengthen this section. b. Clarify whether the studies mentioned are specific to the Trigona honey from Apis trigona bees, as this distinction is crucial.\n4. Methods: a. The research design is clearly described, but it would be helpful to provide a brief rationale for choosing the Wistar strain Rattus norvegicus rats, considering the similarity of their gene structure and physiology to humans. b. Include information on the randomization process for assigning rats to different intervention groups. c. Specify the blinding procedures, if any, during the wound healing assessments.\n5. Results: a. The presentation of results in tables is clear and organized. However, consider providing standard deviations or confidence intervals for the reported mean scores to assess the variability within each group. b. The discussion of the results should reference the relevant tables for better clarity.\n6. Discussion: a. The discussion provides a good interpretation of the results. However, the comparison of the effectiveness between turmeric extract gel and Trigona honey could be more nuanced. Consider discussing potential synergistic effects of combining these treatments. b. The limitations of the study should be explicitly mentioned, such as the use of animal models and the need for further human trials.\n7. Data Availability: a. Ensure that the data availability statement is accurate, and the provided DOI links lead to the correct datasets.\n8. Language and Style: a. The manuscript is generally well-written, but some sentences could be clarified for better readability. Consider revising for conciseness and clarity.\n9. Conclusion: The manuscript presents a promising study on the potential benefits of turmeric extract gel and Trigona honey in wound healing. Addressing the mentioned points would enhance the manuscript's overall quality and impact.",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-1095
|
https://f1000research.com/articles/12-1302/v1
|
11 Oct 23
|
{
"type": "Systematic Review",
"title": "Gender gaps in research: a systematic review",
"authors": [
"Isabel Cristina Rivera-Lozada",
"Oriana Rivera-Lozada",
"Gissel Carolina Escobar",
"Gissel Carolina Escobar"
],
"abstract": "Background: Despite significant advancements in closing the global gender gap, there is still much progress to be made, particularly in the field of science and scientific research. Numerous studies have addressed this issue and identified a variety of factors that contribute to gender asymmetries in research. Methods: This study aimed to identify the determinants of gender gaps in scientific research present in the most cited studies of the past ten years as a first step towards closing these differences. Through a systematic literature review that incorporated the Proknow-C Knowledge Development Process and Constructivism methodology. Results: The results lead us to identify four dimensions to classify the determinants of the gaps in scientific research: academic supply, research policies, scientific production and researcher profile with their respective quantitative or qualitative indicators. Conclusions: As a potential basis for further modeling that offers greater analytical and correlational depth, as well as the identification of targeted strategies aimed at reducing gender gaps in research.",
"keywords": [
"Gender gaps",
"discrimination",
"segregation",
"research"
],
"content": "Introduction\n\nAs indicated by the Global Gender Gap Report 2022, it will take 132 years to close the global gender gap, statistics designed to measure gender equality and inequality such as income, political representation, wealth accumulation, tertiary education levels, stress levels (World Economic Forum, 2022). In the case of Latin America and the Caribbean, based on the current rate of progress, the region will close the gap in 67 years (Mujeres 360, 2022). Despite notable advancements in the region, some countries (Argentina, Brazil, and Mexico) appear to have stagnated, while others (Peru, Guyana, and Chile) are improving their gender parity outcomes. At the other end of the spectrum, countries such as Colombia, Honduras, Barbados, and Belize have widened the gender gap. These results contrast with the Sustainable Development Goals, which aim to reduce gender inequalities by 2030 (United Nations, 2015) and hinder the increase in scientific productivity by 15% to 20% (International Labor Organization, 2017; Science Metrix Inc., 2018), highlighting the impact that achievements in reducing inequality have on the global economy and closing social gaps.\n\nIn recent years, numerous studies have been conducted to investigate differences in scientific productivity (Abramo et al., 2013; López-Bassols et al., 2018; Pinho-Gomes et al., 2020) in various areas such as psychology (Mayer & Rathmann, 2018), elite researchers (Sá et al., 2020), science and technology (Pons et al., 2013). Others have focused on identifying achievements and challenges (Osorio, 2005), obstacles and barriers (García-Jiménez & Herrero, 2022; Ramírez López & Bermúdez Urbina, 2015; Valenzuela et al., 2022), to mention a few. The diversity of research interests exploring aspects of the problem related to the determinants and/or explanatory factors of gender gaps in scientific research leads us to consider it relevant to conduct a comprehensive literature review focused on gender differences in scientific research. The aim is to identify the determinants of gender gaps in scientific research as a first step towards closing these differences.\n\nIn order to conduct a relevant literature review, this research focused on a systematic review that incorporated the Proknow-C Knowledge Development Process and Constructivism methodology (Ensslin et al., 2013) to identify potential factors or determinants that make a difference in research for female researchers in the most relevant studies.\n\nThis research proposes classifying the determinants into four dimensions: i) Academic Offerings, ii) Research Policies, iii) Scientific Production, and iv) Researcher Profile. The proposed classification allows the recognition of each factor and the definition of indicators, whether quantitative or qualitative, that reflect the situation in the respective field. These indicators serve as a basis for subsequent modelling, offering greater analytical and correlational depth, as well as identifying strategies to address and reduce gender gaps in research.\n\n\nMethods\n\nThis qualitative research, based on a documentary design, relies on a systematic review and bibliometric analysis, which enables the study of quantitative aspects of production, dissemination, and use of recorded information (Araújo & Arencibia, 2002; Morales-Morejón & Cruz Paz, 1995). The Proknow-C methodology (Ensslin et al., 2010) is employed, consisting of three stages: Development of the Relevant Bibliographic Portfolio (RBP), bibliometric analysis and systemic analysis.\n\nI) Development of the Relevant Bibliographic Portfolio (RBP). The Relevant Bibliographic Portfolio (RBP) refers to the result of the sampling conducted on the relevant scientific literature concerning the gender gap in research. For defining the databases, we established the axes and keywords for the search, as shown in Table 1.\n\nThe databases were selected to enable filtering with Boolean equations in English and/or Spanish, differentiating the type of publication (book or article) and the temporal horizon (2012-2023).\n\nThe verification of compliance with these requirements is presented in Table 2.\n\nAll documents that provided relevant information on the determinants of scientific research and the gender gaps in it were selected (Table 2a). The selected documentation was tabulated and classified according to objectives, methodology, variables, population, year of publication, results and conclusions. This classification served as a reference to identify the most pertinent, novel, curious or relevant documents that required special attention.\n\nOnce the mentioned filters were applied, the Gross Bank Articles (GBA) was defined, resulting in 636 articles. The GBA was subjected to an adherence test by calculating a sample with a 95% confidence level and a maximum error of 10% to verify that each article contains at least one of the established keywords (Table 1).\n\nThe formula used is the following:\n\nWhere: n is the sample size of the GBA; Z is the parameter for the confidence level (1.96 for a confidence level of 95%); E is the allowable error (10%); p and q (50% each); and N = 636, being n = 83 elements of GBA (13%).\n\nWith these conditions, the sample size was determined to be 83 articles to be classified in descending order of citability, along with their main authors, as shown in Table 3.\n\nAfter the review, it was confirmed that the 83 articles contain the defined keywords in the fields of keywords, title, and/or abstract, verifying adherence. The representation of the used databases in obtaining the RBP is shown in Figure 1. It highlights that the Redalyc database contributes the highest number of articles to the RBP, accounting for 47% of the total. Base-search.net follows with 14%, while the remaining 39% of the RBP is derived from databases such as Web of Science, Scopus, Scielo, La referencia, DOAJ, Ebsco, Redalyc and Base-search.net.\n\nOn the other hand, it is possible to evidence representativeness of RBP through citability of the articles. Table 4 shows the list of 21 articles of RBP which stand out due to a citability of 10 or higher. This number is determined to highlight the 25% of RBP.\n\nRegarding the documentation selection process, it took the documents that met all the keywords proposed in the Boolean equation. The review, filtering of this documentation and analysis was done using the Mendeley literature manager Desktop version 1.19.8 and then exported the metadata of the publications obtained from the search were downloaded from the databases in Microsoft Excel format. For the underlying data, see Rivera-Lozada et al. (2023a). The phases of definition of the protocol, search and extraction of the initial data from the databases were carried out by all the authors of this publication. The search results are current as of the second week of May. The subsequent filtering of the successive phases was carried out by peer review among the authors.\n\nFigure 2 contains the diagram of the process flow carried out to obtain our RBP. In the first instance, duplicate articles and articles that despite carrying out the search determining the interval of years, did not comply with this, are eliminated. Subsequently, those that contain the keywords in the title or in the abstract but any of both shows they are not related to the subject of study are excluded, such as the article “Analysis of the world scientific production on forced sterilization of women with disabilities between 1997 and 2016” (Concha & Ferrer, 2019), our Keyword: scientific production and women or the article “Women and aging in social research (1950-2018)” (Torralbo & Guizardi, 2020), our keywords: women and research. Then we obtained reports sought for retrieval but we do not have access to 40 of these, like the “Chapter 4 Gender and Economics in Latin America: a Systematic Analysis of Scientific Production in Scopus” (Maldonado & Quiñonez, 2021) and finally, the articles are organized from highest to lowest citation ability and the articles that are outside the sample of 83 articles that were determined with the aforementioned formula are excluded.\n\nThe systematic review, like other study designs, can present biases that can lead to errors in the study, for which a series of measures were applied to guarantee the objectivity of the results, such as defining a search protocol with quality criteria, as well as searching the two main research databases such as Web of Science, Scopus, Redalyc, among others. Likewise, there were no spatial or language restrictions for the selection of information.\n\n\nResults\n\nFigure 3 shows the number of articles from the RBP published in the period 2012-2022, as well as the number of highlighted articles from the RBP based on their citability, published within this time interval. It can be observed that the year 2014 marked a turning point in the decline of publications, reaching its peak in 2016, which also had the highest number of highlighted articles. However, this pattern does not repeat when considering the lowest number of published articles. For the RBP, the year with the lowest number of publications is 2014, while in terms of highlighted articles, the year with the fewest was 2021, where not a single article surpassed 10 citations.\n\nFigure 3 highlights the articles from the RBP according to the journals where they were published. The list includes 32 journals that published the respective articles from the RBP, ordered according to the Scimago Journal Rank (SJR) index, which measures the prestige of the journals based on the citation count received by each publication. Notable journals such as BMJ Global Health, Journal of Technology Transfer, and Journal of English for Academic Purposes stand out with SJR indexes of 2.37, 1.70, and 1.32, respectively. There is a significant difference of 0.67 points between the first and second-ranked journals. However, the subsequent journals show a smaller decrease in their scores, as seen in the difference of 0.38 points between the second and third-ranked journals. The journal with the lowest index is Biblios, with 0.10 points.\n\nBased on these prominent journals, the coverage years of the SJR index for the top 10 journals were identified, as shown in Table 5.\n\nFurthermore, the year of the first publication on the gender gap in research was determined for the highlighted journals in the RBP, as shown in Table 6.\n\nAlong with the highlighted journals, information about the prominent authors in the RBP was also collected, selecting authors with the highest citability within the RBP, as shown in Figure 4. The figure compares the total number of publications of each author with the publications they have made related to the gender gap in research. Among these authors, Ana Pinho Gomes stands out with the highest number of total publications. Giovanni Abramo, Sanne Peters, and Ciriaco Andrea D’Angelo also have a percentage of their total publications related to the topic of study, with 1%, 3%, and 4% respectively. In contrast, authors such as Pessoa de Carvalho, Ana Guil Bozal, and Alejandra Montané have a smaller number of publications but a higher involvement in the subject at hand, with 14%, 31%, and 8% respectively.\n\nIt is possible to identify the geographical areas where the studies on the gender gap in research included in the RBP were conducted, as shown in Figure 5.\n\nGeographical location of studies in the RBP.\n\nBased on the information recorded in Figure 5, the evidence indicates that the country with the highest number of studies related to the gender gap in research was Mexico (29%), significantly surpassing other territories. Spanish publications ranked second (12%), followed by Colombian (8%), Argentinean (7%), Brazilian (7%), European (6%), Global Studies (6%), publications without a specific territory (5%), United States (4%), Chile (2%), and to a lesser extent, Venezuela, Turkey, Peru, Norway, Italy, Hungary, Honduras, Ecuador, Costa Rica, Saudi Arabia, and Africa (1% each). This provides the study with global perspectives.\n\nIn addition to the spatial focus, the classification of the RBP was incorporated according to the methodological approach of the studies, indicating that 42% were qualitative and 58% were quantitative.\n\nThe review made it possible to classify the potential determinants of scientific research: geographical location, position, dedication time, type of call, teaching classification or hierarchy, age, dependency load, inclusive financing funds, sexist bias, gender stereotypes, discrimination, institutional determinants, biases of evaluation committees, income, glass ceiling, scientific recognition or status, salary, motivations, sticky floor, labor contract, marital status, professional segregation, visibility of scientific production, among others.\n\nThe systemic analysis of the RBP allowed us to categorize the barriers contributing to the gender gap in research into four dimensions with their respective indicators: i) Academic Offerings: number of higher education institutions total number of careers, female and male enrolment, science careers, female and male enrolment in sciences (natural and social) ii) Research Policies: agency, call for proposals, inclusive funding, evaluation committee, institutional policy, discrimination, recognition or incentive, types of hiring, iii) Scientific Production: research category, publications number, patents, collaboration, segregation, citability, and iv) Researcher Profile: motivations, sticky floor, income, position, geographic location, education level, age, gender, marital status, dependency load, scale, acknowledgment.\n\ni) Academic offerings: Ten percent of the RBP focused on explaining or analyzing gender gaps in research based on considerations that incorporate variables such as the number of educational institutions, professional careers offered, total enrolment, STEM (Science, Technology, Engineering, and Mathematics) careers, and enrolment of women in natural sciences or STEM. In this regard, the results presented by López-Bassols et al. (2018) indicate that beyond acknowledging the existence of gender gaps in research, it is necessary to identify the areas or fields of knowledge where these gaps are most significant in order to correlate them with women’s participation and presence in higher education across various disciplines. Research conducted for Latin America and the Caribbean identifies family pressures, stereotypes, expectations, lack of mentors and role models, as well as vertical segregation and the “leaky pipeline” phenomenon as causal factors contributing to the existing differentials in women’s participation in research.\n\nThe authors propose considering three dimensions: actors within the national science and innovation system (higher education institutions, government, companies, NGOs), activities related to science and technology (teaching, research, publications, patents, funding, and innovative entrepreneurship), and obstacles or motivations (opportunities, attitudes, financial support, other incentives, role models, discrimination, and social biases). Based on the aforementioned, they establish a set of 16 indicators classified under higher education, careers in science and technology, scientific research, and innovation and innovative entrepreneurship.\n\nOn the other hand, the research conducted by García and Ortíz (2014) explores the individual and institutional determinants affecting gender gaps in scientific production in Ecuadorian universities. Using a linear regression model, they propose individual determinants that include academic degree, number of scholarship recipients, hours of dedication, age, and gender, as well as institutional determinants that incorporate the number of R&D projects, laboratories, executed budget for R&D, number of collaborators, among others. The research results indicate that institutional determinants have a significant and positive impact, while the number of PhDs still does not have a significant effect on scientific production. In particular, they find that women are less productive than men and that the age range with the highest productivity is between 30 and 39 years. Additionally, they found that the number of collaborators has a negative effect.\n\nThe UNESCO study on STEM education (2019) identifies four factors affecting gender gaps in research based on women’s participation in STEM education: individual factors (biological and psychological), family factors (parents’ beliefs, parents’ level of education, household socioeconomic status, and other characteristics), school factors (teaching staff, pedagogical strategies, teachers’ perceptions, interactions with students, textbooks, educational materials, curriculum, STEM equipment and resources, evaluation strategies and tools), and social factors (gender equality, social norms, policies and legislation, media and social communication).\n\nThe document debunks the belief in biological differences in the brains of men and women as an explanatory factor for their participation in STEM disciplines and research in this field. In this regard, neurological plasticity, understood as the brain’s ability to create new connections, is the essence of the learning process. The self-selection bias is the reason why girls and women decline STEM education, and this selection is influenced by stereotypes and androcentric biases acquired during upbringing and socialization moments. Similarly, social norms and stereotypes disseminated by the media have a significant impact on the internalization of gender roles, occupations, skills, and capabilities by girls and boys (UNESCO, 2019).\n\nBased on the literature review conducted, the indicators in the dimension of Academic Offerings are:. Based on our review of the literature, we identified the following indicators: number of higher education institutions, total number of offered careers, number of careers in science, total enrolment, total female enrolment, total male enrolment, enrolment of women and men in Natural Sciences, enrolment of male and female in Social Sciences, and enrolment of women and men in Health Sciences (Carrillo & Florez, 2023; Del Valle et al., 2012; Ortiz-Ortega & Sánchez, 2017).\n\nii) Research policies: Twenty-nine percent of the RBP disseminated results regarding the impact of research policies on gender gaps in research. Mexico is the country where the highest number of studies in this field has been conducted, and thus, the equity of gender in research was evaluated in 2012, 2013, and 2015 (Cárdenas Tapia, 2015). With a database that provided gender-specific information, knowledge area, SNI (National System of Researchers) classification, and public universities, it was possible to demonstrate that the participation of female researchers in Mexico is lower than that of men, and they also have a lower level in the SNI in all categories. In more detail, women are not the majority in any of the seven knowledge areas proposed by the SNI. Despite this, from highest to lowest, women are found in 1) biology and chemistry, 2) humanities and behavioural sciences, 3) social and economic sciences, 4) physics, mathematics, and earth sciences, and 5) engineering.\n\nThe results confirm the scissor effect or pyramid effect regarding women’s participation in science, as the number of women decreases as their professional career progresses. This situation demands effective policies that encourage and ensure greater presence and participation of women in scientific research in Mexico.\n\nOn the other hand, the research by González and Álvarez (2016) aimed to determine the factors that influence the achievement of efficient research formulation in Mexico through a descriptive-correlational study. With a sample of 42 researchers, they identified the following factors influencing the achievement of research formulation: development of analytical thinking, efficient database searching, management of research projects, efficient use of software, data analysis and modelling, innovation, and proper time management.\n\nPons-Peregort et al. (2013) analyzed gender equality of opportunities in science and technology to understand the career paths of female scientists in Spain. Using a mixed methodology, they identified that equality of opportunities in internal promotion, salary disparities, and work-life balance are challenges that can be overcome with research policies. The low presence of women in scientific professional careers is based on the hegemony of masculine values, which calls for rethinking the achievement of the critical mass needed to bring about structural transformations in the research field, estimated to be 35% (Langford et al., 1995). The authors propose policies that support maternity, childcare services, tax deductions for women who stay at home to care for children because their absence perpetuates women’s inferior position in the labor market and keeps them away from the research field.\n\nIn this sense, the indicators that contribute to the definition of the dimension of research policies are entities proposing the policy (State, Ministries, Universities, NGOs), research calls, inclusive financing, composition of the evaluation committee, institutional university policy, incentives and/or recognition, organizational culture (discriminatory biases), types of contracts.\n\niii) Scientific production: Twenty-four percent of the RPB aims to study the gender gap in scientific production. Luna & Luna (2018) analyzed Mexico’s scientific production recorded in Web of Science from 1900 to 2000 in the fields of exact sciences and engineering to characterize the involvement of female researchers in these fields of study. As these areas have traditionally been associated with men, the research sought to highlight the breakthroughs and achievements of women, considering that they are not the majority in either field. The research used indicators in regard to gender, scientific production and impact, bibliometric and co-authorship network analysis.\n\nThe results showed that scientific production increased from the 1980s and 1990s, mainly due to increases in postgraduate studies, the consolidation of research groups, and an increase in national and international scientific collaborations (Luna & Collazo, 2002). Scientific production is concentrated in five institutions and is led by UNAM, which has had female representation for 29 years. Additionally, the co-authorship network of research groups in the physical, chemical, mathematical, and engineering studies emerges in various specialties. The increase in scientific productivity is associated with the growth of female enrolment in higher education in natural sciences (47%) and engineering (25%) (UNESCO, 2019), as well as the creation of new educational institutions since the 1960s and the emergence of women in traditionally male-dominated disciplines.\n\nContinuing with Mexican research, Castro (2018) explores how a group of female researchers breaks paradigms and reshapes the line of women in scientific production. To achieve this, they incorporated qualitative-quantitative methods that included Participatory Action Research (PAR), Véster’s sensitive model, as well as validation indexes and indicators; monitoring and prospecting systems. This allowed them to conclude that women construct knowledge supported by a real and symbolic world.\n\nGarcía (2014) explores the situation of women in the research field in Mexico and discovers that difficulties arise in reconciling academic degrees with motherhood, publishing requires fulfilling the double workload, supervising degree projects requires time and mobility availability, lack of transparency in selection processes, and being evaluated by men negatively impact women’s research.\n\nIn Ecuador, Basurto and Ricaurte (2016) used a mixed study to examine the situation of women in the academic field of tourism. The results identified the low representation of women in teaching positions (53%) compared to the percentage of female students in tourism (75%), as well as male leadership in research from participating educational institutions, which are mostly organized by women. The explanatory factors found were difficulty reconciling research roles with motherhood, gender stereotypes, and the social perception of tourism as a feminine disciplinary field.\n\nLópez and Farías (2022) propose a quantitative analysis of the temporal trajectories of gender parity in scientific publications in Colombia. The country ranks fifth in scientific productivity in Latin America and allocates 0.5% of its GDP to R+D (MINCIENCIAS, 2020). English language proficiency is a disadvantage for Colombian researchers and is closely related to socioeconomic status. Similarly, gender stereotypes in the workplace negatively affect female researchers, leading the authors to assert that it is not simply about increasing the number of women in science and their scientific production, but rather reevaluating how science is done and valued in Colombia, which requires an inclusive and equitable ecosystem.\n\nThey highlight that the scientific areas with the highest number of female publications are medical sciences (37.76%), social sciences (35.51%), and natural sciences (29.09%).\n\nRegarding gender gaps in research productivity and recognition among elite scientists in the United States, Canada, and South Africa, as studied by Sá et al. (2020), it was found that women in science in these countries are under-cited, underpaid, underpromoted, and receive less professional recognition compared to their male counterparts, which puts women at a disadvantage when considering the principle of cumulative advantage, indicating that greater recognition leads to more productivity. They identified factors such as differences in family responsibilities, different patterns in the use of time (women spend more time teaching, advising students, and participating in committees), unequal allocation of resources, gender bias in peer review, gender stratification in disciplines, as well as different patterns in academic collaboration and network building as explanatory factors for the low productivity of female researchers.\n\nIn an Italian study conducted by Abramo et al. (2013) using a bibliometric approach, they sought to identify academics’ propensity for collaboration, leading them to conclude that women demonstrate a greater capacity to collaborate in all the analysed forms (intramural, extramural, national, and international), except in international collaboration, where the gap with male counterparts persists.\n\nAmong the explanatory factors for productivity gaps in research compared to men, they found that the low percentage of female academics, discrimination affecting job opportunities, biases, difficulty accessing funding, and limitations due to family responsibilities negatively affect female researchers.\n\nPinho-Gomes et al. (2020) investigate the authorship of women in COVID-19 research by asking “where are the women?” The study shows that women are underrepresented in research, particularly in first and last author positions. These gender biases point to broader inequalities that include authorship in other scientific areas and senior authorship.\n\nBased on the aforementioned, the indicators in the scientific production factor are the following researcher category, number of publications, number of patents, collaborative authorship, type of publication (scientific article, popular article, book chapter, book, collections), segregation (female collaborations), and citability.\n\niv) Profile. Thirty-seven percent of the RBP presented research results addressing the characteristics, motivations, uniqueness, and distinctive traits of researchers. In this perspective, Prieto de Alizo (2008) provides a theoretical approach to the characteristics of researchers in the humanities field using a phenomenological, hermeneutic, and ethnographic approach with successive interviews until theoretical saturation of categories is reached. The study conducted in Venezuela defined researchers as individuals with an active interest in understanding, learning, deconstructing, and constructing their reality. Beyond defining the characteristics of the group of researchers, the research made it possible to address two other fundamental aspects: the researchers’ conception of conducting research and the context in which research is carried out. This includes aspects such as institutional identification, the academic space where they work, the research-teaching relationship, the appreciation of the profession, administrative strategies in terms of institutional and state policies, as well as quality criteria.\n\nIn Spain, Dapía et al., (2019) explored whether science has a gender association among primary school students. Using a gender perspective analysis, they administered the PANA instrument (Project on Attitudes Toward Science in Children and Adolescents) by Pérez and Pro (2005) and the ROSE questionnaire (Schreiner and Sjøberg, 2004) to 378 students. The investigation showed a weak association between gender and science, a more positive attitude towards science among boys, and no gender bias in the desire to become a scientist. This led to the conclusion that there is a need to improve knowledge about the contributions of science and that career aspirations to become scientists in primary education are not associated with gender.\n\nResearch conducted in Mexico by Carrillo and Flores (2023), aimed at describing the educational trajectory of women during their professional studies, surveyed 152 women scientists from the National System of Researchers (SNI) selected through non-probability sampling. The study aimed to identify obstacles, challenges, and experiences in the scientific field. Using descriptive quantitative methodology, they found that women face gender-related barriers such as invisibility, lack of recognition for scientific contributions, inequity, stereotypes associated with the care economy, dual burden of work, and difficulties in achieving work-life balance.\n\nIn the same vein, they identified variables associated with gender such as the choice of professional career, gender division of labour, sociocultural conditions, social valuation, stereotypes, and gender roles. Regarding the academic trajectory, the variables that influence it are discipline, postgraduate studies, periodic publications, difficulties in entering and advancing in the SNI (lower hierarchy, prolonged stagnation, institutional conditions, as well as symbolic and social gender aspects).\n\nAs a result, the main challenges faced by female researchers are related to bureaucracy, in terms of paperwork and procedures, the evaluation system based on quantity rather than quality, funding, lack of job security, competition in what they call the “wolf environment,” excessive workload due to lack of staff, and career advancement understood as continuous training and development processes.\n\nTherefore, the selected indicators for the profile dimension are motivations, existence of a sticky floor, income level, position, geographic location, educational level, career, age, gender, marital status, dependent care burden, rank or category, and recognition.\n\n\nConclusion\n\nResearch focused on gender differences in scientific research has identified a diverse range of determinants or explanatory factors for these gaps. Through a systematic review using the Proknow-C Knowledge Development Process and Constructivism methodology, this research identified the most relevant studies and potential factors influencing scientific research for female researchers and academics.\n\nThe research facilitated the identification of relevant indicators grouped into four dimensions. The first dimension analysed was academic offerings, considering variables such as the number of educational institutions, offered professional careers, total enrolment, STEM careers, and enrolment of women in natural sciences or STEM. Additional indicators included total female enrolment, female enrolment in natural sciences, female enrolment in social sciences, and female enrolment in health sciences.\n\nThe second dimension examined was research policies. The research found that 29% of the Relevant Bibliographic Portfolio (RBP) presented results regarding the impact of research policies on gender gaps in research. Mexico stood out as the country with the highest number of studies in this field. Indicators considered in the analysed documents included policy-proposing organizations (government, ministries, universities, NGOs), research calls, inclusive funding, composition of evaluation committees, university institutional policies, incentives/recognition, organizational culture (discriminatory biases), and types of employment contracts.\n\nThe third dimension focused on scientific production. The research found that 24% of the RBP aimed to study the gender gap in research production. The selected indicators were researcher category, number of publications, number of patents, collaborative authorship, publication types (scientific articles, popular articles, book chapters, books, collections), gender segregation in collaborations, and citability.\n\nThe final dimension addressed the profile of researchers. Approximately 37% of the RBP included studies investigating characteristics, motivations, singularities, and distinctive traits of researchers. Qualitative and quantitative indicators were selected, including motivations, the existence of glass ceiling, income level, position, geographical location, educational level, field of study, age, gender, marital status, dependency burden, rank or category, and recognition.\n\nSystematization processes in the literature review are usually processes whose complexity becomes more evident in the discussion of the results. In particular, because in this case the largest number of documents was concentrated in a single country, Mexico, a situation that leads to conceptual and, above all, contextual biases.\n\nThe proposed dimensions of analysis, along with the derived indicators from the conducted research, aim to contribute to the development of explanatory models for the determinants of gender differentials in research. Furthermore, this research aims to help the formulation of effective public policies that address and reduce these gender gaps.",
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Reference Source\n\nGonzález V, Álvarez NT: Factores que fortalecen la investigación. Caso investigadoras de la FIME-UANL. Opción. 2016; 32(13): 1118–1135. Reference Source\n\nGuil Bozal A: Género y construcción científica del conocimiento. Revista Historia de la de la educación latinoamericana. 2016; 18(27): 263–288. Publisher Full Text\n\nGutiérrez P, Cervantes E, Rojas G, et al.: Investigación educativa en Chihuahua con perspectiva de género. Qartuppi; 2020. Publisher Full Text\n\nGuzmán M d R: La construcción subjetiva de identidades en las académicas-investigadoras desde el espacio personal-familiar y su incidencia en la carrera laboral: caso UJED.2019. Reference Source\n\nHernández E, Treviño R: Perspectiva de género en la investigación urbana. Vivat Academia. 2016; 134: 47–56. Publisher Full Text\n\nJesús M, Quiza M, Romero E: De la excepción a la normalidad: Mujeres científicas en la Historia. Encuentros multidiscip. 2014; 47: 1–10. 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Publisher Full Text\n\nMaldonado C, Quiñonez P: Gender Inequality in Latin America: Chapter 4 Gender and Economics in Latin America: a Systematic Analysis of Scientific Production in Scopus. Brill; 2021. Publisher Full Text\n\nMandıracıoğlu A, Hilal Batı A, Gövsa F, et al.: Health science students’ opinions toward scientific research and women in science. Arastirma. 2018; 14(2): 22–30. Reference Source\n\nMartín GM: Mujeres científicas en la Unión Europea: ¿escasean todavía las mujeres en carreras científicas y en posiciones de liderazgo? Revista de Física Médica. 2012; 13(1). Reference Source\n\nMayer SJ, Rathmann JMK: How does research productivity relate to gender? Analyzing gender differences for multiple publication dimensions. Scientometrics. 2018; 117(3): 1663–1693. Publisher Full Text\n\nMINCIENCIAS: La ciencia en cifras.2020. Accessed 22 February 2020. 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}
|
[
{
"id": "217668",
"date": "22 Nov 2023",
"name": "Lorenzo Escot",
"expertise": [
"Reviewer Expertise Applied Economics",
"Gender Economics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper provides a systematic review that aims to identify the determinants of gender asymmetries in scientific research and provide insights on how to close these differences.\nThe subject is of great interest and relevance. The study identified four dimensions to classify the determinants of gender gaps in scientific research: academic supply, research policies, scientific production, and researcher profile.\nThe document appears to be well structured and provides detailed information on how the systematic review has performed.\n\n1) My main drawback with respect to the systematic analysis of the literature is in the selected databases. There is a clear sample selection bias towards Latin American and Hispanic journals as a consequence of the inclusion of the Redalyc index, since almost 50% of the bibliographic references found come from this repository.\n\nDo the authors think that their results could be generalized to all countries and to any time?. Would the resulting papers selected change if other repositories had been used?\n2) In some cases, the information on the characteristics of the sample of bibliographic references obtained does not allow relevant conclusions to be drawn. For example, Table 5 shows the Coverage years of the SJR index for the highlighted journals in the RBP. I understand that it is total coverage years in SJR, not the years used in the RBP. Is the information in this table really relevant? this information is only of the 5% of the RBP used?, are all the journals and all the papers included in SJR?\n\n3) Section \"iii) Scientific production\" summarizes the main findings of a selection of articles. It is not clear what criteria were used to select the articles explained in this section. How were they selected?, are they the most cited articles? are those published in the highest impact journals? or is it a purely random selection?\nIt is not clear, therefore, how the factors explained in section iii) are select as the main factors behind the gender gap. Are these factor in scientific literature supported by the quality of the journal?, or by the number of cites?, or whether this is simply a purely historical review?.\nIn any case, I would like to congratulate the authors for their excellent work.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": [
{
"c_id": "10915",
"date": "22 Jan 2024",
"name": "ORIANA RIVERA LOZADA",
"role": "Author Response",
"response": "My main drawback with respect to the systematic analysis of the literature is in the selected databases. There is a clear sample selection bias towards Latin American and Hispanic journals as a consequence of the inclusion of the Redalyc index, since almost 50% of the bibliographic references found come from this repository. Do the authors think that their results could be generalized to all countries and to any time?. Would the resulting papers selected change if other repositories had been used? R/ The repositories used for the research were, in order: Scopus, Redalyc, La referencia, Base-Search.net, Web of Science, Scielo, DOAJ and Ebsco, considering that they met the criteria of fields Boolean expressions, temporal horizon and type of publication (Table 2). These repositories were filtered with the keywords shown in table 2a and it is precisely there where Redalyc presents the largest number of documents related to the keywords of interest for this research. Perhaps another type of Boolean expressions in search offers repository participations different from those presented in this document. According to the above, we consider that there is no selection bias. 2) In some cases, the information on the characteristics of the sample of bibliographic references obtained does not allow relevant conclusions to be drawn. For example, Table 5 shows the Coverage years of the SJR index for the highlighted journals in the RBP. I understand that it is total coverage years in SJR, not the years used in the RBP. Is the information in this table really relevant? this information is only of the 5% of the RBP used?, are all the journals and all the papers included in SJR? R/ Accordingly, the years shown in Table 5 refer to the period of JRS coverage for journals and we show this to highlight 10 of the journals of the PBR, the ones with the highest score, thus informing the reader of the time of measurement of these journals by the JRS index and, therefore, their prestige. There are 10 journals that contain 1 PBR article each, so they represent 12.04% of the PBR used. Regarding the last question, not all articles are included in JRS, 44.57% of the PBR is found in journals that are measured with the JRS index, 42.16% of the PBR are articles from journals that have not been measured with this international index, so they are not found in figure 3 or table 5 and 13.26% are articles from web pages. Thesis, a book and a paper. 3) Section \"iii) Scientific production\" summarizes the main findings of a selection of articles. It is not clear what criteria were used to select the articles explained in this section. How were they selected?, are they the most cited articles? are those published in the highest impact journals? or is it a purely random selection? It is not clear, therefore, how the factors explained in section iii) are select as the main factors behind the gender gap. Are these factor in scientific literature supported by the quality of the journal?, or by the number of cites?, or whether this is simply a purely historical review?. In any case, I would like to congratulate the authors for their excellent work. R/ The research proposes to classify the systematic review of literature into four classifications: i) academic offer, ii) research policy, iii) scientific production and iv) research profile. Scientific production grouped the documents that focus their attention on scientific production by profession or by female researchers. In this perspective, the research presented in this section was presented due to its thematic relevance and proposed contributions, as it was selected from the documents with the highest citation. This was added to the paper"
}
]
},
{
"id": "215190",
"date": "18 Dec 2023",
"name": "Yolvi Javier Ocaña Fernandez",
"expertise": [
"Reviewer Expertise Education and invation"
],
"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 research addresses a very interesting and relevant topic at this time as is the identification of the determinants of gender asymmetries in scientific research and provide ideas on how to close these gaps. The dimensions they used to classify gender gaps: academic supply, research policies, scientific production and researcher profile, seem to me appropriate and based on the existing literature, so I congratulate the authors for their choice. The tables and figures help to understand all the information in the article. The conclusions are clear, well-structured and in accordance with the research objectives. The bibliography is well selected and well used throughout the document.\nAdditionally, the document is well structured and well written. As a suggestion I propose:\n1. Consider the inclusion of more articles from other databases, in order to avoid some biases, such as selection bias. It could also help to broaden the discussion of the research. 2.\n\nExpand the introduction so that references from other countries can be included, so that this valuable information can be used in other countries and especially background information related to the dimension of the research. Finally, I would like once again to congratulate the authors for their excellent work.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": [
{
"c_id": "10916",
"date": "22 Jan 2024",
"name": "ORIANA RIVERA LOZADA",
"role": "Author Response",
"response": "Consider the inclusion of more articles from other databases, in order to avoid some biases, such as selection bias. It could also help to broaden the discussion of the research. The repositories used for the research were, in order: Scopus, Redalyc, La referencia, Base-Search.net, Web of Science, Scielo, DOAJ and Ebsco, considering that they met the criteria of fields Boolean expressions, temporal horizon and type of publication (Table 2). These repositories were filtered with the keywords shown in table 2a and it is precisely there where Redalyc presents the largest number of documents related to the keywords of interest for this research. Perhaps another type of Boolean expressions in search offers repository participations different from those presented in this document. According to the above, we consider that there is no selection bias. 2. Expand the introduction so that references from other countries can be included, so that this valuable information can be used in other countries and especially background information related to the dimension of the research. are included in the text"
}
]
}
] | 1
|
https://f1000research.com/articles/12-1302
|
https://f1000research.com/articles/12-795/v1
|
07 Jul 23
|
{
"type": "Genome Note",
"title": "Plastid genome of Passiflora tripartita var. mollissima (poro-poro) from Huánuco, Peru",
"authors": [
"Flavio Aliaga",
"Mario Zapata-Cruz",
"Silvia Ana Valverde-Zavaleta",
"Mario Zapata-Cruz",
"Silvia Ana Valverde-Zavaleta"
],
"abstract": "Passiflora tripartita var. mollissima, known locally as poro-poro, is an important native fruit used in traditional Peruvian medicine with relevant agro-industrial and pharmaceutical potential for its antioxidant capacity for human health. However, to date, only a few genetic data are available, which limits exploring its genetic diversity and developing new genetic studies for its improvement. We report the poro-poro plastid genome to expand the knowledge of its molecular markers, evolutionary studies, molecular pathways, and conservation genetics. Total genomic DNA was extracted from fresh leaves (herbarium voucher: USM:MHN331530). The DNA was sequenced using Illumina Novaseq 6000 platform providing 163,451 bp in length, with a large single-copy region of 85,525 bp and a small single-copy region of 13,518 bp, separated by a pair of inverted repeat regions (IR) of 32,204 bp, and the overall GC content was 36.87%. The chloroplast genome contains 129 genes (112 genes were unique and 17 genes were found duplicated in each IR region), including 85 protein-coding genes, 37 transfer RNA-coding genes, seven ribosomal RNA-coding genes, and 14 genes with introns (12 genes with one intron and two genes with two introns). The phylogenetic tree reconstructed based on single-copy orthologous genes and maximum likelihood analysis demonstrates poro-poro is most closely related to Passiflora menispermifolia and Passiflora oerstedii. In summary, our study provides the basis for developing new molecular markers that constitutes a valuable resource for studying molecular evolution and domestication. It also provides a powerful foundation for conservation genetics research and plant breeding programs. To our knowledge, this is the first report on the plastid genome of Passiflora tripartita var. mollissima from Peru.",
"keywords": [
"Plastid genome",
"Passifloraceae",
"Passiflora tripartita var. mollissima",
"poro-poro",
"native fruit",
"Huánuco",
"Peru"
],
"content": "Introduction\n\nPassiflora tripartita var. mollissima (Kunth) Holms-Niels. & P.M. Jørg (ITIS, 2022) previously known as Passiflora mollissima (Kunth) Bailey (Primot et al., 2005), is a semi-perennial fruit plant (Mayorga et al., 2020). It is a diploid species with a small number of chromosomes (2n = 18) (Coppens D’Eeckenbrugge, 2001), which is placed in the section Elkea of supersection Tacsonia of subgenus Passiflora belonging to the Passifloraceae family (Segura et al., 2005; Ocampo & Coppens d’Eeckenbrugge, 2017). Poro-poro is a native fruit of the Andean region (Ocampo & Coppens d’Eeckenbrugge, 2017). It grows in the Peruvian highlands in the departments of Ancash, Junín, Moquegua, Huancavelica, and Huánuco at altitudes of 1,000–4,000 m.a.s.l. (Tapia & Fries, 2007; Ríos-García, 2017). It is widely used in traditional medicine (Ríos-García, 2017) and is considered one of the best Passiflora species based on its organoleptic characteristics (Primot et al., 2005). This fruit provides a source of vitamins (A, B3, and C) and minerals (magnesium, potassium, phosphorus, sodium, chlorine, iron, calcium, sulfur, zinc, copper, selenium, cobalt, and nickel) (Leterme et al., 2006; Chaparro-Rojas et al., 2014). In addition, it has an elevated antioxidant activity and high content of carotenoids (118.8 mg β-carotene), phenols (460.1 mg gallic acid), and flavonoids (1907.6 mg catechin/100 g) (Leterme et al., 2006; Chaparro-Rojas et al., 2014). Specifically, the high concentration of flavan-3-ols (a group of bioactive compounds) has been associated with beneficial effects on human health, such as cardiovascular protection, neurodegenerative diseases, and as an anti-cancer, anti-microbial, and anti-parasitic agent (Giambanelli et al., 2020; Luo et al., 2022).\n\nPlastome sequences of more than 800 sequenced genomes are small in size with high copy numbers and conserved sequences, enabling a significant understanding of plant molecular evolution, structural variations, and evolutionary relationships of plant diversity (Daniell et al., 2016; Dobrogojski et al., 2020). The plastid genome has a quadripartite structure: a large single-copy (LSC) of 80–90 kilobase pairs (kb), a small single-copy (SSC) of 16–27 kb, and two sets of inverted repeats (IRa and IRb) of 20–28 kb, with 110–130 unique genes, including protein-coding genes, transfer RNA (tRNA), and ribosomal RNA (rRNA) (Ozeki et al., 1989; Wang & Lanfear, 2019). In recent years, declining genome sequencing costs resulted in more than 780 complete plant genomes of different species becoming available (Marks et al., 2021; Sun et al., 2022). Recently, some Passiflora plastid genomes such as Passiflora edulis (Cauz-Santos et al., 2017), Passiflora xishuangbannaensis (Hao & Wu, 2021), Passiflora caerulea (Niu et al., 2021), Passiflora serrulata (Mou et al., 2021), Passiflora foetida (Hopley et al., 2021), and Passiflora arbelaezii (Shrestha et al., 2019), became publicly available. However, despite the scarcity of genomic information on underutilized crops (Gioppato et al., 2019), we have only begun to investigate the genomics of plants of great importance for plant breeding programs. The aim of the present study was to sequence, assemble, and annotate the plastid genome of poro-poro to contribute to plant breeding programs. In the present study, we report the first plastid genome sequence submitted for an isolate of Passiflora tripartita var. mollissima from Peru, a species with great agro-industrial and pharmaceutical potential because of its beneficial characteristics for human health.\n\n\nMethods\n\nIn November 2022, the fresh leaves of Passiflora tripartita var. mollissima were collected from Raccha Cedrón locality of Quisqui District, Huánuco Province from Peru (9°53′37″S, 76°26′02″W, altitude 2,945 m.a.s.l.). A herbarium voucher specimen (USM<PER>:MHN331530) was deposited in the Herbario San Marcos (USM) of the Museo de Historia Natural (MHN) at the Universidad Nacional Mayor de San Marcos (UNMSM) (see the Extended data, Aliaga et al., 2023a).\n\nTotal genomic DNA was extracted from approximately 100 mg fresh leaves (from voucher number USM<PER>:MHN331530) according to Doyle’s (1991) method with slight modifications. The DNA isolation buffer consisted of buffer cetyl-trimethyl ammonium bromide (CTAB) 3% (30g/L CTAB, 100 mM Tris-HCl pH 8.0, 10nM EDTA, 1.4 M NaCl, 0,2% 2-mercaptoethanol), 70% ethanol, chloroform-isoamyl alcohol (24:1), 10 mM ammonium acetate, isopropanol, TE buffer (10 mM Tris-H, 1 mM EDTA), and RNAase A (10 ug/ml). Genomic DNA quality was assessed using a fluorometry-based Qubit (Thermo Fisher Scientific, USA, catalog number: Q33238) coupled to a Broad Range Assay kit (Thermo Fisher Scientific, USA, catalog number: Q33230). High-quality DNA (230/260 and 260/280 ratios >1.8) were normalized (20 ng/μL) to examine its integrity using 1% (w/v) agarose gel electrophoresis (see the Extended data, Aliaga et al., 2023b) with the following equipment: Horizontal gel system (Fisher Scientific, Denmark, catalog number: 11833293, 150mm (length), 100 mm (width)), Transilluminator (Fisher Scientific, Spain, catalog number: 12864008), and digital camera (Canon, Spain, catalog number: 2955C002); Reagents: TAE buffer (40 mM Tris, 20mM NaAc, 1mM EDTA, pH 7.2), loading buffer 6X (Promega, USA, catalog number: G1881, 0.4% orange G, 0.03% bromophenol blue, 0.03% xylene cyanol FF, 15% Ficoll® 400, 10mM Tris-HCl pH 7.5 and 50mM EDTA pH 8.0) and Ethidium bromide (Promega, USA, catalog number H5041, 10 mg/ml), and 1 Kb Plus DNA Ladder (ThermoFisher, USA, catalog number: 10787018).\n\nQualified DNA was fragmented, and the TruSeq Nano DNA kit (Illumina, San Diego, CA, USA, catalog number: FC-121-4001) was used to construct an Illumina paired-end (PE) library. PE sequencing (2 × 150 bp) was performed using the Illumina NovaSeq 6000 platform (Modi et al., 2021) (Illumina, San Diego, Ca, USA, catalog number: 20012850) (Macrogen, Inc., Seoul, Republic of Korea). All adapters and low-quality reads were removed using the FastQC (Wingett & Andrews, 2018) and Cutadapt (Martin, 2011) programs. PE reads (2 × 150 bp) were evaluated for quality using QUAST (Gurevich et al., 2013) analysis, and subsequent steps used clean data. Then, clean reads obtained were assembled into a circular contig using NOVOPlasty v.4.3 (Dierckxsens et al., 2017), with P. edulis (NC_034285) as the reference (Cauz-Santos et al., 2017). The plastid genome was annotated using the Dual Organellar GenoMe Annotator GeSeq (Tillich et al., 2017) and CpGAVAS2 (Shi et al., 2019). A circular genome map was constructed using OGDRAW v.1.3.1 (Greiner et al., 2019). Finally, the completed sequences were submitted to the NCBI GenBank under the accession number OQ910395 (GenBank, 2023).\n\nWe used 26 complete plastome sequences to infer the phylogenetic relationships among Passiflora species, and Vitis vinifera was used as an outgroup (see the Extended data, Aliaga et al., 2023c). Single-copy orthologous genes were identified using the Orthofinder version 2.2.6 pipeline (Emms & Kelly, 2019). For each gene family, the nucleotide sequences were aligned using the L-INS-i algorithm in MAFFT v7.453 (Katoh & Standley, 2013). A phylogenetic tree based on maximum likelihood (ML) was constructed using RAxML v8.2.12 (Stamatakis, 2014) with the GTRCAT model. A phylogenetic ML tree was reconstructed and edited using MEGA 11 (Tamura et al., 2021) with 1000 replicates.\n\n\nResults\n\nThe plastid genome sequences of P. tripartita var. mollissima (poro-poro) (Figure 1) was 163,451 bp in length, with a typical quadripartite structure consisting of a large single-copy (LSC) region of 85,525 bp (52.32% in total) and a small single-copy (SSC) region of 13,518 bp (8.27%), separated by a pair of inverted repeat regions (IRs) of 32,204 bp (19.70%). The poro-poro plastome is 12,045 bp longer than that of one of the most economically important species, passion fruit (P. edulis) (Cauz-Santos et al., 2017), and is only 7,117 bp longer than that of the longest Passiflora plastome reported, i.e., P. arbelaezii (Shrestha et al., 2019). The plastome sequence of poro-poro has a similar quadripartite architecture to other plants (Ohyama et al., 1986; Shinozaki et al., 1986; Nguyen et al., 2021). However, the LSC region is 4,150 bp longer than that of P. xishuangbannaensis but is 98bp, 195 bp, and 1,927 bp shorter than that of P. caerulea, P. edulis, and P. arbelaezii, respectivety. The SSC region is 121 bp, 140 bp, 359 bp, and 754 bp longer than that of P. caerulea, P. edulis, P. xishuangbannaensis, and P. arbelaezii, respectively. The IRs regions are 6,024 bp, 6,050 bp, and 11,600 longer than that of P. caerulea, P. edulis, and P. xishuangbannaensis, respectively; however, it is 2,972 bp shorter than that of P. arbelaezii (Cauz-Santos et al., 2017; Shrestha et al., 2019; Hao & Wu, 2021; Niu et al., 2021). The plastome structure of the P. tripartita var. mollissima consisted of A = 30.79%, T(U) = 32.34%, C = 18.67% and G = 18.20%. The overall AT content of the plastid genome was 63.13%, whereas the overall GC content was 36.87% as similar to that of other reported chloroplast genomes from the same family, such as 36.90% in P. arbelaezii (Shrestha et al., 2019), 37% in P. edulis and P. serrulata (Cauz-Santos et al., 2017; Mou et al., 2021), 37.03% in P. caerulea (Niu et al., 2021), and 37.1% in P. xishuangbannaensis (Hao & Wu, 2021).\n\nThe thick lines indicate the IR1 and IR2 regions, which separate the large single-copy (LSC) and small single-copy (SSC) regions. Genes marked inside the circle are transcribed clockwise, and genes marked outside the circle are transcribed counterclockwise. Genes are color-coded based on their function, shown at the bottom left. The inner circle indicates the inverted boundaries and guanine and cytosine (GC) content.\n\nPoro-poro plastid genome annotation identified 129 genes, of which 112 were unique, and 17 were duplicated in the inverted repeat (IR) region. The plastome contained 85 protein-coding genes, 37 transfer RNA (tRNA)-coding genes, seven ribosomal RNA (rRNA)-coding genes, and 14 genes with introns (12 genes with one intron and two genes with two introns), as shown in Table 1. The poro-poro plastid genome contained 112 unique genes, of which there were 29 tRNA genes, four rRNA genes, and 79 protein-coding genes. The latter comprised 20 ribosomal subunit genes (nine large subunits and 11 small subunit), four DNA-directed RNA polymerase genes, 46 genes were involved in photosynthesis (11 encoded subunits of the NADH oxidoreductase, seven for photosystem I, 15 for photosystem II, six for the cytochrome b6/f complex, six for different subunits of ATP synthase, and one for the large chain of ribulose biphosphate carboxylase), eight genes were involved in different functions, and one gene was of unknown function (Table 2).\n\n1 Poro-poro is the common name of Passiflora tripartita var. mollissima in Peru.\n\na LSC: a large single-copy.\n\nb SSC: a small single-copy.\n\nc IR: inverted repeat.\n\nd A: adenine.\n\ne T(U): thymine (uracil).\n\nf G: guanine.\n\ng C: cytosine.\n\nh rRNA: ribosomal RNA.\n\ni tRNA: transfer RNA.\n\n* Gene contains one intron.\n\n** gene contains two introns; (X2) indicates two gene copies in IRs.\n\nIn the plastid genome, 14 genes contained introns distributed as follows: the LSC, SSC, and IRs regions contained eight genes (petD, rpl16, rpoC1, trnG-UCC, trnK-UUU, trnL-UAA, trnV-UAC, and ycf3), one gene (ndhA), and five genes (ndhB, rpl2, rps12, trnA-UGC, and trnI-GAU) respectively. Similarly, these genes included six protein-coding genes, each with a single intron (petD, ndhA, ndhB, rpoC1, rpl2, and rpl16); six tRNA genes, each with a single intron (trnA-UGC, trnG-UCC, trnI-GAU, trnK-UUU, trnL-UAA, and trnV-UAC); and two protein-coding genes with two introns (ycf3 and rps12). Except for 17 genes that were duplicated in the IR region (ndhB, rps19, rpl2, rpl23, rps12, ycf15, rrn5, rrn16, rrn23, trnA-UGC, trnI-CAU, trnI-GAU, trnL-CAA, trnM-CAU, trnN-GUU, trnR-ACG, and trnV-GAC) all genes contained a single copy, as shown in Table 2. The plastome of P. tripartita var. mollissima contained eight genes (ycf1, ycf2, ycf15, rps16, rpl20, rpl22, accD, infA) that were lost or non-functional genes in P. edulis; and compared to P. edulis, it has one absent gene (trnfM-CAU), as previously reported (Cauz-Santos et al., 2017). In this study, the ycf1 sequence encodes a protein essential for plant viability and a vital component of the translocon on the inner chloroplast membrane (TIC) complex (Kikuchi et al., 2013), and ycf2 is a component of the ATPase motor protein associated with the TIC complex (Kikuchi et al., 2018).\n\nTo identify the evolutionary position of Passiflora tripartita var. mollissima in the Passifloraceae family, phylogenetic relationships based on the OrthoFinder clustering method were used to avoid erroneous rearrangements in phylogenetic tree reconstruction and provides a more reliable evolutionary analysis (Gabaldón, 2005; Zhang et al., 2012). The phylogenetic tree was constructed based on single-copy orthologous genes (Emms & Kelly, 2019) and maximum likelihood analysis with the complete annotated protein sequences of 27 plastid genomes, of which 26 were from Passiflora species. One species, Vitis vinifera, was chosen as the outgroup.\n\nMaximum likelihood (ML) bootstrap values ranged from 38%–92% for seven of the 25 nodes. All nodes except the indicated ones (seven nodes) exhibited bootstrap support (BS) values of 100%. These Passiflora species were divided into four groups: subgenus Passiflora (P. nitida, P. quadrangularis, P. cincinnata, P. caerulea, P. edulis, P. laurifolia, P. vitifolia, P. serratifolia, P. serrulata, P. ligularis, P. serratodigitata, P. actinia, P. menispermifolia and P. oerstedii), subgenus Tetrapathea (P. tetrandra), subgenus Decaloba (P. microstipula, P. xishuangbannaensis, P. biflora, P. lutea, P. jatunsachensis, P. suberosa and P. tenuiloba), and subgenus Deidamoides (P. contracta and P. arbelaezii). The relationships between the four subgenera of Passiflora species (Passiflora, Tetrapathea, Decaloba, and Deidamoides) were congruent and strongly supported by the same patterns as previously reported (Cauz-Santos et al., 2020; Pacheco et al., 2020). These results resolved Passiflora tripartita var. mollissima belonging to the subgenus Passiflora, which was closely related to P. menispermifolia and P. oerstedii with 100% BS, and was sister to P. tetrandra (subgenus Tetrapathea), P. biflora (subgenus Decaloba), and P. contracta (subgenus Deidamoides), as shown in the cladogram (Figure 2).\n\nBootstrap values on the branches were calculated from 1000 replicates.",
"appendix": "Data availability\n\nNucleotide: Passiflora tripartita var. mollissima chloroplast, complete genome. Accession number: OQ910395. https://identifiers.org/nucleotide:OQ910395 (GenBank, 2023).\n\nFigshare: Herbarium specimen voucher of Passiflora tripartita var. mollissima (Kunth) Holms-Niels. & P.M. Jørg (USM:MHN331530). https://doi.org/10.6084/m9.figshare.23556654 (Aliaga et al., 2023a).\n\nFigshare: Gel imagen of DNA isolate from poro-poro sample. https://doi.org/10.6084/m9.figshare.23560755 (Aliaga et al., 2023b).\n\nFigshare: Details of the plastid genome sequences used for phylogenetic analysis. https://doi.org/10.6084/m9.figshare.23556834 (Aliaga et al., 2023c).\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 Universidad Privada del Norte (UPN) for funding the APC. We thank the Servicio Nacional Forestal y de Fauna Silvestre (SERFOR) for authorized this research project (AUT-IFL-2022-058). We thank Prof. Dr. Esteban Hopp (Universidad de Buenos Aires) for their careful reading of the manuscript and their constructive remaks. We thank Petr Sklenář and Filip Kolar for their help in the sample collection. We thank curator Julio C. Torres–Martinez (Museo de Historia Natural, Universidad Nacional Mayor de San Marcos) for the taxonomy identification and deposit of the plant specimen. We thank Dr. Rajest Mahato and Dr. Giusseppe D’Auria for the recommendations and bioinformatics support. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang W, Lanfear R: Long-reads reveal that the chloroplast genome exists in two distinct versions in most plants. Genome Biol. Evol. 2019; 11: 3372–3381. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWingett SW, Andrews S: FastQ Screen: A tool for multi-genome mapping and quality control. F1000Res. 2018; 7: 1338. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang N, Zeng L, Shan H, et al.: Highly conserved low-copy nuclear genes as effective markers for phylogenetic analyses in angiosperms. New Phytol. 2012; 195: 923–937. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "191279",
"date": "30 Aug 2023",
"name": "Rahul G Shelke",
"expertise": [
"Reviewer Expertise Organelle genome sequencing",
"Transcriptome assembling",
"Genetic diversity",
"Barcoding and DNA markers 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 extend my appreciation to the authors for their commendable efforts in extensively exploring the plastid genome of Passiflora tripartita var. mollissima, demonstrating remarkable depth and breadth in their approach. The manuscript substantially enhances our comprehension of this species, emphasizing its plastid genome, genetic diversity, and evolutionary relationships. This newfound insight carries far-reaching implications, fostering the conservation and sustainable utilization of this species. Consequently, the manuscript's significance is markedly elevated, making a noteworthy contribution to the scientific community's understanding of genetic resource stewardship.\nHere is a concise summary of the study's key points:\nImplications and Novelty: The findings of the study hold significant implications. The genetic insights uncovered have the potential to catalyze further investigations in areas such as molecular evolution, conservation genetics, and the development of plant breeding programs. Notably, the manuscript's distinction as the first documentation of the plastid genome of Passiflora tripartita var. mollissima from Peru underscores its novel contribution to the scientific community.\n\nMethodological Rigor: The authors' selection of the Illumina Novaseq 6000 platform for DNA sequencing is well-suited to the research objectives. The subsequent analyses and methodologies applied exhibit robustness and alignment with the research goals.\nMajor comments:\n\nWhile the genes in Table 2 have been organized into categories, it is apparent that certain instances lack gene information or are unclear in their presentation. This calls for a restructuring of the table to ensure a heightened level of clarity and coherence.\n\nIn Table 2, the authors have indicated the absence of a duplicated copy of the rrn4.5 gene. It is advised that the authors review the annotation of this gene. Typically, rRNA genes are located within the IR regions and therefore exist in duplicated copies. However, in Figure 1 of the chloroplast genome, the rrn4.5 gene is depicted in a duplicated copy. I recommend that the authors rectify any discrepancies pertaining to the rrn4.5 gene both in the table and within the text.\n\nThe authors have provided comprehensive insights into the expansion and contraction of the LSC, SSC, and IR regions in the compared species. To further enhance reader comprehension, I recommend that the authors consider incorporating the corresponding IRSCOPE figure within the manuscript. This addition would allow readers to access detailed information more effectively and contribute to a clearer understanding of the discussed concepts.\n\nKindly provide information regarding the genes that are missing or subject to gene loss within the compared species.\n\nIn the abstract, the authors have included the statement: “In summary, our study provides the basis for developing new molecular markers that constitutes a valuable resource for studying molecular evolution and domestication.” However, upon reviewing the manuscript, it is evident that the authors have not conducted any SSR, tandem repeat, or DNA diversity analysis, nor have they proposed any markers. Given this situation, I recommend that the authors consider removing the phrase “developing new molecular markers” from the abstract to accurately reflect the scope of their study.\nMinor comments:\nThe inclusion of specific methodology details such as \"Total genomic DNA was extracted from fresh leaves (herbarium voucher: USM:MHN331531)\" and \"The DNA was sequenced using Illumina Novaseq 6000 platform\" in the abstract might be better suited for the methodology section rather than the abstract itself. Focusing the abstract on the core findings and implications of the study could enhance its conciseness and clarity.\n\nAdd the full botanical name of Passiflora tripartita in the phylogeny tree to ensure consistency.\n\nGene names should be in italics.\n\nIt is recommended to include the coverage of the genome assembly within the main text of the manuscript.\nThe authors adeptly tackle gaps in our understanding of this species' genetics, comparative genomics, and evolutionary relationships. By thoughtfully engaging with reviewer feedback and subsequently refining their manuscript, the authors stand poised to elevate the impact and significance of their research within the realm of plant genomics and beyond. This process will significantly enhance the accuracy and reliability of gene classification and annotation, thereby elevating the overall quality of the manuscript.\n\nAre the rationale for sequencing the genome and the species significance clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of the sequencing and extraction, software used, and materials provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a usable and accessible format, and the assembly and annotation available in an appropriate subject-specific repository? Yes",
"responses": [
{
"c_id": "10829",
"date": "23 Jan 2024",
"name": "Flavio Aliaga",
"role": "Author Response",
"response": "Corresponding Author: Flavio Aliaga Grupo de Investigación en Ecología Evolutiva, Protección de Cultivos, Remediación Ambiental, y Biotecnología (EPROBIO), Universidad Privada del Norte, Trujillo, Peru. Dirección de Investigación, Innovación y Responsabilidad Social, Universidad Privada del Norte, Trujillo, 13011, Peru The authors thank Dr. Rahul G. Shelke for taking the time and effort necessary to review the manuscript. We sincerely appreciate all the valuable comments and suggestions that helped us improve the quality of the manuscript. Answers to Reviewer #1 Major comments: 1. While the genes in Table 2 have been organized into categories, it is apparent that certain instances lack gene information or are unclear in their presentation. This calls for a restructuring of the table to ensure a heightened level of clarity and coherence. Answer: We agree with the reviewer. The manuscript has been revised, thanks. 2. In Table 2, the authors have indicated the absence of a duplicated copy of the rrn4.5 gene. It is advised that the authors review the annotation of this gene. Typically, rRNA genes are located within the IR regions and therefore exist in duplicated copies. However, in Fiure 1 of the chloroplast genome, the rrn4.5 gene is depicted in a duplicated copy. I recommend that the authors rectify any discrepancies pertaining to the rrn4.5 gene both in the table and within the text. Answer: We would like to thank the reviewer for highlighting this important comment. In fact, we checked and updated the duplicated copy of the rrn4.5 gene. Thank you. 3. The authors have provided comprehensive insights into the expansion and contraction of the LSC, SSC, and IR regions in the compared species. To further enhance reader comprehension, I recommend that the authors consider incorporating the corresponding IRSCOPE figure within the manuscript. This addition would allow readers to access detailed information more effectively and contribute to a clearer understanding of the discussed concepts. Answer: Thank you for your comment. According to your suggestions, we have added the figure 2 titled “Comparison of IR/SC boundary regions of four Passiflora species”. 4. Kindly provide information regarding the genes that are missing or subject to gene loss within the compared species. Answer: Thank you for your reminding. Done. 5. In the abstract, the authors have included the statement: “In summary, our study provides the basis for developing new molecular markers that constitutes a valuable resource for studying molecular evolution and domestication.” However, upon reviewing the manuscript, it is evident that the authors have not conducted any SSR, tandem repeat, or DNA diversity analysis, nor have they proposed any markers. Given this situation, I recommend that the authors consider removing the phrase “developing new molecular markers” from the abstract to accurately reflect the scope of their study. Answer. We agree with the reviewer. The manuscript has been corrected: “In summary, our study constitutes a valuable resource for studying molecular evolution, phylogenetics, and domestication…” Minor comments: 1. The inclusion of specific methodology details such as \"Total genomic DNA was extracted from fresh leaves (herbarium voucher: USM:MHN331531)\" and \"The DNA was sequenced using Illumina Novaseq 6000 platform\" in the abstract might be better suited for the methodology section rather than the abstract itself. Focusing the abstract on the core findings and implications of the study could enhance its conciseness and clarity. Answer. Yes, we agree with the reviewer. Done. 2. Add the full botanical name of Passiflora tripartita in the phylogeny tree to ensure consistency. Answer. Done. 3. Gene names should be in italics. It is recommended to include the coverage of the genome assembly within the main text of the manuscript. Answer. Done. 4. The authors adeptly tackle gaps in our understanding of this species' genetics, comparative genomics, and evolutionary relationships. By thoughtfully engaging with reviewer feedback and subsequently refining their manuscript, the authors stand poised to elevate the impact and significance of their research within the realm of plant genomics and beyond. This process will significantly enhance the accuracy and reliability of gene classification and annotation, thereby elevating the overall quality of the manuscript. Answer: We thank reviewer 1 for all constructive comments that led to substantial improvement of the manuscript. Thank you; it is much appreciated."
}
]
},
{
"id": "191281",
"date": "04 Sep 2023",
"name": "Abdullah Abdullah",
"expertise": [
"Reviewer Expertise I can assess all aspects of the manuscript and published up to 18 articles in the same field."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAuthors need to describe how the current genome will be helpful. I found many species of the genus Passiflora in the NCBI. So, authors need clear points about the need for the existing genome. In addition, all the genomes have similar features so the current genome is helpful for the study of evolution and phylogenetics.\n\nThe authors mentioned the number of reported genomes up to 800. This statement is not correct and is based on earlier observations. Now the number has increased significantly.\n\nI found authors are not entirely aware of the utilization of some software. For example, authors mention fastqc for trimming while fastqc checks the quality of reads.\nThe authors used many programs for annotations. I will suggest authors use GeSeq along with Chole, Aragorn and tRNAScan on GeSeq servers for annotation of transfer RNA.\n\nThe authors need to give some information on how the current genome is similar to or differs from other reported genomes of Passiflora.\n\nAre the rationale for sequencing the genome and the species significance clearly described? Partly\n\nAre the protocols appropriate and is the work technically sound? Partly\n\nAre sufficient details of the sequencing and extraction, software used, and materials provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a usable and accessible format, and the assembly and annotation available in an appropriate subject-specific repository? Yes",
"responses": [
{
"c_id": "10830",
"date": "23 Jan 2024",
"name": "Flavio Aliaga",
"role": "Author Response",
"response": "Corresponding Author: Flavio Aliaga Grupo de Investigación en Ecología Evolutiva, Protección de Cultivos, Remediación Ambiental, y Biotecnología (EPROBIO), Universidad Privada del Norte, Trujillo, Peru. Dirección de Investigación, Innovación y Responsabilidad Social, Universidad Privada del Norte, Trujillo, 13011, Peru 1. Authors need to describe how the current genome will be helpful. I found many species of the genus Passiflora in the NCBI. So, authors need clear points about the need for the existing genome. Answer: We would like to thank reviewer 2 for the insightful response. We have considered your comment because the poro-poro plastid genome constitutes a valuable resource for studying the molecular evolution, phylogenetics, and domestication of species with beneficial characteristics for human health. 2. In addition, all the genomes have similar features so the current genome is helpful for the study of evolution and phylogenetics. Answer: We are grateful to reviewer 2 for the constructive and valuable comments. Thank you. 3. The authors mentioned the number of reported genomes up to 800. This statement is not correct and is based on earlier observations. Now the number has increased significantly. Answer. We agree with the reviewer. The manuscript has been corrected: \" Plastome sequences from over 4000 species…”. 4. I found authors are not entirely aware of the utilization of some software. For example, authors mention fastqc for trimming while fastqc checks the quality of reads. Answer. It has been revised, thank you. 5. The authors used many programs for annotations. I will suggest authors use GeSeq along with Chole, Aragorn and tRNAScan on GeSeq servers for annotation of transfer RNA. Answer. It has been revised, thank you. 6. The authors need to give some information on how the current genome is similar to or differs from other reported genomes of Passiflora Answer. Thank you for your comment. We have added the figure 2 titled “Comparison of IR/SC boundary regions of four Passiflora species”."
}
]
}
] | 1
|
https://f1000research.com/articles/12-795
|
https://f1000research.com/articles/13-124/v1
|
19 Feb 24
|
{
"type": "Review",
"title": "A review on diabetes mellitus: complications, synthetic anti-diabetic agents and herbal treatment",
"authors": [
"Toluwani Tella",
"Carolina Pohl",
"Kovalchuk Igor",
"Toluwani Tella",
"Carolina Pohl"
],
"abstract": "Background Diabetes mellitus is a metabolic disorder with multiple symptoms and complications. The management of these conditions involve the use of synthetic anti-diabetic agents, natural products and medicinal plants. Synthetic anti-diabetic agents are associated with side effects whereas medicinal plants have minimal side effects and are less expensive. The aim of this work is to highlight various (i) complications associated with diabetes (ii) synthetic anti-diabetic agents used for treatment (iii) medicinal plants as anti-diabetic agents.\n\nMethods Electronic databases such as Web of Science, Google Scholar, Science Direct, Springer, Pub Med, Medline and Scopus were searched to identify complications linked with diabetes, synthetic anti-diabetic agents, and herbs used in the management of diabetes mellitus.\n\nResults The present article is an updated review of the published literature on types of diabetes and their complications, synthetic anti-diabetic drugs and medicinal herbs used for management of diabetes.\n\nConclusions Given the complications associated with diabetes mellitus, a search for medicinal herbs with anti-diabetic properties will be useful in the management of this disease.",
"keywords": [
"Diabetes",
"medicinal plants",
"synthetic antidiabetic agents",
"toxicology"
],
"content": "Introduction\n\nIt is estimated that 70-80% of people worldwide depend on herbal medicine to meet their health care needs.1 Globally, millions of people depend on medicinal plants for income generation.2 Sales of herbal-based medicines range between 7.5-108 billion US$ worldwide annually, the latter number representing sales of processed medicines.3 Studies revealed that in Canada, annual market sales of medicinal plants reached USD 400 million in 20014 and are growing at a pace of 15% annually.5 Diabetes mellitus (DM) and the complications associated with it constitute a major public health challenge, rates of these complications can decline with improvements in the management of this disease with synthetic anti-diabetic agents and medicinal herbs. Here, we cover various types of diabetes and their complications, synthetic drugs used for treatment of these conditions, and medicinal herbs used for treatment of diabetes.\n\n\nMethods\n\nThe present review is a comprehensive report on DM, incorporating the literature published before 2023. All the current information on DM, complications associated with it, synthetic anti-diabetic agents and medicinal herbs used in the management of the disease was collected via an electronic search using PubMed (RRID:SCR 004846), Science Direct, Springer, Web of Science (RRID:SCR 022706), MEDLINE (RRID:SCR 002185), Google Scholar (RRID:SCR 008878), and Scopus (RRID:SCR 022559) databases. Various articles about DM have been selected from peer-reviewed journals.\n\nDiabetes is a disorder characterized by increased blood glucose levels. The most common classifications include Type I and Type II DM, gestational diabetes mellitus (GDM), maturity onset diabetes of young (MODY), neonatal diabetes mellitus (NDM), Type 3c diabetes (also known as pancreatogenic DM), latent autoimmune diabetes in adults (LADA) and Brittle diabetes (also called labile diabetes). The different types of diabetes, clinical features and mutations associated with diabetes are presented in Table 1.\n\n\n\n• Chromosome 2q, neurogenic differentiation1\n\n• Chromosome 9, carboxyl ester lipase\n\n• Chromosome 7p, glucokinacse\n\n• Chromosome 12q, HNF-1 alpha\n\n• Chromosome 20q, HNF-4 alpha\n\n• Chromosome 17q, HNF-1 beta\n\n• Chromosome 13q, insulin promoter factor-1\n\nPeople with diabetes suffer from several complications that develop rapidly or overtime affecting many organs/system. These complications are discussed below.\n\nDiabetic nephropathy\n\nDiabetes causes damage to kidneys making it difficult to remove waste or extra fluid from the body. Diabetic nephropathy (DNep) is characterized by loss of glomerular filtration rate (GFR), presence of pathological quantities of urine albumin excretion, diabetic glomerular lesions in individuals with diabetes. Some factors that contribute to the development of DNep are hyperglycemia, high blood pressure and dyslipidemia.13\n\nDiabetic neuropathy\n\nHigh blood sugar levels in people with diabetes can cause nerve damage, making it difficult for nerves to carry information or messages between the brain and every part of our body. Hyperglycemia contributes to diabetic neuropathy (Dneu) by producing advanced glycation end products (AGEs).14,15 Various forms of DNeu include mononeuropathy, radiculopathy, autonomic neuropathy, cranial neuropathy, symmetric polyneuropathy.\n\nDiabetic cardiomyopathy\n\nDiabetic cardiomyopathy (DC) affects the myocardium in patients with diabetes, some structural disorders caused by DC include microvascular disease, hypertension, epicardial atherosclerosis, obesity, endothelial and autonomic dysfunction and left ventricular hypertrophy. Impairment in left ventricular systolic and diastolic function can cause heart failure in individuals with diabetes.16\n\nDiabetic retinopathy\n\nHigh blood sugar level damages the blood vessels in the retina. This disease is called diabetic retinopathy (DR), symptoms include blurriness, floaters, macular oedema, microaneurysms, cotton wool spots, hemorrhages, dark areas of vision and difficulty perceiving colors.17\n\nDiabetic encephalopathy\n\nImpairment/damage to neurochemical and structural changes leads to cognitive dysfunction causing a disorder called diabetic encephalopathy (DE) in people suffering from diabetes. There is increased risk of dementia observed in individuals with diabetes.18\n\nPeriodontal disease\n\nPeriodontitis is common among people suffering from diabetes. Clinical features of advanced periodontitis include gingival bleeding, recession, erythema and oedema. Individuals with Type II diabetes who have undergone periodontal treatment have improved blood sugar levels.19\n\nCellulitis\n\nPeople suffering from diabetes are prone to develop diabetic foot ulcerations, which can progress into infections due to neuropathy, motor, and/or autonomic disturbances.20\n\nMusculoskeletal disorders\n\nA variety of musculoskeletal conditions are prevalent among people with diabetes such as adhesive capsulitis, Dupuytren’s contracture, carpal tunnel syndrome, muscle infarction, and sclerodactyly.21\n\nInfections\n\nPeople with diabetes are susceptible to mucocutaneous fungal infections (e.g., oral and vaginal candidiasis), genitourinary infections, bacterial foot infections, gastrointestinal, respiratory infections, skin and soft tissue infections.22\n\nNon-alcoholic fatty liver disease\n\nIndividuals with type II diabetes are susceptible to non-alcoholic fatty liver disease. It can also occur in people with dyslipidemia, obesity, metabolic syndrome in the absence of DM.23\n\nMacrovascular disease\n\nStudies have shown that macrovascular complications are associated with Type II diabetes. Symptoms are peripheral arterial disease, transient ischemic attacks and strokes, angina pectoris and myocardial infarction, cardiomyopathy, arrhythmias.24\n\nErectile dysfunction\n\nErectile dysfunction (ED) is a sexual dysfunction in both men and women and is one of the long term complications of DM.25\n\nGastroparesis\n\nHigh blood glucose causes nerve damage in the body, one of the nerves that is damaged is the vagus nerve, it causes the muscles in the digestive tract and stomach not to function properly, as a result, it slows down the movement of food through the digestive system.26\n\nAlzheimer’s disease\n\nDiabetes increases the risk of developing Alzheimer’s disease. In vitro and animal studies revealed that insulin resistance can lead to the pathogenesis of Alzheimer’s disease.27\n\nDepression and anxiety\n\nDepression occurs more in individuals with diabetes, a number of risk factors have been identified as relevant for the occurrence of depression and diabetes such as lifestyle, low birth weight, obesity and adverse events in childhood.28 Studies also revealed that people with DM had an increased risk of anxiety and eating disorders.29–31\n\nSarcoidosis\n\nSarcoidosis is an inflammatory granulomatosis that has the ability to affect any organ, most often the lungs in the human body. Studies revealed that diabetes is more prevalent in patients with sarcoidosis.32\n\nCancer\n\nDiabetes has been linked to various types of cancer including bladder cancer, liver cancer, gastrointestinal cancer, kidney cancer, pancreatic cancer, colorectal cancer, endometrial cancer, breast cancer and ovarian cancer.33–36 Hyperglycemia increases the production of reactive oxygen species and downregulate antioxidant activity. Markers of inflammation, including secreted cytokines play a vital role in the link between cancer and diabetes. Hyperglycemia also contributes to systemic inflammation.37,38\n\nSleep disturbance\n\nObstructive sleep apnea (OSA) occurs frequently in patients with diabetes. Findings revealed a link between OSA and Type II diabetes, where dysregulation of the autonomic nervous system leads to abnormal breathing pattern in patients with diabetes.39–41\n\nLoss of workplace productivity\n\nDM is reported to impact on productivity outcomes, studies revealed that DM is linked with, increased time off work, decreased productivity while at work and early dropout from the work force.42,43\n\nThere are several strategies involved in the management of DM. Below are the modern approaches for diabetes management.\n\nLifestyle modification\n\nLifestyle modification plays an important role in diabetes management. Healthy diets (such as vegetables, whole grains, fruits, lean meats, non-fat dairy), exercises, increased physical activities, reduced sedentary lifestyle, total abstinence from alcohol, cigarettes, avoid or limit foods that are high in fat/sugar are some of the recommended lifestyle modifications that will help patients with diabetes.44\n\nMedical nutrition therapy (MNT)\n\nMNT is an evidence-based nutrition therapy provided by a qualified dietician and can either be prescribed in a hospital or outpatient setting and involves a comprehensive assessment, nutritional diagnosis and treatment plan. MNT has been employed for the treatment of GDM.45\n\nGene therapy\n\nGene therapy modifies human cells to treat a particular disease. It reconstructs or repair defective or damaged genetic material in the body. Gene therapy is a promising technique in the treatment of DM, gene therapy for DM focuses on Type I diabetes mellitus (TIDM). In TIDM, the absence of islets leads to insulin deficiency, which results in hyperglycemia, gene therapy employs viral and non-viral methods in the treatment of TIDM.46\n\nGene editing\n\nGene editing is slightly different from gene therapy, it reprograms the body’s DNA or cut out the bad parts of the DNA. The focus of gene editing is to create islet cells, encapsulate them and implant them into the body. Encapsulated cells are safe from an immune response (beta cell attack) that people with TIDM experience. In a study, induced pluripotent stem cells produced from the skin of a patient with Wolfram syndrome were transformed into insulin producing cells, CRISPR-Cas9 (a gene-editing tool) was used to correct the genetic defect that caused the syndrome. The insulin producing cells were implanted into lab mice and cured diabetes in those mice.47\n\nNanotechnology\n\nNanoparticles (<100 nm) are manufactured through the manipulation of individual atoms or molecules in a substance. Current issues for nanomedicine involve toxicity and environmental impact of nanoscale materials. The benefit of nanotechnology in diabetes includes non-invasive insulin delivery, beta cell mass, detection of immune cell activity, inventive diabetes diagnosis, and monitoring of glucose level.48\n\nSynthetic anti-diabetic agents\n\nManagement of DM involves the use of insulin and synthetic anti-diabetic agents such as biguanides and sulfonylureas. The functions of synthetic anti-diabetic agents used in the management of DM are shown in Table 2.\n\nMedicinal plants with anti-diabetic properties\n\nSeveral studies reported various side effects associated with the use of synthetic anti-diabetic drugs such as hypoglycemia, weight gain, vomiting, diarrhea, nausea, headache. Medicinal plants with anti-diabetic properties will be beneficial in the management of diabetes. The medicinal plants below have been reported to improve insulin sensitivity and act through various metabolic and cellular targets. Some active compounds present in the medicinal plants include: thyrotundin, tagitinin A, luteolin, multiflorine, sparteine, specioside, lapachol, verminoside, naringenin, monoterpene, sobrerol, nimbidiol, erythribyssin N, lophenol, cycloartanol, annonacin, reticuline, aculeatin borapetoside, quercetin, quercetin 3-O glycoside, methylswertianin, bellidifolin, aloin, aloe-emodin, amorfrutins, 5-bromo-8-(5-nitrosalicylideneamino) quinoline hydrochloride, protocatechuic acid, guavanoic acid, mangiferin, decursin, oleanolic acid, 2α-Hydroxyursolic acid, chlorogenic acid, procyanidin oligomers and ratanhiaphenol.62–64 Table 3 shows the list of medicinal plants with reported anti-diabetic properties. Some work has already been performed on a limited number of these plants and it has been found that Abelmoschus moschatus improves insulin signaling transductions by modification of Serine/Threonine phosphorylation.65 Insulin signaling is also improved by Artemisia herba-alba, which reduces insulin resistance, and by Astragalus membranaceus, which reduces the activity and expression of protein tyrosine phosphatase 1B (which dephosphorylates insulin receptor signaling proteins) in skeletal muscles.66,67 Erythrina abyssinica has also been reported to inhibit PTP1B activity.68 Cornus kousa also stimulates insulin signaling and glucose uptake through peroxisome proliferator-activated receptor gamma (PPARγ) activation as well as 5’ adenosine monophosphate-activated protein kinase (AMPK) activities.69 Another plant that promotes glucose transport is Justicia adhatoda, which activates glucose transporter type 4 (GLUT-4) transporter and increases phosphatidylinositol 3-kinase (PI3-K) and Insulin receptor substrate 1 (IRS-1) levels.70 Rehmannia glutinosa enhances the gene expression of resistin and also improves glucose consumption.71 Vigna unguiculata promoted Akt phosphorylation in rat skeletal muscles.72 In addition, Psidium guajava decreased the activity of hormone sensitive lipase (HSL) in adipose tissue and liver of diabetic rats.73\n\nSeveral plants influence glucose production in the liver, including Artemisia sphaerocephala, which increases liver glycogen and glucokinase and reduces accumulation of fat in the liver; Malva parviflora, which restores glucose-6-phosphatase, glucokinase and hexokinase activities in liver. Bumelia sartorum inhibits glycogenolysis in the liver and increases glucose uptake in skeletal muscle, while Nigella sativa reduces the activities of enzymes involved in the neoglucogenesis pathway in the liver and Stevia rebaudiana reduces the expression of phosphoenolpyruvate kinase enzyme thereby inhibiting the production of glucose by the liver.74\n\nSelected tyrosine sites on receptor substrates are phosphorylated, thereby activating pathways leading to increased protein synthesis, glycogen synthesis, glucose uptake and lipogenesis. Phellodendri cortex reduces tyrosine dephosphorylation and enhances tyrosine phosphorylation, which will aid in the management of diabetes. Intracellular calcium (Ca2+) is the primary signal that stimulates insulin exocytosis by glucose, other cell signals activated by glucose that are involved in this process, are cyclic adenosine monophosphate (cAMP) and inositol 1,4,5-trisphosphate (IP3), cAMP may be the most important one for increasing insulin secretion. Studies revealed that Ziziphus spina-christi increases serum pyruvate level and pancreatic c-AMP levels while Vaccinium angustifolium reduces the plasma concentrations of C-reactive protein, interleukin-6 and tumor necrosis factor-α.75–77\n\nThe degree of medicinal plant toxicity depends on several factors such as method of extraction, species, dosage, route of administration and victim susceptibility. Human organs and systems are affected by some toxic compounds from plants. The toxicity properties of plants in this review have been reported. Findings revealed that the seed of Erythrina abyssinica are traditionally known to be poisonous, at high doses, it may cause paralysis, anesthesia and even death by respiratory failure.92 The fruit and leaf extracts of Annona muricata (106 mg/kg body weight) given to rats intravenously for 28 days showed acute neurotoxicity in rats.93 Phytochemicals such as annonacin and anthraquinones in Annona muricata and Aloe vera, respectively, have also been reported for their toxicity.94,95\n\n\nConclusions\n\nAs presented in this review, a search for medicinal plants and natural products with anti-diabetic properties will be useful in the management of this disease. Given the complications associated with DM, steps must be taken to increase the awareness of emerging complications, synthetic anti-diabetic agents and medicinal plants used in the management of this disease. Further studies are required to determine the mechanism of action, identify and isolate bioactive compounds in some of these medicinal plants. In addition, studies are needed to guarantee the safety/toxicity of the long term consumption of these medicinal plants in people with diabetes.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nFarnsworth NR, Soejarto DD: Global importance of medicinal plants. The Conservation of Medicinal Plants. Akerele O, Heywood V, Synge H, editors. Cambridge: Cambridge University Press; 1991; 25–51. Publisher Full Text\n\nWHO (World Health Organization): WHO traditional medicine strategy 2002-2005. Geneva: World Health Organization; 2002.\n\nScherr SJ, White A, Kaimowitz D: A new agenda for forest conservation and poverty reduction: making markets work for low- income producers. Washington: Forest Trends, CIFOR; 2004.\n\nWHO (World Health Organization): National policy on traditional medicine and regulation of herbal medicines. Report of WHO global survey. Geneva: World Health Organization; 2005.\n\nUprety et al.: Traditional use of medicinal plants in the boreal forest of Canada: review and perspectives. J. Ethnobiol. Ethnomed. 2012; 8: 7. 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PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "289684",
"date": "22 Aug 2024",
"name": "Pranav Kumar Prabhakar",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe title accurately reflects the content of the manuscript. However, consider specifying the scope of the review, such as including \"A Comprehensive Review\" to emphasize the depth of coverage. The content specially the management section need to elaborate in detail. The mechanism of action of the plants will increase the strength of the paper. Currently the paper looks like preliminary data. It need to be reworked in detail. The merits and demerits of using herbal druhs, their dosing and toxicity studies need to documented properly.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-124
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https://f1000research.com/articles/11-1094/v1
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23 Sep 22
|
{
"type": "Software Tool Article",
"title": "Plotly.NET: A fully featured charting library for .NET programming languages",
"authors": [
"Kevin Schneider",
"Benedikt Venn",
"Timo Mühlhaus",
"Kevin Schneider",
"Benedikt Venn"
],
"abstract": "Data visualization is integral for exploratory data analysis and data presentation. Consequently, every programming environment suitable for data analysis needs a feature-rich visualization library. In this paper, we present Plotly.NET - a fully featured charting library for the .NET ecosystem. Plotly.NET requires little ceremony to use, provides multiple API (application programming interface) layers for both low-code and maximum customizability, and can be used in many different visualization workflows - from interactive scripting and notebooks to user interface applications. Plotly.NET brings the charting capabilities of plotly.js to the .NET ecosystem, successfully combining the flexibility of the plotly grammar with the type-safety and expressiveness of .NET.",
"keywords": [
".NET",
"F#",
"C#",
"data visualization"
],
"content": "Introduction\n\nProper visualization of scientific results or data in general is an essential element for teaching, the discussion of analysis results, or the distribution of new insights within the research community. Well structured figures help to improve visibility, explorability, and interpretability of the underlying data, consequently saving tedious searching in order to be able to interpret the presented data. Algorithmic diversity is paramount in exploratory data analysis, but ultimately the goal will always be to produce meaningful figures that represent the obtained information in an optimal way. Even during exploration, figures help to guide the researcher to hidden properties that become apparent when inspected in the form of a figure, especially when the figure is interactive. Therefore, the ability for convenient and streamlined plotting strategies/possibilities is not only important for distributing results, but also helps to get new insights during data analysis, and is an invaluable tool in the data science stacks of any programming language.\n\nplotly.js1 is a popular open source graphing JavaScript library. It provides a well defined grammar for creating visualizations via the figure data structure - a tree with named nodes called attributes. The figure data structure can be represented via JavaScript Object Notation (JSON) - a widespread standard for representation of structured data which can be parsed and created by any modern programming language (see Figure 1 for an example). Due to this interoperability, libraries for creating plotly.js figures are available in many programming languages, most notably in Python2 and R3 which see widespread adoption in the scientific programming landscape.\n\nLeft: The JSON (JavaScript Object Notation) formatted figure object. Lines 2-9 are the data array, which contains trace objects representing individual data visualizations of the figure. Lines 10-13 are the layout object, which contains data-independent styling options such as the axis objects. Right: The respective rendered graph.\n\nIn this paper we present Plotly.NET - a library for creating plotly.js-conform JSON formatted figures for the set of statically typed .NET languages (F#,4,5 C#,6 VB.NET7). Plotly.NET is written in F# and leverages the static type system by providing type-safe domain specific languages (DSLs) for plotly.js attributes and objects, as well as several abstraction layers for ease-of-use. Plotly.NET is feature complete regarding plotly.js API (application programming interface) coverage and is compatible with the .NET kernel for Jupyter, therefore offering a complete suite of data visualization tools for exploratory data analysis unprecedented in the .NET environment.\n\n\nMethods\n\nPlotly.NET is implemented in the open source F# programming language. It creates objects which are serialized into JSON (using the Newtonsoft.Json package8) which can be used by a rendering engine to create the visual equivalent. This is either realized by embedding the generated JSON in a HTML scaffold where plotly.js is used for rendering the plot in a browser (or equivalent environment where JavaScript can be executed), or via an interface for custom rendering engines.\n\nThe API is designed to enable different styles of creating charts and contains several abstraction layers. All (as of v2.6.3) plotly.js trace types have type safe equivalents with additional convenience layers to create derivative charts from these base traces.\n\nPlotly.NET provides multiple API layers with increasing abstraction levels: (1) DynamicObject, (2) plotly.js object mappings, and (3) the high-level Chart API.\n\n(1) DynamicObject: The low-level API builds on top of the DynamicObj package9 which provides a way of setting dynamic members in the statically typed .NET environment. Instances of this class, as well as instances of classes inheriting from it, provide the ?-operator which enables member assignment on runtime. This is usually prevented by the static type system of .NET languages, but necessary to support the highly dynamically typed nature of the JSON objects expected by plotly.js. Static classes are not flexible enough for this, especially because almost all attributes are optional and can be of multiple types.\n\nThis API layer is closest to plotly.js and can be used to directly translate javascript examples, as attribute names must be mirrored exactly. This also means that extensive knowledge of plotly.js, or at least it’s JSON schema is necessary to effectively use it, but makes it easy to implement new features should the underlying plotly.js version be updated. Figure 2 shows an example on how to use this API layer to generate the same plot shown in Figure 1.\n\nLeft: F# code creating the figure data structure. Lines 1-3 are referencing the library, lines 5-8 create the trace object (see equivalent lines 2-9 in Figure 1). Lines 10-23 create the layout object containing the axis objects (see equivalent lines 10-13 in Figure 1). Lines 25-27 create the figure object and render it in a browser. Right: The respective rendered graph.\n\n(2) plotly.js object mappings: plotly.js attributes that are themselves objects are abstracted as classes built on top of (1) and provide static init and style methods, as well as object-specific methods. These methods have a plethora of optional typed arguments which are equivalent to all attributes supported in the respective plotly.js JSON. Additionally, type-safe DSLs for attributes/values used on multiple occasions such as style parameters, color, or enums are provided in the StyleParam namespace. This layer comes with the additional advantage of providing options for auto-completing argument names as well as documentation for them, leading to less plotly.js knowledge being required for its usage. Figure 3 shows an example on how to use this API layer to generate the same plot shown in Figure 1.\n\nLeft: F# code creating the figure data structure. Lines 1-3 are referencing the library. Lines 5-9 create the trace object (see equivalent lines 2-9 in Figure 1). Lines 11-18 create the layout object containing the axis objects (see equivalent lines 10-13 in Figure 1). Lines 20-23 create the figure object with default styling (Line 21) and render it in a browser. Right: The respective rendered graph.\n\nNote that this API layer provides type-safe abstractions, but still needs insights about how plotly.js structures figures: While allowed attribute names and types are abstracted, the user still needs to know that for example axis styles are to be set on a Layout object (see Figure 3 left, lines 11-18). It is also possible to use style presets (see Figure 3 left, line 21) with this API layer.\n\n(3) The high-level Chart API provides type safe abstractions for chart creation and styling without knowledge of the structure of plotly.js JSON. Type-safe methods for creating figure structures for all trace types and derived charts as well as various styling methods are provided.\n\nThe plotly.js figure schema is completely abstracted away. The API surface is only concerned with’creating and styling a chart’. Consider the following example: In plotly.js JSON, the axis style has to be set on the layout object. It also must be specified which type of axis (x, y, z, etc.) it is. Styling the x axis usually requires knowledge of this. The Chart API however provides a Chart.withXAxisStyle function, which also provides arguments for the relevant attributes, and can be applied to any Chart object.\n\nUsing this API layer also significantly decreases the lines of code necessary to create figures, as proper creation of nested objects and argument naming is implicitly done by the Chart methods. See Figure 4 for an example on how to use this API layer to generate the same plot shown in Figure 1. Note that there is a single flow of the initial Chart object, without the need of creating additional objects for axis styling.\n\nLeft: F# code creating the figure data structure. Lines 1 and 2 are referencing the library. In this API layer, there are no clear equivalents to Figure 1: in Lines 4-7, the Chart. Line method creates a figure structure with default styling and the input data. Subsequently, the x and y axes are styled using respective styling methods without the need of creating title objects in contrast to the other API layers. Right: The respective rendered graph.\n\nPlotly.NET however does not enforce the usage of any API layer. The low-level, abstraction-less layer (1) is exposed on purpose as this gradual abstraction via API layers enables users with any kind of knowledge about plotly.js to use it. Additionally, this allows for both imperative and declarative creation of figures. The dynamic assignment of members however might seem not intuitive to .NET users unexposed to dynamically typed languages. The high-level Chart API (3) on the other hand provides type-safe abstractions with the trade-off of reduced customizability. Extending this layer needs a lot of domain knowledge in both plotly.js and the Plotly.NET equivalent DSL. We believe that users are offered the best of both worlds by providing low-code abstractions for common use-cases, while retaining the ability to take full control where needed.\n\nIn addition to the core API, three extension packages - Plotly.NET.ImageExport, Plotly.NET.Interactive, and Plotly.NET.CSharp - are provided. Plotly.NET.ImageExport and Plotly.NET.Interactive cover two specific use cases - static image export and usage with the .NET Jupyter Kernel .NET Interactive - while the aim of Plotly.NET.CSharp is providing a native, idiomatic API surface for consuming the core API for the object-oriented C# language (note that the core API can be consumed in any.NET programming language, this package just provides a more idiomatic API).\n\nPlotly.NET.ImageExport provides an interface for rendering engines that can produce PNG, JPG, or SVG files from plotly.js JSON figures. A reference implementation is provided that uses PuppeteerSharp10 to create a headless Chromium browser to render the figure and save it to the disk in the desired format.\n\nPlotly.NET.Interactive is a formatting extension for .NET interactive, the Jupyter kernel for .NET languages. It enables automatic rendering of figures created with Plotly.NET in the notebook output cells without the need to leave the analysis environment by switching to the browser. Having the charts tied to the code producing them is especially helpful in the context of sharing and comprehension of visualizations. Examples of such notebooks are included in the Plotly.NET repository (see the Data availability section).\n\nPlotly.NET targets the netstandard2.0 framework and is therefore supported on a plethora of compatible target frameworks across the .NET ecosystem. At the time of writing this article, this means that Plotly.NET can be used on any modern desktop operating system, as well as multiple mobile operating systems. It can be either referenced as nuget package or be built from source.\n\nPlotly.NET is available as pre-compiled binary package on nuget.org (see here), which is the central package registry in the .NET ecosystem. It can be incorporated into any .NET project, script or notebook via the respective package reference. A target framework compatibility matrix is available on the nuget package page.\n\nThe source code as well as detailed instructions on how to build it are available on GitHub (see Software availability13). An installation of the .NET SDK of version ≥ 6.0.1 (freely available to readers and reviewers here) is mandatory.\n\n\nUse cases\n\nPlotly.NET aims to be a general-purpose visualization library for the .NET ecosystem. It targets interactive workflows such as visualization in scripting or in notebook environments, as well as visualizations in any kind of application, be it for desktop, mobile, or the web. Therefore, we demonstrate some of the visualization capabilities in the following section instead of specifying use cases.\n\nFigure 5 shows a few more complex charts that can be generated with Plotly.NET:\n\n• Figure 5A shows various variations of box and violin plots for the purpose of visualizing shapes and properties of distributions.\n\n• Figure 5B is a combination of a temperature time course as line chart and a superimposed heatmap indicating correlation coefficients derived by continuous wavelet transform using FSharp.Stats (see Ref. 11 and Underlying data). High values (reddish) indicate high correlation to the frequency given as row indicators on the right. High negative values (bluish) indicate high anti-correlation.\n\n• Figure 5C shows a scatter plot matrix of the classic iris data set (see Ref. 12 and Underlying data) providing an overview of how the respective features in it correlate with each other.\n\n• Figure 5D shows a surface chart of the three dimensional wave function fxy=sinx2+y2.\n\n(A) Box and violin plots to describe properties and shapes of distributions. (B) Combined chart of temperature measurements and their frequency representation as heatmap. (C) Splom chart of the iris data set. (D) Surface chart of a three dimensional wave function.\n\nThe respective code is provided as interactive notebooks in the repository on GitHub (see Software availability13).\n\n\nData availability\n\nThe data underlying Figure 5 are contained in the’publication’ folder in the Plotly.NET GitHub and Zenodo repositories (see Software availability below) as follows:\n\n• iris-data.csv (contains species label, sepal length/width, and petal length/width of observed iris flowers. This data was originally obtained from Ref. 12).\n\n• waveletData.txt (contains water temperature measurements conducted by the authors. Additional correlation coefficients were derived by continuous wavelet transform using Marr wavelets with frequencies specified in the row annotations. This data was made available previously in Ref. 11).\n\n\nSoftware availability\n\n\n\n• Software available from: https://nuget.org/packages/Plotly.NET\n\n• Source code and notebooks generating the example figures are available from: https://github.com/plotly/Plotly.NET\n\n• Archived source code at time of publication: https://doi.org/10.5281/zenodo.682258213\n\n• License: MIT",
"appendix": "Acknowledgements\n\nThe authors would like to thank all independent open source contributors on the GitHub repository, no matter how small the contributions. Special thanks to @WhiteBlackGoose for the extensive conceptual discussions about all things .NET.\n\n\nReferences\n\nPlotly Technologies Inc: Collaborative data science.2015.Reference Source\n\nPlotly Technologies Inc: plotly.py - the interactive graphing library for python (includes plotly express).2022.Reference Source\n\nSievert C: Interactive Web-Based Data Visualization with R, plotly, and shiny.Chapman and Hall/CRC;2020. ISBN 9781138331457.Reference Source\n\nSyme D:Leveraging .net meta-programming components from f#: Integrated queries and interoperable heterogeneous execution. Proceedings of the 2006 Workshop on ML, ML’06. New York, NY, USA:Association for Computing Machinery;2006; page 43–54. ISBN 1595934839.Leveraging.netPublisher Full Text\n\nSyme D, Battocchi K, Takeda K, et al.:Themes in information-rich functional programming for internet-scale data sources. Proceedings of the 2013 Workshop on Data Driven Functional Programming, DDFP’13. New York, NY, USA: Association for Computing Machinery;2013; page 1–4. ISBN 9781450318716. Publisher Full Text\n\nHejlsberg A, Torgersen M, Wiltamuth S, et al.: The C# programming language.Pearson Education;2008.\n\nGrundgeiger D: Programming Visual Basic. NET.O’Reilly;2018.\n\nNewton-King J: Jamesnk/newtonsoft.json.2022.Reference Source\n\nSchneider K: @WhiteBlackGoose, and Timo Mühlhaus. Csbiology/dynamicobj.2022.Reference Source\n\nKondratiuk D: hardkoded/puppeteer-sharp.2022.Reference Source\n\nVenn B, Weil L, Schneider K, et al.: fslaborg/fsharp.stats.May 2022. PubMed Abstract\n\nFisher RA: The use of multiple measurements in taxonomic problems. Ann. Eugenics. 1936; 7(2): 179–188. Publisher Full Text\n\nSchneider K, Mühlhaus T, Goose WB, et al.: plotly/Plotly.NET: 3.0.0-manuscript (3.0.0-manuscript). Zenodo. [Software].2022. Publisher Full Text"
}
|
[
{
"id": "171764",
"date": "02 Jun 2023",
"name": "Mathieu Jacomy",
"expertise": [
"Reviewer Expertise Network visualization",
"network analysis",
"science and technology studies",
"controversy mapping",
"information design"
],
"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 high-level description of Plotly.NET, a tool that brings the charting library \"plotly.js\" into the .NET ecosystem. The article provides elements of justification for the design of the tool, in particular its central choice to offer three distinct API layers, each with their own writing style, and addressed to different publics.\nThe article offers an overview of the tool to researchers who use it or consider to. It documents where the tool comes from, what is its intended purpose, and how it has been architectured. The article is compact and not too detailed, as it should be; it does not try to replace the documentation. The user interested in a more in-depth description of the capabilities of Plotly.NET can browse the online reference instead.\nI see this article as a proxy paper for Plotly.NET, and I see no issue with that. It provides sufficient context to the tool to motivate a short Software Tool paper. This will help the developers of the tool get recognition in the academic sphere, which I wholeheartedly support, as their work is worth it.\nPS: I noted a small typo in the v1: \"or at least it’s JSON schema\" should be \"or at least its JSON schema\".\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": "10809",
"date": "19 Feb 2024",
"name": "Timo Mühlhaus",
"role": "Author Response",
"response": "Thank you very much for taking the time to review our manuscript. We sincerely appreciate your valuable comments. Following the correction of a typo, we have uploaded a new version. Once again, thank you very much."
}
]
},
{
"id": "183698",
"date": "16 Nov 2023",
"name": "Andrea Vázquez-Ingelmo",
"expertise": [
"Reviewer Expertise Data visualization"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 fully featured charting library for the .NET ecosystem, namely Plotly.NET, which brings the charting capabilities of plotly.js to the .NET ecosystem.\nThe paper is well-written and well-structured. However, I think that the paper would benefit with deeper explanations of the charting library, as well as identified limitations and (more) detailed use cases.\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? Yes\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? No\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? No",
"responses": [
{
"c_id": "10810",
"date": "19 Feb 2024",
"name": "Timo Mühlhaus",
"role": "Author Response",
"response": "Thank you for reviewing our manuscript and providing valuable feedback. Plotly.NET is a versatile visualization library for the .NET ecosystem, catering to interactive workflows in scripting, notebooks, and various applications (desktop, mobile, or web). The manuscript aims to highlight a subset of its visualization capabilities, prompting readers to refer to the documentation for comprehensive tutorials and samples. In response to your suggestion, we have included the link to our extensive documentation and code samples at https://plotly.net. We appreciate your input. Thank you very much."
}
]
}
] | 1
|
https://f1000research.com/articles/11-1094
|
https://f1000research.com/articles/13-123/v1
|
19 Feb 24
|
{
"type": "Method Article",
"title": "Design and test of novel scent enrichments to enhance breeding of zoo-housed lemurs",
"authors": [
"Emily Elwell",
"Sara Fontani",
"Stefano Vaglio",
"Emily Elwell",
"Sara Fontani"
],
"abstract": "Background Zoos use environmental enrichments, including scents, which may have applications to improve breeding success for taxa, such as lemurs, which rely heavily on olfactory communication. We aimed to develop novel, biologically-relevant scent enrichments to trigger mating behaviours of zoo-housed lemur species, which are critically endangered in the wild and show a low success rate in captive breeding programmes.\n\nMethods We examined anogenital odour secretions, released by female gentle (Hapalemur alaotrensis) and ruffed (Varecia variegata) lemurs, using solid-phase microextraction and gas chromatography-mass spectrometry techniques. We identified the key compounds distinguishing the volatile chemical profile of female lemurs during the breeding season and used them to develop species-specific scent enrichments. We then tested the scent enrichments, made up of synthesized mixtures conveying information about female lemur fertility, on unsuccessful breeding pairs of lemurs hosted in European zoos. We evaluated the effects of the newly designed scent enrichments on their target species by combining behavioural observations with faecal endocrinology.\n\nResults We identified and reproduced fertility-specific signals associated with female scents. These scent mixtures triggered male sexual behaviours, including mating, during and after the enrichment condition. We also found effects on faecal testosterone levels, with increased levels after the enrichment condition albeit not statistically significant.\n\nConclusions Our findings suggest that biologically-relevant scent enrichments may trigger natural species-specific behaviours, with potential implications for conservation breeding of zoo-based endangered lemur species, and highlight that combining more assessment methods may assist with evaluating the impact of environmental enrichments.",
"keywords": [
"scent enrichment",
"behavioural observations",
"sexual behaviours",
"mating",
"faecal endocrinology",
"semiochemistry",
"gentle lemurs",
"ruffed lemurs"
],
"content": "Introduction\n\nZoo populations are typically managed to provide the public with education about wildlife and their environmental challenges, and to uplift endangered species through both ex-situ conservation breeding and in-situ reintroduction programmes (Schulte-Hostedde & Mastromonaco, 2015). In this context, the maintenance of the genetic variation of such captive populations is imperative (Lacy, 2009). However, captive populations, potentially serving as buffers against extinction, may experience problems that impair them from being viable for reintroduction into the wild. Specifically, zoo populations may face reproductive issues which inhibit them from serving as viable ‘reserve populations’ (Meier, 2016). Furthermore, managing zoo populations is challenging because of the mismatch between natural and captive environments (Carroll et al., 2014). Primates evolved distinct behavioural patterns, and difficulty in engaging in these behaviours can cause frustration or boredom, which, in turn, can lead to stress and development of abnormal behaviours (for around 50% of zoo animals) (Hosey, 2005) that undermine their individual welfare and their breeding success.\n\nTo maintain captive healthy populations, with good genetic variability and thus high survival rate in case of reintroduction, modern zoos take part in conservation breeding programmes (e.g., European Association of Zoos and Aquaria (EAZA)’s Ex situ programmes – EEP). Moreover, as reproductive success is linked to the degree of similarity between captive environmental conditions and those that animals would experience in the wild (Meier, 2016), zoos use environmental enrichments to improve the well-being of captive populations. Environmental enrichments and conservation breeding are closely related, as enrichment is a dynamic process that modifies an animal’s environment, prompting a wider range of species-specific behaviours (Ben-Ari, 2001) promoting resiliency to stress, which in turn helps animals recovering from adverse stimuli (Quirke & O’Riordan, 2011), as well as improving the exhibit from the perspective of visitors (Carlstead & Shepherdson, 1994). Furthermore, enrichment can foster the essential abilities that animals would need for their survival if reintroduced into their natural habitat (Rioldi, 2013). Additionally, conservation breeding programmes, through breeding management recommendations, maximize the genetic diversity and reduce the loss of genetic variation associated with genetic drift, which can be rapid in small captive populations (Ballou et al., 2010).\n\nWith almost 60% of primate species currently facing an extremely or very high risk of extinction in the wild, raising global awareness of the difficulty of the world’s primates is vital (Estrada et al., 2017). Among primates, lemurs are the most endangered taxa; around a third of the 107 species currently living in Madagascar are classified as critically endangered, while almost all of them are at risk of extinction (IUCN, 2023). Lemurs are endemic to Madagascar, which is a recognized biodiversity hotspot and arguably the top priority for primate conservation (Mittermeier, 2014). Moreover, several captive lemur populations are also struggling, in terms of both abundance and demographic trend, almost as much as their wild counterparts, and currently would not support reintroduction into the wild (Meier, 2016). However, captivity, unlike the wild, is a human-controlled environment and thus it is possible to enhance captive breeding via environmental enrichment and evidence-based facilitation of breeding (Meier, 2016).\n\nThe overarching aim of this research work was to develop new scent enrichments to enhance breeding success of zoo-housed lemurs. To achieve this, we investigated the chemical profile of the anogenital odour secretions of successful breeding females, then reproduced the chemical mixture in our semiochemistry laboratory (focusing on volatile compounds) and tested it with unsuccessful breeding pairs (i.e., biologically able to reproduce but never been successful as a breeding pair). Then, to assess the effects of the scent enrichment, we combined behavioural observations (focusing on sexual behaviours) with faecal endocrinology (focusing on sex hormones).\n\nSpecifically, we aimed to:\n\n• Identify the key compounds that convey information about female lemur fertility.\n\n• Design novel scent enrichments made up by species-specific chemical mixtures signalling female fertility.\n\n• Evaluate whether the newly designed scent enrichments trigger sexual behaviours.\n\n\nMethods\n\nThis study adheres to the ARRIVE guidelines (Vaglio, 2024).\n\nThe use cases/studies followed the institutional and international guidelines for the care and use of captive animals, involving non-invasive methods for obtaining behavioural data, faecal and odour samples from the lemurs. Moreover, the studies were conducted in compliance with the Convention on Biological Diversity and the Convention on the Trade in Endangered Species of Wild Fauna and Flora and approved by the Life Sciences Ethics Committee (LSEC) at the University of Wolverhampton (UK) (REC numbers LSEC/201819/CY/166 and LSEC/202021/SV/52) and the Ethics Committees at Jersey Zoo (Channel Islands), Parc Zoologique & Botanique de Mulhouse (France), Birmingham Wildlife Conservation Park, Dudley Zoo & Castle, Shaldon Zoo – Wildlife Trust, Twycross Zoo, and ZSL London Zoo (UK). The authors made all possible efforts to ameliorate harm to animals, which was achieved by using non-invasive methods to collect samples (including behavioural data and biological samples such as anogenital odour secretions and faeces) from the study subjects.\n\nWe studied four pairs of gentle lemurs (Hapalemur alaotrensis) (N = 8), hosted at Birmingham Wildlife Conservation Park (UK), Parc Zoologique & Botanique de Mulhouse (France), Jersey Zoo (Channel Islands) and ZSL London Zoo (UK) (Fontani et al., 2022), and four small groups of red ruffed and black-and-white ruffed lemurs (Varecia spp.) (N=15) at Dudley Zoo & Castle, Shaldon Zoo – Wildlife Trust, and Twycross Zoo (UK) (Elwell et al., unpublished data). All study troops were housed in indoor enclosures (heated to 25-28°C) and had access to outdoor enclosures.\n\nWe divided the study period into three phases: pre- enrichment (i.e., before enrichment condition – two weeks), enrichment (i.e., during enrichment condition – one week), post- enrichment (i.e., after enrichment condition – two weeks). We carried out behavioural observations and faecal sampling every study day from early morning to early afternoon, as they are more active in the morning (~8AM-1PM, 5 hours per day), over five days per week. We assessed the effects of the enrichment combining the observation of sexual behaviours (including mating) and faecal endocrinology (e.g., faecal testosterone levels in males).\n\nWe collected anogenital odour samples by rubbing 10 times a sterile cotton swab around the wall of the vulva, using steady pressure, as described by Vaglio et al. (2021a). Moreover, we exposed control swabs to the air to identify any compounds that did not derive from the lemurs. We placed all samples and controls into sterile vials and immediately stored them in a −20°C freezer at the zoo. We then transferred the vials to the Rosalind Franklin Science Centre, University of Wolverhampton, using a freezer box with ice packs to avoid any risk of defrosting, for laboratory analyses.\n\nWe investigated the volatile component of odour signals using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) techniques, as described by Walker & Vaglio (2021). Briefly, we introduced a 65 μm polydimethylsiloxane/divinylbenzene SPME syringe needle through the vial septum and exposed the fibre to the headspace above the sample in the vial for 15 min at 40 °C. We analysed the adsorbed volatile analytes of all samples using a 5975C mass spectrometer (Agilent Technologies) EI, 70 eV, coupled directly to a 7890B gas chromatograph (Agilent Technologies) equipped with a fused silica HP5-MS UI capillary column (Agilent Technologies) 30 m × 0.25 mm crossbonded 5%-phenyl-95% dimethylpolysiloxane, film thickness 0.25 μm. We maintained the injector and transfer line temperatures at 270 °C and 280 °C, respectively. We made injections in splitless mode (purge valve opened after 1 min) with a constant flow of helium carrier gas of 1 ml/min. We started the oven temperature programme at 45 °C for 2 min, then raised it by 4 °C /min to 170 °C, and finally by 20 °C/min to 300 °C 40.\n\nWe assessed possible environmental contamination via blank analyses using an empty 10 ml vial (Supelco) and control swabs following the same procedure as for the samples and conditioned the fibre at 260 °C pre-injection for 5 min and 260 °C post-injection for 20 min to avoid any possible carry-over effects. We analysed all samples in a short period of time to minimize inter-assay variability. We overlaid chemical profiles from control swabs on lemur chemical profiles to identify compounds that did not derive from the lemurs and removed these from the swab results.\n\nWe tentatively identified eluted compounds by comparing the experimental spectra with those of the mass-spectral library in ChemStation (Agilent Technologies) and NIST Database (National Institute of Standards and Technology), version MSD F.01.01.2317 (Agilent Technologies). We accepted a putative identification if the minimum matching factor was higher than 90%. After that, we carried out the unequivocal identification of the key compounds distinguishing the fertile window of the breeding female comparing these compounds with standard compounds injected and analysed by applying the same SPME and GC-MS protocol (Elwell et al., unpublished data).\n\nBriefly, we diluted each chemical compound separately, placing 1.5 mL of HPLC grade methanol (Fisher Chemical, Cat. number 10499560) in 15 mL test tube, adding 5 μL of compound and 3.5 mL of de-ionised water, and then we vortexed for 15 seconds to dissolve the compound in the mixture. We compared both the retention times of key compounds and standards and the overall patterns of the mass spectra. We accepted the identification only if both the parameters were satisfied. Once the identification was certain, we added 1 mL of each diluted compound into a new test tube and vortexed for 30 second to produce the scent mixtures to test as olfactory enrichment.\n\nWe then presented the enrichment to the study subjects applying the protocol described in Vaglio et al. (2021b). Briefly, we used white cotton sheets cut into 75 cm long and 5 cm wide strips, which were soaked with 20 drops of scent mixture diluted with 12 ml of cold boiled water. Newly soaked cotton strips were prepared each enrichment day. We placed 2 unscented (controls) and 6 scented strips on the climbing frames both indoor and outdoor (Figure 1) and removed them at the end of observations every study day. To avoid habituation, we randomized the locations of both scented and unscented cotton strips daily.\n\nPhoto by Georgia Callagan with permission.\n\nWe collected behavioural data using all occurrences of some behaviours, instantaneous scan, and ad libitum sampling methods (Altmann, 1974) and focused on sexual behaviours (Table 1). For each study subject, we determined the relative frequency of each behavioural category, calculating the number of behaviours performed out of the total hours of observation.\n\nWe performed the inter-observer reliability test to measure the degree of agreement in the behaviour identification by the different observers at the zoo facilities (Wark et al., 2021). Specifically, we used Cohen’s Kappa coefficient to measure the agreement between the observers.\n\nWe collected faecal samples every morning during study days (i.e., when behavioural observations were conducted), right after defecation was observed, when the identity of the study subject was certain. As diurnal secretion patters of hormones, such as testosterone, may be detected in faecal samples (especially for small-bodied species), we restricted the sampling period to approximately the same time of the day (Hodges & Heistermann, 2011). We stored the samples in a −20 °C freezer on site immediately after sampling. At the end of the study period, we transferred the samples to the Rosalind Franklin Science Centre – University of Wolverhampton using a cold bag with ice packs to avoid any risk of defrosting.\n\nHormone analyses\n\nWe used a freeze-drying machine (Beta 1–8 LSC plus, Christ R) to lyophilize the faecal samples for 72 h, and then we pulverized them using a pestle and mortar. We sieved the faecal powder through a stainless-steel strainer, aperture 250 mic, to separate the faecal residue from any fibrous material. With regards to extraction, we followed the methods described in Fontani et al. (2022). Briefly, we extracted 0.05–0.1 g of faecal powder in 3 ml of 80% methanol (Scientific Laboratory Supplies, Cat. number CHE2536) using a 15 ml plastic tube and vortexing it for 15 min with a multi-tube vortexer (Multi-Vortexer V-32, Grant Instruments R). Right after centrifugation for 20 min at 3,300 ×g, we stored the supernatant at −20 °C.\n\nWhen analysing faecal hormones, we considered the time course of hormones metabolite excretion relative to the production and circulation of the native hormones (Hodges & Heistermann, 2011; Wheeler et al., 2013). We measured faecal testosterone levels using commercially available enzyme-linked immunosorbent assay (ELISA) kits (DetectX® Testosterone K032-H5W, Arbor Assays R, USA, Cat. number K032-H5) following kits instructions. Before analysis, we diluted all the samples 1:1 with the assay buffer provided by the kits. We assayed all standards and faecal samples in duplicates, with samples showing a coefficient of variation (CV) exceeding 15% being re-analysed (Macagno et al., 2020). We analysed assay data applying a 4-parameter logistic fitting programme (MyAssays R, – open access, available online at https://www.myassays.com/index.html). Concentrations were expressed as pg/mg. Mean intra-assay coefficient of variation for testosterone, tested on three control samples (all males), was 9.35% ± 2.57. Mean inter-assay coefficient of variation, tested on the same samples measured with four replicates across three assay plates, was 5.96% ± 1.42 for testosterone.\n\n\nUse cases\n\nThe above described methods have been previously implemented in our studies (odour sampling: Vaglio et al., 2021a; odour investigation: Walker & Vaglio, 2021; scent enrichment protocol: Vaglio et al., 2021b; behavioural and endocrinological data collection: Maréchal et al., 2011; Fontani et al., 2022; Vaglio et al., 2021b).\n\nAs case studies to show how the methods are expected to be implemented by the research community, we report the results that we obtained with regards to gentle lemurs (Fontani et al., 2022; Fontani et al., unpublished data) and ruffed lemurs (Varecia spp.) (Elwell et al., unpublished data).\n\nWe unequivocally identified four compounds (2-heptanone; 3-heptanone; 3-octanone; 4-methyl 3-hexanone) that were only present in the chemical profiles of anogenital odour samples collected during the fertile window of the breeding period. A representative chromatogram from the fertile window is shown in Figure 2.\n\nThe peaks of the key compounds are pointed out with a red arrow.\n\nThe frequency of male sexual behaviours significantly increased (β ± SE = 0.605 ± 0.211, t-value= 2.865, p-value = 0.0046) during the enrichment condition compared to the pre-enrichment condition. The post-enrichment condition also showed a higher frequency of sexual behaviours than the pre-enrichment condition with a significant tendency (β ± SE = 0.323 ± 0.184, t-value = 1.754, p-value = 0.081).\n\nWe did not find any significant relationship between faecal testosterone levels and the study period (p-value > 0.05).\n\nWe unequivocally identified 12 compounds (benzaldehyde; 1-hexanol, 2-ethyl; benzyl alcohol; dihydromyrcenol; 1-octanol; 2-phenyl-2-propanol; tetrahydrolinalool; linalool; nonanal; menthol; decanal; 2-phenoxyethanol) as being key to the breeding period (i.e., including compounds present only in the breeding period and compounds with much higher relative abundance over the breeding period) in the chemical profiles of anogenital odour samples collected during the breeding period. A typical chromatogram from the breeding period is shown in Figure 3.\n\nThe peaks of the key compounds are pointed out with a red arrow.\n\nThere was a significant effect of period on male sexual behaviours. Ruffed lemurs increased their sexual behaviours while the scent enrichment was present (Est = 2.069; SE = 1.008; z = 2.052; P = 0.040). In comparison, sexual behaviours continued throughout the study after scent exposure and were highest during the post-enrichment period (Est = 1.931; SE = 0.486; 3.978; P < 0.001) (Figure 4).\n\nBW indicates black-and-white ruffed lemurs (Varecia variegata variegata); RR indicates red ruffed lemurs (Varecia variegata rubra). A * indicates a significant difference (*: P = 0.05-0.01; **: 0.01 > P = 0.001; ***: P < 0.001).\n\nWe found that mating behaviours specific to the breeding season were triggered in males once exposed to the scent enrichment. Overall, there was a significant effect of period on mounting in males and this was highest while the enrichment was present (Est = 2.998; SE = 0.817; z = 3.671; P < 0.001; R2 = 0.228).\n\nWe found a large, but not significant (p-value > 0.05), increase of mean faecal testosterone concentration in the post-enrichment condition following scent exposure (Figure 5).\n\nBW indicates black-and-white ruffed lemurs (Varecia variegata variegata); RR indicates red ruffed lemurs (Varecia variegata rubra). A * indicates a significant difference (*: P = 0.05-0.01; **: 0.01 > P = 0.001; ***: P < 0.001).\n\n\nDiscussion\n\nApplying our semiochemistry methods (Walker & Vaglio, 2021) we found a pool of volatile chemical compounds distinguishing the chemical profile of anogenital odour secretions released by female lemurs during the breeding period, suggesting that there might be fertility-specific signals associated with female scents. After that, we tested our novel scent mixture (Fontani et al., 2022; Elwell et al., unpublished data) and showed that it triggered sexual behaviours, including mating, but no statistically significant effects were found on male faecal testosterone concentration.\n\nOur findings suggest that biologically-relevant scent enrichments may trigger natural species-specific behaviours. Novel scent enrichments have, therefore, the potential to impact on captive management and conservation breeding of endangered lemur species. These results also highlight that combining more assessment methods (behavioural observations and faecal endocrinology) may assist with evaluating the impact of environmental enrichments (although it often proves difficult to find statistically significant changes in faecal hormone levels due to confounding variables).\n\nWe, however, must acknowledge some limitations that could have impacted the use cases. First, we focused on a relatively small sample size. Then, due to the small pool of odour samples, it is challenging to mix the compounds in proportions that reflect exactly the real ratios of the anogenital odour secretions released by the fertile female lemurs. Thus, we aim to conduct further investigations on the chemical profile of the female odour secretions (including non-volatile compounds) and expand the sample size when testing the mixture of compounds conveying information about female fertility (including several unsuccessful breeding groups hosted in various institutions).",
"appendix": "Data availability\n\nOpen Science Framework: Design and test of novel scent enrichments to enhance breeding of zoo-housed lemurs. https://doi.org/10.17605/OSF.IO/W35YZ (Vaglio, 2024).\n\nThis project contains the following:\n\n- Behavioural and endocrinological datasets\n\n- Completed ARRIVE checklist\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nWe are grateful to Birmingham Wildlife Conservation Park (especially Les Basford, Gareth Davies and primate keepers), Dudley Zoo & Castle (especially Christopher Leeson and primate keepers), Durrell Wildlife Conservation – Jersey Zoo (especially Eluned Price, Rachel Cowen and primate keepers), Parc Zoologique & Botanique de Mulhouse (especially Brice Lefaux and primate keepers), Shaldon Zoo – Wildlife Trust (especially Zak Showell and primate keepers), Twycross Zoo (especially Mat Liptovszky, Freisha Patel, Jessica Rendle, Lisa Gillespie and primate keepers), and ZSL London Zoo (especially Lewis Rowden and primate keepers) for their support to the project and assistance with sample collection. We thank Wild Place Project – Bristol (especially Will Walker, Daniella Pierce-Butler and primate keepers) for their help with the pilot study of The Enriched Primate project. We also thank Sherkhan Arangala, Joshua Cox, Elysse Lloyd, Georgia Callagan and Anna Beatrice Costantini for assistance with data collection; Keith Holding, David Walker and Matthew Palframan for assisting with chemical analyses, and David Luckhurst for helping with the endocrinology laboratory setting up at the Rosalind Franklin Science Centre—University of Wolverhampton; Stefano Kaburu for assisting with statistical analyses; Giovanna Marliani and Pier Attilio Accorsi for advising with the interpretation of the physiological results. Furthermore, we thank the University of Wolverhampton’s Animal Behaviour and Wildlife Conservation Group members for their constructive comments and suggestions.\n\n\nReferences\n\nAltmann J: Observational study of behavior: Sampling methods. Behaviour. 1974; 49: 227–266. Publisher Full Text\n\nBallou JD, et al.: Demographic and genetic management of captive populations. Wild Mammals in Captivity: Principles and Techniques for Zoo Management. The University of Chicago Press; 2010.\n\nBen-Ari E: What’s new at the zoo? Zoo biologists are taking a scientific approach to improving the quality of life for captive animals. Bioscience. 2001; 51: 172–177. Publisher Full Text\n\nCarroll SP, et al.: Applying evolutionary biology to address global challenges. Science. 2014; 346: 1245993. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCarlstead K, Shepherdson D: Effects of environmental enrichment on reproduction. Zoo Biol. 1994; 13: 447–458. Publisher Full Text\n\nEstrada A, Garber PA, Rylands AB, et al.: Impending extinction crisis of the world’s primates: Why primates matter. Sci. Adv. 2017; 3: e1600946. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFontani S, Kaburu SSK, Marliani G, et al.: Anogenital scent-marking signals fertility in a captive female Alaotran gentle lemur. Front. Vet. Sci. 2022; 9: 940707. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHodges JK, Heistermann M: Field endocrinology: Monitoring hormonal changes in free-ranging primates. Field and Laboratory Methods in Primatology: A Practical Guide. 2nd Edition.Cambridge University Press; 2011.\n\nHosey GR: How does the zoo environment affect the behaviour of captive primates? Appl. Anim. Behav. Sci. 2005; 90: 107–129. Publisher Full Text\n\nThe International Union for Conservation of Nature (IUCN): Red List of Threatened Species. accessed on 13 October 2023. Reference Source\n\nMittermeier RA: Lémuriens de Madagascar. Conservation International & French National Museum of Natural History. The University of Chicago Press; 2014.\n\nLacy RC: Stopping evolution: Genetic management of captive populations. Conservation Genetics in the Age of Genomics. Columbia University Press; 2009.\n\nMacagno A, et al.: Analytical performance of thrombospondin-1 and cathepsin D immunoassays part of a novel CE-IVD marked test as an aid in the diagnosis of prostate cancer. PLoS One. 2020; 15: e0233442. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaréchal L, et al.: Impacts of tourism on anxiety and physiological stress levels in wild male barbary macaques. Biol. Conserv. 2011; 144: 2188–2193. Publisher Full Text\n\nMeier K: Blue eyes on red lists: Conservation and the future of the blue-eyed black lemur. (Unpublished award - winning anthropology papers.2016.\n\nQuirke T, O’Riordan RM: The effect of a randomised enrichment treatment schedule on the behaviour of cheetahs (Acinonyx jubatus). Appl. Anim. Behav. Sci. 2011; 135: 103–109. Publisher Full Text\n\nRioldi ED: The influence of conservation breeding programs on animal communication and behaviour – a literary review. (Unpublished thesis - Mälardalen University.2013.\n\nSchulte-Hostedde AI, Mastromonaco GF: Integrating evolution in the management of captive zoo populations. Evol. Appl. 2015; 8: 413–422. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVaglio S: Design and test of novel scent enrichments to enhance breeding of zoo-housed lemurs. [Dataset]. OSF. 2024. Publisher Full Text\n\nVaglio S, et al.: Olfactory signals and fertility in olive baboons. Sci. Rep. 2021a; 11: 8506. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVaglio S, et al.: Effects of scent enrichment on behavioral and physiological indicators of stress in zoo primates. Am. J. Primatol. 2021b; 83: e23247. PubMed Abstract | Publisher Full Text\n\nWalker D, Vaglio S: Sampling and analysis of animal scent signals. J. Vis. Exp. 2021; 168: e60902.\n\nWark JD, Wierzal NK, Cronin KA: Gaps in live inter-observer reliability testing of animal behavior: A retrospective analysis and path forward. J. Zool. Bot. Gard. 2021; 2: 207–221. Publisher Full Text\n\nWheeler BC, Tiddi B, Kalbitzer U, et al.: Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella). Int. J. Primatol. 2013; 34: 879–898. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "255001",
"date": "29 Apr 2024",
"name": "Lisa Clifforde",
"expertise": [
"Reviewer Expertise Zoological animal welfare and behaviour 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\nElwell et al. present a study on the application of biologically relevant scent based enrichment to increase the occurrence of sexual reproduction behaviours in two species of zoo housed lemurs. This subject area of scent based enrichment is understudied within zoos, as is the use of enrichment to facilitate breeding, therefore the study has useful application within the field.\nThe introduction provides an explanation as to the need for captive breeding programmes, and the more specific issues facing lemurs. They also discuss the challenges to successful captive breeding programmes and discuss why this area merits further investigation. However, the authors cite Hosey (2005) alongside the claim that 50% of zoo animals exhibit abnormal behaviours. This is a misrepresentation of this paper, in that it only discusses primates, not all zoo housed animals, and also does not contain any quantified figures as to the prevalence of abnormal behaviours. The link between the use of enrichment to further the aim of the study is not well explained, and the referenced paper by Meier (2016) does not cover the subject area, beyond a brief mention of appropriate light cycles. Furthermore, the rationale to trial biologically relevant scent based enrichments is also not explained or developed, leading the reader to wonder why this area of enrichment was decided upon. The introduction would benefit from a discussion of enrichment, including a definition (given the wide variation of interpretations in use), and why the authors hypothesised scent would aid in captive breeding attempts.\nThe technical methodology of extracting odour samples and faecal hormone sampling is not with the scope of the reviewer to evaluate. The study protocol describes a two week before enrichment condition, a one week during enrichment condition, and a two week post enrichment condition, but the difference in condition durations is not explained. An explanation as to why faecal testosterone was chosen as a measurable parameter is absent from the text. A brief note as to why this is the most relevant indicator would be helpful.\nThe discussion is notably brief and does not consider why the use of scent elicited the observed behaviours, or how the enrichment could be utilised in the longer term, or wider context to benefit conservation breeding programmes. The results of this study are promising and should the extraction of odours be logistically and financially achievable, then the findings are widely applicable to a broad range of zoos and species. However, without further explanations as recommended above, it would be difficult for many zoos to understand how or why this approach provides an advantage over any other.\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? Partly",
"responses": []
},
{
"id": "285348",
"date": "04 Jul 2024",
"name": "Marlen Kuecklich",
"expertise": [
"Reviewer Expertise Behavioural ecology",
"olfactory communication"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe present study initially identified olfactory fertility cues in females through chemical analyses. Building on this, the study tested whether a synthesised reproduction of this scent mixture is suitable for stimulating male reproductive behaviour. This is a very interesting study, the results of which could have a real impact on the management and breeding of endangered species.\nOverall, the study is very clearly written, the study design is coherent, and the work has academic merit. However, some methodological information is missing, which would make the study fully comprehensible and allow replication by others. The description of the statistical analysis is completely missing and needs to be added. In the results section, a few more details (complete graphical representation, exact values of non-significant results) could make the interpretation of the results more comprehensible. For the behavioural and endocrinological data, all original data are available. For the chemical part, the underlying data are missing; raw data should be added here (analogous to the other parts, Excel tables with the intensities of the identified peaks per file would be sufficient). The conclusions adequately describe the results but should include a better integration of the findings into existing literature and potential applications. Below, I provide further details on which contents should be added to round off the study and make it a valuable and comprehensible suggestion for using olfactory enrichment for captive animals.\nIntroduction: The first paragraph of the introduction provides many relevant background details, but the thread through the various arguments is somewhat missing. Fundamentally, two main problems should be highlighted more clearly: 1) maintaining genetically diverse reserve populations and 2) creating conditions that allow the animals to exhibit as natural behaviour as possible. If the latter is not achieved, there is a risk of frustration and boredom (the causality here could be better formulated) and the problem that such animals might not survive in their natural habitat (this aspect is missing entirely and is only briefly mentioned in the second paragraph).\nThe second paragraph of the introduction nicely highlights the influence of husbandry conditions on zoo populations. The last sentence on the impact of breeding management recommendations should be moved to the beginning of the paragraph, directly after the introductory sentence about breeding programmes. Additionally, the question arises as to whether there are already study results showing that improved husbandry conditions have a positive impact on reproductive success. If so, this would nicely follow the other cited studies.\nThe third paragraph summarises the necessity of the study based on the threat status of primates. A more current reference on the overall threat status of all primate species would be beneficial. The approximately 60% from the 2017 publication has surely been exceeded by now, and a more up-to-date status (perhaps based on current IUCN data) would be nice, although the urgency is already clear.\nThe last paragraph of the introduction clearly outlines the study's objectives. Here, the use of scent in enrichment is specifically mentioned the first time, and it would be beneficial to provide a brief introduction to this topic, including some examples of how scent is or can be used for animal enrichment and how it can positively influence behaviour.\nMethods: The methods are detailed and comprehensible, although some details are missing that would be necessary for a study's replication. I have some additional questions: - Was there a randomised distribution of different observers (i.e., were the same pairs observed by multiple observers, and did each observer watch multiple pairs)? - What were the results of the inter-observer tests? - Were the behavioural observations conducted 'blind' to the condition and study objective, or were the observers informed about the study's aim and the condition being observed (before enrichment, during enrichment, after enrichment)? - What were the reasons for setting the enrichment condition to one week (shorter than the other two conditions)? - What were the reasons for using cotton swabs for collecting scent samples? The introduction states that the study focused primarily on volatile substances. However, cotton swabs collect significantly fewer volatile substances than, for instance, thermal desorption tubes (see our study, Kücklich et al. 2017 (Ref 1) , even though a different extraction method was used, the pattern should be similar). By choosing this method, a substantial portion of the volatile range of chemical profiles, which this study is interested in, might have been missed. A justification for the choice of adsorption medium in the methods section and a discussion on how the choice of cotton swabs might have influenced the study would be desirable. - How were the cotton swabs prepared/cleaned before sampling? - How long were the samples stored from collection to analysis in the laboratory? - Were the scent samples taken from the same pairs that were also observed in the behavioural observations of the \"unsuccessful breeding pairs\"? Based on the introduction, I would have expected scent samples from \"successful\" breeding animals and the presentation of synthesised scent mixtures to be shown to the \"unsuccessful breeding pairs.\" Why was this not done (if I did not miss this detail)? - Which version of the NIST database was used? - How were the \"key compounds distinguishing the fertile window of the breeding female\" statistically determined? - Why was 1 mL of each substance used for the scent mixture instead of adjusting the concentrations to match the proportions in the analysed scent samples (surely some were significantly more/less intense than others)? - From which phases of the cycle were the samples of females taken (the results only state \"during the fertile window of the breeding period\"), and how was the fertile window determined? - The description of the statistical analysis is completely missing and needs to be added.\nResults: The results section is clear and comprehensible, but a few more details should be added: - Were there no compounds with significantly higher relative abundance during the breeding period in gentle lemurs, similar to those considered in ruffed lemurs? - How was it statistically determined which compounds had significantly higher relative abundance during the breeding period, or what threshold was used for this? - The term \"significant tendency\" is not appropriate for a p-value of 0.081. It seems acceptable not to draw a strict black-and-white line at 0.05 and speak of a \"tendency\" here, but by definition it is not \"significant\". - Why is there no graphical representation of the mean count per hour of sexual behaviours for the gentle lemurs, as for the ruffed lemurs? This would help readers better understand the statistical results. - Why are there two different subtypes of ruffed lemurs mentioned in the plot, but the behavioural results are described together in the text? This needs better explanation and alignment (already in the methods, but also here between the description and the plot). - For the endocrinological results of the ruffed lemurs, the term \"large, but not significant\" difference is used. The magnitude of the result is unclear to the reader as only \"p-value > 0.05\" is provided; a complete presentation of the results with exact values would be desirable.\nDiscussion: The discussion summarises the results clearly and provides some suggestions for future studies. In the second paragraph, the first sentence states that the study triggered \"natural species-specific behaviours.\" This should be more specifically related to sexual behaviours because there are many other natural behaviours one could consider that were not the focus of the study. Proper integration of the results into existing literature is completely missing, and a few discussion points are also lacking. For example: - Is it surprising that the compounds related to the fertile window of the breeding period differed completely between the two study species with no overlap? - Have these compounds been found in other studies on primates or mammals in relation to reproduction? - After what period of time would a change in male faecal testosterone concentration be expected? - Are there other studies to compare with? - What would be the recommendation on how other animal facilities could use these findings? - Can the results likely be generalised or applied to other species and settings?\nMinor comments: - At the end of the description of the GC-MS program, there is a '40' that does not belong there. - There are two different spellings of \"ml\"/\"mL\" in the manuscript that should be standardised.\nCan the authors be sure, that this special compound mixture evoked the behavioural changes? The authors mentioned some blanks, but did not discuss them. Moreover, there was no classical control condition with having only stripes with random odour substances not being the compound mixture being important for reproduction identified in the chemical analyses and observing potential behavioural changes to them.Theoretically, any compound mixture could evoke behavioural changes just because of the additional enrichment and ideally this would be tested in a control condition comparison as well.\n\nIs the rationale for developing the new method (or application) clearly explained? Yes\n\nIs the description of the method technically sound? Partly\n\nAre sufficient details provided to allow replication of the method development and its use by others? Partly\n\nIf any results are presented, are all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? Yes",
"responses": []
},
{
"id": "255000",
"date": "05 Jul 2024",
"name": "Kerry Perkins",
"expertise": [
"Reviewer Expertise Wildlife ontogeny and captive reproductive cues"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nOverall an interesting topic presented. The justification of why the research was conducted was well established within the introduction. Potentially giving a greater explanation on how chemical signals play a role in reproductive success would lead into the specific aims outlined at the bottom of the introduction.\nThe method section was very detailed which is key with a novel or new methodology. The main concern within the methodology is the repetition of 'we' at the beginning of nearly every sentence. This made reading feel a bit repetitive due to lack of variation. It would be worth to revisit the methodology section and possibly vary the sentences more to give a better flow within the section.\nWithin the results section using subheadings and separation of the two species allowed for clear demonstration of the findings.\nIn the discussion potential considerations could have been given to whether the faecal samples methodology gave sufficient sampling considering the change in behaviour within the males. But limitations within the studied were outlined well and future research discussed.\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": []
}
] | 1
|
https://f1000research.com/articles/13-123
|
https://f1000research.com/articles/12-1186/v1
|
22 Sep 23
|
{
"type": "Review",
"title": "From the past to the present, optical coherence tomography in glaucoma: a practical guide to a common disease",
"authors": [
"Izabela Zawadzka",
"Joanna Konopińska",
"Izabela Zawadzka"
],
"abstract": "Glaucoma comprises a group of disorders of the optic nerve that cause degenerative optic neuropathy, characterised by failure of neuroretinal rim tissue in the optic nerve head, retinal nerve fibre layer, and retinal ganglion cells. Glaucoma imposes a serious epidemiological threat, with an steady increase in the global number of cases. In the current ophthalmological practice, glaucoma is diagnosed via a series of examinations, including routine funduscopic examination, ocular tonometry, gonioscopy, measurement of the visual field, and assessment using the optical coherence tomography (OCT) technique. Nowadays, the OCT technique helps in systematising the diagnostic pathway and is a basic diagnostic tool for detection of early glaucomatous eye changes. It is also vital in assessing progression and monitoring treatment results of patients. The aim of this review was to present the OCT technique as a main tool in diagnosing and monitoring glaucoma.",
"keywords": [
"glaucoma",
"optical coherence tomography",
"retinal ganglion cells",
"open-angle glaucoma",
"optic neuropathy"
],
"content": "Introduction\n\nGlaucoma is a chronic, multi-factorial, and progressive optic neuropathy characterised by loss of retinal ganglion cells (RGCs) and their axons, which causes characteristic optic disc and retinal nerve fibre layer (RNFL) structural changes. The RGCs transmit impulses received from photoreceptors through their axons to the optic nerve and then to the brain. The axons of RGCs pass through the collagenous structure lamina cribrosa (LA) and is covered with a myelin sheath that continues as the optic nerve. The main site of RGCs damage is LA, whose remodelling occurs as a result of an increased gradient across LA that causes papillary hypoperfusion, leading to impairment of the optic nerve fibres. These changes occur in cases of high intraocular pressure, low perfusion pressure, and/or low cerebrospinal fluid pressure, which leads to loss of RGCs.1–3 Although glaucoma has a specific definition, there are cases with a different course like acute angle-closure glaucoma in which manifestation of the disease occurs rapidly, and well-controlled steroid-induced glaucoma that does not lead to the progression of glaucomatous neuropathy.4,5 Assessment of structural defects of the optic nerve forms the basic principle for the diagnosis and monitoring of glaucoma. Introduction of new ocular imaging methods, particularly optical coherence tomography (OCT), has enabled the evaluation of optic nerves with the highest quality and objectivity. This enables early detection of glaucoma, which is critical to the treatment, and maintaining vision and good quality of life.3\n\n\nGlaucoma classification\n\nThe group of disorders which forms the glaucoma disease spectrum has a complex aetiology, several risk factors, various manifestations, and several treatment options. Regarding the epidemiology in glaucomatous eye disease, we can distinguish two main types of the disease—the open-angle (OAG) and angle-closure (ACG) types—which may have primary and secondary causes. A sub-type known as normal tension glaucoma (NTG) also exists within the OAG type.1,2,6\n\n\nEpidemiology\n\nGlaucoma is the leading cause of blindness globally. In 2020, 3.6 million people suffered vision loss due to glaucoma, and 11% of all word blindness in adults over aged 50 years has been thought to be caused by glaucoma. In 2013, the prevalence of glaucoma was 2.93% among the population aged 40–80 years in Europe, and the prevalence of OAG is 2.51% in this age group.7\n\nIn a recent meta-analysis, Tham et al. evaluated the number of patients with OAG and ACG globally and made a forward projection of the expected number of patients with glaucoma by 2040. They concluded that the number of glaucoma cases will grow rapidly, especially in Asian and African populations. The highest prevalence of primary ACG (PACG) is in Asia and that of primary OAG (POAG) is in Africa. This increase among Asian and African populations is possibly related to the increased life expectancy of the people, which will equal the life expectancy of European and North American populations in the near future. Another important factor proposed by the authors was that the African and Asian continents represent approximately more than 60% of the global population. The authors estimated that the number of people (aged 40–80 years) with glaucomatous eye disease in the world will increase from 64.3 million in 2013 to approximately 111.8 million in 2040.7–9\n\nIn most countries, the increased incidence of glaucoma is associated with population aging. In addition, the higher identification of people with glaucoma is related with greater availability of diagnostic tests for glaucoma. Therefore, early detection of glaucoma is important to avoid the progression to advanced stages, and faster implementation of treatment to reduce the possibility of irreversible blindness.10 OCT screening has high specificity and can be beneficial for the detection of glaucomatous eye damage in high risk populations; however, some authors state that this kind of screening may not be cost-effective.11\n\n\nRisk factors\n\nOAG risk factors can be divided into two groups: ophthalmological and systemic factors. When considering the ophthalmological risk factors in OAG, elevated intraocular pressure (IOP), high myopia, ocular perfusion pressure, central corneal thickness (CCT), and optic disc haemorrhages should be considered.12 Notably, OAG risk increases at a higher IOP, but approximately half of all patients with OAG have IOP values in the normal range (10–20 mmHg). In contrast, glaucomatous optic neuropathy might not occur in patients with increased IOP.2 In an Ocular Hypertension Treatment Study trial, Kass et al.13 found that reduction of elevated IOP (21–32 mmHg) by 22.5% decreased the 5-year risk of developing OAG from 9.5% to 4.4%. The Ocular Hypertension Study proved that thinner CCT is a significant predictor of the development of OAG in patients with ocular hypertension, and that a patient with a CCT of ≥555 μm had a 3-fold higher risk of developing glaucoma within five years compared to a patient with a CCT >588 μm.14 In addition, men have a higher risk of developing OAG compared to women.15 Interestingly, an enlarged optic nerve disc in a myopic eye and increased thinning of the LA due to eye movement and increased shear forces in people with elongated axial length globes can also be significant factors that determine an increased risk of future glaucoma.1,15\n\nMoreover, systemic risk factors of OAG include African ethnicity, family history, smoking, age, genetic factors, as well as systemic hypertension (HT), nocturnal decrease in blood pressure, Raynaud syndrome, atherosclerosis, obesity, type 2 diabetes mellitus, and severe migraine headaches.12 The prevalence of POAG in the European population increases with age, from 0.4% at the age of 40–44 years, to 2.7% at the age of 70–74 years, and up to 10.0% for persons over the age of 90 years.8 HT is associated with a 16% increase in the risk of OAG, and the severity of glaucoma was found to be higher in patients with HT than that in individuals with normal blood pressure.16,17 Conversely, hypotension may also be associated with the risk of glaucomatous optic neuropathy by reducing ocular perfusion pressure.18–20 For PACG, ocular risk factors include swallowing of the anterior chamber, globe axial length shortening, increased lens thickness, and the anterior positioning of the lens. The demographic risk factors include increasing age, female sex, and East Asian ethnicity.21\n\n\nSymptoms\n\nACG and OAG have no subjective symptoms, but in patients with ACG may exhibit a sudden manifestation due to acute primary angle closure that can cause ocular pain. less frequent visual impairment, conjunctival injection, rock-hard globe, and rare nausea and vomiting. It is essential for the ophthalmologist to diagnose patients accurately based on these symptoms and intervene with immediate treatment. Patients with OAG do not exhibit any symptoms for a long time as OAG develops slowly with a low intensity; hence, in most cases, it is unnoticed by the patient until it has reached an advanced or late stage.1,22 In addition to the patient’s delayed awareness of visual field defects, the defects usually do not correlate in both eyes and leads to compensation due to binocular vision.1\n\n\nGlaucoma detection\n\nGlaucoma can be diagnosed using the following tests: funduscopic examination, ocular tonometry, gonioscopy, measurement of the visual field (VF), and assessment using the OCT technique.1,2 The core of glaucoma diagnosis is the assessment of optic nerve changes mainly in funduscopic examinations, VF tests, and using OCT techniques.\n\nThe fundoscopic examination in the assessment of the optic nerve head (ONH) is based on the evaluation of the neuroretinal rim (NRR), which is an area between the optic disc margin (DM) and cup edge.23 The characteristic ONH changes in glaucoma include a focal or diffuse NRR thinning, specifically in the superior or inferior quadrant of the optic disc with an enlargement of the ONH cup to disc ratio > 0.5.24 The proposal by Jonas et al.,25 the inferior > superior > nasal > temporal (ISNT) rule, states that the thickness of the NRR decreases in the previously mentioned order, and that the NRR in glaucomatous optic discs disturb this relationship. However, several papers also deny the usefulness of ISNT assessment.26\n\nAn important examination for detecting and monitoring functional impairment of the optic nerve in glaucoma is the assessment of VF using static automated perimetry (SAP). VF abnormalities are associated with loss of RGCs and their axons. The glaucomatous visual field defect can the diagnosed using the Hoddap–Parrish–Anderson criteria,24 which include the following:\n\n• Hemifield test that exceeds the normal limit on at least two fields.\n\n• Typical of a glaucomatous changed eye cluster of three or more depressed non-edge points, with a P < 5%, and one that is depressed at a P < 1% on two consecutive fields.\n\n• A corrected pattern standard deviation that occurs in less than 5% of normal fields on two consecutive fields.\n\nGlaucoma diagnosis should be performed in the case of dissymmetry of VF between the eyes. The characteristic defects in VF in glaucoma mainly include narrowing of the peripheral VF, temporal island of VF, temporal wedge, Roenne’s nasal step, and different types of scotomas (paracentral, ring-shaped, Seidel’s, and Bjerrum’s).24\n\nVF examination is highly subjective depending on patient compliance and concentration. The quality of the exam is determined by different factors, such as the patient noncompliance and fatigue especially in elderly patients. In addition to artefacts, such as blepharoptosis, lens defects and refractive errors also decrease the quality of the exam.27 The perimetric examination should be performed on the same device and with the same protocol (e.g., 10-2, 24-2, 30-3) at least three times a year in the first year after the diagnosis – this increases the reliability of the results.1 The result maps out the patients’ VF, which can be helpful in assessing the baseline and tracking disease progression. In the case of a ganglion cell loss of less than 40–50%, there are no reliable VF defects in threshold perimetry, thus, the concept of preperimetric glaucoma was proposed as typical glaucomatous eye changes without the presence of VF defects detected by a perimetric examination.24 Nowadays, the availability of a new technology, such as OCT-based fundus imaging, improves the assessment of preperimetic glaucoma progression.28\n\nThe OCT technique is superior because the automated perimetry examination can lack reproducibility and has some degree of non-objectiveness. Moreover, the OCT examination shows evidence of structural changes, including ONH damage and RNFL thinning, before functional loss is detected by standard automated perimetry. Furthermore, OCT is reliable when performed on both normal and glaucoma patients, and shows superiority in monitoring patients who are unable to undergo VF testing, including children, the elderly, and those with dementia.27 In ophthalmology, the OCT technique is a basic tool in daily clinical practice.29 Hence, its superior resolution renders it as a reliable tool for retinal morphology assessment and the measurement of retinal thickness, which have become important in evaluating patients with wet age-related macular degeneration.30 Retinal thickening is also frequent in patients with type 1 or 2 diabetic retinopathy, approximately 15% of whom develop macular oedema, where OCT can also be one of the first-choice diagnostic tools. The third and leading reason for OCT evaluation is patients with glaucoma, which causes RNFL atrophy and visual loss in advanced stages, is that OCT evaluation can detect RNFL thinning at an early stage, often before a patient’s visual loss, leading to early-stage glaucoma detection. Additionally, OCT is used in nearly all fields of ophthalmological disorders, such as monitoring and follow-up for eye surgery, macular holes, vascular occlusions, and examination of pathologies in the anterior segment of the eye.31\n\n\nOptical coherence tomography – history and basic principles\n\nOCT is a diagnostic imaging method that produces a cross-sectional tomographic image of the eye structures with near-histologic and ultrahigh resolution.30 It was originally developed by researchers from the Massachusetts Institute of Technology in the early 1990s, evolving from optical coherence domain reflectometry (OCDR), which is a method used for finding faults in fibre-optic cables and network components. The first OCT introduced was a two-dimensional, tomographic imaging modality for the biological system. OCT is a similar method to that of ultrasound, but it uses light instead of sound, and produces images of a higher magnitude (it can deliver images of 1–15 μm contrary to traditional ultrasound techniques which have significantly lesser spatial resolution).32–34\n\nOCT imaging is an important non-invasive technology in the detection and monitoring of glaucomatous structural damage. Over the years, OCT techniques have evolved from time-domain OCT (TD-OCT) to spectral-domain OCT (SD-OCT) and swept-source OCT (SS-OCT), which have improved the resolution and speed of scans. TD-OCT, a previously used technique, encoded the location reflections in time information and related the location of the reflection to the position of the moving reference mirror. Therefore, imaging of the fundus was possible, and changes in glaucoma could be evaluated and observed over time; however, the main disadvantage of this method was the slow scan time and two-dimensional imaging, which made the technique prone to artefacts. Another limitation of the TD-OCT technique was the limited maximal oscillating speed of the reference mirror, which performed only 400 axial scans. OCT technology has advanced since its first application in ophthalmology and continues to evolve rapidly. Hardware advances in commercial systems has improved resolution and increased scanning speeds, as a result of the replacement of the TD-OCT technique by the SD-OCT method. SD-OCT, also known as the Fourier-domain OCT (FD-OCT) method, allows acquisition of all information from a single axial sample simultaneously through the tissue by evaluating the frequency spectrum of the interference between the stationary reference mirror and reflected light. This not only improves scan density and resolution, but also significantly reduces imaging artefacts by reducing the scan acquisition time.3,35 In addition, SD-OCT produces 3D datasets that can enable a greater assessment of the ONH parameters in the early evaluation of glaucoma and improved progression monitoring. From 3D images, we can acquire accurate information about the ONH parameters, including the disc area, rim area, cup-to-disc ratio, cup volume, and RNFL thickness.36\n\nSS-OCT is a variation of FD-OCT. The hardware in SS-OCT differs from that in SD-OCT, including the light source, bulk optics components, and photodetection device. In SS-OCT, the wavelength of the light source is approximately 1 μm, which sweeps across a narrow band of wavelengths, whilst the SD-OCT utilises a broadband light source. For the detection of the light waves, SS-OCT uses a point photodetector, whereas SD-OCT uses a spectrometer consisting of a diffraction grating, Fourier transform lens, and a detector array or linescan camera. Notably, the light source of the SS-OCT system is more complex; however, the design of the photodetector device is simpler, which gives the system faster scanning speed, resulting in higher scan rates with deeper tissue visualisation.37,38\n\n\nOptical coherence tomography in glaucoma — diagnosis and progression\n\nThe introduction of the OCT technique over 20 years ago has allowed for supplemental, quantitative, and less operator-dependent precision with near histological-like spatial resolution assessment of glaucomatous eye changes. Using the OCT technique, we can acquire an automated segmentation of the retinal tissue layers, including the macula area, RFNL of the peripapillary region (pRNFL), and ONH area.3 The macular area and pRFNL are the most important parameters in the assessment of glaucomatous eye changes. The OCT acquisition of the ONH region enables accurate and reproducible measurements of ONH parameters, such as the disc area, rim area, cup-to-disc ratio, cup volume, and RNFL thickness, but the large inter-individual variability reduces the reliability of ONH parameters.3,39\n\nThus far, the most popular OCT parameter in assessing glaucomatous eye changes is the pRFNL. pRNFL thinning in OCT is often one of the first signs of glaucoma, and it can be detected even before changes in the VF are observed.39 In the diagnosis and assessment of glaucoma progression, the average pRNFL thickness, especially the pRNFL thickness in the inferior and superior quadrants, should be considered. Thinning of this parameter can have a significant impact on early glaucoma diagnosis, when the VF parameters are normal. The OCT analyses provide the RNFL thickness curve adjusted to the normative databases where green, yellow, and red colours are assigned to normal, borderline, and abnormal values, respectively (RNFL thickness values under the 99th percentile of normal database). Early-stage glaucoma known as ‘green disease’ occurs when green labelling of OCT parameters indicates normal values despite the presence of glaucoma or progressive glaucomatous damage. Thus, in some cases the RNFL parameter must be still monitored even when the curve is on the green area. One must especially consider the fact that an asymmetrical thinning, comparing both eyes, with a value greater than 9 μm in the average pRNFL thickness, can suggest early glaucomatous degeneration.40,41 Some cases of reduced RNFL thickness with red labelling of OCT parameters, despite lacking glaucomatous changes, are considered as ‘red disease’, which can occur in cases of myopia. When monitoring for glaucomatous progression using OCT, the physician must be aware of the accompanying and the abovementioned age- and software-related artefacts and the floor effect. Age-related pRNFL thinning rate, which occurs in healthy eyes at a mean rate of –0.48 μm/year to –0.60 μm/year depending on the OCT device, must also be considered. Software-related artefacts also play a significant role in the accurate assessment of glaucomatous eye damage and/or progression; most of them are operator-dependent and include displacement of optic disk boundaries, myopic eyes, and/or significant media opacities, resulting in erroneous pRNFL values.42 Glaucomatous progression must be suspected when there is a global decrease of ≥5 μm in the average pRNFL thickness. Another important factor of progression is a decrease of ≥7–8 μm in the sectoral pRNFL thickness. ‘Floor effect’ occurs when the pRNFL values decrease to a point where they are undetectable by OCT. Notably, the average pRNFL floor value ranges from 49.2 μm to 64.7 μm depending on the OCT device. This happens first in the pRFNL because the papillomacular region is more resistant to glaucomatous damage than the pRNFL; accordingly, measuring the thickness of the papillomacular structure is of great significance in the evaluation of glaucoma in its advanced stages. Thus, it is crucial to understand that the floor effect is achieved earlier within the pRNFL, and later in the macular region. In such cases, we should consider the use of macular OCT and VF 10-2 testing.43 Despite the pRFNL being a useful and the most commonly used tool in diagnosing glaucomatous eye changes in cases of high myopia, small or tilted ONHs, and swelling of ONH, the measurement result can be unreliable; in these cases, the macular area parameters should be used as reference points.44\n\nEarly-stage glaucoma can cause thinning of the macula area, which consists of macular RFNL (mRFNL) and ganglion cell layer with inner plexiform layer (GCIPL); GCIPL contains RGC bodies and RGC dendrites, which forms the ganglion cell complex (GCC = mRFNL + GCIPL). Assessing the macular region in this case is particularly important because it has the highest concentration of RGCs in the retina (approximately 50% of the RGCs of the entire retina).3 During OCT evaluation of the macular area, the mRNFL thickness, GCC thickness, GCIPL minimum thickness, and GCIPL average thickness must be considered. When assessing these parameters, epidemiological factors, such as age and sex, must be considered. Additionally, central corneal thickness, axial length, and macular GCIPL attrition with aging, which occurs similarly to mRNFL at a rate of approximately –0.31 μm/year, are important and must be considered. In the assessment of the macular region, depending on the OCT device that is used, one can focus on assessing the GCC complex as a whole parameter or the GCIPL. The GCC thickness values range between 95.08 ± 7.88 μm in normal eyes, 83.30 ± 9.27 μm in early stage perimetric glaucomatous eyes, and 80.13 ± 9.60 μm in the moderate stage, and 75.08 ± 11.79 μm in the advanced stage.45 When assessing glaucomatous eye changes, one must be aware that several studies suggest that in early glaucoma the GCC parameter is superior to the pRFNL,46 but there is no clear consensus regarding this statement.47 In establishing the diagnosis, it is crucial to inspect the average GCC thickness, as it is more reliable than the pRNFL in early stage glaucoma and preperimetric glaucoma. The average and inferior GCC thicknesses can be correlated with progressive visual field loss. The examination has greater diagnostic value with more advanced stages of the glaucomatous neuropathy when the signal strength values are higher. Moreover, it is unaffected by the increase in axial length, which results in more specific discrimination of glaucomatous changes in myopic eyes compared to that of RNFL thickness.46 In advanced glaucoma, the early floor effect is achieved when assessing the pRNFL; thus, this parameter is excluded from OCT assessment in advanced stages. In such cases, one should consider a combination of OCT assessment of the macular region and VF 10-2 testing. The static automated perimetry offers various test protocols (10-2, 24-2, 30-2); the test points are localised approximately 6° from each other in the 24-2 and 30-2 protocols.48,49 Due to the GCC thickness, which is strongly correlated with retinal sensitivity within a central range of 10° of the macula, the VF 10-2 should be considered as the main examination in determining the rate of progression in advanced glaucoma. Moreover, glaucomatous damage in advanced stages, when the RGC bodies can be displaced from their receptive fields of the macular area, can lead to false VF testing results. This can result in failure to assess the relationship between the defects and RGC damage; hence, in this case, a 10-2 test protocol with a 2° grid should be considered as the better choice as it displays more accurate results.50 When assessing the GCIPL, Xu et al.51 stated that the average GCIPL thickness is approximately 75.2 ± 6.8 μm in early glaucoma, which thins to 64.4 ± 8.4 μm in moderate glaucoma, and then to 55.6 ± 7.6 μm in advanced glaucoma. Furthermore, an average GCIPL thickness change of >4 μm is suggestive of glaucomatous progression. When monitoring progression, one must be aware that the macular thickness is visible as an arcuate defect on the thickness and progression-change maps. Although appearing later, an important parameter to consider is the floor effect, which is defined as a point at which no further structural loss can be detected. As Chhavi et al. stated, several studies have shown that in advanced stages of glaucomatous damage, when mRNFL thickness is <55 μm, the GCIPL thickness change still correlates with the damage measured using a 10-2 visual field; as mentioned above, the floor effect occurs when the average thickness of macular GCIPL is approximately 45 μm.39 Several vendors provide different OCT devices, and not every OCT device can segment the GCIPL complex. Due to these limitations, some studies focus on assessing the GCC as a whole, whereas some assess the GCIPL complex as a solitary parameter. Despite this, the assessment of the GCIPL can be fraught with high error risk due to several coexisting factors, which warrants the consideration of the presence of an epiretinal membrane, areas of vitreous adhesion, myopic eyes, macular schisis, and drusen.52,53\n\nThe above-mentioned groups of parameters comprise the basis of glaucomatous damage assessment. Importantly, in the clinical assessment of glaucoma progression, the expected results may vary due to a series of artefacts that can occur in the diagnostic process, such as the segmentation error artefact; decentration, especially in myopic eyes; and accompanying pathological changes in the eye, such as media opacities in the form of corneal haze, cataracts, vitreous debris, myelinated RNFL, epiretinal membrane, and swelling of the ONH; these artefacts may falsely decrease or increase RNFL measurements.39\n\n\nConclusion\n\nGlaucoma is a progressive and degenerative disease that leads to irreversible vision loss. Through its rapid developments, which have led to increased resolution and scan speeds, the OCT technique has become a powerful tool for diagnosing and detecting glaucoma progression. All assessed parameters, including RNFL thickness, macular RNFL, and ONH parameters, are valuable tools for early assessment and monitoring of glaucomatous eye changes, and none of these parameters showed significant superiority over the others. Therefore, all parameters are valuable in assessing different stages of glaucomatous disease.",
"appendix": "Data availability\n\nNot applicable as this is a review article.\n\n\nReferences\n\nSchuster AK, Erb C, Hoffmann EM, et al.: The diagnosis and treatment of glaucoma. Dtsch. Arztebl. Int. 2020; 117: 225–234. PubMed Abstract | Publisher Full Text\n\nGupta D, Chen PP: Glaucoma. Am. Fam. Physician. 2016; 93: 668–674.\n\nGeevarghese A, Wollstein G, Ishikawa H, et al.: Optical coherence tomography and glaucoma. Annu. Rev. Vis. Sci. 2021; 7: 693–726. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSun X, Dai Y, Chen Y, et al.: Primary angle closure glaucoma: what we know and what we don’t know. Prog. Retin. Eye Res. 2017; 57: 26–45. Publisher Full Text\n\nPhulke S, Kaushik S, Kaur S, et al.: Steroid-induced glaucoma: an avoidable Irreversible Blindness. J. Curr. Glaucoma Pract. 2017; 11(2): 67–72. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWiggs JL, Pasquale LR: Genetics of glaucoma. Hum. Mol. Genet. 2017; 26(R1): R21–R27. 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Publisher Full Text\n\nGordon MO, Beiser JA, Brandt JD, et al.: The ocular hypertension treatment study: baseline factors that predict the onset of primary open-angle glaucoma. Arch. Ophthalmol. 2002; 120: 714–720. discussion 829–830. Publisher Full Text\n\nZhang N, Wang J, Li Y, et al.: Prevalence of primary open angle glaucoma in the last 20 years: a meta-analysis and systematic review. Sci. Rep. 2021; 11(1): 13762. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhao D, Cho J, Kim MH, et al.: The association of blood pressure and primary open-angle glaucoma: a meta-analysis. Am J. Ophthalmol. 2014; 158: 615–27.e9. Publisher Full Text\n\nKhatri A, Shrestha JK, Thapa M, et al.: Severity of primary open-angle glaucoma in patients with hypertension and diabetes. Diabetes Metab. Syndr. Obes. 2018; 11: 209–215. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTham YC, Lim SH, Gupta P, et al.: Inter-relationship between ocular perfusion pressure, blood pressure, intraocular pressure profiles and primary open-angle glaucoma: the Singapore epidemiology of eye diseases study. Br. J. Ophthalmol. 2018; 102: 1402–1406. PubMed Abstract | Publisher Full Text\n\nTorabi R, Harris A, Siesky B, et al.: Prevalence rates and risk factors for primary open angle glaucoma in the Middle East. J. Ophthalmic Vis. Res. 2021; 16: 644–656. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAschard H, Kang JH, Iglesias AI, et al.: Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis. Eur. J. Hum. Genet. 2017; 25: 1261–1267. Publisher Full Text\n\nWeinreb RN, Aung T, Medeiros FA: The pathophysiology and treatment of glaucoma: a review. JAMA. 2014; 311(18): 1901–1911. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nLaíns I, Wang JC, Cui Y: Retinal applications of swept source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Prog. Retin. Eye Res. 2021; 84: 100951. Publisher Full Text\n\nObuchowska I, Konopińska J: Importance of optical coherence tomography and optical coherence tomography angiography in the imaging and differentiation of choroidal melanoma: a review. Cancers (Basel). 2022; 14: 14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFujimoto JG, Pitris C, Boppart SA, et al.: Optical coherence tomography: an emerging technology for biomedical imaging and optical biopsy. Neoplasia. 2000; 2(1-2): 9–25. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDong ZM, Wollstein G, Schuman JS: Clinical utility of optical coherence tomography in glaucoma. Invest. Ophthalmol. Vis. Sci. 2016; 57(9): OCT556–OCT567. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPodoleanu AG: Optical coherence tomography. J. Microsc. 2012; 247(3): 209–219. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBussel II, Wollstein G, Schuman JS: OCT for glaucoma diagnosis, screening and detection of glaucoma progression. Br. J. Ophthalmol. 2014; 98: ii15–ii19. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRothenbuehler SP, Malmqvist L, Belmouhand M, et al.: Comparison of spectral-domain OCT versus swept-source OCT for the detection of deep optic disc Drusen. Diagnostics (Basel). 2022; 12(10): 2515. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCole ED, Duker JS: OCT technology: will we be “swept” away? A look at the differences between spectral-domain and swept-source OCT, and the potential clinical benefits of swept-source. Rev. Ophthalmol. 2017 April 7.\n\nSaini C, Shen LQ: Monitoring glaucoma progression with OCT. Glaucoma specialists discuss how to get the most out of this technology.2020 May 6.\n\nSayed MS, Margolis M, Lee RK: Green disease in optical coherence tomography diagnosis of glaucoma. Curr. Opin. Ophthalmol. 2017; 28: 139–153. PubMed Abstract | Publisher Full Text\n\nMwanza JC, Durbin MK, Budenz DL: Interocular symmetry in peripapillary retinal nerve fiber layer thickness measured with the cirrus HD-OCT in healthy eyes. Am J. Ophthalmol. 2011; 151: 514–521.e1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAsrani S, Edghill B, Gupta Y, et al.: Optical coherence tomography errors in glaucoma. J. Glaucoma. 2010; 19(4): 237–242. Publisher Full Text\n\nSung MS, Heo H, Park SW: Structure-function relationship in advanced glaucoma after reaching the RNFL floor. J. Glaucoma. 2019; 28(11): 1006–1011. Publisher Full Text\n\nDonaldson L, Margolin E: Visual fields and optical coherence tomography (OCT) in neuro-ophthalmology: structure-function correlation. J. Neurol. Sci. 2021; 429: 118064. Publisher Full Text\n\nKim NR, Lee ES, Seong GJ, et al.: Structure-function relationship and diagnostic value of macular ganglion cell complex measurement using Fourier-domain OCT in glaucoma. Invest. Ophthalmol. Vis. Sci. 2010; 51(9): 4646–4651. Publisher Full Text\n\nScuderi G, Fragiotta S, Scuderi L, et al.: Ganglion cell complex analysis in glaucoma patients: what can it tell us? Eye Brain. 2020; 12: 33–44. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKim NR, Lee ES, Seong GJ, et al.: Structure-function relationship and diagnostic value of macular ganglion cell complex measurement using Fourier-domain OCT in glaucoma. Invest. Ophthalmol. Vis. Sci. 2010; 51(9): 4646–4651. PubMed Abstract | Publisher Full Text\n\nHood DC, Raza AS, de Moraes CG , et al.: Glaucomatous damage of the macula. Prog. Retin. Eye Res. 2013; 32: 1–21. PubMed Abstract | Publisher Full Text | Free Full Text\n\nScuderi GL, Cesareo M, Perdicchi A, et al.: Standard automated perimetry and algorithms for monitoring glaucoma progression. Prog. Brain Res. 2008; 173: 77–99. Publisher Full Text\n\nScuderi G, Fragiotta S, Scuderi L, et al.: Ganglion cell complex analysis in glaucoma patients: what can it tell us? Eye Brain. 2020; 12: 33–44. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXu X, Xiao H, Guo X, et al.: Diagnostic ability of macular ganglion cell-inner plexiform layer thickness in glaucoma suspects. Medicine (Baltimore). 2017; 96(51): e9182. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYoo YC, Lee CM, Park JH: Changes in peripapillary retinal nerve fiber layer distribution by axial length. Optom. Vis. Sci. 2012; 89: 4–11. Publisher Full Text\n\nQiu KL, Zhang MZ, Leung CK-S, et al.: Diagnostic classification of retinal nerve fiber layer measurement in myopic eyes: a comparison between time-domain and spectral-domain optical coherence tomography. Am J. Ophthalmol. 2011; 152: 646–653.e2. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "220515",
"date": "30 Nov 2023",
"name": "Karanjit Kooner",
"expertise": [
"Reviewer Expertise I am a glaucoma specialist practicing at a major academic center in Dallas Texas. USA."
],
"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\nAn excellent review regarding the role of OCT in glaucoma, by Zwadzka and Konopinska, covers a wide range of clinically relevant information for ophthalmologists treating patients with glaucoma. The review combines the pathophysiology and epidemiology of glaucoma leading up to the benefits of relatively objective OCT technology.\n\nThe review however lacks examples of OCT scans in patients with glaucoma and in myopia. The authors should also touch on the role of OCT-angiography (OCTA) which provides details on the vascular parameters as well.\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": [
{
"c_id": "11105",
"date": "13 Apr 2024",
"name": "Joanna Konopińska",
"role": "Author Response",
"response": "Following your recommendations, we have added a chapter dedicated to Angio-OCT in glaucoma, along with examples of OCT examinations of the optic nerve head in patients with glaucoma and patients with myopia"
}
]
}
] | 1
|
https://f1000research.com/articles/12-1186
|
https://f1000research.com/articles/13-121/v1
|
19 Feb 24
|
{
"type": "Case Study",
"title": "Understanding the welfare requirements of a neurologically and physically divergent captive male Sumatran orangutan (Pongo abelii)",
"authors": [
"Lelia Bridgeland-Stephens",
"Susannah K. S. Thorpe",
"Eluned Price",
"Gordon Hunt",
"Jackie Chappell",
"Susannah K. S. Thorpe",
"Eluned Price",
"Gordon Hunt",
"Jackie Chappell"
],
"abstract": "Background Understanding the needs of animals with physical and cognitive impairments is essential for zoos, rehabilitation centres, and other captive contexts. This case study describes the atypical physical and cognitive development of Jiwa, an adult male Sumatran orangutan (Pongo abelii), to evaluate how these differences may impact Jiwa and to explore how cognitive enrichment can be tailored to his skill level.\n\nMethods Keeper records from Jiwa’s birth (1999) to February 2022 were scrutinised to identify key developmental milestones, changes in body weight, and deciduous dental emergence. These were compared with expected milestones for wild and captive orangutans. In addition, a probe feeder apparatus was gradually tailored to an appropriate skill level between January and March 2022.\n\nResults Many of Jiwa’s developmental milestones were consistent with expected orangutan development, although there were noticeable differences in body weight, dental emergence, locomotion, and cognition. The welfare domains most likely to be negatively impacted by these differences were physical health, expression of agency, and mental wellbeing. After the enrichment device was tailored to an appropriate level of challenge, Jiwa showed marked improvement in engagement and ability to use the device.\n\nConclusions This study helps to inform future case studies of atypical great apes by detailing the physical and cognitive development of an individual orangutan. Although Jiwa’s differences may impact his own wellbeing in some areas, he has largely been able to overcome them. However, this case study highlights the challenges involved in tailoring enrichment apparatuses and resilience interventions for atypical individuals.",
"keywords": [
"atypical development",
"captivity",
"disability",
"divergent",
"enrichment",
"life history",
"orangutan",
"zoo"
],
"content": "1. Introduction\n\nHumans responsible for the care of non-human animals (hereafter animals) have a responsibility to ensure that positive welfare is promoted in those individuals, and that they are free from harm. Over the past few decades, there has been a concerted effort to develop a system to measure wellbeing in captive animals. In the 1990s, the UK Farm Animal Welfare Council’s original ‘five freedoms’ of welfare (FAWC, 1992) were adapted by Mellor and Reid (1994) into a grading system known as the Five Domains Model. These overlapping domains are: 1) thirst, hunger, and malnutrition; 2) environmental challenge; 3) disease, injury, and functional impairment; 4) behavioural restriction; and 5) anxiety, fear, pain, and distress. Rather than measuring the presence or absence of each ‘freedom’, this system takes a more nuanced approach, acknowledging the degrees of compromise made in each of these areas of welfare, or ‘wellbeing’ (Mellor and Reid, 1994). The fifth domain, which relates to mental wellbeing, is a cumulative measure of the four physical domains, and therefore determines the overall score. The five domains were extended in 2015, with changes that included broadening the negative affective states with those related to an individual’s cognitive assessment of external circumstances, e.g. anxiety, fear, frustration, anger, helplessness, loneliness, and boredom (Mellor and Beausoleil, 2015). In addition, positive welfare states were taken into consideration. In the mental wellbeing domain, this includes states such as security, confidence, calmness, control, affectionate sociability, playfulness, and sexual gratification (Mellor and Beausoleil, 2015). These are related to behaviours encompassing agency, exercised through activities like environmental challenges, making choices, exploration, bonding with others, playing, and being able to retreat or defend oneself from attack. The latest iteration of the Five Domains Model incorporates both positive and negative human-animal interactions (Mellor et al., 2020).\n\nIdentifying the welfare needs of animals in captivity who diverge neurologically and/or physically from the species-typical ‘norm’ is a complicated issue, partly due to the individual nature of such conditions. Although there is variation within all species, some individuals are divergent to the extent that they experience life differently to others. This means that socio-environmental conditions which are deemed to meet welfare needs in most members of a species may not be able to meet the needs of all individuals. In humans, the 1975 declaration of the Union of the Physically Impaired Against Segregation marked a shift towards emphasising the constraints of external, socio-structural barriers preventing humans from fully participating in society, rather than disability being defined by individual, internal limitations (Edwards and Imrie, 2008). This is relevant for non-human animals in captivity, as there is potential for management changes and enclosure modifications to enable atypical individuals to lead a fulfilling life. However, the first step is to begin to understand the diversity of neurologically and physically atypical characteristics, and the extent to which captive environments can be adapted without compromising the welfare of other individuals.\n\nUnderstanding of the needs of divergent animals is important in all captive contexts. However, for wild-born animals rescued from human-wildlife conflict and undergoing rehabilitation, there is an additional motivation. For example, orangutan (Pongo spp.) rehabilitation centres, which care for orangutans rescued from the illegal wildlife trade and other harmful situations, must make decisions on whether injured and otherwise atypical individuals can and should be released back into the wild or moved to semi-wild environments (Russon, 2008). If great apes are released into more natural environments, where individuals must be self-supporting, physical and cognitive impairments may result in difficulties such as obtaining food (Domain 1), building nests for resting safely (Domain 2), maintaining physical fitness and being able to reach and navigate the forest canopy (Domain 3), and defending against threats (Domain 4). All of these are likely to have a negative impact on mental wellbeing (Domain 5), leading to hunger, anxiety, fear, pain, and distress (Mellor et al., 2020). In some rehabilitation centres, chimpanzees (Pan troglodytes) with physical or psychological disabilities remain in enclosures rather than being released into partially free-range forested islands (Litchholt, 2021).\n\nThese careful management decisions made by rehabilitation centres will depend on the specific nature of an individual’s differences, whether physical or cognitive, and the extent to which they are likely to affect an individual’s ability to support themselves with a reasonable degree of wellbeing. There are complex ethical issues surrounding these decisions (see Palmer, 2018), particularly as it is difficult to predict the outcome of any release effort, and these risks must be balanced against potentially sub-optimal welfare in captivity. Although life in the wild is challenging for any individual, particularly those released from captivity, the challenge may be exacerbated for individuals with physical and/or cognitive differences. For example, severe physical injury can lower the dominance rank for chimpanzees and baboons (Papio cynocephalus) (e.g. Reynolds and Reynolds, 1965; Drews, 1996), indicating a reduction in competitive ability (Beamish and O’Riain, 2014).\n\nThere is poor knowledge of divergent individuals in animal research. There are some examples of studies with primates with physical impairments (Nakamichi, Fujii and Koyama, 1983; Cole, 1989; Hobaiter and Byrne, 2010; Antilla et al., 2013; Turner et al., 2014; Hopper, Shender and Ross, 2016; Matsumoto et al., 2016; Taylor, 2020), but few long-term studies (e.g. Sakuraba, Tomonaga and Hayashi, 2016), and limited research on the life history and development of atypical individuals, although there are some isolated examples (e.g. Savage and Snowdon, 1982; Hirata et al., 2017).\n\nHowever, there are examples of divergent primates coping well in the wild. For example, a male free-ranging Japanese macaque (Macaca fuscata) called Tanago, who had missing hands and ‘distorted’ feet, was assessed during his first year of life and found to have impaired locomotion and social interactions (Nakamichi, Fujii and Koyama, 1983). Although Tanago’s physical impairments meant he struggled to keep up with other infants, leading to lower levels of play behaviours, Tanago was also less likely to receive aggression than other infants, and more likely to be groomed by other juveniles, usually females (Nakamichi, Fujii and Koyama, 1983). Tanago had a closer relationship with adults and female juveniles than other infant macaques, despite the rigid hierarchy in Japanese macaques which would normally have prevented him interacting with older troop members (Nakamichi, Fujii and Koyama, 1983). Therefore, Tanago generally adapted well to his physical impairments. As well as altering social interactions, physical impairments can also influence the length of time atypical individuals spend in different activities. For example, activities like locomotion may be more tiring with a physical impairment. In a long-term study of free-ranging Japanese macaques, disabled females spent more time resting and less time socialising than nondisabled females (Turner et al., 2014). However, as with Tanago, this was not due to social alienation, as disabled females received less aggression, and their groom solicitations were as successful as nondisabled females (Turner et al., 2014). Another study showed similar increased resting time for disabled baboons, but no changes in grooming or social vigilance behaviours (Beamish and O’Riain, 2014). Physical divergence does not necessarily prevent wild animals from living a long and fulfilling life. A wild female Japanese macaque called Mozu, whose hands and feet had an abnormal morphology (possibly from pesticide pollution), became a prominent troop member, living for 28 years and rearing five offspring (Cole, 1989, in Taylor, 2020).\n\nIn captive contexts where long-term care is being provided, there are several key motivations for understanding divergent individuals. The first is that understanding the needs of these individuals is fundamental to promoting their welfare. As there is currently limited research in this area, sharing knowledge about specific cases can help caretakers know what to expect, particularly during an individual’s development. By understanding of how the needs of atypical individuals can be fulfilled in relation to the Five Domains Model, a knowledge base can be established which caretakers can use to guide individual care and husbandry to optimise the quality of life for atypical individuals. Not only does this have clear benefits for animal welfare, but there are also financial implications for the zoo. Atypical individuals whose needs are not being met may exhibit behaviours related to negative affect, e.g. anger and frustration. As well as having the potential to negatively affect visitor perceptions, such behaviours could be destructive and costly and could even put the wellbeing of other individuals in the group at risk. Additional keeper time may be required to manage and care for some individuals with cognitive impairments, e.g. where there are difficulties training an animal to move to a specific area of the enclosure to enable cleaning. An inability to socially coexist with other conspecifics could mean complicated housing arrangements, and additional space requirements to avoid conflict. Therefore, when the needs of atypical individuals are understood and being met, there is likely to be less pressure on the workload of caretakers and less financial pressure on the zoo.\n\nResearch involving atypical animals can also contribute to improved wellbeing for the individuals themselves, as taking part in research can be enriching. There can be both cognitive and physical benefits from taking part in research. For example, cognitive enrichment was used for rehabilitating movement in an adult male chimpanzee (Pan troglodytes) called Reo, who experienced acute transverse myelitis at the age of 24 which resulted in impaired walking ability (Sakuraba, Tomonaga and Hayashi, 2016). Reo was provided with a puzzle task linked to a feeder two meters away, designed to encourage Reo to walk between the puzzle and the feeder. This led to an increased total travel distance from 136.7 meters to 506.3 meters within a ten-day period, and an increase in percentage of walking during the study sessions from 1.2% to 27.2%. In addition, research can help to identify the skill levels of an individual, which can lead to the development of targeted interventions (e.g. Ernst et al., 2005) with ongoing benefits beyond the scope of the study. However, determining an appropriate level of challenge depends on the individual abilities of each animal (Meehan and Mench, 2007), which may be particularly difficult to determine for divergent individuals. Therefore, case studies which involve appropriately tailored enrichment devices could be used as an important point of reference.\n\nIn order to address the gap in research on individuals with unique welfare needs, a case study was carried out on an adult male Sumatran orangutan (Pongo abelii), Jiwa, who is cognitively and physically divergent from other orangutans. The aim of this study was to evaluate areas of the Five Domains Model where Jiwa’s differences may be associated with an impact on wellbeing; and to determine an appropriate difficult level of cognitive enrichment for Jiwa, to aid in tailoring future enrichment to his individual needs.\n\n\n2. Methods\n\nThe research subject, Jiwa, was born in Jersey Zoo and at the time of the study had been living there for his whole life. He was housed during the day in a group with another female orangutan and her son, who was his half-brother. There was another enclosure adjacent to Jiwa’s group, which included his father, and another mother-infant dyad. Both groups could see and hear each other. There was no immersive physical contact between the two groups, although limited tactile contact was possible through the metal mesh partition. At the time of the study, a lar gibbon (Hylobates lar) also had regular access to the orangutan enclosures. All orangutans had access to indoor and outdoor areas. Jiwa was fed separately from the other members of his group, in an off-show bed den, which was where the experiment took place, and this is where he was housed overnight.\n\nThere were two main sources of information on Jiwa’s development. The first was his full daily keeper records from 17/10/1999 (his birth) to 07/02/2022, obtained through his specimen report on the Zoological Information Management System (ZIMS). The second was an unpublished internal report that summarised Jiwa’s development during his first year of life. This was written by a keeper, Rupert Beck, on 22/10/2000. These documents were scrutinised for indications of Jiwa’s developmental milestones, which were then compared with expected milestones for wild (van Noordwijk and van Schaik, 2005; van Noordwijk et al., 2009) and/or captive (Lethmate, 1977a, 1977b; Miller and Nadler, 1981; Beck, 2000; Nakamichi, 2004) orangutans. These milestones were: first break in continuous body contact with his mother, first time being carried by an individual other than his mother (captivity only), first time supporting his body weight on the barwork of the enclosure (captivity only), first independent locomotion from his mother, first attempt at nest-building, first locomotion more than 10 metres away from his mother, first attempt at using tools, first attempt at making tools, and being fully weaned.\n\nAlthough wild Sumatran orangutans as young as three may be able to build arboreal nests adequate for a brief rest (van Noordwijk et al., 2009), fully functional nest-building is rarely possible in the zoo environment due to a lack of appropriate base structures and limited nesting materials (Chappell and Thorpe, 2022). Therefore, only the first attempt at ‘practising’ nest building (van Noordwijk et al., 2009), i.e. arranging nesting materials without building an adequate nest for sleeping, was included as a milestone. The milestone for the first attempt at using tools encompasses tools discarded by mother or peers (van Noordwijk and van Schaik, 2005). Milestones which are not normally possible within the zoo context were excluded, e.g. travelling more than 50 meters away from the mother. Milestones based on activity budgets were also excluded, due to lack of comparative data in the keeper reports.\n\nIn addition to developmental milestones, physical measurements of Jiwa’s growth were compared with expected rates for a male Sumatran orangutan. These included body weight in kilograms and age of deciduous (‘baby teeth’) dental emergence (Beck, 2000; Fooden & Izor, 1983). Male orangutans are known to demonstrate distinctive bimaturism, with secondary sexual characteristics developing at very different ages and, in some individuals, taking as long as 30 years to develop (Utami et al., 2002). However, there is very little data available for the weight of unflanged male orangutans, since in captivity males nearly always develop flanges (Pradhan, van Noordwijk and van Schaik, 2012). Therefore, as Bornean and Sumatran orangutans are considered to be approximately the same size (Smith and Jungers, 1997), the comparative data includes a range of different sources, including captive (Fooden and Izor, 1983) and wild-born (Markham and Groves, 1990; Smith and Jungers, 1997) Sumatran orangutans, wild-born Bornean orangutans living in rehabilitation centres with no flanges or developing flanges (Prasetyo, 2019), and unflanged orangutan skeletal data (species unknown) (Kralick et al., 2023).\n\nThe second part of the study took place from 17th January to 5th March 2022 at Jersey Zoo and involved tailoring a cognitive enrichment device to a suitable level for Jiwa. This involved a probe feeder apparatus which had been previously presented to Jiwa’s peers (see Bridgeland-Stephens et al., in preparation). This was constructed from a 50 cm length of 5 cm diameter hollow plastic pipe with a food reward inside (see Figure 1). The food reward was initially peanut butter, but this was changed to porridge from session 3 onwards, as Jiwa’s preferred food type and therefore a greater incentive.\n\nA food reward was inside the tube which could only be reached using a stick.\n\nThe study methods were adapted on a weekly basis according to Jiwa’s success at reaching the food reward, and the contents of each session are shown in Table 1. Each session lasted 30 minutes and was filmed using two ‘APEMAN’ A77 video cameras, one on a tripod and the other clipped to the front of the researcher. In the first session, the tube was suspended from the ceiling using 15 cm lengths of 4 mm nylon cord. The cords were attached 5 cm from each end of the tube using M8 eye bolts that were screwed into pipe clips clamped around the pipe. At the ceiling end, the cord was tied to carabiners, which hung from eye hooks in wooden batons that were fixed to the ceiling outside the enclosure. In the first session, the tube was suspended outside the enclosure, 25 cm away from the wire mesh, so that the food reward could only be reached using a stick. The intention was that, if Jiwa was successful, the apparatus would be gradually increased in difficulty by moving the cords closer together until Jiwa was no longer to access the food reward, which would provide an indication of Jiwa’s skill level. However, as Jiwa did not use a tool to access the food reward when the apparatus was hung outside the enclosure, out of reach of his hands (session one), the difficulty of the enrichment was lowered to a very basic level.\n\nWhen given the tube part of the apparatus loose inside his enclosure, Jiwa obtained the food reward when within reach of his fingers (session two), but not when the peanut butter was out of reach (20 cm from either end of the tube), even while the researcher was conducting a social learning demonstration using a second tube outside the enclosure and vocalising to draw Jiwa’s attention (sessions three and four). The subsequent four sessions (sessions five to eight) were bi-weekly and required Jiwa to remove the stick (already touching the food reward) while the apparatus was being held outside the enclosure by the researcher. As Jiwa did participate in this form of enrichment, the difficulty level was increased in the final session (session nine) by providing Jiwa a stick, to see whether he would insert this into the apparatus himself to obtain the food reward.\n\nThe full details of the social demonstration procedure can be found in Table 2. The first five sessions took place weekly (17th January until 14th February), and the last four sessions took place biweekly (21st February to 5th March). Ethical approval for this research was obtained from the University of Birmingham Animal Welfare and Ethical Review Body (ERN_19-1935) and the Durrell Wildlife Conservation Trust Ethics Committee (ETH21/2019). The dataset for this article is available on an online repository (Bridgeland-Stephens, 2023).\n\n\n3. Results\n\nJiwa was born in 1999 at Jersey Zoo (UK) and was 23 years old at the time of the study. Although the cause of Jiwa’s atypical development is unknown, Beck (2000) considered the possibility that excessive lip and face sucking behaviour from his mother resulted in a lack of sufficient nutrition and oxygen. However, it is also possible that Jiwa was deprived of oxygen prior to birth, e.g. due to complications with the umbilical cord or function of the placenta, and that his mother’s behaviour was in reaction to Jiwa’s lack of response. Although this behaviour was stopped through keeper intervention with negative reinforcement (water jets), for the following five months “Jiwa appeared to be in a semi vegetative state … giving the impression that he was temporarily brain damaged” (Beck, 2000).\n\nFigure 2 shows Jiwa’s growth rate compared with the expected growth rate of male orangutans with flanges, males developing flanges, and unflanged males (Fooden and Izor, 1983; Prasetyo, 2019; Kralick et al., 2023). On average, captive orangutans are 80% heavier than their wild counterparts (Fooden and Izor, 1983). Jiwa’s weight, last measured in 2001 as 36.8 kg, sits just below the expected range for unflanged males, although it should be noted that both his mother and grandmother were smaller than average in size (Beck, 2000; Fooden & Izor, 1983), weighing 42 kg and 40 kg in adulthood respectively (Deputy Head of Mammals at Jersey Zoo, Gordon Hunt, personal communication).\n\nExpected dental emergence rates for orangutans in captivity can be seen in Figure 3, showing that the eruption of Jiwa’s deciduous teeth generally appears to have taken place later than, or at the late end of, expected ranges of dental emergence reported by Beck (2000) and Fooden and Izor (1983). The exception to this is with his upper lateral incisors, which erupted well within the expected age range of 6.5-13 months for male Sumatran orangutans (Fooden and Izor, 1983). It appears that Jiwa’s teeth emerged within a three-month period, contradicting the expected staggered dental emergence (see Figure 3). There was no available data for the eruption of Jiwa’s canines or secondary premolars. There was also insufficient data to compare the eruption of Jiwa’s permanent (adult) teeth with expected emergence rates, although he was observed to have a possible full set of permanent mandible teeth by eight and a half years old (recorded on 07/06/2008 in the keepers’ contemporaneous notes).\n\nIn addition to Jiwa’s small size, his physical abilities were also impaired at some points in his development. Jiwa was described as being noticeably weak from 11 weeks old, with an insufficient grip that necessitated bodily support from his mother; when this did not take place, Jiwa fell on a number of occasions (Beck, 2000). However, at seven months old, a physical examination found that Jiwa “appeared perfectly healthy with normal audio and visual responses, normal heartbeat, good grip/overall strength, and normal blood count and chemistry” (Beck, 2000).\n\nOrangutan infants would normally be expected to explore away from their mothers, but in very close proximity to them, from around six months old (Gordon Hunt, personal communication). However, Jiwa’s first observed independent locomotion occurred at one year old (milestone four). This involved climbing one foot up the barwork, during which the keeper noted that Jiwa was “still quite slow and shaky” (30/10/2000). A few months later, at 15 months, Jiwa was still unable to walk quadrupedally (26/02/2001), although he started crawling across the floor at 21 months “with his hands holding each other, and pushing himself with his back legs” (13/07/2001). Elsewhere, he was described as crawling as if he was “climbing on a flat surface” (05/09/2001). Despite his difficulty with moving across the floor, as well as finding “smooth right-angle ledges” particularly challenging (08/11/2001), Jiwa’s climbing skills improved considerably during this period (14/08/2001; 22/12/2001). At just over two years old, Jiwa was observed standing bipedally for the first time, using a rope to steady himself (17/11/2001). At around two and a half years old, keepers noted a concern with Jiwa not clinging properly ventro-ventrally and was either having to be supported by his mother’s arm, or carried ventro-dorsally, on his mother’s shoulders (18/04/2002). Approaching three years of age, Jiwa was described as being “confident and competent” walking quadrupedally outside, relatively competent walking quadrupedally inside, with his mobility and arm/leg strength having noticeably improved over the preceding few months (04/09/2002). Although Jiwa was at this point capable of walking “more normally” quadrupedally on the indoor floor, he was still often seen “moving along the floor as though he is swimming” (11/04/2003). This was partially attributed to the ‘slippery’ floor surface (i.e. smooth and flat) and was seen to improve when Jiwa was moving through deep litter, giving him more grip and therefore the opportunity to build strength in his legs (15/01/2004). A photo of Jiwa at around this age is shown in Figure 4.\n\nPhoto credit: Gregory Guida, 2004.\n\nBy five years old, Jiwa’s quadrupedal walking and bipedal standing had noticeably improved, and “his overall movement continues to improve gradually” (16/10/2004). However, even today, Jiwa’s style of locomotion is visibly distinctive compared to his peers (personal observation). For example, when walking quadrupedally, Jiwa’s right shoulder is often hunched; he lands heavily on his limbs and walks with his arms out to the side (rather than in front) of his body, possibly for greater stability. In addition, Jiwa generally moves more slowly than his peers.\n\nIn summary, Jiwa is a particularly small orangutan, even for an unflanged male. His deciduous dental emergence generally took place later than expected, with some exceptions, and occurred within a three-month period, rather than the expected staggered dental emergence rates. Early in life, Jiwa was physically weak, with some difficulty locomoting, and his first independent locomotion took place six months later than expected, at one years old. Jiwa experienced considerably difficulty with quadrupedal walking in his early years, and, even now, continues to have a distinctive and slow locomotion style.\n\nThe expected developmental milestones for wild and captive orangutans (where available) are shown in Figure 5. Although Jiwa’s first break in body contact with his mother was observed around the expected time of one to three months (milestone one), he reached the next two milestones somewhat later. Jiwa was not observed being carried by an individual other than his mother (milestone two) until seven months old (31/05/2000), four months later than other infants born at Jersey zoo (Beck, 2000). However, this would not have been possible for the first five months, as Jiwa and his mother were restricted to a separate part of the enclosure for observational purposes, away from the main group (Beck, 2000). As the initial instance of Jiwa breaking body contact was of Jiwa transitioning from his mother to his grandmother, it is not clear whether Jiwa was taken against his mother’s will. However, Beck (2000) indicates that it would not have been surprising for Jiwa to have been given up voluntarily to his grandmother, due to the close familial relationship. Although Jiwa moved from his mother to the barwork in a stationary position (milestone three) at a later point than the expected range of two to four months, at 11 months old (25/09/2000), Jiwa was observed moving independently soon afterwards (30/10/2000), at an early point within the expected range of one to two years. However, Jiwa’s first attempt at nestbuilding (milestone five) was considerably delayed beyond the expected one to two years.\n\nThe first observed instance of Jiwa being more than 10 metres in distance from his mother (milestone six) occurred when a conspecific stole Jiwa and carried him inside while his mother remained outside, presumed to be unaware of the incident (26/03/2002). Jiwa’s first intentional distancing from his mother may take place much later, but is not detailed in the keeper records. The exact time of weaning (milestone seven) is unclear; it is likely to have taken place at some point between four years and nine months (when the keepers become doubtful of Jiwa’s mother’s milk production) (23/07/2004) and the point at which Jiwa’s younger brother was born, at five years seven months (24/05/2005). Not long after this, Jiwa initiated spending the night apart from his mother and seven-week-old brother (milestone eight), by refusing to enter the back den with them (11/07/2005). Approximately one year after Jiwa started sleeping alone, he was observed sleeping at the far end of the outside island, which is as far away as possible in the orangutan enclosure at Jersey Zoo (11/08/2006).\n\nJiwa’s first recorded mating attempt occurred at just over five and a half years old and was with his mother (21/05/2005). Some secondary sexual characteristics started to emerge at just over eight years old, with a small ‘beard’ (03/12/2007). Soon afterwards, keepers started to encourage him to regularly sleep alone as “he is now maturing” (17/03/2008). The next notable change occurred at just over fourteen years old, after a nine-year-old male conspecific, Jaya (born 13/05/04), left the zoo (14/11/2013). Six weeks later, the keepers observed that “Jiwa’s locomotion and co-ordination seem to have improved markedly; he has shown increased facial development: widening of his face, with cheek pads emerging, and his libido (has) rapidly developed” (25/12/2013). Soon after this, Jiwa’s frequent - and sometimes physically rough - sexual attention towards conspecifics became problematic, and he was put on a one-off, six-week course of cyproterone acetate to reduce testosterone levels and manage his libido (04/02/2014). Five months later, Jiwa was castrated (24/07/2014).\n\nIt is not until over four years later, at the age of eighteen, that Jiwa’s repertoire of vocalisations changed to emulate typical mating calls, with one display-like instance of “a deep guttural vocalisation building up higher in short bursts”, and a few months later “almost producing a long call” (17/05/2018; 01/10/2018). Jiwa’s long call seemed to mature over the next year and was “almost a proper call” by 20 years old (18/11/2019). However, despite some development of secondary sexual characteristics, Jiwa was physically very different from his flanged father, Dagu, and had not yet developed full cheek pads or a throat sac (see Figure 6).\n\nPhoto credit: Jersey Zoo.\n\nJiwa’s cognitive differences were apparent from a young age. At nine months old, keepers noted that Jiwa “shows little or no obvious behavioural development. Appears to only react to objects that are within 6 inches of his face, though he appears fine in every other respect” (08/07/2000). 52 days later, Jiwa began interacting with the keeper (29/08/2000) and with other objects, such as a sunflower leaf and stem (11/09/2000), and a piece of bamboo (15/09/2000). However, at one year old, Jiwa was described as being “to all intents and purposes a 3-4 month old infant” (Beck, 2000). When introduced to glass at nearly two and a half years old, Jiwa “(looks) a little confused when touching the glass, trying to work out why he could not touch (the) keeper behind it” (10/02/2002). However, the keeper noted here that Jiwa responded well to his own name at this stage, as well as visual cues. Around this time, Jiwa was observed to be “increasingly playful and confident, especially when not mixed with other orangs” (03/04/2002). Approaching three years old, Jiwa was recognising familiar people, and showing interest and curiosity toward unfamiliar people, demonstrating that he could tell them apart (10/07/2002). After Jiwa’s younger brother was born, the keepers noted difficulty with Jiwa understanding routines without the direction of his mother: “Jiwa does not appreciate the necessity to move to different parts of the enclosure during routines” (25/05/2005). However, Jiwa appeared to settle into a routine fairly easily after this (18/06/2005).\n\nJiwa displayed some possible nest-building behaviour (milestone five) with wood wool and a paper bag in the nest basket at nearly three and a half years old (17/11/2002), well beyond the expected one to two years (see Figure 5). The next mention of nesting behaviour was five years later, at nearly eight and a half years old although, from the casual tone of the keeper’s note (“Jiwa … made his nest in there”), this does not appear to be the first time Jiwa was seen nest-building (21/02/2008).\n\nBy five years old, tool use is not uncommon in orangutans, and is seen at a younger age in both captivity and in the wild (Galdikas, 1982; Miles, 1990; Nakamichi, 2004). Although Jiwa has been seen by keepers to pick up extractive tools dropped by others, he has never been observed to use a tool to dip for food rewards (Gordon Hunt, personal communication). However, there were some instances where Jiwa used simple tools, i.e. knocking down a thermometer using a piece of bamboo at 20 years old (07/04/2020). Later in the same year, it was noted that “Jiwa (was) very alert and interactive with (the) Keeper this morning, more so than Keeper … has ever seen before, his movements were quick, he made eye contact several times” (11/10/2020).\n\nDuring the nine experimental sessions, Jiwa did not use a tool to access the food reward, whether the apparatus was hanging outside the enclosure, being held by the researcher outside the enclosure, or loose inside the enclosure. However, Jiwa did access the food reward by withdrawing sticks that were placed inside the tube by the researcher. In addition, over the four sessions which involved this activity, Jiwa was consistently successful and showed a marked improvement over time in the number of sticks he withdrew per session (see Figure 7). This is despite several occasions when Jiwa because frustrated, evidenced by repeated ‘distress’ vocalisations (Gordon Hunt, personal communication). Jiwa’s performance can be contrasted with the other orangutans at Jersey Zoo, all of whom attempted to use a tool to obtain the food reward when the apparatus was hanging outside the enclosure (Bridgeland-Stephens et al., in preparation). Although Dagu did not obtain the food reward at any point in a five-week period, the females and infants successfully retrieved the food reward in the first session.\n\nSessions 5 to 8 involved Jiwa withdrawing sticks that were already placed inside the apparatus. Note: Session 2 did not involve sticks.\n\n\n4. Discussion\n\nThere are several limitations with the fact that nearly all information regarding Jiwa was obtained from keeper records and a single report made when Jiwa was one years old. The first is that the keeper records compile observations from several different keepers, who may have interpreted Jiwa’s behaviour in different ways over the two-decade time period. The second limitation is that keepers are not able to continually observe the animals in their care, so first observations of a particular behaviour may not reflect the first occurrence of that behaviour. Lastly, as the study was carried out in hindsight, not all developmental milestones have been recorded for Jiwa. For example, although Jiwa’s initial nest-building behaviour was recorded, there is no further mention of his full nest-building behaviour until years later. Despite these limitations, valuable insights can be drawn about Jiwa’s development and ability.\n\nJiwa reached many developmental milestones at an expected rate: the first break in body contact with his mother, first independent locomotion, first instance of being more than 10 metres away from his mother, and the first night spent apart from his mother. Although some of these milestones were not initiated by Jiwa himself, for example being taken by a conspecific and moved 10 metres away from his mother, others were. For example, Jiwa himself initiated spending the night apart from his mother for the first time when his younger brother was seven weeks old. There are other instances where Jiwa exercised agency and independence, for example spending the night at the far end of the outside enclosure when he was approaching seven years old.\n\nHowever, there were also several key differences between Jiwa and other orangutans, particularly in his cognitive development, which appears to have been noticeably slow. Jiwa’s first observed attempt at nest building does not take place until nearly three and a half years old, considerably longer than the expected age of one to two years for both wild and captive Sumatran orangutans (Lethmate, 1977a; van Noordwijk et al., 2009). It was not possible to determine Jiwa’s nest-building ability from the keeper records. Nest building in the wild is more cognitively demanding than in captivity (van Casteren et al., 2012), but even in captive environments great apes can employ varying levels of complexity (Videan, 2006). However, it is likely that Jiwa and his peers would not have had the opportunity to learn more complex nest-building techniques, such as bending and weaving (Videan, 2006), as the main nesting material provided to the orangutans was wood wool. As well as the delay in nest-building behaviours, Jiwa had not yet learned how to use extractive tools, unlike his peers. However, he was observed to use a simple form of tool, i.e. knocking down a thermometer using a bamboo stick at around 20 years old.\n\nJiwa is also physically atypical, with an unusually low weight, generally late deciduous dental eruptions, some difficulty with locomotion, and only ‘half-developed’ secondary sexual characteristics. Thompson et al. (2012) found that male orangutans (Pongo spp.) with noticeable changes in their secondary sexual characteristics before 14 years old had higher levels of testosterone as adults than those who completed their development from 14 onwards. Although Jiwa’s testosterone levels are not specified in the keeper records, Jiwa comfortably fits into the latter category, as his facial structure widened and cheek pads started to emerge a couple of months after his 14th birthday. In addition, within the following year, Jiwa received a six-week course of a testosterone-lowering medication and was subsequently castrated. This is likely to be a contributing factor to Jiwa having not yet developed full flanges at 24 years old, in addition to the presence of his flanged father in the adjacent enclosure. However, although secondary sexual characteristics are also thought to be delayed by the presence of a dominant male (Maggioncalda, 1995), most males in captivity usually do develop these characteristics, even in the presence of another flanged male (Pradhan, van Noordwijk and van Schaik, 2012). Therefore, it seems more likely in this case that the medical interventions had a greater restrictive effect on the development of Jiwa’s secondary sexual characteristics than the presence of his father.\n\nThe physical and cognitive differences seen in Jiwa are reminiscent of a 1982 case study of two Bornean orangutan twins, with the second born infant suspected to have perinatal hypoxia (oxygen deficiency during birth) (Savage and Snowdon, 1982). Both orangutans were tested at around six years of age, with the second born orangutan exhibiting physical and cognitive differences to her brother. Physical differences included less frequent brachiation and more clumsy and uncoordinated locomotion, with an inability to perform fine motor movements (Savage and Snowdon, 1982). Cognitive differences included deficiencies in learning and short-term memory, and an inability to use tools (Savage and Snowdon, 1982). Although Jiwa was not assessed using the same battery of tests as in this study, it is possible that he was similarly deprived of oxygen, either during birth, or due to his mother’s unusual face- and lip-sucking behaviour immediately afterwards.\n\nRegarding the Five Domains Model, it seems likely that Jiwa’s nutritional and environmental needs are largely unaffected by his condition. The keeper records do not mention difficulties with Jiwa’s food or water intake. The only environmental constraint which may have affected Jiwa and his mother was during Jiwa’s first five months of life, when the mother-infant dyad was kept in the back dens for close observation. Although this may not have been ideal, it was a justifiable - and arguably necessary - intervention due to the concerns regarding Jiwa’s survival and wellbeing at the start of his life. As an adult, Jiwa’s wellbeing is affected in the ‘health’ domain, with a particularly low body weight, low levels of strength, and functional impairments in locomotion. Although Jiwa is able to access the same areas in the enclosure as the other orangutans, it would not be surprising if locomotion in general was more physically demanding for him than for his peers. There may also be more complex locomotion behaviours that Jiwa has not been able to acquire. It would be interesting to conduct a study on activity budgets of Jiwa and his peers, to see whether Jiwa spends more time resting than the other orangutans (e.g. Beamish and O’Riain, 2014; Turner et al., 2014) to compensate for his physical impairments.\n\nIt is somewhat difficult to determine how Jiwa’s differences may affect his wellbeing in the fourth domain, which relates to the exercise of agency. Although Jiwa has access to the same enrichment programme as the other orangutans at Jersey Zoo, his impaired cognitive ability means that is not able to use some forms of enrichment which are accessible to his peers, e.g. extractive foraging. This may be detrimental to his ability to express agency and exercise control over the environment. Regarding social interactions, Jiwa generally appears to have a positive relationship with his peers (Gordon Hunt, personal communication). Although Jiwa has had the opportunity to engage in sexual activity, which is a form of agency, his attention towards his peers was so frequent - and sometimes rough - that it was deemed problematic. As a result, Jiwa was given a libedo-reducing medication to resolve this. Although Jiwa’s sexual agency was curbed by this medication, there was a trade-off involved, as this intervention arguably improved the wellbeing of Jiwa’s peers, who were sometimes distressed by his mating attempts.\n\nIt is not possible to know the extent to which Jiwa’s mental state was affected by the limitations in the physical/functional domains of welfare described above. However, there are several areas which have the potential to result in a negative affective state. For example, it is possible that Jiwa’s physical difficulties lead at times to pain, weakness, or physical exhaustion. Regarding limitations to his agency, Jiwa may experience frustration or helplessness, e.g. when faced with cognitive enrichment he is unable to use. It is possible that he has experienced sexual frustration, although this is likely to have been tempered by his medication. However, in general, Jiwa does not appear to be a particularly anxious individual, and seems relatively secure, with positive social relationships and the opportunity to play with younger conspecifics (Gordon Hunt, personal communication). Therefore, despite the potential impairments to Jiwa’s wellbeing, it seems that he is still able to live a fulfilling and well-rounded life.\n\nAlthough Jiwa did not use tools to obtain the food reward within the assessment period, unlike most of his peers, he did show a marked improvement in the number of sticks he withdrew from the apparatus over the four sessions that involved this activity. This improvement occurred despite the frustration Jiwa appeared to exhibit on several occasions. Jiwa’s increased frequency in withdrawing sticks not only indicates continuing engagement in the activity, but also suggests that Jiwa learned how to use this version of the enrichment, evidenced by his increase success at the task over time. These results suggest that the activity was successfully tailored to Jiwa’s abilities, which is an important requirement when providing captive animals with cognitive enrichment (Meehan and Mench, 2007; Clark, 2011). Jiwa’s participation in this activity is connected with a number of areas of wellbeing, but the most relevant is the opportunity to express agency. By exercising control over his environment, despite the challenge and initial stress involved, Jiwa managed to obtain a food reward. Reward is linked to a number of benefits, including enhanced learning, positive affect, and motivation (Berridge and Robinson, 2003). In turn, agency, effective problem-solving, self-motivation, and positive affect are all aspects of psychological resilience, or the ability to ‘bounce back’ from stress (Mandleco and Peery, 2000; Isen, 2001; Rutter, 2012; Hornor, 2017). Therefore, ongoing participation in cognitive enrichment of this kind may have some very real, long-term benefits for Jiwa’s welfare. In future, this device could be adapted by building a permanent tube into the side of Jiwa’s enclosure, where keepers can place food rewards and sticks in advance, so that Jiwa can use the enrichment by himself without being supervised or encouraged.\n\nJiwa’s differences raise a number of considerations for animal management. At the beginning of Jiwa’s life, his behavioural differences and the concerns about his mother’s maternal behaviour raised challenges for the zoo. These included additional keeper time, general psychological stress that may have been experienced by the keepers due to anxiety about Jiwa’s welfare (e.g. Jensvold, 2022; Marino, 2023), and the financial impact of additional medical requirements relating to Jiwa’s care, i.e. the course of medication to limit his libido. Even now, there are some challenges posed by Jiwa’s needs, for example the fact that he is unable to participate in extractive foraging enrichment, which is regularly provided to the orangutans at Jersey Zoo (Gordon Hunt, personal communication). Although this study shows how cognitive enrichment can be tailored to meet Jiwa’s needs, it should be noted that this process took four and a half hours over a period of five weeks; as keeper time is limited, this may not always be logistically possible to achieve. However, despite these challenges, Jiwa’s conditions have been successfully managed by the zoo, to the extent that Jiwa has managed to develop independence, functional social relationships, and is strong and skilled enough to freely move around the enclosure. As well as benefiting Jiwa’s wellbeing, this is logistically beneficial for the zoo, as it reduces the level of resources required to care for Jiwa.\n\n\n5. Conclusion\n\nJiwa is an important reminder of the individuality present in all animals, and the importance of considering diversity in life experience, development, cognitive and physical abilities, and personality. Understanding how to meet the welfare requirements of individuals like Jiwa is a fundamental need for zoos and other caretakers of animals in captivity. Not only can this directly impact the quality of life of atypical individuals, but it can also help to avoid or reduce the potential financial, logistical, and time pressures associated with their care. In addition, understanding the requirements of divergent individuals is essential for contexts where animals may be returned to the wild. For example, orangutan rehabilitation centres must be able to assess whether an individual’s welfare needs will be met through independent life in the wild, or if they are likely to have a better quality of life remaining in captivity.\n\nIt was surprising to learn that Jiwa’s life history had not been academically reviewed until this point, considering his unusual development and behaviour. It is hoped that this case study will not only help other animal caretakers know what to expect during the development of a divergent orangutan, but that it also provides an insight into the potential areas of wellbeing which might be constrained by these differences, requiring additional care and resources. This is exemplified by the fact that it took several hours, over a five-week period, to identify an appropriate difficulty level for Jiwa’s cognitive enrichment device. However, the increase in engagement and ability demonstrated by Jiwa indicates that tailoring enrichment can contribute towards meeting welfare needs within the ‘expression of agency’ domain. Although animal caretakers may not have the capacity to fine-tune enrichment in this way, developing cognitive enrichment with adaptable difficulty levels could be a useful future avenue for research. It would also be beneficial to carry out a follow-up study, to see whether Jiwa has retained the ability to use this form of enrichment.\n\nJiwa has a unique array of physical and cognitive differences, which distinguish his life experiences from those of his peers. Although some of these differences may negatively impact his wellbeing, the vast majority of Jiwa’s welfare needs are met despite these barriers. In addition, the extra time and resources required to take care of Jiwa have gradually decreased as Jiwa has grown older and developed independence. Although every case is likely to be unique, it is hoped that Jiwa can be the start of a database on physically and neurologically diverse individuals. Such a database could be expanded by future researchers, to enhance knowledge in this area and help caretakers know what to expect, so that individuals like Jiwa can live a rewarding and fulfilling life.\n\nThis research took place as part of the normal husbandry schedule for orangutans at Jersey Zoo, and participation in the research was entirely voluntary for the subject animal. One session was terminated when the subject became mildly frustrated after seeing another orangutan eating food within his line of vision. In all subsequent sessions, food was provided to the subject prior to the research taking place to avoid this scenario. All research sessions took place under the supervision of a keeper and would have been terminated if the subject animal had exhibited any signs of stress.",
"appendix": "Data availability\n\nFigshare: Behavioural observations and extracts from daily keeper records for Jiwa case study, https://doi.org/10.6084/m9.figshare.24887088.v1 (Bridgeland-Stephens et al., 2023).\n\nThis dataset comprises two files. The first file is a table of verbatim extracts from the specific keeper records which are mentioned in this article, alongside the dates of each record. The second file comprises continuous behavioural observations from the experimental research sessions.\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 thank Jersey Zoo and the other members of the great ape team for enabling and supporting this research.\n\n\nReferences\n\nAntilla A, et al.: Allie’s story: The road to recovery—a six year history of a neurological disease. 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Publisher Full Text\n\nPrasetyo D: Understanding bimaturism: the influence of social conditions, energy intake, and endocrinological status on flange development in Bornean orangutans (Pongo pygmaeus wurmbii). Rutgers, the State University of New Jersey; 2019.\n\nReynolds V, Reynolds F: Chimpanzees of the Budongo Forest.DeVore I, editor. Primate Behaviour: Field Studies of Monkeys and Apes. New York: Holt Rinehart and Winston; 1965; p. 368.\n\nRusson AE: Orangutan rehabilitation and reintroduction: Successes, failures, and role in conservation.Wich SA, et al., editors. Orangutans: Geographic Variation in Behavioral Ecology and Conservation. Oxford: Oxford University Press; 2008; pp. 327–350. Publisher Full Text\n\nRutter M: Resilience as a dynamic concept. Dev. Psychopathol. 2012; 24(2): 335–344. Publisher Full Text\n\nSakuraba Y, Tomonaga M, Hayashi M: A new method of walking rehabilitation using cognitive tasks in an adult chimpanzee (Pan troglodytes) with a disability: a case study. Primates. 2016; 57(3): 403–412. Springer Tokyo. Publisher Full Text\n\nSavage A, Snowdon CT: Mental retardation and neurological deficits in a twin orangutan. Am. J. Primatol. 1982; 3(1–4): 239–251. PubMed Abstract | Publisher Full Text\n\nSmith RJ, Jungers WL: Body mass in comparative primatology. J. Hum. Evol. 1997; 32(6): 523–559. Publisher Full Text\n\nTaylor S: Animal crips.Jenkins S, Montford KS, Taylor C, editors. Disability and Animality: Crip Perspectives in Critical Animal Studies. Abingdon: Routledge; 2020; pp. 13–34.\n\nThompson ME, Zhou A, Knott CD: Low testosterone correlates with delayed development in male orangutans. PLoS One. 2012; 7(10): 1–7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTurner SE, et al.: Social consequences of disability in a nonhuman primate. J. Hum. Evol. 2014; 68(1): 47–57. Academic Press. PubMed Abstract | Publisher Full Text\n\nUtami SS, et al.: Male bimaturism and reproductive success in Sumatran orang-utans. Behav. Ecol. 2002; 13(5): 643–652. Oxford Academic. Publisher Full Text\n\nVidean EN: Bed-building in captive chimpanzees (Pan troglodytes): the importance of early rearing. Am. J. Phys. Anthropol. 2006; 68(7): 745–751. Publisher Full Text"
}
|
[
{
"id": "256088",
"date": "25 Apr 2024",
"name": "Amy M. Scott",
"expertise": [
"Reviewer Expertise Primate Behavioral Ecology",
"Orangutan Reproduction and Sexual Selection",
"Conservation genetics and 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\nOverall comments to the Authors:\nThis article presents an interesting case study with broad implications for captive-housed orangutans, and more generally, any primate, with atypical cognitive or physical development. I only suggest minor revisions, that I hope will make the manuscript clearer for readers. My suggested revisions relate to the questions “Is the work clearly and accurately presented and does it cite the current literature?’ and ‘Is the case presented with sufficient detail to be useful for teaching or other practitioners?’\n\nSpecific Comments:\nSection 2.1 Would be helpful to specify that it was his paternal half-brother.\nIn terms of housing, based on results it sounds like the housing conditions changed over his lifespan, which is expected, but is confusing as written. Do you mean housing at the time of the cognitive enrichment experiment? I suggest the authors either add a time frame to the housing statement, summarize his housing history, add a table with his housing history, or drop it all together.\nTable 2: Step 4 Protocol: Typo: delete ‘the’ (Once the Jiwa’s…)\nResults: Overall comment: The results should mention the limitations in the keeper data as they relate to milestones and timing.\nSection 3.1 Paragraph 1: First sentence, could be helpful to specify the study by calling it ‘the cognitive enrichment experiment’. I think of the study as the whole study period from birth to present.\n\n-Did Jiwa’s mother do ‘excessive lip and face sucking behavior’ with any other births? While we will never know what cause the apparent lack of oxygen, it would be helpful to know that his mother did or did not do this at other births.\nParagraph 2: Please list expected size range of unflanged males and adult females in captivity to help reader understand how much smaller Jiwa and his mother and grandmother are.\nFigure 2: Why did you choose to exclude Kralick et al. 2023 flanged male body weights and Prasetyo 2019 flanged male body weights? Or are some of the shapes of flanged male data points coded incorrectly?\n\nAlso, can you add a datapoint for the date of Jiwa’s castration? Seems like his growth levels off at this time around this time, at about age 15. Also, do we know that the wild Sumatran males were Pongo abelii and not Pongo tapanuliensis? I am unable to access these citations to check.\nFigs 3 & 5: It would be helpful to add a note about the limitations of this data to the figure legends-that it is keeper data and therefore inconsistent over time. I understand this limitation and I don’t think it makes these data less valuable. But it is helpful to add it to figures, for casual readers who don’t make it all the way to the discussion.\nSection 4.2 paragraph 2: “…Jiwa had not yet learned to use extractive tools, unlike his peers.” It would be helpful to add a time/age qualifier to this sentence.\nSection 4.2 paragraph 3: It is an overstatement to say that he is unusual in his ‘half-developed’ secondary sexual characteristics when this is due castration. Some males never develop flanges and there is wide variation in how long it takes to flange (Dunkel et al. 2013). Testosterone increases during flange development and without functioning testicles, he likely cannot flange. The other case of a castrated male that I have heard of (sanctuary in Florida), also never flanged. Would be helpful to add that some keepers have thought other flanged males delayed development. We have NO DATA to support this. It is anecdotal stories. While there is a place for anecdotes, it needs to be clarified this is anecdotal. Should add this citation to the Maggioncalda citation: Kingsley 1982\nKingsley, S. (1982). Causes of non-breeding and the development of the secondary sexual characteristics in the male orangutan: A hormonal study. In L. E. de Boer (Ed.), The orang utan: its biology and conservation (pp. 215–229). Springer Science & Business Media.\nRefer 1\nSection 4.2 paragraph 4: It would be helpful to add some information about what we know about perinatal hypoxia (oxygen deficiency during birth). Do Jiwa’s physical differences—delays in deciduous dental eruptions and difficulty with locomotion—and cognitive differences—extremely limited tool use—align with the consequences of perinatal hypoxia in humans?\nSection 4.3 Paragraph 1: This is the first mention of low levels of strength in adulthood. The evidence for this statement should be added to the results (Section 3.1).\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? 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\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Partly",
"responses": []
},
{
"id": "261340",
"date": "09 May 2024",
"name": "Karmele Llano Sánchez",
"expertise": [
"Reviewer Expertise Wildlife conservation veterinarian with experience in orangutan medicine and captive care."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 well written, easy to read, clear and interesting paper in an area of captive husbandry and management of non-human primates, and more specifically great apes that is very important and necessary, and I believe this is quite a unique paper too. Increasing the welfare of wild animals in captivity is a serious issue and this paper can contribute to this goal. I congratulate the authors for this original idea for a paper. Well done.\nI have put together a number of comments that hopefully might help to improve the quality of this paper.\nOverall comments:\nIn my opinion, one of the strengths of this paper is the welfare aspect, not only relevant to captive care of orangutans, but more specifically for disabled orangutans as well as any other non-human primates. I believe this paper can be used as a guideline to establish methodologies to assess developmental issues in divergent captive animals. The use of this Methodology and the determination of milestones to assess developmental and cognitive features in orangutans with disabilities is another strong point of this paper, and perhaps this could be emphasized in the conclusion; There seem to be not much reference to Jiwa’s medical status in this paper. Apparently there is only this mention: “However, at seven months old, a physical examination found that Jiwa “appeared perfectly healthy with normal audio and visual responses, normal heartbeat, good grip/overall strength, and normal blood count and chemistry” ”. In the methods there is no mention to Medical records. Were medical records not used in the analysis? it seems to me that medical records (for instance any handling procedure under anesthesia, or any other particular medical intervention) would help to corroborate the more anecdotal information obtained from the caretakers? I assume that Jiwa’s medical records might have been accessible to the authors? There is a mention about Jiwa’s neurological state in 3.1: “Jiwa appeared to be in a semi vegetative state ... giving the impression that he was temporarily brain damaged” There is another mention about Jiwa’s proprioceptive deficit/disfunction:“Jiwa’s style of locomotion is visibly distinctive compared to his peers (personal observation)” I wonder if Jiwa ever had a neurological examination, including a proprioceptive assessment? You mention a couple of times ‘oxygen deprivation’ and more specifically perinatal hypoxia as potentially responsible for Jiwa’s mental disabilities. What made the authors think this could have been resulted from perinatal hypoxia? Was there any ‘medical information’ on Jiwa’s birth that could corroborate or give weight to this hypothesis? And would you perhaps elaborate on any other potential causes? Perinatal hypoxic-ischemic encephalopathy in humans can cause severe and permanent neurological sequelae, including visual motor or visual perceptive dysfunction. I have noticed that Jiwa might suffer from strabismus. It’s not 100% clear as there is no mention on the paper but looking at Jiwa’s picture seems that might be possible. There is at least one mention of strabismus in an orangutan that had suffered cerebral malaria and as result, her vision was completely impaired (Sanchez et al. 2022 (Ref 1)). As mentioned in the previous comment, it seems that physical examination found that Jiwa had normal “audio and visual responses”. But had he experienced a proper ophthalmologic examination? An impaired vision could perhaps explain, at least in part, some of the behaviors described.\nSpecific comments:\nIntroduction: The introduction discusses the care and welfare needs of neurological and physical divergent animals. However, the explanation in 1.2 regarding ‘existing knowledge’ seems to focus only on physically disabled non-human primates. I think it would be interesting to add any reference about cognitive disabilities in NHP’s? You mention one case in the Discussion section (4.2): \"The physical and cognitive differences seen in Jiwa are reminiscent of a 1982 case study of two Bornean orangutan twins, with the second born infant suspected to have perinatal hypoxia (oxygen deficiency during birth) (Savage and Snowdon, 1982)\". It would be interesting to perhaps reference this and other similar cases in this section.\nMethods:\n2.2. in First paragraph, I like that you have selected specific milestones of Jiwa’s development. I don’t know if you took those from any other reference or did you come up with those? I think it’s a brilliant way to add objectivity to the assessment; just wondered whether there is any previous study using those milestones. I only have a problem about the “nest making” milestone which in my view, given the set up and the captivity condition is extremely difficult to assess, especially since orangutans would learn this behavior from their mothers or peers.\nResults:\n3.1. Growth rate and Dental emergence: you mention “physical measurements of Jiwa’s growth were compared with expected rates for a male Sumatran orangutan”): there are many reason why Jiwa might have got a slow growth rate and be of smaller size. You also mention that “both his mother and grandmother were smaller than average in size.” I am not sure that this is necessarily related to a mental disability? do you have any reference in other animals or even possibly in humans that people with mental disabilities (as those caused by perinatal hypoxia) might also have slowed and limited growth? 3.1. “although he was observed to have a possible full set of permanent mandible teeth by eight and a half years old (recorded on 07/06/2008 in the keepers’ contemporaneous notes).“ I very much doubt this can be true. I have never seen an orangutan with an adult set of teeth at that young age. And unless this was observed under anaesthesia or recorded in medical records, I do not think that this would be easy to corroborate?.\n\nDiscussion:\n4.1- 4.2. I think it is good that you explain the limitations of the study due to be based on sporadic and non-systematic descriptions. I think you should add here the fact that the orangutan was castrated “it seems more likely in this case that the medical interventions had a greater restrictive effect on the development of Jiwa’s secondary sexual characteristics than the presence of his father.” Indeed, castration would definitely be a confounding factor in assessing delayed sexual development. I think this has to be clearly stated.\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? Partly\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": "261350",
"date": "25 May 2024",
"name": "Laura M Bernstein-Kurtycz",
"expertise": [
"Reviewer Expertise Primatology",
"animal welfare",
"animal behavior"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article summaries a case study of a male orangutan who presented with physical and cognitive differences when compared to other individuals. This is a useful description of this individual, although it is naturally somewhat limited in scope. I have a couple of minor comments/revisions:\n1. The authors note that \"it would be interesting to conduct a study on activity budgets of Jiwa and his peers, to see whether Jiwa spends more time resting than other orangutans.\" This would be more than interesting, it would be a valuable addition to this paper, which is otherwise short on quantitative data. Would it be possible to do this? Even a broad-scale, short activity budget would be useful, and would allow for comparision with other zoos and other ape species.\n2. Jiwa's mother's \"unusual face- and lip-sucking behavior\" is mentioned a couple of times, as a possible explanation for Jiwa's disabilities. Did she demonstrate this behavior with her other offspring? Has this behavior been seen in other mother-infant dyads? Answers to these questions might help us infer whether or not Jiwa's differences are due to this behavior, or instead, as was also suggested, his mother was using this behavior to try to elicit a response from him.\nOverall, this is a detailed and clear description of one orangutan's development and will be a useful addition to the literature on physically and cognitively divergent nonhuman apes.\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? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-121
|
https://f1000research.com/articles/13-113/v1
|
19 Feb 24
|
{
"type": "Research Article",
"title": "Public Management for Local Development: Perception from the Administrative Area of a Municipality in Peru",
"authors": [
"Rosmery Sabina Pozo Enciso",
"Susana Marleni Atuncar Deza",
"Oscar Arbieto Mamani",
"Miguel Gerardo Mendoza Vargas",
"Hilda Luzmila Felix Pachas",
"Susana Marleni Atuncar Deza",
"Oscar Arbieto Mamani",
"Miguel Gerardo Mendoza Vargas",
"Hilda Luzmila Felix Pachas"
],
"abstract": "Objective To analyze the perception of the administrative department of a municipality regarding public management.\n\nMethod Qualitative approach through interviews. The sample consisted of 30 employees from the administrative department of a municipality in Peru.\n\nResults It was found that the employees seem to have a clear understanding of the applied public management model and the organization of the administrative area. Responses regarding the management of financial, human, and material resources vary in accuracy and detail, suggesting a possible lack of knowledge in some areas. It is important to enhance communication clarity on these topics and provide precise information to ensure effective and transparent management within the municipality.\n\nConclusion Municipality employees demonstrate an understanding of their roles and face challenges in teamwork and bureaucracy. There is some confusion regarding the “New Public Management” and a lack of knowledge in resource management. Improving training, streamlining procedures, and fostering team participation in planning are crucial aspects. Furthermore, implementing periodic assessments is recommended to enhance administrative efficiency.",
"keywords": [
"Public management",
"state entity",
"administration",
"resources."
],
"content": "Introduction\n\nThe term or concept of public management refers to the planning, organization, direction, and control of various activities carried out by the public sector, with the aim of achieving the objectives and goals set by governmental institutions (Cañari & Hancco, 2021). In other words, public management involves efficiently administering public resources, both in decision-making and implementation, with the purpose of enhancing the societal benefits for the entire community (Morveli, 2021).\n\nGiven the above, it can be inferred that poor public management by governmental entities can lead to various problems and challenges that can affect both internal operations of the organizations and the well-being and trust of the general population (Merchán et al., 2022).\n\nGlobally, the advent of COVID-19 in 2020 not only impacted the economic and political landscape of countries but also unveiled significant issues in public management on a global scale. Over the two years since the onset of the coronavirus pandemic, countries have required not only effective preventive measures and treatments but also targeted and efficient public policies to address the public health emergency. The pandemic has posed a threat to existing governance systems, highlighting issues of management, leadership, and the limitations of modern democracy in various parts of the world (Assefa et al., 2022).\n\nWithin this framework, it’s crucial to understand that public management is a significant factor in society. Hence, it’s essential to comprehend how a state institution behaves and how it assembles different strategic elements to tackle challenges posed by both external and internal agents within its jurisdiction (Ramió, 2020). The upper management should implement proper strategic planning to ensure the institution’s competitiveness and adaptability to changes. Sound management ensures the continuity and longevity of institutions. On the contrary, poor management will have negative impacts not only within the institution, affecting employees and resulting in low motivation and performance but also within the society in which the institution operates (Correia et al., 2019).\n\nArévalo and Barbarán (2021) noted that corruption is a significant issue plaguing Peru, stating that it is “one of the main concerns of Peruvians about the performance of both the State and the Government. One option to combat corruption is to foster transparency mechanisms in the administration of public resources. Public officials are called to serve the interests of the Nation and to ensure the proper use of public resources transparently” (p. 5526). While corruption is a major concern in Peru, it’s also apparent that authorities often lack the support of the population. In Chiclayo, for instance, 69% of citizens feel that the authorities of the municipal district of José Leonardo Ortiz (Chiclayo) do not support them, and 84% indicate that they don’t believe the municipality considers the population’s demands. This is a clear example that local authorities are not effectively practicing public management, as reflected in the opinions of the residents (Mallasca et al., 2018).\n\nWhile public opinion is essential, so is the perspective of those working within public institutions. Public employees often find themselves entangled in the problems faced by the entity, due to bureaucratic obstacles and the complexity of administrative procedures within municipal areas. This often leads to inefficiencies in public management models, administrative processes, and procedures, or lack of planning that result in delays or hindrances to local development. Therefore, this research aims to understand how public management is conducted within a municipality from the viewpoint and perception of administrative staff.\n\n\nMethods\n\nThe research will employ a group interview approach with a qualitative focus (Hernández-Sampieri et al., 2018). The research design will be phenomenological and descriptive. This is because the researcher will use interviews to collect information regarding experiences and opinions of the sample, which could be diverse or common (Hernández-Sampieri et al., 2018).\n\nThe population will consist of 100 employees from the administrative area of a municipality in Peru (Ñaupas et al., 2018). The sample will comprise 30 administrative staff members from a municipality. The specific job titles held within the institution will not be considered; the criterion is that they occupy purely administrative roles within the study site.\n\nThe chosen sample size is based on the nature of the study, which aligns with qualitative research principles. “Sample sizes for qualitative studies, such as grounded theory, interview studies, or observations of people, suggest a sample size of 20 to 30 cases to study” (Hernández-Sampieri & Mendoza, 2018, p. 428).\n\nIt’s important to note that qualitative studies, such as interviews or observations, do not seek to generalize results. The researcher’s focus in such studies is on the depth of the topic. Selecting the sample to study involves considering three factors: the researcher’s operational capacity, the unit of analysis’s knowledge of the phenomenon under study, and the time available for data collection. Furthermore, the sample will be composed of “typical cases,” aiming for rich, in-depth, and high-quality information, without emphasizing quantity or standardization (Hernández-Sampieri & Mendoza, 2018).\n\nConsidering the above, no specific sampling method will be used.\n\nThe technique employed was the interview, and the instrument used was an “interview guide.” This guide was applied between the months of May and June 2023. Participants were previously notified by e-mail. A recording was made of the responses obtained from the interview in order to be able to analyse the responses in depth.\n\nThe researcher respected all aspects related to copyright while conducting the research. Each participant was adequately informed about the research, and their participation was completely voluntary and willing. Anonymity of the interviewees was maintained, and the confidentiality of obtained data was upheld. No modifications were made to the collected responses.\n\nThe research was approved by document CO-001-06-2023/CE issued by the ethics committee of the Universidad Autonoma de Ica.\n\nThe confidentiality and privacy of participants has been ensured in accordance with the ethical principles of confidentiality, respect and transparency. Measures were taken to preserve the identity of the interviewees by means of pseudonyms or codes for anonymity in the results. Participation was voluntary, with written informed consent, detailing objectives and possible implications. A relationship of respect and empathy was maintained, creating an environment of trust for the free expression of experiences. Participants were free to withdraw at any time without adverse consequences.\n\n\nResults\n\nRegarding gender, most individuals within the sample were women, accounting for 71.4% of the participants in the study, while men constituted 28.6%. In terms of age distribution, 33% fell within the 20-25 age range, 37% were aged 26-35, and 30% fell between the ages of 36 and 55.\n\nMoving on to the dimension of administrative workers’ backgrounds, it was observed that most participants were aware of their roles within the municipality. Roles mentioned included administration, administrative assistants, handling paperwork, engineering/technical roles, human resources, and specific responsibilities such as being a manager, tax area supervisor, warehouse manager, logistics coordinator, cashier, among others. Regarding their tenure in these roles, it was found that some had been in their positions for less than six months, others for around 6 months to a year, and some had experience ranging from 2 to 8 years. Some participants mentioned lacking experience or having worked in different fields unrelated to public management. The shortest work experience period mentioned was “3 months,” cited by one participant, while the longest was 8 years.\n\nWhen it comes to the challenges perceived by workers within the municipality, teamwork was a prominent concern. Some considered managing a large team to be the primary challenge, which could complicate internal coordination and communication. Therefore, they felt compelled to apply effective strategies to ensure efficient and smooth management. Another challenge identified was project process control and monitoring, which are crucial elements of public management. Participants indicated that inadequate supervision could impact the achievement of objectives. Excessive bureaucratic procedures and lengthy administrative timelines were also mentioned as daily challenges hindering efficiency among departments and the management of public resources. This often resulted in delays in response times between departments and to the public. Lack of training in certain areas, such as logistics, was recognized as a challenge for employee development and effective job performance. This issue stemmed from the designation of unqualified personnel for certain roles, leading to performance and efficiency problems in the administrative area.\n\nIn terms of the public management model indicator, a considerable number of responses mentioned that the municipality adhered to the “New Public Management” approach as the model for promoting local development. However, some indicated that the “New Public Management” was being implemented based on results. Others perceived a more traditional management approach. There seems to be some confusion and lack of clarity regarding the exact model being implemented by the municipality. Nevertheless, a general sense of ongoing development and implementation of public management was apparent.\n\nRegarding their understanding of the hierarchical organization of both their department and the municipality, responses indicated a clear consensus that the highest authority was the mayor, alongside the overseeing managers. The hierarchical structure mentioned in the responses ranged from the mayor and municipal council as the highest authorities, followed by managers and department heads in various areas. When asked about the management of financial, human, and material resources within the administrative area, responses varied, suggesting a lack of understanding in this regard. Inconsistent and unclear responses indicated a possible lack of information or comprehension regarding resource management within the administrative area of the municipality.\n\nConcerning the administrative processes and procedures indicator, responses regarding “Key Administrative Processes and Procedures” showed significant differences. Many considered process supervision and control as key points, along with training and delegation of tasks. However, some responses indicated that a key process for improving municipality management could be the reduction of bureaucracy and streamlining of documentation. These management processes could enhance institution functionality. To improve process efficiency, many emphasized the importance of continuous employee training, which would enable the utilization of various technologies and platforms to streamline municipality management.\n\nWhen asked about measures taken to ensure efficiency and transparency in resource management, a wide range of approaches were mentioned. Some highlighted the importance of project planning and periodic evaluation, while others emphasized the need for consensus-based and responsible decision-making. Citizen participation was also mentioned as a means of ensuring transparency in management.\n\nRegarding the planning and sustainability indicator, opinions regarding the preparation and execution of strategic plans and development within the municipality highlighted the formulation of short- and long-term plans and goals with execution timelines. Inclusion of the entire team in the planning process was considered vital for clarity and focus during execution. For ensuring project and program sustainability, continuous supervision and monitoring were deemed crucial to ensure proper infrastructure utilization. Being adequately prepared and trained to maintain programs and projects over time was also emphasized.\n\nWhen questioned about potential actions for implementing improvements and optimizing administrative processes, responses mentioned identifying areas for improvement, setting objectives, planning, and continuous monitoring. The significance of personnel training and continuous process review was highlighted. Some mentioned the implementation of internal directives and coordination among management areas.\n\nFinally, in terms of evaluation and continuous improvement, performance and results within the administrative area were measured using internal indicators and tracking, as well as results-based evaluations. Internal surveys and evaluations conducted periodically were also emphasized. Some mentioned that they had not undergone performance evaluations during their time at the municipality but considered it necessary for improving processes through feedback. Potential actions for implementing improvements and optimizing administrative processes included identifying areas for enhancement, formulating objectives, and continuous planning and monitoring. Training staff and ongoing process review were also highlighted. Key indicators for measuring the success and efficiency of the administrative area included resource utilization, service quality, and the final outcomes of both short- and long-term plans.\n\n\nDiscussion\n\nIn relation to the indicator of administrative worker backgrounds, the personnel conveyed that they are aware of and understand their roles within the municipality. They also mentioned the challenges they perceive within the municipality and each specific work area. This is significant as some participants mentioned that this is their first experience in public sector management. Despite the lack of experience in some cases, having a clear understanding of their tasks and responsibilities indicates that topics like control and supervision are emphasized within the institution. Nonetheless, it’s important to note that this is not always the case, as demonstrated by Luna’s study (2021) which found that “most of the workers’ responses were questions, stemming from lack of knowledge and task/function discoordination due to absence of leadership from superiors.”\n\nRegarding the administrative processes and procedures indicator, responses varied. Workers indicated that key points followed by the municipality include planning, periodic project evaluations, and process control. They suggested consensus-based decision-making and citizen participation to ensure transparency and efficiency. These highlighted points and recommendations, from the workers’ perspective, contribute to appropriate and correct public management within the locality. Poor management can result in what Luna (2021) concluded: “there was a level of management with deficiencies due to lack of planning, direction, and strategies, resulting in failure to achieve planned objectives.”\n\nIn relation to planning and sustainability, it was evident that workers consider it crucial to include the entire team in the development and execution of strategic and development plans within the municipality. Continuous supervision is also considered a measure to ensure project and program sustainability. Similar findings were reported by Auccatinco and Auccatinco (2021), whose study revealed that all municipal workers in their research agreed that proper internal control and accountability positively affect development not only within the municipality but also in ongoing and upcoming projects.\n\nIn terms of the evaluation and continuous improvement indicator, workers indicated that the administrative area is measured using internal indicators and tracking, as well as through surveys and periodic evaluations. Key indicators of success and efficiency in the administrative area include resource utilization, service quality, and the final outcomes of both short- and long-term plans. These are important points that must be managed within any government institution. This aligns with the findings of Bautista and Delgado (2020), whose study evidenced challenges faced by administrative staff in a municipality during the COVID-19 pandemic. They reported issues such as a lack of activity planning, lengthy administrative processes, bureaucratic obstacles, and deficient communication among departments.\n\nIn summary, the perceived model of public management among the workers is mainly aligned with the “New Public Management” approach. While responses reflect a mix of understanding and lack of knowledge on some topics, some workers seem to have a clear grasp of the applied public management model and the organization of the administrative area. Although certain areas (such as the management of financial, human, and material resources) reveal confusion or a lack of information, the overall perception of workers appears positive. However, they also acknowledge areas that need improvement to optimize management and contribute to local development. These findings are consistent with Vega’s study (2019), which provided insight into the perception of management within a municipality and revealed that 94% of respondents considered the municipality’s management effective.\n\n\nConclusion\n\nIn conclusion, the majority demonstrated an understanding of their roles within the municipality, encompassing various functions and specific responsibilities. Furthermore, a variety of work experiences in terms of tenure in positions were evident. The primary challenges identified by the workers in the municipality revolved around teamwork, process control, bureaucracy, extended administrative timelines, and a lack of training in certain areas.\n\nWhile the perception that the municipality operates under the “New Public Management” prevails, certain confusions and lack of knowledge about the exact model were also observed. Regarding the management of financial, human, and material resources, a widespread lack of understanding was detected in the responses, suggesting the need to enhance transparency and clarity in this aspect. In the realm of administrative processes and procedures, diverse opinions on key points to improve municipal management were found, with a focus on the importance of continuous training and streamlining documentation. Concerning planning and sustainability, the necessity of involving the entire team in the development and execution of strategic plans was emphasized, as was the importance of constant oversight to ensure project sustainability.\n\nFinally, in the indicator of evaluation and continuous improvement, the need for implementing periodic performance assessments to provide feedback and enhance administrative processes was identified.\n\n\nAuthor roles\n\nRosmery Sabina Pozo Enciso: Conceptualization, Formal Analysis, Investigation, Methodology, Supervision, Visualization and Writing – original draft\n\nSusana Marleni Atuncar Deza: Methodology, Visualization, Formal Analysis and Writing – original draft preparation\n\nOscar Arbieto Mamani: Resources, Validation and Writing – Review & Editing\n\nMiguel Gerardo Mendoza Vargas: Formal analysis, Visualization and Writing – Review & Editing\n\nHilda Luzmila Felix Pachas: Formal analysis, Visualization and Writing – Review & Editing",
"appendix": "Data availability\n\nZenodo. Public Management for Local Development: Perception from the Administrative Area of a Municipality in Peru. https://doi.org/10.5281/zenodo.10511055.\n\nData are available under the terms of the Creative Commons Zero v1.0 Universal (CC0 License).\n\n\nAcknowledgments\n\nWe would like to thank the municipality studied for providing all the facilities to be able to carry out the study without any problems, and also to thank the workers who participated in the interview.\n\n\nReferences\n\nArévalo R, Barbarán H: La transparencia en la administración de los recursos públicos. Ciencia Latina Revista Científica Multidisciplinar. 2021; 5(4): 5526–5539. Publisher Full Text\n\nAssefa Y, Woldeyohannes S, Cullerton K, et al.: Attributes of national governance for an effective response to public health emergencies: Lessons from the response to the COVID-19 pandemic. Journal of Global Health 2022; 12: 05021. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAuccatinco S, Auccatinco C: Percepción del control interno y gestión de tesorería en la Municipalidad Distrital de Rondocan, Cusco, 2021. [Tesis de Licenciatura, Universidad Cesar Vallejo].2021.\n\nBautista J, Delgado J: Evaluación de la gestión administrativa para mejorar el desempeño laboral en la gestión municipal. Ciencia Latina Revista Científica Multidisciplinar. 2020; 4(2): 1737–1753.\n\nCañari C, Hancco P: Influencia de la gestión por resultados en la efectividad de las políticas de reforma y modernización del Estado. Polo de conocimiento. 2021; 54(6): 744–763. Reference Source\n\nCorreia P, Mendes I, Freire A: La importancia de los valores organizacionales en la Administración Pública: un estudio de caso basado en la percepción de los trabajadores de una institución de educación superior. Revista del CLAD Reforma y Democracia. 2019; 73: 227–258.\n\nHernández-Sampieri R, Fernández Collado C, Baptista Lucio P: Metodología de la investigación. McGraw-Hill Interamericana; 2018. Publisher Full Text\n\nHernández-Sampieri R, Mendoza C: Metodología de la investigación. Las rutas cuantitativa, cualitativa y mixta. Grupo editorial Mc Graw Hill Education; 2018.\n\nLuna V: Gestión administrativa y liderazgo asertivo en la Municipalidad Provincial de Chiclayo. [Tesis de Maestría, Universidad Cesar Vallejo].2021.\n\nMallasca E, Bautista E, Ruelas J: Gestión pública, y gobernabilidad democrática, en la municipalidad distrital de José Leonardo Ortiz, Chiclayo. Revista Gobierno y Gestión Pública. 2018; 5(2): 32–50. Publisher Full Text Reference Source\n\nMerchán N, Pinargote N, Acebo R: La gestión pública como factor clave en el desarrollo factible de la gobernanza. Revista Científica FIPCAEC. 2022; 7(1): 751–774. Reference Source\n\nMorveli G: Enfoques de la Gestión pública y su influencia en el gobierno peruano 1990 al 2020. Ciencia Latina Revista Científica Multidisciplinar. 2021; 5(3): 3496–3512. Publisher Full Text\n\nÑaupas H, Valdivia M, Palacios J, et al.: Metodología de la investigación cuantitativa – cualitativa y redacción de tesis. Ediciones de la U.2018.\n\nRamió C: Coronavirus, modelos de Estado, toma de decisiones y la transformación de la gestión pública. GIGAPP Estudios Working Papers. 2020; 7(182-189): 489–512. Reference Source\n\nVega F: Gestión administrativa Municipal de Puente Piedra, según percepción de los trabajadores de la Gerencia de Inversiones Públicas, Lima-2018. [Tesis de Maestría, Universidad Cesar Vallejo].2019."
}
|
[
{
"id": "267976",
"date": "30 Apr 2024",
"name": "Kuno Schedler",
"expertise": [
"Reviewer Expertise Public Management"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe general topic is topical and important, and it justifies a study on this scale. It is right that the authors use a qualitative method, as they give relatively high weight to the \"how\" and \"why\". Overall, I find the focus on Peru particularly interesting, as we in the English-speaking world know too little about public management in the LATAM countries.\nI would like to add a few points that could make the paper a little stronger overall:\n- I miss a focused research question. As it stands, the paper describes the respondents' answers, but it lacks an actual and in-depth analysis in relation to one (!) clear and focused question. For example, what does it mean when respondents see a number of challenges? What is the effect on services? Or for the acceptance by the population mentioned in the introduction?\n- In the description of the method, it would be important to know how the interviews were analyzed. Which coding method was used? With what results? I recommend using a paper that has been successfully published in a journal and contains qualitative evaluations as a guide. There are usually also good visualizations (e.g. with 1st and 2nd order analyses).\n- The discussion section should contain less of a summary of the results and more of a classification of your own findings in the context of existing knowledge. Which statements in the literature can be confirmed? Which ones need to be questioned? Where do the authors have new findings that cannot be found in the literature?\nOverall, I think that the paper can benefit if the focus is even narrower and if there is a concrete statement at the end. \"So what?\" - what do we learn from the analysis of the interviews? Beyond the descriptive, the analytical should be strengthened so that perhaps one or two surprising points come to light.\nI encourage the authors to continue working with this valuable and rich empirical material. We would like to see it published! The paper still needs some work, but it has the potential to be really exciting.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "263191",
"date": "23 May 2024",
"name": "Juliana Abagsonema Abane",
"expertise": [
"Reviewer Expertise Research methodology",
"espcially",
"qualitative analysis. Also",
"my areas of research and expertise include public management and local government."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nREVIEW REPORT: PUBLIC MANAGEMENT FOR LOCAL DEVELOPMENT The research topic is suitable for the study. The study employed a qualitative approach with interviews as stated in the methodology, and the sample size used was appropriate. However, the introduction of the paper needs improvement. The information provided on the topic is too scanty. The concept of “public management” has not been well explored in this study. Also, the right literature was not consulted to identify the theoretical and empirical debates on public management and local development to which the authors seek to contribute or provide the missing link. As a result, the paper lacks a clearly defined research puzzle/problem statement. The study lacks a theoretical and empirical literature review. A section should be created for the review of existing relevant empirical literature on the topic to support the study. The review should be extant and of current literature focusing on different dimensions of public management and local development to provide a better understanding of public management. In the same way, an appropriate theory should be adopted to guide and ground this study. Again, the methodology of the study fails to elaborate on exactly how the data collected using interviews were analyzed. The authors should provide a detailed account of how responses from the interview were analyzed. How were the interviews coded, and what qualitative data analysis method was employed? The discussion section needs improvement. The findings of the study should be well discussed with the outcomes of earlier studies on the topic to identify where the findings of the current study confirm already existing literature or run contrary to the claims of earlier scholarship on the topic under investigation. Finally, the conclusion provides a snapshot of the key findings of the study. Nevertheless, it is important to relate these findings to the possible implications. What is the implication of these observations on policy and practice in public management? What is the implication for future research on the topic?\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "248960",
"date": "29 May 2024",
"name": "Ambrocio Teodoro Esteves Pairazamán",
"expertise": [
"Reviewer Expertise Master's degree in Research and Teaching",
"doctorate in Educational Administration",
"and Bachelor of Science in 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 manuscript explores municipal public management in Peru from the perspective of administrative staff, analyzing topics such as strategic planning, daily challenges, and the adoption of public management models. Based on surveys and qualitative analysis, it offers a detailed view of internal practices and critical areas for efficient and transparent local development.\nThis article is highly relevant as it provides an insider’s perspective on public management in a Peruvian municipal context, identifying challenges and opportunities to improve administrative efficiency and transparency. It is particularly valuable for academics and professionals interested in public administration and local development.\nAs a final recommendation, I would suggest that the institution implement periodic performance evaluations to provide feedback and improve administrative processes.\nI will keep an eye out for any new developments and their potential publication soon.\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/13-113
|
https://f1000research.com/articles/11-1299/v1
|
14 Nov 22
|
{
"type": "Research Article",
"title": "Perioperative care to patients living with HIV by theatre nurses at a South African tertiary hospital",
"authors": [
"Rudzani Ifodia Ngaledzani",
"Avhatakali Allga Ndou-Mammbona",
"Azwihangwisi Helen Mavhandu-Mudzusi",
"Rudzani Ifodia Ngaledzani",
"Avhatakali Allga Ndou-Mammbona"
],
"abstract": "Background: Human Immunodeficiency Virus (HIV) is one of the leading health challenges worldwide that influences the provision of quality patient care. Stigma and discrimination around this condition and the health care needs affect the health care provision. This study aimed to gain an in-depth understanding of theatre nurses’ experiences in providing perioperative to patients living with HIV at a tertiary hospital in South Africa. Methods: This study was conducted at a tertiary hospital in Tshwane district, South Africa. The study was underpinned by an interpretative phenomenological analysis design. Data were collected from 10 criterion purposively selected theatre nurses using in-depth individual interviews. Data were thematically analyzed and guided by an interpretive phenomenological analysis framework for data analysis. Results: The study revealed that theatre nurses work in an under-resourced environment. The resources highlighted are human, materials, including personal protective equipment and life support. The situation negatively affects the perioperative care of HIV-positive patients, who are always prone to perioperative complications, such as profuse bleeding, and even death. The situation increases the occupational risk to the nurses. Conclusions: The researchers proposed several recommendations targeted at improving the resources needed by theatre nurses when caring for people living with HIV perioperatively at South African tertiary hospitals. Findings will add to the body of knowledge of the Nursing profession about offering perioperative care to persons living with HIV.",
"keywords": [
"Experiences",
"interpretative phenomenological analysis",
"perioperative",
"tertiary hospital",
"theatre nurses"
],
"content": "Introduction\n\nThe rate of Human Immunodeficiency Virus (HIV) infections has increased globally since its discovery in 1980.1 According to Joint United Programme on HIV/AIDS (UNAIDS)2 report, people living with HIV were at 37.2 million globally in 2021. Sub-Saharan Africa takes the lead when it comes to the number of people living with HIV at 71%, with South Africa contributing to the high number of people living with HIV at 8.2 million in 2021 with a prevalence rate of 13.7% in 2021.2 There are several strategies to prevent and reduce the incidence and spread of HIV. The strategies include free condoms supply, Antiretroviral Treatment (ART) rollout, Prevention of Mother to Child Transmission and the UNAIDS 90.90.90. targets, which have ended in 2020, all introduce to curb and manage HIV/AIDS infections.3,4 The 90.90.90 program aimed to achieve the following: 90% of citizens know their HIV status, 90% of those to be on ART and 90% to have their viral load suppressed by the year 2020 globally.3 South Africa has not achieved the above target due to people’s reluctance to take ART as they are afraid of being stigmatized by health care workers.5,6\n\nPeople living with HIV shared different views regarding the attitudes and behaviors displayed by health care workers routine reviews and treatment collection. The above attitudes and behavior are related to wearing double or triple gloves, and extra protective gowns when performing surgical/medical procedures, and refusal to perform some medical/surgical procedures on people living with HIV.7 Factors leading to these stigmatizing behaviors and attitudes among health care workers are complex as they emanate from individual, hospital and politics.8,9\n\nReligious beliefs, the age, and gender of the health care workers are the main individual causes leading to stigmatization of people living with HIV. Bureaucracies and hospital policies also have an influence on the management of people living with HIV.9 Hospital policies and bureaucracies are the leading factors in stigmatization. Some authors,9 reported that health care workers turned away patients living with HIV citing that the hospital concerned is not designated for people living with HIV and AIDS. A lack of availability of Post Exposure Prophylaxis (PEP) in the hospitals make some health care workers reluctant to render care to patients living with HIV.10\n\nReluctancy to care for patients living with HIV and lack of knowledge about PEP by some of the health care workers also contribute rendering of substandard care as some patients are turned away even in hospitals where PEP is available.11 Some healthcare workers’ attitudes towards patients living with HIV are based on a limited understanding of the risk related to their specialization and cultural setting.9,12,13 Therefore, the aim of this study was to gain an in-depth understanding of the provision of perioperative care by theatre nurses to patients living with HIV at a tertiary hospital in South Africa.\n\n\nMethods\n\nThe qualitative research approach was used as the researchers wanted to have an in-depth empirical understanding of a phenomenon in its natural setting.14 The researchers used this approach because they wanted to understand the provision of perioperative care rendered to patients living with HIV by theatre nurses to patients living with HIV at a tertiary hospital in South Africa. Interpretative phenomenological analysis design was used in the study. Interpretative phenomenological analysis is a research design used to explore in detail how participants are making sense of their personal and social world.14–16\n\nThe Department of Health Studies, REC-012714-039 (NHERC), and the Research Ethics Committee of the University of South Africa granted the researchers ethical clearance for the study (Ethics Clearance Number HSHDC/987/2020) on 5 June 2020. Permission was also obtained from the Gauteng Department of Health and, the Chief Executive Officer of Kalafong provincial tertiary hospital where interviews were conducted. The researchers also obtained written voluntary informed consent from all participants in the study. Throughout the study, ethical principles were observed by using pseudonyms to ensure confidentiality, respect, privacy, and protection of the participant, researchers, and institutions. The researchers only documented information for which permission was given by each participant.\n\nThis study was conducted in one of the tertiary hospitals in the Tshwane district, which has 12 operating theatres with different areas of specialization. There is one Endoscopy unit, which is situated in the Out Patients Department (OPD), two Obstetrics theatres that are allocated in the Maternity section, Future Laparoscopy theatre, two Orthopedic theatres, Clean emergency theatres, Urology theatre, Ear, Nose and Throat (ENT) theatre, Ophthalmology theatre, Septic emergency theatre, Neurology theatre, Pediatric theatre, and a General surgery theatre.\n\nThe population of this study was all the theatre nurses of a tertiary hospital in the Tshwane district who meet the inclusion criteria and voluntarily agreed to participate. To recruit the participants, the first author presented the study to all theatre nurses who were on duty during different shifts. The potential participants were given information leaflets with all the relevant information regarding the study and the cell numbers of the research team. Those who were interested to participate in the study contacted the researcher using WhatsApp messages or using a ‘call back’ request. The researcher made a follow-up call to further discuss the study.\n\nThe sample size for this study was 10 purposively selected theatre nurses who met the following inclusion criteria: being a theatre nurse; two years of experience working in the theatre; aged 25 to 65 years of age. Only theater nurses who agreed and offered voluntary consent participated in the study. The sample size was determined by data saturation.17 Data saturation is the point where no new information is emerging during the data collection process and analysis, which in most the qualitative studies occurs iteratively.18\n\nThis section provides information concerning the demography of the study participants, which are displayed in Table 1. The information included are participants’ age, sex, years of experience, and qualifications. Demographic data are included to assist the reader in understanding the source of data.\n\nTo cover the list of questions in an interview guide, the researcher used in-depth semi-structured interviews. The interview guide was written in English as it is the medium of communication that all theatre nurses understand well. Piloting was done by interviewing one theatre nurse who was not part of the study. The pilot interview lasted for only 10 minutes and was audio-recorded. The research team listened to the audio recording and discussed the questions where the corresponding author, who was the study supervisor, analyzed the question asked and the response. She highlighting that some of the probes were closed-ended and leading. The corresponding author also highlighted that probing was inadequate as most of the participants’ responses seemed to be ambiguous or incomplete sentences, but no further questions were asking for further clarification. She further demonstrated how IPA interviews are conducted through interviewing the second author. The first author was then requested to conduct a second interview, which on review was considered appropriately done. A permission was granted to the first author to continue with data collection. The interview guide can be found as Extended data.35\n\nSeven participants were interviewed at the hospital premises in the theater seminar room, two in their homes and one at the restaurant of choice. To ensure privacy in the seminar room, a notice was written on the door stating ‘meeting in progress’ to avoid disturbance. For those who preferred the restaurants, we used private tables where there were minimum disturbances. Each interview was initiated by a general conversation focusing on biographical data such as age, marital status, qualification, and experience in theatre. This was followed by the following question: “kindly share with me your experiences of perioperative care to patients living with HIV”. Pre-set questions were used in case where the response to the initial question did not cover them. Probes and follow-up questions were guided by the participants’ responses. The recording was done using an audio digital smartphone of high quality. Each interview lasted for 30–45 minutes. The interview was transcribed verbatim within 24 hours. The original recordings were transferred to a memory stick and deleted from the phone. To ensure confidentiality, the memory stick is kept under a locked cupboard together with the transcripts. These documents will be destroyed after five years. After participant number seven, data saturation was reached, but the researcher continued to interview three more participants searching if there would be new information given. Some scholars19 believe that data saturation is commonly referred to as a point where collected data or analyzed yields no further new information and further data collection is no longer necessary. Field notes were also taken concurrently with the interviews. All COVID-19 protocols were observed through sitting 1.5 meters away from the participant, sanitizing hands and surfaces, wearing masks, and ensuring proper ventilation. The interviews were done from May 2021 to June 2021.\n\nThe data were manually analyzed iteratively with data collection guided by an IPA framework for data analysis. The framework was considered most suitable as the researchers’ focus was not only to analyze, but also to interpret the findings by focusing on how participants interpret their own experiences.20 The following seven steps were followed:\n\nRead and re-reading: In the first step, the researchers repeatedly listens to the recorded interviews, read and re-read the transcripts to have an in-depth understanding. By so doing the researchers were able to correct mistakes that occurred during the verbatim transcribing of participants’ interviews.\n\nInitial noting: In this second step the researchers searched for similarities in each participant’s transcripts and noted them.\n\nDeveloping emergent themes: The researchers grouped the notes into categories of themes.\n\nSearching for connections across emergent themes: The researchers merged similar categories, to develop super-ordinate themes, themes, and sub-themes.\n\nMoving to the next case: After searching for connections across the emergent themes, the researchers summarized the emergent themes. Rechecking all the themes considerately to find out if there are no new emerging themes.\n\nLooking for patterns across cases: The researchers discussed their individual themes and further compressed the themes into smaller themes after checking for patterns in the themes and renamed them.\n\nTaking interpretations to deeper levels: This is the seventh and last step; the researchers used current ideas to contextualize the final themes that emerged from the process. Three super-ordinate themes with themes and sub-themes emerged from data analysis: human resources, material resources, and infrastructural resources.\n\nTo ensure rigor for the study, Guba and Lincoln’s (1994) framework for ensuring trustworthiness was followed. Guba and Lincoln’s criteria of ensuring trustworthiness included credibility, confirmability, dependability and transferability.21 The researchers used the interview guide and audio recorded the interviews, which were transcribed verbatim to ensure credibility. To ensure transferability, the researcher appropriately described the study design, setting, population, sampling, sample, the study’s key informants, data collection, and analysis process to ensure transferability and dependability. To avoid presenting the individual researcher’s biases or perspectives, all the researchers independently analyzed data, came up with a table of themes, and later compared and discussed their themes until they constructed a single master table of themes to ensure confirmability.\n\nAll the researchers are nurses by profession though authors number two and three are now working in the Institution of Higher Education. The first author, who also collected data is a theatre trained nurse who is also a manager of the theatre. Her experience and her position as a manager might have affected how she collected data. However, this was curbed through first piloting data collection and refining how questions should be asked. Moreover, the interviews were audio recorded, transcribed verbatim in preparation of analysis by all researchers who also listened to the audio recordings.\n\n\nResults\n\nThe themes that emerged from data analysis are presented in Table 2. This section provides a summary of the results provided based on super-ordinate themes, themes, and sub-themes that emerged from data analysis. Three superordinate themes emerged from data analysis, which included: human resources, material resources, and infrastructural resources.\n\nThis superordinate theme focuses on challenges experienced by the theatre nurses regarding resources while rendering perioperative care in one of the tertiary hospitals in the Tshwane District. It is composed of the following themes: nursing staff and other members of the support team.\n\nNursing staff\n\nHuman resources in terms of nursing staff and consultants were found to be the most challenging when providing care during the perioperative period to a patient living with HIV by theatre nurses. The theme comprises the following subthemes: shortage of nurses during all shifts and limited knowledge regarding post-exposure prophylaxis.\n\nShortage of nurses during all shifts\n\nParticipants mentioned that there is no enough human resource during all shifts. The study also revealed that there is scarcity of theatre nurses who can relieve and give reports in time. The following participants’ excerpts support the above statement:\n\n“We are not well staffed. Sometimes we are only two and the other person will go off earlier and there is no one to relieve me, especially with Caesarean Sections. I must attend to dire emergencies like fetal distress as I am the only one. There is a gross shortage of staff. I sometimes do not even have time for a break. I am just expected to go on with the operation list.” (Rofunwa)\n\n“There is no staff to relieve us. Shortage of personnel is a huge problem in the department. These long procedures that complicate drain me physically and emotionally. There is no one to relieve me. I must go back and face another patient as if the previous case never happens.” (Avhatakali)\n\nLimited knowledge regarding post-exposure prophylaxis\n\nThe challenge related to human resources is not only shortage but also limited knowledge on HIV PEP among nurses. The study indicated that some of the theatre nurses who are supposed to have pharmaceutical knowledge of medicine do not even know the names of the antiretroviral medication given as prophylaxis following exposure to HIV-contaminated body fluids. Supporting the above are the following participants’ quotations:\n\n“I don’t know the name of the tablets, I have not been in the situation, but what I know is that they are antiretrovirals”. (Mukona)\n\n“I don’t remember the name, but it was a combination pill with Nevofir. I do not remember the other drugs”. (Munyadziwai)\n\nOther members of the support team\n\nThe lack of other support staff in theatre negatively affects the provision of perioperative care in theatre during emergency procedures. The above theme consists of the following sub-themes: lack of consultants after hours and limited time to render preoperative care.\n\nLack of consultants after hours\n\nApart from the shortage of nurses during all shifts, there is always a lack of consultants after hours who are supposed to work during operations. For example, the anesthetist consultant only works during office hours. This poses a challenge for the anesthetist registrars as they are unable to execute certain functions or operate some of the equipment in theatre after hours.\n\n“The consumables of the cell saver machine are not readily available, and some of the anesthetist does not know how to use the cell saver machine. It is normally their consultant who operates that machine. If it is after hours and during the night when the consultant is not there, we cannot use it even if consumables are available. And this put us in danger of losing patients, especially if HIV patients start to bleed.” (Azwimpheleli)\n\nLimited time to render preoperative care\n\nApart from the above concerns, another challenge related to the human resource is limited time to render preoperative care. It was indicated that consultants and theatre nurses do not have an opportunity to visit the patients a day before the operation to conduct pre-operative care due to workload. This is shown by the following excerpt from one of the participants:\n\n“You are supposed to do the preoperative visit, but due to workload, we do not do it. I only meet my patient at the reception area on the day of the operation. This is because we only know where we are supposed to work in the morning.” (Ntshengedzeni)\n\nThe challenge is not only limited to human resources, but also a shortage of material resources. This superordinate theme is composed of the following sub-themes: personal protective equipment (PPE) and pharmaceutical resources.\n\nPersonal protective equipment (PPE)\n\nWithout PPE (gloves, protective apron, google and visors), it is difficult for theatre nurses to render some of the procedures where there is fluid contact, for instance, delivery of a baby (cesarean section) and laparotomy (opening of the abdomen).\n\n“The department does not care about us. How can one assist during a cesarean section without visors when it is known that there is a possibility of blood splashing? It is prone for one to get infected with HIV in the process of delivering a child”. (Malindi)\n\nShortage of PPE\n\nParticipants indicated a shortage of PPE such as masks, gloves, google, and visors from the theatre department, even from the hospital central storeroom at the procurement department.\n\n“Some PPE are readily available like masks, but sometimes we do not have all the sizes of gloves, especially small sizes gloves, because most of the staff members wear from size seven, so the ensure consistent supply of that size. They hardly order smaller sizes making us with tiny hands struggle. If I find size six gloves, I must hide them in my locker so that I don’t struggle in the future when there is no stock. Items such as protective plastic aprons and masks are always available. The goggles are not always there, and we end up purchasing our own goggles. The visors are a serious problem. If you get one, you must finish the whole list with it, and it smells. The surgical masks are easier to get everywhere as it is Covid-19 times.” (Murida)\n\nDiscriminatory supply of protective material\n\nThough there is a shortage of personal protective clothing, there are also discriminatory supply practices between the nurses and doctors. Some participants indicated that certain material resources are distributed with favoritisms between the doctors and the nurses.\n\n“To be honest, the goggles you struggle to get them. They are not readily available to nursing staff, but the doctors are always issued goggles. The anesthetist will tell you that they are buying the goggles themselves or their seniors are buying for them, which we are not even sure of. For nursing staff, the goggles are there, but we are so many, and they are few. Some use them and put them in their lockers instead of putting them in their designated area. The whole department is issued with goggles, but once they break, a person must wait for their turn when they are issuing for everyone.” (Muthelo)\n\nPharmaceutical resources\n\nThe study indicated that there is always availability of pharmaceutical supplies, for instance, frozen dry plasma, which makes the job easy for theatre nurses when there is an emergency in theatre regarding patients living with HIV as most of them need plasma because of their low hemoglobin level.\n\nAvailability of pharmaceutical resources to treat complications\n\nAccording to the study results, there is a good supply of pharmaceutical products between the theatre and pharmacy departments. There is also good management of these pharmaceutical products as most participants indicated that there is always something to utilize in emergencies and routine lists.\n\n“We are using frozen dry plasma. It comes as a dry powder that we mix with two hundred milliliters of saline. The frozen plasma is from the blood bank, and this one is from the pharmacy, and it is always available. This is our first line of defense”. (Avheani)\n\n“We always have resuscitation fluids at all times like voluven, ringer’s lactate and hemostats like spongostan and surgicell.” (Malindi)\n\nEven though pharmaceutical supply is not a problem, there are challenges regarding infrastructure. The above superordinate theme consists of the following sub-themes: space in theatre and location of the theatre.\n\nSpace in the theatre\n\nThe other problem raised is the limited space in the theatre where patients need to be monitored after operations have been performed before they can be sent to the intensive care unit or the various wards.\n\n“It is difficult to observe a patient in theatre after surgery due to limited space. The patients are transferred to the wards regardless of their condition. The above is done to avoid crowding in the theatre observation room, which might also lead to cross infections, as we are dealing with patients living with HIV”. (Rofunwa)\n\nInadequate space for nursing complicated patients in theatre\n\nThe geographical plan of the theatre department of the hospital under study has 13 theatres in total, which are divided into different areas of specialization. There is one endoscopy unit, two obstetrics theatres, two orthopedic theatres, one future laparoscopy theatre that is shared by all disciplines according to days and time of allocation, one Gynecology theatre, one urology theatre, one ENT theatre, one Ophthalmology theatre, one General Surgery theatre, and two Emergency theatres (clean and septic). There is only one recovery room for the whole complex with six recovery cubicles. There is no Boyles Machine in the recovery unit where complicated patients can be nursed. The patient is nursed in the theatre where the operation takes place.\n\n“The patients are being resuscitated in theatre until they wake up or until the anesthetist finds an intensive care unit bed or high care bed. If there is no bed, the patient is nursed in the theatre department by the whole team.” (Azwimpheleli).\n\nLimited space in the Intensive Care Unit (ICU) where the complicated patients can be transferred to\n\nApart from the theatre unit where patients were operated on, there is a challenge of limited space in the ICU where patients must be transferred to post-operation. The results of the study indicated that there are only eight ICU beds in the hospital under investigation, which is a tertiary institution.\n\n“No, the intensive care unit beds are only eight. If it is full, the patient is nursed in the operating theatre, being ventilated until there is a bed available. Most of the time, we arrange an intensive care bed from other hospitals. If we don’t get a bed, it only means that a nurse from theatre must nurse this patient together with the anesthetist”. (Munyadziwa)\n\nLocation of the theatre\n\nEven though the patient got stuck in the theatre due to complications and the unavailability of ICU beds, it was not difficult for staff members to get blood products to the theatre complex.\n\n“The blood bank is next to our theatre, so there is no problem in getting blood on time. There is no delay when it comes to the much-needed blood plasma in theatre.” (Avheani)\n\nThe proximity of theatre to the blood bank\n\nResults of the study indicated that the proximity of the blood blank is near the main theatre which makes it easy to obtain blood in case of emergency.\n\n“Yes, we have a blood bank, and fortunately, it is closer to the theatre. If there is no intern doctor to go collect blood, we just send our general worker to go and collect.” (Rofunwa)\n\n\nDiscussion\n\nThe shortage of human resources, especially professional nurses due to retirement, and absenteeism worsened by contracting the coronavirus is creating many challenges. Most of the time, nurses are allocated in the theatre alone without anyone to relieve them. This creates a challenge because, for patients living with HIV, their procedure takes longer than that of others due to their proneness to complications. In a study conducted in New Zealand22 it was found that there is a tremendous loss of human capital in healthcare facilities. Not just a shortage of nurses but a shortage of experienced nurses. Therefore, the hospitals ought to recognize that their most senior nurses are a valuable resource and that they might extend their careers by offering some of them opportunities to become mentors.\n\nThe study also revealed that even though nurses under training are allocated in the theatre department, there is a need to retain highly experienced and highly trained personnel to transfer the knowledge to the students and newly qualified employees. The same sentiment was shared in the study conducted by one scholar,23 that hospitals are using nurses who are supposed to be training to patch their shortage and those nurses are forced to work without supervision, as it was supposed to be.\n\nThe study also finds that not only limited nursing resources but also the anesthetist consultants are unavailable after hours. That means that the anesthetist registrar does not conduct certain functions due to difficulties in operating some equipment. The same sentiment was shared by other scholar17 that the lack of anesthesia providers means that more people may die in poor countries during operations or due to postponement of operations, and a smaller number of surgeries will be performed by people with poor or no training in anesthesia.\n\nThe results indicated that some professional nurses lack knowledge of PEP. This is due to their nature of work. They do not deal with oral medication in theatre as patients who come to the theatre are starved; they only concentrate on anesthetic agents and intramuscular analgesics. Similar findings were reported in the study conducted in Bhutan,24 among 221 registered nurses working at the hospital regarding knowledge of PEP. Their results revealed that 80% of the participants had poor knowledge regarding PEP.\n\nProtective materials that are continuously available are face masks, especially because of the protocol for the management of the COVID-19 pandemic. With other materials, such as gloves, only people who put on size seven gloves are usually catered for. Those who wear smaller sizes such as size six or six and a half are most of the time not catered for. They are therefore forced to put on oversized gloves, which make them more prone to be pricked. Sometimes they are forced to put on smaller available sizes, which are very uncomfortable. Sharing the same sentiment is a previous study conducted in South Africa,12,25 which stated that shortage of other protective equipment is making it hard for nurses to provide care without being afraid of contracting HIV in the process.\n\nThe type of duties they perform perioperatively makes them prone to be exposed to HIV-contaminated body fluids. The challenge is further worsened because of the lack of protective clothing, such as goggles and visors. This compromises their health especially when the patient is HIV positive as there is a possibility of blood gushing into their eyes and predisposing them to infection. Other scholars26,27 reported that professional nurses raised their concerns in one of the hospitals in the Tshwane District about the supply of protective clothing that was used as a precautionary measure to prevent the transmission of HIV from patient blood and body fluid.\n\nThe study findings also revealed that the shortage of protective materials seems to be discriminatory as, while nurses may not be provided with adequate quality protective equipment, the anesthetists and surgeons are always provided with that material. This means that other members of the health care team are given priority when the PPE is scarce while all team members involved with the patient perioperatively are at risk of contracting the virus. Similar results were shared by other authors,28 highlighting that the staff that is working at National Health System are required to wear different types of PPE depending on their clinical setting according to their level of exposure to infectious conditions such as HIV.\n\nThis study also found that, although there is a shortage of protective materials, pharmaceutical products to help resuscitate HIV-positive patients when they are complicated, especially bleeding profusely, which is common among HIV-positive patients are always available. The available pharmaceutical products include Ringer’s lactate solution, Voluven, Cyklokapron, and dry plasma to help with resuscitation when these patients start to bleed excessively. Contrary to the above statement, a study conducted in South Africa,29 revealed that there is always a shortage of pharmaceutical materials, and medicine in public hospitals, which makes it difficult to provide quality care to the patient.\n\nThe findings indicate the shortage of infrastructure that affects the care of HIV-positive patients if they have perioperative complications. They mentioned that the hospital has several theaters, which most of the time will be utilized simultaneously. According to a study conducted in South Africa,30 shortage of infrastructure contributed negatively to the management of people living with HIV. This is because, after operation, people living with HIV require adequate space with all necessary equipment where they could be nursed until they fully recover. Despite so many theatres, the hospital has only one recovery room for the whole complex with six recovery cubicles. There is no Boyles Machine in the recovery unit where complicated patients can be nursed. This means that if a patient has complications, they are nursed in the theatre where the operation takes place until they recover. That means that a nurse who has scrubbed for the patient has to be with a patient living with HIV for a very long time. Sharing the same narratives is a study conducted by another author,31 which found that lack of proper resources contributes to the preventable death or complications of patients.\n\nThe other challenge is that it becomes very difficult to get a bed in the ICU for HIV-positive patients postoperatively as there are only eight ICU beds in the hospital, which is a tertiary academic hospital that operates many major operations booked routinely and those major cases on emergency from all over South Africa, and even the neighboring countries. This is in contrast with the recommendations by another author32 stating that health care sites, including hospitals, should be integrated with the broader community to promote accessibility. The finding related to limited ICU beds, making it difficult to get a bed for a complicated HIV patient attest to the findings by a study done in South Africa33 that the last national audit of ICU resources in South Africa indicated that there were 4,179 ICU and high care beds in the private and public sector in South Africa to cater for 57 million population of the total number, 75% of beds (3,533) were in the private sector, and only 25% (1,186) were in the public sector, which alone caters for 84% of the population. Gauteng is allocated 49%, which is 2,312 beds, in both the public and private sectors. The other positive thing is the proximity of the theatre to a blood bank, which makes it easy for one to get blood during an emergency and it also fastens the nursing care of the patients and prevents complications or death. Contrary to the above, as shared in a study conducted in Chhattisgarh,34 the proximity of the blood bank to the theatre is very important as it also reduces delays that can lead to complications and death.\n\nThe results did not only show the negative aspects related to infrastructure but also showed the positive aspects. The positive issues are that the blood bank is situated next to the main theatre. Though it is a bit too far from the maternity theatre, it is still a working distance where an intern doctor or the general theatre worker could walk and collect blood. This has assisted in saving the lives of most HIV-positive patients who have complications during surgery. Another author34 agrees with the above that if the blood bank is nearer, it is good for saving patients’ lives before they have serious complications or die.\n\nThe participants were only professional nurses while there are also other categories of nurses who work in theatre. The study was conducted during COVID-19 lockdown, and because of wearing the mask and social distancing, it was difficult to observe some non-verbal cues as the mouth and nose were covered. It was also difficult to maintain eye contact with the participants as some participants put on a face shield. This might have affected the observations of some cues which necessitated further probing.\n\nThe hospital needs to provide adequate staffing in the theatre to ensure that theatre nurses are not overstretched as exhaustion leads to poor quality care for patients living with HIV perioperatively. Supply chain or procurement department need to supply enough protective equipment to theatres as most participants indicated a decline in quality perioperative care due to lack of consumables. The hospital should supply theatre staff with adequate quality protective clothing and safety materials such as masks, plastic aprons, and disposable gloves. The government needs to construct a high-standard hospital infrastructure that is adequate and adaptable for the required patients’ services.\n\n\nConclusions\n\nResults indicated that professional nurses caring for people living with HIV experience a shortage of human resources, material resources, and infrastructural resources. The study indicated that professional nurses in the theatre department fail to provide adequate quality care to people living with HIV perioperatively due to inadequate resources and lack of support. The government should ensure that, theatre nurses are provided with adequate personal protective clothing, theatres are adequately staffed and equipped with all necessary equipment, so that theatre nurses can provide quality nursing care to people living with HIV perioperatively.",
"appendix": "Data availability\n\nThe transcripts and audio-recordings for this study are available from the first authors on request (mmudza@unisa.ac.za or rngaledzani@gmail.com). We could not openly upload data on the website because the transcripts are verbatim. Moreover, when reading those transcripts though the identifiers such as biographical data are removed, people from the hospital where data were conducted could easily link the narratives to a specific participant based on the certain manner in which specific people express themselves.\n\nZenodo: Prof. https://doi.org/10.5281/zenodo.7278296. 35\n\nThis project contains the following extended data:\n\n- Interview guide 2.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\nFamoroti TO, Fernandes L, Chima SC: Stigmatization of people living with HIV/AIDS by healthcare workers at a tertiary hospital in KwaZulu-Natal, South Africa: a cross-sectional descriptive study. BMC Med. Ethics. 2013 Dec; 14(1): 1. PubMed Abstract | Publisher Full Text\n\nGlobal AI: Update. Confronting Inequalities-Lessons for pandemic responses from 40 years of AIDS. Geneva, Switzerland:UNAIDS Joint United Nations Programme on HIV/AIDS;2021.\n\nGrobler A, Cawood C, Khanyile D, et al.: Progress of UNAIDS 90-90-90 targets in a district in KwaZulu-Natal, South Africa, with high HIV burden, in the HIPSS study: a household-based complex multilevel community survey. Lancet HIV. 2017 Nov 1; 4(11): e505–e513. Publisher Full Text\n\nJohnson LF, Dorrington RE, Moolla H: Progress towards the 2020 targets for HIV diagnosis and antiretroviral treatment in South Africa. South Afr. J. HIV Med. 2017 Feb 21; 18(1): 1–8. PubMed Abstract | Publisher Full Text\n\nOfosu NN, Saunders LD, Jhangri G, et al.: The impact of the availability of antiretroviral therapy on personal and community fear of HIV/AIDS, and HIV prevention practices in Rwimi, Uganda: A mixed-method study. Alberta Academic Review. 2018 May 28; 1(1): 1–4. Publisher Full Text\n\nCabal L: The Agenda for Zero Discrimination in Health Care. J. Sex. Med. 2017 May 1; 14(5): e221. Publisher Full Text\n\nNyblade L, Srinivasan K, Mazur A, et al.: HIV stigma reduction for health facility staff: development of a blended-learning intervention. Front. Public Health. 2018 Jun 21; 6: 165. PubMed Abstract | Publisher Full Text\n\nEhiri JE, Alaofè HS, Yesufu V, et al.: AIDS-related stigmatisation in the healthcare setting: a study of primary healthcare centres that provide services for prevention of mother-to-child transmission of HIV in Lagos, Nigeria. BMJ Open. 2019 May 17; 9(5): e026322. PubMed Abstract | Publisher Full Text\n\nDong X, Yang J, Peng L, et al.: HIV-related stigma and discrimination amongst healthcare providers in Guangzhou, China. BMC Public Health. 2018 Dec; 18(1): 738. PubMed Abstract | Publisher Full Text\n\nStringer KL, Turan B, McCormick L, et al.: HIV-related stigma among healthcare providers in the deep south. AIDS Behav. 2016 Jan; 20(1): 115–125. PubMed Abstract | Publisher Full Text\n\nKimaro L, Adinan J, Damian DJ, et al.: Prevalence of occupational injuries and knowledge of availability and utilization of post exposure prophylaxis among health care workers in Singida District Council, Singida Region, Tanzania. Plos One. 2018 Oct 25; 13(10): e0201695. PubMed Abstract | Publisher Full Text\n\nMammbona AA, Mavhandu-Mudzusi AH: Enrolled nurses’ experiences of caring for patients living with HIV in a South African rural hospital. Int. Nurs. Rev. 2019 Mar; 66(1): 139–146. Publisher Full Text\n\nXu P, Chen W, Ju L, et al.: Evolution and perfection of the HIV/AIDS designated hospital system in China. Chinese Journal of Health Policy. 2015; 67–72.\n\nAlase A: The interpretative phenomenological analysis (IPA): A guide to a good qualitative research approach. International Journal of Education and Literacy Studies. 2017 Apr 30; 5(2): 9–19. Publisher Full Text\n\nSmith JA, Osborn M: Interpretative phenomenological analysis as a useful methodology for research on the lived experience of pain. Br. J. Pain. 2015 Feb; 9(1): 41–42. PubMed Abstract | Publisher Full Text\n\nTeherani A, Martimianakis T, Stenfors-Hayes T, et al.: Choosing a qualitative research approach. J. Grad. Med. Educ. 2015 Dec; 7(4): 669–670. PubMed Abstract | Publisher Full Text\n\nBrink H, Van der Walt C, Van Rensburg G: Fundamentals of research methodology for health care professionals. 4th ed.Cape Town:Juta and Company Ltd;2018.\n\nFusch PI, Ness LR: Are we there yet? Data saturation in qualitative research. Qual. Rep. 2015 Sep 7; 20(9): 1408. Publisher Full Text\n\nSaunders B, Sim J, Kingstone T, et al.: Saturation in qualitative research: exploring its conceptualization and operationalization. Qual. Quant. 2018 Jul; 52(4): 1893–1907. PubMed Abstract | Publisher Full Text\n\nCharlick SJ, Pincombe J, McKellar L, et al.: Making sense of participant experiences: Interpretative phenomenological analysis in midwifery research. Int. J. Dr. Stud. 2016; 11: 205. Publisher Full Text\n\nGuba EG, Lincoln YS:Competing paradigms in qualitative research.Denzin NK, Lincoln YS, editors. Handbook of Qualitative Research. Sage Publications, Inc;Thousand Oaks:1994; 105–117.\n\nMoloney W, Gorman D, Parsons M, et al.: How to keep registered nurses working in New Zealand even as economic conditions improve. Hum. Resour. Health. 2018 Dec; 16(1): 1–8.\n\nPettes DE: Staff and student supervision: A task-centered approach. Routledge;2021 Nov 7. Publisher Full Text\n\nTshering K, Wangchuk K, Letho Z: Assessment of knowledge, attitude and practice of post exposure prophylaxis for HIV among nurses at Jigme Dorji Wanghuck National Referral Hospital, Bhutan. PLoS One. 2020 Aug 28; 15(8): e0238069. PubMed Abstract | Publisher Full Text\n\nRidge LJ, Stimpfel AW, Dickson VV, et al.: How clinicians manage routinely low supplies of personal protective equipment. Am. J. Infect. Control. 2021 Dec 1; 49(12): 1488–1492. PubMed Abstract | Publisher Full Text\n\nRowe G, Gee D: Infection settings control in. Health Promotion for Nursing Associates. 2021 Dec 15; 83.\n\nNdou ND: Instrumental support for professional nurses caring for patients living with HIV/AIDS in the Tshwane district of Gauteng, South Africa. Afr. J. Nurs. Midwifery. 2017; 19(3): 13.Reference Source\n\nKarim N, Afroj S, Lloyd K, et al.: Sustainable personal protective clothing for healthcare applications: a review. ACS Nano. 2020 Aug 31; 14(10): 12313–12340. PubMed Abstract | Publisher Full Text\n\nModisakeng C, Matlala M, Godman B, et al.: Medicine shortages and challenges with the procurement process among public sector hospitals in South Africa; findings and implications. BMC Health Serv. Res. 2020 Dec; 20(1): 234. PubMed Abstract | Publisher Full Text\n\nManyisa ZM, van Aswegen EJ : Factors affecting working conditions in public hospitals: A literature review. Int. J. Africa Nurs. Sci. 2017 Jan 1; 6: 28–38. Publisher Full Text\n\nTabish SA: COVID-19 pandemic: Emerging perspectives and future trends. J. Public Health Res. 2020 Jun 4; 9(1): jphr-2020. PubMed Abstract | Publisher Full Text\n\nLuxon L: Infrastructure–the key to healthcare improvement. Future Hosp. J. 2015 Feb; 2(1): 4–7. Publisher Full Text\n\nNaidoo R, Naidoo K: Prioritising ‘already-scarce’intensive care unit resources in the midst of COVID-19: a call for regional triage committees in South Africa. BMC Med. Ethics. 2021 Dec; 22(1): 1–9. PubMed Abstract | Publisher Full Text\n\nJogi SR, Ekka AR: Maternal mortality review by three delay model: a retrospective study from a tertiary care hospital of Chhattisgarh. Int. J. Reprod. Contracept. Obstet. Gynecol. 2021 Jan 1; 10(1): 262–268.\n\nProf Mavhandu-Mudzusi AH :Zenodo. [Dataset]. 2022. Publisher Full Text"
}
|
[
{
"id": "191587",
"date": "04 Sep 2023",
"name": "Victoria Marcia Mutambara",
"expertise": [
"Reviewer Expertise Sexual Reproductive Health",
"Gender and migration."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n1. Utilizing IPA as the research design is suitable as it gives a comprehensive reflection on the participants personal perceptions.\n2. On the discussion under the human resources theme,\n\"The study also finds that not only limited nursing resources but also the anesthetist consultants are unavailable after hours. That means that the anesthetist registrar does not conduct certain functions due to difficulties in operating some equipment.\"\nI would suggest the authors present their data reflecting on how these challenges are particularly specific for HIV patients as these challenges can be faced by any other patient using the hospital.\n3. \"The results did not only show the negative aspects related to infrastructure but also showed the positive aspects. The positive issues are that the blood bank is situated next to the main theatre. Though it is a bit too far from the maternity theatre, it is still a working distance where an intern doctor or the general theatre worker could walk and collect blood.\"\n\nThere was a slight mistake with spelling , I assume it was supposed to be walking distance.\n4. Whilst, the conclusion captures the main themes that emanated from the study, I would suggest the authors strengthen their conclusion and give a synthesis of the key points and also recommend areas of future research.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "204205",
"date": "29 Nov 2023",
"name": "Nnamdi Ndubuka",
"expertise": [
"Reviewer Expertise Sexually Transmitted and Blood Borne Infections",
"Social epidemiology and determinants of health",
"Population health intervention research",
"Indigenous Health",
"Clinical quality improvement",
"Epidemiology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 clearly articulated the aim of the study. The study is very essential recognizing the need for South Africa to reach the UNAIDS 90-90-90 targets.\nResearch design\nThe use of a qualitative research methodology is appropriate for this study. The authors provided a clear justification for the choice of method. The research design also enabled the authors to explore and describe the experiences of theatre nurses in caring for patients living with HIV.\n\nLiterature review\nThe authors demonstrated adequate knowledge of the research topic. Literature review process was appropriate and in-line with study objective. However, the literature review section could be strengthened by including the new set of UNAIDS target of 95-95-95 released in December 2020.\nResearch setting:\n\nIt would be reasonable for the authors to provide a rational for choosing the tertiary hospital in Tshwane district. What informed this choice and not other facilities?\nInclusion criteria:\n\nHaving 2years of experience working in the theatre was identified as a criteria to participate in the study. The authors need to reword this criteria as those more than two years of experience were also included. Suggested wording: \"at least 2 years of experience working in the theatre\".\nData analysis:\nThe authors can strengthen the analysis section by providing the gender of the respondents. It is possible that the experience of the theatre nurses may differ by gender.\n\nRecommendation and Conclusion:\n\nThe authors identified limited knowledge regarding post-exposure prophylaxis as a sub-theme that emerged from the study. This is an important finding that should be highlighted in the recommendation and conclusion section of the manuscript. Strategies to enhance the healthcare workers' knowledge regarding HIV PEP should be an important recommendation.\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": []
}
] | 1
|
https://f1000research.com/articles/11-1299
|
https://f1000research.com/articles/13-108/v1
|
16 Feb 24
|
{
"type": "Opinion Article",
"title": "Unlocking the potential of Tanzania's cashew processing industry: A comparative analysis with Côte d’Ivoire and Mozambique",
"authors": [
"Kulwa Mang'ana",
"Revelian Ngaiza",
"Michael Paul",
"Revelian Ngaiza",
"Michael Paul"
],
"abstract": "Cashew processing is a vital contributor to economic growth in Tanzania, renowned for its cashew nut production. However, despite the country’s historical prominence in cashew production, only 5% of raw cashews undergo local processing, resulting in substantial economic losses. This paper explores the challenges and opportunities within Tanzania’s cashew processing industry, focusing on limited local processing capacity, inefficient tools, raw material availability, market access, and government support. Comparative insights from Côte d’Ivoire and Mozambique further enrich our understanding of the cashew sector. It recommends increasing local processing capacity, enhancing technical expertise through training, ensuring a reliable supply of high-quality raw materials, improving market access via information systems, and strengthening government support with tailored policy frameworks. Notably, the paper emphasizes regional collaboration among African cashew-producing nations as a crucial strategy for collective growth and knowledge exchange. By drawing upon their experiences, this study aims to provide guidance for policymakers, industry stakeholders, and investors to revitalize and sustain Tanzania’s cashew processing sector.",
"keywords": [
"Cashew Processing",
"Challenges",
"Comparative Analysis and Sustainable Growth"
],
"content": "Introduction\n\nCashew processing stands as a cornerstone of economic development in cashew-producing countries, fostering employment and export revenues. Since the early 1960s, cashew production in African countries has demonstrated dynamic shifts (Kit et al., 2019).\n\nHistorically, Mozambique and Tanzania led in cashew production. However, they faced declines in the 1980s and 1990s, before experiencing resurgence. Nigeria witnessed a remarkable surge between 1998 and 2008, followed by a precipitous decline. Côte d’Ivoire emerged as a dominant producer since 2003, outstripping other nations by a significant margin. Steady growth has also characterized Guinea-Bissau, Benin, Ghana, and Burkina Faso over the past two decades. Collectively, these eight countries contributed a staggering 92 per cent of the total African cashew crop in 2017 (Mgonja & Shausi, 2022).\n\nCashew processing plays a pivotal role in Tanzania’s economic landscape, offering employment opportunities and contributing to export revenues. However, despite the high return on investment, a mere 5% of raw cashew nuts are processed locally, with the remaining 95% traversing borders to Vietnam or India for value addition before reaching European and American consumer markets for Tanzania (The Citizen 20th of February 2022).\n\nThis historical context underscores the dynamism of cashew production in Africa, marked by fluctuations, transformations, and the emergence of new leaders. In this paper, we delve into the multifaceted challenges and promising opportunities encountered by cashew processors in Côte d’Ivoire, Mozambique, and Tanzania. Our analysis encompasses the intricacies related to production processes, technical knowledge, and policy frameworks, offering a comparative perspective that draws upon shared experiences and innovative solutions. By addressing these challenges collectively and harnessing opportunities, we aim to provide guidance for stakeholders and policymakers to bolster the competitiveness and sustainability of cashew processing industries across countries.\n\n\nMethods\n\nIn this working paper, it is important to note that the methodology employed a traditional search approach rather than a systematic review. We conducted a review of relevant literature, encompassing academic databases, research repositories, and government publications, with a focus on recent and credible sources addressing the challenges and opportunities within the cashew processing industries of Côte d’Ivoire, Mozambique, and Tanzania. Additionally, we supplemented our literature review with selected case studies that offered valuable insights into specific contexts. This combined approach allowed us to gain a comprehensive understanding of the subject matter while recognizing that it may not encompass all available data and sources.\n\nTo identify recurring themes and trends, findings from the selected literature were qualitatively synthesized under areas of production processes, technical expertise, and policy frameworks. This qualitative analysis provided a nuanced understanding of the cashew processing landscape (Figure 1).\n\nSource: Researcher’s extract analysis using NVivo Word cloud (2023).\n\nLimited local processing capacity\n\nThe foremost challenge plaguing Tanzania’s cashew processing sector is the inherent limitation in local processing capacity (Chimbyangu, 2020; Mgonja & Shausi, 2022; Nkwabi, 2019). Historically, the nation has enjoyed a reputation as a prominent cashew nut producer, often referred to as the “grey gold” due to its high investment returns. However, this potential remains significantly untapped, primarily due to the underdeveloped local processing infrastructure. In consequence, a substantial proportion of raw cashew nuts are exported for processing, resulting in pronounced economic losses. To truly unlock the sector’s potential and reverse these losses, substantial investments in local processing infrastructure are imperative. Such investments should encompass the establishment of modern processing facilities, the adoption of efficient technologies, and the fostering of local processing expertise. This approach not only ensures value addition within the country but also reduces post-harvest losses and enhances overall economic gains.\n\nInefficient tools and equipment\n\nAnother critical challenge that hampers the growth of Tanzania’s cashew processing industry is the prevalent use of inefficient local processing tools and equipment, predominantly employed by small-scale cashew nut processors. These antiquated and often outdated tools contribute to the suboptimal quality of processed products, diminishing the industry’s global competitiveness. A stark example is the reliance on hand-operated processing machines with limited processing capacities, which invariably yield subpar results (Lukurugu et al., 2022; Mgonja & Shausi, 2022). To surmount this challenge, an immediate shift toward modern and efficient processing equipment is necessary. Investments in state-of-the-art machinery, designed to enhance both the quantity and quality of processed cashew nuts, would be a pivotal step forward. Moreover, initiatives that promote technological adoption and skill development among processors are essential for driving innovation within the sector and elevating its global standing.\n\nRaw material availability and consistency\n\nEnsuring consistent access to raw cashew nuts emerges as a significant hurdle within the Tanzanian cashew processing landscape. The interplay of factors such as insufficient investment and working capital, coupled with the erratic availability of raw materials, impedes processors’ ability to operate efficiently and meet market demands. Achieving a reliable and consistent supply of raw cashew nuts is paramount to sustaining the sector’s operations and promoting growth. To address this challenge, strategic investments in cashew nut cultivation and harvesting practices are necessary. These investments should prioritize the enhancement of both quality and quantity in raw cashew nut production (Chimbyangu, 2020). Additionally, mechanisms that promote financial stability among smallholder farmers and processors, such as access to credit and working capital, are pivotal in ensuring a stable supply chain.\n\nMarket access and information\n\nSmall-scale processors in Tanzania frequently grapple with the challenge of accessing markets, stemming from a dearth of market information and a limited understanding of market dynamics. Lukurugu et al. (2022) reported that the major limiting factor in the use of improved cashew technologies was the inadequate information. This predicament significantly curtails their ability to effectively compete on the global stage and capitalize on value addition opportunities. The absence of market insights and inadequate understanding of customer preferences can lead to missed opportunities and suboptimal pricing strategies. Addressing this challenge necessitates a multifaceted approach. Initiatives aimed at providing small-scale processors with access to market information, coupled with training programs in marketing strategies and customer engagement, are essential. These endeavors can equip processors with the knowledge and skills required to navigate dynamic global markets and enhance their competitive edge.\n\nGovernment policy and support\n\nIn the realm of government policy and support, Tanzania’s cashew processing sector faces challenges that are instrumental in shaping its trajectory. The sector needs sufficient government support, encompassing issues related to accessible information on relevant regulations, training facilities, and initiatives aimed at assisting processors. Limited support translates into missed opportunities for growth and sustainability (Mihyo, 2019). Rectifying these gaps is pivotal for the sector’s progress. Clear and accessible policies should be instituted to guide and empower processors. Government-led initiatives aimed at providing essential training, facilitating access to capital, and disseminating information on regulations can bolster the sector’s development. Moreover, fostering collaboration between government agencies, industry stakeholders, and small-scale processors can engender a supportive ecosystem that catalyzes growth and innovation.\n\nTo address the policy framework and government support challenges in Tanzania’s cashew processing industry, it is essential to delve into recent initiatives. Tanzania has undertaken measures such as the Warehouse Receipt System (WRS), signifying a trade arrangement by which produce is kept in accredited storerooms, and commodity possessors are provided with receipts indicating ownership, value, category, quantity, and quality of their produce (Tanzania Warehouse Licensing Board (TWLB), 2013). The WRS is a trade arrangement designed to streamline the storage and transaction processes, providing a structured mechanism for managing produce. According to the Tanzania Warehouse Licensing Board (TWLB) in 2013, the WRS involves the storage of cashew produce in accredited storerooms. Commodity possessors, typically farmers or processors, are issued detailed receipts that include essential information such as ownership, value, category, quantity, and quality of the stored produce. This documentation serves as a legally recognized proof of possession and is instrumental in facilitating secure transactions throughout the cashew value chain. Literature supports the notion that transparent and efficient warehouse systems contribute significantly to agricultural supply chain management. In their study on agricultural value chain development, Lukurugu et al. (2022) emphasized the importance of robust storage and handling systems in enhancing the competitiveness of cashew and other agricultural products. The WRS aligns with this perspective by providing a standardized and regulated platform for storage, reducing the risk of spoilage, and ensuring the quality of the cashew produce.\n\nMuchmore, the literature highlights the role of such systems in improving market access for small-scale producers. In a similar agricultural context, Lukurugu et al. (2022) noted that reliable storage facilities and associated documentation positively influence market participation among small-scale farmers. The WRS in Tanzania acts as a catalyst for market access by establishing a credible record of the cashew produce’s attributes, fostering trust between producers and buyers. The adoption of the WRS reflects a commitment to good governance and accountability within Tanzania’s cashew industry. Mihyo (2019) emphasized the importance of effective agricultural policies and governance structures for poverty reduction in Tanzania. The WRS, by ensuring accurate record-keeping and transparent transactions, aligns with these principles and contributes to the sector’s overall stability and sustainability.\n\nFurthermore, the government is prioritizing the trading of kernels over Raw Cashew Nuts (RCN). This shift allows local processing companies to access loans from the Tanzania Agricultural Development Bank (TADB) to establish state-of-the-art equipment for large-scale production. Moreover, as part of their commitment to bolster the cashew industry, the government has embarked on an initiative to distribute 91,764 kilograms of cashew seedlings valued at TZS 275.9 million through local government councils. This proactive measure is geared towards achieving the ambitious target of producing 700,000 tonnes of cashew nuts by the 2025/26 season (Nelly, 2022). These multifaceted efforts underscore the government’s unwavering dedication to facilitating growth and sustainability within the Tanzanian cashew processing sector.\n\nTo gain deeper insights into the challenges and opportunities faced by Tanzania’s cashew processing industry, we turn our attention to Côte d’Ivoire and Mozambique. These two countries, much like Tanzania, hold significant roles in the global cashew arena, each grappling with its unique set of challenges and experiences in cashew processing. Exploring the commonalities and disparities among them can provide valuable lessons and best practices, shedding light on pathways to sustainable growth and development.\n\nCôte d’Ivoire’s cashew processing industry\n\nCôte d’Ivoire, located in West Africa, has long been a key player in the global cashew landscape. However, its cashew processing sector confronts a series of challenges that mirror Tanzania’s circumstances in various ways (Zandamela, 2021). Key issues include the following.\n\nMachinery deficiencies\n\nIn Côte d’Ivoire, the cashew processing industry grapples with machinery deficiencies, posing significant impediments to efficiency and productivity. The need to import processing equipment introduces logistical complexities, adding layers of intricacy to the entire processing journey. This challenge is echoed in the literature, where Tessmann (2020) highlights the dependence on imported machinery in the cashew industry. Importation not only raises costs but also introduces delays and potential disruptions in the supply chain, emphasizing the importance of locally sourced or manufactured machinery for a sustainable and streamlined processing sector.\n\nInfrastructure and warehousing limitations\n\nLimited infrastructure and warehousing facilities compound the challenges faced by the cashew processing industry in Côte d’Ivoire. Effective storage and logistics are pivotal for efficient processing and the preservation of product quality. Coast and Doktorgrades (2020) and Tessmann (2020) discuss the importance of adequate infrastructure in cashew value chain, emphasizing that storage facilities are critical for maintaining the quality of raw cashew nuts. The literature suggests that investments in infrastructure, including warehouses equipped with modern technologies, are essential for overcoming such limitations and ensuring the smooth functioning of the cashew processing sector.\n\nTechnical expertise and training shortages\n\nCôte d’Ivoire’s cashew processing sector encounters persistent challenges related to technical expertise and training shortages. Maintaining product quality and optimizing efficiency heavily rely on the skills and knowledge of personnel involved in processing practices. Lukurugu et al. (2022) emphasize the significance of skills development in the adoption of enhanced cashew production technologies among smallholder farmers in Tanzania. The shortage of training opportunities within the cashew processing sector in Côte d’Ivoire underscores the need for targeted initiatives to enhance technical expertise, fostering innovation and efficiency in line with global standards.\n\nAccess to financial services\n\nAccess to financial services, including credit and investment options, plays a crucial role in the growth of Côte d’Ivoire’s cashew processing sector. Challenges in this domain have implications for the industry’s overall capacity and competitiveness. Zandamela (2021) notes similar challenges in Mozambique’s cashew industry, where limited access to financial services hampers the sector’s ability to invest in modern technologies and infrastructure. The literature suggests that addressing these challenges requires collaborative efforts involving financial institutions, government interventions, and private sector initiatives to create a conducive financial environment for sustainable growth in the cashew processing industry.\n\nHowever, what distinguishes Côte d’Ivoire is its exceptional success story within the cashew industry. Côte d’Ivoire’s evolution into one of the foremost global cashew nut producers is attributed to a combination of government incentives and collaborative efforts with its partners, all transpiring within a backdrop of favorable market conditions. Government initiatives have played a pivotal role, offering subsidies and waiving taxes and duties on the export of locally processed cashew nuts. A noteworthy instance is the introduction, in 2016, of a subsidy amounting to EUR 0.6 per kg for locally processed and exported cashew nuts, extending over a five-year period. The industry’s resilience is further fortified by strategic investments in research and development, particularly focusing on cultivating high-yield seeds. The active involvement of non-governmental organizations has been crucial, providing essential technical assistance to small-scale producers and contributing significantly to the industry’s strength. To emphasize domestic processing, Côte d’Ivoire has implemented rigorous measures to regulate participants in the value chain. Raw cashew nuts are exclusively sold to duly licensed cooperatives, intermediaries, and processors. Specific licensing requirements for different entities within the value chain, restrictions on purchases before the marketing year commences, and the prohibition of exports through land borders constitute integral measures aimed at ensuring the efficiency and integrity of Côte d’Ivoire’s cashew industry (Zandamela, 2021).\n\nAs Côte d’Ivoire’s experiences intertwine with Tanzania’s, they stand as a testament to the transformative power of government incentives and strategic measures in fostering sector growth and development. These shared experiences underscore the importance of proactive governmental initiatives in steering the cashew processing industry toward prosperity.\n\nMozambique’s Cashew processing industry\n\nMoving to southeastern Africa, Mozambique presents its own distinct array of challenges and opportunities within the cashew processing sphere.\n\nLow-quality raw cashew nuts\n\nMozambique faces a significant challenge in dealing with low-quality raw cashew nuts, posing a considerable threat to overall product quality and market competitiveness. Martin (2016) underscores the impact of such challenges on the industry, emphasizing the need for targeted interventions to improve the quality of raw cashews. In the broader context, the literature suggests that enhancing the quality of raw materials is essential for the success of the cashew processing industry. Initiatives focusing on improved agricultural practices, including proper harvesting and handling techniques, can contribute to mitigating this challenge and ensuring a consistent supply of high-quality raw cashews.\n\nHigh procurement costs\n\nFragmentation in the cashew procurement process in Mozambique results in elevated costs, adversely affecting the industry’s overall profitability. The literature echoes the significance of streamlining procurement processes to enhance efficiency and reduce costs. Costa and Delgado (2019) discuss challenges in Mozambique’s cashew value chain, emphasizing the need for coordinated efforts in addressing procurement-related issues. Lessons from other agricultural value chains, as highlighted by Kit et al. (2019), suggest that establishing efficient procurement systems and fostering collaboration among stakeholders can contribute to cost reduction and increased profitability in the cashew processing sector.\n\nSustainability issues\n\nMozambique’s cashew processing industry grapples with sustainability issues, particularly in the realm of slow replanting programs and limited access to technical assistance. Challenges in primary production, including the replacement of aging trees with improved root stock and the need for increased anti-fungal spraying, present substantial hurdles to achieving sustainable growth. Costa and Delgado (2019) emphasize the importance of addressing sustainability challenges in Mozambique’s cashew value chain. The literature underscores the need for strategic interventions, such as promoting sustainable agricultural practices, investing in research and development, and providing adequate technical support, to ensure the long-term viability and resilience of the cashew processing sector in Mozambique.\n\nHowever, Mozambique’s proactive stance toward innovation introduces intriguing prospects. The nation’s focus on harnessing innovative technology for energy generation and its resolute commitment to carbon sequestration underscore Mozambique’s determination to surmount these challenges. In the realm of cashew processing, Mozambique emerges as a distinctive actor, weaving a narrative uniquely its own—comprising challenges and opportunities that offer alternative perspectives for success. While shared challenges resonate with Tanzania’s experience, Mozambique introduces novel dynamics that illuminate diverse pathways to prosperity. Notably, Mozambique adeptly responds to the surging demand for cashew kernels driven by evolving consumer preferences for healthy snacks and ingredients, thus diversifying its product range. Strategically marketing raw cashew nuts at different times of the year allows Mozambique to capitalize on market gaps and fluctuations, a strategic advantage not fully harnessed by Tanzania. Leveraging preferential trade agreements and exploiting its coastal location with efficient port access further cements Mozambique’s competitive edge.\n\nThe insights derived from the comparative analysis of Côte d’Ivoire, Mozambique, and Tanzania offer a roadmap for the sustainable growth of cashew processing industries in these nations. This section delineates practical strategies, hinging on commonalities and tailored to address disparities, which can guide policymakers, industry stakeholders, and investors toward transformative outcomes.\n\nA paramount challenge shared by these countries is the limitation in local processing capacity, leading to substantial economic losses from exporting raw cashews. To bolster domestic processing and maximize value retention, governments and private sector entities should channel investments into local infrastructure development. This entails the establishment of modern processing facilities, upgrading machinery, and expanding storage capacities. These investments will stimulate local processing rates and enhance economic returns.\n\nAnother commonality among these nations is the dearth of technical expertise within their cashew processing sectors, influencing product quality and competitiveness. To rectify this shortfall, comprehensive skills training programs must be initiated, encompassing all aspects of cashew processing, from harvesting techniques to stringent quality control. Public-private partnerships can prove instrumental in designing and executing these programs, ensuring processors acquire the requisite knowledge and skills for improved product quality and enhanced operational efficiency.\n\nConsistent access to high-quality raw cashew nuts remains a shared challenge among Tanzania, Côte d’Ivoire, and Mozambique. Securing a dependable supply of raw materials is paramount for the sustained operation of processing facilities. To achieve this, governments should proactively promote cashew farming through a multifaceted approach. This includes providing incentives for farmers, facilitating access to improved planting materials, extending financial support, and implementing replanting programs. By stabilizing the supply of top-grade raw cashews, the processing industry’s viability can be ensured.\n\nMarket access continues to be a thorny issue for small-scale processors across these nations due to a lack of market information and limited understanding of market dynamics. To mitigate this challenge, establishing accessible market information systems is imperative. These systems should offer real-time data on cashew prices, demand trends, and market opportunities. Empowering processors with timely and relevant information will enable them to make informed decisions and tap into profitable markets, both locally and internationally.\n\nInsufficient government support, including accessible regulatory information and initiatives for processor assistance, plagues the cashew processing sectors of all three countries. Crafting supportive policy frameworks is critical to overcoming this hurdle. Governments should enact regulations and incentives that cater to the unique needs of the cashew processing sector. Transparency and accessibility should be paramount when providing regulatory information, reducing compliance barriers, and fostering a favorable business environment.\n\nPromoting regional collaboration emerges as a cross-cutting strategy with significant potential. Cashew-producing countries in Africa can collectively thrive through knowledge sharing and coordinated industry development efforts. Consider establishing a Regional Cashew Council, uniting African cashew-producing nations. This platform can serve as a conduit for knowledge exchange, best practice dissemination, and coordinated initiatives spanning the entire cashew value chain, from farming practices to advanced processing techniques.\n\n\nConclusion\n\nTanzania’s cashew processing industry stands at a crossroads, offering immense potential for growth and development. Addressing the challenges of limited local processing, inefficient tools, raw material availability, market access, and government support is imperative. Drawing upon comparative insights from Côte d’Ivoire and Mozambique, we find that shared experiences and best practices offer valuable lessons for Tanzania’s journey towards revitalizing and sustaining its cashew processing sector. Conclusively, the practical strategies outlined here, grounded in the comparative analysis, hold the promise of reshaping the cashew processing landscape. By adopting these strategies and fostering regional collaboration, these nations, along with their African counterparts, can unlock the full potential of their cashew sectors. The journey toward sustainable economic development, job creation, and enduring growth in the global cashew industry beckons, and these strategies pave the way for transformative progress.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nChimbyangu MA: Assessment on Cashew Production in High Income Generation to Small Holder Cashew Farmers in Tanzania: The Case of Mtwara Region. Mzumbe University; 2020; Vol. 2507(February). Reference Source\n\nCoast I, Doktorgrades E: The Embeddedness of Global Value Chains.2020.\n\nCosta C, Delgado C: The Cashew Value Chain in Mozambique. The Cashew Value Chain in Mozambique. 2019; 32. Publisher Full Text\n\nKit N, Joana B, Shanaz B: The role of governments in developing agriculture value chains. Cashew Value-chain Development: Policy Dialogue. 2019; 2(2). Publisher Full Text\n\nLukurugu GA, Mwalongo S, Kuboja NM, et al.: Determinants of adoption of enhanced cashew production technologies among smallholder farmers in Mtwara region, Tanzania. Cogent Food and Agriculture. 2022; 8(1). Publisher Full Text\n\nMartin WI: Mozambican Cashew Industry Analysis. August.2016.\n\nMgonja NS, Shausi GL: Challenges Facing Small-scale Cashew Nut Processors in Ruangwa district, Tanzania: An Implication for Policy Change. European Journal of Agriculture and Food Sciences. 2022; 4(3): 1–8. Publisher Full Text\n\nMihyo PB: Agricultural Policy and Poverty Reduction in Tanzania.2019; 6: 1–4. Reference Source\n\nNelly M: Cashew production heading to the ceiling- CBT. Daily News. 2022, October 9. Reference Source\n\nNkwabi JM: A Review of Factors Affecting the Growth of Small and Medium Enterprises (SMEs) in Tanzania. European Journal of Business and Management. 2019; 2016: 1–8. Publisher Full Text\n\nTanzania Warehouse Licensing Board (TWLB): The warehouse receipts system operational manual, made under section 6 of warehouse receipts. Act No. 10 Of 2005.2013. Reference Source\n\nTessmann J: Global value chains and policy practice: The making of linkages in the Ivorian cashew industry.2020. Publisher Full Text\n\nZandamela RL: Challenges and Opportunities in the Marketing and Processing of Cashew Nuts.2021. Reference Source"
}
|
[
{
"id": "268758",
"date": "22 May 2024",
"name": "Yusuf Momohjimoh",
"expertise": [
"Reviewer Expertise Agronomy",
"soil fertility",
"genetics and seed production",
"agricultural economics."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe research topic potentially reflects the present situation of cashew processing industry of the Tanzania comparing the potential and significant impact of cashew processing industry on Côte d’Ivoire and Mozambique. The topic of the opinion discussed in this research falls within the context of the current literature, however discussion has not been sufficiently standardized with relevant literatures (i.e. citation in-text is scanty). Authors can consult more literatures to substantiate premises and make the write scientifically sound.\nMethodology employed indicated that a secondary data source such as journal publications, case studies, government reports among others were consulted, though very scanty and doesn’t substantiate authors premises and conclusions. Authors may look out for more literatures to substantiate claims and assertions.\nIn general, authors may present this manuscript as a review to become scientifically grounded and acceptable in the research world. Please view the additional review comments in the file found Here.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nAre arguments sufficiently supported by evidence from the published literature? No\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": []
},
{
"id": "268762",
"date": "23 May 2024",
"name": "Edmund Zakayo",
"expertise": [
"Reviewer Expertise Community economic development",
"community participation",
"youth and women development",
"cooperatives",
"financial inclusion",
"blue economy",
"community based organizations",
"community empowerment",
"children violence",
"community Based resource management",
"participatory planning",
"rural development",
"gender equality and social inclusion",
"and agricultural value chain and marketing."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe title need to be rephrased if the focus is Unlocking the potential of Tanzania's cashew processing industry, how is it connected with Côte d’Ivoire and Mozambique? The introduction section of the study lacks sufficient detail and fails to provide a comprehensive overview of the subject matter. For instance, readers would naturally expect information about global cashew nut processing, including which countries lead in production and processing. This comparison between producers and processors piques interest and raises questions. Additionally, it is crucial to address which African country holds the top position in both production and processing, along with the percentage of cashew nuts processed relative to the total amount produced. Presently, the study lacks a clear problem addressed by the study or rationale for its investigation. The fourth paragraph in the introduction has no citation. The methodology is insufficient it lacks Period scope; Literature collection; Criteria for inclusion and exclusion of articles; number of articles and Analysis. The study’s analysis could focus on the efforts made by governments in these countries to promote cashew nut processing. For example, the Tanzanian government has created a favorable environment for processors by facilitating raw material purchases, providing loan opportunities, and implementing an export levy for raw cashew nuts. Despite these initiatives, the quantity of processed cashew nuts remains low compared to the total produced. The discussion is likely to center on the challenges that hinder processing, extending beyond a mere analysis of government actions. While the study acknowledges the market challenge, existing literature indicates a strong demand for processed cashew nuts. However, the primary obstacle lies in the processors’ capacity to supply the required quantity within a specific timeframe. Although there is a considerable amount of literature on processing, the study has only reviewed 13 documents. Unfortunately, this limited review is insufficient for conducting a robust analysis of the sector, drawing strong conclusions, and providing actionable recommendations.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? No\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-108
|
https://f1000research.com/articles/11-433/v1
|
19 Apr 22
|
{
"type": "Research Article",
"title": "Maxillary first premolar shape (and not size) as an indicator of sexual dimorphism: A 2D geomorphometric study",
"authors": [
"Srikant Natarajan",
"Junaid Ahmed",
"Nidhin Philip Jose",
"Shravan Shetty",
"Srikant Natarajan",
"Nidhin Philip Jose",
"Shravan Shetty"
],
"abstract": "Introduction The primary aim of the study is to evaluate the morphological form of the maxillary first premolar using 2D geomorphometry and evaluate the sexually dimorphic characteristics. Methods The present study was carried out on standardized photographs of right Maxillary first premolar from 55 dental casts (33 male and 22 females). Nineteen landmarks (based on geometric and anatomic evidence) were marked on the tooth using TPSdig software and analysed using Morpho J applying procrustes analysis and discriminant function analysis Results The results showed similar centroid sizes between gender (p = 0.606). Procrustes ANOVA for shape analysis showed a greater dimorphism between sexs (f value of 1.4 ; p value=0.0624). Discriminant function analysis based on the procrustes coordinates showed an overall accuracy of 90.91 % in classifying sex based on the landmark coordinates with correct classification of 20/22 (90.99%) females and 30/33 (90.91) males. Conclusion Shape of the tooth can be measured objectively using geometric morphometric methods which can be utilized to identify the sex of an individual. Enamel covering the crown of the teeth is biologically stable resisting climatic, physical and chemical insults. The enamel is derived from ectoderm and once formed does not change during the life. The tooth's structure and shape are determined by the sex chromosomes, which is well represented as sexual dimorphism. The study evaluates the occlusal and contact area morphology of premolars. These are important parameters considered during restorative treatment, functional rehabilitation and forensic investigations.",
"keywords": [
"Sexual dimorphism",
"Geometric morphometry",
"Procrustes analysis",
"Maxillary first premolar",
"Principle component analysis",
"Tooth form",
"Tooth shape"
],
"content": "Introduction\n\nIn biology, “size” and “shape” are vital to describe an organism or a component of an organism, and expressing these involves the use of morphometry. “Size” is usually represented by linear and angular measurements of an entity. “Shape” on the other hand, is more complex to visualize and involves robust statistical procedures. Shape information is essential for bioarchaeology, anthropology, and forensic sciences to interpret evidence obtained from human remains. Rohlf and Marcus (1993) have reviewed the various procedures utilized in describing shape in biology and have termed the use of geometric morphometric analysis as a revolution in describing the “shape”.1 The geomorphometric analysis involves defining landmarks on the biological structure in two or three dimensions followed by statistical procedures using this data for visualizing the changes in shape. Further, the analysis also graphically represents the landmark variations on transformation grids to identify the deviations seen between species, gender, etc. Forensic anthropologists usually employ these landmark coordinates to define the biological profile.2\n\nSexual dimorphism in dentition is a well-established detail. Sexual dimorphism in a tooth may be attributed to variations in genetics, epigenetic factors, and the influences of sex hormones. In a study by Guatelli-Steinberg et al. (2008) on seven different populations, they found no significant association of sex hormone concentrations post-birth and tooth patterning.3 However, Ribeiro D et al (2013) have demonstrated a significant role of intrauterine testosterone levels in dental development and size.4 Taking cognizance of the varied reports pertaining to hormonal regulation of tooth size/shape, genetic influence on tooth shape must be considered primary. Genes that influence tooth patterning during odontogenesis are located in the sex chromosomes.\n\nSexual dimorphism has been researched by numerous morphometric studies involving linear measurements of width, length and diagonal measurements of teeth, measurements of areas of the occlusal surfaces, etc.5-7 Geomorphometric analysis of shape is a relatively new research modality to evaluate shape of the teeth.\n\nThe aim of the present present study is to evaluate the geometric morphometric variations of landmarks of the maxillary first premolar and its sexual dimorphism.\n\n\nMethods\n\nThis study was conducted on the Dakshina Kannada population of Karnataka, India. The study commenced following the approval by the institutional ethics committee of Manipal College of Dental Sciences, Mangalore, Manipal Academy of Higher Education (vide ref no20018, dated 16th March 2020). Dental study casts of 55 individuals were retrieved from the archives of Department of Orthodontics, Manipal College of Dental Sciences, Mangalore. Broad written consent was taken from the patients during treatment, for use of the plaster casts for research assuring anonymization. Individuals born and brought up in Dakshina Kannada region were included in the study and their study casts were retrieved. The maxillary pre-treatment dental casts (poured in dental stone) of individuals meeting the inclusion criterion;, were retrieved for photography. All models with intact maxillary right first premolar, without any evidence of wear, caries, restorations or crown placement were included in the study. Age, sex and demographic details were noted from the patient management system. The randomization of the orthodontics patient box numbers was done using random numbers generated from www.random.org. The study was a time bound study to be completed in three months’ time. Total 55 random numbers were generated, distributed as 22 Females and 33 Male individuals having a mean age of 18.39±5.07 years (males 20.15±4.97 years and Females 17.33±4.91 years).\n\nThe data acquisition process involved photographing the cast, marking the landmarks (using TPS dig and TPS util softwares). The acquired landmark coordinates were then analysed in MorphoJ and PAST softwares. The statistical procedures used were procrustes superimposition, principal component analysis, discriminant function and canonical variate analysis.\n\nStandardised images of the first maxillary premolar’s occlusal surface were taken with a Canon EOS 700D camera (Canon Inc., Japan) using macro mode. Each cast model was placed in the center of the field of focus of the lens with a scale placed adjacent to the cast (positioned at the occlusal surface level). An intermediate value diaphragm was used for an adequately focused photograph of the premolar’s occlusal surface. The Maxillary first premolar was positioned with the cemento-enamel junction (CEJ) perpendicular to the optical axis making it parallel to the camera lens as suggested by Wood and Abbot.8 The photographs were saved in *.tiff format for transfer to the landmark marking software TPSdig.\n\nThe landmarks were determined based on the anatomy (anatomic evidence) as well as the geometric contours (geometric evidence) of the tooth. A total of 19 landmarks were identified (11 based on anatomical evidence of cusp, ridges and grooves, and 8 based on geometric evidence of crest of curvature and line angles) as shown in Figure 1.\n\nUsing the TPSutil software, the *.tps file was generated incorporating 55 photographs of the maxillary casts in high resolution. This was followed by the landmark acquisition using TPSdig2 software. Using the landmark selection tool, the 19 landmarks (as described in Figure 1) were defined for each maxillary right first premolar of the 55 individuals and a *.tps file, (i.e. landmark data file) was generated. This file represented landmarks in two dimensions in “x,y” format. The data was then analyzed using Morpho J and PAST software for performing the principal components analysis, discriminant function analysis, canonical variate analysis, generate transformation grids and graphical representations.\n\nPrincipal Components Analysis (PCA) was used to analyse differences within the individuals Discriminant Function Analysis (DFA) and Canonical Variate Analysis (CVA) were utilized to compare the data of ‘shape’ between the sexes.\n\n\nResults\n\nPrincipal Components Analysis (PCA) showed that the first 11 principal components accounted for 80% of the maxillary first premolar variance, with the first four representing 50% of the variability (Table 1). The scatter was evenly noted on either side of the scatter plot axis, indicating a homogenous distribution of landmarks among individuals. The variability was seen more in males than in females (Figure 2).\n\nA=PC1 vs PC2; B=PC2 vs PC3 and C=PC1 vs PC3, Crimson dots represent female and black dots represent males.\n\nThe deformation graph showed prominent variability in the lingual direction of the buccal and the lingual cusp tips and buccal translation of the buccal as well as lingual crest of curvature. The distal end of the distobuccal cusp ridge and the mesial end of the mesiolingual cusp ridge tends to be shifted more towards the middle of the buccolingual dimension. The mesial marginal developmental groove remains lingual to the groove at all times, but shows some variation buccolingually (Figure 3A).\n\nThe lollipop graphs show the mean shape of the landmarks as circles and the relative position change of the landmarks is represented by sticks.\n\nCanonical variate analysis was used to evaluate the differences in the landmark positioning between gender. The analysis shows that between gender, the Mahalanobis distances was 2.5676 and Procrustes distances among groups was 0.0303. Transformation grids illustrated that male teeth have more buccally placed distobuccal cusp ridge and lingual cusp tip. Further the buccal crest of curvature, the mesial marginal developmental groove, the mesiolingual cusp ridge end and the lingual crest of curvature are more lingually placed in males compared to females (Figure 3B).\n\nOn comparison of the centroid size, females had a mean centroid size of 15.36+1.24 which was marginally larger compared to the male individuals’ centroid size of 15.201+1.33 units. This was however not statistically significant with a p value of 0.606 (t=0.517). Procrustes ANOVA for shape analysis showed a greater variation with an f value of 1.4 and p value of 0.0624, indicating an increased variation in shape of the teeth among gender when compared to size. This result indicated that shape of the premolar was significant at the level of 10% alpha, whereas centroid was not.\n\nDiscriminant function analysis was performed based on the procrustes coordinates. There was 90.91 percent accuracy in classification of gender based on the landmark coordinates. The accuracy was 20/22 (90.99%) among females and 30/33 (90.91) among males accounting for 50/55 (90.91) in the total sample (Figure 4).\n\nBlue bars on left represents male and red bars on right represents females.\n\n\nDiscussion\n\nThe quantification of an object’s geometric shape by measurement of landmark coordinates is done using geometric morphometric analysis. This method utilizes multivariate statistical procedures that allow preservation of the landmark data in its original geometric shape and enables us to visualize the shape changes in real dimensions.9 There are various methods of evaluation of shape or form of a biological structure. These include Euclidean Distance Matrix analysis,10 Elliptical Fournier analysis11 and the most researched and understood procrustes superimposition method.12\n\nMaxillary first premolar is particularly an essential tooth for taxonomic classification. The tooth has a characteristic asymmetry due to the prominent mesial marginal developmental groove and depression making the mesial outline concave compared to distal outline. Bailey and Lynch (2014) have assessed the shape of the mandibular premolars in Neanderthal and Modern humans and found their classification to be more accurate in modern humans with an accuracy of 98.1% as compared to Neanderthals who had an accuracy of 65%.11 The shape of a tooth is said to be a result of genetic drift rather than environmental factors.11 Genes play a primary role in morphodifferentiation of teeth. MSX, DLX, PAX9 genes are responsible for histo- and morpho-differentiation of tooth germ during odontogenesis. Studies have shown that MSX 1 mutation leads to agenesis of teeth especially the premolar segment.13 SPRY2, GAS1 and RUNX2 are potential candidate genes which influence the formation of secondary dentition including premolars.14 These studies indicate that genes play an important role in formation and morphology of premolar.\n\nIn our study, the centroid sizes did not show a significant variation in size of the premolars. This is in line with the other studies in Indian population. Banerjee A et al. (2016) in their odontometric study, showed that the mesiodistal width, buccolingual width and the crown lengths of maxillary first premolar were not significantly different between sexes.15 Yong et al. (2018) have studied the sexual dimorphism of human premolars in the Australian population and found that the centroid size did not show any significant difference by sex. However, Procrustes ANOVA showed significant effects of sex, accounting for 1.1% variation.12 This is in concordance with our present study where we found shape of the tooth to indicate greater sexual dimorphism than the size as seen by procrustes ANOVA.\n\nOne of the limitations of our study is the 2 dimensional analysis. The buccolingual inclination of the premolar might affect the landmark visualization in a two dimension. This can be overcome by incorporation of the third dimension of the coordinates, and performing a 3D geomorphometric analysis. This would yield a better discriminating ability of the landmarks. Secondly, a study evaluating the shape variables of all the premolars and molars of the human arch would give an all-inclusive assessment of tooth shape.\n\nFor future work, newer mathematical and computational models can be explored for shape analysis of teeth. The newer techniques would be capable in obtaining optimal parameters from the landmark data. In this regard, Choi G et al. (2020) in their recent research have compared area based, procrustes based methods with their new shape analysis technique using quasi-conformational theory. They have demonstrated superior results using their newer conformational theory in delineating gender and ancestry among indigenous and European origin Australian population. They have stated that, procrustes based approach gives satisfactory accuracy in discrimination, however, the Teichmuller distance method used is superior owing to the methodologies incorporating mean and Gaussian curvature analysis.16\n\n\nConclusion\n\n2D geomorphometric analysis of the maxillary first premolar was performed utilizing 19 landmarks of geometric and anatomical evidences. The literature shows that size shows minimal variation between gender.12,17 However, the shape using the 19 landmark coordinate data of the premolar teeth, was able to discriminate gender with an accuracy of 90.91% (as demonstrated by discriminant function analysis). Canonical variate analysis showed that the maximum variation was in relation to the positioning of the distobuccal cusp ridge end and the lingual cusp tip, both of which are more buccally placed in males. Such variations play an important role in reproduction of the premolar morphology during restoration and tooth alignment. Further, the shape coordinates can be used to estimate sex of the individual as an adjunct in forensic investigations of skeletonized remains.\n\n\nData availability\n\nFigshare. MAXILLARY Premolar Landmark Data. DOI: https://doi.org/10.6084/m9.figshare.19487717.v118\n\nThis project contains the following underlying data:\n\n- 2 D data of the landmarks of the maxillary first premolar\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nRohlf FJ, Marcus LF: A Revolution in Morphometrics. Trends Ecol. Evol. 1993; 75(4): 129–132. Publisher Full Text\n\nKatherine Spradley M, Jantz RL: Ancestry Estimation in Forensic Anthropology: Geometric Morphometric versus Standard and Nonstandard Interlandmark Distances. J. Forensic Sci. 2016; 61: 892–897. PubMed Abstract | Publisher Full Text\n\nGuatelli-Steinberg D, Sciulli PW, Betsinger TK: Dental crown size and sex hormone concentrations: Another look at the development of sexual dimorphism. Am. J. Phys. Anthropol. 2008; 137: 324–333. PubMed Abstract | Publisher Full Text\n\nRibeiro DC, Brook AH, Hughes TE, et al.: Intrauterine hormone effects on tooth dimensions. J. Dent. Res. 2013; 92: 425–431. Publisher Full Text\n\nZorba E, Spiliopoulou C, Moraitis K: Evaluation of the accuracy of different molar teeth measurements in assessing sex. Forensic Sci. Med. Pathol. 2013; 9(1): 13–23. PubMed Abstract | Publisher Full Text\n\nIl YH, Yang DW, Lee MY, et al.: Morphological analysis of the occlusal surface of maxillary molars in Koreans. Arch. Oral Biol. 2016; 67: 15–21. PubMed Abstract | Publisher Full Text\n\nJames Macaluso P Jr: Investigation on the utility of permanent maxillary molar cusp areas for sex estimation. Forensic Sci. Med. Pathol. 2011; 7: 233–247. Publisher Full Text\n\nWood BA, Abbott SA, Graham SH: Analysis of the dental moprhology of Plio-Pleistocene hominids. J. Anat. 1983; 137(Pt 2): 287–314. PubMed Abstract\n\nMitteroecker P, Gunz P: Advances in Geometric morphometrics. Evol. Biol. 2009; 36(2): 235–247. Publisher Full Text\n\nLele S, Richtsmeier JT: Euclidean distance matrix analysis: A coordinate-free approach for comparing biological shapes using landmark data. Am. J. Phys. Anthropol. 1991; 86: 415–427. PubMed Abstract | Publisher Full Text\n\nBailey SE, Lynch JM: Diagnostic differences in mandibular P4 shape between neandertals and anatomically modern humans. Am. J. Phys. Anthropol. 2005; 126(3): 268–277. PubMed Abstract | Publisher Full Text\n\nYong R, Ranjitkar S, Lekkas D, et al.: Three-dimensional (3D) geometric morphometric analysis of human premolars to assess sexual dimorphism and biological ancestry in Australian populations. Am. J. Phys. Anthropol. 2018; 166(2): 373–385. Publisher Full Text\n\nLidral AC, Reising BC: The role of MSX1 in human tooth agenesis. J. Dent. Res. 2002; 81(4): 274–278. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOlley R, Xavier GM, Seppala M, et al.: Expression analysis of candidate genes regulating successional tooth formation in the human embryo. Front. Physiol. 2014; 5(Nov): 1–8. PubMed Abstract | Publisher Full Text\n\nBanerjee A, Kamath V, Satelur K, et al.: Sexual dimorphism in tooth morphometrics: An evaluation of the parameters. J. Forensic Dent. Sci. 2016; 8(1): 22–27. PubMed Abstract | Publisher Full Text\n\nChoi GPT, Chan HL, Yong R, et al.: Tooth morphometry using quasi-conformal theory. Pattern Recogn. 2020; 99: article 107064 (page 1–11). Publisher Full Text\n\nBourdiol P, El Karam SA, Martin JF, et al.: Age and gender-related differences in premolar and molar functional areas. J. Oral Rehabil. 2007; 34(4): 251–258. PubMed Abstract | Publisher Full Text\n\nNatarajan S: MAXILLARY Premolar Landmark Data. figshare. Dataset. 2022. Publisher Full Text"
}
|
[
{
"id": "164380",
"date": "21 Apr 2023",
"name": "Aman Chowdhry",
"expertise": [
"Reviewer Expertise Dental anatomy",
"Dental Anthropology",
"Forensic odontology",
"Oral Pathology",
"reserach methodology",
"evidence based dentistry."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nNon metric traits (i.e. shape and not size) should be highlighted clearly with its applications not only in domain of forensic but also other dental specialties (in Introduction).\n\nOnly hormonal influence on shape has been discussed and not specific 1-2 genes or embryology (cap stage) which leads to shaping of particular tooth (in introduction). Later on discussion has genes mentioned but hormones absent. I suggest both should be present in 1 place (discussion / introduction)\n\nWhy premolars was choice of sample to be studied and its implications should be mentioned in manuscript.\n\nTry and add https://doi.org/10.1186/s41935-023-00329-2 for premolar recent catalogue of trait. Specially for premolar accessory cusp in 24 (PAC-4), premolar accessory cusp in 25 (PAC-5).\n\nPlease make the methodology/manuscript anonymous (without mentioning the name of particular institute (your details will come affiliation section).\n\nWhat is Dakshina Kannada region/population .. please support it with facts/references.\n\nMean age of patients/cast included should results, although age range of the included sample can be mentioned in methodology.\n\nAbbreviations like *.tiff and TPSdig should be either explained or elaborated as acronyms.\n\n3d geomorphometric surface analysis should be mentioned with reference as future prospects\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": "10329",
"date": "09 Oct 2023",
"name": "Srikant Natarajan",
"role": "Author Response",
"response": "Point 1 Non metric traits (i.e. shape and not size) should be highlighted clearly with its applications not only in domain of forensic but also other dental specialties (in Introduction). reply A paragraph in the introduction is added defining and highlighting the importance of non metric traits in dentistry “The shape of the tooth is determined in the \"morphogenetic stage\" of tooth formation. The tooth's shape is decided by the epithelium's infolding during the cap stage, which results from the expansion of the predecessor bud stage. Independent of the size of the tooth, deeper or additional infolding may result in the creation of conspicuous ridges, extra cusps, and tubercles. The term \"non-metric traits of the tooth\" refers to these anatomical characteristics. Non-metric traits of the tooth are essential for the dentists to plan single tooth restorations, as the internal tooth structure varies as per the outer contours. The variations in the tooth shape may also affect development of occlusion by orthodontics and prosthodontists.” Point 2 Only hormonal influence on shape has been discussed and not specific 1-2 genes or embryology (cap stage) which leads to shaping of particular tooth (in introduction). Later on discussion has genes mentioned but hormones absent. I suggest both should be present in 1 place (discussion / introduction) reply As suggested, hormonal and genetic concepts are introduced in the introduction “The reasons for sexual dimorphism of tooth are different from the craniofacial bones. The facial skeleton including the mandible exhibit sexual dimorphism either directly or indirectly due to the hormones and their muscle activity. However tooth are less influenced by hormones. (Oettlé et al., 2009) In a study by Guatelli-Steinberg et al. (2008) on seven different populations, they found no significant association of sex hormone concentrations post-birth and tooth patterning. 3 However, Ribeiro D et al (2013) have demonstrated a significant role of intrauterine testosterone levels in dental development and size. 4 Taking cognizance of the varied reports pertaining to hormonal regulation of tooth size/shape, genetic influence on tooth shape must be considered primary. Genes that influence tooth patterning during odontogenesis are located in the sex chromosomes. Genes polymorphisms of MSX1, PAX 9, AXIN2 and EDA are associated with hypodontia and change in tooth morphology. (Kerekes-Máthé et al., 2023)” Point 3 Why premolars was choice of sample to be studied and its implications should be mentioned in manuscript. Try and add https://doi.org/10.1186/s41935-023-00329-2 for premolar recent catalogue of trait. Specially for premolar accessory cusp in 24 (PAC-4), premolar accessory cusp in 25 (PAC-5). Reply The justification of assessing the premolars are explained in the introduction. “In their latest work, Chowdhry A et al. (2023) assessed 20 non-metric features of human dentition. They report sexual dimorphism in incisor and molar features in their research. Their research revealed that males and females had slightly larger proportions of premolar accessory cusps in first and second premolars, respectively. (Chowdhry et al., 2023) These patterns show the shape of the premolars and are independent of tooth size. The present study explores the change in the shape of the premolars using landmark based morphometric evaluation. Premolars are in the fields of influence different genes modulating anterior and posterior dentition. The tooth are unique in the permanent dentition as they do not have a deciduous counter part. Thus, our pilot study focused on the evaluation of sexual dimorphism of the premolar class of the tooth.” Point 4 Please make the methodology/manuscript anonymous (without mentioning the name of particular institute (your details will come affiliation section). Reply The methodology is anonymized by removing the name of the institute. Point 5 What is Dakshina Kannada region/population .. please support it with facts/references. reply The details of the region is described in the beginning of the methods with an addition of a new reference “This study was conducted on the Dakshina Kannada population of Karnataka, India. Dakshina Kannada, also known as South Canara, is the southern coastal district of Karnataka State, covering an area of 4859 square kilometers. This district is bordered by the sea to the west, the Western Ghats to the east, Udupi district to the north, and Kerala State to the south. (Lokesh et al., 2022) “ Point 6 Mean age of patients/cast included should results, although age range of the included sample can be mentioned in methodology. reply The age range is mentioned in the methodology and the mean age is shifted to the results. Point 7 Abbreviations like *.tiff and TPSdig should be either explained or elaborated as acronyms. Reply Explanation is included in the methodology section “The photographs were saved in Tag Image File Format (*.tiff) format for transfer to the landmark marking software “TPSdig” for windows available at https://www.sbmorphometrics.org/soft-dataacq.html.” Point 8 3d geomorphometric surface analysis should be mentioned with reference as future prospects Reply Yong R et al’s study in 2018 has been quoted and added under the head of future prospects."
}
]
},
{
"id": "182639",
"date": "13 Jul 2023",
"name": "Julia Aramendi",
"expertise": [
"Reviewer Expertise Geometric morphometrics",
"human evolution",
"biological anthropology",
"biomechanics"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper entitled ‘Maxillary first premolar shape (and not size) as an indicator of sexual dimorphism: A 2D geomorphometric study’ presents the study of the maxillary first premolar in a human population of India using a 2D geometric morphometrics approach. The study intends to evaluate the morphological differences between male and female individuals and states that the differences encountered could be linked to genetic-driven factors.\nIn my opinion, the methodology applied is adequate; however, I think there are some methodological issues that should be considered by the authors before the paper can be accepted for indexing.\nThe most problematic aspect of the study is related to sample size. One of the main concerns when applying statistical tests such as Discriminant Analyses or Canonical Variate Analyses is related to the number of landmarks used with regard to sample size in each group.\nFor geometric morphometrics, there is a rule that states that the smallest group within the sample has to exceed the number of variables used in the analysis. In the case of the present study, the number of variables is 34, as it is calculated as the number of landmarks (19 in the present case) multiplied by the number of dimensions (2 as the analysis is performed in the 2-dimensional space), minus the degrees of freedom removed after Procrustes superimposition (in this case, 4 for the rotation, translation and scaling of the landmark coordinates). The number of male and female specimens is lower than the number of variables, as it is equal to 33 and 22, respectively.\nAnalyses such as CVA or DFA have long been known to be highly sensitive to the data used as input and prone to exaggerate the separation between samples, even if none is supposed to exist, when the sample size is small or when samples are imbalanced (Albrecht 1992; Mitteroecker and Bookstein 2011; Rohlf 2021; Courtenay 2023).\nComparing the results provided in the present study, it seems that differences between the female and male groups might have been exaggerated, as a result of sample size, since the PCAs show a high overlapping degree between both samples. Thus, in order to verify the difference in shape observed by the authors, it would be necessary to enlarge the sample size.\nOn top of that, there are other methodological problems that should be considered by the authors;\nThe figure explaining the landmarks is not clear enough and sensitivity tests regarding landmarking accuracy should be performed to make sure that the analyses can be reproduced. The intra and interobserver’s error could be considered by repeatedly landmarking at least some of the individuals to then assess if landmark definitions are robust enough. I say that because according to Figure 2 there seems to be an outlier, that might be explained by landmarking errors.\n\nThe methodology should be explained in greater detail. There is no mention to a Procrustes superimposition, step that is necessary to perform geometric morphometrics, neither do the authors explain how the analyses they use function (PCA, DFA, CVA, ANOVA). I am afraid that the lack of explanation might be linked to some of the methodological problems of the study.\n\nI also think that results are not explained properly and that unnecessary information is provided instead (i.e., Table 1). Additionally, the threshold for p values to detect significant difference between samples should be set at 0.003, as it is more robust against Type I statistical error, by lowering the risk of making a Type I error from 28.9% when p = 0.05 to 4.5% (Courtenay et al., 2021)\nIn general, it seems that there are some concepts of the methodological approach that have not been fully understood. Explanations are sometimes too vague and/or inaccurate (e.g., “Shape” on the other hand, is more complex to visualize and involves robust statistical procedures).\nI am also worried about the data collection process as many researchers do not scale the landmarks properly after using software pieces such as TPSdig2. If landmark data were not scaled after collection, the analysis on centroid size might also be misleading. For that reason, it would be great to have access to the raw landmark data gathered from the 55 individuals included in the study.\nIt would also be interesting if the authors could combine the shape and size data and perform analyses in form space. Unfortunately, those types of studies cannot be performed in MorphoJ, so a different software piece should be used instead (e.g., R).\nAll things considered, I think the study has the potential to be of interest to the scientific community, if the methodological concerns raised here are tackled. Unfortunately, at the moment, I do not think that the outcomes can be used to support their conclusions, since there are some fundamental problems in their methodological approach.\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? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "11015",
"date": "03 Mar 2024",
"name": "Srikant Natarajan",
"role": "Author Response",
"response": "Reviewer Comment 1: In my opinion, the methodology applied is adequate; however, I think there are some methodological issues that should be considered by the authors before the paper can be accepted for indexing. The most problematic aspect of the study is related to sample size. One of the main concerns when applying statistical tests such as Discriminant Analyses or Canonical Variate Analyses is related to the number of landmarks used with regard to sample size in each group. For geometric morphometrics, there is a rule that states that the smallest group within the sample has to exceed the number of variables used in the analysis. In the case of the present study, the number of variables is 34, as it is calculated as the number of landmarks (19 in the present case) multiplied by the number of dimensions (2 as the analysis is performed in the 2-dimensional space), minus the degrees of freedom removed after Procrustes superimposition (in this case, 4 for the rotation, translation and scaling of the landmark coordinates). The number of male and female specimens is lower than the number of variables, as it is equal to 33 and 22, respectively. Reply to comment 1: Thank you for the suggestions. We have repeated the analysis with an increased sample size and in the methods we have included one more landmark in the middle of the mesial marginal ridge, in the mesial aspect of the premolar occlusal outline accounting for 20 landmarks in total. The sample size calculation mainly depends on the dimensions used for the landmarks and the number of transformations. In our study accounting for the two dimensions used for landmarks and removal of 4 degrees of freedom we need 36 samples per group. As per the suggestion of the reviewer we have substantially increased the sample size to 60 in each group to make it total of 120 samples. Reviewer Comment 2: Analyses such as CVA or DFA have long been known to be highly sensitive to the data used as input and prone to exaggerate the separation between samples, even if none is supposed to exist, when the sample size is small or when samples are imbalanced (Albrecht 1992; Mitteroecker and Bookstein 2011; Rohlf 2021; Courtenay 2023). Comparing the results provided in the present study, it seems that differences between the female and male groups might have been exaggerated, as a result of sample size, since the PCAs show a high overlapping degree between both samples. Thus, in order to verify the difference in shape observed by the authors, it would be necessary to enlarge the sample size. Reply to comment 2: We have expanded the sample size for our study and conducted the analysis again, ensuring a 1:1 male to female sample ratio with 60 samples each. This adjustment has effectively addressed the previous imbalance and mitigated the overemphasis of differences that can occur in studies with smaller sample sizes. Reviewer Comment 3: On top of that, there are other methodological problems that should be considered by the authors; The figure explaining the landmarks is not clear enough and sensitivity tests regarding landmarking accuracy should be performed to make sure that the analyses can be reproduced. The intra and interobserver’s error could be considered by repeatedly landmarking at least some of the individuals to then assess if landmark definitions are robust enough. I say that because according to Figure 2 there seems to be an outlier, that might be explained by landmarking errors. Redoing the analysis will change the graphs also - please see the graph linked here. Reply to comment 3: During the reiteration of the analysis with an expanded sample size, we employed the Intraclass Correlation Coefficient to assess the consistency of the landmark coordinates within a subset of 20 samples. The results of this evaluation have been incorporated into the manuscript as follows “Landmarks of 20 samples (10 male and 10 female) were marked in an interval of 2 weeks by one of the authors (S.N). The sets of coordinates was used to perform the Intraclass correlation coefficient (ICC), to test the reliability of the landmarks. The analysis showed excellent agreement with ICC values of 0.91 with p value of <0.001 indicating high level of interobserver consistency in marking the landmarks.” Also the graphs and figures have been redone as the analysis is repeated with increased samples. Reviewer Comment 4: The methodology should be explained in greater detail. There is no mention to a Procrustes superimposition, step that is necessary to perform geometric morphometrics, neither do the authors explain how the analyses they use function (PCA, DFA, CVA, ANOVA). I am afraid that the lack of explanation might be linked to some of the methodological problems of the study. Reply to comment 4: We have provided a comprehensive explanation of the sequence of Procrustes superimposition, the generation of a covariance matrix, and the execution of PCA, Procrustes ANOVA, and discriminant function analysis. We sincerely appreciate your attention to this matter and trust that our detailed explanation will assist future researchers in accurately reproducing these methods. Reviewer (Julia Aramendi) Comment 5: I also think that results are not explained properly and that unnecessary information is provided instead (i.e., Table 1). Additionally, the threshold for p values to detect significant difference between samples should be set at 0.003, as it is more robust against Type I statistical error, by lowering the risk of making a Type I error from 28.9% when p = 0.05 to 4.5% (Courtenay et al., 2021) Reply to comment 5: Following your advice and the provided references, we have adjusted the p-value threshold to 0.003. We have found that neither the shape nor the size of the tooth is statistically significant. Reviewer Comment 6: In general, it seems that there are some concepts of the methodological approach that have not been fully understood. Explanations are sometimes too vague and/or inaccurate (e.g., “Shape” on the other hand, is more complex to visualize and involves robust statistical procedures). I am also worried about the data collection process as many researchers do not scale the landmarks properly after using software pieces such as TPSdig2. If landmark data were not scaled after collection, the analysis on centroid size might also be misleading. For that reason, it would be great to have access to the raw landmark data gathered from the 55 individuals included in the study. Reply to comment 6: Having expanded our sample size, we have submitted a new dataset of 120 premolar landmarks for review, accessible via a link in the manuscript. We would like to emphasize that the landmarks identified were scaled. The photographs were captured with a scale, which was documented alongside the landmarks. This methodology is detailed in the manuscript’s methods section Reviewer Comment 7: It would also be interesting if the authors could combine the shape and size data and perform analyses in form space. Unfortunately, those types of studies cannot be performed in MorphoJ, so a different software piece should be used instead (e.g., R). Reply to comment 7: We have positively received this suggestion and decided to implement it in a three-dimensional geometric morphometry analysis. This approach may necessitate collaboration with a team proficient in other software, such as ‘R’. We have acknowledged this suggestion and included the absence of this analysis as a limitation of our study in the conclusion. “Potential avenues for expanding the study could include integrating data on shape and size for the evaluation of sexual dimorphism. The emergence of open-source software modules, such as R and its extensions, could facilitate such an analysis, potentially providing deeper insights into shape of a premolar in the form space.”"
}
]
}
] | 1
|
https://f1000research.com/articles/11-433
|
https://f1000research.com/articles/13-103/v1
|
16 Feb 24
|
{
"type": "Study Protocol",
"title": "A Quasi-experimental study to assess the effectiveness of plan teaching on Knowledge regarding Artificial Intelligence-based learning among nursing students in selected College of Wardha City: A Protocol",
"authors": [
"Utkarsh Warghane",
"Seema Singh",
"Seema Singh"
],
"abstract": "Background Artificial Intelligence (A.I.) is revolutionizing various sectors like healthcare, specifically in nursing education, by improving the quality of care, streamlining workflows, and reducing the cost of healthcare. Integrating A.I. into nursing education can enhance students’ personalized and efficient learning experiences. This study will aim to develop and implement research on A.I. and identification among (BSc) nursing students in selected colleges in Wardha.\n\nProtocol 100 students will be selected for the study by using a purposive sampling technique. This study will use one group per test and post-test design, and the structured questionnaires will be delivered to the students. Pre-test and post-test data will be taken to assess the development of student knowledge.\n\nConclusions A.I. can be used to create more realistic stimulation experiences, which can help the students to develop their clinical skills. Furthermore, integrating A.I. into nursing education can revolutionize the sector by benefiting students, tutors, and the healthcare system.",
"keywords": [
"Artificial Intelligence",
"Basic BSc Nursing",
"Healthcare",
"Implications",
"Knowledge",
"Nursing Education"
],
"content": "Introduction\n\nAs healthcare grows, nursing education must evolve to keep nurses updated on nursing care. Higher education has been integrated with Artificial Intelligence (A.I.) technology, which has the potential to develop education by implementing more personalized and efficient student learning.1 The integration of A.I. into the education sector has had a long history since the 1970s, which resulted in the development of multimedia learning resources, interactive stimulation, online learning, and game development.2 A.I. holds significant potential to create more complex stimulation that can help to develop critical thinking capacity in student nurses by preparing them for real-life situations, as A.I. technology simulation will become even more advanced by offering more realistic situations to students, allowing them to practice and help in decision making and critical thinking skills.3 The benefits of A.I. in nursing education, such as interactive learning experiences using chatbot systems, will raise concerns about academics and proper guidance and ethics. However, A.I. can significantly improve nursing students’ learning.4\n\nA.I. is an impactable field for nursing and other healthcare industries. A.I.-based learning in nursing is a new field in nursing in which students will gain hands-on experience. A.I.-based learning has the potential to revolutionize nursing education by engaging learning experiences. There are several challenges in nursing education, including preparing students for rapidly changing healthcare; A.I.-based learning can address challenges in healthcare and improve student skills and knowledge. After an intervention, we will assess students’ post-tests to see significant improvement in knowledge of A.I.-based learning among B.Sc. nursing students.5 For example, by using Artificial intelligence, the patient outcome of the hospital will increase, and by using simulation teaching, the student knowledge and practice will increase.\n\nThis study will assess the knowledge regarding A.I.-based learning and its implication for nursing education, such as the need to provide more resources for A.I.-based learning in nursing to improve the quality of instruction, address student concerns about technology and update the knowledge on A.I. among students of primary BSc nursing students.\n\nThis study will assess the effectiveness of plan teaching on knowledge regarding A.I.-based learning among BSc nursing students in selected colleges in Wardha.\n\n\n\n1. To assess the knowledge of A.I.-based learning among BSc nursing students.\n\n2. To assess the effectiveness of planned teaching among students of BSc Nursing.\n\n\n\n• Assess: According to the Oxford Dictionary, assessment is “evaluating or estimating the nature, ability, or quality”. This study evaluates the effectiveness of planned teaching on the knowledge regarding A.I.-based learning.\n\n• Knowledge: According to Oxford Dictionary, “facts, information, and skills acquired through experience or education; the theoretical or practical understanding of a subject”. This study focuses on knowledge regarding A.I.-based learning.\n\n• Artificial intelligence: According to the Oxford Dictionary, A.I. is “the theory and development of computer systems able to perform tasks that would normally require human intelligence, such as visual perception, speech recognition, decision-making, and translation between languages”.\n\n• BSc nursing students: According to the Oxford Dictionary, A four-year undergraduate degree program that prepares individuals to become registered nurses.\n\n• Plan teaching: According to the Oxford Dictionary, it is a systematic approach to organizing and delivering instruction designed to meet all learners’ needs.\n\n\nProtocol\n\nEthical approval for the study will obtained from the Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research. (Deemed to University) Ref No. D.M.I.H.E.R. (D.U.)/I.E.C./2023/1270. Written informed consent will be obtained from students and the head of the Institution.\n\nThis research study will be conducted at Smt. Radhikabai Meghe Memorial College of Nursing, Datta Meghe Institute of higher Education and Research Sawangi (M) Wardha.\n\nWe will get permission for data collection from the principal of the Nursing college. On the first day, we will take consent from students regarding inclusion in the study. On the same day, a pre-test on knowledge regarding A.I.-based learning will be taken from students. After the pre-test, planned teaching will be given to the students. On the seventh day, the Same group of students’ post-tests will be taken to evaluate the effectiveness of planned teaching.\n\nInclusion criteria\n\n1. Basic BSc nursing students who will enroll at the Datta Meghe Institution of Higher Education and Research.\n\n2. Students who are available at the time of data collection.\n\n3. Students who provide informed consent to participate in this study.\n\nExclusion criteria\n\n3. Students who are not available at the time of research.\n\n4. Students who do not provide informed consent to participate in the study.\n\nThe sample size calculation with reference studies.6 The following formula was used for the sample size calculation:\n\nRepresents the desired level of statistical significance at 5% Type I Error\n\nZβ=0.84: Represents the desired power for 80%\n\nPrimary variable = knowledge of A.I.\n\nThe percentage for knowledge before teaching structured programs regarding A.I. = 34.07% (As per Reference study).6\n\nPercentage for knowledge after teaching structured program = 54.07% (Expected).\n\nConsidering % a clinically significant margin of improvement, 20%\n\nMinimum sample size required\n\nA total of 93 students will be included in the study. The participants will be selected conveniently, and the method used will be a non-probability convenient sampling technique. Figure 1 shows a schematic presentation of the pre-experimental one group and post-experimental research design used for the present study.\n\nChange in knowledge.\n\nThe pre-test and post-test will be used to assess knowledge levels. The change in knowledge after planned teaching intervention will be assessed by source.\n\nThe anticipated bias is possible at the statistical analysis level, which will be mitigated using proper analytical software and double verification of the outputs.\n\nLevel of knowledge.\n\nThe data will be analysed according to sociodemographic data and knowledge scores of students on A.I.-based learning. Frequency, percentage, mean, and S.D. by considering the p-value <0.05 will be calculated, and the chi-square will be used to understand the relationship between various demographics and knowledge. All the statistical analysis will be performed by using S.P.S.S. software version 27.\n\nOnce completed, the study will be published in Indexed Journals (Scopus, Web of Science, PubMed).\n\nCurrently, the study still needs to be started.\n\n\nDiscussion\n\nMany studies have been performed on A.I., but more research is needed for nursing education.7 Harsh et al. provided a comprehensive overview of A.I., Machine Learning (ML) and Deep Learning (DL) in healthcare industries that describes the cost of care, the shortage of staff and the need for better data management. The author then discusses how A.I., ML and DL can address these challenges. The article also discusses the challenges that must be addressed to realize the potential of A.I., ML, and DL entirely in healthcare settings.6 Allam JP et al. proposed a deep learning algorithm for drowsiness detection using single-channel electroencephalogram (E.E.G.) signals. The algorithm is based on the conventional neural networks (CNN) that are trained on datasets of E.E.G. signals collected from awake or drowsy participants. The author evaluated the performance of the algorithms on a test set of E.E.G. signals and found that they achieved an accuracy of 90%9—a significant improvement over previous methods for drowsiness detection, which had 70% detection. The author also discusses the algorithms’ limitations and suggests possible future research directions. One limitation of the algorithm is that it is only designed to work with single channels in people wearing E.E.G. headsets with multiple channels.7 A cross-sectional study conducted in Syria by Sarya Swed et al. on knowledge, attitude and practice of A.I. among doctors. 1494 samples from doctors and medical students. The inclusion was voluntary. Of the total participants, 255 participants (16%) were doctors, and others, 1,252 (83%) were undergraduate medical students, about 1,055 (70%) knew A.I. and 357 (23%) participants knew about an application in the medical field.10\n\nIn Middle Eastern countries, the implication of A.I. for the diagnosis and treatment of patients is more significant for better outcomes.11 There are many articles published on planned teaching related to different medical categories. Nursing education has several challenges, including preparing students for rapidly changing healthcare.6,12,13 A.I.-based learning has the potential to address challenges and provide students with the skills and knowledge they need to succeed.10",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nAllen DMW, Allen JR: How artificial intelligence is transforming the world. Brookings; 2018.\n\nChen X, Xie H, Zou D, et al.: Application and theory gaps during the rise of Artificial Intelligence in Education. Comput. Educ. Artif. Intell. 2020 Jan 1; 1: 100002. Publisher Full Text\n\nTrends M: Artificial Intelligence: Nurses Integral Role in Deployment. Analytics Insight. 2020.\n\nRobert N: How artificial intelligence is changing nursing. Nurs. Manag. (Harrow). 2019 Sep; 50(9): 30–39. Publisher Full Text\n\nKathleen G, John S, Gerardo D: Artificial Intelligence Education for the Health Workforce: Expert Survey of Approaches and Needs.\n\nKhushbu M, Archana M, Mayuri H: the effectiveness of planned teaching and practice regarding growth monitoring of under-five children among Anganwadi workers in a rural area of Wardha district.\n\nZhang K, Aslan AB: A.I. technologies for education: Recent research & future directions. Comput. Educ. Artif. Intell. 2021 Jan 1; 2: 100025. Publisher Full Text\n\nRathi HK, Dawande P, Kane S, et al.: Artificial Intelligence, Machine Learning, and Deep Learning in Health Care. ECS Trans. 2022 Apr 24; 107(1): 15981–15987. Publisher Full Text\n\nAllam J, Samantray S, Behara C, et al.: Customized deep learning algorithm for drowsiness detection using single-channel E.E.G. signal.2022; pp. 189–201.\n\nMehta N, Harish V, Bilimoria K, et al.: Knowledge of and Attitudes on Artificial Intelligence in Healthcare: A Provincial Survey Study of Medical Students medRxiv.2021\n\nRenn BN, Schurr M, Zaslavsky O, et al.: Artificial Intelligence: An Interprofessional Perspective on Implications for Geriatric Mental Health Research and Care. Front. Psych. 2021; 12. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTaksande V, Burbare N, Chaure K, et al.: To Assess the Effectiveness of Planned Teaching on the Knowledge Regarding Epilepsy in Children Among the Anganwadi Workers. Int. J. Curr. Res. Rev. 2020; 12(24): 151–154. Publisher Full Text\n\nMendhe DM, Lohakare A, Lohakare T, et al.: To Assess the Effectiveness of Planned Teaching Regarding Domestic Accidents among the Elderly People. Indian J. Forensic Med. Toxicol. 2020 Oct 29; 14(4): 6641–6645.\n\nKhalid A, Hani H, Daniyal A: A Survey of Artificial Intelligence Techniques Employed for Adaptive Educational Systems within E-Learning Platforms.Publisher Full Text"
}
|
[
{
"id": "258765",
"date": "30 Apr 2024",
"name": "Moustaq Karim Khan Rony",
"expertise": [
"Reviewer Expertise Artificial Intelligence and Nursing"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nComments to authors- This intriguing protocol addressing the integration of AI into nursing education holds immense promise for advancing both learning outcomes and healthcare practices. By designing a quasi-experimental study, you are pioneering a path towards personalised and efficient learning experiences for nursing students. Your dedication to innovation is commendable and promises transformative benefits for the entire healthcare sector. However, please address my following comments: Data Collection Process: -\n\nUtilizing standardized assessment tools for the pre-test and post-test could enhance the reliability and validity of the data collected, ensuring consistency and comparability of results. -\n\nEnsuring consistency in the delivery of planned teaching across all sessions and instructors could minimize variability and ensure the uniformity of the intervention's impact on participants.\nThanks\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-103
|
https://f1000research.com/articles/12-822/v1
|
13 Jul 23
|
{
"type": "Research Article",
"title": "Structural and functional abnormalities of the tongue: An epidemiological study from a tertiary care center",
"authors": [
"Angela Piplani",
"Mathangi Kumar",
"Ravindranath Vineetha",
"Ranjanee Srinivasan",
"Kalyana Chakravarthy Pentapati",
"Angela Piplani",
"Mathangi Kumar",
"Ranjanee Srinivasan",
"Kalyana Chakravarthy Pentapati"
],
"abstract": "Background: The tongue is a prominent muscular organ of the oral cavity and the integrity of the tongue mucosa frequently can reflect the overall health of an individual. There are a number of notable structural and functional alterations that can affect the tongue. These changes may be symptomatic or asymptomatic. Hence, the aim of the present study was to determine the prevalence of structural and functional abnormalities of the tongue in a population reporting to a tertiary care center. We also assessed the prevalence of the normal variants and evaluated the normal tongue protrusion measurement in the study population. Methods: The cross-sectional study included 1,143 dental outpatients above 18 years of age who visited the Department of Oral Medicine and Radiology between October 2021 and February 2022. Demographic details of the patients were noted. Participants were asked questions regarding any symptoms or abnormalities noticed pertaining to tongue. The tongue was examined thoroughly for any structural/ functional abnormalities. The maximal tongue protrusion for each participant was measured by asking them to extend the tongue out. Medical history, drug history and social history were recorded. Results: The study included 564 male and 579 female participants; tongue lesions were positive in 66.5% of the study population. Coated tongue (26.2%) was the most frequent structural abnormality that was noted in the present study. Taste dysfunction (4.6%) was the most frequent functional abnormality. The lesions were most in the anterior two thirds (4.2%) of the tongue. Conclusions: The results of the present study showed that tongue lesions were present in 66.5% of the population. Careful and detailed evaluation of the tongue examination is mandated in routine dental checkup. This shall help in prompt identification of various etiological factors causing structural and functional abnormalities of the tongue.",
"keywords": [
"Tongue Disease",
"Glossitis",
"Prevalence Study",
"Stomatognathic System Abnormalities"
],
"content": "Introduction\n\nThe tongue is a prominent muscular organ of the oral cavity that plays a vital role in speech, mastication and digestion. The integrity of the tongue mucosa frequently reflects the oral and systemic health of an individual.1 Oral cavity, being the portal of entry to various infectious and carcinogenic agents, mucosa of the tongue is easily exposed to pathologic changes.2 Numerous oral and systemic diseases affect the tongue, impairing its structure and function and owing to its strategic position, those tongue changes can be easily appreciated. Notable structural alterations including the color, texture, size, shape, appearance of the tongue can occur due to a variety of local causes or systemic conditions. Functional abnormalities of the tongue include inability/restriction of the tongue movements, taste disturbances and/or discomfort. This can often occur in neurological conditions (palsy), oral submucous fibrosis, malignancy affecting the base of the tongue, neuromuscular disorders and post-radiotherapy. The tongue changes can either be due to local factors like trauma, contact allergy, benign, reactive or malignant growth or due to underlying systemic conditions like anemia nutritional deficiencies, infections, hormonal disturbances, immune-mediated diseases and metabolic conditions.3 Even though tongue manifestations can be the early and easily identifiable diagnostic clue, it is often overlooked during dental examination unless the patients report of specific tongue complaints.\n\nVarious studies have assessed the prevalence of tongue abnormalities in different population groups, however the clinical correlation with the changes noted in the tongue is seldom looked into.1,3 There are no population-specific studies that have assessed both the structural and functional abnormalities of the tongue. The present study intended to assess the prevalence of structural and functional abnormalities of the tongue in patients visiting a tertiary care hospital and its possible association with the patient’s history and the symptoms reported. This study will help in the understanding of the commonly encountered symptomatic and asymptomatic tongue abnormalities in patients. The present study also assessed the physiological range of tongue protrusion in the study population as such data is unavailable in the literature.\n\n\nMethods\n\nThis cross-sectional study included the outpatients visiting the various units of Kasturba Medical College & Hospital and the Dental outpatient department of Manipal College of Dental Sciences, Manipal for a period of 20 weeks from September 1st, 2021. Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee approved the study protocol (IEC 409/2021; approved on 8th August 2021). All research projects carried out in the Health Sciences division at the Manipal Academy of Higher Education come under the purview and scrutiny of the Institutional Ethics Committee, which is named as Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee. This project was registered with the Clinical Trials Registry India (CTRI/2021/09/036996; registered on 30th September 2021).\n\nThe inclusion criteria were all patients above 18 years of age who visited the dental outpatient department. Patients with severe restriction in mouth opening and those who were not willing to participate were excluded from the study. Informed written consent was obtained from individuals who were willing to participate in the study. The tongue examination was performed on patients and the following relevant data parameters were written down for each patient in the specially designed proforma by the principal investigator: age, gender and the participants were asked regarding any symptoms or abnormalities noticed pertaining to tongue. Also, the medical history, drug history and oral abusive habit history were recorded for each patient in a specially designed proforma.\n\nThe clinical examination of the oral cavity and tongue was performed in accordance with WHO guidelines (Geneva, 1997) in a well-lit, noise and crowd free room on a dental chair with artificial lighting and a mouth mirror under aseptic conditions.4 Any structural abnormality of tongue related to color, texture, size, shape and appearance were noted. The tongue was checked for depapillation, coating or inflammation, any ulcers, white lesions, red patches, pigmentation, varices and growth/swelling.\n\nIf any of the aforementioned changes were observed, the location, extent and surface characteristics of these lesions were recorded. The oral mucosal pathologies were clinically diagnosed based on their characteristic history and presenting features. The diagnosis of lichen planus was given when bilateral white lacy pattern was observed with characteristic Wickham’s striae. When scrapable white patches were seen in medically compromised patients leaving behind erythematous surfaces on rubbing a diagnosis of candidiasis was recorded. Leukoplakia is defined as “white plaques of questionable risk having excluded (other) known that carry no increased risk for cancer”. It was diagnosed by excluding other causes of raised non-scrapable white diseases or disorders patches especially in patients with strong habit history. Erythroplakia appeared as raised red velvety patches that could not be attributed to any other disease. Oral submucous fibrosis is typically diagnosed in the presence of fibrotic bands and marbled appearance of the buccal mucosa. Erythema multiforme presents as multiple oral ulcers with crusting of the lips. Allergic stomatitis is established when multiple acute onset ulcers/erythema with the history of known triggering agents.5 Suspicious growth with induration of base is diagnosed as malignancy and were sent for histopathologic examination for definitive diagnosis.\n\nAlso, subjective symptoms and functional abnormalities like dysgeusia, burning tongue, taste loss, and tongue protrusion interferences were noted. Tongue movements were evaluated and maximal tongue protrusion was measured. This was performed by asking the patient to protrude the tongue to the maximum, and measurement was done using a sterile steel scale by measuring the distance between the maxillary incisal tip and the tip of the tongue (Figure 1). Any deviation of the tongue during protrusion or difficulty in protrusion was also recorded.\n\nAll analysis was done using SPSS (RRID:SCR_002865) version 18 (SPSS Inc. Released 2009. PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc.). A p-value of <0.05 was considered statistically significant. Categorical variables were compared using Fisher's exact test or Chi-squared test.\n\n\nResults\n\nThe study population included 1,143 patients, of which 564 were male (49.3%) and 579 were female (50.7%). The mean age of the subjects was 38.59 years old with an age range of 18–85 years old (Standard Deviation; SD= 13.88). The distribution of various structural tongue abnormalities is presented in Table 1.15\n\nThe schematic representation of the common structural abnormalities of the tongue observed in the present study is shown in Figure 2.\n\nAmong the various comorbidities observed, 10.5% of the study population presented with diabetes mellitus followed by hypertension (8.9%), thyroid disorders (5.0%), immunocompromised state (2.8%) and anemia (0.8%). Oral abusive habits were reported by 25.7% of the subjects. Tobacco consumption (14.6%) was more commonly reported than alcohol (11.1%). Subjective symptoms including pain (7.0%) and burning sensation (8.2%) were also reported by the study population.\n\nCoral pink colored physiologic appearance was noted in 91.9% of participants, 5.9% had red tongue and 0.9% had pale tongue. Overall, 91.3% of them had a normal texture of the dorsal surface of the tongue and 7.1% had smooth bald tongues. Figure 3 shows the topographic distribution of the tongue abnormalities observed in the study population. Figure 4 shows the various structural abnormalities observed in the present study.\n\nFunctional abnormalities of tongue were noted in 8.7% of the study participants, of which 3.7% had restricted tongue movement (Table 2).\n\nThe range of tongue protrusion observed in the study was 15 mm to 54 mm with a mean of 40.5 mm. Table 3 depicts the range of tongue protrusion in the study population.\n\nUsing Fischer’s exact test, the association between tongue abnormalities and tobacco associated habits was assessed. There was a positive association of tobacco related habits with burning, pain, oral submucous fibrosis, verrucous carcinoma, squamous cell carcinoma, coated tongue, candidiasis, restricted tongue movement and taste dysfunction (Table 4).\n\n* statistically significant.\n\n\nDiscussion\n\nTongue abnormalities are commonly encountered in dental practice but often overlooked, if asymptomatic. The tongue may be affected by a wide range of local and systemic conditions. Structural and functional tongue abnormalities can be easily recognized on careful and detailed clinical examination. The present study evaluated the prevalence of structural and functional abnormalities of the tongue in a tertiary care hospital-based population. There is limited literature pertaining to the measurements of normal protrusive tongue movements. Understanding the physiologic range of tongue protrusion in a normal population aids in early identification of tongue restriction. Restriction in the tongue protrusion occurs in various conditions like oral submucous fibrosis, carcinomas of the base of the tongue, scleroderma and in neurological disorders.\n\nIn the present study, overall tongue abnormalities were present in 66.5% of the subjects. A Turkish study by Avcu et al. (2003) showed prevalence of tongue lesions in 52.2% of the study subjects.6 Whereas, other studies from Turkey, India and Libya showed a low prevalence of 4.9%, 2.8% and 9.2%, respectively.7,8,9\n\nThe anatomic distribution of tongue lesions was majorly noted on the anterior two thirds of the tongue (4.2%) and least seen in the ventral surface of tongue (0.3%). A study on the Libyan population showed that 90% of the lesions were on the dorsum, followed by lateral border (7%), posterior one third (2%). The least common site was the ventral surface of tongue (1%), which is in accordance with the present study.9\n\nThe most prevalent comorbidity in the study population was diabetes mellitus (10.5%), followed by hypertension (8.9%). Bhattacharya et al. (2016) estimated the prevalence of diabetes mellitus to be 3.1%, which is lower than the observations from the current study.3 A similar study on the Libyan population by Byahatti et al. (2010) found an even lower prevalence of subjects affected with diabetes mellitus (0.4%), followed by hypertension (0.3%).9 Patil et al. (2013) conducted a study in which the prevalence of anemia was 3.8%, which was higher in comparison to the present study.10\n\nIn the present study, 5.9% had red erythematous tongue and 0.9% had pale tongue. Physiologic melanin pigmentation of the tongue was noted in 4.8% of the study subjects, whereas other studies by Mumcu et al.11 (2005) and Shinde et al.8 (2017) noted 6.9% and 2.1%, respectively. There is no literature available that has assessed the prevalence of other color variations on the tongue.\n\nA positive oral abusive habit history was noted in 25.7% of the study population, of which 14.6% were tobacco users and 11.1% had alcohol consumption. In a study done by Motallebnejab et al. (2008), 54.7% of patients smoked tobacco and 35.3% had alcohol habits.12 Other studies had estimated the prevalence of tongue lesions in smokers to be 1.93%.9 A positive association between smoking and presence of hairy tongue was found by Darwazeh et al. (2010).13\n\nThere was a positive association between tobacco related habits and burning sensation of the tongue in the present study. Tobacco related habits were also associated with coated tongue, ulcers, increased incidence of candidiasis, oral lichen planus, oral submucous fibrosis, verrucous carcinoma, squamous cell carcinoma, restricted tongue movement and taste dysfunction. Similarly, Bhattacharya et al., found a positive association between oral lichen planus and oral abusive habit.3 Avcu et al., estimated the correlation between tongue lesions and smoking in the Turkish population and concluded that tongue lesions (hairy tongue, fissured tongue and coated tongue) were increased in smokers and heavy smokers than non-smokers.6 Among the structural tongue abnormalities, coated tongue was the most prevalent finding (26.2%), followed by depapillation (6.3%), ulcers (4.2%), enlarged tongue (3.1%), oral submucous fibrosis (2.5%) in the present study. Similarly, coated tongue was the most prevalent finding (30.6%) followed by fissured tongue (20.1%)3 in a study conducted by Bhattacharya et al., on the Indian population. The prevalence of coated tongue was 28.0% in an Indian study10 by Patil S et al. Shinde et al., (2017) estimated the prevalence of fissured tongue (51.7%) was high, followed by coated tongue (14.3%), geographic tongue (10%).8 A higher prevalence of fissured tongue (48.4%) was observed in a study in the Libyan population.9 By contrast, a very low prevalence of 1.1% with fissured tongue was noted in our study population. Lingual varicosity was noted in 8.5% of our subjects. Whereas, varicosity was the least common finding (0.4%) in an Indian population by Bhattacharya PT.3\n\nTo the best of our knowledge, the present study was the first to evaluate the presence of functional abnormalities of the tongue that included restriction of tongue protrusion and taste dysfunction. There is no literature that has addressed the various functional abnormalities that affect the tongue in a large population. Taste abnormalities were reported in 4.6% of the study population; 6.5% of the study subjects had tongue protrusion less than 30 mm. This is the first study that has evaluated the functional as well as structural abnormalities affecting the tongue. Kotlow et al., (1999) graded ankyloglossia into four classes: Class I- Mild (12-16 mm), Class II- Moderate (8-11 mm), Class III- Severe (3-7 mm), Class IV- Complete (less than 3 mm).14 Considering the tongue protrusion range observed in the present study population and considering the classification of ankyloglossia, we propose a new grading for tongue protrusion, as depicted in Table 5.\n\nLimitations of the present study include the observational nature due to which the contributing factors like oral hygiene, oral abusive habits, medications and systemic disorders could not be associated with the findings on the tongue. Multicentric studies from diverse populations shall aid in deeper understanding about the abnormalities that can affect the tongue.\n\n\nConclusions\n\nThe results from the present study reflected a high prevalence of abnormalities affecting the tongue. Careful and detailed evaluation of the tongue examination is mandated in routine dental checkup. This shall help in the prompt identification of various etiological factors causing structural and functional abnormalities of the tongue. Understanding the normal tongue protrusion range will aid in the early detection of restricted tongue movements.\n\n\nInformed consent\n\nWe confirm that we have obtained permission to use images and data from the participants included in this work.",
"appendix": "Data availability\n\nMendeley Data: Structural and functional abnormalities of the tongue: An epidemiological study from a tertiary center with a proposed grading system for tongue protrusion. https://doi.org/10.17632/k3vx49rbfn.1. 15\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAsakawa M, Takeshita T, Furuta M, et al.: Tongue Microbiota and Oral Health Status in CommunityDwelling Elderly Adults.2018; 3(4): 1–13.\n\nGaddey HL: Oral manifestation of systemic disease. Gen. Dent. 2017; 65(6): 23–29. PubMed Abstract\n\nBhattacharya PT, Sinha R, Pal S: Prevalence and subjective knowledge of tongue lesions in an Indian population. J. Oral Biol. Craniofacial. Res. 2016; 6(2): 124–128. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Health Organization: Oral Health Surveys. 4th ed.WHO Library Cataloguing in Publishing data; 1997.\n\nNeville BW, Damm DD, Allen CM, et al.: Oral and Maxillofacial Pathology, 4e by Brad W. Neville; 2009.\n\nAvcu N, Kanli A: The prevalence of tongue lesions in 5150 Turkish dental outpatients. Oral Dis. 2003; 9(4): 188–195. PubMed Abstract | Publisher Full Text\n\nUgar-Cankal D, Denizci S, Hocaoglu T: Prevalence of tongue lesions among Turkish schoolchildren. Saudi Med. J. 2005; 26(12): 1962–1967. PubMed Abstract\n\nShinde SB, Sheikh NN, Ashwinirani SR, et al.: Prevalence of tongue lesions in western population of Maharashtra. ~ 104 ~. Int. J. Appl. Dent. Sci. 2017; 3(3): 104–108.\n\nByahatti SM, Ingafou MSH: The prevalence of tongue lesions in libyan adult patients. J. Clin. Exp. Dent. 2010; 2(4): e163–e168. Publisher Full Text\n\nPatil S, Kaswan S, Farzan Rahman BD: Prevalence of tongue lesions in the Indian population. J. Clin. Exp. Dent. 2013; 5(3): e128–e132. Publisher Full Text\n\nMumcu G, Cimilli H, Sur H, et al.: Prevalence and distribution of oral lesions: A cross-sectional study in Turkey. Oral Dis. 2005; 11(2): 81–87. PubMed Abstract | Publisher Full Text\n\nMotallebnejab M, Babaee N, Sakhdari S, et al.: An epidemiologic study of tongue lesions in 1901 Iranian dental outpatients. J. Contemp. Dent. Pract. 2008; 9(7): 73–080. PubMed Abstract | Publisher Full Text\n\nDarwazeh A-M-G, Almelaih A-A: Tongue lesions in a Jordanian population. Prevalence, symptoms, subject’s knowledge and treatment provided. Med. Oral Patol. Oral Cir. Bucal. 2010; 16(6): 745–749.\n\nKotlow LA: Ankyloglossia (tongue-tie): a diagnostic and treatment quandary. Quintessence Int (Berl). 1999; 30(4): 259–262.\n\nPiplani A, Kumar M, Ravindranath V, et al.: Structural and functional abnormalities of the tongue: An epidemiological study from a tertiary center. [Dataset]. Mendeley Data. 2022; V1. Publisher Full Text"
}
|
[
{
"id": "222602",
"date": "15 Dec 2023",
"name": "Bijimole Jose",
"expertise": [
"Reviewer Expertise 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\nAn interesting and relevant topic is discussed in this article. Studies on functional abnormalities of the tongue are rare in literature. Researchers included all the relevant tongue lesions and functional abnormalities in this study. comments: 1.Table 1- macroglossia is size variation. 2.Table 2- add restriction of tongue movements and its percentage 3. Abstract; result- Prevalence of functional abnormalities can be added. Article can be accepted with these minor corrections.\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": "10808",
"date": "14 Jun 2024",
"name": "Mathangi Kumar",
"role": "Author Response",
"response": "Dear Reviewer, We thank you for thoroughly reading our manuscript and giving insightful comments in enhancing our manuscript. Based on these, now we have revised the manuscript which are highlighted in the revised manuscript. Our replies to the reviewer’s questions are given below. REVIEWER #1: An interesting and relevant topic is discussed in this article. Studies on functional abnormalities of the tongue are rare in literature. Researchers included all the relevant tongue lesions and functional abnormalities in this study. Article can be accepted with these minor corrections. We sincerely thank Reviewer#1 for the insightful comments on our manuscript. We have tried to incorporate the changes in the revised manuscript as follows: Comment: Table 1- macroglossia is size variation Author response: The suggested changes have been incorporated in Table 1 of the revised manuscript. Comment: Table 2- add restriction of tongue movements and its percentage Author response: The “restriction of tongue movements” have been incorporated in Table 2 of the revised manuscript. Comment: Abstract; result- Prevalence of functional abnormalities can be added. Author response: The data on the prevalence of functional abnormalities of the tongue have been incorporated in the abstract (results section) of the revised manuscript."
}
]
},
{
"id": "228869",
"date": "10 Jan 2024",
"name": "Karpal Singh Sohal",
"expertise": [
"Reviewer Expertise oral and maxillofacial surgery",
"oral medicine",
"head and neck oncology",
"clinical dentistry",
"oral and maxillofacial 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\nReviewer of Manuscript titled: Structural and Functional Abnormalities of the Tongue: An Epidemiological Study from a Tertiary Care Center.\nGeneral Comments This manuscript was meant to report on the incidence and pattern of structural and functional abnormalities of the tongue.\n\nOverall Assessment of the Manuscript First and foremost the authors are congratulated for coming up with such an interesting study. The authors have collected valuable data. There are some flaws in the manuscript as described in section wise comments.\nSection-wise comments\nThe Title:\n\nThe title length is acceptable. The title is specific and concise.\nRecommendation: it would have been better if the title could describe the population studied.\n\nAbstract:\n\nIt is according to the standards of the journal. The aim of the article has been stated. In the methods section, the authors summarize the necessary details. The main result has been described. Conclusion: is out of the context, the aim is to report on structural and functional abnormalities, and not merely lesions of the tongue Few grammatical errors.\nRecommendation: there is room for improving the grammar used and the conclusion\nKeywords:\n\nThe number of Keywords is acceptable. Keywords are not appropriate.\nRecommendation: Please re-write the keywords.\n\nIntroduction:\n\nThe introduction fails to describe the subject at hand adequately, it derails the reader from the main purpose of the study The rationale for carrying out this study is stated. The objective is not apparent A few grammatical errors were noted. The knowledge gap that the authors are trying to address is apparent. A clear flow of thoughts between paragraphs and in some places between sentences within the same text is lacking. The authors have repeated some words and ideas within the same paragraph. Citation is appropriate\nRecommendation: Please re-phrase the introduction. In the introduction section, the authors may add some literature review regarding the subject at hand.\n\nMethods:\n\nThe study design is clearly described. The population studied is not known. Though the authors report that the study was carried out in Manipal, it can not be assumed that the individuals recruited were Indians. Inclusion and exclusion criteria are very narrow. E.g Did the authors include patients with mental challenges, or those presenting with orofacial space infections? How many clinicians examined all the patients? How were inter- and intra-observer reliability taken care of? The statistical analysis carried out has been briefly described Few grammatical errors were noted.\nRecommendation: Please improve the methodology section.\nResults:\n\nThe results have been presented fairly and in a very simplified manned Few grammatical errors.\n\nRecommendation: there is room for improving the results. Considering the vast data authors have collected, it would make sense if the authors could compare the abnormalities by age group and sex, and the structural abnormalities by the site.\n\nDiscussion:\n\nThe authors have tried to discuss the results by basically comparing their results to those of other studies with minimum explanation and interpretation of the similarities and differences noted. There is repetition in reporting the results in the discussion section The flow of information requires improvements. The authors have discussed some of the limitations. The authors have disclosed the importance of the research findings to the community and the practice in brief. Significant grammatical errors.\nRecommendation: There is room for some improvement.\n\nConclusion:\n\nThe conclusion does not reflect the objectives of the study.\nRecommendation: Please re-read the conclusion\n\nReferences and citations:\n\nReferences are written as per journal guidelines. The number of references is acceptable.\nRecommendation: None.\n\nStructure and length:\n\nIt is a lengthy paper. The article is organized and balanced. It has relevant information regarding a tongue abnormalities in x-population.\n\nRecommendation: None\n\nTables :\n\nAn acceptable number of tables. The tables are relevant.\nRecommendation: none\n\nEnglish:\n\nThe English used in the article is acceptable. There are a few obvious grammatical mistakes.\nRecommendation: there is room for improving the language\nLogic:\n\nThe article has been written clearly except for the introduction part. There is a minimum violation of grammar in the manuscript, however, it does not hinder the reader from grabbing information easily.\nRecommendation: There is room for improvements.\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? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "10890",
"date": "13 Apr 2024",
"name": "Mathangi Kumar",
"role": "Author Response",
"response": "We thank you for thoroughly reading our manuscript and giving insightful comments in enhancing our manuscript. Based on these, now we have revised the manuscript which are highlighted in the revised manuscript. Our replies to the reviewer’s questions are given below. REVIEWER #2: Comment: Title: It would have been better if the title could describe the population studied. Author response: The title has been modified as per the suggestions as follows: “Structural and functional abnormalities of the tongue: An epidemiological study from a tertiary care center in India”. Comment: Abstract: there is room for improving the grammar used and the conclusion Author response: The suggested changes have been made in the revised manuscript. Comment: Keywords: Please re-write the keywords. Author response: We had used the MeSH terms for the keywords. Now, we have a few additional keywords. Comment: Introduction: Please re-phrase the introduction. In the introduction section, the authors may add some literature review regarding the subject at hand. Author response: The introduction section has been modified and recent relevant references have been incorporated. Comment: Methods: The study design is clearly described. The population studied is not known. Though the authors report that the study was carried out in Manipal, it cannot be assumed that the individuals recruited were Indians. Inclusion and exclusion criteria are very narrow. E.g Did the authors include patients with mental challenges, or those presenting with orofacial space infections? How many clinicians examined all the patients? How were inter- and intra-observer reliability taken care of? The statistical analysis carried out has been briefly described Few grammatical errors were noted. Author response: The relevant additional information regarding the inclusion and the exclusion criteria and the examiners have been incorporated in the revised manuscript. Comment: Results: There is room for improving the results. Considering the vast data authors have collected, it would make sense if the authors could compare the abnormalities by age group and sex, and the structural abnormalities by the site. Author response: We have depicted the site wise distribution of the tongue abnormalities as a pictorial representation in Figure 3. We have added two additional tables (Table 2 & 3 in the revised manuscript) depicting the site-wise distribution of structural tongue abnormalities in both the genders and various age groups (18-40, 41-65, >65 years of age) in the study population. Comment: Results: The authors have tried to discuss the results by basically comparing their results to those of other studies with minimum explanation and interpretation of the similarities and differences noted. There is repetition in reporting the results in the discussion section The flow of information requires improvements. The authors have discussed some of the limitations. The authors have disclosed the importance of the research findings to the community and the practice in brief. Significant grammatical errors. Author response: The flow of the information in the results have been modified as per the suggestions in the revised manuscript. Comment: Conclusion: The conclusion does not reflect the objectives of the study. Recommendation: Please re-read the conclusion Author response: The conclusion has been revised as per the suggestions in the revised manuscript. Comment: Logic: The article has been written clearly except for the introduction part. There is a minimum violation of grammar in the manuscript, however, it does not hinder the reader from grabbing information easily. Recommendation: There is room for improvements. Author response: All the relevant suggestions have been incorporated in the revised manuscript and the Language check was done using the Grammarly software for the revised manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/12-822
|
https://f1000research.com/articles/12-438/v1
|
24 Apr 23
|
{
"type": "Opinion Article",
"title": "Social influence and external feedback control in humans",
"authors": [
"Martin Weiß",
"Mario Gollwitzer",
"Johannes Hewig",
"Mario Gollwitzer",
"Johannes Hewig"
],
"abstract": "This article aims to describe social influence by elucidating the cognitive, affective, and motivational processes that occur when an individual experiences an attempt at being influenced. We hypothesized that these processes are part of a feedback loop system in an individual. This loop involves the situation (input), a goal state (reference), a comparator, a selection mechanism, a feedback predictor, and an action (output). Each element can become the target of social influence, and different types of social influence can be classified and explained by how these elements are targeted. For instance, attempting to persuade another person with strong arguments targets the goal state of the affected individual, while coercion targets the selection mechanism, and violence targets the action. In summary, this article aims to categorize, order, and explain phenomena in social influence research using a feedback loop framework focusing on the influenced individual.",
"keywords": [
"feedback control",
"social influence",
"social interaction"
],
"content": "Introduction\n\nIndividuals often employ a variety of tactics in everyday life to exert influence over others (Aiello et al., 2018; Higgins et al., 2003). For example, people may offer incentives such as gifts to persuade colleagues to assist with a challenging task, use rewards to encourage children to behave appropriately or present compelling arguments to convince academic peers of the validity of their theories. These tactics have been thoroughly investigated, and social influence is one of social psychology’s most extensively investigated research domains (Harkins et al., 2017). The present article seeks to provide a fresh perspective on social influence by examining the potential goals of an influencer toward an influenced target. Specifically, social influence means producing a particular effect in another individual, whether it is a thought, emotion, decision, or behavior (Moussaïd et al., 2013). Our perspective will focus more on the effects of social influence on an individual’s behavioral control system rather than their perceptual system.\n\nWe build on cybernetic models of behavioral regulation, that is, models that are designed to understand or regulate dynamic processes in complex systems (Leonard et al., 2021), focusing on the fundamental elements that comprise these models. We aim to establish a theoretical connection between cybernetic control models and other feedback regulation models, such as reinforcement learning (i.e., learning the optimal behavior in an environment to obtain maximum reward through observations of how choices are influenced by past decisions and rewards; Sutton & Barto, 1998). By combining these models, we can identify interactions that enhance our understanding and prediction of social influence. For example, combining our proposed model with reinforcement learning can help determine which social influence mechanisms are advantageous and crucial in social interactions. Social influence can target elements in cybernetic models, representing different forms of social influence. We propose a framework that identifies beneficial and detrimental manipulation tactics in everyday life, contributing to a broader understanding of social influence. This article aims to answer the question of how and where the influencer can enter the internal feedback loop system of the target to achieve the desired outcome.\n\n\nFeedback loops and feedback control\n\nA feedback loop is a unit of cybernetic control consisting of four elements in a particular organization: input, reference, comparator, and output (Carver & Scheier, 2000b). Input is often described as the is-state, while reference can be framed as a goal or ought-state. The comparator is a core component that detects the distance to the desired outcome (is-ought discrepancy), and the output refers to the actual behavior. Two types of feedback loops can be differentiated: one that aims to reduce discrepancies between the status quo and a goal (approach) and another that aims to increase discrepancies toward a particular anti-goal (avoidance). Thus, any social influence on another individual will either act through an approach or avoidance feedback loop. The cybernetic feedback model has been associated with the self-regulation of behavior, attention, and affect (Carver, 2004; Carver & Scheier, 1981, 2000a). Different approaches have shown that social influence is related to emotional processes (Fischer et al., 2003), visual attention (Frick et al., 2018), and self-regulation (vanDellen & Hoyle, 2010).\n\nWe believe that the cybernetic model is applicable to social interactions and understanding the self-regulation of behavior, attention, and affect in an actor. Moreover, exploring these processes in a target being influenced by an influencer is beneficial to understand interpersonal communication, improve leadership effectiveness, or to develop effective behavior interventions. Our approach is a potential step towards establishing a stronger connection between research on cybernetic action control, general action control theories, and the social influence literature.\n\nIn social interactions, actions elicit responses from others, leading to the possibility of feedback control where the actions of two or more parties influence each other. Classical frameworks have already investigated the translation of cybernetic regulatory principles into social phenomena (von Bertalanffy, 1950; Wiener, 1949), providing insight into complex behavioral patterns, such as economic exchange and political negotiation (McClelland & Fararo, 2006; Robinson, 2007). Jäger et al. (2015) have illustrated how the cybernetic feedback model applies to negotiation situations, where self-regulation functions as a feedback loop for goal orientation and identifies central challenges in negotiation processes. To address these challenges, specific self-regulation strategies were developed based on the individual components of the cybernetic feedback model.\n\nSimilar control systems were involved in controlling the behavior of social interaction partners. Motor movements (e.g., waving one’s hand) can be equated with communicative signals to other people (Wolpert et al., 2003). The principles governing social behavior, such as communication that influences our social world, also apply to motor behavior that impacts our physical environment. In each interaction, the actor generates motor commands based on predictions regarding the target’s potential reaction to the commands (e.g., raising one’s hand to ask for the waiter). The perceived target behavior is then compared with the predicted reaction, closing the loop of social interaction. Additionally, an individual might respond to the same input with many different patterns. For example, raising a hand in a lecture might indicate a question or stretching owing to tiredness. The professor’s response will depend on their interpretation of this social cue, either asking the student for their question or ignoring the signal altogether. Therefore, the interpretation of social signals may be ambiguous, and there is often a delay between the action and the intended reaction. This feedback loop demands a different approach than interactions with non-human physical objects, which are less likely to deviate from predictable behavior to the same degree.\n\nDepending on the influencers’ objective, they can adapt their social behavior to reduce the discrepancy between the current and desired states. Feedback control theories have previously been applied to explain influencers’ behavior (Diel et al., 2021; Mansell, 2020; Sadiq et al., 2021). We aim to extend this approach by using feedback control theories to explain the target’s (i.e., affected person) behavior. Accordingly, we want to examine the effects of the change in the feedback loop processes from the target’s perspective. Specifically, we seek to understand how and why certain aspects in the target’s feedback loop, which might not be overt, can be effectively influenced to achieve a desired outcome.\n\n\nSocial influence\n\nSocial influence research has a long tradition, with the concept frequently discussed regarding social power (McDonald & Crandall, 2015; Raven, 1964; Turner, 1991). In its early stages, power was defined mathematically as the maximum possible force “Person A” could induce on “Person B,” divided by B’s maximum resistance (Lewin, 1941). Later, “influence” was defined as a force that an agent uses to alter the target’s behavior, opinions, attitudes, goals, needs, and values (French & Raven, 1959). In their framework, French and Raven (1959) primarily differentiated between various types of exerting power, which will not be detailed here. Like influence, social power has often been defined as the ability to control or influence another’s thoughts, behavior, or feelings in a meaningful way (Fiske, 1993; Thibaut & Kelley, 1959; Vescio et al., 2003). Nonetheless, the terminologies of “power” and “influence” are sometimes used interchangeably. French and Raven (1959) attempted to resolve this by defining influence as “kinetic power, just as power is potential influence” (p. 152), thereby distinguishing between potential and actual demonstrations of power.\n\nIt is important to note that not all social influences involve power. This article focuses on influence, defined as “attempts to affect or change other people” (Levi & Askay, 2015, p. 128). Building on previous models, Raven (1992) shifted the focus from power subtypes to interpersonal influence, where agents are rational decision-makers who weigh the costs and benefits of their attempts to influence targets. This approach acknowledges that targets’ internal processes may adapt to agents’ attempts to influence them.\n\n\nCombining feedback loops and social influence\n\nFrom a feedback loop perspective, extending the potential locus of influence may allow for a fresh perspective on human social interaction. Hence, we aimed to differentiate between different forms of social influence using the feedback loop perspective of the target of influence. Within this framework, there are various ways in which an external social agent can target elements of the feedback loop system of the target to achieve a desired outcome.\n\nFeedback loops consist of several stages or elements, including the reference value, comparator, input, and output (Carver & Scheier, 2000b). In adapting the cybernetic feedback model to social influence, we have slightly modified these terms coined by Carver and Scheier (2000b) to better suit our purposes. We refer to the reference value as a goal state as it represents the desired outcome of a sequence of actions. In our case, the input is described as the present social situation. During social influence situations, individuals learn from feedback received from the situation and make predictions about their own success, which we refer to as feedback prediction. This process affects the comparator/reference, just like the goal state and situation. In between these stages, we have included action selection and execution, which operationalize the output function and achieve the desired goal, thereby modifying the classical feedback model for social influence. Our adaptation of the feedback model for social influence is supported by previous research in social psychology, which has highlighted the importance of social norms, expectations, and feedback in shaping behavior (Cialdini & Goldstein, 2004; McDonald & Crandall, 2015; Wood, 2000), thereby providing a basis for understanding the processes involved in social influence. Importantly, some examples of influence aim to target an approach feedback loop in the target, while others address an avoidance loop (Carver & Scheier, 2000b). These two types of loops are conceptually linked to promotion and prevention focused on the target (Higgins, 1998, 1999).\n\nWe propose a model comprising five key elements to access the internal feedback loop of a target, as illustrated in Figure 1. These elements are explained through the example of two roommates negotiating over the division of a shared television. The influencer uses the elements to manipulate the target’s internal goal state, situation, action selection, feedback prediction, and behavior.\n\nImagine two people—an influencer and a target—arguing about the division of a shared television, the goal. Let us consider a situation where the influencer wants to buy a brand-new television. The influencer may try to increase the value of the shared object and negotiate a deal to “sell” the shared television to the target, manipulating the target’s goal state (a). In this situation, the influencer persuades the target to understand that the goal is a worthwhile undertaking with advantages over other goal-like items. Alternatively, the influencer may want to keep the television and try to devalue it to get the target to buy a new one. In this situation, the influencer might persuade the target that the goal is not worthwhile. Both strategies directly manipulate the target’s internal goal state or reference; in these examples, the influencer tries to amplify or attenuate the goal for the target by either increasing or decreasing the value attributed to the goal. Hence, the amplification, attenuation, implementation, and elimination of a goal may be relevant principal target strategies.\n\nTo manipulate the situation (b), the influencer can encourage the target to withdraw or to act. For example, the influencer could give the target a cheap TV as a gift to eliminate the discrepancy between not having a TV and wanting one, or remove the TV from the target’s access to increase the target’s desire for it. When the situation is manipulated, the comparator (which reflects the difference between the goal state, the current situation, and feedback prediction) can guide the target’s action selection.\n\nWhen there is a misalignment between the target’s goal and their current situation, action selection (c) becomes important. The influencer can advise the target to encourage or discourage certain actions. For example, if the influencer wants to support the target’s goal pursuit, they can emphasize the quality of the current television and how difficult it would be to find a new one. On the other hand, if the influencer wants to discourage the target from achieving their goal, they can suggest that the target buys a new TV. Depending on their interests, the influencer may suggest actions that increase or decrease the likelihood of the target achieving their goal, including suggesting dubious alternatives.\n\nInfluencing the target’s feedback prediction (d) mechanism might motivate or discourage them by enhancing or lessening their expectations of achieving the goal. For example, the influencer could say, “I will make it very difficult for you to get this TV!” or “Why bother buying a new TV when you can have this one easily?” Hence, the action might be encouraged or hindered; alternatively, lowering the target’s expectations might result in frustration and disappointment, leading them to discontinue potential further efforts.\n\nLastly, during the action phase (e), the influencer can directly change the target’s behavior by making it easier or harder to perform certain actions. For instance, the influencer might see the target packing up the TV and try to remove it from the house before they do. In some cases, violent or deceptive methods may be used, such as physically stopping someone from running away, not paying a previously negotiated price because no contract was signed, or “accidentally” breaking the TV.\n\nTo illustrate our theoretical views and contribution to the literature, we provide specific examples of negotiation, social norms and sanctions, compliance, advertisement, and nudging in the following subsections. While previous research has identified different strategies of social influence (Bruins, 1999; Higgins et al., 2003), our approach exceeds existing approaches by categorizing these strategies according to the five entrance gates to the internal feedback loop. Thereby, we show how our feedback framework can be used to distinguish and understand the different forms of social influence.\n\n\nSocial influence towards the goal state\n\nTo clarify how influence works, we outline the conceptual differences between persuasion and manipulation; then, we explore how changes in the target can be achieved through persuasion and how this relates to the goal state.\n\nInfluence through persuasion can affect the goal state even before the target takes any action. Persuasion is the most appropriate term for what we consider influence toward the goal state. Falk and Scholz (2018) defined persuasion as changes in the preferences or behavior of recipients of information that conform to the active attempts of a communicator to promote such changes. According to the elaboration likelihood model (ELM; Petty & Cacioppo, 1986), a dualistic process accounts for attitude changes, which is relevant to changing goal states. The central route comprises a deliberate argumentation that requires a high degree of message elaboration to elicit a change in one’s attitudes and beliefs. Moreover, the peripheral route works with stimuli such as the influencer’s attractiveness or level of knowledge, which could lead to increased credibility.\n\nIn addition to the influenced target route, the self-regulatory focus of the target is critical to determining the most effective manner of persuasion (Aaker & Lee, 2001). Individuals with an independent self-view (i.e., a self-regulatory focus on promotion) prefer a persuasion focusing on approach motivation (Aaker & Lee, 2001). In contrast, those with an interdependent self-view (i.e., a self-regulatory focus on prevention) prefer a persuasion that focuses on avoidance (Aaker & Lee, 2001). Matching the persuasion/benefit of the interaction partner with the self-regulatory focus of the target leads to more effective persuasion (Pentina & Taylor, 2013).\n\nAaker and Lee (2001) demonstrated these propositions through experiments, calling this mechanism a “central processing route to persuasion.” Although the authors did not apply a cybernetic view to their study, this perspective might be quite close to persuasion research. Their persuasive approach is characterized by its impact on the goal state or reference value, which constitutes the central mechanism in a cybernetic feedback loop system. Therefore, the persuasive approach aligns with the mechanism proposed by the cybernetic feedback loop system.\n\nEmpirical evidence indicates that negative framing of information in a prevention-focused context is more effective in persuading individuals than positive framing, and vice versa for promotion-focused contexts (Holler et al., 2008; Spiegel et al., 2004). For instance, Holler and colleagues provided a negative framing of insufficient tax provision, stating that “the health care system could not be maintained, and in case of illness outdated methods would be used” (Holler et al., 2008 p. 7). They found that individuals with a prevention focus were more tax compliant when presented with information emphasizing potential danger, and vice versa. Our framework aligns with the idea that persuasion is most effective when it matches the goal category, hence promotion or prevention domains.\n\nOur proposed model suggests that persuasion can be most effective when transforming goals into action plans. This occurs when the goal is roughly defined, and the person considers the steps needed to achieve it. Manipulating goals can involve implementing a new goal or modifying an existing one, such as amplifying, attenuating, or eliminating it. To illustrate these differences, we give the following examples.\n\nAsch (1940) argued that the primary process in influence is not to change the attitude toward but the meaning of the object. Thus, changing the object’s meaning can lead to changes in implicit valuation, cognitive goal structures, attitudes, and behavior. Persuading individuals to frame desired goals can be an effective strategy for influencing action selection. However, framing requires the individual to have relevant knowledge about the object (Nelson et al., 1997). Framing can amplify or attenuate existing goals and their evaluation toward a specific direction using existing knowledge structures and potentially related long-term goals. Examples of this include emphasizing the emotional value of an object (e.g., highlighting the potential for promoting social gatherings like watching sports events with friends or romantic movies with a partner) or related long-term goals (e.g., emphasizing the potential of saving money if the target keeps the TV compared with buying a new one).\n\nHaddock et al. (2008) discovered that matching persuasive messages’ cognitive or affective content with an individual’s initial attitude has a greater impact on goal persuasion than mismatched messages. Cognitive-oriented individuals are more susceptible to cognitive appeals, while affect-oriented individuals are more likely to be persuaded by affective appeals (Petty et al., 2009). For promotion-focused individuals, gain-framed messages are more persuasive, while loss-framed messages are more effective for prevention-focused individuals (Cesario & Higgins, 2008; Lee & Aaker, 2004). Matching the message frame with regulatory focus results in greater fluency and influence (Cesario & Higgins, 2008; Lee & Aaker, 2004).\n\nEvidence from consumer research suggests that the way goals are framed affects persuasion significantly (Min et al., 2013; Poels & Dewitte, 2008). For example, framing goals as pursuing intrinsic rather than extrinsic objectives can lead to more desirable outcomes and higher engagement (Vansteenkiste et al., 2004). Therefore, framing intrinsic motivation, promotion focus, or matching initial attitudes can provide an effective surface for persuasion. This can be applied to the influencer who tries to convince the target that watching TV does not align with their internal life goals (e.g., watching TV is a waste of time).\n\nIn persuasion, the fit between self-regulatory orientations (prevention and promotion) and comparative valence is crucial as persuasion is most effective when promotion-focused individuals are influenced by a positive comparative valence; the opposite is true of prevention-focused individuals (Chang & Chou, 2008). This means that if the influencer aims to convince the target that the goal is unattractive, it will work best if the target is prevention-focused. Conversely, if the influencer wants to persuade the target to believe the goal is worth pursuing, this would work best if the target was promotion-focused. The influencer can attempt to amplify or attenuate a goal state within the target by downplaying or exaggerating its value, respectively.\n\nA manipulator can influence goals to trigger conformity, as shown by an experiment in which people estimated the movement of a dot of light (Sherif, 1936). The individual assessments differed when people were alone versus in a group, suggesting that external factors can influence internal regulation. Social context can implement or amplify social goals in the manipulated person, such as maintaining social relationships or gaining recognition. Social influence is based on normative and informational influence (Deutsch & Gerard, 1955); normative influence aims to conform to expectations, while informational influence aims to reduce uncertainty. Influencers can address both types of conformity and even influence internal goals. Conformity can regulate persuasive processes and affect other levels of the feedback loop, such as restricting or postponing the selection of actions.\n\n\nSocial influence on the subjective situation\n\nTo impact a situation, individuals need to be aware of the situation and how to influence it. In our shared television example, the influencer’s belief in their ability to win the argument can affect the outcome. However, if the influencer is the property owner, they could change the situation by declaring the TV as part of the apartment inventory, altering the legality of the negotiation. This action could make the target rethink their financial situation and potentially withdraw from the negotiation, reducing the risk of a physical conflict (von Hippel & Trivers, 2011).\n\nAnother example of how influence affects the situation is that people are likelier to litter in a polluted environment than in a clean one (Cialdini et al., 1990). However, confederate littering in both environments had contrasting effects: it led to an increase in littering in the polluted environment but a decrease in the clean one. This indicates that situational cues can influence behavior. In the roommate example, the influencer could manipulate the negotiation situation by choosing a location that gives them an advantage. Let us say the influencer is good at gambling at which the target is not good and makes the goal part of a stake, compromising the target, who might feel uncomfortable in the desired scenario. Such an influence changes the current and subjective situation of the target, resulting in subsequent consequences in the feedback loop. The discrepancy between the goal state and the situation (i.e., the goal is not yet in the target’s possession) becomes amplified. The reason for this amplification is not the absolute difference between the goal and situation, as the goal remains unchanged and is still not in the target’s possession; instead, the target may be less capable of demonstrating behavior that could successfully lead to the goal. This ultimately means that the feedback prediction or success probability is lowered. Consequently, a larger discrepancy is created in the comparator.\n\nSocial comparison is an adjacent concept that alters the perception of a situation instead of the facts, with upward and downward comparisons as examples. Upward comparisons aim to increase achievement, while downward comparisons aim to increase subjective well-being (Wheeler, 1966; Wills, 1981). In influencing the television negotiation, the influencer might point to newer and better TV models if the intention is to keep the shared TV; if the intention is to sell it, the reference may be to older TV models or the benefits of the shared TV.\n\nThe specific reason for influencing a situation is often aimed at subsequently affecting the different mechanisms of the feedback model. According to the mechanism of upward and downward comparison, an influence on the perceived state may provoke a discrepancy in the comparator of the feedback loop or obscure an existing one. Furthermore, it is possible to influence the situation to increase the basic physical distance between the goal and the target. Another reason for influencing might be to decrease action opportunities and, thus, influence action selection. In both cases, the performance of a successful action by the target becomes increasingly difficult, indicating that influence decreases the probability of success, affecting feedback prediction.\n\n\nSocial influence on action selection\n\nPersuasion can alter the internal feedback loop of others during action selection. While the concept of persuasion is widely studied in social psychology, we will only discuss a relevant aspect of persuasion in our study—our interpretation of persuasion based on the feedback framework and its impact on the feedback loop. It is difficult to isolate persuasion solely aimed at action selection versus goal structures, such as an individual’s basic preferences. However, differentiating between the two types of persuasion could aid in understanding the persuasion mechanism. We aim to provide a systematic persuasion approach based on the feedback loop’s affected aspects.\n\nMatching the argument in the influencer’s statement to the function underlying the target’s attitudes is an important aspect of persuasion (Lavine & Snyder, 1996). People have different attitude functions for various issues, and not all are equally receptive to persuasion. Knowing the target’s attitude functions helps the influencer evaluate the effectiveness of their persuasive attempts, and using convincing arguments instead of weak ones is crucial for successful persuasion (Petty & Wegener, 1998). Persuasive messages targeting important attitude functions are processed carefully and are less influential (Marsh et al., 1997). Several factors contribute to the success or failure of persuasive attempts aimed at action selection and influencing the internal feedback loop of the target.\n\nChambon and Haggard (2012) proposed a model on the prospect aspect of agency, suggesting that early signals reflecting action selection contribute to a sense of control. A positive sense of agency helps individuals adjust to a dynamic environment and direct their behavior toward a goal (Elsner & Hommel, 2001; Hommel & Elsner, 2009). Thus, it is useful to reinforce prioritized actions that lead to control over the environment (Redgrave et al., 2008; Redgrave & Gurney, 2006). It is challenging to influence directly at this stage. However, an external source might be able to manipulate the internal feedback loop; arguments previously expressed by others before action selection may come to mind at this stage.\n\nIn the context of the shared TV example, imagine that the influencer wants to donate the TV to charity, but the target wants to keep it. If the influencer posts about it on social media, knowing the target will see it, it could lead to the target either withdrawing their desire for the TV or reinforcing their attempts to keep it. This influence strategy is based on the target’s re-evaluation processes and could be successful for the influencer.\n\nAnother way to influence action selection is through obedience. Milgram’s (1963) experiments demonstrated how people comply with commands despite potentially harming others. In these experiments, a fictional authority-subordinate relationship was established to create a goal state that required a predetermined action (i.e., administering electrical shocks to an unseen receiver). Later research replicated these findings, showing the importance of predetermined action selection as a potential influence strategy (Slater et al., 2006). The use of electric shocks as a means of social influence highlights the complexity of social influence and the need for a nuanced understanding of the underlying processes. For instance, the experiment could also influence the goal state, as using electric shocks for education may differ depending on one’s moral objections.\n\nAccording to Stayton et al. (1971), humans are receptive to social influence through external signals rather than internalized control. This suggests that humans are prepared to obey verbal instructions. The foot-in-the-door technique (Freedman & Fraser, 1966) is an example of compliance without the involvement of an authority figure. This technique initially makes a small request, followed by a larger related request. The strategy is successful where the compliance rate is higher for those who received the original request than those who did not (Freedman & Fraser, 1966).\n\nThe influence of an influencer on the target’s action selection can be affected by various factors, such as the influencer’s perceived reputation and trustworthiness. If the target perceives the influencer as highly reputable and trustworthy, they may be more likely to obey or comply with the influencer’s advice. This is true, even if the advice does not necessarily align with the target’s intuitive approach to achieving their goals.\n\nIn our shared TV example, the influencer might suggest a specific action that is purposeful but may not align with the target’s initial preferences. However, this tactic is more likely to be effective if the influencer is perceived as highly reputable and trustworthy, which may lead the target to comply. Depending on the influencer’s goal, they may suggest actions that increase or decrease the probability of the target achieving their goals. For instance, an influencer may suggest dubious action alternatives to compromise the target’s success rate or portray an authority that the target should obey, especially if the influencer appears to have more experience or technical knowledge.\n\nOther social manipulation tactics, such as coercion, hardball, or silent treatment (see Buss, 1992), also fall under this category. These tactics use strong aversive motivational tools to push a particular action selection in the target. However, this study does not address these tactics. Another potential approach to influence action selection is nudging, which uses positive reinforcement and indirect suggestions to encourage a particular behavior or decision without restricting the individual’s freedom of choice (Sunstein, 2014).\n\nIn summary, the effectiveness of an influencer’s strategy in influencing the target’s action selection depends on various factors, including the influencer’s perceived reputation and trustworthiness, their interests, and the type of approach they use.\n\n\nSocial influence on behavior while acting\n\nThe influence on actual behaviors is particularly challenging to isolate in the proposed feedback model. In this article, we tried to address attentional, perceptive, or cognitive manipulations in the stages preceding entering a feedback loop. Hence, we refer to physically-induced manipulation when discussing behavior in this subsection. This subsection focuses on influences closely linked to behavioral change, such as violent or deceptive action redirections (e.g., pretending to be a courier for someone before delivering completely different information).\n\nHowever, most social influence research concerns social norms and subtle psychological processes (Cialdini & Goldstein, 2004). Descriptive norms, for instance, can be sufficient to alter an individual’s behavior through exposure to peer groups (Cullum et al., 2010; Goldstein et al., 2008). The social influence induced by social norms can alter the internal feedback loop regarding action selection. Specifically, exposure to peer groups’ behavior can prime and make a selected action more salient (Do et al., 2022). In contrast, the ability to deduce intentions from peers’ behavior can lead to the formation of goals.\n\nIn addition, actively promoting and enforcing social norms can alter the future behavior of others. For example, people may ostracize norm-deviant behavior to strengthen their position in a group (Willer et al., 2009). This directly affects the punished person and indirectly influences others through previously mentioned mechanisms. The punishment may implement an avoidance goal, influence action selection by favoring active avoidance choices and alter feedback prediction by reducing the expected success of behavior opposing the influencer.\n\nThe distinction between physically-induced manipulations and social influence research is important in understanding the various mechanisms of social influence. While physically-induced manipulations are the focus of this study, social norms and influence processes are important to altering feedback loop behavior. By understanding these mechanisms, we can gain insight into how behavior can be altered in feedback loops, both directly and indirectly.\n\n\nSocial influence on feedback prediction\n\nIn reinforcement learning theories, feedback prediction is the predicted reward value of performing an action. Our brains utilize these values to adapt behavior by biasing action selection towards instrumental actions with the highest predicted reward value (Redgrave et al., 1999). In the broader sense of value based on expectancy models, feedback prediction optimizes goal pursuit and combines reward value and the probability of success. Those behavioral actions that are instrumental to achieving goals with higher predicted outcome values are chosen more often (Samejima et al., 2005) and more rapidly (Brown & Bowman, 1995) than those with lower values. Furthermore, the reward system is also known to prefer actions and goals that implicate actual (Bednark & Franz, 2014; Behne et al., 2008) versus potential (Leotti & Delgado, 2011; Tricomi et al., 2004) control over the environment.\n\nIn our proposed model, an internal feedback loop can be altered by manipulating a target’s subjective probability of success; it can be increased to stimulate or motivate action or reduced to discourage it. As mentioned (see “social influence on the subjective situation”), manipulating the situation may often be a valid pathway to influence feedback prediction.\n\nIn some cases, the influencer may use deception to instill a false belief in the target’s mind to reach their goal. We use deception as a functional strategy to approach goals in a social interaction by influencing others in their feedback prediction process. The central aim is to alter the target’s success predictions, either by exaggerating them to promote success or abridging them to discourage it. We will not delve into the consequences of falsehoods or affective aspects that may arise when deception is detected, as we focus on the framework for entering a feedback loop.\n\nFraming is key in achieving this type of influence, as it emphasizes the distinct attributes of an issue over other potential consequences (Nelson et al., 1997; Nelson & Kinder, 1996; Price & Tewksbury, 1997); its effectiveness seems to depend on familiarity with the issue. The reason might be that persons familiar with a certain topic have a deeper knowledge structure than individuals unfamiliar with it. In the context of our shared TV example, a devaluation framing could be a phrase like “this TV is not that special, you can find it anywhere,” whereas a valorization of the target could be the phrase, “this TV is one of a kind and at such an unbeatable price.” Many studies have explored this persuasive strategy (Druckman, 2001; Gächter et al., 2009; Tversky & Kahneman, 1981).\n\n\nExamples of model applications\n\nIn the following subsections, we describe studies dealing with different aspects of social influence and persuasion. We outline how our model differs characteristically and alters the internal feedback loop of participants at different stages. In Higgins’ (1997) regulatory focus theory, the authors posit two distinct self-regulatory orientations—prevention and promotion focus—relevant to our model as they directly influence the cybernetic feedback loop. Following that model, we posit that a prevention or promotion feedback loop will occur in a target person. There may be overlapping aspects between the studies regarding the different entrance gates to manipulate the target’s feedback loop, which we will present in the following subsections. Moreover, not all aspects of our model will be addressed and easily implemented in every experiment. However, by altering the experiments, we propose simple and creative solutions to describe manipulation options according to our model. While the mechanisms of our feedback model could most effectively be investigated through laboratory experiments, we have decided to include both field and laboratory experiments.\n\nBefore starting with the research examples, we will briefly describe the systematic approach used to analyze studies in this domain. First, we identified the relevant goals in the experiment (e.g., social goals, personal goals) and whether their value was manipulated or an additional goal was included. For instance, introducing a social comparison may add social goals to an otherwise private context. Second, we analyzed the influenced situational characteristics. Third, we examined whether action selection was manipulated—whether a specific behavioral choice was promoted. Fourth, we examined action opportunities or direct effects on action execution. Fifth, we examined the effects of social influence on feedback prediction and goal state versus situation discrepancy, for example, by manipulating a target’s subjective goal attainment probability.\n\nIn the following subsections, we explain the findings, apply our model, and derive additional experimental manipulations based on our framework.\n\n\nDescriptive and injunctive social norms\n\nDescriptive norms refer to the behavior of relevant others (e.g., peers, family, society) and provide a socially determined standard for effective behavior (i.e., what individuals typically do). Injunctive norms refer to appeals about what other members of society approve or disapprove of. Melnyk et al. (2013) argue that descriptive norms motivate engagement in specific behavior depending on their social rewards, while injunctive norms motivate engagement through the threat of punishment. They investigated the effect of regulatory focus on the influence of descriptive and injunctive social norms in the context of sustainable food choices.\n\nIn the first three experiments by Melnyk et al. (2013), state regulatory focus was induced as a between-variable to participants. For norm induction, participants were shown a fictitious website covering information on fair-trade coffee using a text framed with either descriptive or injunctive norms. Participants were then asked to answer questions regarding attitudes toward fair-trade coffee and their planned buying intentions. While controlling for past buying behavior, an induced promotion focus increased the efficiency of descriptive norms, resulting in more favorable attitudes and intentions toward sustainable choices. In contrast, injunctive norms were not influenced by the regulatory focus state.\n\nWhile the second experiment by Melnyk et al. (2013) only targeted the perceived fluency of the different normative messages, the third experiment replicated the first, using organic milk instead of fair-trade coffee. Here, regulatory focus induction was included in the text message and not conducted separately, as in the first experiment. However, the results were comparable to those of the first experiment. When taken together, the results showed that promotion focus increased buying intentions in the descriptive norm condition, while no differences were found in the injunctive norm condition. This may be due to a ceiling effect since intentions were as high in the injunctive conditions as in the promotion-focused descriptive conditions. The former aligns with descriptive norms’ influence on a promotion-feedback loop.\n\nAs participants in the studies conducted by Melnyk et al. (2013) were invited to evaluate the design of a website, their goal orientation was distracted from the actual research goal. However, social comparisons regarding relevant others (i.e., other students), which were used in the descriptive norm induction (“A great number of […] students purchase Fair Trade coffee regularly”), might have activated an explicit awareness of social norms regarding pro-environmental behavior. Importantly, environmental goals were not different between conditions, so only the presence of different social goals was relevant.\n\nParticularly, the presence of an injunctive norm generally increased intentions, so it was sufficient to influence behavior. According to our model, we argued that this was due to the inclusion and presence of a social goal. In the descriptive norm condition, we suggested that the presence of a promotion focus was sufficient to activate a goal in participants. Moreover, participants in the studies of Melnyk et al. (2013) conducted the experiment together in one room, facilitating implicit social comparisons with peers. Consequently, the situation was influenced by the data collection (i.e., in groups), indicating that the state-induced regulatory focus might have become fragile, particularly for individuals sensitive to social pressure.\n\nIn the studies conducted by Melnyk et al. (2013), action selection was manipulated by the different normative framings present in the website content. However, as participants were instructed to focus on design features, the target manipulation tool of the study was implicit. The distraction from the study goal might have enabled participants to answer the dependent variable questions for reasons other than experimental manipulation (e.g., general pro-environmental attitudes). Nonetheless, the experiments did not directly influence action selection because they were based on text reading and questionnaires. However, the success of feedback prediction depends on interindividual differences. Individuals with pro-environmental attitudes and a low budget might have perceived the situation as a trigger for a discrepancy between the personal goal state and the is state (i.e., they would like to buy fair-trade coffee but cannot afford it). Regarding the apparent study goal—evaluating a website design—a discrepancy between the goal state and the situation might only have been present if the website design was overly flawless. Such a scenario would have caused participants to be unable to offer suggestions and fail to achieve the goal.\n\nFuture research based on the cited study might add several conditions and prerequisites to investigate the interaction between regulatory focus, descriptive norms, and the first and injunctive norms. We propose two additional conditions with the explicit goal of focusing on the text by asking participants whether the content could lead to more purchases of fair-trade products (versus a control group). Therefore, differences in the goal state and the influence on action selection could be examined using our framework. Furthermore, we recommend that future studies focus more on goal-framing than on peers’ behavior; for instance, buying fair-trade coffee could be presented to students as promotional material for local and sustainable food production or preventing the exploitation of local resources.\n\nIn two field experiments, Goldstein et al. (2008) investigated the influence of three different towel reuse signs in hotel rooms on pro-environmental behavior. The hotel guests were not informed about their participation in the experiment and were randomly assigned to one of three towel-reuse conditions.\n\nIn the first experiment, the first condition corresponded to an industry standard that emphasized towel reuse for environmental reasons without referring to any descriptive and normative information. The second condition corresponded to a global standard describing the towel reuse behavior of all hotel guests. The third condition was a provincial norm describing the towel reuse behavior of other guests who had booked the same room. The results showed that the third condition (specific hotel room) significantly impacted behavior; the provincial norm led to more towel reuse than the global and industry standards. In the second experiment, the authors replicated the findings of the first experiment, showing that hotel guests conformed more to the provincial norm compared with the norms of other hotel guests (e.g., gender identity).1 Unfortunately, there was no control condition for this experiment.\n\nThe major difference between the three main conditions was the presence of a social comparison in the second and third conditions. This may introduce additional social goals and social motivation for the target. Considering these additions, participants were prompted to compare their behavior with the proposed social comparison group. This may have motivated behavior through goals such as social attachment. As the hotel guests were ostensibly unaware of their study participation, they were also unaware of the manipulation of the goal state and the study aim. This study design has an advantage over laboratory experiments, although the latter might induce an artificial focus on social norms. However, environmental characteristics, such as the hotel type (in this case, a “midpriced chain hotel”), might have subconsciously implemented a general behavioral goal; for instance, an eco-hotel might increase pro-environmental behavior. Replicating these experiments using a controlled setting would allow for investigating general pro-environmental behavior without any norms (e.g., avoid energy-wasting behavior), which might more accurately represent an internal goal state than the signage would.\n\nAn alternative experimental manipulation of the situation could be to measure the number of towels reused per day compared with relative numbers; the situation, in this case, depends on the number of booked nights. With this approach, researchers may assess behavioral changes for guests with different bookings, identifying potential differences between staying only one night and staying one week, for example. In another hypothetical scenario, the signs might focus on different standards rather than specific reuse goals. For example, if the goal is to reuse 10 towels per week, participants’ behavior might differ if eight have already been reused when they enter the room compared with a situation where only two have been reused.\n\nThe selected study aimed to manipulate action selection using different signs. However, the most effective method for manipulating action selection was to address the current situation of participants (i.e., the towel reuse behavior of other guests who had booked the same room). This example illustrates that, during the physical absence of social agents, action selection needs to and can be manipulated via a preceding operation (i.e., manipulating the goal state or the situation). In this scenario, one possibility to influence action directly, in an ethical manner, would have been to implement a condition where cleaning staff would put the towels back, thereby forcing participants to reuse them. Participants would then have to invest more energy into not reusing the towels; for example, hotel guests may need to specifically request that staff clean the towels.\n\nAn additional reward or token system for towel reuse behavior could be applied to directly address the action and feedback prediction simultaneously. In a feedback model, when there is a significant difference between an individual’s internal reference value (such as their preference for reusing towels) and external information (such as a feedback sign in a hotel bathroom evaluating their behavior), this can lead to a larger disparity in the comparator. As a result, the individual may make more significant adjustments in their action selection and execution to decrease this discrepancy, for instance, increasing towel reuse if their initial preference for reusing towels was low. By extending and altering the study setup with these examples, future studies could investigate which pathway for addressing social norms might best foster pro-environmental behavior within a feedback loop framework.\n\n\nCompliance\n\nTo illustrate the merit of our model for compliance, we can apply our framework to research related to health promotion and disease prevention in healthcare (Spiegel et al., 2004) in a study on the nutritional habits of college students. Participants received a daily nutrition log booklet to record their daily consumption of fruits and vegetables; they were instructed to return a week later with a completed booklet. Participants received a questionnaire on food habits and health messages along with the booklet. Using a between-subjects design, participants received four different messages framing the regulatory focus (addressing the imagined benefits of compliance) and the outcome (addressing the imagined costs of non-compliance). The dependent variable was the effectiveness of health messages in changing behavior: eating more fruits and vegetables after one week. Results revealed that messages that focused on the potential benefits of successful dietary change were more effective in promoting behavior change when the goal was presented as health promotion-focused, compared to messages that focused on the potential costs of dietary change failure. The opposite was true when the goal of eating more fruits and vegetables was presented as a health prevention-focused issue, and no main effects of regulatory focus or outcome framing were identified.\n\nExperiment two was notable, where participants were requested to read either a promotion or a prevention-framed health message urging them to eat more fruits and vegetables; a goal was explicitly set. In line with regulatory focus theory and our model, we argue that social influence works best when targeting either a promotion (approach) or a prevention (avoidance) feedback loop in the target. Researchers could directly address action selection by giving participants specific action planning options in addition to the goal state (imagination of benefits). Accordingly, a fit between influencing action selection (e.g., identifying a good time) and influencing the goal (i.e., outcome benefits) may provide the best results in influencing action selection. Future research might manipulate feedback prediction by adding comparative information about the degree and likelihood of success toward dietary change.\n\n\nAdvertisement\n\nZhao and Pechmann (2007) examined the impact of regulatory focus and different framing strategies on the persuasiveness of antismoking advertisements for high school students. The authors created four antismoking advertisements that differed in their regulatory focus (promotion versus prevention) and outcome framing (favorable versus unfavorable). In the first experiment, the authors used a three-factor between-design categorization, classifying participants based on their dominant regulatory focus (assessed via a validated scale), the advertisement’s regulatory focus, and the outcome framing. A control group with a non-smoking-related advertisement was included. The criterion was the intention not to smoke cigarettes. The study found that anti-smoking advertisements were most effective when the viewers’ regulatory focus, the advertisement’s regulatory focus, and the message framing worked together. Specifically, promotion-focused individuals responded best to promotion-focused advertisements with a positive outcome framing, while prevention-focused individuals responded best to prevention-focused advertisements with a negative outcome framing. A second experiment with a similar design, but with an active manipulation of participants’ regulatory focus, replicated the results of the first experiment.\n\nThe participants in this study were randomly assigned to groups and watched an episode of a TV show where the advertisements were shown between several other filler advertisements. The goal to be implemented or strengthened in targets was non-smoking, which might be pursued by addressing health issues. However, advertisements also specifically added social goals to the context of smoking, particularly social acknowledgment and attachment. Thus, the goal level was directly addressed with these advertisements; the social environment provided positive and negative feedback toward the depicted smoker.\n\nPer our framework, the target of the presented experiments in Zhao and Pechmann (2007) was to manipulate behavior (i.e., the post-experimental questionnaire assessing the intention to smoke) via the presentation of these advertisements. The inclusion of the advice, “Don’t smoke!” in the advertisement had a direct influence on action selection but did not seem to change behavior compared to the control group. Feedback prediction was influenced by showing participants the potential social consequences of smoking and non-smoking through the behavior present in the advertisement’s social context. The study clearly showed that a match among individual regulatory focus, outcome type, and the regulatory or motivational state leads to the greatest changes in behavior. In the feedback loop framework, we argue that manipulation works on a specific feedback loop in a target. Ideally, all manipulation aspects should converge on the same feedback loop—either a promotion/approach loop or a prevention/avoidance loop.\n\nSeveral options can be employed to extend the experimental design and add manipulation possibilities using our framework. Although Zhao and Pechmann (2007) included a control condition for the task, all participants were classified by a regulatory focus or induction. An additional, unbiased control group without regulatory focus induction should be included in future research. Furthermore, the intention to smoke may vary in contexts outside the school classroom. Therefore, future studies could examine the influence of situational factors, such as watching a TV show in the classroom and on a smartphone in the corner of the schoolyard. Situational influences on intentions might then be examined by measuring baseline intentions to smoke and previous smoking behavior; these state variables might interact with the implementation of the social goals using the advertisements. In smokers or people with stronger smoking intentions, social goal implementation likely leads to a stronger is-ought discrepancy, which may increase adjustments or reactance; for example, if the discrepancy is too large for an individual to deal with. Future research should assess the level of is-ought behavior discrepancy.\n\n\nNudging\n\nAccording to Thaler and Sunstein (2008), nudging refers to interventions implemented by persons with responsibilities over a group to help those individuals make responsible decisions. We used a study investigating the effects of nudging on when and why users opt for online ID verification in the context of digital platforms to explore the application of our model in an example (Schneider et al., 2017). The researchers combined assurance statements as claims (which were framed as promotion and prevention focus) on a fictional car-sharing platform. The supporting data covered the convenience, security, and privacy aspects of online verification (present versus absent). The dependent variable was the choice for online verification (i.e., a webcam session with a verification agent) compared with offline verification (e.g., physically visiting a post office). A control group without claims and data was included in addition to the four experimental groups (two claims, each with present or absent data). The results showed that participants in the promotion focus group were more likely to choose online verification when no data was available than those in the prevention focus group. However, this effect was reversed in the presence of data, as participants chose online verification more often in the prevention focus group than in the promotion focus group.\n\nConcerning the goal state of achieving verification, two paths of action were available. Regarding action selection, participants faced a binary choice: online versus offline verification. They were asked to put themselves in the position of a prospective car-sharing user, and the goal of completing the registration process was implemented. In this case, the goal value was not manipulated, but the means to achieve it was (i.e., online versus offline verification). Depending on the car-sharing platform’s relevance for participants, their personal goals might have amplified the goal state. For example, participants who used car-sharing platforms more often were motivated to participate. A general bias towards a digital context might have implicitly influenced the situation because the study was conducted online, and participants were asked to take the perspective of a car-sharing user. The manipulation of action selection was targeted by increasing the credibility of online verification by including security-related data on the platform and the regulatory focus framing of the claims. This study is a good case of targeting action selection rather than goal structures.\n\nBy conducting the experiment in a laboratory, researchers could manipulate situational factors—such as conducting offline verification in a controlled manner and in a separate room—which reduced the influence of the distance between participants’ homes and a post office. To manipulate action, a queue condition could be implemented in the offline verification process, highlighting the time-related advantages of the online process. To influence feedback prediction, the researchers could use a sequential design to present regulatory focus framing and supportive security data, evaluate the choice option multiple times, and provide participants with more information about the likelihood of success and the difficulties in attaining the goal.\n\nWe selected a series of studies on dietary decisions to apply our model (Prinsen et al., 2013). The rationale of Prinsen et al. (2013) was that individuals conform to the eating behavior of others and, therefore, should be affected by the corresponding environmental cues. The authors conducted field and laboratory experiments using a between-group design with a bowl of hand-wrapped chocolates. The amount of chocolate taken was the outcome variable. The researchers placed a second bowl next to the bowl of hand-wrapped chocolates; this second bowl had twenty wrappers for one group of participants and was empty for the second group. Participants were more likely to take chocolates in the presence of an environmental cue (i.e., empty wrappers indicating that previous participants also took chocolate). In another experiment, the authors manipulated the healthiness of the snack (healthy snack compared with unhealthy snack) and the goal prime (a magazine on healthy eating versus a magazine on hedonic eating) to measure snack choice. The results indicated that participants conformed to environmental cues about the food type in addition to the eating behavior of others. The participants in all experiments were given a false story that they were waiting for the experiment to start; the authors evaluated the experiments during this waiting period.\n\nIn the first two experiments, no food-related goal state was implemented or directly manipulated for participants. However, since participants had to answer several questions (e.g., the time difference to their last meal), we cannot completely rule out that at least some of the participants focused on the food. Participants in the laboratory settings were told that the study assessed their reaction time (Experiment two) or their completion of a cognitive task (Experiment three). The empty wrappers may have worked to manipulate the situation in two ways: they may disinhibit eating behavior because other participants had already eaten the chocolate, which could activate social motivation to act similarly. Second, they may have directly influenced action selection by promoting simple behavioral imitation.\n\nTo manipulate the goal state, a possible experimental condition would be to label the fake “target” tasks as food-related or not. In the published study, the authors focused on manipulating the situation with the filled and empty bowls, which indicated past participants’ behavior and demonstrated that such behavior impacted decision-making. Moreover, the magazines on healthy versus hedonic eating might be considered manipulation tactics influencing the goal state or action selection. These magazines should only affect behavior if the decision to take food has already been made. In this task, manipulating the action could pose ethical issues involving forcing someone to eat. However, this may be accomplished by experiments relating to tasting and judging food, which makes people eat. Implementing a prediction error in the feedback loop of the participants would suffice to manipulate feedback prediction. For example, if the instruction had been that “eating is voluntary, but healthy versus unhealthy food (or vice versa) that does not get eaten will be thrown away,” they might have experienced a conflict between the behavior of previous participants, the goal prime induced by the magazine they read, and the type of food that would be discarded.\n\nTo ensure the optimal nudging practice, we suggest that it may be critical to reducing the discrepancy between the optimal outcome (choosing more healthy food) and the initial goal state. To disentangle the indirect influences on goal and direct influences on action, one option could be to use videos that depict or do not depict eating behavior. Additionally, the videos could include a verbal message promoting or preventing a certain kind of eating behavior, such as unhealthy food. While the direct influence on action may be the imitation of the seen/condemned behavior, the impact on the goal state should depend on the verbal content of the material. Additionally, all levels of manipulation might address either a promotion or a prevention feedback loop.\n\n\nBoundary conditions\n\nWe deal with apparent boundary conditions to complete the theoretical discourse of the social influence on a target’s feedback loop system. Our proposed model, and probably influence in general, depends on the reactance of the target. Some people may be more susceptible to influence strategies than others, and these differences may hinder or even exclude the success of social influence. Furthermore, the ability of the target to mentalize the influencer’s intentions may interfere with the influencer’s successful exertion of influence. Therefore, highly reactant individuals and people good at mentalizing their social interaction partners might not be good targets for applying this framework. However, it may be interesting to examine whether the discrepancy between the reference or goal state and the current state or situation can predict reactance. Potentially, a discrepancy that seems too large for the individual may promote reactance.\n\n\nConclusions\n\nWe proposed a social influence model that targets different parts of an interaction partner’s internal feedback loop. To illustrate the need for this model, we explained the influence on the goal state, action selection, action, and feedback prediction in detail. Lastly, we analyzed classical experiments on social influence, conformity, and advertisements and applied our model. As many examples have shown, there are different ways to enter another person’s feedback loop by exerting external social influence. However, the affected stage largely depends on the intentions of the influencer, as the same influence tactic might be interpreted differently within another stage of the feedback loop.\n\nWith our proposed model, we aimed to present a new perspective on classic experiments and paradigms that have investigated different kinds of social influence and to classify them according to our model. Future studies should selectively examine the single stages of social influence and combine this model with others, such as reinforcement learning. In addition, future research should carefully consider whether there are interindividual differences in the influenced person, such as gender or personality, that might promote or hinder the effectiveness of different influence strategies according to our model. In our view, understanding how to influence only one particular aspect while excluding the influence of another aspect may be crucial for a more detailed perspective on social influence.",
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}
|
[
{
"id": "187780",
"date": "07 Aug 2023",
"name": "Yanyan Qi",
"expertise": [
"Reviewer Expertise Social psychology",
"social behavior",
"and social emotions"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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, Weiß et al. proposed a social influence model under a cybernetic control system. They hypothesized that social influence can occur by influencing the target’s situation, goal state, comparator, action selection, feedback predictor, or action. Then as model applications, they discussed some commonly-seen social influence tactics, e.g., social norms, and advertisement, under this framework. This paper is interesting and in general easy to follow. While before indexing, I still have some suggestions.\nAbstract\nIn the first sentence the authors said “This article aims to describe social influence by elucidating the cognitive, affective, and motivational processes that occur when an individual experiences an attempt at being influenced.” But when reading the full context, I am still confused about the meaning of “the cognitive, affective, and motivational processes”.\n\nI suggest the authors write the abstract according to the manuscript, e.g., the author mentioned ‘ coercion targets the selection mechanism, and violence targets the action’, which had not been discussed in the full text.\n\nThe full context\nSince the paper is quite long, I suggest the authors give different heading levels, which will make it easier to understand the article structure.\n\nIn “social influence on behaviour while acting” section, the authors first mentioned “descriptive norms” without the definition, while in “Examples of model applications” section, the authors mentioned it again and gave a definition. Please re-organize this part.\n\nSome newly published literature could be added to the manuscript.\n\nJust a suggestion, since the author frequently mentioned “framing”, and “self-regulatory focus”, I am thinking maybe you can add an “influencing factors” section, which can contain not only the “framing” and “self-regulatory focus” from the target’s side, but also the characteristics of the influencer, e.g., as you mentioned, reputation and trustworthiness.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": [
{
"c_id": "10814",
"date": "24 Jan 2024",
"name": "Martin Weiß",
"role": "Author Response",
"response": "Dear Dr. Qi, we appreciate the thoughtful review and have addressed the feedback. These changes are noted below in a point-by-point response. Abstract In the first sentence the authors said “This article aims to describe social influence by elucidating the cognitive, affective, and motivational processes that occur when an individual experiences an attempt at being influenced.” But when reading the full context, I am still confused about the meaning of “the cognitive, affective, and motivational processes”. Response: We agree that this sentence is too vague and not well explained in the abstract. Therefore, we have reworded the beginning of the abstract as follows: “This article aims to unravel the dynamics of social influence by examining the processes that occur when one person is the target of another's influence.” I suggest the authors write the abstract according to the manuscript, e.g., the author mentioned ‘ coercion targets the selection mechanism, and violence targets the action’, which had not been discussed in the full text. Response: We changed “coercion” to “obedience” as an example for the selection mechanism as we discussed obedience in more detail in the corresponding section. For action, however, we stuck to “violence”, as this was one of our examples (“violent or deceptive action redirections”). The full context Since the paper is quite long, I suggest the authors give different heading levels, which will make it easier to understand the article structure. Response: The heading levels were set to one level by the journal during the editing process - we unfortunately cannot change anything in this regard. In “social influence on behaviour while acting” section, the authors first mentioned “descriptive norms” without the definition, while in “Examples of model applications” section, the authors mentioned it again and gave a definition. Please re-organize this part. Response: Thank you. Agreed. We moved the definition to the first mentioned section “Social influence on behavior while acting”. The first sentence of the second paragraph in this section now reads: “However, most social influence research concerns social norms and subtle psychological processes ( Cialdini & Goldstein, 2004). Thereby, descriptive norms refer to the behavior of relevant others ( e.g., peers, family, society) and provide a socially determined standard for effective behavior ( i.e., what individuals typically do), while injunctive norms refer to appeals about what other members of society approve or disapprove of.” Some newly published literature could be added to the manuscript. Response: We have included the following (more recent) papers at appropriate positions in the manuscript. Caspar, E. A., Beyer, F., Cleeremans, A., & Haggard, P. (2021). The obedient mind and the volitional brain: A neural basis for preserved sense of agency and sense of responsibility under coercion. PloS one, 16(10), e0258884. Diel, K., Grelle, S., & Hofmann, W. (2021). A motivational framework of social comparison. Journal of Personality and Social Psychology, 120(6), 1415–1430. Gass, R. H., & Seiter, J. S. (2022). Persuasion: Social influence and compliance gaining. Routledge. Haslam, S. A., Reicher, S. D., & Birney, M. E. (2014). Nothing by mere authority: Evidence that in an experimental analogue of the Milgram paradigm participants are motivated not by orders but by appeals to science. Journal of Social Issues, 70(3), 473-488. Hollander, M. M., & Turowetz, J. (2017). Normalizing trust: Participants’ immediately post‐hoc explanations of behaviour in M ilgram's ‘obedience’experiments. British Journal of Social Psychology, 56(4), 655-674. Legros, S., & Cislaghi, B. (2020). Mapping the social-norms literature: An overview of reviews. Perspectives on Psychological Science, 15(1), 62-80. Ren, Q., Gentsch, A., Kaiser, J., & Schütz-Bosbach, S. (2023). Ready to go: higher sense of agency enhances action readiness and reduces response inhibition. Cognition, 237, 105456. Sosa, M., & Giocomo, L. M. (2021). Navigating for reward. Nature Reviews Neuroscience, 22(8), 472-487. Spears, R. (2021). Social influence and group identity. Annual Review of Psychology, 72, 367-390. Wolske, K. S., Gillingham, K. T., & Schultz, P. W. (2020). Peer influence on household energy behaviours. Nature Energy, 5(3), 202-212. Just a suggestion, since the author frequently mentioned “framing”, and “self-regulatory focus”, I am thinking maybe you can add an “influencing factors” section, which can contain not only the “framing” and “self-regulatory focus” from the target’s side, but also the characteristics of the influencer, e.g., as you mentioned, reputation and trustworthiness. Response: We appreciate the suggestion by the reviewer. Since this opinion piece is focused on how and where the influencer can enter the internal feedback loop system of the target, we have deliberately decided not to address individual differences of the influencer, because we believe that the focus of the paper would otherwise remain less clear and it would be too much for the manuscript in terms of its scope. We have therefore refrained from further elaborating on “influencing factors” in relation to the influencer him/herself although this is a highly interesting topic."
}
]
},
{
"id": "218073",
"date": "21 Nov 2023",
"name": "Robin Willardt",
"expertise": [
"Reviewer Expertise Social psychology",
"motivation",
"affect",
"approach-/avoidance-motivation",
"anger",
"powerlessness",
"threats"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 opinion article “Social influence and external feedback control in humans”.\nIn the article, the authors use a feedback loop model to categorize and describe the different ways in which an influencing person can exert social influence on a targeted person. Most of my comments are concerned with the clarity of the article. In the following, I will outline my feedback in detail following the structure of the paper. Afterwards, I emphasize two points in particular that should be addressed: The justification for introducing the suggested feedback loop model and the nomenclature used to derive at the model.\nThe sentence “Different approaches have shown that social influence is related to emotional processes, visual attention, and self regulation” (page 3) feels like the justification for connecting a feedback loop model with social influence. If that is indeed the case, this should be stated more explicitly. The term feedback control on page 3 (“In social interactions, actions elicit responses from others, leading to the possibility of feedback control…”) should be explained in greater detail.\nOn page 4 under the heading “Social influence”, a sentence is started with the word ‘nonetheless’, even though the preceding sentence does not entail a contradiction to the subsequent one.\nIt might be interesting for the discussion of social influence on page 4 that there is some power research indicating that power actually consists of two subcomponents, namely personal control and influence over others (e.g., Lammers et al, 2016; Van Dijke & Poppe, 2006).\nWhen describing the individual components of the feedback loop model, it would add clarity to specifically state whose goals are meant with the term “goal state”. Those of the target of those of the influencer? The same goes for the feedback prediction component.\nIs the comparator/reference component the plus/minus sign in the graphical depiction of the model? Please clarify.\nOn page 4 the authors introduce the struggle for a TV to illustrate the model. The goal in this case is described as “the division of a shared television”. But this seems to represent a communal goal rather than the individual goals of the two roommates. Maybe it would be better to avoid the term “goal” in this situation and only use it to refer to the target’s goals in the examples that follows.\nIn the subsequent sentence, the goal state is described as the target buying the television. The use of goal and goal state and the lack of a clear attribution of these terms to either one of the two roommates is very confusing.\nSee also the sentence “In this situation, the influencer might persuade the target that the goal is not worthwhile” where it is unclear what goal the authors refer to.\nOn page 5, the heading reads “Social influence towards the goal state”. This is somewhat irritating since social influence towards the goal state was already touched upon in the example of the two roommates (the same applies to the subsequent headings).\nHere, the authors should also explain why a differentiation between persuasion and manipulation is necessary.\nThe sentence “Influence through persuasion can affect the goal state even before the target takes any action. Persuasion is the most appropriate term for what we consider influence toward the goal state” is hard to comprehend: At this point it is yet unclear what the difference between influence and persuasion is. Is persuasion a sub-facet of influence, namely influence towards the goal state? Please explain.\nThe terms ‘message elaboration’ and ‘peripheral route’ should also be outlined in greater detail\nThe authors refer to Sherif’s experiment (p. 7). Outlining the mentioned goal the manipulator is thought to influence (I assume it is the social goal to give group-conform responses) would help to better imbed this research.\nUnder the heading “Social influence on the subjective situation” on page 7, the authors refer to social comparison. The connection of this concept to the example given and to social influence on the situation remains somewhat unclear.\nOn page 8, the authors write “In the context of the shared TV example, imagine that the influencer wants to donate the TV to charity, but the target wants to keep it.” In that case the goal state of the target would be to keep the TV. I suggest to emphasize the connection between the used examples (such as this one) and the components of the proposed model more (in this case: target’s goal à keep TV).\nAlso on page 8, the authors write “If the target perceives the influencer as highly reputable and trustworthy, they may be more likely to obey or comply with the influencer’s advice. This is true, even if the advice does not necessarily align with the target’s intuitive approach to achieving their goals.” This empirical claim should be backed up by a reference.\nUnder the heading “Social influence on behavior while acting”, the authors write “The social influence induced by social norms can alter the internal feedback loop regarding action selection.” This implies that the authors refer to the subcomponent action selection rather than the subcomponent action here (see also the subsequent sentence). It would help the clarity of the paper to precisely state which subcomponents the authors target.\nUnder the heading “Social influence on feedback prediction”, the authors outline the term feedback prediction in greater detail for the first time in their article. I suggest to do so much earlier in the paper in order to facilitate the readers’ ability to understand this important subcomponent of the model. The authors then state that “As mentioned (see “social influence on the subjective situation”), manipulating the situation may often be a valid pathway to influence feedback prediction.” This suggests that social influence on one component of the model might simultaneously affect another one. Can the authors elaborate on this more? When outlining social influence on the individual components of the model earlier in the article, the examples given often appear to be applicable to more than one subcomponent (e.g., influencing the target’s action selection also affects the situation).\nThe authors outline the studies by Melnyk et al. (2013) to show the influence of social norms onto action selection. Are they not also affecting action itself as well as participants’ goal states?\nThe subsequently described studies could be better connected to the feedback loop model. The studies are also analysed regarding their limitations. At times, it is hard to see why these limitations are mentioned in the context of the authors’ model. The description of the study by Zhao and Pechmann (2007) is a good example for how to better connect the presented research with the theoretical model (especially the top paragraph of page 13). The authors state on page 13 that “This study is a good case of targeting action selection rather than goal structures”. A sentence like this at the beginning of each outlined study would help to understand why the authors are referring to these particular studies in light of their model. A possible way to better structure the description of the studies is to first outline what components of the model the studies target. After that, limitations can be described.\nOn page 14, the authors state that “… it may be interesting to examine whether the discrepancy between the reference or goal state and the current state or situation can predict reactance. Potentially, a discrepancy that seems too large for the individual may promote reactance”. Assuming that the goal is the target's goal, wouldn't an enlarged discrepancy rather reduce reactance since the target would not see a point in pursuing the goal anyway? Also on page 14, the authors write “However, the affected stage largely depends on the intentions of the influencer, as the same influence tactic might be interpreted differently within another stage of the feedback loop”. I have troubles understanding this sentence. Please clarify\nAs their very last sentence, the authors state that “understanding how to influence only one particular aspect while excluding the influence of another aspect may be crucial for a more detailed perspective on social influence.” I think this point represents a big argument for the model that should be emphasized more (also in the description of the described studies since it justifies and explains the authors’ effort to point out limitations and weaknesses of the mentioned studies).\nThis brings me to the justification for introducing a feedback loop model in order to investigate social influence. In the introduction of the article, the authors describe past research on social influence. It appears that social influence has already been well studied and the question emerges what the proposed feedback loop model adds to this. The authors occasionally touch upon this question as on page 5 where they state that “While previous research has identified different strategies of social influence, our approach exceeds existing approaches by categorizing these strategies according to the five entrance gates to the internal feedback loop. Thereby, we show how our feedback framework can be used to distinguish and understand the different forms of social influence”. This justification should be mentioned earlier. In general, I would encourage the authors to make clearer why the feedback loop model is necessary and what advantages it entails (e.g., precise description of where and how different kinds of social influence affect a target).\nLastly, I suggest some minor alterations and modifications for the nomenclature used in the article:\nThe authors refer to different feedback loop concepts throughout the article. Among them is the feedback loop system (page 1), the cybernetic feedback model (page3 ), and the cybernetic feedback loop (page 10). An example for how this can lead to ambiguity can be found on page 4: “Feedback loops consist of several stages or elements, including the reference value, comparator, input, and output. In adapting the cybernetic feedback model to social influence…”. Here, it is hard to comprehend whether the authors refer to different concepts or whether they use the different terms interchangeably.\n\nOn page 3, the authors write: “We aim to establish a theoretical connection between cybernetic control models and other feedback regulation models, such as reinforcement learning”. Reading this, I felt overwhelmed by the many terms and concepts introduced at ones. It might help to outline the term ‘cybernetic’ in greater detail. Furthermore, without having been introduced to the model, a reader can struggle to understanding where and how reinforcement learning comes into play here.\n\nI suggest to refrain from using the term ‘study’ (page 7 under “Social influence on action selection”) when referring to the theoretical model outlined in the present article. It suggests that data will be presented.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Partly\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": [
{
"c_id": "10815",
"date": "24 Jan 2024",
"name": "Martin Weiß",
"role": "Author Response",
"response": "Dear Dr. Willardt, thank you for this thoughtful review. We have revised the paper based on the suggestions. See bellow, for our point-by-point response. As our manuscript is already quite long, we have tried to keep the revisions based on your comments as concise and precise as possible. The sentence “Different approaches have shown that social influence is related to emotional processes, visual attention, and self regulation” (page 3) feels like the justification for connecting a feedback loop model with social influence. If that is indeed the case, this should be stated more explicitly. Response: We agree and extended the sentence accordingly. “Different approaches have shown that social influence is related to emotional processes ( Fischer et al., 2003), visual attention ( Frick et al., 2018), and self-regulation ( vanDellen & Hoyle, 2010), thereby providing a connection between social influence and feedback loop models.” The term feedback control on page 3 (“In social interactions, actions elicit responses from others, leading to the possibility of feedback control…”) should be explained in greater detail. Response: We added the following explanation. “Feedback control in social interactions refers to the repeated process by which a person’s activities elicit reactions, generating a dynamic loop that determines subsequent behavior. This system requires constant adjustments depending on feedback and determines the continuing dynamics of interpersonal interactions.” On page 4 under the heading “Social influence”, a sentence is started with the word ‘nonetheless’, even though the preceding sentence does not entail a contradiction to the subsequent one. Response: We deleted “Nonetheless” from this sentence. It might be interesting for the discussion of social influence on page 4 that there is some power research indicating that power actually consists of two subcomponents, namely personal control and influence over others (e.g., Lammers et al, 2016; Van Dijke & Poppe, 2006). Response: We have refrained from a detailed discussion as we have already shortened the power paragraph to avoid distracting the reader from the main topic of this opinion piece. Nevertheless, we have added the aspect mentioned by the reviewer. “Like influence, social power has often been defined as the ability to control or influence another’s thoughts, behavior, or feelings in a meaningful way ( Fiske, 1993; Thibaut & Kelley, 1959; Vescio et al., 2003). In this line, more recent research on social power indicates that power might consist of two subcomponents, namely personal control and influence over others (e.g., Lammers et al, 2016; Van Dijke & Poppe, 2006).” When describing the individual components of the feedback loop model, it would add clarity to specifically state whose goals are meant with the term “goal state”. Those of the target of those of the influencer? The same goes for the feedback prediction component. Response: Thank you. Since we are elaborating on how an influencer can intervene in the feedback loop of the target, it is always about the target. We have specified this in the respective sections. Is the comparator/reference component the plus/minus sign in the graphical depiction of the model? Please clarify. Response: Exactly, we have displayed the comparator with plus/minus signs, as it can lead to two results. Either there is a discrepancy exists or not. Discrepancies can be either positive or negative. We have clarified this in the figure caption: “The ± sign reflects the \"comparator\" and indicates that a possible discrepancy can be either positive or negative.” On page 4 the authors introduce the struggle for a TV to illustrate the model. The goal in this case is described as “the division of a shared television”. But this seems to represent a communal goal rather than the individual goals of the two roommates. Maybe it would be better to avoid the term “goal” in this situation and only use it to refer to the target’s goals in the examples that follows. In the subsequent sentence, the goal state is described as the target buying the television. The use of goal and goal state and the lack of a clear attribution of these terms to either one of the two roommates is very confusing. Response: We have grouped both of the reviewer's points together as they relate to the same paragraph. In this passage, we admit that the distinction between goal and goal state was confusing, as we sometimes referred to the TV as the goal and sometimes to a desire of the target (e.g., keeping the TV). We now always use goal for the TV and goal state for the target’s internal state. Thus, we changed the paragraph in the revised version as follows: “Imagine two people—an influencer and a target—arguing about the division of a currently shared television. Let us consider a situation where the influencer wants to buy a brand-new television for him- or herself. The influencer may try to increase the value of the currently shared object and negotiate a deal to “sell” the shared television to the target to receive some money, by manipulating the target’s goal state (a), that is ‘owning the shared TV’ in this example. In this situation, the influencer persuades the target to understand that the goal (i.e., the shared television) is a worthwhile undertaking with advantages over other goal-like items. Alternatively, the influencer may want to keep the shared television and try to devalue it (the goal) to get the target to buy a new one. In this situation, the influencer might persuade the target that the goal is not worthwhile. Both strategies directly manipulate the target’s internal goal state or reference; in these examples, the influencer tries to amplify or attenuate the attractiveness of the goal for the target by either increasing or decreasing the value attributed to the goal and thus changing the desirability of the goal state. Hence, the amplification, attenuation, implementation, and elimination of a goal state may be relevant principal target strategies.” See also the sentence “In this situation, the influencer might persuade the target that the goal is not worthwhile” where it is unclear what goal the authors refer to. Response: In our example, the goal is always the television. To make our example easier to understand, we have included the specific terms in brackets in the first paragraph in which we introduce the example. On page 5, the heading reads “Social influence towards the goal state”. This is somewhat irritating since social influence towards the goal state was already touched upon in the example of the two roommates (the same applies to the subsequent headings). Response: We have used the paragraph about the example with the two roommates and the TV to give a naturalistic overall impression of the proposed framework. The following headings serve to discuss the entrance gates in more detail with empirical findings. In our view, this is made clear by the last paragraph preceding the sections on the individual aspects: “To illustrate our theoretical views and contribution to the literature, we provide specific examples of negotiation, social norms and sanctions, compliance, advertisement, and nudging in the following subsections. While previous research has identified different strategies of social influence ( Bruins, 1999; Higgins et al., 2003), our approach exceeds existing approaches by categorizing these strategies according to the five entrance gates to the internal feedback loop. Thereby, we show how our feedback framework can be used to distinguish and understand the different forms of social influence.” Here, the authors should also explain why a differentiation between persuasion and manipulation is necessary. Response: We provided the following explanation. “A differentiation between persuasion and manipulation is necessary since persuaders usually have transparent intentions and are open about their goals, whereas manipulators may hide their true intentions, using tactics that intentionally mislead or deceive others.” The sentence “Influence through persuasion can affect the goal state even before the target takes any action. Persuasion is the most appropriate term for what we consider influence toward the goal state” is hard to comprehend: At this point it is yet unclear what the difference between influence and persuasion is. Is persuasion a sub-facet of influence, namely influence towards the goal state? Please explain. Response: When we talk about influence directed toward achieving a particular goal or outcome, especially through communication and reasoning, the term \"persuasion\" is the most fitting descriptor. It's not that persuasion is a sub-facet of influence; rather, it's a specific type of influence with a focus on communication and achieving a defined goal state. However, we understand that our initial formulation needs to be improved. “For influence directed toward achieving a particular goal, especially through communication and reasoning, the term \"persuasion\" is the most fitting descriptor. We do not aim at conceptualizing persuasion is a sub-facet of influence; rather, we use persuasion as a specific type of influence with a focus on communication and achieving a defined goal state.” The terms ‘message elaboration’ and ‘peripheral route’ should also be outlined in greater detail Response: We added explanations for both aspects. “Message elaboration refers to the extent to which individuals actively process information contained in a message. Thus, it involves the cognitive effort and depth of thinking invested in understanding and evaluating a message. In contrast, when a person lacks the ability or motivation to process a message in-depth, they may rely on the peripheral route, which means that peripheral cues or superficial aspects of the message rather than engaging in elaborate cognitive processing. These peripheral cues could be the influencer’s attractiveness or level of knowledge, which could lead to increased credibility.” The authors refer to Sherif’s experiment (p. 7). Outlining the mentioned goal the manipulator is thought to influence (I assume it is the social goal to give group-conform responses) would help to better imbed this research. Response: We have gratefully integrated the useful addition provided by the reviewer. “A manipulator can influence goals to trigger conformity (e.g., the social goal to give group-conform responses), as shown by an experiment in which people estimated the movement of a dot of light ( Sherif, 1936).” Under the heading “Social influence on the subjective situation” on page 7, the authors refer to social comparison. The connection of this concept to the example given and to social influence on the situation remains somewhat unclear. Response: In line with the reviewer’s comment, we emphasized the connection between social comparison and influence on the situation. “Social comparison is an adjacent concept that alters the perception of a situation instead of the facts. Social comparison involves comparing oneself to others, which can influence how individuals perceive their own circumstances. Hence, the influencer's actions may lead the target making upward and downward social comparisons. Upward comparisons aim to increase achievement, while downward comparisons aim to increase subjective well-being ( Diel et al., 2021; Wheeler, 1966; Wills, 1981). Accordingly, the target may perceive the situation differently when making either of these two kinds of comparisons.” On page 8, the authors write “In the context of the shared TV example, imagine that the influencer wants to donate the TV to charity, but the target wants to keep it.” In that case the goal state of the target would be to keep the TV. I suggest to emphasize the connection between the used examples (such as this one) and the components of the proposed model more (in this case: target’s goal à keep TV). Response: Thank you for pointing this out. We rewrote the section to clarify this in the mentioned paragraph. “In contrast, to make some action options less likely, the opposite would be promising, namely a reduction in the expected agency and sense of control. In the context of the shared TV example, imagine that the influencer wants to donate the TV to charity, but the target’s goal state would be to keep it. If the influencer posts about giving it to charity on social media, knowing the target will see it, it could lead to the target withdrawing their own action plan to get the TV since they might feel unable to oppose such a socially desirable action option. In this case, the influencer would have promoted an alternative course of action by raising doubts in the target about their own potential action. The action selection in the target may thus result in withdrawing from keeping the TV and the decision to let it go. This influence strategy is based on the target’s re-evaluation processes and could be successful for the influencer.” Also on page 8, the authors write “If the target perceives the influencer as highly reputable and trustworthy, they may be more likely to obey or comply with the influencer’s advice. This is true, even if the advice does not necessarily align with the target’s intuitive approach to achieving their goals.” This empirical claim should be backed up by a reference. Response: Agreed. We added the following references. Haslam, S. A., Reicher, S. D., & Birney, M. E. (2014). Nothing by mere authority: Evidence that in an experimental analogue of the Milgram paradigm participants are motivated not by orders but by appeals to science. Journal of Social Issues, 70(3), 473-488. Hollander, M. M., & Turowetz, J. (2017). Normalizing trust: Participants’ immediately post‐hoc explanations of behaviour in M ilgram's ‘obedience’experiments. British Journal of Social Psychology, 56(4), 655-674. Under the heading “Social influence on behavior while acting”, the authors write “The social influence induced by social norms can alter the internal feedback loop regarding action selection.” This implies that the authors refer to the subcomponent action selection rather than the subcomponent action here (see also the subsequent sentence). It would help the clarity of the paper to precisely state which subcomponents the authors target. Response: We specified the potential influence on the action itself more clearly in this paragraph. “The social influence induced by social norms can alter the internal feedback loop regarding action selection but also action itself. Specifically, exposure to peer groups’ behavior can prime and make a selected action more salient ( Do et al., 2022) or the mere adaption of an action more likely ( Albert et al., 2013).” Under the heading “Social influence on feedback prediction”, the authors outline the term feedback prediction in greater detail for the first time in their article. I suggest to do so much earlier in the paper in order to facilitate the readers’ ability to understand this important subcomponent of the model. The authors then state that “As mentioned (see “social influence on the subjective situation”), manipulating the situation may often be a valid pathway to influence feedback prediction.” This suggests that social influence on one component of the model might simultaneously affect another one. Can the authors elaborate on this more? When outlining social influence on the individual components of the model earlier in the article, the examples given often appear to be applicable to more than one subcomponent (e.g., influencing the target’s action selection also affects the situation). Response: We agree with the reviewer that the influence on one component may not only affect this component, but also other components. We have included a brief explanation on this topic before presenting all the individual components in detail. “Prior to an in-depth exploration of each component within our proposed framework in detail, we want to clarify that our discussion emphasizes the predominant influence on individual components. This focus does not mean that influencing one component has no effect on other components. For instance, influencing the target's action selection could also affect the goal state or situation. This interplay among components underscores the complexity of social influence, suggesting that interventions on one component may cascade into multifaceted consequences. However, our primary goal is to delve into the fundamental elements of influencing another person’ internal feedback loop. Developing an understanding of how to influence only one particular aspect while excluding the influence of another aspect can be crucial for a more detailed perspective on social influence.” We also extended the section on feedback prediction in the introduction: “Influencing the target’s feedback prediction (d) mechanism might motivate or discourage them by enhancing or lessening their expectations of achieving the goal. For example, the influencer could say, “I will make it very difficult for you to get this TV!” or “Why bother buying a new TV when you can have this one easily?”. Hence, the action might be encouraged or hindered by manipulating expectations; in particular, lowering the target’s expectations of success might result in frustration and disappointment, leading them to discontinue potential further efforts. Accordingly, feedback prediction mainly refers to the likelihood of reaching the desired goal state when selecting a certain action.” The authors outline the studies by Melnyk et al. (2013) to show the influence of social norms onto action selection. Are they not also affecting action itself as well as participants’ goal states? Response: Since previous studies do not build on our framework, it is not trivial to select exemplary research to illustrate the application of the model. We agree that some of the studies concern not only the part for which we selected them, but also other parts of the model. In the previous version of the manuscript, we already informed the reader about these overlaps, but have now added an extension. “There may be overlapping aspects between – but also within – the studies regarding the different entrance gates to manipulate the target’s feedback loop, which we will present in the following subsections.“ The subsequently described studies could be better connected to the feedback loop model. The studies are also analysed regarding their limitations. At times, it is hard to see why these limitations are mentioned in the context of the authors’ model. The description of the study by Zhao and Pechmann (2007) is a good example for how to better connect the presented research with the theoretical model (especially the top paragraph of page 13). The authors state on page 13 that “This study is a good case of targeting action selection rather than goal structures”. A sentence like this at the beginning of each outlined study would help to understand why the authors are referring to these particular studies in light of their model. A possible way to better structure the description of the studies is to first outline what components of the model the studies target. After that, limitations can be described. Response: Thank you. In the manuscript, we already explained our systematic approach in more detail before discussing the concrete examples: “Before starting with the research examples, we will briefly describe the systematic approach used to analyze studies in this domain. First, we identified the relevant goals in the experiment ( e.g., social goals, personal goals) and whether their value was manipulated or an additional goal was included. For instance, introducing a social comparison may add social goals to an otherwise private context. Second, we analyzed the influenced situational characteristics. Third, we examined whether action selection was manipulated—whether a specific behavioral choice was promoted. Fourth, we examined action opportunities or direct effects on action execution. Fifth, we examined the effects of social influence on feedback prediction and goal state versus situation discrepancy, for example, by manipulating a target’s subjective goal attainment probability. In the following subsections, we explain the findings, apply our model, and derive additional experimental manipulations based on our framework.” To address the reviewer’s point without losing our systematic structure, we have added/revised the introductory sentences of each example to make it clearer which component(s) of our model are covered in more detail. On page 14, the authors state that “… it may be interesting to examine whether the discrepancy between the reference or goal state and the current state or situation can predict reactance. Potentially, a discrepancy that seems too large for the individual may promote reactance”. Assuming that the goal is the target's goal, wouldn't an enlarged discrepancy rather reduce reactance since the target would not see a point in pursuing the goal anyway? Response: This is an interesting thought experiment. We admit that there could be a sweet spot where the discrepancy could become large enough that the goal pursuit could become obsolete, which would mean that the reactance would be reduced. We have extended the sentence to this point. “Alternatively, there may be a threshold at which the magnitude of the discrepancy between the goal state and the current state renders the pursuit of the goal obsolete, thus resulting in a decline in reactance.” Also on page 14, the authors write “However, the affected stage largely depends on the intentions of the influencer, as the same influence tactic might be interpreted differently within another stage of the feedback loop”. I have troubles understanding this sentence. Please clarify Response: We revised this sentence as follows: “Depending on the influencer’s intentions, one specific influence tactic might affect different stages or even more than one stage at the same time.” As their very last sentence, the authors state that “understanding how to influence only one particular aspect while excluding the influence of another aspect may be crucial for a more detailed perspective on social influence.” I think this point represents a big argument for the model that should be emphasized more (also in the description of the described studies since it justifies and explains the authors’ effort to point out limitations and weaknesses of the mentioned studies). Response: This is a valid and very helpful suggestion. We incorporated this aspect in the section we inserted before the in-depth discussion of the components of our framework. “Prior to an in-depth exploration of each component within our proposed framework in detail, we want to clarify that our discussion emphasizes the predominant influence on individual components. This focus does not mean that influencing one component has no effect on other components. For instance, influencing the target's action selection could also affect the goal state or situation. This interplay among components underscores the complexity of social influence, suggesting that interventions on one component may cascade into multifaceted consequences. However, our primary goal is to delve into the fundamental elements of influencing another person’ internal feedback loop. Developing an understanding of how to influence only one particular aspect while excluding the influence of another aspect can be crucial for a more detailed perspective on social influence.” This brings me to the justification for introducing a feedback loop model in order to investigate social influence. In the introduction of the article, the authors describe past research on social influence. It appears that social influence has already been well studied and the question emerges what the proposed feedback loop model adds to this. The authors occasionally touch upon this question as on page 5 where they state that “While previous research has identified different strategies of social influence, our approach exceeds existing approaches by categorizing these strategies according to the five entrance gates to the internal feedback loop. Thereby, we show how our feedback framework can be used to distinguish and understand the different forms of social influence”. This justification should be mentioned earlier. In general, I would encourage the authors to make clearer why the feedback loop model is necessary and what advantages it entails (e.g., precise description of where and how different kinds of social influence affect a target). Response: In line with the reviewer’s suggestion, we shifted the motivation for our model to an earlier point in the manuscript (section “Introduction”) and refined the necessity of such a model. “We propose a framework that identifies beneficial and detrimental manipulation tactics in everyday life, contributing to a broader understanding of social influence. While previous research has identified different strategies of social influence ( Bruins, 1999; Higgins et al., 2003), our approach exceeds existing approaches by categorizing these strategies according to distinct entrance gates to the internal feedback loop. Thereby, the proposed framework helps to develop a precise description of where and how different kinds of social influence affect another person’s internal feedback loop.” Lastly, I suggest some minor alterations and modifications for the nomenclature used in the article: The authors refer to different feedback loop concepts throughout the article. Among them is the feedback loop system (page 1), the cybernetic feedback model (page3 ), and the cybernetic feedback loop (page 10). An example for how this can lead to ambiguity can be found on page 4: “Feedback loops consist of several stages or elements, including the reference value, comparator, input, and output. In adapting the cybernetic feedback model to social influence…”. Here, it is hard to comprehend whether the authors refer to different concepts or whether they use the different terms interchangeably. Response: We understand the confusion and deleted the sentence on page 4 as it was also redundant (see first sentence in the section “Feedback loops and feedback control”). To avoid misunderstandings, we used the term cybernetic feedback model consistently. On page 3, the authors write: “We aim to establish a theoretical connection between cybernetic control models and other feedback regulation models, such as reinforcement learning”. Reading this, I felt overwhelmed by the many terms and concepts introduced at ones. It might help to outline the term ‘cybernetic’ in greater detail. Furthermore, without having been introduced to the model, a reader can struggle to understanding where and how reinforcement learning comes into play here. Response: We improved the order of our arguments as the reinforcement learning part was more like a future use case of a theoretical connection to our model. The revised paragraphs are as follows: “We build on cybernetic models of behavioral regulation, that is, models that are designed to understand or regulate dynamic processes in complex systems ( Leonard et al., 2021), focusing on the fundamental elements that comprise these models. Cybernetic models illustrate a closed system that regulates itself using a feedback loop. Social influence can target elements in cybernetic models, representing different forms of social influence. We propose a framework that identifies beneficial and detrimental manipulation tactics in everyday life, contributing to a broader understanding of social influence. While previous research has identified different strategies of social influence ( Bruins, 1999; Higgins et al., 2003), our approach exceeds existing approaches by categorizing these strategies according to distinct entrance gates to the internal feedback loop. Thereby, the proposed framework helps to develop a precise description of where and how different kinds of social influence affect another person’s internal feedback loop. Our framework helps establishing a theoretical connection between cybernetic control models and other feedback regulation models, such as reinforcement learning ( i.e., learning the optimal behavior in an environment to obtain maximum reward through observations of how choices are influenced by past decisions and rewards; Sutton & Barto, 1998). By combining these models in the future, researchers might be able to identify interactions that enhance our understanding and prediction of social influence. For example, combining our proposed model with reinforcement learning can help determine which social influence mechanisms are advantageous and crucial in social interactions.” I suggest to refrain from using the term ‘study’ (page 7 under “Social influence on action selection”) when referring to the theoretical model outlined in the present article. It suggests that data will be presented. Response: Agreed. We replaced the term “study” by “article” or “opinion piece”."
}
]
}
] | 1
|
https://f1000research.com/articles/12-438
|
https://f1000research.com/articles/13-101/v1
|
16 Feb 24
|
{
"type": "Study Protocol",
"title": "Assessment of the status of presentation and management of tuberculosis patients in central India",
"authors": [
"Mitul Saha",
"Swarupa Chakole",
"Swarupa Chakole"
],
"abstract": "Tuberculosis (TB) continues to pose a notable public health issue not just within India but on a worldwide scale. Analyzing the causes of presentation, management, and treatment delays of tuberculosis can offer valuable understanding into local trends and aid in crafting specific approaches for the successful management of TB. This research involves a cross-sectional examination conducted among TB patients residing in the regions served by the District Tuberculosis Centre, Wardha, and the directly observed treatment short course center in Sawangi. Information will be collected using a standardized questionnaire endorsed by the World Health Organization.",
"keywords": [
"tuberculosis",
"National Tuberculosis Elimination Programme",
"directly observed therapy short course",
"presentation delay",
"diagnosis delay",
"treatment delay"
],
"content": "Introduction\n\nIn 2021, approximately 10.6 million individuals globally received a tuberculosis (TB) diagnosis, with a 95% confidence interval ranging from 9.9 to 11 million. This count comprised 6.0 million males, 3.4 million females, and 1.2 million children. Among the total cases, 6.7% were individuals coexisting with HIV. Over the same year, TB claimed the lives of 1.6 million people, with 187,000 of these fatalities occurring in individuals with HIV. More than two-thirds of the total worldwide TB cases were attributed to eight countries: India, Indonesia, China, Philippines, Pakistan, Nigeria, Bangladesh, and the Democratic Republic of the Congo. From 2000 to 2021, TB treatment has led to the preservation of 74 million lives. On a global scale, the count of individuals who received new TB diagnoses and those reported to their respective national authorities declined from 7.1 million in 2019 to 5.8 million in 2020, with a partial rebound to 6.4 million in 2021.\n\nTB continues to be a significant public health issue in India. The difficulty lies not only in delivering successful treatment but also in minimizing the gap between identifying TB symptoms and promptly commencing treatment.\n\nPrompt and effective identification and treatment of TB cases play a pivotal role in managing the disease. If TB diagnosis is delayed, it can amplify the spread of infection, exacerbate illness severity, elevate mortality rates, and might be a factor contributing to the limited reduction in TB incidence, despite the worldwide expansion of the directly observed treatment, short course (DOTS).1\n\nIdentifying the reasons behind delays can contribute to achieving India’s goal of eliminating tuberculosis by 2025. Hence, a primary area of emphasis within India’s National Tuberculosis Elimination Programme (NTEP) is rapid diagnosis and timely treatment.2 Having information about the diagnostic routes is crucial for devising strategies to minimize the delays in diagnosis or treatment.1\n\nIndia possesses a multifaceted and diverse healthcare delivery structure, encompassing public and various forms of private healthcare providers, including both formal and informal sectors. Private and informal healthcare providers frequently serve as the initial point of contact for addressing illnesses, including tuberculosis.3\n\nThe time taken for diagnosis and treatment delay, along with the factors contributing to these delays, vary among different communities, types of healthcare facilities visited, and geographical regions. This variation holds true even within population groups within the same local context and disease category.3\n\nResearch indicates that elements leading to patient delay encompass aspects such as family size, employment, household income, social stigma, awareness about TB, proximity to healthcare facilities, and the practice of self-medication.3\n\nThe increasing volume of research on delays in diagnosis and treatment underscores the need for conducting studies tailored to specific populations. This is crucial for identifying factors unique to each population that contribute to delays in diagnosing and treating TB.\n\nAs per the 2014 guidelines from the World Health Organization (WHO), individuals displaying indicative symptoms and signs of TB, which encompass a cough lasting more than two weeks, fever persisting for over two weeks, considerable weight loss, coughing up blood, and any irregularities detected in a chest X-ray, as well as children experiencing continuous fever and/or a cough lasting more than two weeks, failure to gain weight or losing weight, and/or having been in contact with individuals diagnosed with pulmonary TB, should undergo an assessment to ascertain the presence of TB.\n\nMultiple diagnostic tests are accessible for pulmonary TB, including confirming the presence of the bacteria through sputum analysis, examining chest X-rays, conducting serological assessments, employing tests like tuberculin skin test and interferon gamma release assay. In the case of children and individuals living with HIV (PLHIV), the preferred initial diagnostic method is the cartridge-based nucleic-acid amplification test.\n\nExisting TB diagnostic methods like culture, sputum smear examination, tuberculin skin tests, and molecular assays, entail lengthy processing times, and certain methods are financially inaccessible for countries with limited economic resources.4\n\nEnsuring widespread availability for prompt and precise TB diagnosis and improving the efficiency of identifying potential TB cases right at the initial care encounter, followed by connecting them with optimal diagnostic assessments, holds immense significance. Swift identification of potential cases during the early stages is critical for halting the spread of TB infection.\n\nEvery new tuberculosis patient in India should be provided with a globally recognized initial standard treatment plan (referring to the prescribed treatment course, which includes the TB medications) for newly diagnosed patients.\n\nThe beginning intensive phase incorporate the medications Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E). Subsequently, the follow-up phase, with the administration of the trio of medications Isoniazid, Rifampicin, and Ethambutol. This regimen is also expressed as 2HREZ/4HRE. There is no requirement for prolonging the follow-up phase.\n\nPatients’ medication dosages must correspond to their body weight and fall within one of four specified weight ranges. All patients are required to take their daily tuberculosis medications while being directly observed by a designated DOTS provider. DOTS mandates that patients ingest their TB drugs in the presence of a DOTS agent. This agent is typically a volunteer from the patient’s local community and could potentially be a family member. DOTS doesn’t specify the particular medications to be taken; rather, it applies whenever a DOTS volunteer oversees the patient taking any TB medications.\n\nWhile there might be existing studies on TB delays, an updated study in 2023 can provide insights into the evolving healthcare landscape. Factors such as the COVID-19 pandemic’s impact on healthcare seeking behaviour and service delivery could influence TB-related delays differently, making up-to-date research essential.\n\nThis study on assessing delay in presentation, diagnosis, and treatment of TB patients in central India in 2023 is important for understanding the specific challenges in this region, improving patient outcomes, reducing disease transmission, and contributing to effective TB control strategies. The aim of this study is to assess the status of presentation and management of tuberculosis patients in central India. We used the STROBE reporting guidelines to aid our reporting of this protocol.2\n\n\nProtocol\n\nEthical approval was obtained from the Institutional Ethics Committee of Datta Meghe Institute of Medical Science, DMIMS (DU), Sawangi, Wardha with reference no. DMIMS (DU)/IEC/2022/213 on 30th August 2022. Written informed consent for participation and publication of this study will be obtained from the study participants and from the parents of children below 18 years of age.\n\nThis will be a hospital based, observational cross-sectional study.\n\nThe study will be carried out in the area covered under the District Tuberculosis Centre, Wardha and the DOTS centre, Sawangi.\n\nInclusion criteria\n\n1. Newly diagnosed TB patients registered under National Tuberculosis Elimination Programme.\n\n2. Tuberculosis patients of age seven years or older.\n\nExclusion critera\n\n1. Multidrug resistant TB (MDR TB) patients\n\n2. Extensively drug-resistant TB (XDR TB) patients\n\n3. TB patients registered under NTEP in Wardha but migrated or planning to transfer to another city or state.\n\nThe study will be conducted on TB patients registered in DTC Wardha and the DOTS centre under the NTEP.\n\nA detailed list of all the sputum positive TB individuals for the period of 1st July 2022 to 30th December 2023 will be obtained from Nikshay, the web enabled patient management system for TB control under the National Tuberculosis Elimination Programme (NTEP). with prior permission from the DTO Wardha. This list will be used as a sampling framework to select a simple random sample of 377 individuals who are registered under the NTEP and attending the outpatient department (OPD) or admitted at DTC, Wardha and DOTS centre, Sawangi. The Random Number Generator app, version 1.0.11, will be used on the Samsung A34 mobile will be used to carry out the selection of individuals. Further data collection will be carried out at the OPD from patients attending OPD and from patients admitted at tuberculosis wards.\n\nData will be gathered through the utilization of a structured questionnaire, Diagnostic and treatment delay in tuberculosis, created by the World Health Organization (WHO). The questionnaire has been translated into the Marathi and Hindi language. Subsequently, direct interviews will be conducted with patients, following the acquisition of written informed consent from the patients. No pretesting phase will be conducted.\n\nThe sample size was calculated using Open Source Epidemiologic Statistics for Public Health (OpenEpi), Version 5.5.11. For this study delay in presentation, diagnosis and treatment were included as outcome variables. The hypothesized frequency of outcome variables (p) were taken to be 56.9%, 38% and 8% respectively. The Confidence Interval (CI) was kept at 95%, with an absolute error of 5% for all variables and design effect (DEFF) was 1.0. The sample size was calculated to be 377, 362 and 114. The sample size was calculated using the formula:\n\nKey results of this study will be the current status of presentation, diagnosis and treatment of tuberculosis cases in recent times. In case we find any delay, we will calculate the mean duration for the total pathway including presentation delay, diagnostic delay and treatment delay.\n\nRegarding the scoring methodology, the scores will be initially reversed before their integration into the relevant domains. This reversal will be executed to accurately reflect the positive trajectory of the studied variable. The mean percentage score for socioeconomic status, stigma, satisfaction with care, and knowledge will be ascertained using the following formula: (Sum of attained scores/Maximum attainable scores) × 100. Following this, the mean percentage scores will be computed to establish the variables’ scaling ranging from 0 to 100%. The highest percentage value will signify the most significant improvement in that particular characteristic or variable.\n\nInstances that exhibit prolonged delays will be categorized as “cases,” whereas those with shorter delays will be denoted as “controls.” The threshold for defining “extended” delays will be established by considering the median value achieved for each respective cases. This median value will also serve as the criterion for classifying other variables such as stigma, knowledge, and satisfaction with care into categories of satisfactory and unsatisfactory. Data analysis will be executed utilizing the statistical software package, R,Version -4.3.1. Descriptive statistics including measures like frequency, mean, standard deviation, median, minimum, and maximum will be employed. For qualitative/categorical variables, group comparisons will be conducted using the Chi-square test or Fischer’s exact test as suitable. Similarly, quantitative variables will be compared using the t-test or Mann-Whitney test. To account for the influence of various identified factors affecting diagnostic and treatment delays in TB patients, a multivariate regression analysis will be carried out. The significance level will be set at 95% (with a P value <0.05 considered significant), and all tests will be two-sided.\n\nArticles arising from this study will be published in indexed journals of public health.\n\nThe study is yet to be started. We envisage it will start by November 2023.\n\n\nDiscussion\n\nIn a study carried out in Mumbai, India, by Mistry and colleagues, it was found that the average duration for the entire pathway of uncomplicated pulmonary TB patients was 65 days, and approximately 29% of patients fell outside this average duration. Notably, the average time taken for initial care seeking was consistent for both new patients (24 days) and retreatment patients (25 days).5\n\nAccording to Mundra and colleagues, the midpoint duration for seeking initial care and diagnosis was 10 days each, while treatment initiation had a median delay of two days. The areas recognized as causes for delay in care seeking encompassed disregard for health, health-related factors, facility-associated challenges, as well as domestic and societal considerations. For delays in diagnosis, the factors identified were linked to the system and the patients, with each having two distinct subcategories.6\n\nThe research of Paramasivam and colleagues showed that the average age of participants was 48.6 years with a standard deviation of 14.5 years. Among the study population, males comprised 76.5%. The average time of diagnostic delay was approximately 43.5 days, with a standard deviation of 29.1 days (median: 37 days). The median durations for patient delay and health system delay were 16 days and 15 days, respectively. Patient delay was more predominant, accounting for 55.6% compared to the 44.4% attributed to health system delay. Notably, poor understanding of TB, initial consultation with a private physician, and a higher number of medical visits were significantly linked to diagnostic delay.7\n\nAccording to Sreeramareddy and co-authors, the median estimates (with interquartile ranges) for patient, diagnostic, and treatment delay were found to be 18.4 days (with a range of 14.3 to 27.0 days), 31.0 days (with a range of 24.5 to 35.4 days), and 2.5 days (with a range of 1.9 to 3.6 days), respectively, when considering both TB and chest symptomatic patients together. The total median delay encompassing all these factors was approximately 55.3 days (with a range of 46.5 to 61.5 days). Notably, about 48% of all patients initially sought care from private healthcare providers, and an average of 2.7 healthcare providers were consulted before a diagnosis was established.3\n\nPatki and colleagues found that the median duration of delay was 35.5 days, with diagnostic delay constituting 84% of this duration. Male patients and those from families falling below the poverty line exhibited notably shorter median delay, and these differences were statistically significant (P < 0.05). Notably, a distinct delay was observed in the initiation of TB treatment, with diagnostic delay being the primary contributor to the overall delay.\n\nThere are several possible limitations to this study:\n\nCultural differences: The WHO questionnaire may have been developed with a global perspective, which might not fully account for cultural nuances and variations specific to central India.\n\nQuestionnaire validity: While the WHO questionnaire is widely used, its applicability and validity in the context of central India may not have been thoroughly assessed. Certain questions might not accurately capture the region-specific factors contributing to delays.\n\nResponse bias: Participants’ responses can be influenced by social desirability bias or recall bias. This could affect the accuracy and reliability of the collected data, particularly when reporting sensitive information or events related to delays.\n\nWhen complete this study in central India can be generalised to over the whole of India due to similarity in cultural believes and practices.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nZenodo: STROBE checklist for ‘Assessment of the status of presentation and management of tuberculosis patients in central India’, https://www.doi.org/10.5281/zenodo.8285467. 4\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nI would like to thank the District Tuberculosis Officer, Wardha for permitting data collection.\n\n\nReferences\n\nChandra A, Kumar R, Kant S, et al.: Diagnostic Pathways and Delays in Initiation of Treatment among Newly Diagnosed Tuberculosis Patients in Ballabgarh, India. Am J Trop Med Hyg. 2021 Feb 1; 104(4): 1321–1325. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSaha M: Assessment of the status of presentation and management of tuberculosis patients in Central India (version v1). [Data]. Zenodo. 2023. Publisher Full Text\n\nSreeramareddy CT, Qin ZZ, Satyanarayana S, et al.: Delays in diagnosis and treatment of pulmonary tuberculosis in India: a systematic review. Int J Tuberc Lung Dis Off J Int Union Tuberc Lung Dis. 2014 Mar; 18(3): 255–266. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMartin DR, Sibuyi NR, Dube P, et al.: Aptamer-Based Diagnostic Systems for the Rapid Screening of TB at the Point-of-Care. Diagnostics. 2021 Jul 28; 11(8): 1352. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMistry N, Rangan S, Dholakia Y, et al.: Durations and Delays in Care Seeking, Diagnosis and Treatment Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India. PLoS One. 2016; 11(3): e0152287. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMundra A, Kothekar P, Deshmukh P, et al.: Why tuberculosis patients under revised national tuberculosis control programme delay in health-care seeking? A mixed-methods research from Wardha District, Maharashtra. Indian J Public Health. 2019; 63(2): 94.\n\nParamasivam S, Thomas B, Chandran P, et al.: Diagnostic delay and associated factors among patients with pulmonary tuberculosis in Kerala. J Fam Med Prim Care. 2017; 6(3): 643–648. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "253402",
"date": "28 Mar 2024",
"name": "Yogendra Shah",
"expertise": [
"Reviewer Expertise 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\nTitle: Assessment of the status of presentation and management of tuberculosis patients in central India Reviewer: I respectfully suggest the following improvements to enhance the manuscript's format :\nAbstract:\nEmphasize the significant findings of the manuscript, including background, rationale, study objectives, methods, results, conclusions, and recommendations. Select only the most essential keywords from the abstract for better searchability.\n\nIntroduction:\nBegin by providing a concise overview of global tuberculosis statistics, with a specific focus on India, highlighting drug resistance issues including multi-drug resistant (MDR) and extensively drug-resistant (XDR) strains. Clearly state the rationale and justification for the study, emphasizing any existing gaps in knowledge or clinical management of pulmonary tuberculosis patients in central India. Discuss the rationale behind employing genotypic and phenotypic diagnosis methods, as well as the Directly Observed Treatment, Short-course (DOTS) treatment strategy. Justify the objectives of the current study in an easily understandable manner to capture the reader's interest and demonstrate their relevance.\nMethods:\nClearly describe the study design, including inclusion and exclusion criteria, determination of sample size, collection of clinical data, laboratory tests performed, and statistical analysis methods, ensuring simplicity for better comprehension. Present a flow chart illustrating the procedure employed in the current study.\nResults:\nDiscuss the significant findings of the study in a straightforward manner, avoiding complex formats to enhance clarity.\nDiscussion:\nRevisit the discussion to include a comparison of the current study's findings with previously published literature, offering logical explanations for better comprehension. Address any limitations of the research, acknowledging potential constraints or biases that could impact result interpretation. Conclude with practical recommendations for implementing the study findings in clinical practice, emphasizing real-world applications and strategies to enhance pulmonary tuberculosis management, while also considering potential barriers to implementation.\nBy incorporating these suggestions, the manuscript can be improved in terms of format, clarity, and relevance.\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Partly\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Partly",
"responses": []
},
{
"id": "304072",
"date": "22 Aug 2024",
"name": "Harsh D Shah",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors are encouraged to carefully review the following comments:\nIntroduction:\nThe authors may refer Global TB report 2023 for latest data counts on TB. Please ensure that the Tuberculin Skin Test (TST) and Interferon-Gamma Release Assays (IGRA) are correctly referenced as tools for identifying TB infection rather than diagnosing TB. The authors should adhere to the diagnostic algorithms outlined by the National Tuberculosis Elimination Program (NTEP).\nStudy Objectives: Several studies in India have already identified delays in TB care and proposed public health actions. This study could provide valuable additional insights specific to particular geographies, such as specific districts or states. Study Method:\nThe study focuses exclusively on drug-sensitive TB patients within a specific age range. There is a risk of overlooking drug-resistant cases and pediatric patients under seven years old, who may be more susceptible to delays. Clarification is needed on whether the study includes both pulmonary and extrapulmonary TB, public and private sector patients, seriously ill or hospitalized individuals, etc. The suggested tools for the questionnaires require updating in accordance with the latest NTEP guidelines. Notably, changes related to the oral daily dose and weight-band drug regimen should be reflected.\nDiscussion: The discussion section references studies on overall delays in TB care, rather than focusing solely on drug-sensitive TB as per the study design. Please revise this section to align with the study's scope.\nYou may refer following studies: 1. Shah HD,.et.al., 2022 (Ref1) 2. Yasobant S,. et.al., 2023 (Ref 2) 3. Subbaraman R,.et.al.2019 (Ref 3)\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? Partly",
"responses": []
},
{
"id": "269584",
"date": "26 Sep 2024",
"name": "Erlina Burhan",
"expertise": [
"Reviewer Expertise Tuberculosis",
"COVID-19",
"Pulmonary infection"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSummary of Manuscript The protocol outlines a study aimed at assessing the presentation and management of tuberculosis (TB) cases in central India. It encompasses a hospital-based observational cross-sectional design, targeting newly diagnosed TB patients registered under the National Tuberculosis Elimination Programme (NTEP). The study will investigate the status of presentation, diagnosis, and treatment of TB cases, with data collection conducted through structured interviews using a translated questionnaire. A sample size of 377 individuals will be selected using a random sampling method. Statistical analysis will involve descriptive statistics, group comparisons, and multivariate regression analysis. The study aims to provide insights into the specific challenges in TB management in central India, contributing to effective TB control strategies and patient outcomes.\nOverall Assessment:\nThis manuscript provides a concise overview of the research design to be conducted by the researchers. Although the researchers have developed a structured protocol, there are several major sections that can be improved to enhance clarity and comprehensiveness. The reproducibility of this study is relatively low and improvements are needed to enhance the quality of the protocol.\nSpecific Comments:\nIntroduction/Aims:\nBe more concise, avoid verbosity. No need to explain the theoretical basis of diagnosis or therapy. Paragraphs should be constructed instead of sentence-by-sentence. Ensure accurate citations, as there are no citations from WHO guidelines. Pay attention to the risk of self-citation. Highlight the novelty of the research. Clearly explain the aim of the study. Is it to assess delays or to evaluate the factors causing delays? There is inconsistency between the manuscript and the abstract. Keywords: Determine the most appropriate and representative ones, align with MeSH terms.\n\nMethods:\nThe research design needs to be elaborated in more detail and consistency is required, as there is a statement of a cross-sectional study design but the data analysis is grouped based on cases and controls. Informed consent needs to be detailed, specifying who is eligible to provide consent (adult, parent, adolescent, child). Detailed timeline of the research plan is required. Elaborate on the subject recruitment process to enhance clarity in data collection. Eligibility criteria need to be more detailed, including whether extrapulmonary TB is included, whether relapsed TB is included, and combining MDR and XDR into DR TB. Detailed explanation of the research location is needed, including the context and rationale for selecting the location (readers are confused whether Wardha and Sawangi are cities, districts, or other administrative regions) Explain which variables are collected and provide the intended questionnaire. The sample size calculation results in 3 digits, but it is not explained why the authors wrote the number of samples to be taken in the protocol. Dissemination plan should be more detailed, indexed where.\n\nSignificance:\nProvide a more comprehensive discussion, comparing the potential results of the current study with previous studies. Make implementation recommendations based on the results of this study in the real world.\n\nRecommendations:\nImprovements are needed in every section of the protocol to enhance clarity, relevance, and comprehensibility.\nConclusion:\nThe authors have provided a structured outline of the research plan in the field of TB and addressed the issue of delayed TB services for patients. Although some sections need major improvement and further elaboration, this manuscript has the potential to be a reference for addressing TB service delays, particularly in the Indian context. Therefore, I recommend returning this manuscript to the authors and rejecting it for its current state of quality.\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Partly\n\nAre sufficient details of the methods provided to allow replication by others? No\n\nAre the datasets clearly presented in a useable and accessible format? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-101
|
https://f1000research.com/articles/13-100/v1
|
16 Feb 24
|
{
"type": "Research Article",
"title": "Attitudes and practices regarding COVID-19 preventive measures in diverse settings of Mozambique: a qualitative study",
"authors": [
"Amílcar Magaço",
"Constantino Cumbane",
"Olga Cambaco",
"Helena Boene",
"Estevão Mucavele",
"Saquina Cossa",
"Felizarda Amosse",
"Felisbela Materrula",
"Hermínio Cossa",
"Khátia Munguambe",
"Constantino Cumbane",
"Olga Cambaco",
"Helena Boene",
"Estevão Mucavele",
"Saquina Cossa",
"Felizarda Amosse",
"Felisbela Materrula",
"Hermínio Cossa",
"Khátia Munguambe"
],
"abstract": "Background: Coronavirus disease (COVID-19) first broke out in Wuhan, China, on 29 December 2019; since then, it has taken hundreds of thousands of lives worldwide. Although adopting different containment measures, it spread rapidly over the world. In Mozambique, the government declared a state of emergency in March 2020, associated with a number of preventive measures to reduce the spread and delay the peak of virus’ infections. This paper seeks to analyze the attitudes and practices related to COVID-19 preventive measures during first period of state of emergency in Mozambique in both in rural and urban settings. Methods: A community-based, cross-sectional and qualitative study was conducted in six urban and five rural settings in Mozambique. In total, 295 semi-structured interviews were conducted with community members, of which 23 were face-to-face and 272 through telephone interviews. Interviews were digitally audio recorded, verbatim transcribed, and entered into an Excel matrix followed by a structured data content analysis. The Consolidated criteria for reporting qualitative research (COREQ) guidelines for reporting qualitative studies were performed. Results: In general, participants reported that it was necessary to change their habits, reducing activities and their mobility, such as: going out to work, for business, and visiting family, to reduce the risk of contracting COVID-19. In addition, some participants reported adopting several COVID-19 preventive measures in public spaces and at home, such as: wearing a mask, washing their hands, and social and physical distancing. Conclusions: Although the majority of participants reported adopting most of COVID-19 preventive measures at home and in public spaces, much work is still needed to improve the knowledge of COVID-19 preventive measures and practices. The results of our study suggest a greater awareness of residents and users of public places about established standards and preventive procedures concerning COVID-19.",
"keywords": [
"COVID-19",
"attitudes",
"practices",
"public places",
"Mozambique."
],
"content": "Introduction\n\nThe new Coronavirus SARS-CoV-2 (responsible for the Coronavirus Disease 19 or COVID-19) emerged in December 2019 in Wuhan, China, and spread quickly to other countries, creating a global pandemic situation worldwide.1 Many countries, high, middle, and low income alike, imposed several restrictions to prevent the disease from spreading quickly.2 In response to this difficult situation, the World Health Organization (WHO) declared COVID-19 a global health emergency and called for collaborative efforts by all countries to reduce the spread of the pandemic.3 In response, several public health measures were put in place to reduce the virus’s transmission and minimize the disease’s impact.2,3\n\nEssential questions related to countries’ preparedness of the health systems in responding to patient demand were raised, particularly regarding low-income countries, which were already overburdened before the pandemic.4 In such countries, preventive measures should have been highly reinforced to reduce pressure on the health system. However, adequate enforcement of preventive measures requires governments to be able to provide support to the most vulnerable populations, including those living in poverty, and limited access to the required information to enable them to collaborate with the emergency public health response.5,6 In such situations, the public is likely unable to comply with the imposed measures, even if enforcement is in place.\n\nIn Mozambique, the government registered the first case of COVID-19 officially confirmed on 22 March 2020.7 At that time, most patients comprised of people returning from international travel.8 When community transmission became a concern, the government adopted measures to contain the spread and to delay disease transmission peaks to gain time while a pharmacological solution was still being searched for globally.9,10 At that point, Mozambique experienced a level three state of emergency, aligned with the following measures: closure of schools; limitation of international travel (cessation of visa issuance); a minimum physical distance of 1.5 meters between individuals; mandatory use of masks; encouragement of hand hygiene practices; banning of overcrowding; crucial turnover among on-site employees and; prohibition of all social and recreational and religions events, as well as sports activities.11 The broad dissemination of these prevention measures triggered a negative population-wide response characterized by panic and confusion8 and unexpected patterns of reactions and behaviors such as migration to sites where law enforcement is poor.12 These actions were perceived to increase resilience and subsistence in a poor country where most income-generating activities come from the informal sector.12 Considering that Mozambique ranked as the third poorest country globally (based upon their 2020 GNI per capita in current USD), reflecting the above scenario.13 In additional, in this scenario, the subsequent extensions to the initial state of emergency continuously posed new challenges to ensure strict compliance with the guidelines for preventive measures.14 Earlier analysis on the issue of the feasibility of implementing COVID-19 risk reduction measures in impoverished communities had already acknowledged that the implementations of some measures would be a challenge in many cities and rural areas of middle and low-income countries.15 Indeed, Manjate and colleagues confirmed these challenges in Mozambique.16\n\nThe study assessed knowledge, attitudes, and practices regarding COVID-19 prevention and reported that more than 50% of participants claimed to take COVID-19 prevention measures because of the obligations established by government authorities.15 Therefore, exploring people’s attitudes and practices concerning COVID-19 are essential to understanding how the general population copes with abrupt behavioral change requirements in a public health emergency.14 Even though a state of emergency was declared with several imposed measures, studies are still scarce with methodological approaches and representativeness limitations for different contexts of Mozambique.\n\nIn the past, the present study results and recommendations significantly contributed to the decision-making process and development of effective public health communication strategies aiming at behavior change to reduce disease transmission at the community level.7,14 The lessons learned from it are relevant to the current scenario—where the pandemic has reached a certain level of maturity —and for future occurrences of public health emergencies.\n\nThis study aimed to analyze the attitudes and practices related to COVID-19 prevention measures during first Mozambique’s state emergency period to contain the spread of COVID-19 in rural and urban settings.\n\n\nMethods\n\nThis study was ethically evaluated and approved by the Comité Institucional de Bioética em saúde - Manhiça Health Research Center (CISM) (approval ref. CIBS-CISM/026/2020). Before starting the interviews, all participants were informed about the study objectives and procedures and the voluntary nature of participation through information from the participant’s information sheet, followed by oral voice recorded consent to participate in the study. We chose oral consent over written consent to minimise the risk of COVID-19 infection, both for the participant and the interviewer, particularly for those invited to participate in person interviews by reducing contact between the interviewee and the interviewer, sharing of objects (e.g., paper and pens) and maximizing social distancing. Oral consent recorded was also a recommendation from the committee in the conduct of studies for maximizing protection against COVID-19 infection. The interviews were conducted in a private room/environment where only the interviewee and the researcher could participate and feel comfortable. No one else were allowed to participate in the individual interviews. For the telephone interviews, the researcher asked if the participant was alone, quiet, and safe place before start starting the interview. During the consent and interview the confidentiality and anonymity of participants were assured for this article. This approach to consent was accepted to approved by the ethics committee which approved the conduct of the research.\n\nWe analyzed qualitative data gathered in the frame of a larger, national representative and mixed-methods study, aiming to investigate the community’s behavior related to home confinement, household members’ mobility, and people’s territorial mobility during the first state of emergency in Mozambique. As mentioned in the qualitative tools tab of the recently published data-note,17 this qualitative analysis comprised a generic design of qualitative inquiry focused on attitudes related to adopting preventive measures and behaviors out of home confinement and mobility of the household members during the first period of a state of emergency in selected districts of rural and urban settings in Mozambique.16 The data were gathered in the context of imposed preventive measures to contain the spread of COVID-19 using a combination of data collection techniques based on rapid ethnography and rapid rural assessment as described elsewhere.17,18\n\nStudy participants were selected for convenience through the study team’s contacts on their mobile phones. During this process potential participants were contacted by phone and asked for an interview which was either scheduled for an in-person meeting (face-to-face interview) or a virtual, telephone-based interview.\n\nThe data collection was conducted in eight provinces, 13 municipalities, and 12 districts of Mozambique (all referred to as sites) (Figure 1). These locations were selected based on convenience sampling, as they represent the geographical areas where (i) the Centro de Investigação em Saúde de Manhiça (CISM) has active studies (i.e., Manhiça, Maputo, Xai-Xai, Quelimane, and Mopeia), (ii) are also residential areas of study team members, and (iii) are places where team members have contacts with people they know (e.g., Maputo, Matola, Moamba, Inhambane, Morrumbene, Beira, Mocuba). Study participants comprised a range of socio-cultural and economic backgrounds in 222 neighbourhoods.\n\nAt these sites, the study targeted groups included young people (18–29 years old), adults (30–49 years old), and the older population (50 years and older). For this analysis, only participants aged 18 to 60 years old were included. Study participants were selected for convenience through the study team’s contacts on their mobile phones.\n\nData collection was conducted from 16 to 21 May 2020, shortly after the upsurge of cases in Mozambique. Altogether, 18 interviewers conducted 295 semi-structured interviews (SSI) with adult household members, of which 23 were in-person SSIs, and the remaining 272 SSIs were conducted by telephone. The latter were privileged to minimize the risk of both participants and the researcher’s exposure.\n\nThe SSIs were conducted based on a topic guide focused on the following topics: (i) change in routine; (ii) practical aspects of mobility (who, when, and why people leave their homes); (iii) adoption of COVID-19 containment measures in the daily lives of families and public places; and (iv) importance given to hand washing and disinfection, use of masks and physical distance. Socio-demographic characteristics of the participants were also collected using a standardized structured form. The interviews were conducted in Portuguese and local languages according to participants’ preferences, such as: Changana, Cena, and Chuabo dialects. Most of the SSI (272), were conducted by telephone whenever the participants showed availability to be interviewed, whether they were at home, on the street or at their workplaces, and the other 23 SSI were conducted face-to-face at homes or workplaces of the participants, and those intreviews lasted between 45 and 60 minutes.\n\nThe SSIs were audio-recorded using a digital voice recorder or a personal mobile phone. The audio files were listened to, and their contents were summarised through tabulation based on a pre-established matrix format in Microsoft Excel (Microsoft Excel 2010, Microsoft Corp.; Redmond, WA, USA). The interviews summarized in the matrix were reviewed by two qualified data managers who were part of the study team. They cleaned and reviewed all identified errors before validating the summarizations in the matrix for analysis. Qualitative data analysis was mainly conducted using the framework and content analysis,19 where data were analyzed directly in the MS Excel matrix. This process analyzed concepts, messages, and their meanings and relationships within the text, considering the culture and context studied. In addition, the data were organized according to the themes related to the research questions, going from broad to specific.\n\nFurthermore, although the constructs were predetermined, the categories (corresponding to the participants’ responses) were open to emerging dimensions. Thus, the content of data inserted in the categories were analyzed. From this process, the main conclusions emerged. Underlying data for the study are publicly available.20,35\n\n\nResults\n\nA total of 295 community members participated in the interviews. The median age was 35 years old, and more than half of the participants (59%) were heads of households, married, or living with a partner. Roughly over half of the participants were female. Table 1 describes the characteristics of SSI respondents. Among the SSI respondents, 19% were self-employed in the informal business sector, 14% provided services, and 12% were retired or unemployed. Most respondents had completed high school or higher education levels (84%), while 14% had completed elementary school, and 2% had no education.\n\na The category “others” corresponds to several occupations such as administrative secretary, administrative assistants driver, painter, locksmith, tailor, craftsman, workers, community adviser, and hairdresser.\n\nAs shown in Table 2, the majority SSI respondents felt that it was necessary to change their routine to reduce the risk of contracting COVID-19. Participants from both formal and informal sectors reported adopting home office practice (i.e., work) and having stopped going out to school, physical activities, recreational and socializing activities. For those participants, these routine changes contributed directly to reducing their mobility. In addition, participants claimed it was impossible not to go out twice a week for basic needs, such as the market to buy and/or sell products such as food and water. A hybrid strategy to prevent COVID-19 consisting of “stay at home” and “go out to work” was also mentioned.\n\nLess than one-tenth of participants, particularly those in small and informal businesses, reported not changing routines. These participants said they had to go to work daily to put food on the table because they needed to eat every day.\n\n“If we do not work, we will not be able to have food for our families, so we cannot just stay at home” (SSI, Male, Manhiça).\n\nA small proportion of the participants reported that they did not change their routines much as they continued to go out sometimes to spend time with friends. These participants also mentioned that members of their households, in particular their children, no longer go to school or go out to play.\n\nAll participants mentioned having adopted at least one measure of COVID-19 prevention. As shown in Table 3, the three most reported COVID-19 preventive measures carried out in public places and when they are at home are: (i) frequent hand washing, (ii) the use of masks, and (iii) physical distancing. The participants highlighted hand washing as the most relevant preventive measure against COVID-19 infection because—in their voices—this measure had an immediate power to eliminate the virus in the hands.\n\n“We have to wash our hands always. For example, in my house, normally, when a person arrives from the street, the first thing they do is wash their hands because on the street we pick up and touch things and we take the virus to our pockets or our objects, so washing our hands comes first” (SSI, Female, Quelimane).\n\nIn regards to different measures to prevent COVID-19, participants (4%) mentioned eating foods or drinking liquids containing vitamin C and mineral salts in high concentrations, such as warm lemon juice or boiled water with salt. A relatively small proportion of participants (1%), mentioned that they adopted the inhalation of steam from eucalyptus leaves as a preventive measure.\n\n“… we also make lemon teas with honey or even strong lemon juice to drink and have more vitamin C and gain more immunity, we hear that this helps prevent this disease [COVID-19]” (SSI, Female, Maputo).\n\n“Eucalyptus and lemon leaf breath help burn all the viruses in the lungs” (SSI, Male, Maputo).\n\nAs shown in Table 3, when the participants are inside the house they reported to adopt several measures to prevent COVID-19. Frequent hand washing or disinfection with alcohol hand sanitizer gel were considereted as a primary measure to prevent COVID-19. Hand washing and disinfection was always prioritized, especially when picking up objects and touching the nose, eyes and mouth. According to the participants, the only way to avoid COVID-19 even at home is to always wash your hands. Some participants also mentioned that they used ashes and water to wash their hands in the lack of soap.\n\nWe must always wash our hands, if we don't, we can scratch our nose and then infect others (SSI, Female, Quelimane).\n\nRegarding physical distancing, participants claimed to face big challenges in practicing physical distancing within their homes to prevent COVID-19 transmission between family members. They consider it necessary especially for those who work out of the home and can put the most vulnerable at risk of COVID-19 infection. According to participants’ perception, challenges for physical distancing lies in the fact that children inevitably touch each other while playing and when adults—especially mothers and caregivers—take care of children. Another situation that poses challenges for practicing physical distancing is when adults arrive home— either from work or other activities—and children seek hugs from their parents. Unlike these, few participants reported not practicing or worrying about physical distancing at home due to poor housing conditions. According to their voices, house buildings are disproportionately smaller for the family size, making it impossible to keep distance between household members.\n\n“At home, we cannot avoid it, our house is small, and we have no other option” (SSI, Male, Maputo).\n\n“They stay together because there is no way to separate [Practice distance]. Then they can only trust God not to get infected” (SSI, Female, Matola).\n\nAccording to the participants, wearing the mask is one of the most critical and influential measures to prevent COVID-19 at home (37%). These participants voiced that the masks should be used at home to avoid being infected by domestic workers often exposed in public transport and markets. Some participants working in high-exposure settings such as health facilities and markets mentioned that they wear masks at home to avoid infecting people who stay at home. Participants also noted that although the mask is a more effective prevention method, it should be used with some care so that the person does not contract COVID-19 from a contaminated mask.\n\nParticipants mentioned that when they are leaving home they worry about all the COVID-19 prevention measures. They consider having alcohol sanitizer with them for hand disinfection, masks for face protection, and they also think about the distancing measures they should adopt when they arrive in crowds.\n\nWhen asked about specific preventive practices in public places, less than half of the participants mentioned having increased the frequency of hand washing when there is soap and water in the establishments where they go, or disinfecting, while few reported using surgical gloves after disinfecting hands to prevent infection.\n\nOn one hand, some participants agreed with implementing the mandatory measure concerning masks in public places. According to participants’ perceptions, the use of a mask is considered an individual protection measure against COVID-19 infection. All but a few pariticipants from rural areas such as Manhiça and Mopeia districts were willing to accept wearing masks in public spaces to protect themselves from COVID-19. At the same time, urban communities stated that mask-wearing in public spaces is an essential preventive measure to reduce the spread of COVID-19 in the country. Far beyond being a protective measure against COVID-19, on the other hand, mask-wearing was also perceived to be only necessary for accessing public transportation and public and private institutions (e.g., banks, health facilities, and commercial establishments) and to avoid problems with the police.\n\n“I wear my mask to be admitted to the institutional transport. When I get to work, I take it off because it is [the mask] not comfortable” (SSI, Male, Maputo).\n\n“When I am out of the house, I wear a mask, so I do not get in trouble with the police, and I wash my hands so I can be allowed into places [shops, markets, and other places.]” (SSI, Female, Manhiça).\n\n“When they go out, they do not feel comfortable because they have to wear a mask, but it is a law” (SSI, Male, Matola).\n\nThe study participants also identified mixed views about the barriers to wearing masks. For example, a participant from Quelimane city mentioned that when wearing a mask, she has difficulty breathing and reported being dissatisfied that wearing a mask is mandatory rather than voluntary. A minority of participants mentioned that wearing a mask makes communication difficult, bringing other complications to respiratory health.\n\n“This [Mask] is a prison. We cannot breathe with it. We are under arrest in it… and if we are to die, Allah will receive us” (SSI, Female, Quelimane).\n\n“The problem is that the mask suffocates. The person may even want to comply [using a mask], but after a while, they will not be able to breathe perfectly” (SSI, Female, Matola).\n\nIn addition, when they are away from home, physical distancing was the measure preferred and practiced by most participants. For instance, merchants mentioned that they ask customers to stay at least a meter away from the counter to ensure the minimum safe distance. However, participants acknowledge that this is not the recommended physical distance for COVID-19 prevention. Likewise in-home environments, participants reported it challenging to maintain the recommended physical distance outside the home. Shared spaces such as small offices, stores, stalls, and markets were perceived as places where it is impossible to keep the recommended distance to safeguard against COVID-19 infection.\n\nParticipants reported doing everything at their fingertips to cope with these challenges to avoid being in public and very bustling environments, including markets, public transport, and other crowded places. In the cases where busier areas were inevitable, preventing being side-by-side with other people was perceived as the best strategy for most participants, reflecting that participants were aware of and acknowledged risky environments while doing their best to avoid infections.\n\nParticipants mentioned that when they return home they face the fear of having brought the virus with them, so the measures of cleaning and disinfecting themselves are key to preventing and eliminating COVID-19.\n\nLess than one-fifth of participants stated that they organized a handwashing or hand disinfection point at the entrance of their homes to allow all household members and visitors to wash or disinfect their hands before entering the house.\n\n“The person must wash their hands before entering the house so as not to bring diseases from outside to infect others here in the house” (SSI, Male, Quelimane).\n\nWhen asked about the care taken when returning home, the practice of washing and disinfecting hands was also highlighted. In this regard, most participants mentioned that they wash or disinfect their hands (90%) and change their clothes for laundry (59%). In addition, a group of these participants mentioned that shoe disinfection points are also installed at the entrance to the house to prevent household members and visitors from entering with virus-infected shoes picked up from the street.\n\n“We put footbaths for people to disinfect their shoes before entering the house with viruses they are catching in the street” (SSI, Female, Maputo).\n\n\nDiscussion\n\nWe investigated behaviors, attitudes, and practices related to COVID-19 preventive measures during the first state of emergency period of COVID-19 in rural and urban settings in Mozambique. Analysis of 295 interviews revealed that most participants changed their routine by (i) adopting a home office and (ii) reducing their mobility. However, home confinement was observed to be partially adopted due to the need for basic home supplies. The main context where COVID-19 preventive measures where adoped included (i) inside the house, (ii) when leaving or away from home, (iii) when returning home. Reported preventive measures included increased frequency of hand washing, wearing the mask, and physical distancing. While patterns and frequency of practice of these preventive measures vary with participants’ location and living conditions, it was partially driven by fear of infection and prosecution by the authorities. Some participants reported to follow preventive measures to ensure to access to essential public services such as transportation. Our findings show that the majority of communities followed most of preventive measures against COVID-19 infection as stated by the government. At the same time, the need to increase awareness concerning COVID-19 prevention at the community level and among users of public places was shown to be a necessary strategy for reducing the spread of the virus. This was also seen with an increase in positive cases in the country as one of the indicators of this low awareness of the need for prevention.21\n\nWe found that most participants (47.1%) reported to have changed their routine and reduced their mobility (e.g., adoption of home confinement, no travel) to avoid exposure to COVID-19, and thus, complying with most established preventive measures. Our findings is consistent with a study involving public workers in Mozambique conducted in the initial public health emergency declaration in March 2020, which showed that a large proportion of participants changed their routines, having remained confined at home to avoid exposure and contraction of the disease.22 Findings from our study are also in line with another study carried out in Nepal reporting that human mobility patterns as a measure of prevention behavioral responses during the COVID-19 pandemic was significantly reduced during the first wave of COVID-19.23 This was notable when people started to be confined to their homes to avoid exposure to COVID-19 in the streets, stopped traveling to and from work (primarily through crowded transport) and stopped engaging in non-essential shopping.23 In the present study, the observed higher compliance to home confinement as a preventive measure was linked to the need for avoiding COVID-19 exposure. We hypothesize that the higher adoption of home confinement is partially explained by the fact that it was the preventive measure mostly disseminated in media (e.g., newspapers, television and social midia) and was an enforcement in the public and private sector. However, these results show that in public health emergencies due to pandemic outbreaks like that of COVID-19, continuous monitoring of these practices at the community level to better understand the current trend of infections and case fatalities and inform strategic preventive planning is advisable. This may also include efforts to improve vaccine adherence behavior as one of the prevention strategies.\n\nAlthough reporting reduced mobility and activities, the adoption of home confinement was notable partial to most participants and their family members for two reasons: (i) work for income and (ii) acquisition of essential supplies for family survival. These tendencies toward partial home confinement reflect the need of some heads of households to keep the routine considering the importance of work to guarantee the income for supporting the family needs. This is particularly because in Mozambique, most families live off small informal businesses, so regardless of the situation they feel forced to leave home to acquire income for the daily family's survival24; an issue hard to reveal when using quantitative approaches in investigating attitudes and practices at the community level. These findings corroborate with a study from South India where participants, especially those who suffered a significant impact on income reduction, chose to keep their routine of working outside home as the primary source of income for the family.25 It is worth noting that discourses of home confimenment were frequent and revealed an attitude to reduce dangers and thus protect “their home” environment. This may explain, even though partially, why there was a reduction in mobility over time mainly occurred during the first wave of COVID-19 pandemic despite the low number of positive cases and deaths from COVID-19 compared to the subsequent waves in Mozambique.26 These results reveal an excellent starting point for implementing awareness-raising interventions to reinforce existing knowledge about, and practices adopted against COVID-19.\n\nAt the individual level, the most reported preventive measures against COVID-19 infection were increased frequency of hand washing (42.4%) and use of a mask (43.4%), particularly in public places. Attitudes towards these two measures can be considered positive as most participants mentioned practicing at least one. Nevertheless, some participants were fed up with following some mandatory measures, such as wearing a mask in public places and spaces. Most participants reported practicing at least one of the COVID-19 prevention measures, particularly when in public places and/or when seeking public services, and this can be noted by the frequency of wearing masks when they are leaving home (60.7%) and keeping their distance when away from home (65.8%). This reveals that participants comply with the mandatory individual preventive measures, but these attitudes and pratices varied depending on where the participants were located.\n\nCompliance with health authorities’ recommendations on wearing mask and frequent hand hygiene was perceived as the most essential preventive measure in mitigating the spread of COVID-19 infections over the country. Surprisingly, hand hygiene was reported with a marked preference of using ‘water and soap’ instead of disinfectants, such as sanitary alcohol, regardless of location. For participants, washing hands with soap and water makes it cleaner and ensures that the virus is eliminated. Similar results were reported in a study conducted in Ethiopia, revealing that around 78.5% of community members wash their hands while inside and away from home to prevent COVID-19.27 These results show that frequent hand washing is one of the most common practice for preventing COVID-19 infection, and a positive attitude by household members in different scenarios, such as when they return home and when they are inside the home.\n\nExpectedly, reporting wearing a mask was as frequent as hand washing in all scenarios (First most frequent when leaving home and second most frequent when inside and away from home). Further, as a physical barrier, it was perceived as one of the most critical and influential measures in preventing COVID-19, whether at home or in public spaces. The behavior of wearing masks particularly in public places observed in our study is similar to the reported in an online survey regarding the adherence to measures to prevent COVID-19 conducted in three main cities of Mozambique, which showed that more than 90% of respondents claimed wearing a mask when leaving home.7 Although reported as a challenging, participants mentioned that the use of masks inside the house is necessary to avoid infection among household members and also to avoid being infected by domestic workers often exposed in public transport and markets. These findings were contrary to two studies from Bangladesh and Ethiopia that were conducted with community members reported that less than a third of the participants wore masks every time they left home.28,29\n\nThe rapid introduction of mandatory mask-wearing in public places for large-scale COVID-19 prevention was challenging. Our findings reveal that perception of discomfort, difficulty in communication and breathing were the most relevant barriers to wearing masks. Moreover, the participants claimed that compliance is motivated by the need to access public services and avoid complications with the police or inspection authorities. Our findings, however, corroborate with previous studies conducted in several settings reporting low mask-wearing due to difficulty in breathing, discomfort, communication and medical reasons.28–30 This result calls for a reflection concerning recommendations given by the health authorities on the importance of using masks in public places. Some participants in this study reveal that they wear masks to comply with the authorities’ exigencies and not because of the risk perception of COVID-19 infection. In addition, clear messages about the importance of using a mask and complying with measures to prevent COVID-19 are needed.\n\nOur data also highlight that at the community and family level, physical distance was one of the measures followed by community members, although it was hardly mentioned. Our results show that keeping physical distance was challenging in several locations. For example, inside the home physical distance between household members was considered to be challenging but necessary to avoid infection with COVID-19, including physical contact with objects. For instance, only 20% of participants mentioned complying with physical distancing at home. In contrast, a quarter of the same population perceives family proximity as a relevant challenge.31 Contrarily to our finding, Manjate and colleagues (2020) found a lower percentage of participants perceiving family proximity as a challenge for preventing infection from COVID-19.16 Family proximity probably suggests the existence of a feeling of trust between the same family members or of the same household, which influences the non-compliance with the measure of physical distancing at home. Previous studies show that this trust between people also extends to co-workers, friends and other people considered close.7,32,33\n\nWe also found that maintaining physical distance in crowded public spaces to reduce the risk of infection was of concern but perceived as essential among study participants. Further, study participants perceived it to be extremely tough to comply with physical distancing when at home with the family. Our findings are in line with a previous study reporting the importance of maintaining distance in all environments to prevent COVID-19 infections.32 Physical distancing is widely reported as one of the most practiced methods for COVID-19 prevention, however, its compliance varies on several factors.29,33,34 For instance, Benham and colleagues (2021) reported that compliance in maintaining safe distance for COVID-19 prevention was often found challenging in closed, public, and busy environments, such as supermarkets, shopping malls and elevators.32 Additionally, an international study reported that one-third of the adult population perceives crowded public spaces such as streets as a motivation against physical distancing. Thus they consider that in a public and open spaces the distance between people is guaranteed, and that other preventive measures, such as wearing masks for example, are also mandatory, which in a way ensures that everyone is well protected against COVID-19. These results suggest that public health policies with specific strategies such as affirmative action and public education still need to promote positive attitudes towards physical distancing.\n\nThis study presents notable strengths that can be used to design messages that can be used to improve community behavior on adherence to COVID-19 prevention measures. The study was designed to inform policymakers about the possible impact of aggravation or alleviation of specific measures throughout the evolution of the pandemic, adapt interventions in a strategic and evidence-based manner, and that interventions are designed based on the social reality of households and neighborhoods in the country’s districts and municipalities.\n\nHowever, this study has some significant limitations that may have influenced the reliability of the data. Interviews were conducted over the phone, culminating in several challenges of clear listening and cancellation of some interviews because of the audio quality, lack of time for some participants to finish the phone interviews, or having their mobile phone discharged during the interview. Study participants were intentionally selected through the contacts the study team had on their mobile phones, contributing to selection bias. This factor may have been exacerbated because the interviewees knew the interviewers.\n\n\nConclusions\n\nThis study suggests the introduction of awareness campaigns for community members and public place users, evidenced by structural and routine changes in households and the efforts of household members to adopt preventive measures. Attitudes and practices toward the COVID-19 preventive measures varied among participants’ locations and the concerns were dominated by widespread panic and insecurity. The compliance with preventive measures was partially driven by the need to access public services, which diverted the focus from the effort for people to put into practical measures to prevent and control COVID-19, especially concerning the use of masks and physical distancing practices in public places. Thus, in addition to monitoring compliance with the state of emergency measures to contain COVID-19, it is necessary to develop clear messages to encourage behavior change and increase adherence to health measures to reduce the transmission of COVID-19 among community members. Future studiesshould address barriers to public health measures that reduce COVID-19 transmission in communities.",
"appendix": "Data availability\n\nOpen Science Framework: Dataset for the attitudes and practices regarding COVID-19 preventive measure in diverse settings of Mozambique. https://doi.org/10.17605/OSF.IO/B58PM. 35\n\nThis project contains the following underlying data:\n\n- SOCIO DEMOGRAFICOS_DATABASE_MASTER_COVID SOND_MOZ___02003023_HC_.csv (Socio-demographic data)\n\n- Tele-Interview_SSI_COVID SOND_MOZ___23022023.csv 17012023 (Interview responses)\n\nOpen Science Framework: Dataset for the attitudes and practices regarding COVID-19 preventive measure in diverse settings of Mozambique. https://doi.org/10.17605/OSF.IO/B58PM. 35\n\nThis project contains the following extended data:\n\n- Appendix 5 Data record sheet of informal conversations.docx\n\n- Anexo 8 Interview Guide.docx\n\n- Anexo 6 Non Participation observation.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nWe would like to thank the study team members who dedicated themselves to the study design, training the interviewers, and everyone who dedicated themselves to collecting data on all sites covered by the study. We would also like to thank all study participants who took the time to answer the interviewers’ questions. We also acknowledge the support of Centro de Investigação em Saúde da Manhiça, which is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID).\n\n\nReferences\n\nMohamed T, El-aziz A, Stockand JD: Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19. The COVID-19 resource centre is hosted on Elsevier Connect, the company’ s public news and information.2020. (January).\n\nZhu N, Zhang D, Wang W, et al.: A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 2020; 382(8): 727–733. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCucinotta D, Vanelli M: WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020; 19(1): 157–160.\n\nGreer SL, King EJ, da Fonseca EM , et al.: The comparative politics of COVID-19: The need to understand government responses. Glob. Public Health. 2020; 15(9): 1413–1416. PubMed Abstract | Publisher Full Text\n\nUnited Nations in Mozambique: Unpacking the Potential Socioeconomic Impact of the Coronavirus Pandemic in Mozambique. A United Nations Situation Analysis and policy recommendations.2020; pp. 1–17.\n\nOffice of Human Services Policy: The Impact of the First Year of the COVID-19 Pandemic and Recession on Families With Low Incomes|ASPE.2021;(September); pp. 1–12. Reference Source\n\nINS: AVALIAÇÃO DA ADESÃO ÀS MEDIDAS DE PREVENÇÃO DA INFECÇÃO POR SARS-cov-2 EM MOÇAMBIQUE-2020.2020.\n\nGuambe Júnior JJ: Efeitos da Pandemia de Covid19 sobre o turismo na África subsaariana e em Moçambique Effects of the Covid19 Pandemic on tourism in sub-Saharan Africa and Mozambique José Júlio Júnior Guambe. Univ Pedagógica Maputo. 2020; pp. 59–78.\n\nMISAU: Estratégia Nacional de Resposta Comunitária à COVID-19 Estratégia Nacional de Resposta Comunitária à COVID-19. Estrateg Nac resposta ao COVID-19.2020.\n\nNAÇÕES UNIDAS: PLANO DE RESPOSTA MULTISSECTORIAL À COVID-19.2020; 5604.\n\nBOLETIM DA REPÚBLICA: Decreto Presidencial n.o 11/2020, de 30 de Março que Decreta o Estado de Emergência. Mocambique.2020; pp. 0–1.\n\nCTA: IMPACTO DO COVID-19 NA SECTOR EMPRESARIAL MOÇAMBICANO E. CTA; 2020.\n\nThe World Bank: GNI per capita, Atlas method (current US$)|Data. The World Bank; 2022 [cited 2022 Dec 18]. Reference Source\n\nJúnior A, Dula J, Mahumane S, et al.: Adherence to COVID-19 preventive measures in mozambique: Two consecutive online surveys. Int. J. Environ. Res. Public Health. 2021; 18(3): 1–9.\n\nDahab M, Van Zandvoort K, Flasche S, et al.: COVID-19 control in low-income settings and displaced populations: What can realistically be done? Confl. Heal. 2020; 14(1): 54. PubMed Abstract | Publisher Full Text | Free Full Text\n\nManjate J, Chavane F, Martins H, et al.: Knowledge, Attitudes and Practices of Mozambican Public Employees on the Prevention of Covid-19. Rev. Produção e Desenvolv. 2020; 6: 1–9. Publisher Full Text Reference Source\n\nMelville B: Rapid rural appraisal: Its role in health planning in developing countries. Trop. Dr. 1993; 23(2): 55–58. PubMed Abstract | Publisher Full Text\n\nIsaacs E: The Value of Rapid Ethnography.2014. (May).\n\nPope C, Ziebland S, Mays N: Principles of statistical data analysis. Pharm Pract Second Ed. 2017; 320(January): 455–466.\n\nMagaço A, Cumbane C, Cossa H: Dataset for the attitudes and practices regarding COVID-19 preventive measures in diverse settings of Mozambique: a qualitative study [version 1; peer review: awaiting peer review]. F1000Res. 2022; 11: 1123. Publisher Full Text\n\nBoletim Diário C-19: Coronavírus (covid-19).2020.\n\nManjate J, Felix S, Martins, et al.: Knowledge, Attitudes and Practices of Mozambican Public Employees in relation to the Prevention of COVID-19 TT - Conhecimentos, Atitudes e Práticas dos Funcionários Públicos de Moçambique em relação à Prevenção da COVID-19.2020. Reference Source\n\nChan HF, Skali A, Savage DA, et al.: Risk attitudes and human mobility during the COVID-19 pandemic. Sci. Rep. 2020; 10(1): 19913–19931. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHenrique J, Stacciarini S, Cristina Da Silva L: O mercado informal de Maputo (Moçambique) e a feira de Xipamanine: entre curiosidades e vivências no continente africano.2017.\n\nSingh K, Kondal D, Mohan S, et al.: Health, psychosocial, and economic impacts of the COVID-19 pandemic on people with chronic conditions in India: a mixed methods study.2021; pp. 1–15.\n\nMISAU: BOLETIM DIÁRIO COVID-19.2020.\n\nAkalu Y, Ayelign B, Molla MD: Knowledge, Attitude and Practice Towards COVID-19 Among Chronic Disease Patients at Addis Zemen Hospital, Northwest Ethiopia.2020; pp. 1949–1960.\n\nRabbani G, Akter O, Hasan Z, et al.: Knowledge, Attitude and Practice towards COVID-19 among people in Bangladesh during the pandemic: a cross-sectional study. Author; 2020.\n\nMola S, Aweke Z, Jemal B, et al.: Magnitude and associated factors for attitude and practice toward covid-19 and its prevention among the residents of gedeo zone, southern ethiopia: A community-based cross-sectional study. Risk Manag. Healthc. Policy. 2021; 14: 253–262. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRhyan NV, Lazard AJ, Frank SC, et al.: recommendations for promoting face coverings during the COVID-19 pandemic: Survey findings from a diverse sample. Press. 2021; 16(2019): 1–12. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCoroiu A, Moran C, Campbell T, et al.: Barriers and facilitators of adherence to social distancing recommendations during COVID- 19 among a large international sample of adults.2020; pp. 1–20. Publisher Full Text\n\nBenham JL, Lang R, Burns KK, et al.: Attitudes, current behaviours and barriers to public health measures that reduce COVID-19 transmission: A qualitative study to inform public health messaging.2021; pp. 1–14.\n\nGonzalez CJ, Almeida BA, Corpuz GS, et al.: Challenges with social distancing during the COVID-19 pandemic among Hispanics in New York City: a qualitative study.2021; pp. 1–8.\n\nEraso Y, Stephen H: Intentional and unintentional non-adherence to social distancing measures during COVID- 19: A mixed-methods analysis.2021; pp. 1–29. Publisher Full Text\n\nMagaço A: Dataset for the attitudes and practices regarding COVID-19 preventive measure in diverse settings of Mozambique. [Data]. Open Science Framework. 2023. Publisher Full Text"
}
|
[
{
"id": "251262",
"date": "04 Sep 2024",
"name": "María Romay-Barja",
"expertise": [
"Reviewer Expertise Behavioural insights and health"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article is sound and well written, however some issues need to be addressed. Pp. 3 “the present study results and recommendations significantly contributed to the decision-making process and development of effective public health communication strategies aiming at behavior change to reduce disease transmission at the community level” with cites 7 and 14. Are those results from the present study? It does not look like it, please improve the paragraph. Also, please add in the introduction a little more information on the epidemiological situation of COVID-19 in the country at the time of the study. Pp 4 “Study participants were selected for convenience” why? What justified such a convenience sample in this case? Pp 10 Discussion: “While patterns and frequency of practice of these preventive measures vary with participants’ location and living conditions” This has not been shown in the results, please add some results that reflects this relevant point. “Our findings show that the majority of communities followed most of preventive measures” this has not been shown by this study, we know what some people in some communities have done but they are not representative of the whole community. “At the same time, the need to increase awareness concerning COVID-19 prevention” please indicate which ones needed to be reinforced. “In the present study, the observed higher compliance to home confinement as a preventive measure was linked to the need for avoiding COVID-19 exposure” This may also be related to the socio-economic level of the sample, please discuss. Pp 11 “These results show that in public health emergencies due to pandemic outbreaks like that of COVID-19, continuous monitoring of these practices at the community level to better understand the current trend of infections and case fatalities and inform strategic preventive planning is advisable” Please provide references of countries that have conducted such studies and shared their findings. “This reveals that participants comply with the mandatory individual preventive measures, but these attitudes and practices varied depending on where the participants were located” and perhaps also with the socio-economic level of the people interviewed, please analyze and discuss it. “These results show that frequent hand washing is one of the most common practice for preventing COVID-19 infection, and a positive attitude by household members in different scenarios, such as when they return home and when they are inside the home.” Yes, but they also reflect a misunderstanding of the importance of alcohol handwashing as the only effective means of eliminating the virus from hands, which reflects that either the measure was not well explained by authorities or there were economic constrains or a shortage of hydroalcoholic gel to comply with it. Pp 12 Limitations “Study participants were intentionally selected through the contacts the study team had on their mobile phones, contributing to selection bias. This factor may have been exacerbated because the interviewees knew the interviewers.” Have the participants a level of education and employment higher than the average for the country? If yes, findings might not be generalizable, especially to the most vulnerable.\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? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-100
|
https://f1000research.com/articles/13-99/v1
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16 Feb 24
|
{
"type": "Research Article",
"title": "Comparative evaluation of surface microhardness and microleakage after application of commercially available G-Coat Plus, nano silver fluoride resin coat and petroleum jelly over glass ionomer cement restoration: an in vitro study",
"authors": [
"Dr. Pranjali Vilas Deulkar",
"Dr. Nilesh V Rathi",
"Dr Nilima Thosar",
"Dr Chitrika Subhadarsanee",
"Dr. Nilesh V Rathi",
"Dr Nilima Thosar",
"Dr Chitrika Subhadarsanee"
],
"abstract": "Background Glass ionomer cement (GIC) is a widely used tooth coloured material. However, GIC holds certain undesirable properties. In order to overcoming the major drawback of moisture sensitivity, surface coatings like petroleum jelly, varnish are applied over GIC restoration. Thus, the present study was planned to compare efficacy of newly formulated nano silver fluoride resin coat with G Coat Plus and petroleum jelly on microhardness and microleakage of Type IX GIC.\n\nMethods Class V cavities were prepared on the buccal surface of thirty-six non carious premolars and restored with type IX GIC. The restored teeth were divided into 3 groups: Petroleum gel, G Coat plus and Nano silver fluoride resin coat. Protective surface coatings were applied over the restorations, dried for 2 minutes and thermocycled. Teeth were then placed in 1% methylene blue for 24 hours. Longitudinally sections were prepared and were observed under stereomicroscope at 25x magnification for dye penetration. Forty-five blocks of PVC were prepared and restored with GIC. Samples were divided into three groups equally as mentioned earlier and a layer of each coating was applied on all samples according to the groups and dried for 2 minutes. Further, surface microhardness (SMH) of the samples was tested by Vickers microhardness machine under a load of 50 grams for 10 seconds at 3 sites and a mean was calculated. Statistical analysis was conducted using post hoc and one way-ANOVA tests.\n\nResults The microleakage scores of three groups were statistically insignificant. The mean microhardness of all samples in the three groups showed no statistically significant difference. The mean surface microhardness of group 1 was 66.44±4.57 whereas for group 2 and group 3 it was 76.15±3.02 and 79.22±4.03 respectively.\n\nConclusions The novel agent containing nano silver fluoride is showed superior results and is intended to augment the properties of GIC.",
"keywords": [
"NANO SILVER FLUORIDE",
"GLASS IONIMER CEMENT",
"G C COAT PLUS",
"VASELINE"
],
"content": "Introduction\n\nGlass ionomer cement (GIC) is a widely used fluoride releasing tooth coloured material.1 It has good dimensional stability and coefficient of thermal expansion similar to the tooth structure. However, GIC holds certain undesirable properties like early moisture sensitivity, low strength, poor marginal integrity, and wear resistance.2–4\n\nIn order to overcome the major drawback of moisture sensitivity, various surface coatings like petroleum jelly, varnish, cocoa butter are applied over the GIC restoration.5–7 The nanofilled, self-adhesive agent G-Coat Plus (GC Corp., Tokyo, Japan) has a single dispersion nano-filler technology for dispersion of silica particles. This gives internal protection to the restorations against cracks and voids for increased fracture toughness. It also reinforces the outer layer for increased wear resistance and protection against acid erosion. G-Coat Plus lamination strengthens, protects and enhances the glass ionomer restorations by giving it a finished superficial surface. However, recent literature evaluating the efficacy of G-Coat Plus states that its application over GIC severely impede its fluoride releasing property. This may predispose it to restoration failure and secondary caries.\n\nNano silver fluoride is a unique material with amalgamation of silver and fluoride, making it an antibacterial and remineralising agent. The silver nano particles (AgNPs) are claimed to act as fillers and increase the wear resistance of any surface. The incorporation of nano silver fluoride in a resin base was presumed to be a good surface coating over glass ionomer cement and thus, the present study was performed to compare the efficacy of newly formulated nano silver fluoride resin coat with commercially available G Coat Plus and petroleum jelly on microhardness and microleakage of Type IX GIC, under in vitro conditions.\n\n\nMethods\n\nThe present study was carried out in the Department of Pediatric & Preventive Dentistry, Sharad Pawar Dental College, Wardha after obtaining the institutional ethical approval on 29th August 2019 with the reference number DMIMS (DU)IEC/Aug-2019/8298. Sample size was calculated using the following formula: n= Zα+Zβ[P11−P1+P21−P2]P1−P22 and it came down to 15 in each group. Non-carious premolar teeth were taken from healthy patients who underwent extraction for orthodontic purpose.\n\nThirty-six non-carious premolars extracted for orthodontic purpose were collected from the patients after taking a written informed consent. The teeth were cleaned with sodium hypochlorite for 10 minutes and stored in 0.1% thymol solution at 4°C, till needed. A Class V cavity was prepared on the buccal surface of each tooth with 4 mm length, 2 mm width and 0.75 mm depth using No.1 round bur, No. 57 straight fissure bur with high-speed air rotor headpiece under water irrigation. All cavosurface margins were kept at 90° without bevel and burs were changed for each preparation. A William’s graduated periodontal probe (Hu-friedy, Chicago, IL, USA) was used to gauge the dimensions of the cavity. These prepared samples were divided into 3 groups: Group 1: Petroleum jelly (Vaseline™), Group 2: G Coat plus and Group 3: Nano silver fluoride resin coat. Protective surface coatings were applied over the restorations, dried for 2 minutes and placed in artificial saliva mimicking the clinical conditions. Thermocycling of all the samples was carried out at 5°C and 55°C for 500 cycles with a dwelling time of 30 seconds. The restored teeth were placed in 1% methylene blue for 24 hours. The longitudinal sections were prepared in a bucco-lingual plane using a double sided disc (Horico, Berlin, Germany) in a straight headpiece and were observed under stereomicroscope (M9; Wild Heerbrugg, Switzerland) at 25× magnification for dye penetration.\n\nAssessment Criteria Score (Saboi et al. 2002)\n\nNo dye penetration 0\n\nDye penetration up to 1/3 cavity depth 1\n\nDye penetration 1/3-2/3 cavity depth 2\n\nDye penetration >2/3 of cavity depth or full extent of axial wall 3\n\nMicrohardness assessment\n\nForty-five blocks of PVC were prepared and restored with glass ionomer cement using a spatula. The blocks were overfilled to some extent, covered with mylar strips and compressed with glass slab, allowing proper condensation. The samples were divided into three equal groups: Group 1: Petroleum jelly, Group 2: G Coat plus and Group 3: Nano silver fluoride resin coat and a layer of each coating was applied on all the samples according to the groups and dried for 2 minutes. Further, the surface microhardness (SMH) of all the samples was tested by Vickers micro hardness testing machine under a load of 50 grams for 10 seconds at 3 different sites and a mean for each sample was calculated.\n\n\nResults\n\nTable 1: The mean microleakage levels of all the samples in the three groups are compared. In Group 1, all the samples showed dye penetration. Of which, 60% of the samples showed dye penetration of more than 2/3 of cavity depth. Indicating a poor coverage over the GIC surface. 33.3% samples in Group 2 also showed no dye penetration. Remaining samples showed some amount of penetration, however the extent was less than 2/3 depth of the cavity. In Group 3, 46.7% of the samples showed no dye penetration. Remaining 40% and 13.3% samples showed less than 1/3 and 1/3-2/3 penetration respectively. Though Group 3 showed best results, the difference between the all groups is statistically insignificant.\n\nThe difference between the groups is statistically insignificant.\n\n* p<0.001 – statistically significant.\n\nTable 2: The mean micro hardness levels of all the samples in the three groups are compared. The comparison between Group 1 (66.44±4.57) and Group 2 (76.15±3.02) showed no statistically significant difference (p<0.001). The mean microhardness values of Group 2 (76.15±3.02) and Group 3 (79.22±4.03) has no statistical difference (p=0.095). The difference between Group 1 (66.44±4.57) and Group 3 (79.22±4.03) has no statistical difference (<0.001).\n\n* p<0.001 – statistically significant.\n\n\nDiscussion\n\nConventional glass ionomer cement (GIC) is a fluoride releasing cement which sets by acid base reaction.8,9 Water content in GIC is critical in attaining optimal properties. It acts as a medium for the dissolution of the polymeric acid, and allows it to ionise and donate protons, thereby behaving as a Bronsted-Lowry acid. The cations are released from the glass and are hydrated unbound water. The unbound water hydrates the cations released from the glass to form a sheath of water around aluminium, magnesium and silica ions. The bound water sheath matures in a centripetal fashion to polymerise the cement.8 Maintaining the water balance early in the life of the cement is important. Loss of water leads to formation of microscopic cracks by local contraction as the water escapes.10 Similarly, contamination with excessive water leaches out the ions causing dissolution of the cement. To prevent this, clinicians are advised to cover the surface of newly placed glass ionomer cement with a protective coating. Various studies are in agreement with this fact that surface protective coatings over Glass ionomer cement are helpful to avoid loss and gain of water during the setting reaction.5,7,11,12\n\nIn the present study, G-Coat plus group showed better results when compared to Petroleum jelly group with respect to both microhardness and microleakage. This is in congruence with studies conducted by Mandikos MN et al.13; Tantbirojn D et al.14 and Arthilakshmi et al. who assessed the microhardness.15 A study done by Tyagi S. et al. assessed microleakage of dye using spectrophotometer and showed results analogous to the present study.16 This can be attributed to the even dispersion of nanofillers (30 nm) that have a ‘micro-lamination effect’ giving it an uniform flow over the cement forming a protective coating of about 35-40 μm.17,18 Though Petroleum jelly is the most commonly used surface protective agent, studies depict its limited efficacy as it gets easily washed away. It may also leave its residues in between the restoration and cavosurface margins leading to persistence of the nanogaps.\n\nIn the present study, efficacy of a novel preparation containing nano silver fluoride, resin and tartaric acid was assessed.19,20 The microhardness of GIC was highest when coated with NSF resin followed by G Coat Plus and Petroleum jelly. This is accredited to the addition of d-tartaric acid which acts as an accelerator aiding in the extraction of ions from the aluminosilicate glass and facilitates their binding to the polyanion chains.21 Tartaric acid, also acts as a crosslinking agent in the matrix formation of GIC acting as a base in the setting reaction, thereby accelerating early maturation. This action depends on its concentration. Low concentrations accelerate the development of viscosity of the cement paste, while high concentrations retard it. Literature suggests that enhancement of physical properties of GIC occurs on the addition of 10% (w/w) tartaric acid.21 At intermediate concentrations, tartaric acid has an interesting, uniquely favorable effect on setting characteristics. First, it induces a lag period in the setting process during which the viscosity of the cement paste remains constant. This lag period is followed by a sharp, almost exponential, increase in viscosity. Thus, tartaric acid is found to have a dual effect on setting, first inhibiting gelation and then accelerating it. The practical effect is to prolong working time and sharpen setting. A study conducted by Ahmadi Jaya Permana et al. found that addition of tartaric acid enhanced compressive strength of GIC and quoted similar reasons for it.22\n\nOn assessing microleakage, it was found that NSF resin coat had the best results in the present study. However, the difference between G Coat plus group and NSF resin coat group was not statistically significant. NSF resin coat is a self-cured adhesive, hydrophilic resin which polymerises within 20 seconds of application to form a thin film over the restored GIC. It provides convenience of handling and prevents the probability of contamination. The low viscosity aids in sealing the microgaps in between the margins and restoration. The uniformly dispersed nano silver particles present in the coat may also protect the resinous coat from abrasive wear.\n\nResearchers claim that AgNPs are more potent in having bactericidal and bacteriostatic action than silica nano particles present in G Coat Plus.22 The indigenious product used in the present study has additive antibacterial and fluoride releasing property. Application of nano silver fluoride resin coat will aid in halting the initiation secondary caries in the restored teeth by having an anti-plaque action.23 A study conducted by Rekhalakshmi K. et al. compared the fluoride release after application of Petroleum jelly and G Coat plus, and stated that there was a remarkable decrease in the fluoride release after coating the tooth with G Coat Plus.16 However, nano silver fluoride resin coat overcomes this shortcoming because of the presence of fluoride in it. It can provide a sustained fluoride release after application.\n\nThe present study concluded that nano silver fluoride resin coat over Glass ionomer cement restoration demonstrated better mechanical properties than G Coat Plus and Petroleum jelly, within the limitations.\n\n\nConclusion\n\nThe novel surface protecting agent containing nano silver fluoride is a self-cured adhesive possessing antibacterial and fluoride releasing properties is thereby intended to augment the properties of glass ionomer cement.",
"appendix": "Data availability\n\nFigshare: Comparative evaluation of surface microhardness and microleakage after application of petroleum jelly, commercially available G-Coat plus and Nano silver fluoride resin coat over Glass ionomer cement restoration: An in vitro study, https://doi.org/10.6084/m9.figshare.23290592.v1. 24\n\nThis project contains the following underlying data:\n\n- Masterchart.xlsx (microhardness and microleakage)\n\nFigshare: Comparative evaluation of surface microhardness and microleakage after application of petroleum jelly, commercially available G-Coat plus and Nano silver fluoride resin coat over Glass ionomer cement restoration: An in vitro study, https://doi.org/10.6084/m9.figshare.23305895.v1. 25\n\nThis project contains the following extended data:\n\n- tables.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\nKamatham R, Reddy S: Surface coatings on glass ionomer restorations in Pediatric dentistry-Worthy or not? J. Indian Soc. Pedod. Prev. Dent. 2013; 31(4): 229–233. PubMed Abstract | Publisher Full Text\n\nWilson AD, Kent BE: A new translucent cement for dentistry: the glass ionomer cement. Br. Dent. J. 1972; 132: 133–135. Publisher Full Text\n\nCroll TP, Nicholson JW: Glass ionomer cement in pediatric dentistry - review of the literature. Pediatr. Dent. 2002; 24: 423–429. PubMed Abstract\n\nMount GJ: Glass-ionomer cements: Past, present and future. Oper. Dent. 1994; 19: 82–90. PubMed Abstract\n\nBrito CR, Velasco LG, Bonini GAVC, et al.: Glass ionomer cement hardness after different materials for surface protection. J. Biomed. Mater. Res. A. 2009; 93A: 243–246. Publisher Full Text\n\nPilo R: The effect of resin coating on the shear punch strength of restorative glass ionomer cements. Clin. Oral Investig. 2017; 21: 1079–1086. Publisher Full Text\n\nWilliams JA, Billington RW, Pearson GJ: Effect of moisture protective coatings on the strength of a modern metal reinforced glass ionomer cement. J. Oral Rehabil. 1998; 25: 535–540. PubMed Abstract | Publisher Full Text\n\nBarry TI, Clinton DJ, Wilson AD: The structure of a glass ionomer cement and its relationship to the setting process. J. Dent. Res. 1979; 58: 1072–1079. PubMed Abstract | Publisher Full Text\n\nWilson AD, Mclean JW: Glass Ionomer Cements. Vol. 164. . Chicago: Quintes Pub Co. Inc; 1988; pp. 293–300. Publisher Full Text\n\nEarl MSA, Hume WR, Mount GJ: Effect of varnishes and other surface treatments on water movement across the glass ionomer cement surface. Aust. Dent. J. 1985; 30: 298–301. Publisher Full Text\n\nValera V, Navarro MFL, Taga EM, et al.: Effect of nail varnishes and petroleum jelly combination on glass ionomer dye uptake. Am. J. Dent. 1997; 10: 253–351.\n\nHattab FN, Amin WM: Fluoride release from glass ionomer restorative materials and the effects of surface coating. Biomaterials. 2001 Jun; 22(12): 1449–1458. PubMed Abstract | Publisher Full Text\n\nMandikos MN, McGivney GP, Davis E, et al.: A comparison of the wear resistance and hardness of indirect composite resins. J. Prosthet. Dent. 2001; 85: 386–395. PubMed Abstract | Publisher Full Text\n\nTantbirojn D, Versluis A, Cheng Y, et al.: Fracture toughness and microhardness of a composite: do they correlate? J. Dent. 2003; 31: 89–95. PubMed Abstract | Publisher Full Text\n\nArthilakshmi VC, Annamalai S, Baghkomeh PN, et al.: Effect of protective coating on microleakage of conventional glass ionomer cement and resin-modified glass ionomer cement in primary molars: An in vitro study. Indian J. Dent. Res. 2018; 29: 744–748. Publisher Full Text\n\nTyagi S, Thomas AM, Sinnappah-Kang ND: A comparative evaluation of resin- and varnish-based surface protective agents on glass ionomer cement – a spectrophotometric analysis. Biomater. Investig. Dent. 2020; 7(1): 25–30. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNinawe N: A comparative evaluation of microleakage of glass ionomer restoration with different surface protectors - an in-vitro study. DJAS. 2014; 02(II): 105–108. Publisher Full Text\n\nBagheri R, Taha N, Azar M, et al.: Effect of G-Coat Plus on the mechanical properties of glass-ionomer cements. Aust. Dent. J. 2013 Dec; 58(4): 448–453. PubMed Abstract | Publisher Full Text\n\nZhang K, Cheng L, Imazato S, et al.: Effects of dual antibacterial agents MDPB and nano-silver in primer on microcosm biofilm, cytotoxicity and dentine bond properties. J. Dent. 2013; 41: 464–474. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTargino AGR, Flores MAP, dos Santos Junior VE , et al.: An innovative approach to treating dental decay in children. A new anti-caries agent. J. Mater. Sci. Mater. Med. 2014 Aug; 25(8): 2041–2047. PubMed Abstract | Publisher Full Text\n\nCrisp S: Reactions in Glass lonomer Cements: V. Effect of Incorporating Tartaric Acid in the Cement Liquid. J. Dent. Res. November-December 1976; 55: 1023–1031. Publisher Full Text\n\nPermana AJ: The Influence of Dicarboxylic Acids: Oxalic Acid And Tartaric Acid On The Compressive Strength Of Glass Ionomer Cements. Basic and Applied Sciences (ICOWOBAS 2015). 050003–050006.\n\nDeulkar PV, Rathi N, Thosar N, et al.: Impact of sodium fluoride and nano silver fluoride-based varnishes on remineralisation of enamel caries: an in-vitro study [version 2; peer review: 1 approved with reservations]. F1000Res. 2023; 12: 643. Publisher Full Text\n\nDeulkar PV, Rathi N, Thosar N, et al.: Comparative evaluation of surface microhardness and microleakage after application of petroleum jelly, commercially available G-Coat plus and Nano silver fluoride resin coat over Glass ionomer cement restoration: An in vitro study. Dataset. figshare. 2023. Publisher Full Text\n\nDeulkar PV, Rathi N, Bane S: Comparative evaluation of surface microhardness and microleakage after application of petroleum jelly, commercially available G-Coat plus and Nano silver fluoride resin coat over Glass ionomer cement restoration: An in vitro study. figshare. Figure. 2023. Publisher Full Text"
}
|
[
{
"id": "268023",
"date": "29 Apr 2024",
"name": "Handially Vilela",
"expertise": [
"Reviewer Expertise Remineralization dentin / Glass ionomer cement"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors proposed a study of high clinical relevance and the methodology adequately answers the initial question. I suggest a minor review:\nINTRODUCTION • In the statement: “However, recent literature evaluating the efficacy of G-Coat Plus states that its application over GIC severely impedes its fluoride releasing property”, what is the reference? • “Nano silver fluoride is a unique material with amalgamation of silver and fluoride, making it an antibacterial and remineralizing agent.” What is the reference? There are studies proving that the release of fluoride from glass ionomer cement, as it is low, does not act as a remineralizing agent. It works by hindering the demineralization process. I understand that this contradiction present in the literature should be mentioned in the text. I suggest the following articles demonstrating the failure of glass ionomer cement in the remineralization process [Ref 1,2]\nMETHODOLOGY • It would be interesting to add an illustration to the topic “Microleakage assessment”.\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": "268024",
"date": "05 Jun 2024",
"name": "Baranya Shrikrishna Suprabha",
"expertise": [
"Reviewer Expertise Pediatric and Preventive Dentistry"
],
"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. Introduction: reference not provided for the details on nano silver fluoride 2. Methods: A. For the sample size, instead of the formula, the assumptions on the effect size and/or error margin, power and confidence interval should be stated in a sentence. B. Brand name, Company name, place and country details to be specified for all the products used in the study, including the Stereomicroscope and the Vicker Hardness Tester. C. What type of GIC was used for restorations prepared for microleakage testing? Details on manipulation of the material needs to be explained. Similarly specify details of the GIC used for microhardness measurement D. The authors claim that \"Nano silver fluoride coat\" is novel. How was the solution prepared? Details on its composition required. E. How do authors justify using the term \"microhardness\" over \"hardness\" based on the procedure used for testing? F. Details of the statistical methods used not provided. How was the percentage of the microleakage arrived at? The scoring criteria used suggests it to be nominal data. Specify the software used for statistical analysis. G. How was the reliability of the readings ascertained for microleakage and microhardness assessment? Was the assessor blinded to the groups? 3. Results: should be in past tense at all places. Please check and correct the write up under Table 1 for the correct tense. The result write up for microhardness contradicts the tables: It should be corrected as \"There was statistically significant difference between Group 1 and 2, Group 1 and 3 for microhardness with no statistically significant difference between Groups 2 and 3.\" Page 5 Last paragraph: \" This can be attributed to the even dispersion of nanofillers\" Specify what \" This\" means here. 4. Discussion: what do authors mean by \"indigenous product\" in reference to the nano silver fluoride? What is the basis for this: \"However, nano silver fluoride resin coat overcomes this shortcoming because of the presence of fluoride in it.\" Provide a reference. Provide literature evidence for fluoride release after nano silver fluoride coat. What are the suggestions for future research based on the current study results? What are the study limitations? Conclusion is not in accordance with the study objective/ study results. Please change in both abstract and main text.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "292768",
"date": "09 Jul 2024",
"name": "Maha Jamal Abbas",
"expertise": [],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear authors,\n\nThe subject of the study is interesting that deals with efficacy of newly formulated nano silver fluoride resin coat with G Coat Plus and petroleum jelly on microhardness and microleakage of Type IX GIC. This study investigates the effects of G-Coat Plus, nano silver fluoride resin coat, and petroleum jelly on the microhardness and microleakage of Type IX glass ionomer cement restorations. The article's strength lies in its relevant and timely exploration of new treatments for enhancing restoration durability. Major strengths include the comprehensive methodology and clear presentation of results. However, minor weaknesses include referencing issues in the introduction and methodology sections. Summary of Findings: The findings indicate that all three coatings influence the surface properties of the glass ionomer cement, with varying impacts on microhardness and microleakage. The study concludes with recommendations for further research and clinical implications. Title: The title is so long so the title prefers as following: Comparative Evaluation of Surface Microhardness and Microleakage in Glass Ionomer Cement Restorations Treated with G-Coat Plus, Nano Silver Fluoride Resin Coat, and Petroleum Jelly: An In Vitro Study The abstract a study of high clinical relevance and the methodology adequately answers the initial question. I suggest a minor review Introduction:\nLine 6-14 need reference\n\nLine 14-18 need reference Material and method: Sample size was calculated using the following formula: n= (Zα+Zβ)[P1(1−P1)+P2(1−P2)](P1−P2)2 need more explanation about formula for other researcher Conclusion: The conclusion needs to be rewritten because it does not reflect the research results as it did not mention the results about microhardness and microleakage.\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? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-99
|
https://f1000research.com/articles/13-97/v1
|
15 Feb 24
|
{
"type": "Research Article",
"title": "Evaluating Wilson sims tool: Quality improvement on fall risk in UAE psychiatric patients",
"authors": [
"Crisostomo Valondo",
"Ahmad Muneer",
"Lynn Itani",
"Tarik Qassem",
"Hessa AbdulQader",
"Crisostomo Valondo",
"Lynn Itani",
"Tarik Qassem",
"Hessa AbdulQader"
],
"abstract": "BACKGROUND Falls among patients in psychiatric inpatient healthcare settings present a significant global challenge, despite ongoing efforts to reduce the risks. Falls negatively impact patient safety, post-treatment recovery, and medical costs.\n\nAIM This study aimed to evaluate the predictive validity of the Wilson Sims Fall Risk Assessment Tool (WSFRAT), investigate predictors of falls, and determine the optimal cut-off point for the WSFRAT. Additionally, we aimed to assess the predictive validity of clinical judgement in identifying individuals at high risk of falls.\n\nMETHODS We conducted a psychometric study at a specialized psychiatry hospital in Dubai, United Arab Emirates, using data collected from hospital-wide quality projects between April 16, 2019, and March 31, 2021. Our sample comprised 492 patients.\n\nRESULTS Contrary to the recommended cut-off point of 7 in the literature, this study results indicate that the optimal cut-off point for the WSFRAT was 5+. This yielded an accuracy of 87%, a diagnostic odds ratio (DOR) of 0.728, a kappa value of 0.208, a sensitivity of 83%, and a specificity of 87%. Furthermore, the regression analyses identified significant predictors of fall risk, including age, gender, assistive device, WSFRAT, and evaluation duration. Notably, clinical judgement did not significantly predict fall risk (p=0.331).\n\nCONCLUSION In conclusion, the present research demonstrates that the WSFRAT is a reliable tool with high sensitivity and specificity for predicting falls in psychiatric inpatient settings. The findings emphasize the importance of employing evidence-based tools and a comprehensive assessment approach to prevent falls. Furthermore, our findings challenge the recommended cut-off point of 7 and highlight the need for further research to confirm the optimal cut-off point. Finally, this investigation revealed that clinical judgement alone is not an effective method for predicting falls in this population.",
"keywords": [
"Patient falls - risk assessment tools in Mental health settings- predictive validity - predictors of fall risk -Wilson Sims Fall Risk Assessment Tool"
],
"content": "1. Introduction\n\nPatient falls during hospitalization are a significant concern in healthcare due to the serious consequences they can have. These consequences range from physical injury to costly medical care and prolonged hospital stays (Watson et al., 2011). Hospital fall prevention programs are typically implemented to minimize the risk of patient falls, which include various tools for evaluating and predicting fall risk in admitted patients. However, psychiatric units pose a particular challenge, as falls are more frequent due to the combination of risk factors that patients face (Carpels et al., 2022). These risk factors include behavioural and cognitive manifestations of illnesses, medication side effects, and increased mobility during therapeutic activities (Lu et al., 2018).\n\nAlthough fall prevention strategies are important in all healthcare settings, research about fall risk assessment tools specific to psychiatric patients remains limited. In 2016, Abraham looked at the applicability of several fall risk assessment tools in hospitals, and found that the majority of these tools were better suited for use in surgical or medical departments and with elderly patients, such as the Hendrich II Fall Risk Model (Abraham, 2016). While two tools have been developed for the assessment of fall risk in psychiatric patients, these studies were based on relatively small sample sizes (Edmonson et al., 2011; Healey, 2010). Specifically, the Edmonson Psychiatric Fall Risk Assessment Tool (EPFRAT) and the Wilson Sims Fall Risk Assessment Tool (WSFRAT) were identified, with the former showing a sensitivity of 63% and a specificity of 85%, and the latter having a sensitivity of 100% and a specificity of 63.1% (Edmonson et al., 2011; Healey, 2010). One notable difference between these tools is that the WSFRAT includes a field for nurses to provide their clinical judgment regarding whether a patient is at risk of falling or not. This evaluation takes priority over the final WSFRAT score.\n\nFurther research is necessary to evaluate the psychometric properties of these tools. Studies from Hong Kong and Taiwan have evaluated the psychometric properties of the WSFRAT, but these studies had limitations. In the study from Taiwan, the details of the research were not accessible, and the study from Hong Kong was limited to a geriatric patient population and calculated psychometric indicators based on the number of patients rather than the number of observations. The study recommended the WSFRAT due to its high sensitivity (Chou & Hung, 2019; Wong et al., 2021). Falls in psychiatric wards remain a persistent problem, so it is critical to obtain data from large datasets for the development of effective fall prevention strategies. Therefore, the aim of the current study is to evaluate the psychometric properties of the WSFRAT based on a large number of observations from different psychiatric wards in a specialized mental health hospital. Such research will provide valuable insights into the fall risk assessment tools for psychiatric patients and aid in the development of effective fall prevention strategies.\n\n\n2. Methods\n\nSecondary data analyses from hospital-wide quality projects between April 16, 2019, and March 31, 2021.This study aim to Assess the predictive validity of the Wilson Sims Fall Risk Assessment Tool (WSFRAT), Another objective of our study was to determine how well nurse clinical judgment can identify those who are at a high risk of falling. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and optimum cut-off value of the WSFRAT are all to be determined.\n\nThe data was collected from Al Amal Psychiatric Hospital, a specialized psychiatry hospital based in Dubai, United Arab Emirates. Data collection took place between 16th of April 2019 and 31st of March 2021.\n\nUnder the auspices of the nursing and Quality Department at Al-Amal Psychiatric Hospital, first authorized for the Quality Improvement Project (QIP) was granted, denoted by the reference number NQD-QIP-1903-WSFRAT. Subsequent approval was obtained from the Research and Development (R&D) committee at the same institution in October 2020, leading to the formal registration of the project under the reference number R&D-QIP-2010-WSFRAT.\n\nThe primary focus of this inquiry centered on assessing the effectiveness of the Wilson Sims Fall Risk Assessment Tool among psychiatric patients. The study strictly adhered to the standard treatment protocols for patients, refraining from introducing any additional procedures or interventions. As a result, the investigation was deemed exempt from an exhaustive review by the Research Ethics Committee (REC) under reference number R&D-QIP-2010-WSFRAT. This exemption was granted based on the understanding that the project’s methodology did not warrant an extensive REC evaluation due to its alignment with established ethical standards and its limited impact on routine patient care.\n\nThe sample comprised of 492 patients admitted to male and female acute mental health inpatient treatment units.\n\nA secondary analysis for Data was derived from hospital-wide nursing quality projects, a database of patients’ profiles was developed with the support of two senior nurse managers and information from hospital electronic medical records. The database included the following characteristics of patients: gender, age, nationality, diagnosis, number of observations, history of falls, use of assistive devices, and if the patients had a fall while hospitalized. Data on fall risk assessment was collected using the Wilson Sims Fall Risk Assessment Tool (WSFRAT).\n\nInitially created in Michigan United States of America, the WSFRAT is completed by nurse staff during the admission of adult inpatients to the hospital. The scale consists of ratings for nine risk factors: “(a) age; (b) mental status; (c) physical status; (d) elimination; (e) sensory impairments; (f) gait or balance; (g) history of falls in the past 6 months; (h) medications (e.g., mood stabilizers, benzodiazepine agents, narcotic agents, sedative/hypnotic drugs, antipsychotic agents); and (i) a detoxification protocol” (Van Dyke et al., 2014). A low risk corresponds to a total score of 0-6 while a score ≥7 is high risk. As mentioned previously, the WSFRAT also takes into consideration the nurse’s clinical judgement and this takes precedence over the risk score for the classification of fall risk (Wilson et al., 2014).\n\nAll Hospital inpatients must be screened for risk of falls on admission and every 24 hours to determine the ongoing need for fall prevention precautions. Inpatients considered at risk of falls should be re-assessed every 12 hours, additionally, the assigned nurse/health care provider must apply the appropriate fall prevention precaution Interventions to protect patients at risk for falling and harming themselves using the least restrictive alternative available.\n\nThe falls risk evaluation using WSFRAT was completed upon admission, once per day and until discharge. If the patient had been admitted before the start of data collection, then the evaluation was made on 16th May 2019. Named patient’s nurse was requested to give an opinion about the patient’s overall falls risk. The opinion took binary format, whether high risk or low risk. This was done independent to patient’s score on WSFRAT.\n\nIn accordance with established criteria, a fall was precisely delineated for the purposes of this study. As per the definition provided by The National Database of Nursing Quality Indicators (NDNQI), a fall is characterized as an unplanned descent to the floor or extension of the floor, which may involve contact with any other equipment, and can occur with or without resultant injury (Montalvo, 2007). This definition aligns with the understanding that a fall constitutes an event during which an individual inadvertently comes to rest on the ground or another lower level, with or without a concurrent loss of consciousness, as outlined by Nice (2014). Furthermore, recent global health estimates as reported by the World Health Organization (WHO, 2021) specify a fall as an incident leading to an individual unintentionally resting on the ground, floor, or any other lower level. It is noteworthy that fall-related injuries encompass outcomes that range from non-fatal to fatal, underscoring the severity and diverse consequences associated with such incidents.\n\nThe present study employed the R programming language (Team, 2021) along with several libraries, namely psych (Revelle, 2020), cutpointr (Thiele & Hirschfeld, 2020), ggplot2 (Wickham et al., 2016), pROC (Robin et al., 2011), tidyverse (Wickham et al., 2019), and caret (Kuhn, 2015), to conduct data analysis. The analysis encompassed the computation of descriptive statistics for age, WSFRAT, and evaluation duration. T-tests were applied to discern significant distinctions between groups, and the cutpointr library was utilized to establish the optimal cut-off point through receiver operating characteristic (ROC) curve analysis, alongside measures such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy.\n\nBoth simple logistic regression and multiple logistic regression were employed to investigate the relationship between the binary outcome variable (Actual Fall) and individual or multiple predictor variables. Various metrics including accuracy, diagnostic odds ratio (DOR), Kappa, sensitivity, specificity, PPV, NPV, and area under the curve (AUC) were calculated and subjected to appropriate statistical tests.\n\nThe diagnostic test accuracy was computed as the ratio of correctly identified cases to all tested cases, using the formula (true positive + true negative) / (true positive + false positive + true negative + false negative). T-tests were conducted to compare continuous variables, including age, WSFRAT, and evaluation duration, across different groups.\n\nThe diagnostic odds ratio (DOR) was employed as a measure of diagnostic accuracy, combining sensitivity and specificity, with the formula (TP/FN) / (FP/TN). Kappa assessed the agreement between predicted and actual outcomes, accounting for chance agreement, using the formula (p_o - p_e) / (1 - p_e), where p_o represents observed agreement and p_e represents agreement expected by chance.\n\nSensitivity, as the proportion of actual positives correctly identified as positive by the test, was computed using the formula true positive / (true positive + false negative). Specificity, reflecting the proportion of actual negatives correctly identified as negative by the test, was calculated as true negative / (true negative + false positive).\n\nPositive predictive value (PPV), denoting the proportion of positive test results that are true positives, was determined as true positive / (true positive + false positive). Negative predictive value (NPV), indicating the proportion of negative test results that are true negatives, was derived as true negative / (true negative + false negative).\n\nArea under the curve (AUC) was employed to assess the overall performance of a diagnostic test, considering both sensitivity and specificity. It was calculated by plotting the true positive rate (sensitivity) against the false positive rate (1-specificity) at various threshold values and computing the area under the resulting curve.\n\nFor the analysis of ROC curves, including AUC calculation, confidence intervals, and comparison of multiple ROC curves, the pROC library was utilized. The ggplot2 library facilitated the creation of high-quality visualizations, including bar plots, scatter plots, and line plots, for effective presentation of findings. The tidyverse library streamlined data cleaning, manipulation, and visualization tasks through its consistent grammar and principles. Finally, the caret library was instrumental in building and assessing predictive models, encompassing data pre-processing, model training, model selection, and performance evaluation.\n\n2.8.1R programming language\n\nIs a free software programming language for statistical computing and graphics, which sponsored by the R Core Team and the R Foundation for Statistical computation. It is used for statistical computation and graphics. Ross Ihaka and Robert Gentleman, two statisticians, developed R, which is used by data miners, bioinformaticians, and statisticians for data analysis and creating statistical software.\n\n\n3. Results\n\nThe characteristics of the selected participants in the current study are described in Table 1. A total of 492 patients with various psychiatric disorders were included in the study, with a majority of male patients (62.4%) and a median age of 32 years. The most common diagnosis was a psychotic disorder (40.0%). The fall risk in these patients was evaluated using the Wilson Sims Fall Risk Assessment Tool (WSFRAT), with a mean score of 2.2.\n\n* Statistically significant P ≤ 0.05.\n\nWe compared fall and non-fall cases finding significant differences in age, WSFRAT score, and evaluation duration between the two groups presented in Table 2. The mean age of fall cases was 46.4, while the mean age of non-fall cases was 34.3. The mean WSFRAT score of fall cases was 7.9, compared to 2.0 for non-fall cases. The mean evaluation duration of fall cases was 287.6, compared to 26.3 for non-fall cases. The Welch Two Sample t-test showed a significant difference in age, WSFRAT score, and evaluation duration between fall and non-fall cases.\n\n* Statistically significant P ≤ 0.05.\n\nWe also investigated the association between fall risk and various patient characteristics which are illustrated in Table 1. A Fisher exact test showed a significant association between gender and fall risk (p=0.00143). There was also a significant association between the use of an assistive device and fall risk (p=0.0482). A previous history of falls was significantly associated with fall risk (p=0.000546). However, there was no significant association between clinical judgement and fall risk (p=0.331). The most common diagnosis was a psychotic disorder, which was significantly associated with fall risk (p=0.0003).\n\nReceiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut points for the WSFRAT (Table 3 and Figure 1). The analysis showed that the optimal cut point at 5+ had an accuracy of 87%, a diagnostic odds ratio (DOR) of 0.728, a kappa value of 0.208, a sensitivity of 83%, a specificity of 87%, a positive predictive value (PPV) of 0.14, and a negative predictive value (NPV) of 0.99. The area under the curve (AUC) for the WSFRAT method was 0.85, indicating a good level of discrimination (Figure 1). Additionally, the cut point at 7+ had an accuracy of 94%, a DOR of 0.114, a kappa value of 0.323, a sensitivity of 67%, a specificity of 95%, a PPV of 0.24, and an NPV of 0.99. We also evaluated the accuracy of clinical judgement in predicting fall risk, with an accuracy of 95%, a DOR of 0.002, a kappa value of 0.045, a sensitivity of 8%, a specificity of 97%, a PPV of 0.06, and an NPV of 0.98.\n\nA. Receiver Operating Curve (ROC).\n\nB. Changes in the values of Area Under the Curve (AUC) with different cut-off points.\n\nFurthermore, we performed several regression analyses to identify predictors of fall risk. Simple logistic regression with individual predictors studied separately described in Table 4, presented that age, gender, assistive device, WSFRAT, and evaluation duration were significant predictors of fall risk. Finally, a stepwise multiple logistic regression analysis was conducted to identify predictors of future falls. The analysis included variables that showed a significant relationship in simple regression models. Although not statistically significant, the analysis showed a relationship between gender (male) (coefficient = -3.94, SE = 2.05, p = 0.05465) and future falls. The use of assistive device (coefficient = 6.32, SE = 2.63, p = 0.01641), WSFRAT score (coefficient = 0.42, SE = 0.13, p = 0.00088), and evaluation duration (coefficient = 0.01, SE = 0.002, p = 0.00014) were significantly associated with future falls. The current study revealed that the WSFRAT score was a significant predictor of fall risk in both simple and multiple logistic regression analyses.\n\nSimple logistic regression with individual predictors studied separately.\n\n\n4. Discussion\n\nThere is a scarcity of research on fall risk assessment tools for psychiatric patients. This study included 492 patients in a busy acute mental health hospital.\n\nThis prospective study aimed to evaluate the predictive validity of the WSFRAT, a tool designed to identify patients at risk of falls, in psychiatric inpatient settings. In addition, the study aimed to determine the optimal cut-off point for the WSFRAT while comparing its effectiveness to “clinical judgement,” a common method used by clinicians to assess fall risk.\n\nThe results of the study showed that the WSFRAT is a reliable tool with an accuracy of 85%. The sensitivity and specificity of the WSFRAT were also high at 84.6% and 85.5%, respectively. The optimal cut-off point was identified as 5, which has practical implications for clinical practice. The findings highlight the importance of using evidence-based tools to identify patients at risk for falls, as they can significantly reduce the incidence of falls and associated injuries.\n\nIt is worth noting that the choice of cut-off value can have a significant impact on the performance of a screening tool. The higher sensitivity and specificity values for the cut-off of 7+ suggested in the literature may be more conservative in identifying individuals at high risk of falls. In contrast, the cut-off of 5+ may be more sensitive in identifying a larger proportion of individuals at risk, but may also result in more false positives.\n\nThe unexpected inefficiency of clinical judgement in predicting falls within psychiatric inpatient settings, as revealed by this study, underscores a critical area of concern in contemporary healthcare practices. The strikingly low sensitivity of 0.08, denoting a mere 8% accuracy in identifying actual falls, challenges the conventional reliance on clinical expertise for fall risk evaluation in psychiatric care contexts.\n\nSeveral complex factors may underpin this inadequacy. The intricate nature of psychiatric patients’ conditions, coupled with a myriad of environmental variables, potentially exceeds the capabilities of clinical judgement alone. While nursing expertise remains invaluable, its augmentation with standardized assessment tools tailored specifically for the psychiatric patient population might be imperative. Furthermore, nuanced environmental aspects, such as distinct patient behaviours or specific ward layouts, could significantly influence the accuracy of clinical judgement. Understanding the intricate interplay between these elements and fall risk is crucial for refining risk assessment methodologies.\n\nThe study’s revelation of clinical judgement’s high specificity (0.97) suggests its proficiency in accurately identifying non-fall cases, indicating a robust ability to rule out individuals not at risk. However, the potential pitfall lies in the overemphasis on correctly identifying non-fall instances, possibly leading to a false sense of security and overlooking individuals genuinely susceptible to falls. This underscores the need for a balanced approach, where sensitivity, the capability to identify true positive cases (actual falls), is prioritized alongside specificity.\n\nGiven these findings, it is evident that comprehensive research is imperative to delve into the intricacies of why clinical judgement falls short in psychiatric inpatient settings. Such investigations are pivotal to bridging the existing knowledge gap and may pave the way for the development of more effective and nuanced fall risk assessment strategies tailored specifically to the unique challenges posed by psychiatric patients and their environments. This study serves as a clarion call for a revaluation of current practices and advocates for an integrated approach that harmonizes clinical expertise with evidence-based tools, ultimately enhancing patient safety and well-being in psychiatric healthcare settings.\n\nIn fact, the study found that a coin toss would have very close performance (AUC=0.5) in identifying falls than clinical judgement (AUC=0.53). The Kappa statistic also confirmed that clinical judgement is only better than chance in 0.4% of cases. Therefore, in this case, clinical judgement cannot be relied upon to predict falls accurately. The possibility exists that the poor predictive power of clinical judgement in identifying fall risks in the study population is due to clinicians’ awareness of labelling patients as high-risk, prompting them to take robust preventive measures. However, this explanation is unlikely since the actual prevalence of falls in the study population was 2.4%, which is much lower than the expected rate of falls in psychiatric inpatient settings.\n\nThe study analysed predictors of fall risk in psychiatric patients using logistic regression. Age, gender, assistive device, WSFRAT, and evaluation duration were found to be significant predictors. Previous falls and clinical judgement were not significant. A comprehensive assessment should consider all factors to identify high-risk patients and prevent falls. Stepwise analysis showed that assistive device, WSFRAT, and evaluation duration remained significant predictors, but not age or gender. WSFRAT is a significant predictor of fall risk in psychiatric patients, even when controlling for other factors.\n\n\n5. Limitations\n\nThe first limitation of this study is the lack of mention of any medications when assessing predictors of falls. Medications have been shown to be a significant risk factor for falls in patients with psychiatric disorders. However, due to the nature of acute mental health units, medications tend to change in acute phases of admission, which was difficult to track and analyse systematically. The lack of consideration of medications as a predictor of falls could limit the conclusion of the results, and future studies should take this into account.\n\nThe second limitation of the study is the variable duration of observation. Some patients left early against medical advice, and others left shortly after stabilization. This is a common issue in acute mental health units, where patients often have shorter lengths of stay than in other settings. The variable duration of observation could affect the accuracy of the results, and future studies should try to account for this by implementing standardized observation periods.\n\nDespite these limitations, the study has important implications for fall prevention in psychiatric inpatient settings. The findings suggest that the WSFRAT is a reliable tool for identifying patients at risk of falls, and preventive measures should be implemented based on a more objective assessment tool such as the WSFRAT rather than relying on clinical judgement. Additionally, a comprehensive fall risk assessment that considers age, gender, assistive device use, WSFRAT score as well as other unstudied variables, such as medications, could help to identify patients at the highest risk for falls and reduce the incidence of falls in this vulnerable population.\n\n\n6. Conclusion\n\nThe study highlights the importance of using evidence-based tools to identify patients at risk for falls in psychiatric inpatient settings. The WSFRAT was found to be a reliable tool with high sensitivity and specificity, and an optimal cut-off point of 5. The study also revealed that clinical judgement is not an effective method for predicting falls in this population. The study’s limitations, including the lack of consideration of medications and the variable duration of observation, should be addressed in future studies. Overall, a comprehensive fall risk assessment that considers multiple factors can help to identify high-risk patients and prevent falls in this vulnerable population. The findings of this study have important implications for fall prevention and patient safety in psychiatric inpatient settings.\n\n\n7. Implications for nursing practice\n\nBased on the study findings, there are several implications for nursing practice in psychiatric inpatient settings:\n\n1. Use of evidence-based fall risk assessment tools: Nurses should use evidence-based tools such as the WSFRAT to identify patients at risk of falls. The tool has high sensitivity and specificity, making it a reliable way to assess fall risk. Nurses should be familiar with the updated optimal cut-off point of 5 and use this score to determine appropriate interventions.\n\n2. Avoid relying solely on clinical judgement: The study findings suggest that relying on clinical judgement alone is not an effective method for predicting falls in psychiatric inpatient settings. Nurses should use objective assessment tools such as the WSFRAT and consider multiple factors to identify patients at high risk for falls.\n\n3. Consider multiple factors in fall risk assessment: The study found that age, gender, assistive device use, and evaluation duration were significant predictors of fall risk in psychiatric patients. Nurses should consider these factors in addition to the WSFRAT score to identify patients at high risk for falls.\n\n4. Address medication use: The study limitations highlight the need for future studies to consider medication use as a predictor of falls. In the meantime, nurses should be aware that medications can be a significant risk factor for falls in patients with psychiatric disorders and should monitor patients for adverse effects.\n\n5. Implication of a Holistic Assessment: Nurses must conduct holistic evaluations that consider the patient’s emotional, psychological, and social requirements in addition to their physical health. As Patients in specialized settings may face increased stress, anxiety, and uncertainty. A holistic evaluation assists nurses in identifying and addressing these non-physical elements that can have a substantial influence on a patient’s overall health and rehabilitation. By addressing patients’ holistic needs, nurses contribute to increased mental and emotional well-being, which can affect physical recovery.\n\n6. Implementing a centralized reporting system, nursing administration may look for patterns in everyday operations that highlight safety issues, such as inadequate documentation or possibly risky shift patterns. Using this knowledge, nurse leaders may find ways to streamline processes and reduce those risks. Furthermore, frontline Nurse management are accountable for conveying risk management goals to their employees and developing a safety culture by acting as positive role models. Nurse leaders are ultimately responsible for designing and implementing risk management strategies for their organizations, in collaboration with other health care professionals. When challenges develop, they may examine what went wrong and offer methods to enhance operations and minimize future errors.\n\n7. Personalized Care Plans: Nurses should create personalised care plans for each patient based on their specific requirements, medical history, and treatment objectives. This entails conducting extensive evaluations and reassessing the patient’s status on a continuous basis. Patients with complicated medical issues are frequently housed in specialized settings. Personalized care plans guarantee that each patient receives the most effective treatments and interventions for their individual circumstances. This method reduces the risk of adverse events, improves outcomes, and promotes patient-centered treatment, all of which are necessary for holistic health.\n\n8. Interdisciplinary Collaboration: To guarantee complete and coordinated treatment, nurses should work closely with other healthcare professionals such as doctors, therapists, and pharmacists. as Patients in highly specialized settings may require multifaceted treatment. Collaborative cooperation ensures that all areas of a patient’s health are addressed, including physical, psychological, and social well-being. This integrated strategy not only improves patient outcomes but also lowers the likelihood of medical mistakes and enhances the entire patient experience.\n\n9. Implication of Patient and Family Education: Nurses should educate patients and their families about their disease, treatment plan, and self-care behaviors on a continuous basis. As Patients and their families may encounter novel and difficult medical information in specialized care settings. Education enables people to actively engage in their treatment, make educated decisions, and maintain their health outside of the hospital. This can result in better adherence to treatment programs, lower readmission rates, and a higher quality of life for patients.\n\nOverall, the study findings emphasize the importance of using evidence-based tools and a comprehensive assessment approach to prevent falls in psychiatric inpatient settings. Nurses play a vital role in fall prevention and should be familiar with these implications to provide safe and effective care for their patients. In conclusion, these considerations are crucial for nursing practice in settings that need highly specialized patient care for a number of reasons. They highlight the comprehensive aspect of health while also improving the standard of treatment and patient outcomes. Nurses help to make healthcare more all-encompassing and patient-cantered by addressing the patient’s physical, emotional, psychological, and social well-being. In turn, this promotes confidence, raises patient satisfaction, and ultimately adds value to the conversation about nursing practice in specialized settings.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nAbraham S: Managing patient falls in psychiatric inpatient units. Health Care Manag. 2016; 35(2): 121–133. PubMed Abstract | Publisher Full Text\n\nCarpels A, de Smet L , Desplenter S, et al.: Falls among psychiatric inpatients: a systematic review of literature. Alpha Psychiatry. 2022; 23(5): 217–222. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChou S-P, Hung T-M: Comparison of clinical diagnostic effectiveness between psychiatric inpatient and Wilson-Sims fall risk assessment tools. Hu Li Za Zhi. 2019; 66(3): 35–45. PubMed Abstract | Publisher Full Text\n\nEdmonson D, Robinson S, Hughes L: Development of the Edmonson psychiatric fall risk assessment tool. J. Psychosoc. Nurs. Ment. Health Serv. 2011; 49(2): 29–36. Publisher Full Text\n\nHealey F: A GUIDE ON HOW TO PREVENT FALLS AND INJURY IN HOSPITALS. Nurs. Older People. 2010; 22(9): 16–22. Publisher Full Text\n\nKuhn M: Caret: classification and regression training. Astrophysics Source Code Library. 2015; ascl-1505.\n\nLu S-H, Chen K-H, Pan Y-C, et al.: Influence of medications and psychotic symptoms on fall risk in acute psychiatric inpatients. J. Med. Sci. 2018; 38(3): 117–121. Publisher Full Text\n\nMontalvo I: The National Database of Nursing Quality Indicators® (NDNQI®). OJIN: The Online J. Issues Nurs. 2007; 12(3). Publisher Full Text\n\nNice.: Assessment and prevention of falls in older people. NICE guidance june 213. Nurs. Older People. 2014; 26(6).\n\nRevelle W: psych: Procedures for Personality and Psychological Research.2020. Reference Source\n\nRobin X, Turck N, Hainard A, et al.: pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011; 12: 77. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTeam, R. C: R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. 2021.\n\nThiele C, Hirschfeld G: Cutpointr: Improved estimation and validation of optimal cutpoints in R. ArXiv Preprint ArXiv:2002.09209. 2020.\n\nVan Dyke D, Singley B, Speroni KG, et al.: Evaluation of fall risk assessment tools for psychiatric patient fall prevention: A comparative study. J. Psychosoc. Nurs. Ment. Health Serv. 2014; 52(12): 30–35. PubMed Abstract | Publisher Full Text\n\nWatson WL, Clapperton AJ, Mitchell RJ: The cost of fall-related injuries among older people in NSW, 2006–07. N. S. W. Public Health Bull. 2011; 22(4): 55–59. PubMed Abstract | Publisher Full Text\n\nWickham H, Averick M, Bryan J, et al.: Welcome to the Tidyverse. J. Open Source Softw. 2019; 4(43). Publisher Full Text\n\nWickham H, Chang W, Wickham MH: Package ‘ggplot2.’. Create Elegant Data Visualisations Using the Grammar of Graphics. Version. 2016; 2(1): 1–189.\n\nWilson SC, Fettes S, Sims K: Gravity: It’s Not a Suggestion-It’s the Law! The Development of the WilsonSims Psychiatric Fall Risk Assessment Tool. J. Am. Psychiatr. Nurses Assoc. 2014; 20(1): 83.\n\nWong MMC, Pang PF, Chan CF, et al.: Wilson Sims Fall Risk Assessment Tool Versus Morse Fall Scale in Psychogeriatric Inpatients: a Multicentre Study. East Asian Arch. Psychiatr. 2021; 31(3): 67–70. PubMed Abstract | Publisher Full Text\n\nWorld Health Organization: Falls, World Health Organization.2021. (Accessed: 20 September 2023). Reference Source"
}
|
[
{
"id": "269898",
"date": "09 Aug 2024",
"name": "Roger Hilfiker",
"expertise": [
"Reviewer Expertise Clinical Epidemiology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe present manuscript reports on an evaluation of the predictive validity of the Wislon SIMS Fall Risk Assessment Tool with a prospective cohort study including 492 patients. The manuscript is well written. I have some comments on the reporting:\n\nPage 3, Methods. Please be specific whether the inclusion of participants was consecutive or whether not all eligible patients were included. Page 4, Methods. Does the following sentence \"If the patient had been admitted before the start of data collection, then the evaluation was made on 16th May 2019.\" mean that not all patients were included prospectively, i.e. that for some patients the data were assessed retrospectively from medical records? Please clarify.\n\nMethod section: I assume that the hospitalisation duration was different for all patients and the length of the stay might increase the risk for falls. As some of the predictor variables might be associated with the length of stay and with the falls risk, it might be helpful to discuss this aspect. This would not be a problem for prediction, but might be worth being discussed. And maybe the length of stay should be reported in the descriptive tables.\n\nMethod section: Please provide precise information on how you established the \"optimal\" threshold. Viewing the Figure 1B, I think that the authors dichotomised at different threshold, calculated the area under the curve for each dichotomisation and chose the threshold that provided the highest AUC. I do not know this approach, which does of course not mean that it is wrong. But please provide some arguments on why this approach is good (best with references).\nThe approaches I know are different: They all create one receiver operating characteristic curve, which already integrates all the different thresholds. Then one of the many methods to decide on the so called optimal threshold is applied (which of the methods from cutpointr did you chose?). The authors probably already did this with the cutpointr package and a command similar to this: opt_cut <- cutpointr(suicide, dsi, suicide, direction = \">=\", pos_class = \"yes\", neg_class = \"no\", method = maximize_metric, metric = youden) [(here with the method \"youden index\")].\nRecommended threshold: In several places of the manuscript, the authors write that the recommended threshold is 7. Please provide references to these statements. Please discuss how the threshold was established in the primary study and how this difference in your study.\n\nPage 7, Discussion: Please consider to remove the first sentence \"There is a scarcity of research on fall risk assessment tools for psychiatric patients.\" to the introduction or to the discussion section where you discuss your results with other published 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? 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": "12712",
"date": "26 Oct 2024",
"name": "ahmad muneer",
"role": "Author Response",
"response": "Response to Reviewer Comments We sincerely thank the reviewer for their thoughtful and constructive feedback on our manuscript. The reviewer’s insights have greatly contributed to enhancing the clarity and rigor of our study, particularly in areas such as methodological transparency and the justification of analytical approaches. We appreciate the opportunity to address these comments, which have helped us refine our manuscript and improve its contribution to the field of fall risk assessment in psychiatric settings. Comment 1 (Page 3, Methods): Specify whether participant inclusion was consecutive. Response: We appreciate this insight. To clarify, participants were included consecutively, with eligibility determined by admission criteria to the acute mental health unit between April 16, 2019, and March 31, 2021. This approach minimizes selection bias and strengthens the external validity of our findings by ensuring a representative sample of psychiatric inpatients. Comment 2 (Page 4, Methods): Clarify the timing of patient evaluation for those admitted before data collection. Response: We recognize the need for clarification. For patients admitted prior to the official start of the study on April 16, 2019, assessments were conducted retroactively using hospital records from May 16, 2019, ensuring that evaluations aligned with the methodology of prospectively collected data. This approach enabled consistent and comprehensive data collection across the sample. Comment 3 (Method Section): Discuss length of stay and its potential association with fall risk and predictor variables. Response: We concur that the duration of hospital stay may indeed influence fall risk, with extended stays potentially increasing exposure to fall risks. In our revised manuscript, we will include this discussion, emphasizing that while our model was predictive, future research should consider hospitalization length as an additional factor in fall risk models. We will also add length of stay data to the descriptive tables to enhance the clarity and scope of our findings. Comment 4 (Method Section): Provide details on establishing the \"optimal\" threshold for the WSFRAT. Response: We thank the reviewer for highlighting this methodological point. In Figure 1B, we indeed tested multiple thresholds for the WSFRAT, determining the optimal point based on maximizing the area under the receiver operating characteristic curve (AUC). While our approach aligned with established practices in predictive diagnostics, we will expand the methods section to detail the rationale and cite relevant literature supporting AUC-based threshold selection (e.g., Thiele & Hirschfeld, 2020). Additionally, we utilized the cutpointr package, following commands similar to those the reviewer mentioned, such as maximize_metric with the Youden index. Comment 5: Clarify the basis for the recommended threshold of 7 and provide supporting references. Response: In our manuscript, the threshold of 7 was referenced based on prior studies of WSFRAT’s application in psychiatric settings (Wilson et al., 2014; Wong et al., 2021). We will include these references and expand on how our study's threshold of 5 differs from this recommendation, discussing the implications of a lower threshold for heightened sensitivity and clinical applicability. Comment 6 (Page 7, Discussion): Move the introductory sentence on scarcity of research to a more appropriate section. Response: We agree that this point is better placed in the introduction. The introductory sentence on the scarcity of fall risk research in psychiatric populations will be relocated to the introduction, with further context in the discussion on comparing our findings to existing literature. By addressing these points, we aim to enhance the clarity and scientific rigor of our manuscript, ensuring it meets high standards of methodological transparency and relevance. Thank you for your valuable insights"
}
]
}
] | 1
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https://f1000research.com/articles/13-97
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https://f1000research.com/articles/11-1068/v1
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20 Sep 22
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{
"type": "Systematic Review",
"title": "Biopsychosocial factors associated with depression in the elderly: A systematic literature review",
"authors": [
"Yanti Harjono Hadiwiardjo",
"Rita Damayanti",
"Rita Damayanti"
],
"abstract": "Background: One of the most common mental illnesses worldwide and that has significant negative effects on well-being and physical health, is depression. Many factors that affect the occurrence of depression are biopsychosocial. Elderly people have high risk factors for depression. This study aims to review and find a gap in current evidence of biopsychosocial factors affecting depression in the elderly. Methods: We conducted an advanced search on PubMed database between October and November 2021. We screened the bibliographies of the articles from the database search using a set of inclusion criteria: studies with quantitative design; elderly population sample; exploration of at least one biopsychosocial factor; depression as the outcome or dependent variable; written in English; and published between 2011 and 2021. Results: We found 54 studies that met the inclusion criteria. Of these, five papers discussed biopsychosocial factors, 18 discussed biological and psychological/social factors, five discussed psychosocial factors, and the rest of the studies discussed one component of biopsychosocial factors. Biological factors influencing elderly depression include being female, having health problems or low health status, older age, genetics, brain structure, and biomarkers, taking certain drugs, and lack of or inability to carry out daily activities. Psychosocial factors include lack of social support, low education level, financial problems, single/unmarried, lack of contact with family/friends, living alone, low self-perceived health, stressful life events, loneliness, and losing hobbies. From the literature search, it was also found that there are biopsychosocial factors that have not been studied and are expected to be able to make references for future research. From this literature review, we found gaps in the availability of evidence about biopsychosocial factors that require further research. Conclusions: Knowing the biopsychosocial factors that affect them can help to prevent depression in the elderly.",
"keywords": [
"elderly",
"depression",
"biopsychosocial",
"systematic review"
],
"content": "Introduction\n\nMany developing countries are experiencing rapid growth in their older populations (Isdijoso et al., 2020). The elderly are predicted to become 25% of the global population, or 74 million people by 2050 (Isdijoso et al., 2020). In Indonesia, citizens 60 years old or older have reached about 25.7 million people (Isdijoso et al., 2020). The older population in the UK is projected to grow, with people aged 65 and over making up 24% of the population by 2043 (17.4 million people) (Lewis, 2021). The proportion of the population aged 75 and over is projected to rise from 8% in 2018 to 13% in 2043, while the proportion aged 85 and over is projected to rise from 2% to 4% (Lewis, 2021). The elderly can have specific physical and mental health issues, including decreased mobility and increased frailty, with some of them losing their independence due to such issues. In the USA, 20% of adults aged 55 and over suffered from a mental health disorder at the beginning of the millennium (World Federation for Mental Health, 2013).\n\nIn older people, mental health problems can affect their ability to carry out the basic activities of daily living, reducing their independence, autonomy, and quality of life. A common mental health problem that occurs in older people is depression (Carayanni, Stylianopoulou, Koulierakis, Babatsikou, & Koutis, 2012). Depression is related to distress and suffering and can cause impairment in mental, physical, and social functioning (World Federation for Mental Health, 2013).\n\nDepression is one of the most common mental illnesses worldwide, with serious consequences for one’s well-being and physical health (Thipprakmas, 2021). The elderly may be particularly impacted by depression due to high levels of risk factors including illnesses, social isolation, and lack of emotional support. Depression is considered as a clinical syndrome. Low mood, anhedonia, and decreased energy levels are the three basic symptoms of depression, according to the International Classification of Diseases (ICD) diagnostic classification systems (Pocklington, 2017; Thipprakmas, 2021).\n\nOther clinical findings which were listed include loss of confidence, impaired concentration, disturbances in sleep, suicidal ideation, and changes in appetite. If the above symptoms are present for at least in two weeks, then a diagnosis of depression can be established (Pocklington, 2017).\n\nMajor depression presents with all three core symptoms according to ICD criteria, and at least five other symptoms also present (Pocklington, 2017).\n\nDepression consists of two types: early-onset and late-onset depression. In individuals over the age of 65, there is a new diagnosis for depression, namely late-onset depression in which more than half of cases of depression in older adults are newly emerged i.e., the person has never experienced depression. Late-type depression is related to structural changes in the brain, cognitive deficits, and vascular risk factors (Pocklington, 2017).\n\nThere are two principal points of view commonly used to explain depression, the bio-medical perspective, and the psychosocial perspective. These perspectives oftentimes conflict with each other. The biomedical perspective asserts that disturbances in the functioning of the brain manifest as psychopathological symptoms, whereas the psychosocial perspective maintains that mental issues are caused by disruptive life experiences (Garcia-Toro & Aguirre, 2007).\n\nFrequently, this twofold viewpoint influences certainly the different affirmations that are made about mental problems, albeit expressly it is progressively perceived that organic and psychosocial angles are generally involved, interfacing in a complex way. Indeed, this is the explanation for why the term “biopsychosocial model” has flourished (Garcia-Toro & Aguirre, 2007).\n\nDepression in older adults is related to cognitive, physical, and social functional impairment (Pocklington, 2017). It is also related to a variety of psychological, biological, and social factors causing it (Alexopoulos & Kelly, 2009; Blazer, 2003). It has a variety of biopsychosocial risk variables that interact to predict the onset of depressive symptoms in a single person. However, it is unclear how much each risk factor contributes to the onset of depressive symptoms. A greater understanding of the individual contributions of biological, psychological, and social risk factors can have a big impact on the adoption of preventive actions to lower the population's risk of depression (Diniz, 2020). Several studies have investigated several biological, psychological, and social factors associated with depression in the elderly, so this systematic review aims to review and synthesize current evidence of biopsychosocial factors affecting depression in the elderly and can also contribute to future research on factors that affect depression which can eventually contribute to the decrease in the incidence of depression in the elderly.\n\nThis systematic review aims to examine and find gaps or current evidence regarding biopsychosocial factors that influence depression in the elderly. The review is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. See Reporting guidelines (Hadiwiardjo and Damayanti, 2022c) for the completed checklist.\n\n\nMethods\n\nWe conducted an advanced search on PubMed database using a set of keywords which consisted of population sample keywords (elderly OR geriatric OR late life OR older) combined with independent variable keywords (psychological factors OR social factors OR biological factors OR biopsychosocial), and the outcome (depression). After obtaining these search results, we downloaded the records into our reference manager software Mendeley and removed any duplication. From those search results, we gathered 728 records of studies. The data search on PubMed was conducted in October - November 2021. The last data search was carried out on November 18, 2021.\n\nWe applied a two-step screening process that involved two reviewers. Both reviewers worked independently, and any disagreements were resolved through discussion. First, we screened the title and abstract of the bibliography using a set of eligibility criteria. The inclusion criteria were original studies with a quantitative design, that were peer-reviewed, with elderly people (over 60 years) as the population sample, and that explored at least one biopsychosocial factor, with depression as the outcome or dependent variable. Articles also needed to be written in English and published between 2011 and 2021 to be included. Studies published as review articles, qualitative studies, brief reports, letters to the editor or editorial comments, and working papers published in a language other than English were all excluded. In the first stage of screening, we removed studies before 2011 and collected 470 records to be screened. After further screening, 99 studies are eligible for the next screening process.\n\nFurther screening of 99 eligible studies was conducted with Population, Intervention, Comparison Outcome and Study (PICOS) criteria where if not appropriate it would be excluded. We retrieved the full text of the potentially relevant studies and conducted a second screening process. The selection process can be seen in the flowchart presented in Figure 1, also available in Extended data (Hadiwiardjo and Damayanti, 2022b). The eligible studies were extracted for the design of the study, country of origin, number of samples, the instrument used to measure depression, and factors associated with depression. That information was extracted from each included study into a standardized spreadsheet and checked by two reviewers. The two reviewers worked independently and if there were any disagreements, these were resolved by discussion between the two reviewers. Any ambiguous material from an included paper was clarified after contacting the respective authors, or else only the available data was analyzed. Microsoft Excel was used to organize the identified papers. The results were described narratively and helped to identify the gaps in the literature that can be filled by future studies.\n\nThese studies included quantitative synthesis. After the two-step screening process was conducted, 54 papers were reviewed and extracted. We first described the number of articles based on the country of origin of the article, the type of research design, and the year. Next, we extracted the data based on the research design, the number of samples, the measuring instruments used to measure depression and factors related to depression. After that, the purpose of the content analysis was to identify and assess the primary research streams, reporting in an objective manner on the various domains while also addressing future research prospects and problems.\n\nThe 54 papers were then reassessed using the Joanna Briggs Institute (JBI) checklist which is a tool for critical appraisal of a paper. The risk of bias can occur if the quality of the data from the reviewed papers is mostly of low quality. To determine the quality of the data, the JBI critical appraisal tool was used (we accessed this JBI checklist here). This critical appraisal was carried out by two reviewers and if there was a disagreement, it was discussed. From the critical appraisal results it was determined that 53 papers were high quality, and one paper was low quality. The last articles obtained are all used in this systematic review.\n\n\nResults and discussion\n\nA total of 54 studies met the inclusion criteria after the full-text screening. Previously there were papers that were eventually excluded because there were discrepancies in terms of population and outcome (Pollock & Berge, 2018). The full list of the 54 studies are available in Underlying data (Hadiwiardjo and Damayanti, 2022a). The process using the PRISMA flowchart is shown in Figure 1. The majority of the 54 studies came from the United States, followed by China, as seen in Figure 2.\n\nTwenty-two papers used a cohort study design, two studies used a combination of cohort and a cross-sectional design, and 24 studies used cross-sectional design. We also included experimental and case-control studies. An illustration of the number of types of study designs used in all studies can be seen in Figure 3. Figure 3 shows that most studies use cross-sectional research designs which are then followed by cohort research designs.\n\nThe graph of publication shows the number of studies during the last eleven years from 2011 to 2021 as shown in Figure 4. The total number of publications collected from PubMed database are shown in Figure 4. In 2012 there were nine studies related to biopsychosocial factors related to depression in the elderly but from 2013 to 2020 there were less. In 2021 there was an increase in the number of studies related to depression in the elderly. This can be attributed to an increase in the elderly population globally which was also followed by an increase in the incidence of depression, so it was necessary to conduct more research.\n\nAn overview of critical appraisal using JBI Checklist shows that there are 53 papers with high quality paper and one paper with low quality as illustrated in Figure 5.\n\nThe data extraction of each study can be seen in Table 1. Five papers discussed biopsychosocial factors, 18 papers discussed biological and psychological/social factors, five papers discussed psychosocial factors, and the rest of the studies discussed one component of biopsychosocial factors associated with depression. Now we outline the results for the biological, psychological, and social factors of depression (examples of determinants and consequences are shown below).\n\nBiological factors were frequently found to influence geriatric depression. Such factors mentioned included gender (Brinda et al., 2016; Carayanni et al., 2012; Glei, Goldman, Liu, & Weinstein, 2013; Gureje, Oladeji, & Abiona, 2011; Kuroda et al., 2017; Leggett, Zarit, Nguyen, Hoang, & Nguyen, 2012; Misawa & Kondo, 2019; Odlum et al., 2018; Piboon, Subgranon, Hengudomsub, Wongnam, & Louise Callen, 2012; Rzewuska, Mallen, Strauss, Belcher, & Peat, 2015), health problems (Arve et al., 2012; Carayanni et al., 2012; Choi, Kim, Marti, & Chen, 2014; Horita et al., 2013; Jovanova et al., 2016; Karczewska & Młynarska, 2021; Leggett et al., 2012; Meesters et al., 2014; Nicolosi et al., 2011; Olsen, Schirmer, Wilsgaard, Bønaa, & Hanssen, 2018; Popescu et al., 2012; Pusswald et al., 2012; Rhee, Jang, Kim, & Chang, 2021; Rzewuska et al., 2015; Sadler, McLaren, & Jenkins, 2013; Sanders, Comijs, Bremmer, Deeg, & Beekman, 2015; Wang et al., 2016; Ylli et al., 2016), older age (Olsen et al., 2018; Rippon & Steptoe, 2018; Rzewuska et al., 2015), genetics (Klinedinst, Resnick, Yerges-Armstrong, & Dorsey, 2015; Stringa et al., 2020), brain anatomical (Laird et al., 2019; Wang et al., 2018), cytokine level (Derry et al., 2021), taking drugs (Bond et al., 2020), low activity (Davison, McCabe, Knight, & Mellor, 2012; Kobylańska et al., 2019; Leggett et al., 2012; Meesters et al., 2014; Piboon et al., 2012; Rzewuska et al., 2015), diet (Ferrand et al., 2018) and BMI (body mass index) status (Horita et al., 2013). One study has found that women showed a significant positive association with geriatric depression (Brinda et al., 2016). Other literature found that the prevalence of depression is higher in women than in men (Piboon et al., 2012; Ylli et al., 2016). In total, ten different kinds of studies have shown that women were more likely to have depression or higher depressive symptoms than men, indicating a relationship between gender and older age depression.\n\nEighteen studies in this review have found that the presence of depression is associated with health problems including pain, degenerative diseases, multimorbidity, poor respiratory indicators, cardiovascular morbidity, insomnia, and a falling incident. One of the literature obtained a p<0.001, showing the significant relationship between health problems and depression (Nicolosi et al., 2011).\n\nThere were three studies in this review that have found that older age is associated with depression (Olsen et al., 2018; Rippon & Steptoe, 2018; Rzewuska et al., 2015). One of the literature showed that age of ≥70 year associated with depression disorder (Rzewuska et al., 2015). Another study showed with increase in the subject age, greater depressive symptoms were present (Rippon & Steptoe, 2018). Other factors mentioned concerning older age depression were genetic, brain anatomical, and cytokine levels (Derry et al., 2021; Klinedinst et al., 2015; Laird et al., 2019; Stringa et al., 2020; Wang et al., 2018).\n\nOne study, namely research conducted by Bond, revealed that taking drugs such as mood stabilizers, anxiolytics, and hypnotic or sedatives were associated with depression (Bond et al., 2020). They obtained a p=0.001 for mood stabilizers, p<0.001 for anxiolytic, and p=0.009 for hypnotic or sedatives, suggesting a significant relationship for this drug-taking factor.\n\nLow activity or low activity tolerance and disability were also found to have a positive relationship with older age depression (Davison et al., 2012; Kobylańska et al., 2018; Leggett et al., 2012; Meesters et al., 2014; Piboon et al., 2012; Rzewuska et al., 2015). Lastly, diet and BMI status were explored as possible biological factors (Ferrand et al., 2018; Horita et al., 2013).\n\nFrom one study, it was found that female gender was significantly associated with depression where p<0.001 was found (Piboon et al., 2012). Gender differences in depression can potentially be explained genetically, where genetic studies have found that female twins with a history of depression in the family were more likely to develop depression, and according to the psychological perspective, men and women have different personality features, which could explain the gender variations in depression. A study showed that females are more nurturing, non-aggressive, modest, and reliant than males, and they are more likely to have a relationship-oriented disposition (Piboon et al., 2012).\n\nIndividuals who had a chronic disease or health problems, particularly related to the musculoskeletal system such as arthritis and osteoporosis, are likely to had a weakened sense of self-efficacy, which can cause functional impairment and their presence has been associated with depression (Nicolosi et al., 2011). Health problems like pain were a predictive of depressive symptoms (Leggett et al., 2012). Some other studies showed that once pain and depression occurred, they will remain associated (Sanders et al., 2015). People with comorbidities are more likely to suffer from depression, indicating that it is another risk factor (Carayanni et al., 2012).\n\nThe results of this research showed that seventeen studies discussed psychological factors that influence the occurrence of depression in the elderly. These factors were low self-perceived health, stressful life events, loneliness, and losing hobby/interest/purpose in life.\n\nAccording to research conducted by Nicolosi et al. (2011), poorer self-perceived health leads to more depressive symptoms (Nicolosi et al., 2011).\n\nOne of three studies on stress in life, namely the study conducted by Chan (2012), found that there is a relationship between the number of stressful events in life and the incidence of depression (p=0.0020), with the number of stressful events associated with an increased risk of having depression (Chan et al., 2012). In both men and women, life events predicted the odds of depression among older people (Misawa & Kondo, 2019).\n\nAccording to research conducted by Bond et al. (2020), there is a significant relationship between loneliness and the occurrence of depression, where p<0.05 (Bond et al., 2020). Piboon (2012) found that loneliness had a significantly positive impact on depression, with an obtained p<0.001. Chan et al. also found that loss of hobbies is related to an increased incidence of depression (Chan et al., 2012).\n\nLoneliness had a significantly positive relationship and was a predictor of depression among older adults because they are more likely to experience losses and changes in later life, so those that may feel lonely are more likely to suffer from depression than younger adults who do not feel lonely (Piboon et al., 2012).\n\nIn this literature study, there were 20 studies that discussed social factors that affect the occurrence of depression in the elderly. The social factors were social/emotional support, education level, financial problem, marital status, lack of contact with family/friends, living alone, dependency, environmental and religious beliefs. According to three from 12 that examined social support, social support was associated with depression. Research conducted by Bui (2020) found that there was a reciprocal relationship between social support and depressive symptoms, with p<0.001 (Bui, 2020). Meanwhile, research by Piboon (2012) found that there was a positive relationship between social support and depression (Piboon et al., 2012). Chen et al. found in their research that social frailty may be a predictor of depression among community-dwelling older adults (Chen et al., 2021).\n\nThis study found seven papers that discussed the relationship between education levels and the incidence of depression. In research conducted by Brinda (2016), it was found that low education correlated with geriatric depression (Brinda et al., 2016). Other studies have also found that less educated people have higher depressive symptoms (Akila, Arvind, & Isaac, 2019; Kobylańska et al., 2018; Leggett et al., 2012; Nicolosi et al., 2011; Olsen et al., 2018; Sjöberg et al., 2013).\n\nEducation was the key indicator of social risk for depression. Individuals with lower education tend to feel more uncertain about the future and on a higher poverty level which makes greater prevalence of depression (Nicolosi et al., 2011). Individuals with lower education and income may have less access to health services, putting them at higher risk of getting depressive symptoms (Nicolosi et al., 2011).\n\nFinancial problems or poverty were also found to be factors that influence the incidence of depression. In this study we found seven papers that discusses financial problems or poverty as factors that influence the occurrence of depression. Brinda (2016) showed that poverty had a positive association with depression in the elderly (Brinda et al., 2016). Other literature studies have suggested that a significant lack of income is associated with the prevalence of depression (Ylli et al., 2016), furthermore showing that income has a negative effect on depression (Piboon et al., 2012). Income also had an indirect effect on depression in older adults. Some studies reported that elderly people living alone are single, divorced or lost a partner where they then unknowingly suffer from financial burdens and look at their health status negatively (Koo, Son, & Yoo, 2021). It is also reported that elderly people who are reluctant to live alone are prone to depression (Koo et al., 2021).\n\nEight literature studies discussed the relationship between marital status and (Koo et al., 2021) depression. According to Manaf (2016), marital status was a factor that was significantly associated with depression where they obtained a p=0.00l. Single elderly people experienced depression three times more often compared to elderly who are married (Manaf, Mustafa, Rahman, Yusof, & Aziz, 2016). Other literature showed that single/divorced/widowed people had more depressive symptoms than those who are married (Paralikas et al., 2021; Sjöberg et al., 2013).\n\nIn this study, we found that people with poor social networks, especially those lacking contact with friends, had an elevated risk of an incident of depression (Gureje et al., 2011). The frequency of meetings with friends predicted reduced odds of depression in older men (Misawa & Kondo, 2019).\n\nIt was also found that living alone is a risk factor associated with depression, where p<0.001 was obtained (Carayanni et al., 2012). Additionally, Living with an unmarried son was linked to a higher risk of depression than living with a married son and daughter-in-law (Glei et al., 2013). A study conducted by Koo (2021) also stated that those living alone are at higher risk of suffering from depression compared to those living with others (Koo et al., 2021). Lastly we found one study that stated that religious beliefs were associated with depression (Wang et al., 2018).\n\nThe risk of bias in this systematic review is that depression is assessed as all depression that occurs in the elderly, whether they have a chronic disease and not. In this literature review, based on the JBI checklist, high-quality papers were obtained.\n\nThe limitation of the results of this systematic literature review is that most papers do not clearly identify the confounding factor. Papers included in this review are varied, so they do not allow for quantitative synthesis. Therefore, we discuss the results narratively in order to provide the big picture of the topic.\n\n\nConclusions\n\nThe results confirmed that biopsychosocial factors were correlated with depression within a population of older individuals. Depression is a clinical condition that requires a holistic approach with biopsychosocial factors. From the results of this literature search, it was also found that there are biopsychosocial factors that have not been studied and are expected to be able to make references for future research. As for the variables that have not been discussed before such as in biological factors are the weakening that occurs in the elderly and psychological factors are a history of previous mental status and coping style. Understanding the biopsychosocial factors influencing them is paramount in developing the management programs to tackle depression in the elderly.\n\n\nData availability\n\nFigshare: Data Extraction_Depression in Elderly from 54 research papers.csv. https://doi.org/10.6084/m9.figshare.19661373.v1 (Hadiwiardjo and Damayanti, 2022a).\n\nThis project contains the following underlying data:\n\n- Data Extraction_Depression in Elderly from 54 research papers.csv.\n\nFigshare: Prisma flowchart depression in Elderly. https://doi.org/10.6084/m9.figshare.19991789.v1 (Hadiwiardjo and Damayanti, 2022b).\n\nThis project contains the following extended data:\n\n- Prisma search figure_Depression in Elderly.jpg (PRISMA flowchart).\n\n\nReporting guidelines\n\nFigshare: PRISMA checklist for ‘Biopsychosocial factors associated with depression in the elderly: A systematic literature review’. https://doi.org/10.6084/m9.figshare.20152346.v1 (Hadiwiardjo and Damayanti, 2022c).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgements\n\nThe author would like to thank the faculty members at the University of Indonesia and University of Pembangunan Veteran Jakarta for their support and providing a good research environment. Furthermore, ‘thank you’ to the Research Synergy Foundation for the recommendations and support in making this research more successful.\n\n\nReferences\n\nAkila GV, Arvind BA, Isaac A: Comparative assessment of psychosocial status of elderly in urban and rural areas, Karnataka, India. J. Family Med. Prim. Care. 2019.\n\nAlexopoulos GS, Kelly RE: Research advances in geriatric depression. World Psychiatry. 2009; 8(3): 140–149. PubMed Abstract | Publisher Full Text\n\nArve S, Eloranta S, Rovio S, et al.: Depressive symptoms among older people: A 15-year follow-up. Aging Clin. Exp. Res. 2012; 24(5): 501–508. Publisher Full Text\n\nBlazer DG: Depression in late life: Review and commentary. J. Gerontol. A Biol. Sci. Med. Sci. 2003; 58(3): 249–265. 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PubMed Abstract | Publisher Full Text\n\nHadiwiardjo YH, Damayanti R: Data Extraction_Depression in Elderly from 54 research papers.csv. figshare. Dataset.2022a. Publisher Full Text\n\nHadiwiardjo YH, Damayanti R: Prisma flowchart depression in Elderly. figshare. Figure.2022b. Publisher Full Text\n\nHadiwiardjo YH, Damayanti R: Prisma Checklist Depression in Elderly. figshare. Journal Contribution. 2022c. Publisher Full Text\n\nHong JH, Lachman ME, Charles ST, et al.: The positive influence of sense of control on physical, behavioral, and psychosocial health in older adults: An outcome-wide approach. Prev. Med. 2021; 149(May): 106612. PubMed Abstract | Publisher Full Text\n\nHorita N, Kaneko T, Shinkai M, et al.: Depression in Japanese patients with chronic obstructive pulmonary disease: A cross-sectional study. Respir. Care. 2013; 58(7): 1196–1203. PubMed Abstract | Publisher Full Text\n\nIsdijoso W, Kusumastuti Rahayu S, Indriani K, et al.: The Situation of the Elderly in Indonesia and Access to Social Protection Programs: Secondary Data Analysis. 2020.Reference Source\n\nJovanova O, Luik AI, Leening MJG, et al.: The long-term risk of recognized and unrecognized myocardial infarction for depression in older men. Psychol. Med. 2016; 46(9): 1951–1960. Publisher Full Text\n\nKarczewska O, Młynarska A: The Influence of Antiarrhythmic Device Intervention on Biopsychosocial Functioning and Anxiety in Patients with an Implanted Cardioverter Defibrillator. Medicina (Kaunas). 2021; 57(2). PubMed Abstract | Publisher Full Text\n\nKato K, Zweig R, Schechter CB, et al.: Positive attitude toward life, emotional expression, self-rated health, and depressive symptoms among centenarians and near-centenarians. Aging Ment. Health. 2016; 20(9): 930–939. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlinedinst NJ, Resnick B, Yerges-Armstrong LM, et al.: The interplay of genetics, behavior, and pain with depressive symptoms in the elderly. Gerontologist. 2015; 55: S67–S77. PubMed Abstract | Publisher Full Text\n\nKobylańska M, Kowalska J, Neustein J, et al.: The role of biopsychosocial factors in the rehabilitation process of individuals with a stroke. Work (Reading, Mass.). 2018; 61(4): 523–535. PubMed Abstract | Publisher Full Text\n\nKobylańska M, Kowalska J, Neustein J, et al.: The role of biopsychosocial factors in the rehabilitation process of individuals with a stroke. Work. 2019; 61(4): 523–535. PubMed Abstract | Publisher Full Text\n\nKoo JH, Son N, Yoo K-B: Relationship between the living-alone period and depressive symptoms among the elderly. Arch. Gerontol. Geriatr. 2021; 94: 104341. PubMed Abstract | Publisher Full Text\n\nKuroda Y, Iwasa H, Goto A, et al.: Occurrence of depressive tendency and associated social factors among elderly persons forced by the Great East Japan Earthquake and nuclear disaster to live as long-term evacuees: A prospective cohort study. BMJ Open. 2017; 7(9): e014339. PubMed Abstract | Publisher Full Text\n\nLaird KT, Siddarth P, Krause-Sorio B, et al.: Anxiety symptoms are associated with smaller insular and orbitofrontal cortex volumes in late-life depression. J. Affect. Disord. 2019; 256: 282–287. PubMed Abstract | Publisher Full Text\n\nLeggett A, Zarit SH, Nguyen NH, et al.: The influence of social factors and health on depressive symptoms and worry: A study of older Vietnamese adults. Aging Ment. Health. 2012; 16(6): 780–786. PubMed Abstract | Publisher Full Text\n\nLewin A, Jöbges M, Werheid K: The influence of self-efficacy, pre-stroke depression and perceived social support on self-reported depressive symptoms during stroke rehabilitation. Neuropsychol. Rehabil. 2013; 23(4): 546–562. PubMed Abstract | Publisher Full Text\n\nLewis A: Housing an ageing population: a reading list. House of Commons Library;2021.\n\nManaf MRA, Mustafa M, Rahman MRA, et al.: Factors influencing the prevalence of mental health problems among Malay elderly residing in a rural community: A cross-sectional study. PLoS One. 2016; 11(6): 1–12. PubMed Abstract | Publisher Full Text\n\nMatthieu MM, Lawrence KA, Robertson-Blackmore E: The impact of a civic service program on biopsychosocial outcomes of post 9/11 U.S. military veterans. Psychiatry Res. 2017; 248(December 2016): 111–116. PubMed Abstract | Publisher Full Text\n\nMeesters PD, Comijs HC, Sonnenberg CM, et al.: Prevalence and correlates of depressive symptoms in a catchment-area based cohort of older community-living schizophrenia patients. Schizophr. Res. 2014; 157(1–3): 285–291. Publisher Full Text\n\nMisawa J, Kondo K: Social factors relating to depression among older people in Japan: analysis of longitudinal panel data from the AGES project. Aging Ment. Health. 2019; 23(10): 1423–1432. Publisher Full Text\n\nNadimpalli SB, James BD, Yu L, et al.: The association between discrimination and depressive symptoms among older African Americans: The role of psychological and social factors. Exp. Aging Res. 2015; 41(1): 1–24. PubMed Abstract | Publisher Full Text\n\nNicolosi GT, Falcão DVDS, Batistoni SST, et al.: Depressive symptoms in old age: Relations among sociodemographic and self-reported health variables. Int. Psychogeriatr. 2011; 23(6): 941–949. PubMed Abstract | Publisher Full Text\n\nOdlum M, Davis N, Owens O, et al.: Correlates and aetiological factors associated with hedonic well-being among an ageing population of US men and women: Secondary data analysis of a national survey. BMJ Open. 2018; 8(11): e020962. PubMed Abstract | Publisher Full Text\n\nOlsen SJS, Schirmer H, Wilsgaard T, et al.: Cardiac rehabilitation and symptoms of anxiety and depression after percutaneous coronary intervention. Eur. J. Prev. Cardiol. 2018; 25(10): 1017–1025. PubMed Abstract | Publisher Full Text\n\nParalikas T, Maria M, Dimitrios T, et al.: Physical and Mental Health Level of the Elderly Living in Central Greece. Materia Socio Medica. 2021; 33(1): 16–20. PubMed Abstract | Publisher Full Text\n\nPark SD, Yu SH: The effects of Nordic and general walking on depression disorder patients’ depression, sleep, and body composition. J. Phys. Ther. Sci. 2015; 27(8): 2481–2485. PubMed Abstract | Publisher Full Text\n\nPetkus AJ, Gum A, Wetherell JL: Thought suppression is associated with psychological distress in homebound older adults. Depress. Anxiety. 2012; 29(3): 219–225. PubMed Abstract | Publisher Full Text\n\nPiboon K, Subgranon R, Hengudomsub P, et al.: A causal model of depression among older adults in Chon Buri Province, Thailand. Issues Ment. Health Nurs. 2012; 33(2): 118–126. Publisher Full Text\n\nPocklington C: Review Article Depression in older adults. Br. J. Medical Pract. 2017; 10(1): 7. https://www.bjmp.org/files/2017-10-1/bjmp-2017-10-1-a1007.pdf .\n\nPollock A, Berge E: How to do a systematic review. Int. J. Stroke. 2018; 13(2): 138–156. Publisher Full Text\n\nPopescu ML, Boisjoly H, Schmaltz H, et al.: Explaining the relationship between three eye diseases and depressive symptoms in older adults. Invest. Ophthalmol. Vis. Sci. 2012; 53(4): 2308–2313. PubMed Abstract | Publisher Full Text\n\nPusswald G, Fleck M, Lehrner J, et al.: The “Sense of Coherence” and the coping capacity of patients with Parkinson disease. Int. Psychogeriatr. 2012; 24(12): 1972–1979. PubMed Abstract | Publisher Full Text\n\nRhee MK, Jang Y, Kim SY, et al.: The moderating role of social factors in the relationship between an incident of fall and depressive symptoms: a study with a national sample of older adults in South Korea. Aging Ment. Health. 2021; 25(6): 1086–1093. PubMed Abstract | Publisher Full Text\n\nRippon I, Steptoe A: Is the relationship between subjective age, depressive symptoms and activities of daily living bidirectional? Soc. Sci. Med. 2018; 214(August): 41–48. PubMed Abstract | Publisher Full Text\n\nRzewuska M, Mallen CD, Strauss VY, et al.: One-year trajectories of depression and anxiety symptoms in older patients presenting in general practice with musculoskeletal pain: A latent class growth analysis. J. Psychosom. Res. 2015; 79(3): 195–201. PubMed Abstract | Publisher Full Text\n\nSadler P, McLaren S, Jenkins M: A psychological pathway from insomnia to depression among older adults. Int. Psychogeriatr. 2013; 25(8): 1375–1383. PubMed Abstract | Publisher Full Text\n\nSakurai R, Kawai H, Suzuki H, et al.: Poor Social Network, Not Living Alone, Is Associated With Incidence of Adverse Health Outcomes in Older Adults. J. Am. Med. Dir. Assoc. 2019; 20(11): 1438–1443. Publisher Full Text\n\nSanders JB, Comijs HC, Bremmer MA, et al.: A 13-year prospective cohort study on the effects of aging and frailty on the depression-pain relationship in older adults. Int. J. Geriatr. Psychiatry. 2015; 30(7): 751–757. Publisher Full Text\n\nSjöberg L, Östling S, Falk H, et al.: Secular changes in the relation between social factors and depression: A study of two birth cohorts of Swedish septuagenarians followed for 5 years. J. Affect. Disord. 2013; 150(2): 245–252. Publisher Full Text\n\nStringa N, Milaneschi Y, van Schoor NM , et al.: Genetic Liability for Depression, Social Factors and Their Interaction Effect in Depressive Symptoms and Depression Over Time in Older Adults. Am. J. Geriatr. Psychiatr. 2020; 28(8): 844–855. Publisher Full Text\n\nThipprakmas R: Prevalence and Factors Associated with Depression in the Elderly: A Systematic Review. Regioanal Health Promotion Center 9. 2021; 15(37): 325–338.\n\nWang J, Li W, Yue L, et al.: The Study of White Matter Hyperintensity (WMH) and Factors Related to Geriatric Late-Onset Depression. Shanghai Arch. Psychiatry. 2018; 30(1): 12–19. Publisher Full Text\n\nWang L, Tao Y, Chen Y, et al.: Association of post stroke depression with social factors, insomnia, and neurological status in Chinese elderly population. Neurol. Sci. 2016; 37(8): 1305–1310. Publisher Full Text\n\nWild B, Heider D, Maatouk I, et al.: Significance and costs of complex biopsychosocial health care needs in elderly people: Results of a population-based study. Psychosom. Med. 2014; 76(7): 497–502. PubMed Abstract | Publisher Full Text\n\nWoods A, Solomonov N, Liles B, et al.: Perceived Social Support and Interpersonal Functioning as Predictors of Treatment Response Among Depressed Older Adults. Am. J. Geriatr. Psychiatr. 2021; 29(8): 843–852. PubMed Abstract | Publisher Full Text\n\nWorld Federation for Mental Health: Mental health and older people. 2013. Publisher Full Text\n\nYlli A, Miszkurka M, Phillips SP, et al.: Clinically relevant depression in old age: An international study with populations from Canada, Latin America and Eastern Europe. Psychiatry Res. 2016; 241: 236–241. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "155782",
"date": "16 Dec 2022",
"name": "Acharaporn Seeherunwong",
"expertise": [
"Reviewer Expertise Depression",
"mental health",
"nursing"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study's objective should be \"...biopsychosocial factors associated with or predictors of depression in the elderly.\"\nComment from reviewer:\nThe study of “Biopsychosocial factors associated with depression in the elderly: A systematic literature review” is an exciting paper. I have the following comments for the authors to address.\nThe title: I suggest using “A systematic review” instead of “A systematic literature review”.\n\nIntroduction section: In the 1st paragraph, \"In Indonesia, citizens 60 years old or older have reached about 25.7 million people\" should be revised to calculate to be a percentage of the total population. As a result, the amount of elderly in Indonesia is comparable to the proportion of elderly in the UK and other countries worldwide.\n\nResult: The outcome has varied the severity of depressive symptoms. I suggest categorizing the paper into two groups, as the outcomes differ in severity. The first group is the elderly diagnosed with MDD or depressive disorder (article nos. 2, 6, 9,13, 30). The second one is elderly with depressive symptoms who were not diagnosed with depressive disorders. The associated factors may be different as well.\n\nPlease separate the result section from the discussion section. In addition, the authors should find previous studies to explain the results.\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": [
{
"c_id": "10280",
"date": "14 Feb 2024",
"name": "Yanti Harjono Hadiwiardjo",
"role": "Author Response",
"response": "One of the key areas of focus in this revision has been the enhancement of the synthesis level in our article. We have made concerted efforts to this revision. By meticulously reorganizing and rephrasing sections of the manuscript, we have aimed to present a more cohesive and integrated narrative. Additionally, we have addressed your recommendation regarding the introduction of a JBI score. We have now included this score as a vital component of our methodology, providing a transparent and standardized measure of the quality and reliability of our research."
},
{
"c_id": "10438",
"date": "14 Feb 2024",
"name": "Yanti Harjono Hadiwiardjo",
"role": "Author Response",
"response": "The title the title has been changed to \"Biopsychosocial factors associated with depression in the elderly: A systematic review\" Introduction section: In the 1st paragraph changed to \"Demographic Profiles and Implications of the Top 10 Countries with the Highest Number of People Aged 65+ in 2020\" delves into a significant global demographic shift observed in the year 2020 with calculations conducted by ESCAP based on the United Nations' Department of Economic and Social Affairs, Population Division (2019). The data reveals the following key insights China emerged as the country with the largest elderly population, with a staggering 172,262 individuals aged 65 and above, representing 46.05% of its total population, India follows closely, with 90,720 seniors, constituting 24.25% of the population, Japan recorded 35,916 elderly citizens, making up 9.60% of its populace, The Russian Federation reported 22,633 seniors, accounting for 6.05% of its total population, Indonesia had 17,219 elderly individuals, representing 4.57% of the population, Pakistan's elderly population reached 9,606, making up 2.56% of its total, Thailand reported 9,044 seniors, equivalent to 2.41% of its population, Bangladesh recorded 8,608 elderly citizens, constituting 2.30% of its populace and Korea reported 8,096 elderly individuals, representing 2.16% of the total population. Regarding categorizing the paper into two groups, the author feels objections and does not want to categorize it into two groups. Just following the initial research with the expected results as of now. In the latest and revised article, the author has categorized the results and discussion into different sections according to the reviewer's input."
}
]
},
{
"id": "155783",
"date": "17 Feb 2023",
"name": "Rahul Shidhaye",
"expertise": [
"Reviewer Expertise Depression",
"Anxiety Disorders",
"Elderly",
"Pregnant women",
"Yoga",
"Implementation Science"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn the paper titled, ‘Biopsychosocial factors associated with depression in the elderly: A systematic literature review’, the aim of the authors is to review the evidence related to the contribution of biopsychosocial factors to depression in the elderly.\nMy comments and suggestions on this paper are as follows:\nLarge number of studies have investigated the role of biological, psychological, and social factors associated with depression in the general population and in the elderly. In this backdrop, the rationale for undertaking the current systematic review is not clear. Authors mention, \"a greater understanding of the individual contributions of biological, psychological, and social risk factors can have a big impact on the adoption of preventive actions to lower the population's risk of depression\", but this review doesn’t seem to assess the individual contribution of each of these factors.\n\nMethods section can be re-structured based on the points included in the PRISMA guidelines.\n\nWhy was the search limited to the last ten years only?\n\nThe meaning of the sentence, \"these studies included quantitative synthesis\", is not clear. The following sentence is included in the limitations section, \"papers included in this review are varied, so they do not allow for quantitative synthesis.\" Kindly clarify.\n\nWho completed the critical appraisal of all the included papers? The score for each included paper based on the JBI checklist could be presented in a table as part of the supplementary material.\n\nOne of the biological factors mentioned is \"brain anatomical\". Kindly explain.\n\nLimitations of the review and limitations of the included studies need to be described much more elaborately. There are multiple limitations of this study/review which are not discussed at all.\n\nIt will be good to compare the findings of this review with other similar studies.\n\nResults from individual papers are presented without a clear high-level synthesis of these findings.\n\nThe aim of this review is to identify the research gaps, but this doesn’t seem to be covered anywhere in the paper.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? No\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Partly\n\nAre the conclusions drawn adequately supported by the results presented in the review? No",
"responses": [
{
"c_id": "10281",
"date": "14 Feb 2024",
"name": "Yanti Harjono Hadiwiardjo",
"role": "Author Response",
"response": "One of the key areas of focus in this revision has been the enhancement of the synthesis level in our article. We have made concerted efforts to this revision. By meticulously reorganizing and rephrasing sections of the manuscript, we have aimed to present a more cohesive and integrated narrative. Additionally, we have addressed your recommendation regarding the introduction of a JBI score. We have now included this score as a vital component of our methodology, providing a transparent and standardized measure of the quality and reliability of our research."
},
{
"c_id": "10465",
"date": "14 Feb 2024",
"name": "Yanti Harjono Hadiwiardjo",
"role": "Author Response",
"response": "After the author reviews it further, what the author means by individual contribution is if a person already knows these risk factors so they can be prevented, and the incidence of depression can decrease. The author changed the paragraph to “A greater understanding of the individual factors of biological, psychological, and social risk factors can have a big impact on the adoption of preventive actions to lower the population's risk of depression.” Done for submission, the article re-structured based on the PRISMA guidelines. The selection of the last 10 years for research is driven by the need to focus on recent and relevant information. This time frame allows us to capture the most up-to-date developments, trends, and insights in the field. The requirement for articles to be written in English and published between 2011 and 2021 further ensures that the sources are contemporary and provide valuable insights within a reasonable time span. This approach enhances the accuracy and relevance of the information gathered for the study. After reviewing it again, the author revised the limitations sections in the article to be “The limitation of the results of this systematic review is that most papers do not clearly identify the confounding factor so it cannot be determined whether there is bias in the study. Therefore, we discuss the results narratively in order to provide a big picture of the topic.” Completed for submission, the article includes a paper based on JBI checklist scores as an attachment. The means of brain anatomical is like a history of trauma, infectious diseases and other abnormalities in the brain. The limitation of the results of this systematic review is that most papers do not clearly identify the confounding factor so it cannot be determined whether there is bias in the study. Therefore, we discuss the results narratively in order to provide a big picture of the topic. Thank you for the suggestion, the author will add the section comparing the findings of this review with other similar studies. The author had limited time, so he did not have time to carry out a meta-analysis. This article aims to identify research gaps, which means the authors want to analyze current risk factors. The reason is the author feels that the risk factors for depression are different between now and then."
}
]
}
] | 1
|
https://f1000research.com/articles/11-1068
|
https://f1000research.com/articles/12-155/v1
|
10 Feb 23
|
{
"type": "Research Article",
"title": "Investigating ultrastructural morphology in MIRAGE syndrome (SAMD9)-derived fibroblasts using transmission electron microscopy.",
"authors": [
"Federica Buonocore",
"Monika Balys",
"Glenn Anderson",
"John C. Achermann",
"Monika Balys",
"Glenn Anderson"
],
"abstract": "Background: Heterozygous de novo variants in the gene SAMD9 cause the complex multisystem disorder, MIRAGE syndrome. Patients are characterised by myelodysplasia, infections, growth restriction, adrenal insufficiency, gonadal dysfunction and enteropathies. Pathogenic variants in SAMD9 are gain-of-function and enhance its role as a growth repressor, leading to growth restriction of many tissues. Two studies have reported changes in skin fibroblasts derived from MIRAGE patients, more specifically identifying enlarged endosomes. We have also previously shown subtle changes in endosome size in patients’ fibroblasts compared to controls. However, these variations in endosomes were not as marked as those described in the literature. Methods: We have performed an observational study using transmission electron microscopy (EM) in a larger number of cells derived from three patients’ fibroblasts to assess ultrastructure morphology compared to control images. Results: Consistent changes were observed in cell organelles in all patient samples. In particular, increased endosomal activity was detected, characterised by augmented pinocytosis and vesicle budding, increased endosome number, as well as by large lysosomes and endosomes. Endoplasmic reticulum was also prominent. Mitochondria appeared enlarged in selected cells, possibly due to cellular stress. Cell nuclei did not display major differences compared to controls. Conclusions: EM is a powerful tool to investigate morphological features of tissues and cell organelles, although EM data could be affected by sample preparation methodology, therefore potentially explaining the variability between independent studies, and its analysis can be dependent on the experience of the researcher. The increased endosomal activity we have observed in patients’ fibroblasts could indicate that SAMD9 regulates endocytosis of receptors, acting as an endosome fusion facilitator, or in lysosomal activation. However, the precise mechanism(s) by which SAMD9 regulates cell growth is still not fully understood, and further studies are needed to elucidate its pathogenic pathway and develop therapeutic approaches to support patients.",
"keywords": [
"SAMD9",
"endosomes",
"MIRAGE syndrome",
"transmission electron microscopy."
],
"content": "Introduction\n\nMIRAGE syndrome (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital (gonadal) phenotypes, and enteropathy) (OMIM: 617053) is a well-established complex multisystem disorder caused by pathogenic gain-of-function variants in the gene SAMD9.1,2 Changes in this gene were first described in 2016 and to date more than 100 affected individuals have been reported. We have recently undertaken a meta-analysis of all published SAMD9-associated variants and shown that the range of clinical phenotypes is very variable.3 Increasingly, children with MIRAGE syndrome are diagnosed who do not have adrenal insufficiency, and a large proportion of children and young people with SAMD9 variants present with myelodysplastic syndrome (MDS) alone.3,4\n\nSAMD9 has been extensively shown to be a growth repressor in in vitro cellular models, explaining the typical phenotypic growth restriction and tissue hypoplasia observed in children with this condition. However, the molecular mechanism or mechanisms by which SAMD9 affects cell growth and proliferation are still unknown. Two studies have reported characteristic enlarged endosomes in skin fibroblasts derived from MIRAGE patients, including “giant” endosomes in some cells.1,5 These authors proposed that endosome dysfunction results in reduced recycling of epidermal growth factor receptor (EGFR), with consequent decreased cell growth and proliferation.1 We have also observed somewhat larger vesicles in our patients’ fibroblasts using transmission electron microscopy (EM) imaging and Rab5a and Rab7a as early- and late- endosomal markers respectively, in live fibroblast cultures.2 However, these EM studies were only reviewed at low power and in limited sections, and more detailed high-power imaging was not undertaken.\n\nEM remains an extremely powerful approach for visualising and analysing intracellular structures in biological samples. This technique is extensively used in clinical diagnosis as well as research settings, and therefore represents an invaluable analytical tool. In this study, we have used EM to systematically analyse ultrastructural morphology of skin fibroblasts, which had been previously derived from MIRAGE patients,2 to investigate any potential characteristic features that could help elucidate the molecular role of SAMD9.\n\n\nMethods\n\nThe clinical phenotypes and initial EM findings have been previously described in our original report of MIRAGE syndrome.2 In brief, these eight patients were all delivered preterm with fetal growth restriction and needing intensive care. Additional features included primary adrenal insufficiency, recurrent viral and bacterial infections, persistent diarrhoea, and bone marrow dysfunction. Fibroblasts from three of the eight patients were obtained: patient 1 with a c.1376G>A, p.R459Q change; patient 2 with a c.2054G>A, p.R685Q change; patient 3 with c.2948T>G, p.I983S. Patient 3 was also found to harbour a secondary somatic mosaic c.2294delA, p.N765Tfs*13 change in haematopoietic cells. All three patients had a 46,XY karyotype.\n\nWritten informed consent of the patients’ parents was obtained for research and diagnosis prior to inclusion in the study (NRES London-Bloomsbury 07/Q0508/24).\n\nSkin fibroblasts from three patients and from one control (46,XY) were grown in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% FBS and 1% penicillin/streptomycin at 37°C in a humidified atmosphere (5% CO2). All fibroblast cultures used were negative for mycoplasma contamination.\n\nFibroblasts were detached from culture flasks by trypsin digestion and centrifuged at 3000 rpm for 15 minutes to form a pellet for EM processing. After removal of the medium, all cell pellets were fixed in 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer followed by secondary fixation in 1% osmium tetroxide. Samples were dehydrated in graded ethanol, transferred to a transitional fluid (propylene oxide) and then infiltrated and embedded in Agar 100 epoxy resin. Polymerisation was at 60°C for 48 hours. Ultrathin sections (90 nm) were cut using a Diatome diamond knife on a Leica Ultracut UC7 ultramicrotome (Leica Microsystems, Germany). Sections were picked up on Athene 300 mesh copper grids and stained with 70% alcoholic uranyl acetate and Reynold’s lead citrate for contrast. Sections were then examined using a JEOL 1400 transmission electron microscope (JEOL, Japan) and images recorded using an AMT XR80 digital camera (Advanced Microscopy Techniques, US). Independent images from randomly selected control or patient fibroblasts were studied. A total of 100 fibroblasts were examined from each culture, initially at x1,000 magnification. Representative cells showing particular ultrastructural features were recorded at higher magnifications for further assessment. Interpretation of EM changes was made by comparing patient-derived samples with the control sample that was processed in parallel, as well as based on the extensive experience of EM analysis of one author (G. A.).\n\n\nResults\n\nAll three patient samples showed similar ultrastructural features which were distinct from the control sample. Given the qualitative, observational nature of EM, the major consistent changes are described below.\n\nA general increase in endosome number and activity was observed in the patients’ fibroblasts (Figure 1). Characteristic features of increased endosomal activity included pinocytic vesicles, early endosomes showing chains and clumps of vesicles, as well as vesicle budding (Figure 1). Several late endosomes had multivesicular bodies (MVB) (Figure 2). Evidence of increased endosomal activity was also demonstrated by enlarged empty endosomes and large (over 1.0 μm diameter), single membrane bound lysosomes, which were mainly empty with a rim of electron dense material (Figure 2).\n\nAll three patients’ samples displayed features of increased endosomal activity. These included increased number of pinocytic vesicles, many endosome chains (C) and budding (indicated by arrows), as well as clusters of endosomes (CE). Scale bars 500 nm.\n\nIncreased endosomal activity was also demonstrated by the presence of large, mainly empty lysosomes (LY) with dense debris localised to the border; enlarged empty endosomes (EN) and late endosomes filled with multivesicular bodies (MVB). Rough endoplasmic reticulum (rER). Control, Patient 1 and Patient 2 scale bars 500 nm; Patient 3 scale bar 2 μm.\n\nAll patient-derived cells displayed a regular array of organelles (Figure 3). Mitochondria did not show any significant pathological features except swelling and internal cristae disruption in a few cells. Endoplasmic reticulum was prominent in several fibroblasts and was mainly of the rough endoplasmic type (rER). A moderate distention of the cisternae was observed, with granular electron dense material. Dilatation of smooth endoplasmic reticulum (sER) was also present, indicated by an irregular outline with granular material within, but without any obvious ribosomes lining the membranes (Figure 3, Patient 1, top left).\n\nBoth control and patients’ cells displayed a regular array of organelles. Often patients’ mitochondria (MI) were expanded. Smooth endoplasmic reticulum (sER) appeared dilated and was filled with granular material (Patient 1), but without any ribosomes lining the membrane. Rough endoplasmic reticulum (rER) was full of granular electron dense material, and a moderate distention of the cisternae was also observed. Lysosomes (LY). Scale bars 500 nm.\n\nNo major differences in cell nuclei between control and patient samples were observed (Figure 4). Several features were common in both control and patient cells, including an irregular nuclear envelope with a marginated chromatin pattern, nucleoli often prominent in size and occasionally multiple nucleoli present in one cell.\n\nNuclei (N) had an irregular nuclear envelope, with a marginated chromatin pattern in both control and patients’ cells. Nucleoli (indicated by the white asterisk *) were pronounced in size and in various cells multiple nucleoli were seen. Several cytoplasmic features in patients’ cells (described in Figures 1–3) are also seen at lower power here. Scale bars 2 μm.\n\n\nDiscussion\n\nIn this study, we have used EM to examine ultrastructural morphology of fibroblasts derived from MIRAGE patients. Although our early specimens were variable,2 we have now obtained and systematically analysed more images from our original fibroblast samples. All samples were well preserved with ample numbers of cells for analysis. The three patients’ samples showed essentially similar features and were distinct from the control sample, demonstrating that carrying SAMD9 variants resulted in differences in intracellular structures.\n\nEvidence of increased endosomal activity was present in all patients’ samples. This was reflected by an increase in pinocytosis and budding in early endosomes, and the presence of large endosomes and lysosomes. Endosomes can be broadly classified as early endosomes, late endosomes and recycling endosomes, which will fuse with lysosomes for degradation of waste matter. Lysosomes are single membrane bound organelles filled with hydrolytic enzymes capable of degrading many types of biomolecules, cellular organelles and micro-organisms.6 Thus, lysosomes typically appear as sphere-shaped sacks with electron dense contents. Taken together, consistent markers of increased endosome activity in patients’ samples were seen.\n\nWe also observed a dilation of both rER and sER. The main function of rER is the synthesis and modification of proteins that need to be delivered to organelles within the cell or secreted from the cell. sER is associated with the synthesis of lipids such as cholesterol and phospholipids, which are essential for the formation of cellular membranes. sER also plays a role in glycogen metabolism.7 Glycogen content and intermediate filaments were at varying levels in all samples and no excess lipid was detected.\n\nMitochondria were easily detected in EM images, as they are bounded by a double membrane and the inner membrane forms the characteristic infolding of lamellar cristae and matrix space. Their major role is the provision of energy by the production of ATP and phosphorylation of ADP to regulate cellular metabolism.8 We detected bloated mitochondria in a few cells; however, this is quite a common feature and could indicate a sign of cellular stress, such as a delay in fibroblast preservation.\n\nCell nuclei did not show any major differences between control and patients’ samples and appeared with an irregular nuclear envelope. Irregularity of nuclear membrane provides an increased area of contact between the nucleus and the cytoplasm and may suggest heightened metabolic activity.9\n\nEM is widely used in clinical settings to diagnose specific conditions, such as lysosomal storage disorders, glomerular diseases and metabolic and congenital myopathies,10–12 however, over the past years its use has been valuable in research settings too. Indeed, EM has been used to further investigate the detailed structures of cell organelles to validate potential novel findings discovered through research studies. For example, EM has been used to: a) assess ciliary ultrastructural defects in ciliary disorders13; b) identify stored material in lysosomal storage disorders, including neuronal ceroid lipofuscinoses and Batten disease14; and c) isolate highly infectious and contagious microorganisms, primarily viruses, to enable production of vaccines in microbial diseases, e.g. SARS-CoV-2/coronavirus.15 However, there is no standard protocol for EM and different preparation methods can be used, which can often affect the observed results.\n\nThe most widely used method is “traditional ultrathin-section EM”,16 which in brief consists of a series of steps (fixation, wash, dehydration, embedding) to preserve the specimen before sectioning and staining. This has been proven to maintain cellular integrity and sample structure, without leading to cellular artefacts. This approach is, therefore, potentially more reliable. In our original study, cultured fibroblasts were first pelleted and then fixed in 2.5% glutaraldehyde followed by 1% osmium tetroxide. They were then processed into agar 100 resin, sectioned (90 nm) and stained with uranyl acetate and lead citrate. In contrast, in other studies reporting giant endosomes in MIRAGE patients,1,5 fibroblasts were seeded on a chamber slide and then fixed with 2.5% glutaraldehyde followed by 1.0% osmium tetroxide. They were then embedded in Epon, sectioned (70 nm) and stained with uranyl acetate and lead citrate. The use of different methodologies, especially the initial step of cell pelleting compared to growing cells directly on chamber slides, might therefore account for some of the variability in the appearance of the vesicles and endosomes in different, independent studies.\n\nWhilst SAMD9-associated conditions provide a fascinating model for the dynamic evolution of genetic disease, the exact mechanism by which SAMD9 regulates cell growth and mediates a cellular effect is yet to be fully established. The paralogous gene SAMD9L has been shown to regulate endosomal fusion through degradation of EGFRs.17 Several patients with MIRAGE syndrome had characteristic enlarged endosomes,1,5 therefore SAMD9 could potentially be involved in the regulation of endocytosis of receptors acting as an endosome fusion facilitator,1 or in lysosomal activation.18 In our original study, we showed some large vesicles in our patient fibroblasts, but these were quite heterogenous. We also carried out live cell imaging of early and late endosomes and the changes in early endosomes from live imaging were only subtle.2 In the present study, all three MIRAGE patients’ fibroblasts exhibited increased endosomal activity compared to controls, as well as large lysosomes. These data could, therefore, still support the role of SAMD9 in recycling of EGFRs.\n\nSAMD9 has also been associated with the viral host defence mechanism, especially poxviruses,19–21 and tumour suppression.17,22 More recently, it has been shown to have nucleic acid binding capacity, important for antiviral and antiproliferative functions.23 As more insight is obtained on the biological function or functions of SAMD9, detailed data from patient-derived materials, and associated cellular ultrastructural changes, could provide more evidence for underlying disease mechanisms.\n\nThis study has several limitations. EM is a powerful tool, however its assessment remains subjective, as it mainly relies on the experience of the individual analysing the images. Qualitative evaluation can be difficult since the cells are in a three dimensions and EM is allowing visualisation of a very thin slice through the cell. The number of individuals with MIRAGE syndrome studied to date is relatively small, so data are limited.\n\nIn conclusion, we have observed evidence of increased endosomal activity in patients-derived fibroblasts carrying SAMD9 variants compared to controls. These findings provide more data for ultrastructural morphology of SAMD9-associated conditions and supports the original findings of enlarged vesicles in patients’ fibroblasts. However, more insight into the pathogenic mechanisms of SAMD9 disruption is needed. Indeed, induced pluripotent stem cell lines (iPSC) have been generated from fibroblasts from two MIRAGE patients.2,24 These represent a potentially important resource to further investigate the disease mechanisms of MIRAGE syndrome and model the underlying molecular basis, at least in vitro. Understanding the molecular function of SAMD9 is extremely important to help us develop personalised management and effective therapies for individuals with SAMD9-associated variants.",
"appendix": "Data availability\n\nOSF: Investigating ultrastructural morphology in MIRAGE syndrome (SAMD9)-derived fibroblasts using transmission electron microscopy. https://doi.org/10.17605/OSF.IO/Z8WVE. 25\n\nThis project contains the following extended data:\n\n• Control (17.TIF files)\n\n• Patient1 (19.TIF files)\n\n• Patient2 (19.TIF files)\n\n• Patient3 (21.TIF files)\n\nData are available under the terms of the Creative Commons BY (CC-BY) 4.0.\n\n\nAcknowledgments\n\nWe are grateful to the physicians and families who contributed to our original report of SAMD9-related disorders.\n\n\nReferences\n\nNarumi S, Amano N, Ishii T, et al.: SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7. Nat. Genet. 2016; 48(7): 792–797. Publisher Full Text\n\nBuonocore F, Kühnen P, Suntharalingham JP, et al.: Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans. J. Clin. Invest. 2017; 127(5): 1700–1713. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSuntharalingham JP, Ishida M, Del Valle I, et al.: Emerging phenotypes linked to variants in SAMD9 and MIRAGE syndrome. Front. Endocrinol (Lausanne). 2022; 13: 1794. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSahoo SS, Pastor VB, Goodings C, et al.: Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes. Nat. Med. 2021; 27(10): 1806–1817. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIshiwa S, Kamei K, Tanase-Nakao K, et al.: A girl with MIRAGE syndrome who developed steroid-resistant nephrotic syndrome: A case report. BMC Nephrol. 2020; 21(1): 340. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJeger JL: Endosomes, lysosomes, and the role of endosomal and lysosomal biogenesis in cancer development. Mol. Biol. Rep. 2020; 47(12): 9801–9810. PubMed Abstract | Publisher Full Text\n\nChaudhari N, Talwar P, Parimisetty A, et al.: A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress. Front. Cell. Neurosci. 2014; 8(July): 213. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFreya TG, Mannellab CA: The internal structure of mitochondria. Trends Biochem. Sci. 2000; 25(7): 319–324. Publisher Full Text\n\nGauthier BR, Comaills V: Nuclear envelope integrity in health and disease: consequences on genome instability and inflammation. Int. J. Mol. Sci. 2021; 22(14): 7281. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAnderson GW, Smith VV, Brooke I, et al.: Diagnosis of neuronal ceroid lipofuscinosis (Batten Disease) by electron microscopy in peripheral blood specimens. Ultrastruct. Pathol. 2006; 30(5): 373–378. Publisher Full Text\n\nHowell DN, Herrera GA: Electron microscopy in renal pathology: overall applications and guidelines for tissue, collection, preparation, and stains. Ultrastruct. Pathol. 2021; 45(1): 1–18. Publisher Full Text\n\nSanthoshkumar R, Narayanappa G: Electron microscopy in the diagnosis of skeletal muscle disorders: Its utility and limitations. Indian J. Pathol. Microbiol. 2022; 65(Supplement): S291–S299. PubMed Abstract | Publisher Full Text\n\nRezaei M, Soheili A, Ziai SA, et al.: Transmission electron microscopy study of suspected primary ciliary dyskinesia patients. Sci Reports. 2022; 12(1): 2375–2379. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAnderson GW, Goebel HH, Simonati A: Human pathology in NCL. Biochim Biophys Acta - Mol Basis Dis. 2013; 1832(11): 1807–1826. Publisher Full Text\n\nGoldsmith CS, Tatti KM, Ksiazek TG, et al.: Ultrastructural characterization of SARS Coronavirus. Emerg. Infect. Dis. 2004; 10(2): 320–326. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTizro P, Choi C, Khanlou N: Sample Preparation for Transmission Electron Microscopy. Methods in Molecular Biology. Vol. 1897.. Humana Press Inc.;2019; pp. 417–424. Publisher Full Text\n\nNagamachi A, Matsui H, Asou H, et al.: Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7. Cancer Cell. 2013; 24: 305–317. PubMed Abstract | Publisher Full Text\n\nNagamachi A, Kanai A, Nakamura M, et al.: Multiorgan failure with abnormal receptor metabolism in mice mimicking Samd9/9L syndromes. J. Clin. Invest. 2021; 131(4). PubMed Abstract | Publisher Full Text | Free Full Text\n\nMeng X, Zhang F, Yan B, et al.: A paralogous pair of mammalian host restriction factors form a critical host barrier against poxvirus infection. Sutter G, ed. PLoS Pathog. 2018; 14(2): e1006884. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSivan G, Ormanoglu P, Buehler EC, et al.: Identification of restriction factors by human genome-wide RNA interference screening of viral host range mutants exemplified by discovery of SAMD9 and WDR6 as inhibitors of the vaccinia virus K1L-C7L-mutant. MBio. 2015; 6(4): e01122–e01115. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu J, Wennier S, Zhang L, et al.: M062 is a host range factor essential for myxoma virus pathogenesis and functions as an antagonist of host SAMD9 in human cells. J. Virol. 2011; 85(7): 3270–3282. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMa Q, Yu T, Ren Y-Y, et al.: Overexpression of SAMD9 suppresses tumorigenesis and progression during non small cell lung cancer. Biochem. Biophys. Res. Commun. 2014; 454(1): 157–161. PubMed Abstract | Publisher Full Text\n\nPeng S, Meng X, Zhang F, et al.: Structure and function of an effector domain in antiviral factors and tumor suppressors SAMD9 and SAMD9L. Proc. Natl. Acad. Sci. 2022; 119(4): e2116550119. Publisher Full Text\n\nFischer I, Küchler J, Schaar C, et al.: Generation of human induced pluripotent stem cell lines from 2 patients with MIRAGE syndrome. Stem Cell Res. 2021; 54: 102417. PubMed Abstract | Publisher Full Text\n\nBuonocore F, Balys M, Anderson G, et al.: Investigating ultrastructural morphology in MIRAGE syndrome (SAMD9)-derived fibroblasts using transmission electron microscopy. Extended data. 2023. Publisher Full Text"
}
|
[
{
"id": "162984",
"date": "16 Feb 2023",
"name": "Satoshi Narumi",
"expertise": [
"Reviewer Expertise molecular genetics",
"pediatric endocrinology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 by Federica Buonocore and colleagues, skin fibroblasts established from three patients with MIRAGE syndrome (with distinct SAMD9 variants) were analyzed by TEM with a standardized protocol. The authors described the presence of disease-specific features, including ones previously reported and the others (increased pinocytosis and budding in early endosomes) that are novel. These observations suggest that the endosome-lysosome system is not only morphologically but also functionally abnormal. The extended data of this article contain a large number of images, which is highly appreciated as a very useful resource for researchers.\nMinor comments\n(SAMD9) in the title necessary? I think all three patients had typical MIRAGE syndrome.\n\nPatient 1 in this paper is the same person as Patient 4 in JCI 2017? Patient 2 is this paper is the same person as Patient 6 in JCI 2017?\n\nCells derived from Patient 3 are unreported?\n\nIt would be easier to understand if you clarify the relevance of JCI 2017 and this paper in the Methods section. Did you thaw the frozen stored cells and re-prepare the TEM samples? Or is this a re-observation of a previously prepared TEM samples that were in storage?\n\nAll results presented in this study are qualitative. If possible, I think objectivity in the features would be increased if there is something that can be evaluated quantitatively, such as the number and size of organelles per field of view. (If it is difficult, I think it is acceptable to leave it as it is now)\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": "11018",
"date": "13 Apr 2024",
"name": "Federica Buonocore",
"role": "Author Response",
"response": "We thank Dr Narumi for providing his review report. We have addressed the comments below. 1. (SAMD9) in the title necessary? I think all three patients had typical MIRAGE syndrome. We included SAMD9 in the title to increase the changes of the paper being captured by a search engine, but we agree this seems out of place without further details, and the paper should be accessed through the abstract and keywords. Thus, we have omitted SAMD9 from the title. All three patients had MIRAGE syndrome, although the phenotypic spectrum can be wide. 2. Patient 1 in this paper is the same person as Patient 4 in JCI 2017? Patient 2 is this paper is the same person as Patient 6 in JCI 2017? Cells derived from Patient 3 are unreported? In this paper, patient 1 refers to patient 4, patient 2 refers to patient 6, patient 3 refers to patient 8 in our original study published in JCI 2017. Fibroblasts from all three patients were included in our cell structure (TEM) and endosome (early Rab5a and late endosomes Rab7a) studies, but the TEM images from patient 3 were not included in JCI 2017 due to space constraints, and only very limited data from patients 1 and 2 were shown. We have clarified in the methods section (“Samples”) how the current labelling links to the original report. We now make all these original lower magnification TEM images from JCI 2017 available for all three patients, as well as the new higher magnification TEM images that were generated specifically for this current report (see point 3 below). 3. It would be easier to understand if you clarify the relevance of JCI 2017 and this paper in the Methods section. Did you thaw the frozen stored cells and re-prepare the TEM samples? Or is this a re-observation of a previously prepared TEM samples that were in storage? Thank you for this comment. Patients’ fibroblast TEM samples were re-imaged using the original TEM samples kept in storage. Higher magnification and more images were taken in order to better analyse ultrastructural features. We have now also made extensive original images available through the Open Science Framework link (2017 Electron Microscopy Images) (the current ID system has been used for consistency). We have clarified the methods to say: “For the original preparation and analysis of the samples, fibroblasts were detached from culture flasks…….\" We have now added a subsequent paragraph to the methods sections to clarify: “In the current study, patient and control fibroblast samples prepared for TEM for our original work detailed above2 were re-imaged using higher magnification. The aim of this approach was to better analyse a range of ultra-structural features and organelles in more detail, and to make these images (n=78) available as well as the of original set of generally lower magnification TEM images (n=80).” The Data Availability Statement has been modified to read: “OSF: Investigating ultrastructural morphology in MIRAGE syndrome-derived fibroblasts using transmission electron microscopy. https://doi.org/10.17605/OSF.IO/Z8WVE25. This project contains the following extended data (2023 Electron Microscopy Images) (n=78): Control (19 .TIF files) Patient1 (19 .TIF files) Patient2 (19 .TIF files) Patient3 (21 .TIF files) Data are available under the terms of the Creative Commons BY (CC-BY) 4.0. Original images taken in general at lower magnification have now also been uploaded (2017 Electron Microscopy Images) (n=80).” 4. All results presented in this study are qualitative. If possible, I think objectivity in the features would be increased if there is something that can be evaluated quantitatively, such as the number and size of organelles per field of view. (If it is difficult, I think it is acceptable to leave it as it is now) Thank you for this point, which is also raised by Reviewer 3. We agree it would be good to be able to count, measure and characterise features of organelles to be able to quantitate them in more detail. However, this is well-established as being challenging as TEM is 2-dimentional and it can be difficult to accurately define some of the subtle features we report even with large number of images, such as vesicle chains and differences in endoplasmic reticulum. Currently there is much interest in developing artificial intelligence/machine learning approaches for TEM characterisation, but these approaches require large numbers of samples and datasets, and processing. Unfortunately, this is beyond the scope of this current study."
}
]
},
{
"id": "162985",
"date": "27 Feb 2023",
"name": "Timothy S Olson",
"expertise": [
"Reviewer Expertise MIRAGE Syndrome. Pediatric MDS Predisposition Syndromes. Bone Marrow Failure"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nBuonocore and colleagues present a reanalysis of Electron Microscopy samples derived from primary fibroblasts of 3 patients with MIRAGE syndrome originally published in their 2017 J Clin Invest report. In this prior report they had concluded that the endosomal abnormalities identified in MIRAGE fibroblasts by other investigators (Narumi, 2016, etc.) were not a consistent feature in their samples. However, using different prep techniques and a co-author with extensive EM analysis experience, they now conclude that Narumi and colleagues were correct in identifying increased endosomal activity and number, as well as large late endosome/lysosome structure as a characteristic feature of MIRAGE.\n\nComments:\nThis study presents a reanalysis of EM studies that have been previously published, and essentially refute the interpretation of these studies that was published in 2017. While I think this update is indeed critical to provide, since it does not involve analysis of new samples or by new techniques and is rather a reinterpretation of the previously published EM studies, this reviewer wonders whether these updated data would be better to include as an erratum to the original study, rather than as an independent report. If the authors feel differently, they should comment as to why these data represent sufficient originality that they should be considered as an independent report.\n\nHave the authors studied EM appearance of fibroblasts from patients with SAMD9/SAMD9L mutations who lack syndromic features of MIRAGE? Do such samples still show endosomal abnormalities, or are those abnormalities characteristic only of a MIRAGE phenotype? What about GoF versus LoF mutations, both of which are associated with MDS, though at distinct ages?\n\nNo source of the control fibroblasts is provided. Healthy individual? Age-matched? Cell line? How can the control cell have an irregular nuclear envelope (page 4) if it is in theory a normal cell? Is the irregularity artefactual based on the EM prep?\n\nIn the discussion, the authors suggest that the EM prep used in the original study was to fix the fibroblasts after pelleted and before placement on a slide, whereas other investigators have plated live fibroblasts on slides first and then fixed. I'm confused as to which technique was used in the current study, and whether difference in technique can explain why the current study confirms the work of Narumi et al., whereas the previous 2017 work from these investigators saw only mild endosomal abnormalities.\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": "11019",
"date": "13 Apr 2024",
"name": "Federica Buonocore",
"role": "Author Response",
"response": "We thank Dr Olson for providing his review report. We have addressed the comments below. 1. This study presents a reanalysis of EM studies that have been previously published, and essentially refute the interpretation of these studies that was published in 2017. While I think this update is indeed critical to provide, since it does not involve analysis of new samples or by new techniques and is rather a reinterpretation of the previously published EM studies, this reviewer wonders whether these updated data would be better to include as an erratum to the original study, rather than as an independent report. If the authors feel differently, they should comment as to why these data represent sufficient originality that they should be considered as an independent report. Thank you for this point. In our J Clin Invest publication in 2017 we did report endosomal abnormalities, but these were not as marked as shown by Narumi and colleagues and we did not see the massively enlarged endosomes reported by them. For example, we stated in: a) Fig 6a and legend- “Electron microscopy of fibroblasts from controls and patients showed a modest increase in the number and size of cytoplasmic vesicles (V) and mildly dilated rough endoplasmic reticulum (ER) in a small subpopulation of patient cells, but the effects were very heterogeneous” b) Supplementary Fig 7 - data c) Fig 6c and 6d and legend – (Using Rab5a to show early endosomes and Rab7a to show late endosomes in cultured fibroblasts) “Early endosome volumes were greater in fibroblasts from patients 6 and 8 compared with controls, with greater variability in patients’ samples.”……..” A distribution analysis of early endosome volume for all cells studied also showed a shift toward larger early endosome volume for patients 6 and 8.” d) Results - SAMD9 mutations produce subtle changes in early endosome size. Electron microscopy of patient fibroblasts compared with control cells showed that a small subpopulation of patient cells contained multiple large vesicles (>1.5 μm) as well as dilated endoplasmic reticulum and enlarged mitochondria, but these changes were heterogeneous, and extensive areas of cytoplasm containing large vesicles were not seen (Figure 6, A and B, and Supplemental Figure 7). No marked differences in late endosome structure were seen between patient and control fibroblasts (Figure 6B, green structures). A modest increase in the size of early endosomes (red structures) was identified in 2 of the patient cell lines (patients 6 and 8), as shown in representative images (Figure 6B) and in quantitative analysis of early endosome size (Figure 6, C and D).” To clarify this point in context we have changed the introduction from: “Two studies have reported characteristic enlarged endosomes in skin fibroblasts derived from MIRAGE patients, including “giant” endosomes in some cells1,5. These authors proposed that endosome dysfunction results in reduced recycling of epidermal growth factor receptor (EGFR), with consequent decreased cell growth and proliferation1. We have also observed somewhat larger vesicles in our patients’ fibroblasts using transmission electron microscopy (TEM) imaging and Rab5a and Rab7a as early- and late- endosomal markers respectively, in live fibroblast cultures2. However, these TEM studies were only reviewed at low power and in limited sections, and more detailed high-power imaging was not undertaken.” to: “Two studies have reported characteristic enlarged endosomes in skin fibroblasts derived from MIRAGE patients, including “giant” endosomes in some cells1,5. These authors proposed that endosome dysfunction results in reduced recycling of epidermal growth factor receptor (EGFR), with consequent decreased cell growth and proliferation1. We have also observed somewhat larger vesicles in our patients’ fibroblasts using transmission electron microscopy (TEM) imaging and Rab5a and Rab7a as early- and late- endosomal markers respectively, in live fibroblast cultures2. Massively enlarged or giant endosomes were not seen. Of note, these TEM studies were only reviewed at low power and in limited sections, and more detailed high-power imaging was not undertaken.” The aim of the study presented here is to make a larger dataset available of TEM images from SAMD9-MIRAGE fibroblasts, that show a wider range of ultrastructural morphology. We feel sharing any data available for this rare condition is important. We have also added a comment to the results that “No giant endosomes were seen” (Note: The co-author with extensive experience of TEM (Dr Glenn Anderson) was a co-author on the original study too.) 2. Have the authors studied EM appearance of fibroblasts from patients with SAMD9/SAMD9L mutations who lack syndromic features of MIRAGE? Do such samples still show endosomal abnormalities, or are those abnormalities characteristic only of a MIRAGE phenotype? What about GoF versus LoF mutations, both of which are associated with MDS, though at distinct ages? We have not had an opportunity to do this and cannot easily take this forward. It is an interesting and important point and we have added a comment to the discussion. Thank you for raising this. “It would be of interest to study cellular ultrastructure from individuals with other gain-of-function or loss-of function changes in SAMD9, who do not have classic MIRAGE syndrome features, to see if similar changes are seen there too.” 3. No source of the control fibroblasts is provided. Healthy individual? Age-matched? Cell line? How can the control cell have an irregular nuclear envelope (page 4) if it is in theory a normal cell? Is the irregularity artefactual based on the EM prep? Control fibroblasts were derived from a healthy individual. We have added “healthy” to the fibroblasts’ method section. These control fibroblasts are routinely used in our lab for several different experiments. A convoluted nuclear envelope provides an increased area of contact between the nucleus and the cytoplasm and may suggest heightened metabolic activity. In our samples, the nuclear outline was very smooth with fairly dispersed diffused chromatin pattern. This is linked to cell growth and it is not an atypical nuclear envelope. We understand that the word “irregular” might be confusing, so we have now changed this to “convoluted”. We feel that the nuclear envelope is within normal range for the control and MIRAGE samples. Therefore, we have changed the results and discussion to say “convoluted” instead of irregular, and the Figure 4 legend to: “Nuclei (N) had a convoluted nuclear envelope, with a marginated chromatin pattern in both control and patients’ cells, within normal range.” Finally, one co-author (G.A.) has many years’ experience of specialist diagnostic and research electron microscopy and leads the clinical service. He therefore provides extensive insight for the range of typical findings seen in fibroblast TEM, even though we provide data on just one control sample. 4. In the discussion, the authors suggest that the EM prep used in the original study was to fix the fibroblasts after pelleted and before placement on a slide, whereas other investigators have plated live fibroblasts on slides first and then fixed. I'm confused as to which technique was used in the current study, and whether difference in technique can explain why the current study confirms the work of Narumi et al., whereas the previous 2017 work from these investigators saw only mild endosomal abnormalities. In the current study we have used slides from fibroblast preparations that we also used in the “original study” published in 2017. The method we have used is the traditional ultrathin-section EM, as we describe in the methods section and briefly in the discussion. No new fibroblasts have been prepped in the current study. Potentially, the preparation method can result in structural variability. We feel this is reduced by the method reported, as outlined in the discussion. We have extensive experience of this approach."
}
]
},
{
"id": "162986",
"date": "19 Jun 2023",
"name": "Sushree Sangita Sahoo",
"expertise": [
"Reviewer Expertise bone marrow failure",
"myelodysplastic syndromes",
"HSC biology",
"experimental hematology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nBuonocore and colleagues present a research article titled \"Investigating ultrastructural morphology in MIRAGE syndrome (SAMD9)-derived fibroblasts using transmission electron microscopy\". The authors have provided a detailed description of SAMD9 patient fibroblast ultrastructure using TEM. In addition, the authors have outlined all specific cellular organelles with major or minor changes, and concluded that SAMD9 patient fibroblasts have increased endosomal activity. The paper's contents are interesting and will be helpful for researchers to focus on the outlined cell organelles to understand the physiological relevance of SAMD9 mutations. However, I have a major concern that the authors do not provide any statistical tests to delineate the mutant-specific cellular differences, especially for their increased endosomal conclusion.\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": "11020",
"date": "13 Apr 2024",
"name": "Federica Buonocore",
"role": "Author Response",
"response": "We thank Dr Sahoo for her comments. Quantification of early endosome volume was provided using transfection of Rab5a in the original J Clin Invest manuscript 2017, and shown to be statistically significantly larger for fibroblasts from two patients (6 and 8). As highlighted in response to Reviewer 1, we feel that TEM analysis is still very qualitative. We have looked at options for better quantification, but this really needs 3-D reconstruction and modelling that is not yet widely available, nor possible here. Our aim here is to provide more extensive TEM image data from the samples we have for the research community, and to show a greater range of changes in ultrastructural morphology in patient fibroblasts."
}
]
}
] | 1
|
https://f1000research.com/articles/12-155
|
https://f1000research.com/articles/12-407/v1
|
17 Apr 23
|
{
"type": "Brief Report",
"title": "A Lorentz variant theory that passes fundamental tests of special relativity and makes diverging, testable but as of yet untested predictions",
"authors": [
"Daniël Bischoff van Heemskerck"
],
"abstract": "Background: Tests of special relativity have been conducted over the past century with increasing accuracy and none have showed violations of Lorentz invariance. In this paper we will examine whether these tests are together sufficient to rule out theories that violate observational symmetry.\nMethods: A variant theory is outlined where relativistic effects such as length contraction and time dilation are purely local consequences of the relative velocity between a system and its medium. The outlined theory is tested against the fundamental tests of special relativity.\nResults: It is found that although this alteration does not align with the principle of relativity, it quantitatively aligns with the experimental results of the fundamental tests of special relativity and their modern variations, and makes diverging, testable but as of yet untested predictions concerning Doppler shift and time dilation.\nConclusions: These results warrant a closer theoretical inspection of the outlined theory, and could provide a direction to test for new physics. A modified Ives-Stilwell experiment is proposed to test between this model and special relativity.",
"keywords": [
"Special Relativity",
"Fundamental physics",
"Superluminal jets of matter"
],
"content": "Introduction\n\nAlthough all our physical theories are ultimately based on assumptions, some of our theories have been so predictive and well-tested that it’s easy to mistake their underlying assumptions for proven laws of nature. Perhaps the foremost example of this is the principle of relativity. Of course the principle is fundamental to both the special 1 and the general theory of relativity developed by Einstein in the early 20th century, as well as to Lorentz’ ether theory, 2 , 3 but even before that it had been an integral part of physics for almost three hundred years, being a cornerstone of Newtonian mechanics. The principle was formulated first by Galileo in 1632. In his ‘Dialogue Concerning the Two Chief World Systems’ 4 he argues one cannot measure absolute motion. Using a thought experiment concerning a ship that sails in uniform motion on a perfectly smooth sea, he showed that an observer below deck would observe all to be the same as when the ship had not been moving at all.\n\nExamining Galileo’s thought experiment we can say it is no coincidence that it took place within the ship as opposed to on deck. If the ship had been in motion relative to the medium of air it was sailing through, physical experiments conducted on deck would be affected by that relative motion. Of course one could still not ascertain if the ship was absolutely in motion or the air was, but there would be no observational symmetry between the reference frame at rest relative to the air and one in motion. Observational symmetry between two reference frames in relative motion seems to necessitate at least one of two conditions to be true: Either the medium surrounding the reference frames needs to be locally co-moving with the reference frames, or the reference frames need to be within a vacuum.\n\nIn this paper we will assume that there is no such thing as vacuum, but that every single part of is space if ‘filled’ with matter, so that every body may be considered to be surrounded by a material medium. If all space contains matter, all motion through space naturally influences observation. As such, the principle of relativity would not be a general law at all, only a special case that arises when special local conditions are met.\n\nIn essence the inquiry underlying this paper is simple. Could the relativistic effects we have directly or indirectly measured be caused not by the relative motion between a body and an observer, but by the relative motion between a body and its material medium?\n\n\nThe basic assumptions\n\nLet us assume there to be no empty space in our universe and also, ad hoc, that as the local velocity between a reference frame and its medium increases, quantities such as time, length and energy in that frame will differ in magnitude from the same quantities observed in a frame at rest relative to its medium by a factor of:\n\nWhere v is the velocity of a reference frame relative to its medium and c is the (unattainable) velocity of a zero mass system travelling through zero-mass space, as opposed to the Lorentz factor ( γ ) within the context of special relativity, 1 where v is the relative velocity between two reference frames and c the invariant speed of light in vacuum.\n\nIn special relativity relativistic effects could be called kinematic in nature, arising from the relative velocity between two space-separated symmetric reference frames. Following this alternative reinterpretation of the Lorentz factor, we should interpret relativistic effects as mechanical in nature, arising from the local relative velocity between a body and its medium. If we take for example time dilation, we could say that physically a clock, simply, is an oscillation of a material system. So when we increase the velocity of a clock relative to the material medium surrounding it, the clock’s oscillation is expected to be retarded. The higher the velocity of a system relative to the medium it is travelling through, the more resistance or inertia it encounters, the more the motions of a clock carried with it will be retarded. At very high velocities the effects on the system will be substantial, even if we consider the medium it’s traveling through to have such a low energy density that we would call it a ‘vacuum’.\n\nIn this paper it will be investigated whether we can assume the above and still align with fundamental tests of special relativity.\n\n\nAligning with experiments\n\nFollowing special relativity the null result of the Michelson – Morley experiment 5 can easily be explained. In a comoving frame the apparatus can be considered at rest, thus the beam travel times are the same.\n\nFollowing our assumptions the explanation is perhaps as simple. Regardless of their orientation with regard to any space-separated place in the universe, the conditions in both arms the light is travelling through are equal and every part of the apparatus can be considered at rest with regard to its medium. Therefore, the travel time of the split light remains the same and the light remains in phase.\n\nKennedy’s and Thorndike’s experiment 6 is much the same as Michelson’s and Morley’s. A similar kind of interferometer was used with the difference being that one arm was shorter than the other, and measurements were made throughout the year, to measure the possible effects of the (orbital) velocity of the apparatus relative to a luminiferous ether. This experiment returned a null result as well. It can be explained for by special relativity in much the same manner as Michelson – Morley type experiments.\n\nAgain, we also find a simple explanation for experimental results within the framework of our material universe. The lack of fringe shift is easily explained for by considering that the conditions in the apparatus are uniform regardless of the orientation or orbital velocity the apparatus.\n\nModern variations of Kennedy – Thorndike experiments 7 have confirmed the original with much greater precision, but they may be explained for in exactly the same way. We could continue improving the accuracy of Kennedy – Thorndike experiments for years to come, getting the same results with increasing precision and yet they would not allow us to differentiate between the special relativity and our alternative theory.\n\nIves and Stilwell utilized hydrogen canal rays, beams of positive ions, to test if the frequency of light emitted by particles travelling with high velocities would follow classical or relativistic theory.\n\nTheir experiments 8 , 9 did not return a null result. Michelson – Morley and Kennedy – Thorndike experiments could be explained for by any theory that supposes that the motion of Earth through the solar system does not physically influence the measurements made in our laboratories or any theory that supposes it does, but in a manner that prevents us from detecting it. Ives’ and Stillwell’s experimental results are much more solid evidence for special relativity (or Lorentz’ ether theory) because they align with relativistic Doppler shift as opposed to classical Doppler shift. 8 As such, they are direct, positive evidence for relativistic time dilation.\n\nDoppler shift, a change in the frequency of waves experienced by the receiver and the source of a signal that are moving in relation to each other can classically be described as such:\n\nWhere fr is the observed frequency of the receiver, vw is the speed of propagation of waves in the medium, vr the speed of the receiver relative to the medium, vs is the speed of the source relative to the medium and fs is the frequency observed by the source. The convention used here is that v is negative when source and receiver are approaching each other.\n\nLongitudinal Doppler shift in the context of special relativity can be described 10 as such:\n\nWhere β is the relative velocity between source and receiver in terms of c .\n\nIt shows the expression for observed Doppler shift in the context of our theory would have to be different from special relativity. For one, relativistic Doppler shift doesn’t allow for the source and receiver to approach each other faster than c , while our reinterpretation only limits local velocities. Secondly the reference frames of the source and the receiver are not interchangeable like they are in special relativity – they are uniquely dependent on local principle. More specifically, the time dilation a source or receiver experiences is a local phenomenon that relates to their velocity relative to their medium.\n\nA thought experiment concerning alternative Doppler shift\n\nLet us imagine a source and a receiver approaching each other through a medium. Both of them have some velocity relative to the medium they are moving through. Both the source and the receiver carry with them a Cesium atomic clock.\n\nThey have agreed to record the times at which they send and receive signals and compare these when they meet. To visualize this we could say the source will send a signal, or we could say the waves it emits will crest each 9.192.631.770 periods of its Cesium atomic clock. 11 As receiver and source approach or recede from each other the frequency of the signal the receiver measures blue- or redshifts because the distance and time between emission and measurement decrease or increase, following classical Doppler shift. But that is not all: as the source moves through the medium the Cesium atoms’ periods will be retarded compared to when it would be ‘at rest’ relative to the medium. For each second that seems to pass in the frame of the source 1/1−βs2. seconds would seem to pass in a frame locally at rest, where βs is the velocity of the source relative to the medium in terms of c . Thus the source’s local time, which dictates the frequency by which it sends and records its signals would be observed to be retarded by a factor of 1−βs2 , and the receiver would observe the frequency by which the source sends out wave crests to decrease by a factor of 1−βs2 .\n\nFurthermore, the receiver has its own local time dilation dependent on its own velocity relative to the medium. The higher the velocity, the more its own Cesium clock is retarded, and the higher it would observe the frequency by which the signals reach him (by a factor of 1/1−βr2 ). If receiver and source would meet and compare their logs of signals sent and received, it follows that their results would align with the equation:\n\nWhere:\n\n• fr= the frequency observed by the receiver\n\n• βw=vc or the velocity of the wave relative to the medium in terms of c\n\n• βr=vc or the velocity of the receiver relative to the medium in terms of c\n\n• βs=vc or the velocity of the source relative to the medium in terms of c\n\n• fs= the frequency observed by the source\n\nConditional equivalence Lorentz variant alternative and special relativistic Doppler shift\n\nEquation 3 converges to Equation 1 when considering non-relativistic velocities and it can be shown that it is exactly equivalent to Equation 2 if at least one of the source or the receiver can be considered ‘at rest’ relative to the medium:\n\nLet us consider a source in motion ( βs>0 ) relative to its medium and a receiver in and at rest relative to the same medium ( βr=0 ). We assume here that βw→1 so that:\n\nWhere β is both the local velocity of the source relative to its medium and the global relative velocity between source and receiver. When examining the ratio between the predicted Doppler shifted frequencies of special relativity and the Lorentz variant alternative we find:\n\nAnd if we consider a receiver in motion and a source at rest, so that βr>0 and βs=0 and again assuming that βw→1 , we can see that again Equation 2 and Equation 3 are equal:\n\nWhere β is both the local velocity of the receiver relative to its medium and the global relative velocity between source and receiver.\n\nConditional equivalent Doppler shift in arbitrary direction of motion\n\nEquation 1–6 are valid for cases where the velocity of source and receiver can be considered to be aligned with the line between source and receiver, or one could say parallel or antiparallel to the direction of motion of the signal being sent.\n\nSpecial relativity\n\nWithin the context of special relativity the observed Doppler shift when considering relative motion in an arbitrary direction can be described as 1 :\n\nWhere θs is the angle of the line between source - receiver with respect to the velocity of the receiver, as seen from a system of co-ordinates which is at rest relatively to the source.\n\nIf we instead describe the relation as seen from a system of co-ordinates which at rest with the receiver the equation is:\n\nWhere θr is given by the angle between the direction of the line receiver – source and the direction of the velocity of the source.\n\nLorentz variant alternative\n\nWithin the context of the Lorentz variant alternative theory discussed in this paper the more generalized form of Equation 3 is described as such:\n\nWhere cosθr and cosθs are the cosines of the angle of the velocity of the receiver or source relative to the direction of the line source – receiver and receiver – source respectively.\n\nLet βs=0 and βr>0 and βw→1 . The alternative theory describes it as such:\n\nWhere β. is both the local velocity of the receiver relative to its medium and the global relative velocity between source and receiver and γ a function of β .\n\nLet βr=0 and βs>0 and βw→1 . The alternative theory describes it as such:\n\nWhere β is both the local velocity of the source relative to its medium and the global relative velocity between source and receiver and γ a function of β .\n\nConditional equivalence\n\nWhen examining the relation between the angles utilized in special relativity (SR) and the alternative (ALT) one can see that θrALT=θsSR and θsALT=θrSR and thus in the case of a source at rest:\n\nAnd in the case of a receiver at rest:\n\nDue to the relativistic aberration of light the relation between cosθsALT and cosθrALT and consequently between Equation 12 and 13 is given by the equation 1 :\n\nInteresting to note is that when we set the angle to π/2 we obtain the transverse Doppler effect:\n\nWhere in the context of the alternative theory 1−β2fs is a more apt description, because it is the time dilation that the source experiences that is indicative of the change in observed frequency.\n\nGeneral inequality special relativity and variant Doppler shift\n\nWe can remark that up until now there’s a striking similarity between the predictions made by special relativity and the alternative. But this equivalence ceases to exist when considering (most) cases where both source and receiver can be considered in motion relative to their medium. The difference between the predictions of Equation 9 and those of Equation 7 or 8 becomes more and more pronounced as β, βr and βs approach c .\n\nAligning with Ives – Stilwell tests\n\nIves – Stilwell type experiments have been conducted throughout the years with increasing accuracy 12 – 14 but as far as the author knows up until now have always involved either a receiver or a source that could be considered at rest relative to the ‘vacuum’ medium surrounding it. They have thus not been able to differentiate between the alternative theory outlined in this paper and special relativity.\n\n\nOn superluminal velocities\n\nLet us imagine a layered cylinder of matter inside a rest frame medium in the context of the theory outlined in this paper. The outer layer moves with relativistic velocity relative to the ‘rest frame’ medium it is travelling through, and the inner layer is moving with relativistic velocity relative to the outer. Following our assumptions the inner layer would be able to achieve a super-c velocity relative the outer ‘rest frame’ medium, or an observer co-moving with it.\n\nOne might argue that this would allow us to observe superluminal velocities, and because we haven’t the outlined theory is disproven. But, already in 1851 Fizeau 15 proved that the refraction index of a medium, which is directly related to its energy density, is indicative of the effect of the movement of the medium on the passage of light going through it. Water drags light and other matter more than air does, which drags it more than a ‘vacuum’ does. This shows that in ordinary circumstances we would not observe ‘superluminal’ velocities for even if a ‘vacuum’ medium were to move with relativistic velocity relative to us, it would have a nigh zero effect on light passing through it. And considering the energy required to accelerate a medium of water such that the light passing through it reaches a global super-c velocity, it is clear why we don’t observe this every day on Earth.\n\nYet we might be observing something just like it in outer space on a regular basis, for example in so called relativistic jets of matter expulsed by active galactic nuclei. These jets of matter have apparent superluminal speeds of up to almost 10 times the speed of light, 16 with the innermost parts of the jets attaining the highest speeds while the outermost parts appear slower and are themselves propagating through and interacting with a constant pressure cocoon, either a very hot gas or a magnetized sheath. 17 In essence these jets are layered cylinders of matter, with the highest velocities achieved in the inner layers. Precisely the conditions in which you would expect to possibly observe superluminal matter such as light, following our theory.\n\nIt follows that Equation 9 is not complete. It still misses a term that would relate to the drag coefficient. We would expect the term to approach 1 for vacuum-like states, and to not be of great concern regarding experiments conducted in ‘vacuum’.\n\n\nTesting new physics\n\nTo test between the theory outlined in this paper and the special theory of relativity we would need to conduct experiments where both the source and the receiver can be considered to be in motion relative to their supposed medium with some velocity. The experiment would have to be conducted in such a way that we can assume the clocks of the source and receiver to be sufficiently exposed to the medium they’re travelling through.\n\nCuriously, although the predictions of the alternative theory diverge with those of special relativity, the convention currently used to ascertain the accuracy of Ives – Stilwell type experiments cannot be used to differentiate between the two.\n\nModern Ives – Stilwell tests 13 , 14 try to experimentally confirm the validity of special relativity’s prediction that:\n\nWhere fa and fp are the frequencies of the lasers propagating antiparallel and parallel to the ion beam and f1 and f2 are the rest-frame transition frequencies.\n\nThe most accurate Ives- Stilwell experiment that has been conducted up until now, by Botermann et al in 2014, 14 found experiment to align with special relativity’s prediction with an accuracy of α≤2,0×10−8 , where α=εββ2 and εβ=fafpf1f2−1\n\nSetting f1f2 to unity, we can show that in the case that if at least one of βr=0 or βs=0 is true, our outlined theory predicts εβ=0 just as special relativity, assuming βw→c :\n\nAnd:\n\nAs is to be expected considering faSR=faALT and fpSR=fpALT .\n\nFor the more general case where βr>0 and βs>0 it is necessary to employ Equation 3.\n\nConsidering that:\n\nIt shows that even in the general case the alternative predicts εβ=fafpf1f2−1=0.\n\nInterestingly, Ives-Stillwell type experiments do provide us with an upper limit of the value of c within the context of the alternative theory. Equation 19 assumes that βw→c and therefore βw=1 . Following the theory light would never physically be able to reach a velocity equal to c . Since βw≠c , an accurate enough Ives – Stillwell experiment would in theory be able to distinguish between special relativity and the alternative. Looking at the accuracy achieved in 2014, 14 |α|≤±2×10−8 , and assuming that the velocity of light in our ‘vacuum’ chambers is vlight=299.792.458m/s then it follows that vlight<c≤±299.792.461m/s.\n\n\nConclusions\n\nThis paper shows that by assuming that the universe contains absolutely no free space we can derive an ad hoc reinterpretation and slight alteration of the mathematical framework of the theory of special relativity, that is incompatible with both the postulates of special relativity and with the Galilean principle of relativity, yet can quantitatively account for all fundamental tests of the special theory of relativity.\n\nThe outlined model’s predictions diverge with special relativity’s regarding Doppler shift in most situations where both the source and the receiver would be considered in motion relative to their medium, but would exactly align with special relativity’s predictions otherwise.\n\nOf course, the basis of the argument needs to be more thoroughly examined before we follow it to its conclusions. A more thorough investigation is needed to ascertain if there are indeed no tests that have experimentally ruled out the outlined theory, and perhaps a more thorough theoretical examination of the outlined theory is in order. But as of now the idea outlined in this paper seems to show there could be a Lorentz variant theory that is not ruled out by the fundamental tests of special relativity that we have conducted up until now. We could however conduct modified Ives-Stilwell experiments to differentiate between them and to possibly probe for new physics.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nEinstein A: On the Electrodynamics of Moving Bodies. Ann. der Phys. 1905; 322(10): 891–921. Publisher Full Text\n\nLorentz HA: Electromagnetic phenomena in a system moving with any velocity smaller than that of light. Proceedings of the Royal Netherlands Academy of Arts and Sciences. 1904; 6: 809–831.\n\nPoincaré H: Sur la dynamique de l'électron. Rend. Circ. Mat. Palermo. 1905-6; 21: 129–175. Publisher Full Text\n\nGalilei G: Dialogue Concerning the Two Chief World Systems. Berkeley: University of California Press; 1967.\n\nMichelson AA, Morley EW: On the Relative Motion of the Earth and the Luminiferous Ether. Am. J. Sci. 1887; s3-34(203): 333–345. Publisher Full Text\n\nKennedy RJ, Thorndike EM: Experimental Establishment of the Relativity of Time. Phys. Rev. 1932; 42(3): 400–418. Publisher Full Text\n\nTobar ME, Wolf P, Bize S, et al.: Testing local Lorentz and position invariance and variation of fundamental constants by searching the derivative of the comparison frequency between a cryogenic sapphire oscillator and hydrogen maser. Phys. Rev. D. 2010; 81: 022003. Publisher Full Text\n\nIves HE, Stilwell GR: An experimental study of the rate of a moving atomic clock. J. Opt. Soc. Am. 1938; 28(7): 215. Publisher Full Text\n\nIves HE, Stilwell GR: An experimental study of the rate of a moving atomic clock II. J. Opt. Soc. Am. 1941; 31(5): 369. Publisher Full Text\n\nFeynman R, Leighton R, Sands M: The Feynman Lectures on Physics 34-6. Reading, MA: Addison-Wesley; 1963—1965.\n\nSI Brochure: BIPM.2019; p. 130.\n\nKündig W: Measurement of the Transverse Doppler Effect in an Accelerated System. Phys. Rev. 1963; 129: 2371–2375. Publisher Full Text\n\nGwinner G, Botermann B, Geppert C, et al.: Modern Ives-Stilwell experiments at storage rings: Large boosts meet high precision. Proceedings of the Sixth Meeting on CPT and Lorentz Symmetry. 2014; 180–183.\n\nBotermann B, Bing D, Geppert C, et al.: Test of Time Dilation Using Stored Li+ Ions as Clocks at Relativistic Speed. Phys. Rev. Lett. 2014; 113: 120405. Erratum Phys. Rev. Lett. 114, 239902(E) (2015). PubMed Abstract | Publisher Full Text\n\nFizeau H: Sur les hypothèses relatives à l'éther lumineux. Comptes Rendus. 1851; 33: 349–355.\n\nPorcas R: Superluminal motions: Astronomers still puzzled. Nature. 1983; 302(5911): 753–754. Publisher Full Text\n\nBlandford R, Meier D, Readhead A: Relativistic Jets in Active Galactic Nuclei. Annu. Rev. Astron. Astrophys. 2019; 57: 467–509. Publisher Full Text"
}
|
[
{
"id": "200395",
"date": "24 Nov 2023",
"name": "Roman Szostek",
"expertise": [
"Reviewer Expertise Special Theory of Relativity",
"Special Theory of Ether",
"Mechanics",
"applications of mathematics",
"cosmology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 deals with a very interesting topic, i.e. the mathematical study of a theory that is an alternative to the Special Theory of Relativity and the problem of testing such a theory.\nThe work is interesting. In my opinion, the article should be indexed, but after taking into account the following additions and corrections:\n1. I suggest that the author provide an explicit definition of the principle of relativity. In the 'Introduction' the author discusses this topic, but does not explicitly define the principle of relativity.\n2. In the chapter \"Michelson-Morley\" the author wrote:\n„Regardless of their orientation with regard to any spaceseparated place in the universe, the conditions in both arms the light is travelling through are equal and every part of the apparatus can be considered at rest with regard to its medium”.\nWhy \"can be considered at rest with regard to its medium\"? This statement requires further explanation.\nThe same explanation is necessary in the \"Kennedy – Thorndike\" chapter.\n3. On page 7 it says \"more pronounced as β, βr, and βs approach c\".\nThis statement requires more detailed comment. After all, β = v/c. If β approach c, this means that v approach c2. Is this really what the author means and what it would mean?\n4. In the section \"On superluminal velocities\" the author wrote:\n„Following our assumptions the inner layer would be able to achieve a super-c velocity relative the outer ‘rest frame’ medium, or an observer co-moving with it”.\nIt is unclear what the author means by \"super-c\". The author did not show the formula for summing the speeds in the alternative theory, so it is not obvious what the speed of the inner layer of the cylinder will be. That's why I think this part of the article needs clarification. The formulas for summing the velocities in such alternative theories were derived, for example, in the article [2], which I have provided below.\n5. The author should provide information about other articles that present research on the same topic.\nThere are other studies on relativism with a universal frame of reference, presented in the series of publications [1]-[4]. Numerous models with a universal reference frame have been derived that are consistent with experiments in which the speed of light was measured [1]. The article [2] presents an original method of deriving transformations for kinematics with a universal reference system. The article [3] explains the phenomenon of time dilation in relativistic theories with a universal frame of reference. The article [4] presents a proposal for a mechanical system for testing the Special Theory of Relativity and relativistic theories with a universal frame of reference (Special Theory of Ether).\n[1] Szostek Karol, Szostek Roman, The existence of a universal frame of reference, in which it propagates light, is still an unresolved problem of physics, Jordan Journal of Physics, Vol. 15, № 5, 457-467, 2022, ISSN 1994-7607, https://journals.yu.edu.jo/jjp/JJPIssues/Vol15No5pdf2022/3.html1 [2] Szostek Roman, The original method of deriving transformations for kinematics with a universal reference system, Jurnal Fizik Malaysia, Vol. 43, Issue 1, 10244-10263, 2022, ISSN 0128-0333, https://www.researchgate.net/publication/3688483932 [3] Szostek Roman, Explanation of what time in kinematics is and dispelling myths allegedly stemming from the Special Theory of Relativity, Applied Sciences, Vol. 12(12), 6272, 01-19, 2022, ISSN 2076-3417, https://www.mdpi.com/2076-3417/12/12/6272/htm3 [4] Szostek Karol, Szostek Roman, The concept of a mechanical system for measuring the one-way speed of light, Technical Transactions, Tom 120, No. 2023/003, e2023003, 1-9, 2023, ISSN 2353-737X, https://sciendo.com/pl/article/10.37705/TechTrans/e20230034\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? 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? Yes",
"responses": [
{
"c_id": "11012",
"date": "13 Apr 2024",
"name": "Daniël Bischoff van Heemskerck",
"role": "Author Response",
"response": "First of all I'd like to thank you for spending your valuable time to review my work, it is very much appreciated! 1. I have included a more explicit definition of the principle of relativity in the introduction. 2. You are completely right in that the assumptions regarding the dynamics between the medium and the apparatus or lack thereof should be more thoroughly explained. I have provided a more thorough explanation of the physical picture of the 'vacuum medium' that is assumed in my paper in the introduction, and explained why it is as natural to assume the medium is at rest with the apparatus as to assume it isn't in the Michelson Morley section. For the sake of completeness, I also included a section near the end of the paper which considers a scenario where the apparatus and the medium are not at rest, but their relative motion uniform regardless of Earth's orbit by considering gravity. 3. Perhaps as you suspected: A mistake on my part, I meant to say as β approaches 1, or v approaches c. Thanks for catching this mistake. 4. I have tried to explain more thoroughly what I meant by super-c velocities and have included some studies in the field to highlight the potential need for a theory that allows for global velocities that exceed the speed of light. I'm not sure if the transformations you've provided, their merit notwithstanding, could be extended without additional considerations to these superluminal jets, whose dynamics might not be well suited to be treated purely kinematically, although it might be an exciting topic for future work. For the sake of simplicity I would just want to state here that if we're relieved of SR's second postulate, we could in theory observe global velocities greater than the speed of light, but still we would expect there to be physical, local limits. Therefore these layered cylinders are places where we could expect to possibly observe these high velocities. Although of course, as you posit, even from the perspective of SR one could argue that c should not necessarily be treated as an universal, global limit. 5. Thank you for introducing me to your work! I have included a reference to your work on a physical explanation for time dilation, which I think is a very fundamental approach that aligns with the investigation in my paper, and should indeed be referenced. I have made a preliminary inquiry into formulating time dilation by treating a clock as an underdamped harmonic oscillator, whose damped frequency of oscillation is given by ω_1=ω_0sqrt(1-ζ^2) and the damping ratio ζ∝ v/c. When the relative velocity between the medium and the clock reaches c the oscillator becomes critically damped, and no longer functions as a clock, much like the light clock considered in your paper. Perhaps sometime we could discuss further. Thank you again for your time and consideration, DMF Bischoff van Heemskerck"
}
]
}
] | 1
|
https://f1000research.com/articles/12-407
|
https://f1000research.com/articles/12-911/v1
|
31 Jul 23
|
{
"type": "Research Article",
"title": "The attitudes and practices of United Arab Emirates consumers towards food waste: A nationwide cross-sectional study",
"authors": [
"Lynne Kennedy",
"Samir Safi",
"Tareq. M. Osaili",
"Ala Al Rajabi",
"Ayesha Alblooshi",
"Dima Al Jawarneh",
"Ahmed Al Kaabi",
"Fakhra Al Rubaei",
"Maitha Albreiki",
"Maryam Alfadli",
"Aseilah Alhefeiti",
"MoezAlIslam Ezzat Faris",
"Kholoud Allaham",
"Sameeha Junaidi",
"Moien AB Khan",
"Lynne Kennedy",
"Samir Safi",
"Tareq. M. Osaili",
"Ala Al Rajabi",
"Ayesha Alblooshi",
"Dima Al Jawarneh",
"Ahmed Al Kaabi",
"Fakhra Al Rubaei",
"Maitha Albreiki",
"Maryam Alfadli",
"Aseilah Alhefeiti",
"MoezAlIslam Ezzat Faris",
"Kholoud Allaham",
"Sameeha Junaidi"
],
"abstract": "Background: Reducing global food waste is an international environmental, health, and sus-tainability priority. Although significant reductions have been achieved across the food chain, progress by UAE households and consumers remain inadequate. This study seeks to understand the association between consumer attitudes, knowledge, and awareness relating to food waste practice of residents living in the UAE. to help inform policy and action for addressing this national priority. Methods: A cross-sectional study was conducted using a validated semi-structured online questionnaire through stratified sampling (n =1052). The Spearman correlation coefficient was performed to determine the correlations. Two independent regression analysis were used to determine the association between food waste practice with: 1) knowledge and awareness and attitude subdomains, and 2) sociodemographic characteristics. Respondents (n=1072) largely reflect the socio-demographic characteristics and population distribution across the seven Emirates. Results: As expected, a significant and negative correlation was found between food waste practice knowledge and awareness and overall attitude. The regression models showed reduced food waste practice was associated with better knowledge, personal attitude, financial attitude (first model), older age and fewer adults in the household (second model). We found a significant and negative association of personal attitude (a commitment, intention), financial attitude (cost-saving motivation), and (existing) knowledge of Food waste (FW) with practice of food waste, indicating that better knowledge about FW, personal attitude or financial attitude was associated with reduction in undesirable food waste practice. While awareness and emotional attitude (moral concerns) were positively and significantly associated with food waste practice (undesirable behaviour). Conclusions: Food waste poses significant challenges in the UAE, and addressing it requires a comprehensive understanding of the multifaceted factors influencing consumer behavior. By promoting knowledge, fostering positive attitudes, and considering socio-cultural factors, policymakers can develop effective strategies to reduce food waste in households and contribute to sustainable development goals.",
"keywords": [
"Household",
"Consumer",
"Food Waste",
"United Arab Emirates",
"Sustainable Development Goals",
"Environment",
"Culture",
"Incentivising Behaviour"
],
"content": "1. Introduction\n\nA precise measure of global food waste (FW) is difficult to obtain however according to a report by UNEP and WRAP, an estimated 931 million tonnes of food were wasted in 2019.1 An amount arguably sufficient to feed the world’s hungry and malnourished twice over.2 FW not only reduces the amount of food and drinking water available for human consumption but removes essential macro and micro-nutrients from the human food chain with severe consequences for human growth, development, and survival. FW therefore undermines the foundation of food and water security globally, highlighting the unethical distribution and consumption of finite planetary resources. FW is a major contributor to our global food-related carbon footprint3,4; causing deforestation, desertification, and depletion of natural land and water resources locally.5 FW contributes to greenhouse gas (GHG) emissions, and is therefore directly associated with climate change and global warming; as the largest waste component sent to landfill, FW decomposes anaerobically and produces methane, the greenhouse gas, which is reportedly a 25 times more potent pollutant to the ozone compared with carbon dioxide.3 The economic losses associated with FW for farmers, landowners, producers, and retailers are also considerable,6,7 reducing staple food supplies and foods for exports, a cost passed onto consumers. The environmental, economic, ethical, and social cost of FW to individuals, societies, and globally are therefore considerable. Furthermore, FW poses major challenges in terms of meeting global and multilateral commitments such as the 2014 Paris Climate Agreement and the United Nations (UN) Sustainability Development Goals (SDGs).8 Unless urgent action is taken to prioritise the reduction of household FW, especially in specific regions of the world, including the UAE, then global objectives to halve food waste by 2030 (SDG 12.3; Responsible Consumption and Production (SDG 12), will be unachievable. Moreover, as this year’s host country for COP 28, all of the world’s attention will be focused on practices in this region.\n\nThe United Arab Emirates (UAE) in the Middle East and North African region (MENA), has a population of almost ten million and globally is reportedly a leading producer of food waste (FW). Regionally the UAE is the third largest producer of FW, behind Saudi Arabia, which is five times larger than the UAE, and the largest and most populated country in the GCC, and then Egypt.9 With an estimated annual 95 kg food waste/per capita, the average UAE household generates some 923,675 tonnes of FW annually.10 The two Emirates of Abu Dhabi and Dubai have a combined food waste of approximately 12.84 million tonnes annually,11,12 equivalent to 1/130th of the previously estimated total annual global food waste (1.3 billion tonnes/p.a.).3 In response, the UAE government has declared urgent action to reduce its carbon footprint, setting ambitious targets towards achieving the SDGs by the year 2030.13 Policymakers have actioned its commitment to tackling food waste across the food chain (https://www.foodwastepledge.ae/), focusing on the consumer end stage where the greatest losses are known to occur. Considerable progress has been made within the hospitality sector in the UAE, with highly innovative and successful programs and initiatives reported (see below), however the hospitality sector only represents one of the two key elements of FW at the consumer end stage. Therefore, achieving the UAE’s target of reducing food waste by 50% by 2030 to meet the country’s food security strategy, and UN sustainable development goals, policymakers are now keen on targeting household food waste, where the amount of food waste is both significant and largely avoidable. This will require a shift in consumer behaviour, based on a greater understanding of the factors influencing food waste by consumers and households, including more reliable estimates of FW by households and individual consumers.\n\nThe terms food loss waste (FLW), food loss (FL) and food waste (FW) are all used interchangeably in the literature, however Food Loss is commonly used to refer to upstream losses, the reduced amount of edible food, quantity or quality, occurring during initial production, postharvest and processing stages of the food chain; whilst the term Food Waste, refers to any raw or cooked quality foods, including inedible items (i.e., skin, seeds, etc.) that is produced for human consumption, and then discarded at the procurement and consumption stages.11,14 For the present paper we focus on FW, however it is important to consider how FW relates to the wider elements of this concept. Lipinski et al. (2013), characterised the term FLW as occurring across the entire food chain, with amounts lost or wasted varying both by country and region, or by commodity (key food groups, bread, starchy cereals, fruits, vegetables, etc.). More importantly, whether FLW is classified further i.e., as FW or FL appears to be influenced by several factors, namely the characteristics of a population, a country’s stage of economic development (developed, developing) or measure of GDP, climate, and political stability. Low-income or developing countries for example are more likely to incur the greatest losses upstream, i.e. Food Loss (FW), at pre or post-harvest/pre-processing stages i.e. Food Loss, primarily due9 to issues relating to inhospitable climates, drought, water scarcity, inadequate storage and distribution infrastructures, war and civil unrest. In contrast, industrialised or developed countries, including countries in the MENA region, such as the UAE, typically experience the greatest food wastage at post-production – i.e. downstream loss, in the food retail and hospitality sector and at the household consumption stage. Almost a third (28%) of the FLW produced by developed countries, including the UAE, occurs at the consumption stage, and consists mostly as household waste, compared to just 7% consumer stage waste for developing countries.9 A level associated with food insecurity, a lack of available foods, and in response more frugal food management strategies. Many developed countries, particularly those located in the Northern hemisphere, have successfully implemented policies to reduce waste in the retail and hospitality sectors, and with some success in changing consumer behaviour, resulting in FWL at the consumption stage, similar to developing countries.\n\nThis is not the case however for some countries in the southern hemisphere, which have experienced increased development and affluence. Considerable progress has been made by the UAE government in addressing FW within the food retail and hospitality sectors. Upstream action directed at addressing FW, i.e. at the consumption stage of the food chain, including household food waste (HFW), is however an under-developed area.15 The UAE government has invested substantial funds to support multi-sectoral partnerships to create innovative and sustainable food waste solutions, with additional investment promised.16 One example, Winnow,17 has helped save an estimated three million meals associated with FW. Significant success with food repurposing efforts is also evident.18 Whilst this action is commendable, the savings are insignificant compared with the overall costs associated with downstream losses, i.e., FW, in the UAE, since the value-added lost to waste is the highest at the consumption stage; moreover, when approximately 90% of all food consumed in the UAE is imported the value-added losses are even more considerable and therefore critical to address. Thus, calls have been made for government and industry to partially shift some of the current emphasis on targeting hospitality and retail, to focus on the neglected component of FW arising at the household or consumer end of the food chain. Such calls have been echoed by other countries with similar FW profiles, i.e. countries that have experienced rapid economic development, such as Saudi Arabia and Qatar, who rely on importing the majority of its food. In order to effectively address FW in the UAE, a better understanding of consumers FW behaviour and the various factors influencing this is a fundamental requirement. As part of the present study, we have reviewed the FW literature, with specific reference to studies undertaken in countries similar to the UAE, in the MENA or Arab speaking region.\n\nRegardless of social context, FW at the household level (HFW) occurs at three stages, (a) after purchase but before preparation, (b) between preparation and serving, or (c) after serving (as leftovers).19,20 In each of these stages a variety of factors have been identified as influencing food waste and consumer’s behaviour, which in turn is directly influenced by a range of socio-demographic and environmental factors.21 All human behaviour including HFW is socially and culturally nuanced, so research aimed at understanding HFW must be socially situated, in order to provide insight into the sociocultural practices in that specific context. Moreover, the UAE is socially and culturally unique with an extremely diverse population; depending on the specific Emirate, 80-90% of the population are expatriates, originating primarily from India, Pakistan, Philippines, USA, Canada, and Western Europe, respectively. Some of these cultures, including Emirate households, typically cohabit with non-family members, as intergenerational families, whilst others live as smaller and homogenous units. Household composition affects how food is accessed, procured, stored, cooked, consumed, and wasted. In order to understand how the sociocultural context and demographic factors influence HFW in the Arab region, and the UAE specifically, we created a conceptual framework from HFW studies conducted in The Near East and North Africa (NENA) and MENA regions. There was a distinct paucity of studies pre-2010, before the establishment of the UN SDGs and calls22 for more research were made. In the past decade the number of published studies has increased, including several systematic reviews.7,23 The majority of these studies are undertaken in Egypt or Saudi Arabia with only limited research undertaken by the smaller Arab countries. This particular body of literature also examines a wide range of factors relating to HFW: levels of HFW; consumer or HFW practice (i.e. behaviours relating to or resulting in HFW) and the knowledge, attitudes, intentions, motivations, relating to HFW practice; household food management practices; and strategies associated with reducing HFW. More research is needed to increase understanding about consumer behaviour as it relates to HFW, including individual’s attitudes, beliefs, and motivations towards HFW behaviour, but especially studies specific to the UAE’s heterogenous population and socio-cultural context.\n\nIt is widely accepted that socio-cultural, economic, and socio-demographic factors are directly linked with HFW. Household income, size and composition are all acknowledged as key determinants of HFW24 as age, level of education, and income significantly influence intention to reduce food waste. Households in rural areas are likely to consume food prepared at home, compared with those living in urban areas who favour convenience, processed i.e. value-added foods and imported foods; being employed outside the home, or self-employed, is positively correlated with food waste; eating out and purchasing food on special promotion have been linked with regular and higher levels of FW.25\n\nUnderstanding consumer behaviour is also key to developing a better understanding of HFW and how to prevent or reduce this. Many attempts to understand consumer behaviour, in any area, have utilised behavioural theories as a conceptual framework, with varying success. Several Arab-based studies of HFW have used Ajzen’s (1991) Theory of Planned Behaviour (TPB). The basic theory of TPB is an explanatory or predictive model that hypothesises consumer behaviour is directly influenced by an individual’s ‘attitudes towards a particular behaviour’ (positive or negative evaluations of self-performance relating to a behaviour; the influence of ‘subjective norm’ or an individual’s response towards social pressure to conform, or significant others, to conform to particular behaviour; ‘perceived behavioural control’ or a belief in one’s ability to perform the (desired) behaviour (i.e. self-efficacy) and perceived behavioural control or the perceived ease of difficulty in behaving a specific way.26 For example, an individual’s motivation or intention to reduce FW might be determined by their predisposition towards waste control (subjective norm) i.e. whether society or significant others value FW avoidance behaviour. As one study in Tehran27 reported, the TPB was helpful in directing attention on factors influencing practice and they found that good food management skills (food procurement, food storage and handling, etc.,), may be a strong predictor of HFW behaviour; this however might be moderated by the trade-off between knowing what is considered socially acceptable (social norms) and confidence in their ability to adopt and carry out good management practices (self-efficacy). Whilst the TPB has been successfully used to help explain consumer behaviour in the field of FW, some researchers have found that the model only partially explains variations in participants behaviours. For example, Karim-Ghani et al., 2013, explained 13.7% of variation in consumers’ intention to adopt waste separation behaviour to avoid FW. Whilst Chalek et al. 2016, cited in Aktas et al. 2018, used TPB to help determine regional differences in FWL, estimating almost 65% of the variation between country-level food waste could be determined by gross national income.28–30 Researchers have argued that consumer management skills (CMS) and specifically food management strategies, directly influence FW behaviour, for example, consumers who make shopping lists are less likely to over-purchase31 whilst consumers who regularly over-purchase and buy more food than needed, are enticed by special offers and promotions and potential economies of scale from buying in bulk, are more likely to waste food, due to poor ‘food control management’ practices (FCM); this however may be moderated by certain attitudes for example anxiety relating to the cost of FW and feeling guilty as a result of over-buying, is negatively associated with household FW loss.32 With the latter found to be important in studies conducted in the Arab region, as mentioned below. Consumers who tend to adopt less healthy dietary patterns have been shown to positively influence FW, yet higher economic status may increase the relative frequency or occurrence of household food waste linked with over-purchasing behavior and food abundance due to increased affordability of food for high-income households.33 Since our initial review of the literature suggested a contradiction around affluence and financial attitudes, including food management behaviour, associated with cultural traditions around hospitality, we considered utilising TPB as a general framework, whilst also including focus on the wider socio-cultural literature on FW behaviour, particularly relevant in studies undertaken in the Arab region, and not restricting our study to this framework. The development of the present study was therefore influenced by the wider literature on FW practices and behaviour, values, beliefs, and attitudes across MENA.\n\nDiaz-Ruiz et al. (2018), identify six predictors of HFW: environmental awareness; materialism (consumerism); purchasing behaviour; dietary choice; attitudes towards waste recycling; and waste prevention.34 Abdelradi (2018) adopts this framework, extending this to include knowledge of food waste as a problem, personality traits and religion; this aligns with Elshaer et al. (2021) who posited that religion is a key predictor of adverse HFW in Saudi and therefore the wider Muslim region.35 One explanation for religiosity as a predictor of adverse FW behaviour is the importance of frugality, morality and altruism in religious codes,36 which reportedly contradicts with respondents aspiration to be perceived as a ‘good provider’, as a precursor to increased food waste. The cultural importance of Arab traditions rooted in food, hospitality and expressions of generosity may also accentuate the influence of religiosity as a determinant of HFW in the UAE and especially in countries where the population is predominantly Muslim; whereby people who have a positive and moral attitude towards the environment and the importance of food waste have a greater intention to reduce food waste, yet this contradicts with pressures associated with cultural traditions (hospitality). This aligns with Hedari et al. (2020), who suggested that this influence is developed through the effect on subjective norm and attitude, and waste-avoidance or prevention behavior may be a stronger predictor of intention to reduce household food waste than previously thought; therefore, interventions to reduce consumer food waste should concentrate on establishing waste avoidance attitudes.37 This concurs with a study conducted in the U.S.,38 whereby consumers who are aware of the consequences of food waste are also more receptive towards food waste reduction. Suggesting that considering the consequences of food waste, i.e. economic cost, needless hunger, and climate change, may encourage consumers to act sustainably and avoid waste. A sense of community has also been found to encourage food waste reduction, repurposing and recycling behavior. However, a study of youth in Pakistan suggests people who perceive they are excessively busy are significantly less likely to engage in the same food waste avoidance behaviors.38 Although knowledge, attitudes and practice influence the participants’ decisions in determining what types of food are appropriate for them and their families to consume and which foods should be discarded. Despite this understanding of food labels with respect to food shelf-life is limited amongst consumers, thus, more food than necessary is discarded.39 Having a strong sense of social responsibility, including particular religious values or environmental concerns, is also reported with conserving food and reducing food waste behaviours.40 Food-related practices (procurement, cooking, storage and consumption) of a household vary according to cultural values, beliefs and socio-economic status (SES) i.e., educational attainment, occupational and income status.41 Research also suggests that food waste may be higher in households where the woman is employed outside of the home42 and whilst women may traditionally stay at home, in the UAE, where the majority are expatriates, a high proportion of women are in employment.\n\nThe rapid societal and economic transition experienced by oil-producing Arab states, from traditional nomadic to wealthy industrialized societies, may compound consumer food waste behavior in countries such as the UAE. Baig et al. (2019), reported how HFW in Saudi Arabia, the leading producer of HFW regionally, is positively associated with economic affluence. In addition to cultural traditions (i.e. the need to express hospitality), widespread lack of awareness about issues relating to FW and the absence of policies targeting consumers to reduce FW, is believed to compound food waste behavior.43 As a study undertaken in KSA44 explains, how surplus food is classified as ‘unclean’ or ‘bayt’ by its people is an important determinant and predictor of HFW. This is especially relevant for families who eat from individual rather than traditional practice of communal plates. The sensory properties of food are key when deciding whether to use ‘bayt’ food (cooked food that is kept for at least one night). Leftovers are sometimes deemed unwanted because of the desire to avoid eating the same food on consecutive days. Although ‘bayt’ food is perceived as less desirable, it is considered edible and so it is haram (forbidden) to waste it. This raises a dilemma, in choosing enjoyment by serving fresh food vs. performing duties as Muslims by reusing edible leftover, or ‘bayt’, food. To escape the sin of waste, some interviewees reported passing unwanted food to their house staff or forcing themselves to eat it. During Ramadan meat-less surplus food becomes bayt and is unwanted because it is a ‘light’ dish. The authors also explain that rapid economic development, resulting in an affluent population has directly encouraged surplus generation and the attractiveness of leftovers. Where a preference for abundance and the multiplicity of choices, but also having the option not to consume leftovers, are related to this rapid rise in affluence. Social norms, as our data suggests, are more important than economic status in the rejection of surplus food. In Saudi, eating flavorless food was once common, today, however, it is no longer the norm to eat and serve such food – even amongst less affluent interviewees. Reliance on restaurants while eating outside the home during Ramadan also results in greater amounts of home-cooked foods being rejected. Whereas the fear and embarrassment of being criticized or bullied can deter some people from repurposing household food and taking leftovers to consume outside of the family home.44\n\nAs the current literature suggests many factors are involved in determining consumer food waste and encouraging food waste avoidance behaviour. These factors are also socially and culturally situated and therefore require context specific research. Efforts to reduce household food waste therefore require research that helps illuminate the determinants of FW behaviours, including knowledge and attitudes towards household FW, amongst consumers living in the UAE. The present study will address this by contributing to the understanding of consumer knowledge, attitudes and behaviours relating to FW in the region. Based on our review of the current FW literature in this region, we can assume that FW is positively associated with certain socio-demographic characteristics, such as age, social status and household income, including anxiety relating to food insecurity by low-income households; household composition, ethnicity; religious beliefs; cultural values; knowledge and attitudes towards food waste and food waste avoidance. FW behaviour is also likely to be directly influenced by consideration of social norms related to FW; consumers who adopt highly processed, less traditional middle eastern or Mediterranean dietary patterns are likely to be positively influenced to FW compared with those who adopt traditional dietary patterns and traditions, including acceptance for repurposing foods i.e. ‘bayt’; as is with lack of knowledge and awareness of food and nutrition labelling or the nutrition content of foods; and poor household food-management skills. As stated, the purpose of the present study is to provide much needed baseline data collected in the UAE on consumers attitudes, opinions, knowledge and practice (behaviours), relating to household food waste and is guided by the above conceptual framework.\n\n\n2. Methods\n\nA cross-sectional study was undertaken to collect data on household food waste knowledge, attitudes and practices (KAP) from people within the UAE. For inclusion, participants needed to be UAE residents aged 18 or above. The minimum sample size was calculated to be 637 with a population of 9.89 million, with a margin of error of 5%, 95% confidence interval (95% CI) and response rate of 40%.45\n\nTo obtain a representative sample of the population in the United Arab Emirates, a stratified sampling technique was employed. The population of the emirates was divided into three geographical areas: Abu Dhabi, Dubai, and the Northern Emirates. Each geographical area was considered a stratum. Participants were randomly selected from each geographical area in proportion to their population. To increase the representativeness of the sample with respect to households in the UAE, survey responses were collected from the UAE resident population in the three main zones: Abu Dhabi, Dubai and Northern Emirates. The survey was created using google forms. The survey was distributed via email and social media platforms to all participants. The survey was accessible via an anonymous link between 14th December 2021 and 8th February 2022. At the end of the study period, the survey was automatically disabled. Collaborators from each emirate collected the data to ensure that it was representative of the population. A question in the survey response inquired about the participants’ current residence.\n\nThe Social Sciences Research Ethics Committee (REC) from the United Arab Emirates University (UAE-U) approved the study (reference number is ERS_2021_8380). The study was conducted in accordance with Helsinki Declaration guidelines.46 Informed consent was obtained from all participants involved in the study prior to commencing the online survey. They were provided with clear and detailed information about the purpose of the study, the procedures involved, and how their data would be used and published. Participants were explicitly informed that their identities would remain confidential and would not be disclosed in any publications or presentations resulting from the study. The focus would solely be on the aggregated data and group-level findings, ensuring anonymity and privacy for each individual participant.\n\nThe design of the semi structured survey was informed by relevant existing validated questionnaires from the literature.7,35,47–51 Four experts from the field were requested to rate the questions on a scale of 1 to 10 for clarity, validity (ability to meet study objectives) and reliability. Any question which scored below seven on any aspect was removed. Feedback from the experts was addressed to strengthen the survey design. Reliability was tested using Cronbach Alpha. A reliable score of 0.80 was observed. The questionnaire was bilingual, English and Arabic; with forward and backward translation from English to Arabic undertaken by bi-linguists as per the methodology.52 The final survey, with Arabic translations, was piloted on 30 candidates for comprehensiveness and clarity. No major issues were received. The structure of the survey included a clear statement of the details of the study, necessary for informed consent, which was obtained from participants prior to starting the questionnaire. Participants were advised that they could exit the study by quitting the survey at any time, without consequence.\n\nThe questionnaire collected data on sociodemographic characteristics, and food waste knowledge, attitudes, and practices (KAP). For KAP-related questions, participants were asked to score their responses based on a five-point ordinal Likert scale which was later computed (mean) to estimate knowledge and awareness, attitude, and practice scores (Supplementary Table 1).\n\n2.4.1 Knowledge and awareness\n\nThe knowledge subdomain had two items while the awareness subdomain had a single item (Supplementary Table 1). Participants knowledge, and participants knowledge and awareness, were assessed by calculating the mean score of the two knowledge items and the three items of the knowledge and awareness subdomains, respectively. Higher scores reflected better knowledge and awareness regarding food waste (i.e. desirable behavior).\n\n2.4.2 Attitude\n\nValidated questions related to personal, emotional, behavioral, and financial subdomains of the attitude towards food waste were used and contained five, three, two, and four items, respectively (Supplementary Table 1).35,47,48,50 Participants ‘personal, emotional, behavioral, and financial attitudes were assessed by calculating the mean score of the items included in their respective subdomains. The overall attitude was assessed by calculating the mean score of all fourteen items included in all four attitude subdomains. Higher scores reflected better attitude regarding food waste (i.e., desirable).\n\n2.4.3 Practice\n\nThe practice domain had fifteen items (Supplementary Table 1), and their mean score was used to assess participants’ practice of food waste. Higher scores reflected worse practice of food waste (i.e., undesirable).\n\nData was analyzed using the statistical software Statistical Package for the Social Sciences (SPSS) (version 28).53 The mean and standard deviation (SD) were used to summarize continuous data. The mean percentage was calculated as a percentage of the maximum possible score. Categorical data were presented using frequencies and percentages. Spearman rank correlation coefficients were utilised to examine correlations between practice and each of knowledge and awareness, total attitude, and their subdomains. Furthermore, multiple regression model was used to examine the association of all independent variables (knowledge, awareness, personal attitude, behavioral attitude, emotional attitude, and financial attitude) with practice. In a separate analysis, multiple regression model was used to examine the association of sociodemographic characteristics (gender, age, number of adults in household, marital status, area of residence, number of children, educational level, and household income) with practice. The 95% confidence intervals (95% CIs) were used to determine the strength and direction of the associations. Type I error was fixed at 5% for all tests.\n\n\n3. Results\n\nA total of 1052 participants were included in the study. A total of 70.9% of participants were from Abu Dhabi, 17% from Dubai, and 12% from Northern Emirates (Sharjah, Ajman, Umm Al Quwain, Ras Al Khaimah and Fujairah). The distribution of the survey responses matches the distribution of the population and the area of the UAE (Supplementary Figure 1). The majority of participants were female (76%) aged between 18 and 30 years (58.2%) (Supplementary Table 2). The lowest response rates 1.3%, 6.6%, and 6.6% were received from ages 61-70, 51-60 years, and 41-50 years respectively. The most common household compositions reported by participants were homes of seven or more adults (25%) and two adult households (19.8%). Additionally, six (12.1%), five (13.6%), four (15.5%), three (10.1%) and one adult (4%) household occupancy were reported. Over half (54.8%) of the participants were single compared with 42.6% married. Whilst only 0.3% and 2.4%, were reported to be widowed or divorced, respectively. The majority of participants lived in the city (87.4%), while 7.3%, and 5.3% of participants living in towns and villages, respectively (Supplementary Table 2).\n\nNearly a third (27.5%) of participants lived in households without children, while 56.1% lived in households with 1, 2 or 3 children (19.9%, 18.7%, and 17.5%, respectively). A total of 17% of the participants lived in households with more than three children (four, five, or six children, 9.5%, 3.7%, and 3.1%, respectively). The majority of participants were reportedly educated to degree level, with most having undergraduate degrees (65.8%), whilst almost a quarter of the sample (23.3%) reported having postgraduate degrees and 8.7% had a PhD or higher. A minority (0.6%) reported having attained less than secondary school education, 1.7% less than high school education. Over half of participants (55.7%) reported basic middle income, 13.4% marginal middle income, 24.6% upper middle income, 2.4% lower income, and 4.2% upper income (Supplementary Table 2). The full anonymised dataset can be found under Underlying data.66\n\nIn Supplementary Table 3, we present the descriptive data and analysis of estimated self-reported food waste-related Knowledge and Awareness, Attitude, their respective subdomains, and Practice.\n\nAmong those surveyed, mean (95% CI) knowledge, awareness and knowledge and awareness combined were 83.00 (81.91- 84.10), 63.29 (61.92-64.65), and 76.43 (75.56-77.30), respectively. Mean (95% CI) personal, behavioural and emotional attitude “toward avoiding” food waste were all above 80% [84.32 (83.55-85.09), 87.60 (86.81- 88.40), and 83.95 (83.01-84.90), respectively], with mean (95% CI) financial attitude of 68.89 (68.26-69.53). Mean (95% CI) overall attitude was 80.56 (80.00-81.13). Practices of food waste had a mean (95% CI) of 19.92 (18.77-21.07).\n\nIn Table 1, we show the correlations between practice as a response variable and knowledge, awareness, knowledge and awareness, personal attitude, behavioural attitude, emotional attitude, financial attitude and overall attitude, as independent variables. The correlation coefficients indicate the strength and direction of the relationship between two variables.\n\n** Correlation is significant at the 0.01 level (1-tailed).\n\n* Correlation is significant at the 0.05 level (1-tailed).\n\nThe undesirable food waste practice was negatively and significantly correlated with (Spearman’s rho correlation coefficient, p-value) knowledge (-0.155, <0.001), knowledge and awareness (-0.123, <0.001), personal attitude (-0.303, <0.001), behavioural attitude (-0.237, <0.001), financial attitude (-0.165, <0.001) and overall attitude (-0.276, <0.001). The significance of all the correlations continued even after controlling for the effect of age, as shown in Table 1. This indicates that age did not have a significant impact on the observed associations between the variables. These results indicate that an increase in each of these variables (knowledge, knowledge and awareness, personal attitude, behavioural attitude, financial attitude and overall attitude) is correlated with a reduction in food waste practice. The correlation between practice and emotional attitude was not significant (-.051, 0.051), however; it reached significance after adjusting for age (-0.075, 0.015). Overall, the results suggests that better attitude, knowledge and awareness are correlated with reduction in food waste practice.\n\n3.4.1 Multiple Regression Models\n\nWe ran a multiple regression model to further clarify the associations of all independent variables (knowledge, awareness, personal attitude, behavioural attitude, emotional attitude, and financial attitude) with practice as the dependent variable (Table 2). Analysis of variance (ANOVA) for the multiple regression model indicated that at least one of the independent variables (the six subdomains) is significantly associated with the predictor variable (practice domain) (F=21.563, p-value <0.001; Supplementary Table 4).\n\n** Statistically significant at 0.01 level.\n\n* Statistically significant at 0.05 level.\n\nResults of the multiple regression models showed that (regression coefficient, p-value) knowledge (-0.077, 0.003), personal attitude (-0.282, <0.001), and financial attitude (-0.150, 0.001) were significantly and negatively associated with food waste practice, indicating that better knowledge, personal attitude, or financial attitude was associated with reduction in the undesirable food waste practice. While awareness (0.046, 0.021) and emotional attitude (0.074, 0.029) had positive significant association with food waste practice.\n\nWe ran a seperate multiple regression model to assess the associations of sociodemographic variables (gender, age, number of adults in household, marital atatus, area of residence, number of children, educational level, household income) with practice as the dependent variable (Table 3). Analysis of variance (ANOVA) for the multiple regression model indicated that at least one of the independent variables (sociodemographic variables) is significantly associated with the predictor variable (practice domain) (F=5.983, p-value <0.001; Supplementary Table 5).\n\n** Statistically significant at 0.01 level.\n\n* Statistically significant at 0.05 level.\n\nResults from the second multiple regression model (regression coefficient, p-value) indicated that being 18-30 years old is significantly and positively associated with higher food waste practice compared to those 51 years old and above (0.211, 0.046). In addition, having 1-3 (-0.247, 0.001) or 4-6 (-0.204, 0.001) adults in the household was associated with less food waste practice compared to households with 7 or more adults. No other associations reached statistical significance.\n\n\n4. Discussion\n\nUsing a nationwide cross-sectional survey of adults residing in the UAE, we recruited 1072 participants from the seven Emirates of the UAE. Approximately two thirds of the survey sample were collected from the Abu Dhabi Emirates, which represents the majority of the UAE’s land area and population distribution, while the rest came from other Emirates (Supplementary Figure 1). Our sample is skewed towards the most populated Emirates of Abu Dhabi and Dubai, (70.9%; 17% respectively), with only 12% of participants recruited from the five much smaller Northern Emirates, however this is representative of the geographic distribution. The majority of participants were single (55%), female (76%), aged 21-30 years (40%), living in households of multiple occupancy, with 7 or more adults, and living in the city (85%). A third of our sample lived in households without children, whilst most (56%) were small households, with 1-3 children; the educational attainment of respondents was above average, with two-thirds of participants educated to degree level, a further 23% and 8% achieving postgraduate or doctorate degrees, which is higher than expected in terms of the general population and suggests recruitment bias towards highly educated/skilled ex-pat workforce. Household income was also skewed towards middle income (55.7%) and upper middle income (24.6%) compared with just 2.4% for lower-income households. This may reflect above average ex-pat population in these two Emirates, and since we know that the UAE population is extremely diverse and heterogenous, is representative of the wider UAE population. Nonetheless, future surveys should seek to recruit a larger proportion of Arab and Emirati Nationals, living in Abu Dhabi and Dubai. In the absence of data on consumers and food waste within the UAE, our findings are still useful in highlighting potential trends and suggesting areas for further research.\n\nThe purpose of the present study is to explore the level of participants knowledge and awareness, attitudes, and practice of food waste (FW); and factors associated with FW. We found a significant and negative association of personal attitude (a commitment, intention), financial attitude (cost-saving motivation), and (existing) knowledge of FW, with practice of food waste, indicating that better knowledge about FW, personal attitude or financial attitude was associated with reduction in the undesirable food waste practice. While awareness (0.046, 0.021) and emotional attitude (0.074, 0.029) had a positive and significant association with food waste practice, as the undesirable behaviour.\n\nOur findings align with the wider literature on FW behavior, knowledge and awareness whereby the majority of respondents are aware that FW is an important issue. The mean for awareness (63.3%), as an important societal issue, was relatively high and also the mean knowledge (76%) about FW. Despite this however, our study did not find a significant association between awareness and FW avoidance. As one recent systematic review reported, studies undertaken in this region suggest that knowing FW is problematic, and should be reduced, is not necessarily the most important predictor of behavioral intention; the authors suggest that practice may be more influenced by negative attitudes towards FW by other family members; lack of food management skills; lack of storage facilities; inconvenience of storing leftover foods, such as large (bulky) packaging of food items, combined with limited storage space; lack of knowledge of food safety, spoilage and food-poisoning risks, as practical factors hindering consumer intention to reduce food waste.54 Additionally, in contrast to some researchers, we observed that concerns relating to guilt associated with food waste practice as measured by the domain emotional attitude, was not a significant motivator for behavior avoiding food waste in our sample. Nonetheless, personal attitude (domains relating to environmental concerns of food waste) was a significant motivator of practice, which concurs with.55 Given the current increased media and government attention towards the importance of reducing food waste and SDG 12 within the UAE, and as hosts of the forthcoming COP 28 meeting in 2023, we might reasonably expect to see a positive association with practice (i.e., reduced food waste). Further research is recommended to better understand how public attitudes towards environmental concerns may provide effective leverage, or not, in shifting food waste practice in the UAE context. Additionally, if awareness is not significantly associated with food waste avoidance, then identifying the salient elements of environmental or personal attitudes, associated with FW avoidance practice, may offer promising alternatives.\n\nAs our data suggests, practice - food waste was significantly and positively associated with younger age (18-30 years) and household composition (households of multiple occupation, with more than 7 adults). The reference categories in Table 3 are used as a comparison point to interpret the coefficients for the other categories. For example, the coefficient for Female is -0.013, which means that, on average, females practice 0.013 times less than males, after controlling for the other demographic variables, and the coefficient indicates a small, non-significant difference between the genders in terms of practice. Similarly, the coefficients for the age categories (Age: 18-30 and Age: 31-50) are compared to the reference category of Age: 51 and older. The coefficients for Age: 18-30 and 31-50 are 0.211 and 0.062, respectively, indicating that, on average, individuals aged 18-30 and 31-50 practice 0.211 and 0.062 times more than individuals aged 51 and older, after controlling for the other demographic variables. Similarly, the coefficient for number of adults in house 1-3 and 4-6 are -0.247 and -0.204, respectively, indicating that, on average, households with 1-3 and 4-6 adults’ practice 0.247 and 0.204 times less than households with 7 or more adults, after controlling for the other demographic variables. Thus, efforts targeting younger generations in the UAE, and smaller households are worth considering. Since many of the cultures represented in the UAE population are traditionally patriarchal, targeting men and involving elders as social influencers, could also be useful for designing effective public campaigns and community-based intervention strategies. According to the literature FW behaviour is significantly associated with good household food management skills, food service/provision knowledge and skills, effective procurement (shopping) and cooking skills, in addition to knowledge, and attitudes.42 Raising awareness and developing skills associated with avoiding FW could also target couples and households, rather than just women as the main homemakers.\n\nA better understanding of consumers’ shopping behaviours is important for addressing the issue of food waste. We found that financial attitudes were negatively associated with practice (food waste avoidance). In the UAE, as in other developed countries, increased accessibility, abundance and variety of foods available to consumers encourages people to purchase more food than they need.11,56 The literature suggests that overbuying of food is directly influenced by retailing offers, e.g., ‘buy one get one free’, multi-packs, however since the standard of living and average salaries, particularly amongst nationals who are supported financially by government, are amongst the highest globally, this may help explain why financial attitude was negatively associated with practice. Since the majority of people living in the UAE, especially ex-pats with higher degrees, as in this study, may not be overly price sensitive or price conscious, this may contribute negatively to over-purchasing and inadequate meal planning, leading to food waste. Failure to check expiry dates, or to estimate supplies needed, may also be a factor in the large volume of food waste, due to increased likelihood of food-spoilage24 especially because of the short shelf life of many foods in the UAE climate. Some consumers purchase daily to ensure they are eating fresh food; others gather food for the whole week, which tends to be wasted, with more than half (50-75%) of households globally disposing of meal leftovers.11\n\nUnderstanding the problem of food waste from a consumer perspective may offer opportunities to reduce high rates of food waste. A recent study in the UAE showed that 96% of participants agreed that food waste is a problem11 whilst many consumers regret wasting food. On the other hand, the literature suggests that many (60%) consumers do not believe that food waste is a serious issue since food is biodegradable.57 As our data suggests, personal attitudes (concerns about the environmental issues) was significantly associated with FW avoidance practice. So further insight into the importance of this domain is recommended. In line with our observation, previous research suggests that individual attitude has a significant effect on food wastage behavior. Attitude towards food wastage has been observed to be influenced by the cost of food (i.e. financial attitude), based on prior experience of household food scarcity (food insecurity), societal norms, identity of self as a ‘good provider’, whether food is convenient or homemade, who was responsible for preparing the food, or the ease with which the food could be stored.58,59 However, in contradiction to the “Theory of Planned Behavior”, we did not observe a clear and significant link between overall attitude and practice in our sample.\n\nIn order to address the problem of household FW in the UAE, it is evident that more research is needed to help understand consumer behavior and the factors influencing this, in the local context; Additionally, national policies and initiatives to influence consumer knowledge, attitudes and thus behavior are urgently required. Introducing information about the negative impact of food wastage in school curriculums may help educate children/youth and help encourage wider cultural shifts in FW behavior. Discussing the issue frequently on social media, newspapers or other multimedia channels would be a good reminder to the public. Government supported incentives/food banks/ competitions/cash rewards would also inspire the public to act. The awareness needs to be rigorous and planned in a manner that reducing food wastage becomes a permanent habit for at least some portion of the public.60,61 Our research suggests more effort needs to be targeted at influencing consumer attitudes towards food waste; including supportive education around improving consumer knowledge about the shelf life, storage, preservation and packaging of different foods, to help reduce waste through spoilage; better food provisioning strategies, especially to avoid over-purchasing of foods in excess of normal and physiological need.\n\nFuture investments could be made in technology that automatically informs the user about expiration dates, items currently in the refrigerator/at home, and suggest recipes to utilise the foods currently available at home etc. Studying country case studies which have successfully tackled food wastage could prove to be of great help to develop future action plans for the country.58,62 Building on the successful technological developments and mobile apps which help guide consumers to distribute excess food conveniently and safely to those in need are also promising, to help repurpose and distribute excess foods, thus helping to reduce household food waste.\n\nTo the best of our knowledge, this is the first study to look at consumer knowledge and practice relating to FW in the UAE and as such provides useful insight into this area and the factors influencing consumer behavior or intentions to reduce FW within this particular social and cultural context. A key limitation of the study relates to the challenges associated with sampling and recruitment. Since there is no formal postal service, even in major cities, the ability to survey households is restricted. This is not unique to the UAE and is an issue in similar countries in the MENA regions. Thus, researchers rely mainly on social media as a vehicle for disseminating surveys, or alternatively use personal contacts for convenience and snowball sampling. Governmental surveys and commercial survey companies exist, and could be approached to undertake a more representative national cross-sectional survey in the future. Nevertheless, with the intended outcome of the research and the types of factors used, such sampling with a minimal bias is considered acceptable.63 This selection bias was reduced by using an optimal sample size.64 A further limitation is the reliance on self-reported food waste behavior. Additionally, such self-reported food waste behavior might be subjected to social desirability bias by participants reporting what they consider morally acceptable instead of how much food is actually wasted.65 Based on our aims, it is not feasible to conduct an observational study of food behavior. As a result, we relied on consumer recalls of food waste over the past month. While the study has some limitations, including relying on self-reported food waste behavior, its findings have important implications for future research. In terms of practice, the findings suggest the need for targeted interventions and policies to address food waste in the UAE. Efforts should be focused on younger generations and smaller households, as they are more likely to waste food. Social influencers, particularly men and elders could play a key role in changing behavioral patterns through public campaigns and community-based interventions. Furthermore, interventions should focus on addressing consumer attitudes towards food waste, including environmental concerns and personal attitudes. It is also possible to reduce household food waste by increasing consumer knowledge about food storage, preservation, and packaging, as well as improving food provisioning strategies to prevent over-purchasing. Further, investing in technology, such as smart apps that provide expiration dates and provide recipes based on ingredients available, can help individuals better manage their food and minimize waste. Future studies should examine the coherence between self-reported and observational measures of behavior. In order to change food waste habits and behaviors, future research is needed to assess the impact of key determinants, attitudes, behaviors, and emotions.\n\n\n5. Conclusions\n\nFood waste knowledge, attitudes, and behavior were examined in a first nationwide study in the United Arab Emirates. Whilst we found that positive consumer attitude towards avoiding FW are positively associated with behavioral intention (behavior attitude), this was not a good predictor of FW behavior in our study. Practice may be better determined by other factors, including food management skills, such as better meal planning and shopping to reduce over purchasing, having a greater awareness or knowledge of food safety, particularly safe handling and storage of leftover foods to help avoid food poisoning, practical constraints such as limited storage, and strong cultural or religious values. FW also appears to be more prevalent amongst younger generations (adults aged 18-30) and houses of multiple occupancy. More research involving a larger, more representative sample is, however, recommended before targeting such groups. Instead, government and policy makers should urgently consider developing public health campaigns, to educate people on safe storage of foods and product shelf-life to significantly reduce household consumer food waste in the UAE. Food manufacturers might be involved in such initiatives or be encouraged to provide better labelling. In parallel, incentives to encourage food manufacturers, retailers and consumers to avoid FW caused by over-purchasing and excess food preparation are needed, since individuals alone are not responsible for the problem of FW. In addition to reducing the economic, ethical, and sustainability issues associated with food waste, and ensuring future food security, urgent action will be required if the UAE is to contribute to achieving global sustainability.",
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}
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[
{
"id": "225482",
"date": "14 Dec 2023",
"name": "Dalia Bedewy",
"expertise": [
"Reviewer Expertise educational psychology",
"social 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\nThis study seeks to understand the association between consumer attitudes, knowledge, and awareness relating to food waste practice of residents living in the UAE. to help inform policy and action for addressing this national priority. The aim of the study is clear, and the topic is demandingly important. The literature covers the socio-economic factors in a good way, however, a more detailed reflection to the psychological factors is neglected. Certain factors like compulsive buying attitude or other psychological factors could be included. The methodology and results are well presented; however, the conclusion needs to be more coherent.\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": []
},
{
"id": "225474",
"date": "08 Feb 2024",
"name": "Breda McCarthy",
"expertise": [
"Reviewer Expertise Consumer behaviour",
"food waste."
],
"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 presents research on consumers' attitudes and practices in relation to food waste in the United Arab Emirates. Since studies of food waste in this geographic location are limited, the study is important from a consumer, policy and industry perspective, as well as from a sustainability perspective.\nMinor changes are recommended.\nThe literature review is reasonable and the writing style is good.\nIt is recommended that the authors remove the words on page 3, that \"food loss and food waste are used interchangeably in the literature\" since this is not exactly correct. Further, the definition of household food waste, in several quality publications, does not include inedible items, so I suggest the authors clarify what definition of food waste they use for their study, and the definition of food waste given to respondents in the survey. Refer to the distinction made between avoidable and unavoidable food waste (Secondi et al., 20151; https://wrap.org.uk/resources/report/household-food-and-drink-waste-united-kingdom-2021-22, Parfitt et al., 2010). Most respondents would not see inedible food (egg shells, peelings) as food waste. Please reconsider the definition of food waste by referring to highly cited scholars in this field. It is also recommended that the scales used for the survey questions be given in the supplementary data section.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-911
|
https://f1000research.com/articles/11-1491/v1
|
12 Dec 22
|
{
"type": "Research Article",
"title": "General anaesthetics reduce acute lymphoblastic leukaemia cell migration and homing in vitro and in vivo via CXCR4 and osteopontin mediated mechanisms",
"authors": [
"Cui Jiang",
"Sara Gonzalez-Anton",
"Xiaomeng Li",
"Emma Mi",
"Lingzhi Wu",
"Hailin Zhao",
"Ge Zhang",
"Aiping Lu",
"Cristina Lo Celso",
"Daqing Ma",
"Cui Jiang",
"Sara Gonzalez-Anton",
"Xiaomeng Li",
"Emma Mi",
"Lingzhi Wu",
"Hailin Zhao",
"Ge Zhang",
"Aiping Lu"
],
"abstract": "Background: Acute lymphoblastic leukaemia (ALL) is the most common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of two commonly used general anaesthetics, intravenous propofol and inhalational sevoflurane, on the migration and homing of ALL cells in vitro and in vivo. Methods: NALM-6 cells were treated with propofol (5 and 10 μg/ml) or sevoflurane (3.6%) in vitro for six hours. Then, cells were harvested for flow cytometry analysis. For in vitro migration experiments, NALM-6 cells were pre-treated with propofol and sevoflurane for six hours before being loaded onto the upper chamber of a migration chamber and cells were collected in the lower chamber after six hours of migration. For in vivo adhesion assays, NALM-6 cells were pre-treated with propofol and sevoflurane before an adhesion assay was carried out. In in vitro experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL/6 female mice followed by intravital microscopy. Results: Both anaesthetics reduced in vitro migration, in vivo migration and in vivo homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to the nearest endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression. In addition, the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced by general anaesthetics. Those changes might result in the alterations in migration and homing. Conclusion: Together, our data suggest that both propofol and sevoflurane could reduce ALL migration and homing in vivo and in vitro via CXCR4 and OPN mediated mechanisms.",
"keywords": [
"General anaesthetics",
"Propofol",
"Sevoflurane",
"Acute lymphoblastic leukaemia",
"Migration",
"Homing"
],
"content": "Background\n\nLeukaemia is the most common cancer in children, accounting for approximately one third of all childhood cancers, and the vast majority of cases (78%) are acute lymphoblastic leukaemia (ALL). ALL is the main cause of death before the age of 20 in the young with cancer.1 During ALL treatments, patients repeatedly receive painful and anxiety-inducing procedures, including bone marrow biopsy, bone marrow harvest, insertion of central lines, and intrathecal chemotherapy. Young patients generally cannot tolerate these procedures under local anaesthesia alone and normally require general anaesthesia. Additionally, general anaesthesia is often required to facilitate radiotherapy procedures, to ensure immobilization in young children. Therefore, paediatric patients frequently receive anaesthetics when invasive procedures are essential for diagnosis, treatment, and disease monitoring throughout treatment cycles from the induction phase to the surveillance phase, thus providing several opportunities for anaesthetics to have potential effects (if any) on leukaemia cells.2,3\n\nIt has been long assumed that the behavioural and systematic effects of general anaesthetics are entirely reversible and that the central nervous system (CNS) and whole body completely recover once the anaesthetic agent is eliminated from the body. However, an increasing number of studies have shown that anaesthetics can cause long lasting effects. For example, our group firstly found that xenon (an inhalational general anaesthetic) protects the kidney against ischemia-refusion injury by upregulating hypoxia-inducible factor-1α (HIF-1α).4 Following this discovery, other inhalational general anaesthetics like isoflurane have been shown to enhance cancer malignancy by enhancing angiogenesis, migration, invasion, and proliferation in vitro.5,6 In line with in vitro findings, recent retrospective clinical data have shown an association between inhalational general anaesthesia and reduced long-term survival in cancer patients undergoing elective surgery.7 Taken together, this evidence suggests that anaesthetics used during procedures may affect cancer outcomes; however, this warrants further investigation.\n\nMigration, homing, and subsequent adhesion of leukaemia cells to a specific niche in the bone marrow are vital in leukaemogenesis, propagation of the disease, and chemoresistance. The chemokine receptor C-X-C chemokine receptor type 4 (CXCR4) and its ligand stromal-cell-derived factor 1 (SDF-1, also known as CXCL12) mediates the homing and migration process in ALL.8 Sipkins et al. demonstrated that B-ALL cells selectively homed to adhesion molecule E-selectin and SDF-1-expressing vessels via a CXCR4-dependent process. Disruption of the interaction between SDF-1 and CXCR4 inhibited the homing and migration process.8 Osteopontin (OPN) is an adhesive glycoprotein mainly secreted by osteoblasts and serves complex functions in bone marrow. Several isoforms of OPN exist in bone marrow due to cleavage by thrombin9 and are associated with different functions. In particular, thrombin-cleaved OPN could act as an adhesion molecule for leukaemia cells in the bone marrow.10\n\nWe hypothesized that general anaesthetics may affect the migration and homing of ALL cells by impacting CXCR4 and OPN-mediated mechanisms. The present study, therefore, aims to investigate the impact of two commonly used general anaesthetics (propofol and sevoflurane) on leukaemia cell homing and migration by using a well-established ALL cell line (NALM-6) in vitro and an engineered GFP-NALM-6 cell line in vivo.\n\n\nMethods\n\nHuman authenticated leukaemia NALM-6 cells, RRID:CVCL_0092 were cultured in T175 tissue culture flasks (VWR, Leicestershire, UK). They were maintained at 37°C in humidified air balanced with 5% CO2 in RPMI 1640 medium (GIBCO, Invitrogen, Paisley, UK) supplemented with 10% heat-inactivated fetal calf serum (Thermo Scientific, Epsom, UK), 2 mM L-glutamine and 100 U ml-1 penicillin-streptomycin (Invitrogen). Culture medium was replaced every day.\n\nBefore gas exposure, NALM-6 cells were cultured at 1 × 106 per ml density on 30 mm2 Petri dishes (VWR, Leicestershire, UK), or 24-well plates with a seeding density of 5 × 104 per ml. Cells were used 12 hours after seeding. Cells were placed in 1.5 L purpose-built airtight, temperature-controlled chambers equipped with inlet and outlet valves and an internal electric fan, which was used to provide a continuous delivery and mixture of gases. The chamber was connected to calibrated flow meters and an in-line vaporizer was used to deliver the desired composition (Datex gas monitor, Helsinki, Finland) of sevoflurane (3.6%, MAC 2.0) (Abbott Laboratories, Maidenhead, UK) in 21% oxygen and 5% CO2 balanced with nitrogen (BOC, Guildford, UK). The chamber was pre-flushed with the aforementioned gas mixture to ensure that a stable gas composition was achieved, and a closed system was established to prevent leakage. Gas treatment was given at the desired sevoflurane concentration for two, four, and six hours at 37°C. At the end of treatment, cells were harvested for further analysis. Cells used as the naïve control group were placed in an identical gas chamber containing 21% oxygen and 5% CO2 balanced with nitrogen at 37°C.\n\nA clinical formulation of propofol was used. It was dissolved in 10% intralipid (Astra-Zeneca, London, UK). On the day of the experiment, the stock solution of propofol was diluted with medium to the desired concentrations (5 and 10 μg/ml, equivalent to 28 and 56 μM, respectively). For the intralipid control (vehicle control), 10% intralipid was added to the cell medium to recreate the amount of intralipid in the highest (10 μg/ml) dose of propofol being used. Propofol-supplemented medium was added to the cell cultures for six hours. At the end of treatment, cells were harvested for further analysis. Cells used as the naïve control group were treated with identical medium with no propofol or intralipid.\n\nFor cell surface receptor experiments, leukaemia cells were incubated with CXCR4 (eBiosciecne, 17-9999-42, APC) and CD49d (eBioscience, 12-0499-42, PE) antibodies for 30 minutes at 4°C. After incubation, cells were washed with PBS and samples were run on a flow cytometer (CyAn ADP; Beckman Coulter, US). In addition, isotype controls were used to establish background fluorescence signals including: 1) mouse IgG2a kappa isotype control eBM2a (eBioscience, 17-4724-81, APC) and 2) mouse IgG1 kappa isotype control P3.6.2.8.1 (eBioscience, 12-4714-82, PE). In order to gate cells, the scatter plot of forward scatter versus side scatter was initially gated to have viable cells. Then, duplicates were excluded by plotting forward scatter height versus area. Finally, protein expression represented by mean fluoresce intensity (MFI) was recorded using a histogram. Each assay included 50,000 gated events. All samples were analysed via FlowJo software. For propidium iodide experiments, cells were stained with propidium iodide (e-Bioscience, 00-6990-50, PE-Texas red) and incubated in the dark at room temperature for 5 minutes. A count of 50,000 cells per sample were analysed with a flow cytometer (CyAn ADP; Beckman Coulter, US). In order to determine the cell death via propidium iodide, the scatter plot of forward scatter versus the PE-Texas was initially analysed in naïve control samples to determine the population of healthy cells. We determined any cells with an intensity larger than 102 in the PE-Texas red channel to be dead cells.\n\nIn vitro migration assay was performed by loading 2 × 105 pre-treated cells into the upper chamber of the migration chamber. Cells were allowed to migrate for six hours before being collected in the lower chamber. The lower chamber was supplied with 20 ng/ml SDF-1 as a chemoattractant. Finally, samples were run on a flow cytometer (CyAn ADP; Beckman Coulter, US) with Accu check counting beads (Thermo Fisher, PCB 100, UK) to determine absolute cell counts in each sample.\n\nNALM-6 cells were pre-treated with propofol and sevoflurane with respective concentrations. Recombinant human OPN (R&D systems, 1433-OP-050/CF) was thrombin-cleaved by incubating 24 μg recombinant full length human OPN in 20 mM Tris-HCL (pH7.6), 80 mM NaCl, 2 mM CaCl2, and 0.1 unit thrombin (Merck, 10602400001) for ten minutes at 37 degrees. Then, full length OPN and thrombin-cleaved OPN were coated at 20 μg/ml the night before experiment. Then, 5 × 105 cells of NALM-6 cells were labelled with calcein-AM stock solution from the Vybrant cell adhesion assay kit (ThermoFisher, UK). Pre-labelled NALM-6 cells were allowed to adhere for two hours under 37°C. Finally, fluorescence readings were read at 494 nm. The percentage of adhesion was determined by dividing the corrected (background subtracted) fluorescence of adherent cells by the total corrected fluorescence of cells added to each microplate well and multiplying by 100%.\n\nAll animal work was in accordance with the animal ethics committee (AWERB) at Imperial College London, UK and the UK Home Office regulations (ASPA, 1986). C57BL/6 female mice were purchased from Charles rivers UK Ltd with minimum age >6 weeks with weight around 20-22 g. All animals were allowed for 7 days of acclimation before procedures.\n\nPrior to procedures, animals were randomly allocated into three groups: 1) naïve control group, 2) propofol treated group and 3) sevoflurane treated group. In naïve control group, animals were given one million untreated GFP-NALM-6 cells through tail vein injection followed by intravital microscopy. In propofol and sevoflurane treated group, animals were given one million pre-treated GFP-NALM-6 cells (pre-treated with 10 μg/ml propofol and 3.6% sevoflurane for six hours in vitro, respectively) followed by intravital microscopy. On the day of experiments, we would normally do three intravital microscopy procedures in the order of 1) naïve control group, 2) propofol treated group and 3) sevoflurane treated group to minimise potential confounders. All members involved in the mouse study were aware of group allocations at all stages.\n\nInitially, 5 × 104 of NALM-6 cells were seeded in a 24-well plate. After 12 hours, TransDux and TransDUX MAX enhancer (System Biosciences, Palo Alto, USA) were mixed and added to culture at a concentration of 1X. Then, pre-packed GFP lentivirus (System Biosciences, Palo Alto, USA) was added to NALM-6 cells at a multiplicity of infection (MOI) of 20. Cells were incubated in 5% CO2 at 37°C for 72 hours. Finally, GFP-expressing NALM-6 cells were sorted using FACS Aria-II cell sorter (BD, USA), before seeding in a T175 flask with fresh medium.\n\nIntravital microscopy was performed using a Leica SP5 and a Zeiss LSM 780 upright confocal microscopes, both with a motorized stage.11 The SP5 was fitted with the following lasers: Argon, 546, 633 and a tunable infrared multiphoton laser (Spectraphysics Mai Tai 690-1020). The Zeiss LSM 780 was fitted with the following lasers: Argon, 561, 633 and a tuneable infrared multiphoton laser (Spectraphysics Mai Tai DeepSee 690-1040). The signal was visualized with a Leica HCX IRAPO L ×25 water immersion lens (0.95 N.A) and a W Plan-Apochromat ×20 DIC water immersion lens (1.0 N.A), respectively. Collagen bone second harmonic generation signal and GFP and CFP signals were generated through excitation at 840 and 870 nm and detected with external detectors. Internal detectors were used to collect DsRed and Cy5 signals (and on some occasions, GFP). Anaesthesia was induced in mice with 4% isoflurane mixed with pure oxygen. This was gradually reduced to approximately 1% as anaesthesia stabilised. Animals were randomly assigned to each group (naïve control, propofol treated, and sevoflurane treated).\n\nSurgery to attach the headpiece was then performed as described below.\n\n1) Sterile forceps and scissors were used to carefully remove the central portion of the scalp to expose the calvarium area to be imaged. Then, a small incision was made at the back of the head between the ears by lifting the skin up with the forceps. While holding the skin up, scissors were slid under the skin and gently cut along the outside of the desired imaging area.\n\n2) An adequate amount of dental cement was mixed in a weigh boat until it became a paste and it was quickly applied to the bottom surface of the headpiece that will attach to the skull.\n\n3) Before the cement set, headpiece was placed onto the skull of the mouse, making sure not to get any dental cement on the imaging area. Then, it was important to wait for it to set.\n\n4) The headpiece was attached to the holder and secured in place using the screw, ensuring that the grooves fit within the holder notches.\n\nLarge three-dimensional ‘tile scans’ of the entire BM cavity space were acquired by stitching adjacent, high-resolution z-stack images using a surgically implanted imaging window that ensures steady positioning of mice on the microscope. Time-lapse datasets were acquired by focusing on one area of BM. One image was taken every three minutes for a total of 22 images. Then, all 22 images were combined together to produce a movie (time-lapse). The calvarium has been demonstrated to be equivalent to the long bones such as the femur with regards to haematopoietic stem cell frequency, function, and localization, and is the only BM compartment that allows longitudinal imaging through minimally invasive surgery. Blood vessels were highlighted by I.V. injection of 50 μl of 8 mg/ml 500 kDa Cy5-Dextran (Nanocs, MA). After the intravital microscopy, all mice were euthanised via cervical dislocation.\n\nMicroscopy data was processed using multiple platforms. Tile scans were stitched using ZEN black, RRID:SCR_018163 (Zeiss, Germany) software. Raw data were visualised and processed using Fiji/Image J, RRID:SCR_00285 (National Institutes of Health, Maryland, USA). Cell tracking was performed using FIJI plugin MTrackJ. For accuracy in cell tracking data, videos were registered when required before using four-dimensional data protocols implemented in Fiji. Three-dimensional data rendering and measurement of cell distances were performed in Volocity, RRID:SCR_002668 (Perkin Elmer, MA, USA).\n\nThe sample size required for the experiments was estimated based on the results of preliminary data. Statistical differences between the means of two data groups were determined using two-tailed unpaired Student’s t-test, and p values<0.05 were considered statistically significant. Multiple group comparisons were performed using ANOVA with a Kruskal-Wallis nonparametric or Bonferroni’s post hoc test for comparisons GraphPad Prism 7.0, RRID:SCR_002798. A p value<0.05 was considered statistically significant.\n\n\nResults\n\nBefore assessing their effects on cell migration, cell toxicity of propofol and sevoflurane were assessed via propidium iodide staining. No cell death was detected in NLAM-6 and Reh cells after exposure to propofol and sevoflurane (Figure 1a-c).\n\na-b) NALM-6 cells were treated with intralipid, 10 μg/ml propofol and 3.6% sevoflurane for six hours. Cell viability was detected using through flow cytometry by propidium iodide-based assay. Data are illustrated as mean±sd (n=4). NC: Naïve control. VC: Vehicle control (Intralipid). c) NALM-6 cells were treated with 10 μg/ml propofol and 3.6% sevoflurane for six hours. Cell viability was detected through flow cytometry by propidium iodide-based assay. Images shown here are representative images selected from 4 repeats.\n\nWe investigated whether the migration of leukaemia cells was affected by general anaesthetics. An in vitro migration chamber was set up where 2 × 105 of NLAM-6 (pre-treated with propofol or sevoflurane for six hours) were loaded into the upper chamber and allowed to migrate for six hours to the lower chamber where 1 nM of SDF-1, a CXCR4 ligand, was applied. We observed that 10 μg/ml (56 μM) of propofol led to a significant reduction in the number of cells migrating to the lower chamber (almost a 50% decrease) (Figure 2a). Similarly, sevoflurane, on average, reduced cell migration to the lower chamber by approximately 35%, compared with naïve control (Figure 2a). Intralipid (vehicle control) had no effect on cell migration.\n\na) NALM-6 cells were initially treated with intralipid (VC), 10 μg/ml propofol and 3.6% sevoflurane for six hours. Then, treated cells were loaded into the migration chamber with 1 nM SDF-1 in the lower chamber as the chemoattractant. Cells were allowed to pass through migration chambers for six hours. Cells in the lower chamber were collected and counted in a flow cytometer. Data are shown as mean±sd (n=4). For propofol statistics, *p<0.05 vs naïve control (NC). ##p<0.01 vs vehicle control (VC). Data are analysed by one-way ANOVA followed by Bonferroni’s post hoc test. For sevoflurane statistics, *p<0.05 vs naïve control (NC). Data are analysed by unpaired t-test. NC: naïve control, VC: intralipid, P10: 10 μg/ml propofol, and Sevo: 3.6% sevoflurane. b) Intravital confocal calvarium imaging of GFP-transduced NLAM-6 cells (red) was performed after injection of GFP-NALM-6 cells into C57BL/6 mice IV. GFP-NALM-6 cells were pre-treated with either 10 μg/ml of propofol or 3.6% sevoflurane overnight in vitro prior to injections. Respective time-lapses were shown following IV injection of tritc-dextran to identify blood vessels (green); non leukaemia cells with high autofluorescent signals (blue) were recorded as well to improve the identification of target cells. Scale bar: 50 μm. Each position was imaged at three-minute intervals for 66 minutes. We only investigated the migration of cells in bone marrow. Cells in blood vessels were excluded from our investigations. Top row: Mouse injected with untreated cells (red). NC: naïve control. Middle row: Cells were pre-treated with 10 μg/ml of propofol overnight in vitro prior to injection. Bottom row: Cells were pre-treated with 3.6% of sevoflurane prior to injection. Displacement of each cell captured in all time-lapses was recorded. Data are pooled from 3 naïve control mice (N=3, 113 cells), 4 mice injected with propofol treated cells (n=4, 86 cells) and 4 mice injected with sevoflurane treated cells (N=4, 88 cells). Data are illustrated as mean±sd. For displacement data, *p<0.05, ***p<0.001, vs naïve control (NC). Data are analysed by one-way non-parametric ANOVA test (Kruskal-Wallis test). Propofol: 10 μg/ml of propofol and Sevoflurane: 3.6% of sevoflurane.\n\nMean speed of each cell captured in time-lapses was recorded. Data is pooled from 3 naïve control mice (N=3, 113 cells), 4 propofol pre-treated mice (N=4, 86 cells) and 4 sevoflurane treated mice (N=4, 88 cells). Data are illustrated as mean±sd. *p<0.05, **p<0.01, vs naïve control (NC). Data is analysed by one-way non-parametric ANOVA test (Kruskal-Wallis test). Propofol: cells were pre-treated with 10 μg/ml of propofol for six hours and Sevoflurane: cells were pre-treated with 3.6% of sevoflurane for six hours.\n\nIn order to validate our in vitro migration results, we set up a mouse model to study migration using intravital microscopy.12 In our model, we used immune-competent C57BL-6 mice instead of SCID mice for homing and migration experiments as it is a well-established model for non-maintenance cancer studies.13 GFP-NALM-6 cells (pre-treated with 10 μg/ml propofol or 3.6% sevoflurane for six hours) were injected intravenously. Then, intravital microscopy was performed. Only cells present in all time lapse images were tracked and included in our displacement analysis. In addition, cells inside blood vessels were not included in analysis. Displacements were calculated by adding all displacements in each time interval. The mean speed was calculated by averaging all mean speed recorded in each time interval. Our results showed that general anaesthetic pre-treated cells appeared to achieve smaller displacements compared to naïve cells, and their mean migration speed was also significantly reduced (Figure 2b). It was very obvious that after propofol and sevoflurane exposure, the number of fast-moving cells was significantly reduced (Figure 2b).\n\nAfter revealing that cell migration was reduced by general anaesthetics, we investigated whether the homing process was affected by anaesthetics specifically in terms of 1) homing location of cells (expressed by the distance between each cell to the nearest endosteal surface); 2) The number of cells entering bone marrow. Tile scan imaging (Figure 3a) of large areas of mouse calvarium bone marrow was carried out and the distance between each cell and the nearest endosteal bone surface was calculated. We used this distance as an indication for homing location. Cells in the blood vessels were not included in our analysis. Results showed that the average distance between a leukaemia cell and the endosteal bone surface was increased by propofol and sevoflurane, indicating disruption of the homing process (Figure 3b). Naïve control cells consistently move to locations approximately within 100 μm of the endosteal surface in bone marrow (Figure 3b). Presumably, this is a discrete region near vessels demonstrated previously,8 though the previous publication did not measure the distance between cells and the endosteal bone surface. After exposure to propofol or sevoflurane, a fair proportion of cells was found in locations further away from the endosteal bone surface (Figure 3b).\n\na) Upper left: diagram showing strategy for calvarium imaging.\n\nIntravital confocal calvarium imaging of GFP-transduced NLAM-6 cells (red) was performed after injection of GFP-NALM-6 cells into C57BL/6 mice IV. GFP-NALM-6 cells were pre-treated with either 10 μg/ml of propofol or 3.6% of sevoflurane prior to injection. Representative maximum projection tile scans and corresponding high-magnification inserts were shown following IV injection of tritc-dextran to identify blood vessels (green); non leukaemia cells with high autofluorescent signals (green, spotty signal) were recorded as well to improve the identification of target cells. Higher magnification images show portions of low magnification tile scans. Scale bar: 500 μm for low magnification tile scan. 50 μm for high magnification images. b) The distance between the nearest bone surface (not shown) and each GFP-NALM-6 cell was measured. Data illustrated as mean±sd. Data are pooled from 4 naïve control mice (N=4, 279 cells), 4 mice injected with propofol treated cells (n=4, 134 cells) and 6 mice injected with sevoflurane treated cells (n=6, 366 cells). *p<0.05 vs naïve control (NC). Data are analysed by one-way non-parametric ANOVA test (Kruskal-Wallis test). c) We calculated the number of cells enter bone marrow space from IVM images for each treatment group. Data are illustrated as mean±sd. Data are pooled from nine naïve control mice, eight mice injected with propofol pre-treated cells and six mice injected with sevoflurane pre-treated cells. *p<0.05 vs naïve control (NC). Data are analysed by one-way non-parametric ANOVA test (Kruskal-Wallis test). Propofol: cells were pre-treated with 10 μg/ml of propofol for six hours, Sevoflurane: cells were pre-treated with 3.6% of sevoflurane for six hours.\n\nWe then studied whether treatment with general anaesthetics affected the number of cells entering bone marrow by counting the number of GFP+ cells from tile scans. Our results demonstrated that treatment with propofol and sevoflurane caused a significant reduction in the number of NALM-6-GFP cells entering bone marrow (Figure 3c). After either treatment, fewer than 100 GFP-NLAM-6 cells entered the bone marrow compared to an average of nearly 200 cells entering the bone marrow for naïve control cells.\n\nCXCR4 is crucial for migration14 and homing8 of leukaemia cells in the bone marrow. One study demonstrated that B-ALL cells (NALM-6 cells) home to discreet, discontinuous locations near vessels in bone marrow that express the adhesion molecules E-selectin and SDF-1.8 Disruption of the interactions of the SDF-1-CXCR4 axis inhibited the homing of GFP-NALM-6 cells to these vessels.8 We hypothesised that CXCR4 was one of the key factors in general anaesthetics-mediated reduction of the migration and homing of GFP-NALM-6 cells in vivo. In order to validate this, we treated NALM-6 cells with propofol (5 and 10 μg/ml) and sevoflurane (3.6% MAC 2) followed by flow cytometry analysis of surface CXCR4 expression. Our results indicated that both propofol and sevoflurane significantly reduced surface CXCR4 expression (Figure 4a). More specifically, 5 and 10 μg/ml of propofol (28 and 56 μM) reduced CXCR4 expression in a dose-dependent manner (Figure 4a). Only six hours of sevoflurane significantly reduced CXCR4 (Figure 4a). These results suggest that CXCR4 might be the key behind general anaesthetics-mediated reduction of homing and migration in leukaemia cells.\n\na) NALM-6 cells were treated by intralipid (VC), 5 μg/ml and 10 μg/ml of propofol for six hours. Or cells were treated by 3.6% of sevoflurane for two, four, and six hours. Following the general anaesthetics treatment, treated cells were stained with a CXCR4 antibody and analysed by flow cytometer for mean fluorescence intensity. Data are illustrated as mean±sd (N=4). Data are analysed by one-way ANOVA followed by Bonferroni’s post hoc test. For propofol statistics, *p<0.05, **p<0.01, vs naïve control (NC). #p<0.05 vs vehicle control (VC). For sevoflurane statistics, *p<0.05. VC: intralipid, P5: 5 μg/ml of propofol, P10: 10 μg/ml of propofol, Sevo 2: two hours sevoflurane, Sevo 4: four hours sevoflurane and Sevo 6: six hours sevoflurane. b) NALM-6 cells were either untreated or treated with 3.6% sevoflurane for six hours initially. Then they were allowed to adhere to plates pre-coated with thrombin cleaved osteopontin for two hours. Data are illustrated as mean±sd (N=4). *p<0.05 vs thrombin-cleaved OPN. Data are analysed by one-way ANOVA followed by Bonferroni’s post hoc test. c) NALM-6 cells were either untreated or treated with 10 μg/ml of propofol for six hours initially. Then they were allowed to adhere to plates pre-coated with thrombin-cleaved osteopontin for two hours. Data are illustrated as mean±sd (N=4). *p<0.05. Data are analysed by one-way ANOVA followed by Bonferroni’s post hoc test. LIPID: intralipid.\n\nIn addition to CXCR4, we then speculated that the changes in the number and position of GFP-NALM-6 cells homed to the BM was due to the disruption of interactions between leukaemia cells and components of bone marrow matrix. We firstly investigated the expression of integrin α4 (CD49d), which is one of the dimers of α4β1 integrin or very late antigen 4 (VLA-4) (the other one being integrin β1), after exposure to general anaesthetics. VLA-4 is an essential mediator for engraftment of NALM-6 cells in bone marrow by anchoring NALM-6 cells to bone marrow matrix and supporting leukaemia growth.10,15,16 The prime target for VLA-4 adhesion is osteopontin (OPN). Interestingly, no significant change was detected in the expression of the α4 subunit after anaesthetics exposure (Supplementary figure 1a and b). Next, we hypothesised that general anaesthetics might affect the adhesion of NALM-6 cells to OPN. Given that OPN has various isoforms in bone marrow, we tested the adhesion of leukaemia cells to thrombin-cleaved OPN, which is the most dominant form of OPN in bone marrow.9 Similar to a previous study,10 NALM-6 cells only weakly adhered to full-length OPN but they showed strong adhesion to thrombin-cleaved OPN (Supplementary figure 1c). Consistent with our hypothesis, when cells were pre-treated with propofol and sevoflurane, the percentage of cells adhered to thrombin-cleaved OPN was significantly reduced (Figure 4b and c).\n\n\nDiscussion\n\nOur work, for the first time, demonstrates that general anaesthetics reduce the migration and homing of ALL cells via CXCR4 and OPN mediated mechanisms. By using in vitro models and an immunocompetent mouse model, we found that both propofol and sevoflurane lead to a reduction in CXCR4 expression and disruption of adhesion to thrombin-cleaved osteopontin in leukaemia cells. These effects were associated with reprogramming of the bone marrow microenvironment to unfavourable conditions for leukaemia cells, as illustrated in the reduction of migration speed, the disruption of homing locations, and the reduction in the number of cells entering bone marrow.\n\nThe importance of CXCR4 (specifically the SDF-1-CXCR4 axis) in B-ALL homing and migration has been well documented.8,14,17 Our CXCR4 expression data is novel and provides direct evidence for the effect of anaesthetics on migration, demonstrating that general anaesthetics reduce CXCR4-dependent chemotaxis in NALM-6 cells.\n\nHoming is a vital process in the early stages of leukaemia development. It allows leukaemia cells to seed, multiply, and importantly, evade detection by the immune system. B-ALL cells have been demonstrated to home to unique anatomic regions in bone marrow.8 It was reasonable to assume that the suppression of CXCR4 by general anaesthetics was one of the reasons for the disruption of homing in our study. Our in vitro data also showed that the adhesion of ALL to thrombin-cleaved osteopontin is reduced by propofol and sevoflurane. Thrombin-cleaved osteopontin is a prominent adhesion molecule in bone marrow, which regulates the binding of leukaemia to bone marrow niches required for homing. The mechanism behind the reduction in adhesion caused by general anaesthetics is not known as VLA-4 receptor expression is not affected by general anaesthetic exposure. In addition to homing disturbance, we found that the number of leukaemia cells entering the bone marrow space was reduced by general anaesthetic treatment in vivo. This may possibly be due to the reduction of surface CXCR4 on NALM-6 cells caused by general anaesthetics.\n\nLooking at clinical studies, a few retrospective studies and one meta-analysis have investigated the beneficial effect of general anaesthetics on cancer outcomes, and propofol may be associated with improved recurrence-free survival and overall survival in patients having cancer surgery.7,18–22 Further clinical studies, including whether propofol is beneficial for ALL patients, are urgently needed. Ideally, anaesthetics without any effects on cancer cell malignancy or, even better, with some potential anti-cancer properties should be chosen to use in cancer patients during surgery. Ultimately, cancer patients will get enormous benefits from such changes in clinical practice and very importantly, such changes will not incur significant cost on the healthcare system.\n\nOur study is not without limitations. Firstly, leukaemia cells were pre-treated with propofol or sevoflurane before injection in in vivo models, which eliminates the complexities of drug metabolism in vivo. For further studies, it would be interesting to treat mice with propofol and sevoflurane directly. In addition, long-term studies could be established in which propofol and sevoflurane are given to leukaemia-bearing mice with established disease to mimic real clinical scenarios.\n\nSecondly, the concentration of anaesthetics used for our study may be more applicable to paediatric patients. Clinical doses of general anaesthetics for invasive procedures in adult patients are generally lower and shorter in duration for such procedures. However, the clinical doses of general anaesthetics in paediatric patients are relatively high; for example, the use of 3.6% or higher concentrations of sevoflurane for paediatric leukaemia treatment procedures is well documented.3,23–25 Additionally, the plasma concentration of propofol was reported to be high in paediatric procedures (plasma concentration range between 6 μg/ml to 2 μg/ml).3 Furthermore, these patients are subject to frequent exposure to general anaesthetics. Therefore, the cumulative dose of anaesthetic exposure for this group of patients is considerably high.\n\n\nConclusion\n\nIn the present study, we investigated the effect of two commonly used general anaesthetics, propofol and sevoflurane, on ALL cell migration and homing exemplified by 1) the number of cells entering bone marrow and 2) the homing location in relation to the nearest endosteal surface. Our data suggest that both general anaesthetics reduced the homing and migration of ALL cells in vitro and in vivo. Our results indicated that general anaesthetics reduced the surface CXCR4 expression. In addition, the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced by general anaesthetics.\n\nWe focussed on changes driven by ex vivo exposure to propofol and sevoflurane, however it is possible that these drugs might also re-program the bone marrow to be a more hostile environment for ALL cells and thus, in turn reduce the overall malignancy of ALL. Therefore, both anaesthetics may be safely used in patients undergoing procedures during ALL treatments but this warrants further clinical studies.\n\n\nEthics\n\nAll procedures performed relating to animal experiments in this study were approved by the Animal Welfare and Ethical Review Body (AWERB), Imperial College London and the Home Office, United Kingdom with PPL number 70/8496.\n\n\nAuthors’ contributions\n\nJ.C., D.Q.M. and C.L.C. conceived the project. C.L.C. developed the intravital microscopy (IVM) method. J.C. performed all experiments, data analysis and wrote the manuscript. S.G.A. and X.M.L. helped perform the IVM experiment and helped IVM data analysis. All authors read and approved the final submission.",
"appendix": "Data availability\n\nZendo: General anaesthetics reduce acute lymphoblastic leukaemia cell migration and homing in vitro and in vivo via CXCR4 and osteopontin mediated mechanisms, https://doi.org/10.5281/zenodo.7261294. 26\n\nThis project contains following underlying data:\n\n- Author Checklist - Full.pdf\n\n- Cell adhesion assay.xlsx\n\n- Flow data.xlsx\n\n- IVM data.xlsx\n\n- Nc cells.avi\n\n- propofol cells.avi\n\n- sevoflurane cells.avi\n\n- sub Figures F1000 JC.dox\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nHunger SP, Mullighan CG: Acute Lymphoblastic Leukemia in Children. N. Engl. J. Med. 2015; 373(16): 1541–1552. Publisher Full Text\n\nPercival ME, Lai C, Estey E, et al.: Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia. Blood Rev. 2017; 31(4): 185–192. PubMed Abstract | Publisher Full Text\n\nGaynor J, Ansermino JM: Paediatric total intravenous anaesthesia. BJA Education. 2016; 16(11): 369–373. Publisher Full Text\n\nMa D, Lim T, Xu J, et al.: Xenon preconditioning protects against renal ischemic-reperfusion injury via HIF-1alpha activation. J. Am. Soc. Nephrol. 2009; 20(4): 713–720. PubMed Abstract | Publisher Full Text\n\nHuang H, Benzonana LL, Zhao H, et al.: Prostate cancer cell malignancy via modulation of HIF-1alpha pathway with isoflurane and propofol alone and in combination. Br. J. Cancer. 2014; 111(7): 1338–1349. PubMed Abstract | Publisher Full Text\n\nBenzonana LL, Perry NJ, Watts HR, et al.: Isoflurane, a commonly used volatile anesthetic, enhances renal cancer growth and malignant potential via the hypoxia-inducible factor cellular signaling pathway in vitro. Anesthesiology. 2013; 119(3): 593–605. PubMed Abstract | Publisher Full Text\n\nWigmore TJ, Mohammed K, Jhanji S: Long-term Survival for Patients Undergoing Volatile versus IV Anesthesia for Cancer Surgery: A Retrospective Analysis. Anesthesiology. 2016; 124(1): 69–79. Publisher Full Text\n\nSipkins DA, Wei X, Wu JW, et al.: In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature. 2005; 435(7044): 969–973. PubMed Abstract | Publisher Full Text\n\nGrassinger J, Haylock DN, Storan MJ, et al.: Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with alpha9beta1 and alpha4beta1 integrins. Blood. 2009; 114(1): 49–59. PubMed Abstract | Publisher Full Text\n\nBoyerinas B, Zafrir M, Yesilkanal AE, et al.: Adhesion to osteopontin in the bone marrow niche regulates lymphoblastic leukemia cell dormancy. Blood. 2013; 121(24): 4821–4831. PubMed Abstract | Publisher Full Text\n\nLo Celso C, Fleming HE, Wu JW, et al.: Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature. 2009; 457(7225): 92–96. PubMed Abstract | Publisher Full Text\n\nHawkins ED, Duarte D, Akinduro O, et al.: T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments. Nature. 2016; 538(7626): 518–522. PubMed Abstract | Publisher Full Text\n\nLee SH, Park SA, Zou Y, et al.: Real-Time Monitoring of Cancer Cells in Live Mouse Bone Marrow. Front. Immunol. 2018; 9. PubMed Abstract | Publisher Full Text\n\nSpiegel A, Kollet O, Peled A, et al.: Unique SDF-1-induced activation of human precursor-B ALL cells as a result of altered CXCR4 expression and signaling. Blood. 2004; 103(8): 2900–2907. PubMed Abstract | Publisher Full Text\n\nFilshie R, Gottlieb D, Bradstock K: VLA-4 is involved in the engraftment of the human pre-B acute lymphoblastic leukaemia cell line NALM-6 in SCID mice. Br. J. Haematol. 1998; 102(5): 1292–1300. PubMed Abstract | Publisher Full Text\n\nRyan DH, Nuccie BL, Abboud CN, et al.: Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells. J. Clin. Invest. 1991; 88(3): 995–1004. PubMed Abstract | Publisher Full Text\n\nShen W, Bendall LJ, Gottlieb DJ, et al.: The chemokine receptor CXCR4 enhances integrin-mediated in vitro adhesion and facilitates engraftment of leukemic precursor-B cells in the bone marrow. Exp. Hematol. 2001; 29(12): 1439–1447. PubMed Abstract | Publisher Full Text\n\nYoo S, Lee HB, Han W, et al.: Total Intravenous Anesthesia versus Inhalation Anesthesia for Breast Cancer Surgery: A Retrospective Cohort Study. Anesthesiology. 2019; 130(1): 31–40. Publisher Full Text\n\nZheng X, Wang Y, Dong L, et al.: Effects of propofol-based total intravenous anesthesia on gastric cancer: a retrospective study. Onco. Targets. Ther. 2018; 11: 1141–1148. PubMed Abstract | Publisher Full Text\n\nWu ZF, Lee MS, Wong CS, et al.: Propofol-based Total Intravenous Anesthesia Is Associated with Better Survival Than Desflurane Anesthesia in Colon Cancer Surgery. Anesthesiology. 2018; 129(5): 932–941. PubMed Abstract | Publisher Full Text\n\nEnlund M, Berglund A, Andreasson K, et al.: The choice of anaesthetic--sevoflurane or propofol--and outcome from cancer surgery: a retrospective analysis. Ups. J. Med. Sci. 2014; 119(3): 251–261. PubMed Abstract | Publisher Full Text\n\nYap A, Lopez-Olivo MA, Dubowitz J, et al.: Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia. Can. J. Anaesth. 2019; 66(5): 546–561. PubMed Abstract | Publisher Full Text\n\nGlaisyer HR, Sury MR: Recovery after anesthesia for short pediatric oncology procedures: propofol and remifentanil compared with propofol, nitrous oxide, and sevoflurane. Anesth. Analg. 2005; 100(4): 959–963. PubMed Abstract | Publisher Full Text\n\nDi N, Guo Y, Ding N: Effect of combined propofol-sevoflurane anesthesia on immune function in pediatric patients with acute lymphoblastic leukemia. Oncol. Lett. 2019; 18(1): 35–42. PubMed Abstract | Publisher Full Text\n\nOduro-Dominah L, Brennan LJ: Anaesthetic management of the child with haematological malignancy. Contin. Educ. Anaesth. Crit. Care Pain. 2013; 13(5): 158–164. Publisher Full Text\n\nCui J, Gonzalez-Anton S, Li XM, et al.: General anaesthetics reduce acute lymphoblastic leukaemia cell migration and homing in vitro and in vivo via CXCR4 and osteopontin mediated mechanisms.2022.Publisher Full Text"
}
|
[
{
"id": "158793",
"date": "26 Jan 2023",
"name": "Koichi Yuki",
"expertise": [
"Reviewer Expertise Anesthesia 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 is the study that investigated the role of commonly used anesthetics propofol and sevoflurane in ALL cells, considering these drugs are often administered to patients with ALL. Authors found that anesthetics attenuated recruitment of ALL cells in vitro and in vivo.\nA very interesting study by the group that heavily studies the role of anesthetics. I have one very simple comment.\n\nAs authors mentioned in the introduction, patients with ALL often receive procedures. Those procedures are often short (< 2 hours). Would you mind to elaborate your finding based on the duration of exposure?\n\nWhat is the pathological significance of ALL cells recruited back to the bone marrow? Does this have any implication in the disease process? Authors found that ALL cells migrated less to the bone marrow. Does this effect last?\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": "9397",
"date": "12 Feb 2024",
"name": "cui jiang",
"role": "Author Response",
"response": "Thank this reviewer for their kind comments Response Question 1: We did acknowledge the longer exposure time is a limitation of the study. We have put in the discussion section: “Clinical doses of general anaesthetics for invasive procedures in adult patients are generally lower and shorter in duration for such procedures.” 6 hours exposure time was chosen because: We wish to do a proof-of-concept studies on whether long exposure time would yield significant results before designing shorter time period experiments given the how expensive it is to run such experiments. Although the initial half-life of propofol and sevoflurane is very short and patients recover from anaesthesia within minutes, the terminal half-life of propofol and sevoflurane can be theoretically long (4-7 hours for propofol reference: Khurram Saleem Khan, FCAI FJFICMI, Ivan Hayes, FCAI FJFICMANZ, Donal J Buggy, MD MSc DME FRCPI FCAI FRCA, Pharmacology of anaesthetic agents I: intravenous anaesthetic agents, Continuing Education in Anaesthesia Critical Care & Pain, Volume 14, Issue 3, June 2014, Pages 100–105 and up to 20 hours for sevoflurane reference: Clin Pharmacokinet 1999 Jan; 36 (1). Page 19). Long terminal half life may hypothetically give time for general anaesthetics to act on leukaemia cells With all being said, we did perform in vitro experiments measuring cellular parameters for other parallel studies e.g. protetin expressions and in vitro functional assays with shorter time period i.e. 2 hour; we could see significant cellular changes following 2 hours exposure time of propofol and sevoflurane; we may publish those results in the near future Question 2: Recruitment of ALL to the bone marrow is the first step of the homing process which allow the disease to happen in this murine model – given these mice are not genetically modified to have ALL genes. Reduction of recruitment of ALL cells to bone marrow translates into reduction in homing hence lower possibility of disease-causing cells in bone marrow."
}
]
},
{
"id": "187198",
"date": "21 Aug 2023",
"name": "Paul M Maciocia",
"expertise": [
"Reviewer Expertise Cellular immunotherapy",
"ALL",
"lymphoma."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to 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 yet somewhat incomplete article: as the authors note, general anaesthetics may have some potential anti-cancer properties. The authors investigated the effect of two commonly used anaesthetics, propofol and sevoflurane, in acute lymphoblastic leukaemia cells. Anaesthetics-treated ALL cells showed reduced migration and homing both in vitro and in vivo, and the authors suggested its mechanisms. This article is concise and well-written, and provides meaningful messages. I have only a few comments.\nIn Figure 4a, the authors tested the different concentrations of propofol and the different exposure time of sevoflurane. Is there a rationale for the propofol exposure time (ie. 6 hours)?\n\nAs the authors mentioned, the effects of general anaesthetic are thought to be reversible. How long does the anaesthetic effect last in ex vivo treated ALL cells? This is quite important for establishing if the phenomena reported here might have any clinical impact\n\nThe authors used isoflurane for anesthesia when imaging intravital microscopy. Is there any possibility that isoflurane interferes with propofol or sevoflurane?\n\nIn patients, the anaesthetics may affect the activity of normal cells as well. From the therapeutic point of view, do the authors think the reduced migration of ALL cells will outweigh the slowing of normal cell activity?\n\nOne cell line is not enough to draw conclusions – the authors need to test multiple cell lines and primary B-ALL samples. This is the most critical point to accept for publication.\n\nIts not at all clear what the functional consequences of these findings might be (I still don’t really know if anaesthetics are potentially good or bad for patients from this study) and I would like to see this explored more, though appreciate this would be a much more in-depth paper.\nAnd here are my suggestions for minor revision:\nIt is unclear when intravital imaging was performed after ALL injection.\n\nTo represent multiple statistical significance between groups, it would be better to draw a line between comparing groups and put an asterisk mark over the line than ## symbol.\n\nIntroduction – ‘radiotherapy’ does not refer to diagnostic radiological procedures, there are also numerous typos\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": "11009",
"date": "13 Apr 2024",
"name": "cui jiang",
"role": "Author Response",
"response": "Thanks this reviewer's insighful comment here is our point to point reply: In Figure 4a, the authors tested the different concentrations of propofol and the different exposure time of sevoflurane. Is there a rationale for the propofol exposure time (ie. 6 hours)? Reply: We did run a time course experiment with propofol at the beginning of the project i.e., 2 and 4 hours of propofol exposure, we only found 6 hours of propofol exposure to produce significant effect; hence 6 hours of propofol exposure is used As the authors mentioned, the effects of general anaesthetic are thought to be reversible. How long does the anaesthetic effect last in ex vivo treated ALL cells? This is quite important for establishing if the phenomena reported here might have any clinical impact Reply: As we have updated in the figure 4, propofol’s effect seems to be short-lived given after 24 hours of recovery time, propofol stop having effect on cxcr4 expressions but sevoflurane seems to have potent reductive effect on the CXCR4 expression given after 24 hours of recovery time, CXCR4 expression is still reduced The authors used isoflurane for anesthesia when imaging intravital microscopy. Is there any possibility that isoflurane interferes with propofol or sevoflurane? Reply: This point has been discussed in the discussion section as systemic delivered isoflurane may need longer exposure time and more importantly repeated administrations to reach concentrations to significantly affect the experiment results as injected leukaemia cells were pre-treated ex-vivo before injections. In addition, if isoflurane had any effect on injected leukaemia cells, then such effect would affect sevoflurane group and propofol uniformly In patients, the anaesthetics may affect the activity of normal cells as well. From the therapeutic point of view, do the authors think the reduced migration of ALL cells will outweigh the slowing of normal cell activity? Reply: Some studies have been carried out by our lab and others. And we found general anaesthetics have minimal toxicity against normal tissue. However, no one has studied whether general anaesthetics can reduce or interrupt normal bone marrow activity i.e., haematopoiesis given CXCR4 is an important receptor for such activity. With this being said, for ALL patients, killing of leukaemia cells and re-shape bone marrow niche to be more hostile to ALL cells would likely outweigh the effect of general anaesthetics on normal bone marrow activity One cell line is not enough to draw conclusions – the authors need to test multiple cell lines and primary B-ALL samples. This is the most critical point to accept for publication. Reply: Reh data has been added in the manuscript per comment Its not at all clear what the functional consequences of these findings might be (I still don’t really know if anaesthetics are potentially good or bad for patients from this study) and I would like to see this explored more, though appreciate this would be a much more in-depth paper. Reply:Chemoresistance data has been added in the manuscript to show the functional consequence of general anaesthetics And here are my suggestions for minor revision: It is unclear when intravital imaging was performed after ALL injection. Reply: Updated in the method section To represent multiple statistical significance between groups, it would be better to draw a line between comparing groups and put an asterisk mark over the line than ## symbol. Reply:This has been rectified in all figures Introduction – ‘radiotherapy’ does not refer to diagnostic radiological procedures, there are also numerous typos Reply: Added texts in introduction to minimise confusion"
}
]
}
] | 1
|
https://f1000research.com/articles/11-1491
|
https://f1000research.com/articles/12-4/v1
|
03 Jan 23
|
{
"type": "Data Note",
"title": "University students dataset related to achievement, classroom practices, perceptions and attitudes of multimedia-based learning quantum physics",
"authors": [
"Pascasie Nyirahabimana",
"Evariste Minani",
"Mathias Nduwingoma",
"Imelda Kimeza",
"Evariste Minani",
"Mathias Nduwingoma",
"Imelda Kimeza"
],
"abstract": "This dataset presents data collected to assess teaching and learning of quantum physics at the University of Rwanda - College of Education (UR-CE), Rwanda. Data were collected between August and November 2019 as the baseline, and between January and April 2022 under a quasi-experimental design. Three sets of data were collected. The first set was about students' performance and conceptual understanding collected before and after teaching intervention (lecture method or multimedia-aided approach) using mainly Quantum Physics Conceptual Survey (QPCS). The second set documented classroom practices during teaching and learning using the Classroom Observation Protocol for Undergraduate STEM (COPUS). The last set is comprised of the data related to lecturers' and students' perceptions before teaching and learning quantum physics and students' attitudes after learning Quantum physics. The Quantum Physics Attitude Test (QPAT) was mainly used to collect these data. The dataset is important to education stakeholders because university managers can visualize the status of teaching and learning outcomes, lecturers can reflect on the study, and researchers can use the data to analyze various independent variables.",
"keywords": [
"Dataset",
"Conceptual understanding",
"Rwanda",
"Student academic achievement",
"Student attitude",
"Quantum mechanics",
"Quantum physics",
"University students."
],
"content": "Introduction\n\nThe education system in Rwanda has seen many transitions, including after the Tutsi genocide of 1994. In 2008, Rwanda transitioned from French to English as a language of instruction at all levels of education1; in 2012, a policy for 12 years of basic education was adopted,2 and in 2013 the public higher education institutions were merged into a single University of Rwanda.3 Several studies have so far documented learning of physics4–6 after a competence-based curriculum was implemented in secondary schools in 2016.7 Few people have chosen the direction of higher learning institutions.8 However, few of them focused on teaching and learning practices of quantum physics at the university level. Quantum mechanics is a discipline that is introduced by quantum physics, and quantum physics is a set of principles used to explain the behavior of matter and energy. Thus, these two terms were used interchangeably in this manuscript and served as a focus of data collection. This branch of physics consists of many important phenomena in nature despite the difficulty faced by students to interpret various concepts9–11 such as blackbody radiation, the photoelectric effect, Compton Effect, the wave aspects of particles, De Broglie’s hypothesis, diffraction and interferences, the model of the atom, uncertainty relations, the wave function, and Schrodinger Equations. Therefore, this served as a motivation for researchers to investigate the teaching and learning of quantum physics at the University of Rwanda – College of Education (UR-CE). Before the implementation of the intervention, a baseline study was conducted. This baseline study aimed to determine the prime indicators of current teaching methodologies and students’ perceptions of quantum physics for quality knowledge delivery at the University of Rwanda College Of Education.9 For this study, attitude tests (Quantum Physics Attitude Test, QPAT) for students and Educators were used. These research instruments were designed and validated by university experts in science education. We piloted them on 30 physics students and two Educators from the University of Kibungo, Rwanda. These participants were not part of this study.\n\n\nMethods\n\nThe study was quasi-experimentally designed.12 Before data collection was initiated, ethical clearance was applied to and approved and provided by the Unit of Research and Innovation, University of Rwanda-College of Education. Lecturers were briefed on required teaching approaches, and students and physics lecturers were informed of voluntary participation. The study was conducted at UR-CE in the department of Mathematics, Science, and Physical Education (MSPE) with groups of second-year undergraduate students from Mathematics-Physics-Education (MPE), Physics-Chemistry-Education (PCE) and Physics-Geography-Education (PGE) combinations assigned to experimental and control groups. Teaching intervention was delivered from 28 January to 1 April 2022. Lecturers in Quantum Physics were agreed to help the respective groups to understand the subject. Thus, while traditional lecture group or lecture class were taught using marker and whiteboard and PowerPoint presentations, the experimental group or multimedia class was taught using animations, PhET simulations, and YouTube videos. Animation introduced a concept while teaching with multimedia to engage students. Before playing a simulation or a video, students were given prediction questions to help them predict the outcomes of the experiment. Before intervention (December 2021), a pre-test was administered using an adapted Quantum Physics Conceptual Survey (QPCS).13 It was adapted because it was not used alone, as it lacks some elements taught in the UR-CE Quantum Mechanics module. Researchers added some questions (see Table 1) about blackbody radiation from textbooks and total energy, and the probability of finding a particle from the Quantum Mechanics Conceptual Survey (QMCS).14 This decision was advice from four university physics lecturers who validated the test’s content.\n\nWe used a test-retest method for checking reliability and the internal consistency revealed a high Cronbach alpha coefficient (a = 0.718) of 32 QPCS items used. The first author and her trained assistants made follow-ups by doing classroom observations to see whether there were any challenges during the intervention. After six weeks of teaching, the post-test was also given to all participants to examine if the multimedia intervention had some effects on students’ conceptual understanding. We used the Classroom Observation Protocol for Undergraduate STEM (COPUS) developed by Northern American researchers.15 This protocol comprises 12 codes for instructor activities, 13 codes for student activities, and three codes for student engagement. Before data collection, interrater reliability were obtained between each of the two pairs of classroom observers. Student codes generated a Kappa value of 0.652, instructor codes 0.805, and student participation codes generated 0.625. These values are considered very high in inter-observer reliability.16\n\nThe Quantum Physics Attitude Test (QPAT) was adapted from the Evaluation Questionnaire for Computer Simulations (EQCS)17 and designed based on the literature review, daily teaching experiences, and students’ group discussions. The formulated 29 questions were content validated by five university experts in research, and the final QPAT comprised 24 items. The test had four sections: (i) College students’ perceptions of quantum physics concepts, (ii) Use of multimedia in teaching and learning quantum physics, (iii) Students’ feelings towards learning quantum physics, and (iv) the extent students recommend the actions to be taken in improving teaching and learning quantum physics. The test was implemented after getting a 0.74 reliability of internal consistency. We also need to note that while achievement data were collected before and after the intervention, classroom observation data were collected during the teaching and learning period; however, students’ attitude data were collected after teaching and learning follow-up, and the staff and students’ perceptions before teaching and learning activity.\n\n\nDescription of dataset\n\nThis dataset comprises five Excel files and five pdf files. These pdf files are research tools used to collect data, while these Excel files are data files. The first file is students’ achievements (named: Data Related to Academic Achievement 2022). This file has four sheets. (1) Pre-test of the Control group, (2) Post-test of the Control group, (3) Pre-test of the Treatment group, and (4) Post-test of the Treatment group. In the sheet, the first column shows the study combination as mentioned in the above section and the second column consists of serial number (s/n). From the third column or column-C to column-HA, the students’ answer choices for each of the 32 questions are entered. Correct answers are presented above each question. From column-AK to column-PB, each question is marked. The same analysis as that in Ref. 18 was adopted. The formula used was “= IF (EXACT(E18, E$15),1,0). This means we matched the answer of the first students on row-18 and column-C with the expected answer on row-15 and column-C on the first question. The dollar sign was used to avoid the formula to shift the rows down. If the answers matched, the software assigned one mark, and a zero otherwise. We summed these scores up in column-BR and computed their respective percentage in column-BS. A total of 385 undergraduate students participated in the pre-and post-tests.\n\nBelow the data, the number of students who chose a certain answer was computed (see row-198 and column-C) using the “COUNTIF” function. After this, a percentage was computed. Likewise, the sum and corresponding percentage were calculated under the assigned marks (see row-199 and column-AK).\n\nThe second data file (named “Data related to baseline study_Post teaching and learning Quantum Physics_2022”) presents the students’ and educators’ perceptions of teaching methodologies used while teaching quantum physics. It contains two sheets with quantitative and qualitative data collected from students who have previously learned quantum physics and educators who taught this course in past years. Thus, this was used for the baseline study, where we investigated the impact of current teaching methodologies and teaching staff and students’ perceptions of quantum physics for a quality knowledge delivery system.9\n\nThe third and four files are related to classroom observation data. One comprises data for the control group (named: Data related to Classroom Observation 2022_Control group), while the other comprises data for the experimental group (Data related to Classroom Observation 2022_Experimental group). These files have four sheets each. The first sheet contains raw data, the second sheet presents the meaning of codes used in the first sheet, the third sheet present analyzed data by activity, and the fourth sheet present analyzed data by time interval. Data were entered in a way that when an activity was observed, a mark of “1” was entered and when an activity was not observed, an empty space is left. The intervention was carried out for 80 minutes per week for weeks. For this reason, the first column (or column A) consists of two-minute time intervals of observed activities, and column AF shows the week (weeks 1-6). Rows 14 and 15 show the codes or observed activities, while the sum and total of observed activities are computed at the end of the table of activities. These sums are used to plot the activities graph (see sheet 3) as they do not consider time intervals. Thus, the proposition of each activity is calculated based on all activities. That is why all activities’ occurrence add up to 100. On the other hand, when considering activities and the sometimes time interval, the computed proportions of activities do not add up to 100. They can go beyond (see sheet 4). This was computed referring to the total intervals calculated in column AE. A Classroom Observation Protocol for Undergraduate STEM (COPUS) tools was used to collect and analyse data.15\n\nThe fourth file data file (named “Data Related to Students Attitude_Post assessement 2022”) presents the students’ perceptions on multimedia usage in teaching and learning quantum physics attitude. It contains five sheets. The first sheet explains the codes or assigned numbers used in the second and fourth sheets. The second sheet (Experimental group _QPAT) and the third sheet (Experimental_G_QPAT-Open Q) contain quantitative and qualitative data, respectively. Likewise, the fourth sheet (Control group_QPAT) and the fifth sheet (Control_G_QPAT_Open Q) contain quantitative and qualitative data, respectively. This was done to ease the visualization of data since the attitude test contained both closed and open questions. Thus, quantitative data from closed-question items were put in a separate sheet, and qualitative data from open-ended question items were put in their separate sheets. 385 undergraduate students who have completed the learning of quantum physics using either lecture or multimedia application methods participated in the survey. The reason why fewer students attended the attitude test than those who attended the achievement test may be that the achievement test was performed on paper while the attitude test was performed online. The questions under the “Student feelings towards learning Quantum physics” were answered using five scales. Strongly agree (5), Agree (4), Neutral (3), Disagree (2), and Strongly disagree (1). Therefore to analyze such data, a COUNTIF function was again employed as in the achievement test.",
"appendix": "Data availability\n\nThe data are available to use from the Mendeley repository. Readers are able to view the raw data, replicate the study, and re-analyze and/or reuse the data (with appropriate attribution).\n\nMendeley Data: Dataset from the University of Rwanda College of Education during Learning Quantum Physics. https://data.mendeley.com/datasets/gm49fmx86t/5. 19\n\nThis dataset contains the following underlying data:\n\n• Data file 1. (Data Related to Academic Achievement 2022)\n\n• Data file 2. (Data related to baseline study_Postteaching and learning Quantum Physics_2022)\n\n• Data file 3. (Data related to Classroom Observation 2022_Control group)\n\n• Data file 4. (Data related to Classroom Observation 2022_Experimental group)\n\n• Data file 5. (Data Related to Students Attitude_Post assessment 2022)\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: Dataset from the University of Rwanda College of Education during Learning Quantum Physics. https://data.mendeley.com/datasets/gm49fmx86t/5. 19\n\nThere are five other files connected to these data. The achievement and attitudes tests were used to collect students’ data. The first one is named “Final Quantum Physics Conceptual Survey (QPCS)_adapted&used,” while another is named “Quantum Physics Attitude Test (QPAT)_data collection Tools_2022.” The file of a questionnaire administered to lecturers and students as a baseline survey is named “Data related to baseline study on Quantum Physics teaching and learning_2022.” The last files are the “Participants sheet and consent form” and “Researh ethical Clearance approval.”\n\n\nAcknowledgments\n\nWe have the pleasure of thanking all people that participated in this study: Students who willingly showed interest in being observed and sitting for tests; Lecturers who supported in delivering lessons and were willing showed interest in being interviewed; Research assistants who helped in gathering data.\n\n\nReferences\n\nNsengimana T, Ozawa H, Chikamori K: The implementation of the new lower secondary science curriculum in three schools in Rwanda. African J. Res. Math. Sci. Technol. Educ. 2014; 18(1): 75–86. Publisher Full Text\n\nMinistry of Education [MINEDUC]: Republic of Rwanda Ministry of Education Education Sector Strategic Plan 2018/19 to 2023/24.2018.Reference Source\n\nNdihokubwayo K, Byusa E, Yutaka I: Redistributing Public Institutions to Rural Areas: A Case of the University of Rwanda College of Education, Rukara. African J. Gov. Dev. 2019; vol. 8(no. 1): pp. 24–35.Reference Source\n\nNdihokubwayo K, Uwamahoro J, Ndayambaje I: Usability of Electronic Instructional Tools in the Physics Classroom. EURASIA J. Math. Sci. Technol. Educ. 2020; 16(11): 1–10. Publisher Full Text\n\nNdihokubwayo K, Ndayambaje I, Uwamahoro J: Analysis of Lesson Plans from Rwandan Physics Teachers. Int. J. Learn. Teach. Educ. Res. 2020; 19(12): 1–29. Publisher Full Text\n\nNyirahagenimana J, Uwamahoro J, Ndihokubwayo K: Assessment of Physics Lesson Planning and Teaching based on the 5Es Instruction Model in Rwanda Secondary Schools. Contemp. Math. Sci. Educ. 2022; 3(1): 1–10. Publisher Full Text\n\nREB: Comptence-Based Curriculum. Curriculum Framework Pre-Primary to Upper Secondary. 2015.Reference Source\n\nMukagihana J, Nsanganwimana F, Aurah CM: Effect of resource-based instructions on pre-service biology teachers’ motivation toward learning biology. LUMAT Int. J. Math, Sci. Technol. Educ. 2021; 9(8): 262–277. Publisher Full Text\n\nNyirahabimana P, Minani E, Nduwingoma M, et al.: Prime indicators of current teaching methodologies and students’ perceptions in Quantum physics. Int. J. Eval. Res. Educ. 2022; 11(3): 1134–1142. Publisher Full Text\n\nAkarsu B: Einstein’s Redundant Triumph ‘Quantum Physics’: An extensive Study of Teaching/Learning Quantum Mechanics in College. Latin-American J. Phys. Educ. 2010; 4(2): 273–285.Reference Source\n\nRyan QX, Wilcox BR, Pollock SJ: Student difficulties with boundary conditions in the context of electromagnetic waves. Phys. Rev. Phys. Educ. Res. 2018; 14(2): 20126. Publisher Full Text\n\nFraenkel JR, Wallen NE, Hyun HH: How to Design Research in Education and Evaluate. 2012.\n\nWuttiprom S, Sharma MD, Johnston ID, et al.: Development and use of a conceptual survey in introductory quantum physics. Int. J. Sci. Educ. 2009; 31(5): 631–654. Publisher Full Text\n\nMcKagan SB, Perkins KK, Wieman CE: Design and validation of the quantum mechanics conceptual survey. Phys. Rev. Spec. Top. - Phys. Educ. Res. 2010; 6(2): 1–17. Publisher Full Text\n\nSmith MK, Jones FHM, Gilbert SL, et al.: The Classroom Observation Protocol for Undergraduate STEM (COPUS): A New Instrument to Characterize University STEM Classroom Practices. CBE—Life Sci. Educ. 2013; 12(4): 618–627. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNyirahabimana P, Minani E, Nduwingoma M, et al.: Instructors and Students’ Practices and Behaviours during a Quantum Physics class at the University of Rwanda: Exploring the Usage of Multimedia. Int. J. Learn. Teach. Educ. Res. 2022; 21(9): 309–326. Publisher Full Text\n\nChou CH: The effectiveness of using multimedia computer simulations coupled with social constructivist pedagogy in a college introductory physics classroom. Teachers College, Columbia University;1998.\n\nNdihokubwayo K, Ralph M, Ndayambaje I, et al.: Dataset for measuring the conceptual understanding of optics in Rwanda. F1000Res. 2022; 10(May): 613–679. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNyirahabimana P, Minani E, Nduwingoma M, et al.: Dataset from the University of Rwanda College of Education during teaching and Learning Quantum Physics. Mendeley Data. 2022; V5. Publisher Full Text"
}
|
[
{
"id": "158997",
"date": "18 Jan 2023",
"name": "Peter C. Samuels",
"expertise": [
"Reviewer Expertise Applied statistics (scale reliability analysis)",
"Excel",
"science education"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe datasets are definitely useful, and much effort has gone into organising them. The rationale is clear in the introduction. The method is also clearly presented. The description of the datasets is clear and helpful.\nHowever, there are a few issues I would recommend improving:\nThe 1994 Rwandan genocide is not known outside of Rwanda as the Tutsi Genocide. This name might cause confusion to an international audience.\n\nThe test-retest method for checking the reliability of the QPCS may need additional thought. Cronbach's alpha values tend to be high for scales involving larger numbers of items. The sample size is not stated. A citation should be given to justify this analysis.\n\nA sample size should also be provided for the interrater reliability of COPUS.\n\nSome of the data sets (such as Data related to baseline study _Post teaching and learning Quantum Physics_2022.xlsx) include very long question fields (such as Q3) and multiple answer fields. These will be difficult to analyse in the current format. Shorter names and a coding system could be used to make them more accessible.\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? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Partly",
"responses": [
{
"c_id": "11032",
"date": "13 Apr 2024",
"name": "Pascasie Nyirahabimana",
"role": "Author Response",
"response": "Thank you so much for your constructive feedback. The response on some issues raised are here below: 1. The 1994 Rwandan genocide is known outside of Rwanda as the 1994 Genocide Against the Tutsi and the reference was provided. (See reference 1 in the revised version). 2. The sample size was stated in revised version ( 30 physics students) and the appropriate citation was added: reference 20 3. A sample size was also provided and the citation was added (Reference 16) 4. The question three stated in the comment 4 was well analyzed as shown by reference 18 and 20 All comments proposed were addressed in revised version of this manuscript"
}
]
},
{
"id": "214701",
"date": "08 Nov 2023",
"name": "Nicolas Labrosse",
"expertise": [
"Reviewer Expertise Physics Education Research",
"Scholarship of Learning and Teaching"
],
"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 data note provides information necessary to review and analyse the data collected by the authors. The method of data collection is well described.\n\nA few more details on the teaching interventions and their pedagogical motivations would be really interesting to have. However this may be beyond the scope of this data note.\n\nIt would be interesting to see what possible investigations the authors envisage to carry out with the data collected.\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and materials provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "11031",
"date": "13 Apr 2024",
"name": "Pascasie Nyirahabimana",
"role": "Author Response",
"response": "Thank you so much . I agree with your comment. For more details, please check all publications related to these data on the following link: https://bit.ly/3TTAFdN"
}
]
}
] | 1
|
https://f1000research.com/articles/12-4
|
https://f1000research.com/articles/11-1273/v1
|
08 Nov 22
|
{
"type": "Research Article",
"title": "Is Taylor Swift leading a new Pop revolution? A cross-generation analysis of Pop/Rock cover songs",
"authors": [
"José Luis Ortega"
],
"abstract": "Background: The aim of this paper is to find evidence of a changing pattern in cover songs by 21st-century artists. To this end, over 76,000 covers performed by artists who grew up in the 2000s were quantitatively analyzed. Methods: SecondHandSongs.com was crawled to extract the cover relationships, and Allmusic.com to obtain the genre and starting decade of each performer. Results: The results show that the current music panorama is dominated by Pop/Rock music and, for the first time since the 1960s, artists from the 2010s generation prefer to cover more songs by contemporary artists than by classic figures from the 1960s. Pop and Dance are the emerging sub-genres with the largest proportion of covered musicians, while Taylor Swift, Justin Bieber and Ed Sheeran are responsible for this changing trend. Conclusions: These results provide an interesting opportunity to introduce quantitative studies in cultural studies about music, cinema and arts.",
"keywords": [
"Contemporary popular music",
"Cover songs",
"Pop/Rock",
"Taylor Swift",
"SecondHandSongs",
"digital humanities",
"popular culture"
],
"content": "Introduction\n\nWith the proliferation of new forms of data collection (data repositories, public APIs and web scrapping), the appearance of more advanced processing tools (OpenRefine, R packages, etc.) and the increase of storage space, digital humanities are becoming established as reference discipline in the study of complex cultural and historical phenomena (Black, 2016). This freely accessible information is fostering new quantitative research fronts that are exploring historical, cultural and social phenomena from a quantitative perspective. In this sense, multiple web platforms are expanding, providing music information about releases (Discogs), artists (MusicBrainz, Allmusic), samples (Whosampled), lyrics (Genius) and cover songs (SecondHandSongs). This great variety of web sources offers the chance to explore the evolution and impact of contemporary popular music, and concretely, the influence among artists through cover songs.\n\n700,830 artists and 96,133 original songs. According to “https://secondhandsongs.com/”1, original performers are those that perform, record or release a song for the first time. A cover is a version of the same song performed, recorded or released by subsequent artists. This definition excludes songwriters, who could be the original authors, but not the original performers. This database is limited to versions, including a list of covered songs and initial performers by artist (SecondHandSongs, 2020). This database is limited to versions, including a list of covered songs and initial performers by artist (SecondHandSongs, 2020).\n\nAllmusic is a comprehensive music web database created in 1994 and owned by TiVo Corporation. The platform provides 30 million tracks and three million albums (Smith, 2016). However, the site’s most valuable information is the classification scheme. Each artist is arranged according to 21 genres and over 100 styles. Styles are not considered sub-categories of genres, but labels or keywords freely assigned to an artist. Allmusic also includes an artist’s active period expressed in decades. This information means that artists can be located in time and their influence tracked across decades.\n\nStudying connections between musicians through cover versions provides an opportunity to analyze music performers’ influence on their contemporaries and later artists, build impact indicators and track links between music genres. In a previous study, the global network of artists connected through cover songs was modeled and analyzed (Ortega, 2021). One of the most important results was the detection of time patterns in covers. The results mainly pinpointed two waves in which songs were covered by artists raised in specific periods. Thus, a first wave involved performers from the first half of the 20th century who mainly covered artists from the 1920s, when Jazz music was booming. Meanwhile, a second wave, with performers from 1950–2000, preferred covering songs by musicians that started their musical career in the 1960s, the decade when Pop/Rock music took off (Hall, 2014).\n\nHowever, these results also suggested that musicians beginning their careers in the 21st century were again changing their preferences, choosing to cover more contemporary musicians than 1960s old Pop/Rock glories. That being the case, we would be witnessing a third wave in popular music. This study will thoroughly analyze contemporary musicians’ behavior when covering songs, to discover whether a third wave is emerging and who is responsible for the change.\n\n\nRelated research\n\nImportant studies have focused on the transformations of popular music in the 21st century. From a business point of view, VanDen Heuvel (2020) perceived that artists are using sales and streaming to attract concert goers, rather than sales of recorded music as in the 20th century. Tan et al. (2020) examined how the new digital environment is influencing the business ecosystem of popular music, K-Pop, in Korea. Meier (2017) also emphasized the power of digital media in promoting popular music artists. Another important aspect is the role of social networks in the emergence of new artists and genres (Cayari, 2011). Verboord and van Noord (2016) observed that artists on the periphery with a good fan base in social networks could improve their visibility, while Oh and Lee (2013) described the importance of YouTube in the emergence of K-Pop. Other authors have pointed out the influence of TV song contests promoting new talent (Kjus, 2017).\n\nCover songs in contemporary popular music have always been studied from a theoretical and cultural perspective. Some authors (Weinstein, 1998; Coyle, 2002; Plasketes, 2005) have reported a loss of originality in covers, with actions of appropriation in some cases. Others (Cusic, 2005; Solis, 2010), however, have defended the value of cover versions in transmitting new styles and ideas. In this context, most analyses of covers are case studies that focus on content and the consequences for popular music. For example, Doktor (2008) analyzed cross-gender adaptations of the song Satisfaction, while Chu and Leung (2013) studied the importance of remakes in the fall of Cantopop.\n\nFrom a quantitative perspective, the work of Anderson (2015), who quantified the wave of ‘adaptations’ in French Pop, is worthy of mention. And more recently, Ortega (2021) was the first to map the entire network of cover songs between artists, revealing two clear musical waves: Jazz in the 1920s and Pop/Rock in the 1960s. There is, however, a gap in the exploration of cover songs and their role in transforming Pop/Rock music today.\n\n\nObjectives\n\nThe main objective of this study is to find evidence of a changing pattern in cover versions by 21st-century artists. To that end, we analyzed covers between generations to discover which new artists or genres are leading these changes. Several research questions were formulated:\n\n• Is there a pattern of change in contemporary music related to covers?\n\n• Is a specific music genre influencing this change?\n\n• Which musicians are leading this change and attracting more covers?\n\n\nMethods\n\nThis research is based on the analysis of quantitative data extracted and compiled from two web sources: SecondHandSongs and Allmusic. The first one was used to extract the connections between original and versioned songs. This site was selected because it is the most comprehensive source of cover songs. Allmusic was selected for extracting the music gender and starting decade of each artist. The reason for using this platform is because it is the only database that classifies artists by decade and music genre. A web crawler was built to sequentially extract information about performers and cover songs. This task was accomplished during January 2020. Data were analyzed using descriptive statistics, using R packages and Excel for the tables and graphs.\n\nAfter the selection of the web sources, several scripts in WebQL were written to extract specific items from each source:\n\nSecondHandSongs: The first step was to design a crawler to extract the internal ID of each performer. The platform assigns a sequential number, then numbers from 1 to 175000 were automatically generated (no more than 175000 artist codes were detected) and these codes were inserted in the url: https://secondhandsongs.com/artist/{artist code}/covers#nav-entity. This page shows the list of cover songs by each artist. Song titles, song codes, performers, performers code, artist, artist code, nationality, born date and dead date were extracted from this web page.143,707 artists were retrieved, a 99.9% of the total number of artists reported by the site in that date.\n\nAllmusic: As with SecondHandSongs, sequential IDs are assigned to each performer. Codes from mn0000000001 to mn0003600000 were generated and added to the url: https://www.allmusic.com/artist/{artist code}. Information about the fields title, active, genre and styles were extracted from the section Artist details, resulting in 871k performer profiles.\n\nThe next stage was to match the artists list of SecondHandSongs with the Allmusic’s one. However, this process was problematic because an artist’s name could be written differently in each platform. Thus, certain characters, such as ampersands and punctuation marks, were removed or replaced by letters (Iron & Wine by Iron and Wine, Eli “Paperboy” Reed by Eli Paperboy Reed). In other cases, different variations of names were normalized (B.R.M.C. became Black Rebel Motorcycle Club, Tatu became t.A.T.u); synonymy between different artists (Nirvana, 1960s British pop band and Nirvana, 1990s American alternative band) was solved by adding a digit to the name. Finally, a total list of 106k artists (73.8% of the initial sample) and 855k (96.6% of the total songs indexed in the platform) cover and original songs were obtained.\n\nFor this analysis, 11,614 soloists and bands starting their music career in the 21st century were selected and 76,177 covers associated with these artists were identified, along with the name, genre and decade in which the covered artists initially appeared.\n\nIn SecondHandSongs, each cover has an ID because a song could have a different title from the cover version. Translations and reworking of lyrics could cause slight variations between the original song and the cover (i.e., “That’s all right” by Arthur Crudup and “That’s Alright Mama” by Bob Dylan). Therefore, links between artists were established according to the number of times an artist covered another, regardless of song title. In the rare event that an artist covered the same song more than once, it was counted as a different version.\n\nMedleys were removed because they include parts from more than one song and SecondHandSongs does not accurately identify which performer is the author of each part. Samples were also removed because they do not reuse an entire song.\n\nSecondHandSongs usually assigns a generic unknown to traditional songs or when the original performer is unknown. These covers were removed because no connection can be created between artists. The platform also joins the codes of two or more artists when they perform together (e.g., Jennifer López and Ll Cool J, Holly Golightly and The White Stripes). These cases were duplicated and the same song was assigned to each artist.\n\n\nResults\n\nFirst, the distribution of artists by genre and sub-genre on the current music scene is important to identify which music genres are more popular in the 21st century. Figure 1 shows that over half the musicians belong to Pop/Rock (55.6%), while Alternative/Indie Rock (40.3%) and Pop (37.3%) are the most salient sub-genres within Pop/Rock. Other important genres today, but with considerably fewer artists, are Jazz (8.3%), Electronic (6.4%) and Country (5.1%). Therefore, Pop/Rock music is currently the most dominant music genre and both aspects, Rock (Alternative/Indie Rock) and Pop, are the principal sub-genres in similar proportion. The full dataset can be found under Underlying data (Ortega, 2022).\n\nFigure 2 depicts the proportion of artists’ covers according to decade and by the music genre of the performers. This graph illustrates differences between genres when they are covered by artists from other periods and pinpoints which artists from different decades exert most influence in each genre. Thus, for example, the artists most covered by Latin singers are those who started their career in the 1960s (32.6%), while performers raised in the 1950s (20.8%) are the biggest influence for Blues artists. The general pattern is that in most genres covers are mainly of artists from the 1960s, ranging from 33.6% of Children’s to 18.1% of Vocal music. This result can be interpreted in two ways. First, most genres are mainly influenced by artists from the 1960s, when Pop/Rock appeared. Second, 1960s music cuts across all genres: Reggae, Rhythm and Blues (R&B) and Country musicians also cover artists from the 1960s, many of them Pop/Rockers. This would suggest that 1960s music influences all kinds of music today.\n\nBut not all genres follow this pattern. Some pre-Rock genres with a glorious past retain their connections with previous periods. Jazz, Blues and Vocal focus their covers on artists who emerged before the 1950s, a time when these genres flourished and hit their height of popularity. Thus, Jazz performers mainly cover songs from the 1920s (19.6%), Blues from the 1950s (20.8%), and Vocal music from the 1920s (16.1%) and 1930s (16.3%).\n\nAlso worthy of mention is the particular case of Stage & Screen, a genre with a high percentage of covers of artists from the 1990s (20.9%) and 2000s (33.7%). These outlier values stem from The Piano Tribute Players, a band specializing in adapting songs by successful artists to piano pieces for movie soundtracks. Interestingly, this example shows how today’s artists value the influence of their contemporaries, using them as recent classics. This issue will be explored further below.\n\nAs we have seen in Figure 1, more than half of current music is made by Pop/Rock musicians. However, Figure 2 indicates a more homogeneous distribution of covers throughout the decades. The graph shows that Pop/Rock performers only covered 22.9% of songs from 1960s artists, while other covers are distributed across other decades, such as the 1970s (15.8%) and 1980s (12.6%). This pattern could suggest that today’s Pop/Rockers are influenced by a wide range of musicians from different periods, not only by 1960s artists.\n\nFigure 3 gives a detailed view of Pop/Rock covers, distinguishing those performed by generations from the 1990s, 2000s and 2010s. It illustrates how the cover preferences of different generations of musicians change according to when artists began their careers. Thus, for example, 13.1% of the cover songs made by the 1990s generation was of 1950s artists, while the 2010s generation covered 17.2% of songs by 1970s artists.\n\nIn general, the graph shows that the 1960s remains the decade of reference for generations from the 1990s (29.2%) and 2000s (25.1%). However, artists from the 2010s have changed this pattern and, for the first time, prefer to cover more songs by contemporary artists from the 2000s (21.9%) than by 1960s oldies (16.1%). In fact, this change in trend already occurred in the 1990s when the following generations began covering more young artists than older ones. For example, 7.3% of 1990s performers were covered by their contemporaries, and 9.5% and 14.8% by the generations of the 2000s and 2010s, respectively. For musicians from the 1980s, 1970s and 1960s, the pattern is just the opposite. 1990s artists, for example, cover more songs by artists from those decades than from the 2000s and 2010s generations.\n\nFigure 4 represents the evolution of Pop/Rock musicians’ genre preferences when they come to cover songs by artists from different generations. Thus, for example, the most covered artists from the 1960s are Pop (14.3%) and R&B (12.5%) performers. In the 1980s, however, the most covered artists are Alternative/Indie Rock (9.9%), Pop (9.7%) and Hard Rock (9.6%) musicians.\n\nThe aim was to observe whether today’s Pop/Rock performers’ preference (Figure 3) for covering contemporary artists has some connection with music sub-genres. The graph clearly shows that Alternative/Indie Rock (16.1%), Pop (13.5%) and Dance (5.9%) versions proliferated in the 2010s. This increase is especially significant in Dance (Δ562%) and Pop (Δ40%) in the 2000s. Interestingly, Pop made by 1960s–1980s generations fell from favor, stalled in the 1980s–2000s and firmly bounced back in the 2010s. These results suggest that 21st-century Pop/Rock artists are covering more contemporary musicians due to a possible reevaluation of Pop and the emergence of Dance music.\n\nFinally, Table 1 ranks the ten artists most covered by musicians from the 2000s and 2010s. This comparison clearly shows how 2000s performers’ preference for classic 1960s artists is being replaced that of 2010s artists for contemporary Pop/Rock singers. Thus, the most covered artists in the 2000s are key figures in the history of Pop/Rock such as The Beatles (3.1%), Bob Dylan (1.7%) and David Bowie (.8%), all raised in the 1960s. Also appreciable is the emergence of covers of more recent artists like Queen (.62%), Bruce Springsteen (.57%) or Pink Floyd (.41%), though they belong to the 1970s and 1980s.\n\nHowever, the ranking of the most covered artists in the 2010s reveals a radical change in positions, with many more 21st-century artists now appearing. For the first time, The Beatles are no longer the most covered band since the 1960s. Taylor Swift (1.58%) has replaced them as the most covered artist by the 2010s generation. Other important contemporary performers such as Justin Bieber (1.03%), Ed Sheeran (.98%) and Adele (.87%) also figure among the most covered. This weighty presence of contemporary performers in the top positions demonstrates that this change is not caused by specific stars only. Rather there is a genuine generational shift in preferences for more covers of contemporaries than of 1960s Pop/Rock classics. The table also indicates that the most frequent sub-genres of these top covered artists are Pop (Taylor Swift, Adele) and Dance (Justin Bieber, Katy Perry, Rihanna), which fits with the results shown in Figure 4.\n\n\nDiscussion\n\nQuantitative analysis of cover songs between music artists offers the opportunity to track the influence and impact of musicians on their contemporaries and next-generation artists. A broader perspective, encompassing genres and the decades when performers began their careers, can provide insights into the evolution of popular contemporary music since the early 20th century. Concretely, more than half of all active performers of 21st-century music are Pop/Rock musicians. Since appearing in the 1960s, Pop/Rock music has grown considerably and is today the main music genre in popularity and releases (Resnikoff, 2016; Music & Copyright, 2018). One explanation for the continuity of this genre is that, since the 1960s, some of its most salient founders, such as The Beatles, Bob Dylan and Elvis Presley, have been covered by subsequent generations (Ortega, 2021) and are the main reference for current popular music. That today performers from many different genres such as Latin, Reggae, Rap or R&B are increasingly covering 1960s artists is a sign that Pop/Rock influence transcends genres.\n\nHowever, results have shown that early Pop/Rock is starting to lose ground. Artists raised in the 2010s are tending to cover more songs by contemporary 21st-century artists than classic performers from the 1960s (Crane, 2005). This change in trend arises mainly from Pop and Dance music, the sub-genres most covered by Pop/Rock performers today. Unlike the 1960s Pop/Rock revolution, this new wave has not emerged from a new music genre attempting to replace old music traditions, but from an internal revolution or reevaluation of Pop music. Bolstered by Dance music, a transformation is giving rise to a new language and new inspirations. Headed by Taylor Swift, a new generation of Pop and Dance artists are becoming the main influence of current Pop/Rock music and perhaps of up-and-coming artists. Young artists raised in the 21st century like Taylor Swift, Justin Bieber and Ed Sheeran are the most covered artists in the 2010s, overtaking classic stars like The Beatles, Bob Dylan and David Bowie, who had led the ranking of the most covered artists since the 1960s. The reasons behind this generational replacement could be related to the appearance of new media (i.e., YouTube, TikTok) and TV song contests (i.e., Idol, The Voice) popularizing new young artists that mainly opt to cover songs by today’s idols (Cayari, 2011; Kjus, 2017).\n\nNevertheless, these results should be considered cautiously, given the limitations in the data. The categorization of analyzed units might produce misclassifications and the creation of spurious groups. In our study, the Dance sub-genre is somewhat imprecise and many artists in this category could also belong to Pop (i.e., Justin Bieber, Katy Perry, Rihanna). Therefore, this music genre classification should be seen in perspective.\n\nA more important limitation is associated with the completeness of the data. Many databases often lack comprehensive data of the latest events, depicting an incomplete picture of recent years. That the number of covers in the 2010s is less than half of the 2000s could indicate that SecondHandSongs has yet to index all the cover songs from recent years. Although the number of covers has dropped since the 1950s (Ortega, 2021), new records could complete this picture in the future. Further studies are needed to confirm these results and uncover more clues about this generational change.\n\n\nConclusions\n\nSeveral conclusions can be drawn from the results of this study. The findings reveal a clear change in pattern in contemporary popular music concerning covers. Pop/Rock artists raised in the 2010s are covering more songs by contemporary musicians than by the music legends of the 1960s. This change means that important 1960s figures like The Beatles and Bob Dylan are no longer the most covered artists for the first time since the 1960s. Dance and Pop sub-genres—the sub-genres most covered by the 2010s generation—are responsible for this transformation. This new wave is led by Taylor Swift and followed by emerging 21st-century figures like Justin Bieber, Ed Sheeran and Adele, who are the most covered by the 2010s generation. These results allow us to conclude that the quantitative study of cover songs between artists can be a good approach to understanding the evolution of musical influences.\n\n\nData availability statement\n\nOSF: Is Taylor Swift leading a new Pop revolution? A cross-generation analysis of Pop/Rock cover songs. https://doi.org/10.17605/OSF.IO/9JRGC (Ortega, 2022).\n\nThis project contains the following underlying data:\n\n• Cover_songs.csv [list of performers and cover songs]\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "References\n\nAnderson K: Song ‘adaptations’ and the globalisation of French pop, 1960–1970. Fr. Cult. Stud. 2015; 26(3): 330–342. Publisher Full Text\n\nBlack ML: The World Wide Web as complex data set: Expanding the Digital Humanities into the twentieth century and beyond through Internet research. Int. J. Humanit. Arts Comput. 2016; 10(1): 95–109. Publisher Full Text\n\nCayari C: The YouTube Effect: How YouTube Has Provided New Ways to Consume, Create, and Share Music. Int. J. Educ. Arts. 2011; 12(6): n6.\n\nChu YW, Leung E: Remapping Hong Kong popular music: covers, localisation and the waning hybridity of Cantopop. Pop. Music. 2013; 32(1): 65–78. Publisher Full Text\n\nCoyle M:Hijacked hits and antic authenticity: cover songs, race, and postwar marketing.Beebe R, Fulbrook D, Saunders B, editors. Rock over the Edge: Transformations in Popular Music Culture. Duke University Press;2002; pp. 133–158.\n\nCrane D: Cover Me: Introducing the Instant Tribute. The New York Times.2005. (accessed 5 April 2021).Reference Source\n\nCusic D: In defense of cover songs. Pop. Music Soc. 2005; 28(2): 171–177. Publisher Full Text\n\nDoktor SD: Covering the Tracks: Exploring Cross-gender Cover Songs of the Rolling Stones ‘Satisfaction’. University of Georgia;2008. Ph.D. thesis.\n\nHall MK: The emergence of rock and roll: Music and the rise of American youth culture. Routledge;2014.\n\nKjus Y: Harmonious or out of tune? Cooperation between the television industry and the music business in talent contests of the 2000s. Media Cult. Soc. 2017; 39(7): 1011–1026. Publisher Full Text\n\nMeier LM: Popular music as promotion: Music and branding in the digital age. John Wiley & Sons;2017.\n\nMusic & Copyright: Streaming growth boosts R&B/hip-hop share of global recorded-music sales.2018. (accessed 5 April 2021).Reference Source\n\nOh I, Lee H-J: Mass media technologies and popular music. Korea Journal. 2013; 53(4): 34–58. Publisher Full Text\n\nOrtega JL: Cover versions as an impact indicator in popular music: a quantitative network analysis. PLoS One. 2021; 16(4): 0250212. (accessed 5 April 2021). PubMed Abstract | Publisher Full Text\n\nOrtega JL: Is Taylor Swift leading a new Pop revolution? A cross-generation analysis of Pop/Rock cover songs. [Dataset].2022. Publisher Full Text\n\nPlasketes G: Re-flections on the Cover Age: A Collage of Continuous Coverage in Popular Music. Pop. Music Soc. 2005; 28(2): 137–161. Publisher Full Text\n\nResnikoff P: What Are the Most Popular Music Genres In America? Digital Music News.2016. (accessed 5 April 2021).Reference Source\n\nSecondHandSongs: Introduction to the database.2020. (accessed 5 April 2021).Reference Source\n\nSmith E: The Story of AllMusic, the Internet’s Largest, Most Influential Music Database. Motherboard.2016. (accessed 5 April 2021).Reference Source\n\nSolis G: I did it my way: rock and the logic of covers. Pop. Music Soc. 2010; 33(3): 297–318. Publisher Full Text\n\nTan FT, Ondrus J, Tan B, et al.: Digital transformation of business ecosystems: Evidence from the Korean pop industry. Inf. Syst. J. 2020; 30(5): 866–898. Publisher Full Text\n\nVanDen Heuvel K: Changes in Live Performance of Popular Music in the 21st Century. Ph.D. thesis, St. Norbert College.2020. (accessed 5 April 2021).Reference Source\n\nVerboord M, van Noord S : The online place of popular music: Exploring the impact of geography and social media on pop artists’ mainstream media attention. Pop. Commun. 2016; 14(2): 59–72. Publisher Full Text\n\nWeinstein D:The History of Rock’s Pasts Through Rock Covers.Swiss T, Sloop JM, Herman A, editors. Mapping the Beat: Popular Music and Contemporary Theory. Basil Blackwell Publishers;1998; pp. 137–151.\n\n\nFootnotes\n\n1 https://web.archive.org/web/20200129161939/, https://secondhandsongs.com/"
}
|
[
{
"id": "155272",
"date": "30 Nov 2022",
"name": "Tim Wall",
"expertise": [
"Reviewer Expertise Tim Wall is Professor of Radio and Popular Music Studies and Ben Torrens is a researcher in popular music production cultures."
],
"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 research makes a contribution to quantitative data retrieval and analysis of popular music, which are relatively neglected, and the use of recent and now readily-available datasets is very welcome. The wider implementation of approaches like this has real value for rethinking the assumptions of existing qualitative research done in the field, and for unearthing new findings.\nThere are, though, some fundamental problems with clarity of research question, the concept of a cover, and models of history and generation used in the research.\nThe explicit questions provided seek answers to patterns which are not defined. The first question seems to assume only who was covered, by whom and when are important. The second attributes agency to an undefined concept of genre as a determining force. Finally, the articulation of the third question suggests musicians whose songs attract covers somehow have agency in determining the cover activities of other musicians. It isn’t clear that the methods proposed can answer these sorts of questions, even if they were articulated with less ambiguity. Ultimately, this leads the author to seem to ascribe the trend they have identified in the data, solely to artist intention.\nThere is, though, a set of potentially interesting methodological questions that could be posed through such research about the degree to which we can know things through such research and the extent of the limitations of these approaches. Such a study would be particularly valuable given the rarity of these sorts of approach.\n\nTo be more successful in revealing important aspects of covering as a popular music practice, we need a clear definition of what we mean by a cover. The research does not take full advantage of the existing literature (which is effectively cited) on covers, or on the history of popular music in order to create a specific activity.\nThis links to the need for a fuller grasp of a history of popular music practices. Specifically, the idea of a cover is a relatively new one which emerged at a point in the 1960s in which artists increasingly recorded songs they had themselves written, and the songs became indelibly linked to their performance by the ‘original’ artist. The widespread split between artist and repertoire role in the preceding decades meant that all artists shared a wide repertoire of songs written by professional songwriters. Performing and recording a song that had previously been recorded by another group or artist, therefore, was not always considered as ‘a cover’ in the ‘pop/rock’ world, as the author implies. Nor do similar practices carry the same connotations in different popular music cultures, for example in jazz, where the common repertoire is established as a canon of standards.\nA more historical sense of popular music would also allow for a more developed idea of artist generation and consideration of any other important factors, like strategic input of music industry organisation, practices and key figures, or significant cultural phenomena resonating with the cover version like Radio 1’s Live Lounge in the UK or ‘Carpool Karaoke’ in the US.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "9234",
"date": "31 Jan 2023",
"name": "José Luis Ortega",
"role": "Author Response",
"response": "This review starts from a misunderstanding between fact and meaning. A cover is a fact and its definition is presented in the Introduction: “A cover is then a version of the same song performed, recorded or released by subsequent artists.” However, the meaning or idea of cover would change throughout time, and it depends on the sociological, cultural and historical context. The problem here is that you never would know the meaning if you do not previously analyze the fact. That is, it is impossible to know why musicians cover songs if you do not describe patterns and trends that point to changes in the use of covers. For example, the number of covers increases in the period 1900-1950, but from 1960s this practice went down until 2000s. Why? Because there was a change in the meaning. In the 1920s, during the jazz era, cover could be associated with an instrumental use for developing technical skills (standards). But from 1960s, pop/rock emerged and the meaning changed (Ortega, 2021). Now, covers would be a sign of lack of originality and could only be used for tribute. An example of this confusion between fact and meaning is the following comment: “Specifically, the idea of a cover is a relatively new one which emerged at a point in the 1960s in which artists increasingly recorded songs they had themselves written, and the songs became indelibly linked to their performance by the ‘original’ artist.” Covers as fact exist since the start of the recorded music in the first decades of the 20th century. Therefore, they did not “[emerge] at a point in the 1960s”. That which did emerge in the 1960s is a new way of understanding a cover. But that new idea of cover cannot be known if you do not uncover changes in its evolution. “Performing and recording a song that had previously been recorded by another group or artist, therefore, was not always considered as ‘a cover’ in the ‘pop/rock’ world, as the author implies.” A cover as a fact is the same all the time. Duke Ellington performing “Yellow Dog Blues” by the Prince’s Band in 1928 is the same action as Nirvana's cover of “Song of a Gun” by The Vaselines in 1990, but the meaning of those actions is different. We know different meanings because the frequency of covers in the jazz era is much higher than in the 1990s, which suggests that the meaning is different. Therefore, you need to detect a pattern and then suggest a meaning. The contrary is just interpretations based on speculations, and not on scientific evidence. To reinforce the objectives of the paper, I have decided to rewrite this section to better explain the aim of the paper and to present more precise research questions. A paragraph has also been introduced in Introduction and Study design to emphasize that this is a quantitative study based on the processing and analysis of a large data set of cover songs. Those sections explain now that this approach is the most suitable to answer research questions on the evolution and changes in the covering of songs in the 21st century."
}
]
}
] | 1
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https://f1000research.com/articles/11-1273
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