Emergence delirium is a kind of mental disorder during the early awakening period after general anesthesia, which is manifested as the combination of perceptual disturbance and psychomotor agitation. It is an independent risk factor for postoperative delirium and even long-term postoperative cognitive decline, which often affects the postoperative outcome and deserves the attention of clinical anesthesiologists. There are many studies on emergence delirium, but the quantity and quality of these studies are unclear. Therefore, we conducted a bibliometric analysis of studies on emergence delirium between January 2012 and December 2021. Through the analysis of relevant literature, the research hotspots and trends of emergence delirium are understood, which can provide a reference for future research.We searched the Web of Science Core Collection (WoSCC) for original articles and reviews related to emergence delirium published between 2012 and 2021, and collected a variety of bibliographic elements, including annual publications, authors, countries/regions, institutions, journals, and keywords. Three different science-based tools  were used for this comprehensive analysis.From January 2012 to December 2021, a total of 912 emergence delirium (ED) related literature were published, including 766 original research articles and 146 review articles. The number of publications has increased every year except 2016. The United States published 203 articles, ranking first with China, followed by South Korea (95 articles). The United States is also the country with the most citations , and Yonsei Univ is the most productive institution. The most published journal was PEDIATRIC ANESTHESIA, with the highest h and g index. LEE JH is the most influential author in this field.“Children, emergence agitation, delirium, dexmedetomidine” are the hot topics in this field in recent years. The bibliometric analysis in this field will provide the future direction for the study of emergence delirium for clinicians. The verStudies have reported a wide variation in the incidence of emergence delirium in adults, with an observational study involving 91 patients reporting a 45% incidence using DSM-IV diagnosis and a study involving 1,000 patients using Nu-DESC reporting a 4.3% incidence. The large differences in reported incidence among different studies may be related to the large differences in sample size, different diagnostic tools and control of risk factors. Many risk factors are associated with emergence delirium, such as surgical procedure, the score of PAB (pediatric anesthesia behavior), time of anesthesia, age, etc. . Age is Bibliometric analysis is a quantitative and qualitative analysis method. It uses mathematical and statistical tools to evaluate the correlation between publications in a certain field, and can objectively analyze the research impact, so as to evaluate its development trend and summarize the research direction . Althoug2.2.1.Web of Science, as a high-quality digital literature resource database, is considered the most suitable database for bibliometric analysis due to its powerful functions . We sear2.2.via WoSCC. All records retrieved were downloaded in “plain text” format and relevant information was extracted: number of papers, title, keywords, Hirsch index (H-index), country/region and citations, branches, authors, journals and references, etc. Three different sciometrics tools  were used for knowledge mapping.Raw data is downloaded 2.3.The online analysis and retrieval functions from Web of Science(Wos) include: research field, document type, journal, author, affiliate, country, language and the number of articles cited, citation times, etc. The information we gleaned from these publications, including titles, authors, affiliations, languages, document types, abstracts, keywords and citation references, is imported into Biblioshiny (a web-based interface for bibliometric measurement), the VOSviewer software and the CiteSpace software, to get visual analysis and knowledge mapping.Bibliometrix is a comprehensive R language package for bibliometric analysis and scientific visualization, which is developed and maintained by Massimo Aria and Corrado Cuccurullo. Bibliometrix is used for computation and visualization to extract bibliographic information for descriptive analysis . The datVOSviewer is a software tool for constructing and visualizing document metering networks. This software can extract country, keyword, author, and other relevant information from literature retrieval data, and use it for relationship construction and visual analysis, realize the drawing of a scientific knowledge map , and disCiteSpace is a data standardization method based on set theory, which is used to measure the similarity of knowledge units and obtain time zone and timeline views in time slices to understand the development process and trend of this field. It focuses on identifying key points in the development of a field or domain, especially knowledge turning points and key points. It helps to get the reference pulse of the reference and find keywords with strong reference pulse .We expor3.3.1.In the past 10 years, the total number of documents related to this topic retrieved from WoS is 912. The overall trend of publication output is increasing year by year, with an annual growth rate of 19.15%, as shown in 3.2.n = 10, 1.10%) and KIM JT . Based on the h-index, LEE JH was the top 1 (h-index =7), KIM HS and ZHANG Y ranked No. 2 (h-index = 6). M-index is used to eliminate the influence of different experiences or ages among authors, helping to identify truly successful scientists (m-index of 0.833 and then ZHANG Y (m-index = 0.75), LEE JH (m-index = 0.7), LI J (m-index = 0.556), and KIM HS (m-index = 0.545) followed him.In our data set, a total of 3,743 authors participated in this study, including 58 authors of single-authored documents and 3,685 authors of multiauthored documents. ientists . GARCIA We use VOSviewer software to perform co-citation analysis of cited authors . One hun3.3.The 912 literature retrieved in WOS were widely distributed, up to 67 countries, and the average citation times (including self-citation) were 14.29. Global contribution of publications on emergence delirium as shown in 3.4.Keywords embody the core and essence of a paper, and are also the concentration of a scientific research field, Keywords plus is a word or phrase that often appears in the title of the reference cited by the retrieved article . VOSviewIn order to understand the progress of emergence delirium research in the time dimension the Timezone graph provided by CiteSpace was used to present the map of the keyword co-occurrence network . The sizIn this study, CiteSpace was also used to evaluate the first 18 mutant words and their citation history . The so-3.5.n = 56). The second most popular journal was BMC ANESTHESIOLOGY, which has 30 publications. BRITISH JOURNAL OF ANAESTHESIA ranked No. 3 (n = 22) and was followed by INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE (n = 21), JOURNAL OF PERIANESTHESIA NURSING (n = 20). These journals focus on anesthesia and drugs. We use VOSviewer software to perform citation analysis of sources , ANESTHESIA AND ANALGESIA (h-index =11), and BMC ANESTHESIOLOGY (h-index =10).During that time, 409 journals published literature related to emergence delirium. The top 10 most productive journals in this area are shown in  sources . Thirty-4.Bibliometrics is a branch of information science. It is a quantitative and qualitative analysis method that uses statistical data to describe or show the relationship between publications in a certain research field and objectively analyze the influence of research . HoweverEmergence delirium is a transient organic brain syndrome characterized by disturbances in attention, memory, feeling, thinking, psychomotor and sleep cycles. Clinically, emergence delirium usually presents as acute onset, mainly hyperactivity and agitation, and does not act according to instructions. Meanwhile, various degrees of involuntary movement occur. In serious cases, it may cause NSSI, fall from the bed and fall, and there are no clear diagnostic criteria. Waking agitation and emergence delirium are closely related and emergence delirium can be regarded as further development on the basis of waking agitation. The etiology and mechanism of emergence delirium remain unclear. Clinicians and researchers believe that the occurrence of emergence delirium is related to its risk factors. Possible risk factors currently considered include age, preoperative anxiety, pain stimulation, preoperative medication, mode of anesthesia, type of surgery, and time to recovery. Studies have shown that emergence delirium leads to an increased incidence of postoperative delirium (POD) . Early dIn this study, we performed a bibliometric analysis of trends and research hotspots in emergence delirium using data extracted from the Web of Science database using VOSviewer, CiteSpace and Bibliometrix software. Since the database was established, we have retrieved 912 original articles and reviews. As shown in n = 31), Seoul Natl Univ (n = 27), Harvard Med Sch (n = 23), Korea Univ (n = 19). Although South Korea is lower than the US and China in terms of total national citation frequency, its two research institutions Yonsei Univ and Seoul Natl Univ occupy two of the top three places in the ranking of research institutions, which indicates that the average paper quality of these two institutions is slightly better than that of other national research institutions.Through the country/region distribution of literature, we can master the distribution of foreign research forces in this field, which provides a reference for our investigation. A total of 912 articles on emergence delirium were published in the last 10 years by research teams in 67 countries. The United States and China were the most prolific, each accounting for 22% of all countries’ publications, followed by South Korea (10%). There are 1,194 institutions involved in this area, Korea has the largest number of Yonsei Univ publications (n = 41), followed by Sichuan Univ , PEDIATRIC ANESTHESIA journal has the largest number of publications and the highest H index. The number OF citations  is second only to the BRITISH JOURNAL OF ANAESTHESIA, which is the most closely cooperated with other journals in this research field.By studying the distribution of source publications, it is helpful to find the main research positions in this field. According to the statistics, from 2012 to 2021, the literature was published in 409 different journals, and the top 10 journals were all influential in this field. Among them, the BRITISH JOURNAL OF ANAESTHESIA is the most cited journal , the most cited publications and extensive international cooperation. In recent years, the research focus of emergence delirium has gradually shifted from the assessment of its risk factors  to the timely identification of high-risk patients, diagnosis and treatment with drug therapy and/or non-drug intervention, so as to achieve the purpose of prevention and control. Additionally, by processing a large number of scientific data and generating research influence to clarify the current research status, the study may attract the attention of more researchers and lay the foundation for subsequent mechanism and treatment research. We summarized the above aspects, and in the long run, it may have certain guidance for the existing and future treatment mode.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.KW, JW, and RD contributed to the conception and design of the study. KW and JC extracted data sets from the Web of Science for statistical analysis and was a major contributor to writing the manuscript. JC participated in the interpretation of the research results. All authors contributed to the article and approved the submitted version.This work was supported by Medical Science and Technology Research Foundation of Guangdong Province, China (grant number B2022115).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The SARS-CoV-2 pandemic exacerbated existing health-related challenges in schools and created new ones. Under pandemic conditions, health risks increased, and with them the requirements for occupational safety and health (OSH) measures. The aim of the study was (a) to examine the status quo of OSH measures in German schools, (b) to analyze whether the implementation of OSH measures was associated with preferable outcomes and (c) to identify predictors for the implementation of OSH measures.A nationwide cross-sectional online survey was conducted among teachers at all school types in Germany in March 2021. Data on the implementation of OSH measures , associated health-related parameters  and predictor variables  were assessed using descriptive statistics, analysis of variance and multiple linear regression analysis.N = 31,089) reported that their schools met legal requirements for occupational safety and health measures. Beneficial associations became apparent where more measures were implemented, e.g., significantly better somatic and mental health. Predictors for the implementation of OSH measures were found, especially on a systemic level .Less than 10% of surveyed teachers (Our study can serve as a basis for future studies. It provides a status quo regarding the implementation of, associations with and predictors for OSH measures in German schools. Our results are best understood as evidence-based arguments to encourage political decision makers to improve the implementation of OSH measures in German schools and thereby foster teachers' health. From March 2020, about 1.5 billion students worldwide as well as their teachers were absent from schools as a result of extensive measures to mitigate the spread of SARS-CoV-2 . This reTargeting teachers' health is highly relevant from a public health point of view since teachers are a huge occupational group in Germany  and responsible for the education of approximately 10,000,000 students, which amplifies their relevance even further  defines the term “at work” .risk assessment, a structured survey, documentation and evaluation of environmental conditions that represent a possible hazard for employees have to be conducted. It is a basis for the systematic and effective management of OSH. All employers in Germany are legally obliged to conduct risk assessments in accordance with the Act on the Implementation of Measures of Occupational Safety and Health to Encourage Improvements in the Safety and Health Protection of Workers at Work, Section 5  and the Institute of Occupational, Social and Environmental Medicine, University Medical Center of the University of Mainz, Germany. Therefore, for these three a priori selected OSH measures, data has been collected in a nationwide survey on teachers in Germany . AnotherGiven the absence of school-related data on the impact of these measures, especially during pandemic conditions, the aforementioned justification of the relevance of the selected OSH measures by experts and lawmakers was the rational starting point for our research. Still, this justification can and should be tested empirically by analyzing associations with and predictors for OSH measures, which could help to prove their actual relevance. Due to the lack of literature regarding associations with health outcomes and predictors for the implementation of OSH measures in German schools, an explorative approach seemed to be suitable to close this gap.Therefore, the aim of the present study was (a) to examine the status quo of OSH measures in German schools, (b) to analyze whether the implementation of OSH measures was associated with preferable outcomes and (c) to identify predictors for the implementation of OSH measures. This may enable us to formulate recommendations on how to raise the level of implementation of OSH measures in German schools.Between March 1st and March 31st, 2021, teachers from all federal states in Germany were invited to participate in an online survey, presented using the web-based software LimeSurvey . The participants were recruited in cooperation with governmental  and non-governmental institutions , teacher-related societies (German Teachers Association), and projects associated with education (Monitor Lehrerbildung). There was an unconditional non-monetary incentive (EUR 2000.00 donation to the German Children's Fund) to foster the willingness to participate. Informed written consent was obtained at the beginning of the online survey. The ethical committee of the Medical Association of Rhineland-Palatinate approved the study before it was conducted (Application Number: 2020-15531).Participants completed an online questionnaire with approximately 350 items, covering a wide range of topics, which were arranged under the following categories: (1) sociodemographic and workplace information; (2) identification of SARS-CoV-2-specific stresses and challenges in schools for teachers; (3) implementation, communication, and compliance with hygiene policies/plans, both general and school-based; (4) impact of school operations during the SARS-CoV-2 pandemic on teachers; and (5) collection of best practices for infection protection and the implementation of the educational task during the pandemic. Before being applied in the present study, the questionnaire was pretested and revised in three steps. In the first step, experts from the Institute for Teachers' Health and the Institute for Occupational, Social and Environmental Medicine of the University Medical Center Mainz answered and commented on the questionnaire. In the second step, after revising the questionnaire, we invited teachers to take part in a comprehensive probing for the exact understanding of and associations with all items. We did this to ensure that the items were understood in the way we intended or were otherwise able to collect suggestions for (mostly minor) linguistic adaptations. In the third step, after the probing, the whole questionnaire was revised again, and our team conducted a final  quality check to eliminate final flaws .Has a risk assessment already been carried out at your school?” . Infection protection instructions were measured by the item “How long has it been since your last infection prevention training?” . Instructions on occupational safety were measured by the item “Did briefings on special hazards take place due to the COVID-19 pandemic?” . For further analysis, the responses to all three questions were condensed to the scale “Implementation of OSH measures” ranging from 0 to 3. For this purpose, answers to the three questions were dichotomized into “fulfilled” (= 1) and “not fulfilled” (= 0) before being accumulated into the OSH scale. Requirement fulfilled was defined as “yes” for the items on risk assessment and instructions on occupational safety and “ < 1 years” or “1-2 years” for the item on infection protection instructions, since these two answers comply with the legal requirements. A Principal Component Analysis (PCA) including the three aforementioned OSH measures was calculated to check if they load on more than one component. The Kaiser-Meyer-Olkin value for the PCA was.58 and the Bartlett-test was significant, p ≤ 0.001, so both requirements were sufficiently met. One component was extracted with loadings of 0.72 , 0.70 (infection protection instructions) and 0.62 (risk assessments), therefore the OSH scale was used for further analysis.The items regarding the school-related implementation of OSH measures were self-designed with high standards in a mutual process with experts from the German Federal Institute for Occupational Safety and Health (BAuA) and the Institute of Occupational, Social and Environmental Medicine, University Medical Center of the University of Mainz, Germany. Risk assessment was measured by the item “The following variables were used as dependent variables in research question (b) and as candidates for independent variables in research question (c).How strong is your fear of being infected with the SARS-CoV-2 virus?” on a scale from 0 (no anxiety) to 100 (powerful anxiety). We were given permission to use the item, which had also been used in other studies , ranging from 1 to 5. The item was created by the Institute for Teachers' Health, University Medical Center of the Johannes Gutenberg University of Mainz and is frequently used. To measure meaning of work, the item “Is your work meaningful?”  was taken from the validated German version of the Copenhagen Psychological Questionnaire , ranging from 1 to 5.Participants were asked to complete the validated German version of the Patient Health Questionnaire 4 , an est studies , 7. Job ionnaire . A self-Somatization symptoms were assessed with the German version of the PHQ-15 , 21 rangr > 0.1  were seDescriptive statistics were calculated (a) to examine the status quo of the implementation of OSH measures in German schools. Analysis of variance (ANOVA) were calculated (b) to analyze whether the implementation of OSH measures was associated with somatic and psychological health outcomes. Linear multiple regression was calculated (c) to identify predictors for the implementation of OSH measures.For analysis (a) and (b), the total sample (teachers and school management members) was used. For analysis (c), the prediction of the implementation of OSH measures, a subsample of school management members only was used, because the legal responsibility for implementation OSH measures in German schools is with them. Statistical analysis was performed using SPSS Statistics Version 27 .N = 31,089 was used for further analyses. In a mutual decision making process, our research team determined criteria for exclusion. First, only answering the sociodemographic question section at the beginning of the survey and no further question with regard to the research questions. And second, providing (very likely) inappropriate answers . 77.5% of the participants were female, the mean age was 45.8 years (SD: 10.5). Detailed sample characteristics are displayed in Overall, 39,359 teachers from all federal states and school types in Germany participated in our survey. The median answer time was 38.3 min. After data cleansing, a sample of Regarding our first research question, the status quo of OSH measures in German schools, only 8.3% of the participants reported that all three OSH measures were implemented. More than a third (36.6%) reported the implementation of none of the measures. For more details see When analyzing the OSH measures separately, the majority (76.2%) of the surveyed teachers stated that no risk assessment had been conducted at their school. Similarly, 67.1% of the teachers stated that infection protection instructions had not been carried out within the last 2 years. Regarding the implementation of instructions on occupational safety due to the SARS-CoV-2 pandemic, 55.8% of the teachers answered that they did not receive any. Regarding associations with somatic and psychological outcomes, our analysis revealed that teachers working at schools with a better implementation of OSH measures significantly differed from those working in schools with less implementation. ANOVA results can be found in p < 0.001, η2 = 0.004. Tukey's post hoc test revealed significant differences (p < 0.05) between all mean values of somatic symptoms for the subgroups by implemented OSH measures (0–3).Significant differences in the mean values of somatic symptoms were found when the number of implemented OSH measures was used to divide into subgroups: F = 24.15, p < 0.001, η2 = 0.010. Tukey's post hoc test revealed significant differences (p < 0.05) between all mean values of depression and generalized anxiety for the subgroups by implemented OSH measures (0–3).A similar pattern was found in the mean values of symptoms for depression and generalized anxiety when the number of implemented OSH measures was used to divide into subgroups: F = 70.89, p < 0.001, η2 = 0.006. Tukey's post hoc test revealed significant differences (p < 0.05) between all mean values of corona associated anxiety of getting infected with COVID-19 for the subgroups by implemented OSH measures (0-3).The corona associated anxiety of getting infected with COVID-19 also differed significantly when the number of implemented OSH measures was used to divide into subgroups: F = 43.82, p < 0.001, η2 = 0.016. Tukey's post hoc test revealed significant differences (p < 0.05) between all mean values of health concerns for the subgroups by implemented OSH measures (0–3).Regarding health concerns too, significant differences were found when the number of implemented OSH measures was used to divide into subgroups: F = 112.50, p < 0.001, η2 = 0.012. Tukey's post hoc test revealed significant differences (p < 0.05) between all mean values of satisfaction with work for the subgroups by implemented OSH measures (0–3).Significant differences in satisfaction with work were found when the number of implemented OSH measures was used to divide into subgroups: F = 100.90, p < 0.001, η2 = 0.006. Tukey's post hoc test revealed significant differences (p < 0.05) between all mean values of meaning of work for the subgroups by implemented OSH measures (0–3).For the meaning of work too, significant differences were found when the number of implemented OSH measures was used to divide into subgroups: F = 48.84, r > 0.1) to be included into the multiple linear regression model, 18 significantly predicted the number of implemented OSH measures. The R2 for the regression model was 0.17 and the adjusted R2 was 0.15, indicative for a moderate goodness-of-fit according to Cohen . Detailed information regarding the predictive value and significance of the independent variables can be found in Of the 32 independent variables that met the requirement (to Cohen . The indp < 0.001) followed by the federal states Saxony , Mecklenburg-Vorpommern  and North Rhine-Westphalia . The variables with the highest negative beta-coefficients for the implementation of OSH measures in German schools were the school types academic secondary school , comprehensive school , health concerns  and depression symptoms .The variables with the highest positive beta-coefficients for the implementation of OSH measures in German schools were, existence of a concept for the implementation of digital teaching  to examine the status quo of OSH measures in German schools, b) to analyze whether the implementation of OSH measures was associated with preferable outcomes and c) to identify predictors for the implementation of OSH measures. Regarding all three aims—to our best knowledge—there were research gaps to be filled. Therefore, we were very interested to close these gaps.With regard to the first aim, our results show that OSH measures were implemented insufficiently in German schools. Less than 10% of the teachers in our sample reported that their schools met the legal requirements for all three studied OSH measures. Especially during a global pandemic, it was a shocking result that the majority of schools did not have conducted risk assessments (76.2%), infection protection instructions (61.1%) or instructions on occupational safety (55.8%). Schools seemed to perform worse regarding the implementation of OSH measures, when data on the proportion of companies that had not carried out risk assessments (49%) or instructions on occupational safety (19.5%) is used for comparison , 16.2 = 0.016 , so from a statistical point of view the reported effect sizes should be considered as small regarding to Cohen  and significantly higher levels of satisfaction with and meaning of work . Due to to Cohen . Still, Referring to our third aim, the identification of predictors for the implementation of OSH measures in German schools, the best predictor variables were existing concepts for the implementation of digital teaching and federal states  in which the schools were located in. The provision of concepts for implementing digital teaching in schools is, at least to some extent, within the responsibility of the individual federal states. Since each state in Germany has the freedom and responsibility to shape its education system, it seems worthy and is therefore recommended to take a closer look at what is being done differently in the states with better implementation of OSH measures to be able to transfer knowledge. Overall, it became evident, that out of the big number of potential predictor variables for OSH measures in our survey , systemic influences  were more important for the prediction of the implementation of OSH measures relative to individual factors . Nevertheless, it should be kept in mind that the proportion of variance explained (around 15%) by the variables we examined signals that there are other influences for which we had no data to detect them. Still, our results suggest that necessary improvements of OSH measures in German schools should include actions targeting the aforementioned systemic level to ensure that the somatic and psychological wellbeing of teachers in Germany can be sustained and promoted.One potential limitation of our study might have been, that information regarding the implementation of OSH measures was collected on the basis of self-reports. It is possible, that measures—e.g., risk assessments—had been implemented without all surveyed teachers in a school being aware of it. This might have led to an underestimation of the number of implemented OSH measures. Another potential limitation might have been, that the survey took place during the “third wave of SARS-CoV-2” in Germany, while infection numbers were rising rapidly and a new virus variant of concern (B.1.1.7) was spreading . The acuRegarding scientific implications, our study may represent the basis for future studies, since it provides a broad-scale  actual status quo regarding the implementation of, associations with and predictors for OSH measures in German schools. Due to the fact, that the operative responsibility for implementing OSH measures lies with the school management, in depth data at this organizational level would be a useful extension of the approach used in our study. In addition, a broader range of data is needed to explain relationships with OSH measures in schools, since only a fraction (15%) of the variance could be explained by the variables we were able to use in our regression model. For example, it could be a promising direction to analyze whether schools that are better-funded, better-managed or have lower teacher to student ratios are systematically conducting more OSH measures. With additional data, it might be possible that the differences and associations that became apparent in our study, could be  explained or moderated by other variables. Regarding the detection of causal links and to increase granularity, experimental study designs, such as a random assignment of schools to a group where specific OSH measures are conducted  compared to schools where the measures are not (or later) carried out, represent a feasible way to be able to determine concrete contributions of individual measures in a more finely resolved manner.With respect to practical implications, our study demonstrated that teachers working in schools with better implementation of OSH measures showed less somatic and psychological burdens and higher satisfaction with and meaning of work. This is why we do hope that our results are understood as evidence-based arguments to encourage political decision makers to improve the implementation of OSH measures in German schools and thereby foster teachers' health. One possible way to achieve this goal could be the providence of wide spread information on why  as well as practical guidelines on how to perform OSH measures to teachers and school management teams. Since all OSH measures analyzed in this study are already legally obligatory in Germany, the assurance of their implementation by monitoring combined with reminders or potential sanctions (in case of non-compliance) might be a feasible adjuvant way to increase awareness. Overall, a goal worth achieving and useful framing for the implementation of OSH measures in schools should be the creation of working environments that sustain and foster teachers' health, with expectable benefits not only for them, but also for their students.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethical Committee of the Medical Association of Rhineland-Palatinate (Application Number: 2020-15531). The patients/participants provided their written informed consent to participate in this study.Conceptualization: CK, VE, PD, TB, and SL. Data curation: CK, VE, TD, CZ, and PD. Formal analysis: CK, VE, and TD. Funding acquisition: CK, PD, TB, and SL. Investigation, validation, visualization, and writing—review and editing: CK. Methodology: CK, VE, TD, KK, CZ, TB, and PD. Project administration, resources, and writing—original draft: CK and PD. Software: CK, TD, KK, and CZ. Supervision: CK, TB, PD, and SL. All authors have read and agreed to the published version of the manuscript.


The term “Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND)” has recently been coined to describe a new eating pattern. Recent research is looking at how this food pattern affects chronic illnesses. Thus, this study aimed to investigate the association between the use and adherence to the MIND diet with general obesity and blood lipid profile.In this cross-sectional study, 1,328 Kurdish adults between the ages of 39 and 53 had their dietary intake evaluated using a valid and reliable 168-item Food Frequency Questionnaire (FFQ). Adherence to the MIND diet was examined based on the components advised in this eating pattern. Each subject’s lipid profiles and anthropometric measurements were documented.2, respectively. The chances of having increased serum triglycerides (TG) were 42% lower in those in the third tertile of the MIND diet score compared to those in the first tertile . In the crude model and after adjusting for confounders, lowering high-density lipoprotein cholesterol (HDL-C) .The mean age and BMI in the study population were 46.16 ± 7.87 year and 27.19 ± 4.60 kg/mWe found that greater adherence to the MIND diet was associated with the decrease odds of general obesity and lipid profile. Further study is essential owing to the relevance of chronic diseases like MetS and obesity in health status. N = 1,480 adults in 2017) in Erbil city, Iraq, the prevalence of overweight was 33.4% and obesity was 40.9%, and in Basrah, Southern Iraq (2003–2010), overweight/obesity was 55.1%  diet  and the The MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, based on nourishing and harmful foods for the brain, has recently been proposed . It inclThis cross-sectional study was performed on 1,328 Kurdish adults, who referred to Health centers in Kalar, Sulaymaniyah, and Erbil city. After the random selection of 3 health centers from 18 health centers in these three cities, an identical number of subjects were randomly chosen from each center. We included only healthy participants in the current study since CVD, diabetes, thyroid diseases, pregnancy, etc., significantly affect general obesity and lipid profile. In addition, these conditions seem to lead to changes in diet and specific medication use.Moreover, due to the possibility of under- or over-reporting of dietary intake, individuals with a total energy intake outside the range of 800–4,200 kcal/day for men and 600–3,500 kcal/day for women were excluded. Also, subjects with missing data were excluded from the study.The study staff  obtained the primary data, including demographics , smoking, alcohol use, dietary intake, physical activity (PA)  , anthropA bioimpedance analyzer  was used to determine body weight to the nearest 0.1 kg. BSM 370  was used to measure height. The formula for determining a person’s body mass index (BMI) is to multiply their weight in kilograms by the square of their height (in meters).7 mL of blood samples were taken and placed into the clot tubes after 8–12 h of fasting. Serum samples were centrifuged at 4°C for 10–15 min, then kept at −80°C until bioanalysis. TG, HDL-C, LDL-C and total cholesterol, and serum concentrations were assessed using commercially available assays according to the manufacturer’s instructions.via face-to-face interviews.Usual dietary intake was estimated using a valid and reliable 168-item Food Frequency Questionnaire (FFQ)  which inParticipants stated how often they consumed each substance daily, weekly, monthly, and yearly.Household measurements were used to convert the amount of food eaten to grams  and calcData derived from the FFQ was utilized for the development of the MIND diet score. Components of the MIND diet that we used in this study are presented in 2 tests were used, respectively, to analyze the characteristics of the study participants by the MIND diet score tertiles. Logistic regression was used to assess the odds ratio and 95% confidence intervals for the link between the MIND diet score and obesity and lipid profile. Three adjusted models and a crude model each revealed the risk. This study’s first tertile of exposure was used as the reference category.Version 14.2 of STATA software was used for the analysis . At 0.05, the significance level was established. Using a standard BMI cut-off for each sex, data were presented as mean, standard deviation, and percentages (frequency) for quantitative and qualitative characteristics, respectively. For continuous and categorical variables, one-way analysis of variance (ANOVA) and χThe Ethics Committee of Sulaimani Polytechnic University, Kalar technical college approved the study (No: KTC: 0629092022). Both verbal and written informed permission was obtained from each participant. All procedures followed the necessary rules and regulations. The Declaration of Helsinki authorized the conduct of this research.P < 0.001). Participants in the third tertile had lower TG and BMI than participants in the second and first tertiles, (P < 0.001)  were female. Most of the participants 637 (47.96%) had moderate physical activity. Significant differences were observed between the three tertiles in terms of BMI, TG, and HDL-C, (< 0.001) .P = 0.001). While higher tertile of MIND score recorded a lower daily intake of tea and coffee, potatoes, sweets and desserts, sodium, and CHO, (P = 0.001).P = 0.001). This result was still significant when confounders were taken into account. Additionally, we found that adhering to the MIND diet increased the probability of having lower HDL-C values . Even after potential confounders were considered, there was still a significant correlation for lower HDL-C levels .Using binary logistic regression analysis, In this cross-sectional study, we found a significant association between adherence to the MIND diet and general obesity and lipid profile in Kurdish adults. As far as we know, this is the first study that investigates the association between the MIND diet score and general obesity and lipid profile in the adult Kurdish population.Obesity and being overweight are linked to a higher risk of morbidity and death . In recen = 31) on T2D patients might enhance HDL cholesterol by following the DASH diet. In contrast, in the study of Obarzanek et al.  in white adipose tissue, which boosts thermogenesis and reduces waist circumference . FurtherFruits are an excellent source of phytochemicals, fiber, and antioxidants that may help with weight control , inhibitThe major source of dietary fat and phenolic compounds on the MIND diet may have been olive oil, which also has other health benefits. George et al.  found thThe analysis was performed on a large sample size, and statistical controlling for potential confounders is among the strengths of the present study. Also, the major limitation of the present study is its cross-sectional design, which prohibits inferring causal relationships between the MIND diet and general obesity and lipid profile.Significant associations were found between adherence to the MIND diet and odds of general obesity and lipid profile in this cross-sectional study among Kurdish adults. This finding suggests that despite the usefulness of the MIND diet for having a healthy brain it might be able to predict other chronic conditions like obesity. Given the limitations we had in the study, investigations are needed to further examine the association between this dietary pattern and the risk of obesity.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Sulaimani Polytechnic University, Kalar Technical College approved the study (No: KTC: 0629092022). The procedure for obtaining informed consent was approved by the Ethics Committee of Sulaimani Polytechnic University, Kalar Technical College. All methods were carried out by relevant guidelines and regulations. This study was conducted by the Declaration of Helsinki. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.HF and NK designed the study. SM and HF collected and analyzed the data. All authors prepared the draft of the manuscript, contributed to the article, and approved the submitted version.


Infant mortality rate (IMR) is a crucial indicator of healthcare performance and a reflection of a country’s socioeconomic development. We analyzed the trends of IMR in Central Asia (CA) countries and its determinants in Kazakhstan, which is a middle-income country. Linear regression was used for IMR trend analysis in CA countries from 2000 to 2020 and for exploring associations between IMR and socioeconomic factors, health service-related factors, and population health indicators-related factors. A gamma generalized linear model was applied to define associations with various determinants. Our analysis revealed that IMR has decreased in all CA countries, with Kazakhstan having the lowest rate in 2000 and 2020. Our results suggest that socioeconomic indicators, such as total unemployment, Gini index, current health expenditure, gross domestic product (GDP), proportion of people living in poverty, and births by 15–19-year-old mothers, were associated with increased infant mortality rates. Improving socioeconomic conditions, investing in healthcare systems, reducing poverty and income inequality, and improving access to education, are all potential issues for further development. Addressing these factors may be critical for improving maternal and child health outcomes in the region. Infant mortality rate (IMR) is widely considered as a major public health criterion and a reflection of a country’s socioeconomic development. It is closely linked to maternal health and is a key determinant of a nation’s health ,2. For cKazakhstan has witnessed a notable reduction in mortality rates among all age groups, including infants, since 2000 . NeverthUzbekistan has also achieved a decline in the death rate across all age groups, thanks to improvements in the healthcare system and an enhanced focus on maternal and child health . DespiteOfficial data provide consistent evidence that IMR has decreased steadily in the EU and its member states over the past few decades, particularly in Baltic states and some East European countries. However, some developed countries have seen an increase or plateau in IMR in the last decade . In the We also looked at the IMR situation in some middle-income countries. In Hungary, between 1963 and 2012, a notable seasonal (end of winter) impact on neonatal and infant mortality was identified. This effect was more pronounced among infants with low birthweight and mothers with lower levels of education. It is suggested that respiratory infections may be linked to this observed phenomenon . In VeneThe World Health Organization (WHO) emphasizes that maternal and child health is influenced by various social determinants of health that extend beyond access to healthcare. In addition to health policies, addressing socioeconomic factors and living conditions is equally crucial for infant survival . VariousRecent research found that adequate funding of healthcare systems is crucial. These studies demonstrated that, for every 1 percent increase in public health expenditure, there is a corresponding decrease in the IMR of approximately 0.6 to 1 percent ,35.Additionally, healthcare policies and actions have a significant impact on the reduction of IM. In Brazil, establishing the unified health system and the family health strategy were important factors in reducing infant mortality . Other fEnvironmental factors also play a role in infant mortality rates. For instance, poor working environments and industrial pollution are significantly related to infant mortality, while urbanization, employment in the service sector, and economic wealth are not . FurtherAlthough the COVID-19 pandemic has had little direct effect on IM, its indirect impacts on the economy and the effectiveness of the health system are anticipated to result in higher death rates among this vulnerable population in low- and middle-income nations. In cases where the mother is positive for SARS-CoV-2 PCR, the baby is at increased risk of complications and adverse outcomes, which may include specialized neonatal care and prolonged hospitalization ,39.Previous research reported difficulties in delivering healthcare services to families, particularly in rural areas, and a disrupted referral chain, resulting in a decrease in stillbirth and infant mortality rates, during the COVID-19 pandemic. However, the pandemic has also led to a reduction in the number of follow-up visits during pregnancy, and pregnant women have had their regular antenatal care disrupted ,41. In aStrict preventive efforts implemented by the government at the outset of the pandemic have led to a comparatively low prevalence of COVID-19 in Kazakhstan, a middle-income country in CA ,44. A riA retrospective analysis of secondary data was conducted.Data on the numbers of live births and infant deaths were obtained from the published nationwide population register.Monitoring of IM cases in Kazakhstan is conducted on a daily basis, with the following three levels of information collection and analysis: at the health organization level, the territorial branch level of the Republic Center for Health Development, and the central office of the Republic Center for Health Development.At the health organization level, data are collected from newborns based on hospital records, or in cases of stillbirth or death of children under one year old. At the territorial branch level of the Republic Center for Health Development, data are collected from all medical organizations, and output forms are generated for each region, including districts and health organizations within them. At the central office of the Republic Center for Health Development, data are collected from the entire republic, and output data are generated at the country level, including regions and districts.Each health organization designates responsible individuals for monitoring and analyzing incoming data on a daily, monthly, or yearly basis. Trained medical personnel with expertise in examining documents related to live births, stillbirths, and deaths of children under one year old ensure the reliability of the registers and transmit the data to the next level. The compiled data are made available to the public in annual compilation reports entitled “Population Health and Healthcare Organizations’ Performance in the Republic of Kazakhstan” from 2000 to 2020.The mandatory documentary evidence for infant mortality cases includes the medical certificate of death and the conclusion of perinatal death. These documents must be promptly completed, regardless of where the death occurs . The doctor responsible for handling the death observation must possess the necessary medical knowledge and qualifications .IMR data, socioeconomic, health service-related, and population health-related indicators of Kazakhstan were obtained from the annual statistical reports “Population Health and Healthcare Organizations’ Performance in the Republic of Kazakhstan” from 2000 to 2020. These reports contain country- and region-level data on health services and population health. Kazakhstan’s health data collection policy adheres to international guidelines to guarantee statistical data comparability. The IMRs of Kyrgyzstan, Tajikistan, Uzbekistan, and Turkmenistan were derived from World Bank databases .Data were analyzed with IBM SPSS Statistics version 26.0. Linear regression was used for IMR trend analysis in CA countries from 2000 to 2020 and for exploring associations between IMR and socioeconomic factors, health service-related factors, and population health indicators-related factors. Due to the non-normal distribution of the IMR variable, a gamma generalized linear model was used. For the regression, the dependent variable used was the infant mortality rate, which is calculated as the ratio of the number of children who died before the age of 1 year in a given year to the number of live births in the same year, multiplied by 1000. However, to ensure more accurate calculations, the authors adopted the methodology proposed by the German statistician Johannes Raths . Before A decline in IMR is observed in all CA countries. The lowest IMR in the CA countries, in 2000 and 2020, was in Kazakhstan and was 36.7 per 1000 live births and 8.9 per 1000 live births, respectively. In 2000, Tajikistan had the highest IMR among CA countries (67.6 per 1000 live births), while in 2020, IMR was highest in Turkmenistan , and the infant mortality rate in 2020 decreased by 75% compared to 2000. The annual IMR reduction in Turkmenistan over 20 years was on average 0.94 , and IMR in 2020 decreased by 37% compared to 2000, which is the lowest in CA. The annual IMR, decreasing in Kazakhstan over 20 years, was on average 1.49 , and IMR in 2020 decreased by 76% compared to 2000.In general, in all CA countries, a 20-year decreasing trend of IMR is observed. Thus, a regression analysis of IMR in the CA over 20 years showed that the largest annual decline in IMR was detected in Uzbekistan. The annual value of IMR in Uzbekistan decreased by an average of 1.97 , defined as the number of maternal deaths per 100,000 live births within a specific period, averaged 29.50 ± 16.12, ranging from 12 to 61.00. The mortality rate from respiratory system diseases per 1000 live births ranged from 5.00 to 52.90, with a mean value of 18.39 ± 15.19. The average mortality rate from acute upper respiratory infections, influenza, and pneumonia per 1000 live births was 17.66 ± 15.09, ranging from 4.44 to 51.80. Infectious and parasitic diseases had an average mortality rate of 6.72 ± 4.03 per 1000 live births, ranging from 3.07 to 17.00. The mortality rate from intestinal infectious diseases per 1000 live births ranged from 0.10 to 7.70, with a mean value of 1.86 ± 2.09. The mortality rate from congenital malformations per 1000 live births ranged from 15.61 to 38.90, with a mean value of 25.95 and a standard deviation of 6.81. Mortality rate from injury, poisoning, and other external causes per 1000 live births ranged from 2.64 to 10.30, with a mean value of 6.26 ± 2.01. The average malnutrition rate was 26.48 ± 19.26, with a range of 3.30 to 57.80. For the remaining indicators, please refer to Regression analysis showed that socioeconomic indicators , such asAdditionally, bed density  was associated with decreased IMR. All population health-related factors were associated with increased IMR. Thus, MMR , the infant communicable diseases morbidity rate , intestinal infectious diseases , sepsis , diseases of the blood and blood-forming organs , nutritional anemias , endocrine disorders , malnutrition , disorders of the central nervous system , respiratory diseases , acute upper respiratory infections , digestive system diseases , diseases of the genitourinary system , certain conditions originating in the perinatal period , injury, poisoning and certain other consequences of external causes , mortality rate from diseases of the respiratory system , mortality rate from acute upper respiratory infections, influenza and pneumonia , mortality rate from intestinal infectious diseases , mortality rate from congenital malformations , and mortality rate from injury, poisoning and certain other consequences of external causes  were associated with increased IMR.In this study, we analyzed trends in infant mortality rates in CA countries and its determinants in Kazakhstan. We found that all CA countries have successfully decreased their IMR from relatively high levels, with Kazakhstan having the lowest rate in 2000 and 2020. Our results suggest that socioeconomic indicators, such as total unemployment, Gini index, current health expenditure, GDP, the proportion of people living in poverty, and births by 15–19-year-old mothers, were associated with increased infant mortality rates in Kazakhstan, which is consistent with findings from other studies conducted in middle-income countries ,50,51. HUzbekistan’s socio-demographic development during the years of independence has resulted in a decline in mortality across all age groups. The country has improved its healthcare system and focused on enhancing maternal and child health . DespiteAccess to healthcare resources is another major element in lowering IMR. It has been found that the risk of infant mortality lowers in higher income families, i.e., those with the best access to healthcare services. At the same time, the risk of IM is higher in rural households than in urban ones, which can be explained by the difficulty of obtaining health services in rural regions . In receRising income and access to safe water are some of the reasons for improved health outcomes in low- and middle-income countries . HoweverIt is important to acknowledge the limitations of our study. One of the main limitations is that we did not take into account the impact of the COVID-19 pandemic on infant mortality rates in Kazakhstan. The pandemic has had direct and indirect effects on infant mortality rates, especially in low- and middle-income countries . DisruptSudden infant death syndrome (SIDS) used to be one of the major causes of death of infants . Even thIt Is worth noting that data quality and accessibility of vital and health statistics are important considerations in IMR. While data quality and accessibility are generally good in Kazakhstan, other countries in the CA region may face some difficulties in this regard . In concThe decline in infant mortality rates in CA countries over the past two decades is encouraging. However, significant challenges remain in reducing IMR in the region further. This study identified various social determinants of infant health that require attention for improving infant health outcomes in a middle-income country from the region. Improving socioeconomic conditions, investing in healthcare systems, reducing poverty and income inequality, improving access to education, reducing fertility rates, addressing environmental factors, and reducing domestic violence are all potential avenues for further improvement. Furthermore, the study identified several population health and health service-related factors that were associated with increased infant mortality rates. Addressing these factors may be critical for improving maternal and child health outcomes in the region.


We examined postmortem brain tissue from men, over the age of 50, for chronic traumatic encephalopathy neuropathologic change (CTE-NC). We hypothesized that (i) a small percentage would have CTE-NC, (ii) those who played American football during their youth would be more likely to have CTE-NC than those who did not play contact or collision sports, and (iii) there would be no association between CTE-NC and suicide as a manner of death.Brain tissue from 186 men and accompanying clinical information were obtained from the Lieber Institute for Brain Development. Manner of death was determined by a board-certified forensic pathologist. Information was obtained from next of kin telephone interviews, including medical, social, demographic, family, and psychiatric history. The 2016 and 2021 consensus definitions were used for CTE-NC. Two authors screened all cases, using liberal criteria for identifying “possible” CTE-NC, and five authors examined the 15 selected cases.The median age at the time of death was 65 years . There were 25.8% with a history of playing American football and 36.0% who had suicide as their manner of death. No case was rated as definitively having “features” of CTE-NC by all five authors. Ten cases were rated as having features of CTE-NC by three or more authors (5.4% of the sample), including 8.3% of those with a personal history of playing American football and 3.9% of those who did not play contact or collision sports. Of those with mood disorders during life, 5.5% had features of CTE-NC compared to 6.0% of those who did not have a reported mood disorder. Of those with suicide as a manner of death, 6.0% had features of CTE-NC compared to 5.0% of those who did not have suicide as a manner of death.We did not identify a single definitive case of CTE-NC, from the perspective of all raters, and only 5.4% of cases were identified as having possible features of CTE-NC by some raters. CTE-NC was very uncommon in men who played amateur American football, those with mood disorders during life, and those with suicide as a manner of death. The terall parts of the criteria verbatim. Features of CTE-NC were identified in 21 cases . They reasoned that coding cases as having features of CTE-NC was reasonable because of their limited sampling, and that more exhaustive sampling might have revealed more definitive lesions.In a large-scale study by Bieniek and colleagues , CTE-NC Other authors have recommended coding “components” of CTE-NC, not just whether it was definitively present or absent . ForrestIn 2021, the second consensus definition of CTE-NC was published , and the1.1.The purpose of the present study was to examine postmortem brain tissue for CTE-NC from a large sample of men, over the age of 50, most of whom had neuropsychiatric problems during life. The sample was obtained from the brain donation program at the Lieber Institute for Brain Development. This institute collaborates with medical examiner offices to obtain brain tissue from people who had neuropsychiatric problems during life to better understand the molecular mechanisms associated with these illnesses. Researchers from the institute collect detailed demographic and clinical histories from next of kin of the decedents. In a previous study using the same cases we examined the association between participation in high school football and suicide . There wUsing a methodology similar to Bieniek and colleagues , we scre2.2.1.via Gift of Life Michigan, under the same protocol, consenting procedures, and screening procedures, but did not undergo forensic examination at WMed because cause and manner of death were apparent with death investigation. Brain procurement, tissue sampling, and immunostaining were otherwise identical.Postmortem brain tissue and accompanying information were obtained from the brain donation research program at the Lieber Institute for Brain Development (LIBD). The samples examined in this study were obtained from a collaboration between LIBD and the Office of the Medical Examiner of the Western Michigan University Homer Stryker M.D. School of Medicine (WMed), Department of Pathology (WIRB protocol #1126332). Informed consent from legal next of kin was obtained in each case at the time of autopsy. Importantly the WMed collaborative effort with LIBD includes a substantial percentage of people who completed suicide (36.0% in our study sample). Cases were identified after reviewing death scene investigations in counties subserved by the WMed Medical Examiners, typically in the 24 h preceding autopsy. The WMed catchment area at the time of case collection between 2016 and 2020 consisted of 13 counties in Western Michigan. Exclusionary criteria were as follows: not-at-fault motor vehicle accidents, homicides, suspicious deaths , certain infectious diseases , brain-destructive processes , encephalopathy, isolated seizure disorder (with no psychiatric history), maintenance on artificial life support for greater than 24 h, last known to be alive greater than 72 h prior, and gross evidence of autolysis or decomposition. There were 21 cases in this study that were referred at the time of organ donation via medical record review, and telephone interviews with the legal next of kin (described below). Subjects were consecutively referred men aged 50 and older  with completed immunohistochemistry performed on selected brain regions per the LIBD protocol (described below). Men were selected because the goal was to examine the association between CTE-NC and a personal history of participating in American football. Age 50 was the lower bound for inclusion in the study because the protocol at the LIBD is to conduct immunohistochemistry on tissue from people aged 50 and older. Complete clinical information, tissue samples, and immunohistochemical stains were available for 186 men.Next, of kin for potential donors who met inclusion criteria were then contacted by LIBD for consent for donation. According to previous study, 57.0% of all African–American families and 74.1% of all Caucasian families who were contacted by the LIBD agreed to donate at the time of autopsy . Donor h2.2.Cases were reviewed by the medical examiner’s investigative team in a multidisciplinary morning conference prior to case selection for consent and brain procurement. Following review, manner of death  was determined by a board-certified forensic pathologist, in general according to guidelines from the National Association of Medical Examiners . The man2.3.Initial information was obtained via a 36-item telephone interview, with the next of kin, including medical, social, demographic, family, and psychiatric history. The next of kin were also asked about a history of head trauma, personal history of concussions in sports, head injury in civilian life, and/or history that suggested severe traumatic brain injury. Although very pronounced acute structural brain injury from trauma is exclusionary for brain donation, this does not preclude consenting donors with a history of traumatic brain injury who lack obvious structural brain damage, or a history of traumatic brain injury that was not uncovered in the family interview or during the initial death scene investigation. It is also possible to uncover evidence of structural brain injury  that was not diagnosed during life. In our sample, 3 out of 186 cases had remote contusions detected at autopsy. Overall, a broad range of injury mechanisms  and severities/types were described in the case material . All levels of brain injury severity were included based on history, but for most cases there was insufficient information to classify brain injury severity more precisely. Detailed notes on traumatic brain injury were variable, and it was coded as binary.The collective data was reviewed for retrospective clinical diagnostic interpretation, consisting of the telephone screen, autopsy results and other forensic data including toxicology, psychiatric and substance abuse treatment records, and/or general medical record reviews, and any family informant interviews that were available. All data were assembled into a comprehensive narrative summary for review by two board-certified psychiatrists. A list of lifetime diagnostic and statistical manual of mental disorders (DSM-5) psychiatric diagnoses and medical diagnoses was then compiled. LIBD also recruits control subjects, defined as subjects who were free from psychiatric and substance use diagnoses, and had negative toxicology . Forensic toxicological analysis covered ethanol and volatiles, opiates, cocaine/metabolites, amphetamines, and benzodiazepines. In a subset of cases, toxicological analysis using National Medical Services, Inc., was obtained, including nicotine/cotinine testing, cannabis testing, and an expanded forensic panel to cover any substances not otherwise tested including prescription medications.2.4.The next of kin informants were also asked about decedents’ history of engagement in contact or collision sports, such as boxing, football, and rugby, and this variable was coded as yes or no. Study subjects were categorized into groups based on whether they played contact sports in general, played American football specifically, or played no contact or collision sports. The informants reported that 48 men played high school football and 4 played college football. Six other subjects were identified as playing football, but their level was not clear. Hockey was played by three men, and two men played both hockey and football. Three men were noted to have participated in wrestling. Three men participated in kickboxing or boxing, and two men participated in either auto racing or motorcycle racing with multiple possible concussions (head injuries) noted by the persons’ next of kin.2.5.A minimum of seven brain samples per donor were obtained for histopathology: right middle frontal gyrus (Brodmann area 8), right superior/middle temporal cortex (Brodmann area 22), right inferior parietal lobule (Brodmann area 40), right occipital calcarine cortex (Brodmann area 17), hippocampus at the level of the lateral geniculate nucleus , midbrain, and cerebellar hemisphere with dentate nucleus . The samTissue samples were fixed in 10% neutral buffered formalin, processed through graded ethanol and xylene solutions, and embedded in paraffin. Five μm-thick sections were prepared from all samples and stained with hematoxylin and eosin for routine histopathology. Five μm-thick sections of the cortical samples and hippocampus were prepared for p-tau immunohistochemistry, along with 5 μm thick sections of the cortical samples for amyloid-β (Aβ) immunohistochemistry , which iAll slides were scanned into virtual microscopy at 20× magnification. They were examined using Aperio ImageScope Pathology View software.The histopathological analyses were customized for the case material obtained by the Lieber Institute for Brain Development, which focuses on neuropsychiatric disorders and generally avoids cases with confounding structural pathology or neurodegenerative diseases. The analyses are therefore a screening process for age-related proteinopathy or early/preclinical neurodegenerative disease, and they are abbreviated in comparison with recommended methodology for Alzheimer’s disease neuropathologic change (ADNC) . They arper se. This is an appropriate modification with increased sensitivity of detection of age-related Aβ deposits, given the Lieber Institute’s focus on psychiatric diseases rather than Alzheimer’s disease.P-tau and amyloid-β were semi-quantitated using modifications of Braak  and CERA2.6.We defined the presence of CTE-NC using both the 2016 and the 2021 consensus definitions. Using the first consensus definition of CTE-NC : “cases In 2021, the second consensus definition of CTE-NC was published, and the defining pathognomonic characteristic of CTE-NC changed with a particular emphasis on trying to disambiguate CTE-NC from ARTAG —especialFeatures of CTE-NC were assessed, meaning that some of the characteristics of CTE-NC were present but the case did not meet strict criteria for CTE-NC. These include, for example, tau-positive astrocytes, neurons, or neurites concentrated around a perivascular space but not clearly in the sulcal depth, or tau-positive astrocytes, neurons, or neurites in a patchy distribution at the sulcal depth but not clearly concentrated around a blood vessel.Interpreting CTE-NC in the presence of aging-related pathologies and Alzheimer’s disease changes is challenging. The authors of the 2021 consensus criteria, in the limitations section of their article, wrote: “the study cases were relatively “pure” CTE (with the exception of some AD pathology) despite reports indicating that comorbid neurodegeneration  is common in older individuals with CTE , 31, 32.possible CTE-NC for review by the expanded panel of neuropathology experts. These two authors used the following guidelines for screening for possible CTE-NC: Patchy p-tau aggregates apparent at medium or low magnification either around blood vessels, and/or at or near a sulcal depth, that could reasonably raise the possibility of CTE-NC. The two reviewers worked independently. If either reviewer identified the case as having possible features of CTE-NC, that case was included in the sample for all reviewers to examine. Five authors from three countries and four academic institutions independently examined, or re-examined, the cases identified through the initial screening process .Two authors  blinded to all clinical and demographic information (including age) screened all the cases, with the purpose of selecting cases for 2.7.2χ tests. Using G*Power 3.1.9.7 for z tests and differences between two independent proportions, assuming an allocation ratio of 3  and assuming that CTE-NC would be identified in 10% of those who played football and 1% of those who did not, using a one-tailed directional test, with a critical z = −1.645  and power = 0.80, a total sample size of 175 would be required to detect this 9% effect size difference in proportions . Using the same parameters , but assuming that CTE-NC would be detected in 5% of those who did not play football and 15% of those who did play football, detecting that difference in proportions would require a sample size of 269 . Mann Whitney U tests were used to compare groups based on age. All statistical analyses were conducted using IBM SPSS Statistics 26.The proportions were computed and compared using 3.The sample included 186 men. The median age of the men at the time of death was 65 years . One-quarter of the sample had a history of playing football (25.8%), one-quarter had a history of TBI (26.9%), half had a history of a mood disorder during life (55.4%), and approximately one-third of the sample had suicide as their manner of death (36.0%). The characteristics of the sample are presented in 3.1.a priori exclusionary for screening or for the assessment of “features of CTE-NC.”Of the 186 men, 15 initially screened positively for review by the expanded panel of authors with expertise in neuropathology, representing 8.1% of the total sample. This initial screening was designed to be overly inclusive to identify cases that could then be reviewed by more authors. For the purposes of this study, the presence of ADNC  was not 3.2.Those 15 cases were then examined, or re-examined, by five authors , also blinded to all clinical and demographic information. No case was identified as definitively meeting criteria for CTE-NC based on the 2016 or 2021 definition by the authors. No case was rated as having “features” of CTE-NC, based on the 2016 or the 2021 definition, unanimously by all five reviewing authors . There were two cases that were rated by four authors (out of the five) as having features of the 2016 definition and one case that was rated by four authors as having features of the 2021 definition. Cases rated as “possible,” or having “features,” by three or more authors were selected for further analysis. Using these criteria, there were six cases (3.2%) that had features according to the 2016 definition and eight cases (4.3%) that had features according to the 2021 definition, and a total of 10 cases that had features of one or both of the definitions (5.4%). Examples of neuropathology visualized in these cases are provided in U = 1,161, p = 0.09). There was no significant association between a personal history of playing American football  or contact sports broadly   and screening positively for features of CTE-NC. There was no significant association between having a history of TBI and screening positively for features of CTE-NC . There was no significant association between having a mood disorder and screening positively for features of CTE-NC . There was no significant association between suicide as a manner of death and screening positively for features of CTE-NC .Those 10 cases who screened positively for features of CTE-NC  were a median of 11.5 years older than those who did not have features of CTE-NC , although this difference was not statistically significant  (N = 532) (N = 310) reported no cases of CTE-NC   and a coN = 532)  have ideN = 532) . A largef CTE-NC  and in af CTE-NC . These lWe hypothesized that there would be no association between CTE-NC and suicide in this study, given the literature indicating that suicide is not likely to be a clinical feature of CTE or be associated with participation in football , 17–22. 4.1.This study has several unique features and strengths. First, the brain bank is different from all prior brain bank studies in that it specializes in donations from people who suffered from psychiatric and neuropsychiatric disorders. The sample size was larger than many prior studies , 44, 45,4.2.per se. Finally, this study suggests that CTE-NC is uncommon in men who played high school American football, a substantial percentage of whom had serious psychiatric and substance misuse problems. However, data derived from an autopsy sample that requires tissue donation and consent from legal next of kin have inherent bias in acquisition. The present sample, without question, has a major inherent bias because the research program specializes in donations from people who suffered from psychiatric and neuropsychiatric disorders—this sample clearly is not representative of men from the general population. This is a sample of convenience, not a cohort or case–control study that can be used to examine prevalence or to examine issues relating to causation.This study has important conceptual limitations. First, the exposure variable was based on information obtained from the next of kin, and it was binary. Similar to most previously published postmortem studies, we could not document, classify, quantify, or analyze number of years of exposure to football or contact sports. Second, although our sample size was larger than some prior studies, and sufficiently powered to detect small-medium effect sizes, our pathology was so uncommon that we were underpowered to detect small group differences. Third, our pathology sampling was less than what is recommended by the two consensus conference statements , 9, alth4.3.characteristic of CTE-NC or as a supportive feature of CTE-NC  appeared to overlap with CTE-NC , 58, 59.rom ADNC . PART isrom ADNC . Like CT4.4.Large studies from Australia , the UniThe original contributions presented in the study are included in the article/GI conceptualized the study, conducted the literature review, conceptualized and conducted the statistical analyses, wrote sections of the manuscript, and agrees to be accountable for the content of the work. PJ conducted the initial neuropathology screening of the entire sample, conducted in-depth analysis of the selected cases, edited versions of the manuscript, and agrees to be accountable for the content of the work. AF-H conducted in-depth neuropathological analysis of the selected cases, edited drafts of the manuscript, and agrees to be accountable for the content of the work. AD-S completed team-based clinical diagnostic reviews for each case, managed the brain bank data, participated in conceptualizing the study, reviewed drafts of the manuscript, and agrees to be accountable for the content of the work. TH administratively manages the brain bank, conducted interviews with next of kin, completed team-based clinical diagnostic reviews for each case, participated in conceptualizing the study, reviewed drafts of the manuscript, and agrees to be accountable for the content of the work. JK administratively manages the brain bank, conducted interviews with next of kin, completed team-based clinical diagnostic reviews for each case, participated in conceptualizing the study, reviewed drafts of the manuscript, and agrees to be accountable for the content of the work. JJ serves as the site principal investigator for the brain donation program, wrote portions of the manuscript, edited drafts, and agrees to be accountable for the content of the work. CS conducted in-depth neuropathological analysis of the selected cases, edited drafts of the manuscript, and agrees to be accountable for the content of the work. L-NH conducted in-depth neuropathological analysis of the selected cases, edited drafts of the manuscript, and agrees to be accountable for the content of the work. RC assisted with conceptualizing the study, assisted with the literature review, conducted the initial neuropathology screening of the entire sample, conducted in-depth analysis of the selected cases, wrote portions of the manuscript, edited drafts of the manuscript, and agrees to be accountable for the content of the work. All authors contributed to the article and approved the submitted version.GI acknowledges unrestricted philanthropic support from ImPACT Applications, Inc., the Mooney-Reed Charitable Foundation, the National Rugby League, and the Schoen Adams Research Institute at Spaulding Rehabilitation. He has received research funding from the Wounded Warrior Project™ to conduct research relating to CTE and traumatic encephalopathy syndrome, but not for this study. The above entities were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.GI serves as a scientific advisor for NanoDX®, Sway Operations, LLC, and Highmark, Inc. He has a clinical and consulting practice in forensic neuropsychology, including expert testimony, involving individuals who have sustained mild TBIs (including former athletes), and on the topic of suicide. He has received research funding from several test publishing companies, including ImPACT Applications, Inc., CNS Vital Signs, and Psychological Assessment Resources . He has received research funding as a principal investigator from the National Football League, and subcontract grant funding as a collaborator from the Harvard Integrated Program to Protect and Improve the Health of National Football League Players Association Members.RC is subcontracted to the Lieber Institute for Brain Development to assist with brain examinations. He is a consultant on a grant from the National Football League. He has a consulting practice in forensic neuropathology, including expert testimony, some of which involves former contact sport athletes.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Stroke is the leading cause of functional disability worldwide. With the increase of the global population, motor rehabilitation of stroke survivors is of ever-increasing importance. In the last decade, virtual reality (VR) technologies for rehabilitation have been extensively studied, to be used instead of or together with conventional treatments such as physiotherapy or occupational therapy. The aim of this work was to evaluate the GestureCollection VR-based rehabilitation tool in terms of the brain changes and clinical outcomes of the patients.Two groups of chronic patients underwent a rehabilitation treatment with  or without (control) complementation with GestureCollection. Functional magnetic resonance imaging exams and clinical assessments were performed before and after the treatment. A functional connectivity graph-based analysis was used to assess differences between the connections and in the network parameters strength and clustering coefficient.Patients in both groups showed improvement in clinical scales, but there were more increases in functional connectivity in the experimental group than in the control group.The experimental group presented changes in the connections between the frontoparietal and the somatomotor networks, associative cerebellum and basal ganglia, which are regions associated with reward-based motor learning. On the other hand, the control group also had results in the somatomotor network, in its ipsilateral connections with the thalamus and with the motor cerebellum, which are regions more related to a purely mechanical activity. Thus, the use of the GestureCollection system was successfully shown to promote neuroplasticity in several motor-related areas. AlthougAs stated by Weiss and colleagues, VR is the ‘use of interactive simulations created with computer hardware and software to present users with opportunities to engage in environments that appear and feel similar to real-world objects and events’ . VR alloThe GestureCollection system  is a lowIndeed, a way to investigate the effects of rehabilitation in the brain that has been widely used is resting state (rs) functional magnetic resonance imaging (fMRI) associated with graph theory to measure the topological changes in brain networks . fMRI b. rs-fMRIOther papers have reported using fMRI to investigate brain changes resulting from the use of VR solutions for rehabilitation of stroke patients  for a m). HoweveThe aim of this work was to investigate changes in functional connectivity and network parameters in stroke victims as a result of motor rehabilitation, performed with or without complementation with GestureCollection. We hypothesize that patients who undergo therapy along with this VR approach are going to show larger increased connectivity with motor-related areas than patients who undergo conventional therapy.2.2.1.Fifteen patients with ischemic stroke diagnosis were recruited through the Neurovascular Outpatient Clinic in the Clinics Hospital of University of Campinas and by spontaneous search of volunteers. The patients were assessed for eligibility by a blinded assistant and allocated into groups through alternation. One patient was lost to follow-up and four others had their data discarded during the preprocessing of the MRI data, resulting in a sample of 10 individuals .Inclusion criteria were: (1) patients with ischemic stroke between 6 and 24 months after onset; (2) age 45–70 years; (3) both genders; (4) motor and functional impairment measured by modified Rankin Scale (mRS 1–4); and (5) signed Informed Consent Form. Exclusion criteria were: (1) contraindications to the MRI exam ; (2) lack of capacity to understand or follow verbal commands; and (3) serious visual impairments. All research was performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments. The study was approved by the Ethics Committee of University of Campinas (protocol 60860616.0.0000.5404) and all subjects signed an informed consent form prior to entering the study.2.2.Participants were alternated into two groups: the control group received 1 h of “conventional physiotherapy” (CPT) , plus 30 min of visual stimulation (video showing movements of lower and upper limbs); and the experimental group received 1 h of CPT followed by the application of VR for 30 min. Rehabilitation sessions were conducted twice a week, for six consecutive weeks . CPT included: joint mobilization, stretching for upper and lower limb and trunk, proprioceptive neuromuscular facilitation exercises, training of postural transfers  and gait training in a proprioceptive circuit. Clinical data such as heart and respiratory rate, blood pressure and effort reported by the patient were considered for the conduction of the treatment.2.3.The GestureCollection VR set  was used2.4.To verify functional outcomes, we used the Fugl-Meyer Assessment (FMA), the Berg Balance Scale (BBS), the Timed Up and Go (TUG) test and the Montreal Cognitive Assessment (MoCA). Evaluations were conducted at the beginning and the end of the study period by a physiotherapist blind to group assignment.FMA is considered one of the most complete measures for post-stroke functions , consistBBS was used to assess balance , consistTUG  is a tesMoCA  is a fas2.5.3, field of view (FOV) = 240 × 240 × 180 mm3 repetition time (TR) = 6.9 ms, echo time (TE) = 3.2 ms) and T2*-weighted functional images .Two MRI acquisitions were performed in a 3.0 Tesla scanner , one before the first therapy session, and one after the last therapy session. These consisted of a T1-weighted anatomical image . First, the reorientation of the images to the anterior commissure was manually performed in the SPM12 toolbox. Further steps of the preprocessing were performed in the software UF2C , which rThe original dataset was composed of two groups of seven subjects. Four subjects (two from each group) were excluded due to excessive movement during fMRI, resulting in five subjects per group . To perf2.5.1.Regions of interest (ROIs) were derived from the MIST functional atlas  containiTime series extraction was conducted as follows: each ROI had its mask applied to the functional image. Null time series, relative to borders or voids, and time series whose correlation coefficient to the mean were smaller than two standard deviations were excluded. Finally, the mean was computed again with the remaining time series.A 16 × 16 adjacency matrix was built for each subject using the Pearson correlation values of each pair of ROIs.2.6.2.6.1.2.6.1.1.In this analysis, we sought the pairs of regions with the highest connectivity difference between the pre- and post-MRI. To this end, the negative correlations were excluded from the weighted adjacency matrix (wAM) of every subject and, for each subject, the difference matrix (wdM) of the positive correlations between the timepoints was computed, through the subtraction of pre from post wAM:t-test was applied to each wdM, generating t-value difference matrices (t_wdM). The t-values were calculated as follows:A where The resultant group weighted difference matrix (gwdM) was obtained through the median of the t_wdM matrices from the group’s subjects:where p-values were calculated for the gwdM matrix and filtered for significance  and the clustering coefficient (CC) to measure changes on the network topology .To mathematically describe the measures, we must consider some definitions. In a weighted network formed by the set S is the most basic measure in a weighted network. It represents the sum of the weights from the connections that a node has:CC measures how much the neighborhood of a node is connected to itself. It is quantified by the number of triangles formed by the nodes directly connected to the node of interest. A densely connected network region is associated with specialized local information processing. The expression for CC is:S and CC. For these computations, only the positive correlations in the wAM were considered. The group result for each study was obtained through the median of the subjects’ relative differences. Considering the generic parameter P, the relative difference  was computed as follows:Relative differences in network parameters, from the first to the last scans, were computed for 3.3.1.The results of the clinical evaluations performed with FMA, BBS, TUG and MoCA for both groups are shown in 3.2.Connectivity difference matrices (gwdM) for the experimental and control groups are shown in 3.2.1.In the experimental group, there were seven significant connections with positive differences and four with negative differences . Two of 3.2.1.1.All positive differences involved the frontoparietal network. In the left  hemisphere, the correlations between the left frontoparietal executive (LFPe) region and the left nucleus accumbens (LNAC) and between the left frontoparietal task control (LFPtc) and the left associative cerebellum (LaCER) increased from the beginning to the end of the treatment. On the right side, the positive differences occurred in the connections between the right frontoparietal task control region (RFPtc) and the right frontoparietal executive region (RFPe) with the right somatomotor network (RMN). Finally, the increased interhemispheric connections were between the RFPe and the left somatomotor network (LMN) and between the LFPtc and the right associative cerebellum (RaCER) and right striatum (RSTR).3.2.1.2.Both ipsilesional decreased connections involved the right dorsal striatum (RSTR), in one case with the right thalamus (RTHA) and in another with the right motor cerebellum (RmCER). The interhemispheric decreased connection involved the RTHA and the left dorsal striatum (LSTR). In the contralesional hemisphere, the decreased connection was between the LMN and the left thalamus (LTHA).3.2.2.Four increased and five decreased connections were found in the control group difference matrix . Two pos3.2.2.1.One connection presented a positive difference and three showed negative differences in the frontoparietal network. The positive difference was in the interhemispheric connection LFPe-RmCER. The negative differences were between the right and left frontoparietal network, RFPtc-LFPe and RFPtc-LFPtc, and in the ipsilesional intra-network connection RFPtc-RFPe.3.2.2.2.Three positive differences occurred in the somatomotor network, two in the ipsilesional and one in the contralesional hemisphere. On the right side, the RMN had positive differences with the RTHA and the RmCER; while on the left side, the LMN had an increase in its connection with the LTHA.3.2.2.3.As mentioned, the thalamus had increased connections with the somatomotor networks at both hemispheres (RTHA-RMN and LTHA-LMN). However, a negative difference occurred in the interhemispheric connection between both thalami, RTHA-LTHA.3.2.2.4.The RmCER had two  positive differences: in the ipsilesional connection RmCER-RMN and in the interhemispheric connection RmCER-LFPe. A negative difference occurred in the interhemispheric connection between the right and left motor cerebellum (LmCER), RmCER-LmCER.3.3.Relative changes (RMV) in CC and S [according to 3.3.1.The experimental group had more increases than decreases in all metrics, with the greatest increases being in the strength parameter. The following regions had increases in the range : RFPtc, in CC; and LFPtc, LNAC and the right nucleus accumbens (RNAC), in S. Smaller increases, in the range , were found in LFPe, LMN, RFPe, RMN and RmCER, in CC; and LFPe, RFPe, RFPtc and RMN, in S. Decreases in the range  can be seen in: LTHA and RaCER, in CC; LmCER and RmCER, in S.3.3.2.The control group had more decreases than increases in the graph metrics, with only two regions where the parameters increased . Regions with increases in the range  were: RmCER, in CC; and RMN, in S. Regions with decreases in the range  were: LMN, LTHA, LaCER, RMN, RSTR and RTHA, in CC. Besides, LTHA had a decrease in the range  in S.4.Clinical scales were used to assess physical and cognitive improvements in the subjects submitted to rehabilitation: FMA, BBS, TUG and MoCA. The improvement in FMA, BBS and MoCA is associated with an increase in these scales, while for TUG improvement is related to a decrease in the corresponding value. The RMV  of FMA, The analysis of group connection changes resulted in more connection increases than decreases for the experimental group , while for the control group, there were fewer connection increases than decreases (4 vs. 5).Looking more closely at the increased connections , we see Regarding the topology of the networks, both groups presented changes in all analyzed parameters (CC and S) . The expIt is important to highlight that there is a lack of literature on resting state functional connectivity and network changes after motor rehabilitation with VR systems for a direct comparison. Nevertheless, some studies have presented brain activation results in similar areas to the ones found in the present work. Activations in the prefrontal/frontoparietal cortex were found in Orihuela-Espina et al.  after VRNevertheless, comparing both treatments underwent by the groups in this study, one main differential of VR rehabilitation is that it is more engaging than conventional treatments. Also, VR allows for the use of several mechanisms to stimulate the user’s brain. The GesturePuzzle application uses false positive feedback, i.e., it amplifies the user movements (in case of need) to aid the user to complete the task, which stimulates reward-based learning mechanisms. In GestureMaps, the user’s body and movements are reproduced in the screen, which can give a sensation of immersiveness and allow action observation, which activates the brain in regions related to motor function. GestureCollection games also stimulated cognition of the participants.Notwithstanding, the experimental group was composed of younger subjects than those of the control group . Yoo et al.  found thFinally, it is necessary to add that, since we were not able to collect longitudinal data, i.e., to evaluate subjects a few weeks or months after the end of the intervention, we cannot assert that “learning” has effectively occurred, because we do not know if the neuroplasticity changes had a lasting effect. In future studies we intend to perform such a follow up.The main limitation of this work was the small sample size. This is a recurrent difficulty in this kind of work. More than 50% of the stroke-related studies revised in Feitosa et al.  had up tAnother major difficulty was the data’s heterogeneity. With such a small sample, it was not possible to select subjects with more similar lesion locations and clinical conditions, which would be the perfect scenario. Also, the groups were very dissimilar at baseline, with the control group presenting scores close to the maximum on the FMA and BBS scales, and low values at the TUG test, while the experimental group was much more heterogeneous and had worse scores on those scales. This made it difficult to compare the clinical improvement between the two groups. Besides, the subjects with lesions in the left hemisphere had their data flipped with respect to the x-axis, in order to homogenize the lesion side, which can also be an issue, since the brain’s hemispheres are not completely functionally symmetric . Other lFinally, in this study only ischemic stroke patients were enrolled, due to this type of stroke being more common and homogeneous. Future studies should also include hemorrhagic stroke patients.In summary, patients in both experimental (with GestureCollection complementation) and control (without GestureCollection complementation) groups showed improvement in clinical scales after therapy. Despite the difficulty in comparing those clinical outcomes due to the groups’ disparity, in terms of brain changes, we can say that the differences between the groups were unequivocal. VR treatment induced changes in regions that are related to learning, planning and motor execution, while conventional treatment had limited effects in terms of neuroplasticity. There were more increases in functional connectivity in the experimental group than in the control group. The use of the VR system promoted changes mainly in the frontoparietal networks, strengthening the connections between the frontoparietal and motor cortex in the ipsilesional side and interhemisphericaly. The increase in strength in the nucleus accumbens, in both sides, shows how these regions became more important in the network, promoting reward-related motor learning in the subjects that used GestureCollection. Therefore, the use of the GestureCollection system in addition to conventional treatment was successfully shown to promote neuroplasticity in motor-related areas. Nevertheless, the evaluated patient sample was small, and further studies should be conducted to confirm these results. This is the first work of such type performed with stroke patients and the GestureCollection system, and its results may direct the adoption of this low-cost solution in clinics and hospitals across the country.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving humans were approved by Comitê de Ética em Pesquisa da Universidade Estadual de Campinas (Research Ethics Committee of University of Campinas). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.GC, AC, AB, and LL: conceptualization. JF, RC, GC, AC, and LL: methodology. AB: software. JF, RC, and GC: validation and formal analysis. JF, RC, GC, and AC: investigation. GC and LL: resources, project administration, and funding acquisition. AC and AB: data curation. JF: writing – original draft preparation. RC, AB, LL, and GC: writing – review and editing. GC, RC, and LL: supervision. All authors have read and agreed to the published version of the manuscript.