In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function.

Hennekam Lymphangiectasia-Lymphedema Syndrome 3 (HKLLS3) is a rare genetical disorder caused by mutations in a few genes including ADAMTS3. It is characterized by lymphatic dysplasia, intestinal lymphangiectasia, severe lymphedema and distinctive facial appearance. Up till now, no extensive studies have been conducted to elucidate the mechanism of the disease caused by various mutations. As a preliminary investigation of HKLLS3, we sorted out the most deleterious nonsynonymous single nucleotide polymorphisms (nsSNPs) that might affect the structure and function of ADAMTS3 protein by using a variety of in silico tools. A total of 919 nsSNPs in the ADAMTS3 gene were identified. 50 nsSNPs were predicted to be deleterious by multiple computational tools. 5 nsSNPs (G298R, C567Y, A370T, C567R and G374S) were found to be the most dangerous and can be associated with the disease as predicted by different bioinformatics tools. Modelling of the protein shows it can be divided into segments 1, 2 and 3, which are connected by short loops. Segment 3 mainly consists of loops without substantial secondary structures. With prediction tools and molecular dynamics simulation, some SNPs were found to significantly destabilize the protein structure and disrupt the secondary structures, especially in segment 2. The deleterious effects of mutations in segment 1 are possibly not from destabilization but from other factors such as the change in phosphorylation as suggested by post-translational modification (PTM) studies. This is the first-ever study of ADAMTS3 gene polymorphism, and the predicted nsSNPs in ADAMST3, some of which have not been reported yet in patients, will serve for diagnostic purposes and further therapeutic implications in Hennekam syndrome, contributing to better diagnosis and treatment.

Exploring the Epidemiology of Injuries in Athletes of the Olympic Winter Games: A Systematic Review and Meta-Analysis.

This study sought to provide a comprehensive assessment of the incidence of sports injuries among athletes participating in the Olympic Winter Games and to investigate contributing factors. We gathered injury data from athletes participating in the recent four Olympic Winter Games, incorporating details on the sports event, sex, injury location, and type. Through a meta-analysis, we calculated the injury incidence rates for each sport and examined the influence of sex and the type of sport on these incidence rates. Out of 11,197 registered athletes, we documented 1,304 sports injuries. The sports events with the highest injury rates were freestyle skiing, snowboarding, alpine skiing, bobsleigh, and ice hockey, with the most frequent injury locations being the knees, thoracic/lumbar/back regions, and the wrist/hand/fingers. Contusions, hematomas, and bruises were the most prevalent injuries, followed by strains (including muscle rupture, tearing, or tendon rupture) and sprains (covering dislocations, subluxations, and ligament ruptures). In the Olympic Winter Games, events such as freestyle skiing, snowboarding, alpine skiing, bobsleigh, and ice hockey pose a particularly high risk. Predominant injury sites include the knee, spine/back, and wrist and hand, with injuries ranging from contusions and hematomas to strains and sprains. For effective injury prevention, it is crucial to emphasize proper medical resource allocation, specialized training for medical personnel, and meticulous venue maintenance.

Quantifying the dose-response relationship between exercise and health-related quality of life in patients undergoing haemodialysis: A meta-analysis.

Objective: This meta-analysis aims to explore the dose-response relationship of aerobic exercise or aerobic combined resistance exercise on cardiopulmonary function in maintenance hemodialysis（MHD）, with the goal of aiding in the formulation of precise exercise prescriptions. Methods: A literature search up to August 18, 2023, was conducted in databases including Web of Science, among others, focusing on the effects of exercise interventions on cardiopulmonary function in hemodialysis patients.Two researchers independently conducted literature screening, data extraction, and an assessment of study methodology quality. A dose-response meta-analysis was carried out using a one-stage cubic spline mixed-effects model, followed by stratified analyses based on intervention period, intervention method, and exercise environment. Results: A nonlinear dose-response relationship was observed between exercise and 6-minute walk test (6WMT) as well as peak oxygen uptake (VO2Peak) in hemodialysis patients. The optimal exercise dose for the 6WMT across the full exposure range was 922 METs-min/week, with VO2Peak increasing with the dose. The effects were influenced by the type of exercise, intervention period, and exercise environment. An exercise dose of 500 METs-min/week and 619 METs-min/week was found sufficient to achieve the minimal clinically important differences (MCID) for 6WMT and VO2Peak, respectively. Conclusion: There is a significant association between the dose of exercise and its effects. With appropriate adjustment of variables, even low-dose exercise can lead to clinically significant improvements in cardiopulmonary function.

Health-related quality of life in patients with inborn errors of immunity: a bibliometric analysis.

Background: Inborn Errors of Immunity (IEI) are characterized by a heightened susceptibility to infections, allergies, and various other health complications. Health-Related Quality of Life (HRQOL) in patients with IEI is a critical area of research that demands attention due to the impact of IEI on patients' lives. This study utilized bibliometric methods, aiming to comprehensively explore the research content and hotspots in the field of HRQOL in patients with IEI. Methods: This bibliometric analysis utilized data from the Science Citation Index Expanded (SCIE) and Social Sciences Citation Index (SSCI) within the Web of Science core datasets up to January 1, 2024. The study focused on literature that addressed HRQOL in IEI patients, involving a total of 1,807 authors and 309 articles published across 112 journals. The analysis included publication volume and growth trends, country and institutional contributions, authorship, and journal analysis. Results: The research found that despite the importance of HRQOL in IEI, the volume of publications in this field remains consistently low, with no significant increase in trend. The USA leads in publication and citation volumes, reflecting a geographical imbalance in research contributions. Key journals in this field include the Journal of Clinical Immunology, Frontiers in Immunology, and the Journal of Allergy and Clinical Immunology. The study highlights that while treatments like hematopoietic stem cell transplants and gene therapy have improved patient IEI survival rates, they still often come with significant side effects impacting HRQOL. The analysis underlines the need for comprehensive HRQOL assessments in IEI, considering the physical and psychological impacts of treatments. Conclusions: This study represents a bibliometric analysis focusing on HRQOL in patients with. It underscores the need for more extensive and systematic research in this area, emphasizing the importance of a multidisciplinary approach. Despite advancements in medical treatments for IEI, there is a crucial need to focus on HRQOL to enhance patient satisfaction and overall well-being. The findings advocate for more personalized treatment plans and a better understanding of the psychosocial needs of patients with IEI to improve their quality of life.

Effectiveness of animal-assisted activities and therapies for autism spectrum disorder: a systematic review and meta-analysis.

Background: Given the rising interest in complementary therapeutic strategies for autism spectrum disorder (ASD), this research aims to provide a comprehensive analysis of the impact of animal-assisted activities and therapies (AAAT) on various ASD symptoms. Methods: A meticulous search of databases, including Scopus and PubMed, was conducted to gather relevant research on AAAT for ASD. This process led to the selection of 45 studies encompassing 1,212 participants. The chosen studies were then subjected to a meta-analysis to evaluate the efficacy of AAAT in alleviating core ASD symptoms. Results: The meta-analysis revealed significant improvements in several core ASD symptoms due to AAAT. Notably, there were improvements in social communication (MD = -4.96, 95% CI [-7.49, -2.44]), irritability (MD = -2.38, 95% CI [-4.06, -0.71]), hyperactivity (MD = -4.03, 95% CI [-6.17, -1.89]), and different word usage skills (MD = 20.48, 95% CI [7.41, 33.55]). However, social awareness (MD = -1.63, 95% CI [-4.07, 0.81]), social cognition (MD = -3.60, 95% CI [-9.36, 2.17]), social mannerisms (MD = -0.73, 95% CI [-2.55, 1.09]), social motivation (MD = -1.21, 95% CI [-2.56, 0.13]), lethargy (MD = -1.12, 95% CI [-3.92, 1.68]), and stereotypical behaviors (MD = -0.23, 95% CI [-1.27, 0.80]) did not significantly improve. Conclusion: The study demonstrates the potential of AAAT in improving certain core symptoms of ASD, such as social communication, irritability, hyperactivity, and word usage skills. However, the effectiveness of AAAT in other ASD symptom domains remains uncertain. The research is limited by the absence of long-term follow-up data and a high risk of bias in existing studies. Therefore, while the findings indicate the promise of AAAT in specific areas, caution is advised in generalizing its efficacy across all ASD symptoms.

Effects of aerobic exercise on children's executive function and academic performance: A systematic review and meta-analysis.

Objective: To investigate the effects of exercise on executive function in children, providing an evidence-based foundation to inform future research in school physical education and health education. Methods: We searched ten databases: Cochrane Library, Scopus, OVID, Web of Science, PubMed, EBSCOhost, SPORTDiscus, PsycINFO, CNKI, WANFANG DATA, VIP, and SinoMed, and eight articles were included. Applying the revised Cochrane Risk of Bias Tool for Randomized Trials (RoB2), funnel plots and Egger regression analysis were integrated with R meta-analysis to screen for publication bias. The quality of the evidence was appraised using the Grading system. Results: The included literature contained 2655 participants, with 1308 in the experimental group and 1347 in the control group. The results indicated that the aerobic exercise group considerably improved inhibitory control in children compared to the control group [SMD = 0.29, 95% CI (0.05, 0.54), P = 0.018]; working memory [SMD = 0.25, 95% CI (0.07, 0.42), P = 0.005]; and cognitive flexibility [SMD = 0.36, 95% CI (0.17, 0.54), P < 0.001]. However, the findings indicated that only aerobic exercise interventions extending beyond 50 weeks positively influenced academic performance in children [SMD = 1.19, 95% CI (0.34, 2.04), P = 0.006]. The results of an Egger regression analysis revealed that the p-values for inhibitory control, working memory, cognitive flexibility, and academic performance were more significant than 0.1. The Grade system said that the quality of evidence was all low regarding the level of evidence. Conclusion: Aerobic exercise enhanced executive function but only aerobic exercise interventions extending beyond 50 weeks demonstrated a significant effect on the academic performance of children. Due to the low quality of evidence presented in this study, additional high-quality randomized controlled trials are needed to confirm these findings.

Effects of Equine-Assisted Activities and Therapies for Individuals with Autism Spectrum Disorder: Systematic Review and Meta-Analysis.

Autism spectrum disorder (ASD) has become a critical public health issue that affects more than 78 million people. In many recent studies, the authors have demonstrated that equine-assisted activities and therapies (EAATs) can substantially improve the social and behavioral skills of children with ASD. However, the qualities of the studies differ, and some authors reached opposite conclusions. In this review, we systematically and objectively examined the effectiveness of EAATs for people with ASD, combining both qualitative and quantitative methods. We searched five databases (PubMed, Scopus, ERIC, ProQuest, and MEDLINE) and added relevant references, and we identified 25 articles for data extraction and analysis. According to our results, EAAT programs can substantially improve the social and behavioral functioning and language abilities of children with ASD. However, among the subdomains, the results were inconsistent. According to the meta-analyses, there were considerable improvements in the social cognition, communication, irritability, and hyperactivity domains, but not in the domains of social awareness, mannerisms, motivation, lethargy, stereotypy, or inappropriate speech. Moreover, there was a lack of sufficient comparative data to conclude that EAAT programs lead to substantial improvements in motor and sensory functioning. In addition, among the included studies, we noted the indicator of whether EAAT programs decreased parental stress and improved family functioning, and although there were four articles in which the researchers considered this aspect, we were unable to draw any conclusions because of the insufficient data and conflicting descriptive evidence. However, we need to consider the improvement in parental mental health as a factor in the effectiveness of this complementary intervention. We hope that in future studies, researchers will focus on family functioning and conduct more randomized controlled trials (RCTs) with blinded assessments using different scales and measures.

The safety and efficacy of oral antiviral drug VV116 for treatment of COVID-19: A systematic review.

BACKGROUND: Recent trials have highlighted the potential of oral antiviral VV116 in the treatment of patients with mild COVID-19. However, no comprehensive studies have assessed the safety and efficacy of VV116. Therefore, we conducted a systematic review to assess the safety and efficacy of VV116. METHODS: A comprehensive search was conducted on PubMed, Scopus, and Google Scholar websites, with a cutoff date of March 23, to identify pertinent studies. RESULTS: The results from the 3 included studies indicated that no serious adverse events were reported in the VV116 experimental groups, which exhibited a 2.57-day faster time to viral shedding than the control group and demonstrated non-inferiority to the nirmatrelvir-ritonavir control group in alleviating major symptoms. DISCUSSION: Collectively, available studies suggest a reliable safety and efficacy profile for VV116. However, the limited number of trials was insufficient for meta-analysis, and the included population consisted of younger individuals with mild and moderate symptoms, not encompassing the elderly who are severely affected by COVID-19. We hope that more studies will be conducted in the future to ensure that VV116 has a more reliable safety and efficacy profile in the clinical setting, especially in severe or critical patients.

Research trends and hotspots of exercise for people with sarcopenic: A bibliometric analysis.

This study aimed to analyze the trends and themes in exercise and sarcopenia research using a bibliometric approach. The Web of Science citation database was used to identify papers published on exercise and sarcopenia. The retrieved data on institutions, journals, countries, authors, journal distribution, and keywords were analyzed scientometric ally using CiteSpace and VOSviewer. 2895 papers were included according to our specified inclusion criteria eventually. The data showed an upward trend in the number of published articles on exercise and sarcopenia. The countries with the highest number of publications were the United States, Japan, and England; research institutions were mainly composed of universities in Europe and the United States, and high-producing authors formed major collaborative teams, but cross-geographical and cross-institutional collaboration was not apparent; research was closely focused on 3 aspects: resistance exercise, resistance combined with other forms of exercise, and exercise combined with nutritional supplementation, of which resistance exercise was a particular focus; and recently, the research hotspots were mainly the effects of exercise on grip strength. The most cited articles were consensus guidelines published by the working group on sarcopenia in the elderly from different continents. The prevention and rehabilitation of sarcopenia in the elderly are gaining attention. Current primary exercise therapies for sarcopenia and exercise combined with nutritional supplementation have significant advantages and the potential to delay muscle decay. This suggests a promising area for future research that could benefit from further advances.