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Cross-Correction in HSC Gene Therapy for Metachromatic Leukodystrophy
Targeting Trichophyton rubrum with phytochemicals: a computational approach for antifungal drug discovery
Resilience factors, pain, and physical activity in adolescent chronic musculoskeletal pain: Design and protocol of a pilot phase 2 single-group, non-randomized clinical trial
Introduction Chronic musculoskeletal pain (CMSKP) in adolescence is associated with physical, psychological, social, and academic impairment and increased risk for chronic pain in adulthood. Although physical activity interventions are an evidence-based approach for managing pediatric chronic pain, many adolescents with CMSKP avoid physical activity due to fear of increased pain, low confidence in physical functioning, and other pain-avoidance behaviors. Resilience-focused interventions targeting self-efficacy, motivation, and mental flexibility may improve engagement in valued activities despite pain. This study describes the design and protocol of the Pain REsilience Promotion for Youth (PREP-Y) intervention, a resilience-focused physical activity intervention for adolescents with CMSKP. Methods and analysis This single-site, pilot phase 2, single-group, non-randomized clinical trial will enroll 40 adolescents aged 12–17 years with CMSKP from Nationwide Children’s Hospital in Columbus, Ohio, USA. Participants complete questionnaires, objective physical functioning assessments, and physical activity monitoring using activPAL devices as baseline measures. Participants then complete 4 virtual resilience-focused intervention sessions targeting pain resilience, self-efficacy, motivation, and adaptive coping related to physical activity. Garmin watches are used to track activity during the intervention period. Follow-up assessments occur post-intervention and at 3 months post-intervention. Primary outcomes include feasibility and acceptability, assessed through recruitment, retention, attendance, intervention fidelity, and completion of study measures. Exploratory outcomes include physical activity, sedentary behavior, pain-related functioning, pain catastrophizing, kinesiophobia, self-efficacy, and resilience-related constructs. Ethics and dissemination The study was approved by the Nationwide Children’s Hospital Institutional Review Board. Findings will inform a future randomized clinical trial. This manuscript reflects protocol version 5.0 dated 23 March 2026. Trial registration ClinicalTrials.gov NCT06923891 .
Medical Standards by Federal Fiat
Comparative analysis of ocular surface restoration following different techniques of allogeneic limbal transplantation in a rabbit model of limbal stem cell deficiency
Current immunosuppressive treatment and self-reported lifetime stroke history among United States adults: A cross-sectional study
Current immunosuppressive treatment is used for autoimmune, inflammatory, malignant, transplant-related, and other chronic conditions that may carry elevated cerebrovascular burden. Nationally representative evidence on current immunosuppressive treatment status and self-reported lifetime stroke history remains limited. This cross-sectional study used pooled 2023–2024 National Health Interview Survey Adult Sample data. The analytic sample included adults aged 18 years or older with valid survey weights and complete data on exposure, outcome, and selected covariates. The exposure was current self-reported use of medications that weaken the immune system. The outcome was self-reported lifetime stroke history. Survey-weighted logistic regression estimated odds ratios and 95% confidence intervals, accounting for National Health Interview Survey stratification, clustering, and adjusted sampling weights. The final analytic sample included 60,026 adults, representing approximately 250 million United States adults. The weighted prevalence of current immunosuppressive treatment was 4.6%. Stroke history was more common among adults receiving immunosuppressive treatment than among those not receiving treatment (6.0% versus 2.8%). In unadjusted analysis, immunosuppressive treatment was associated with higher odds of stroke history (odds ratio 2.24, 95% confidence interval 1.86–2.70, p < 0.001). After full adjustment for age, sex, race/ethnicity, hypertension, diabetes, smoking status, coronary heart disease, and income-to-poverty category, the association persisted (adjusted odds ratio 1.71, 95% confidence interval 1.40–2.08, p < 0.001). Current immunosuppressive treatment status, likely reflecting both medication exposure and underlying disease burden, was associated with higher odds of self-reported lifetime stroke history among United States adults. Because of the cross-sectional design, broad exposure definition, self-reported outcome, and potential confounding by indication, these findings should be interpreted as an association rather than evidence of causation.
Platelet-Activating Anti–Platelet Factor 4 Disorders
Comprehensive analysis of mitochondrial metabolism–associated clusters and prognostic scoring model index construction in breast cancer
Negative interpretation bias and emotional responses to positive contexts
Negative interpretation bias, the tendency to interpret ambiguous situations as negative or threatening, is associated with reports of intense and more frequent negative affect. However, there is a relative paucity of work seeking to determine whether this cognitive bias might account for individual differences in affective responses to positive content. Given the wealth of benefits associated with positive emotional experiences, such as greater psychological wellbeing and better physical health, this investigation tested the influence of negative interpretation bias on emotion responses to evocative positive film clips as positive emotion-eliciting contexts. Negative interpretation bias was indexed using a novel word matching task. In each investigation, careful consideration of dispositional or trait-level influence on interpretation bias (i.e., dispositional negativity) was considered. Investigations conducted across three samples of college students at a large, Midwestern public university reveal complexity to this question: in one study, a small significant indirect effect of negative interpretation bias on the association between dispositional negativity and self-reported affect following positive emotionally-evocative films was found, while in the two subsequent studies, no significant mediation was found. Certain contextual factors, such as the explicit or discrete nature of the clip presentation as well as more stable tendencies toward positive emotional responsivity and the capacity to self-report emotional experiences, appear to be important. Finally, the novel task was found to be reliable and demonstrated convergent validity with established indicators. Future work should continue to clarify the conditions under which negative interpretation bias may influence responses to positive emotional contexts, given the importance of positive emotionality for lifelong physical and mental health.
The Paradox of Medical Aid in Dying
Isolation and preliminary characterization of a glucan-type exopolysaccharide produced by Bacillus tequilensis strain HH from Egyptian fermented cucumber
Abstract Exopolysaccharide (EPS) production is a common feature of microbial carbohydrate metabolism during fermentation; however, glucan-type EPS produced by Bacillus species in fermented vegetable systems remain insufficiently characterized. This study aimed to isolate an EPS-producing bacterium from naturally fermented cucumber and to perform a preliminary physicochemical and spectroscopic characterization of the produced polymer. An EPS-producing bacterial isolate was recovered and identified as Bacillus tequilensis , a member of the Bacillus subtilis species complex, based on 16 S rRNA gene sequence analysis. The extracellular polysaccharide was partially purified and analyzed using FTIR and ¹H NMR spectroscopy, revealing structural features consistent with a glucan-type EPS. Rheological analysis demonstrated a concentration-dependent increase in viscosity, confirming the macromolecular nature of the polymer in aqueous systems. Sucrose-hydrolyzing activity was detected under optimized conditions, indicating active carbohydrate metabolism associated with EPS production. In vitro cytocompatibility assessment using Vero and WI-38 cell lines showed high cell viability at low to moderate concentrations, with a dose-dependent reduction observed at higher levels. Overall, this study reports the isolation of an EPS-producing Bacillus tequilensis strain from Egyptian fermented cucumber and provides preliminary insights into the properties of its glucan-type exopolysaccharide, highlighting fermented vegetable microbiota as a potential source of functional biopolymers.
Primary cesarean section in Sub-Saharan Africa: A systematic review and meta-analysis using the Robson Ten-Group Classification System
Background The overuse of cesarean sections, mainly of primary procedures, is a major contributor to perinatal mortality in Sub-Saharan Africa. The Robson Ten-Group Classification System is the global standard for cesarean section rate. Evidence on the pooled primary cesarean section rate using this system in Sub-Saharan Africa SSA remains limited. Materials and methods A systematic review and meta-analysis were conducted. PubMed, Scopus, ScienceDirect, Google Scholar, Google, and ResearchGate were searched for studies published between 2001 and February 22, 2025. Data were extracted into Microsoft Excel and analyzed using Stata 17. A random-effects model was applied to calculate the pooled rate. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Publication bias was assessed using a Doi plot and the Luis Furuya-Kanamori index. Heterogeneity was assessed using the I² statistic. Results The pooled facility‑based primary cesarean section rate, derived from 25 institution‑based studies (213,117 births; predominantly secondary and tertiary hospitals), in Sub-Saharan Africa was 18.7% (95% CI: 16.2–21.4; 95% prediction interval: 8.4%−36.8%). Robson Groups 1 and 2 were the largest contributors (47.5%), with Group 1 alone accounting for 37.1%. In both nulliparous and multiparous women, primary cesarean section was more common after spontaneous labor than after induction or elective procedures. Significant heterogeneity was observed across studies (I² = 99.64%, p < 0.001). No evidence of publication bias was found (LFK index = −0.27). Conclusion The facility‑based primary cesarean section rate in Sub-Saharan Africa exceeded the WHO global reference, with Robson Groups 1 and 2 being the largest contributors. High rates of prelabor cesarean and elevated rates following spontaneous labor raise concern for possible overuse, but unmeasured comorbidities and referral bias cannot be excluded. Stricter adherence to evidence-based protocols, routine use of the Robson classification for clinical audits, and linkage with indication‑level data are essential for improving obstetric care.
Case 22-2026: A 37-Year-Old Woman with Persistent Nasal Ulceration
Development of shelf stable formulation for adenovirus vectored vaccines and therapeutics
Abstract A major limitation of therapeutic delivery is the cold chain storage requirement. Adenoviruses (AdV) have been demonstrated to be an effective delivery vector for several indications including COVID-19 vaccines but are limited by storage and transportation conditions. Previous work has demonstrated formulation and drying of vectored vaccines with pullulan and trehalose-based (PT) films significantly improves thermostabilization. To increase the accessibility of AdV based therapeutics, we developed a vacuum based drying methodology with optimized PT excipients resulting in a shelf stable product. We demonstrate the thermostability of formulated and dried AdV at 55°C for 7 weeks with less than 0.5 total log IU loss, and over 44 weeks at 37°C with less than 0.25 total log IU loss. Additionally, murine vaccination with the ChAd-TriCoV/Mac vaccine showed no difference in response between fresh and aged at 37°C for 44 weeks. These data demonstrate our formulation methodology’s performance, resulting in a shelf stable formulation for AdV based therapeutics.
Prevalence and associated factors of intimate partner violence against reproductive-age women in Africa and Asia regions: Insights from 2022–2024 DHS datasets
Background Intimate partner violence is a major public health and human rights issue, affecting one in four women globally. It is particularly prevalent in low‑ and middle‑income countries, where reproductive‑age women face heightened risks due to cultural norms, poverty, and weak legal protections. It is linked to severe mental, physical, and reproductive health consequences, as well as intergenerational and societal impacts. Using recent demographic and health survey data, this study provides updated cross‑regional insights into intimate partner violence among women in Africa and Asia to inform culturally tailored interventions and strengthen policy frameworks. Methods A cross-sectional study was conducted using recent demographic and health survey data (2022–2024) from twelve countries in sub-Saharan Africa and Asia, including 88,414 women aged 15–49 years. Intimate partner violence was measured using 13 self‑reported items adapted from the Conflict Tactics Scale and coded as a binary outcome. Explanatory variables were selected based on the WHO ecological model, covering individual, relationship, community, and societal factors. Weighted data were analyzed in STATA 17 using multilevel logistic regression to account for clustering, with associations reported as adjusted odds ratios and 95% confidence intervals. Results The overall prevalence of intimate partner violence among reproductive‑age women in sub-Saharan Africa and Asia was 29.51% (95% CI: 29.21–29.81), with emotional (21.03%) being most common. Prevalence ranged from 51.74% in the Democratic Republic of Congo to 13.53% in the Philippines. Multilevel analysis identified significant predictors, including age, education, marital and employment status, early cohabitation, number of children, maternal abuse exposure, attitudes toward wife‑beating, partner jealousy, fear of partner, smoking, partner alcohol use, and region. Notably, partner alcohol consumption (AOR = 3.10), fear of partner (AOR = 2.98), and partner jealousy (AOR = 2.96) showed the strongest associations with intimate partner violence. Conclusions Nearly one in three reproductive‑age women experienced intimate partner violence, highlighting its magnitude and public health importance. Intimate partner violence was strongly associated with socio‑demographic, behavioral, and attitudinal factors and regional differences. These findings call for multi‑level interventions that promote women’s empowerment, challenge harmful gender norms, strengthen legal frameworks, and expand community‑based support, while future longitudinal and qualitative research should deepen understanding and guide evidence‑based policy.
Braking Bad News
Correction: FSP1 + fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells
First report of Corynespora cassiicola causing leaf spot on Begonia fimbristipula in China
Background Begonia fimbristipula , an economically important medicinal plant in southern China, has recently suffered severe yield losses from leaf spot disease in Guizhou and Hunan Provinces; the causal pathogen remains unknown. Methods Field surveys were conducted across multiple locations in Guizhou and Hunan Provinces to record disease symptoms and incidence. The pathogen was isolated from diseased leaves via tissue culture, and identified by combining morphological characteristics and multilocus phylogenetic analysis (ITS, TEF1α, RPB2). Pathogenicity was verified by fulfilling Koch’s postulates through artificial inoculation and re-isolation assays. Results Severe leaf spot outbreaks were observed in August 2024, with over 60% disease incidence across 667 hectares and >20% fresh leaf yield loss. The isolated pathogen was identified as Corynespora cassiicola based on gray to dark-gray colonies, pale-brown olivaceous conidia with 0–15 pseudosepta, and ≥98% bootstrap support in phylogenetic clustering with known C. cassiicola strains. Koch's postulates were fulfilled by reproducing typical field symptoms on inoculated B. fimbristipula seedlings and re-isolating the pathogen. Conclusions This is the first report of C. cassiicola causing leaf spot on B. fimbristipula in China, expanding the host range of this pathogen. Our findings provide a critical basis for the accurate diagnosis of this newly emerging disease on the medicinal plant.