Major depressive disorder (MDD) is strongly associated with suicide risk. While lipid metabolism dysregulation is implicated in MDD pathophysiology, its specific relationship with suicide attempts (SA), particularly regarding sex-specific patterns, requires precise quantification. This study examined associations between lipid profiles and SA in young adults with first-episode, drug-naïve (FEDN) MDD, investigating sex differences and developing sex-stratified predictive models. We conducted a cross-sectional analysis of 1,289 young adults with FEDN-MDD, of whom 244 (18.9%) reported a history of SA. Comprehensive demographic, clinical (including Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale [HAMA], and Positive and Negative Syndrome Scale scores), and metabolic data (lipid profiles, thyroid function, glucose) were collected. Sex-specific multivariate regression and LASSO-optimized machine learning (ML) models (XGBoost, Random Forest) were used to identify risk profiles and evaluate predictive discrimination. Significant sex interactions were identified for multiple clinical and metabolic variables. Sex-specific multivariate regression (following LASSO feature selection) revealed distinct SA risk profiles. For males, suicide risk was independently driven by severe anxiety (HAMA), hypercholesterolemia (TC), and profound thyroid axis dysregulation. For females, risk factors included greater depression/anxiety severity, prolonged illness duration, and specifically reduced HDL-C. To address dataset imbalance, ROSE resampling was applied. In the independent testing sets, XGBoost achieved optimal balanced performance for males (Area Under the Curve [AUC] = 0.760, Specificity = 0.836), while Logistic Regression provided the highest discrimination and sensitivity for females (AUC = 0.809). These findings quantify clinically relevant, sex-divergent associations between metabolic dysregulation and SA in FEDN MDD. The development of sex-specific models demonstrates promise for objective risk stratification. However, their translation into clinical tools necessitates robust external validation in independent cohorts.

Social self-efficacy (SSE) is a key cognitive-motivational construct predicting social adjustment and mental health. However, existing SSE scales were developed in Western individualistic cultures, neglecting collectivistic characteristics (e.g., relational harmony, emotional restraint) and online social contexts. This study developed and validated a culturally adapted multidimensional College Students 'Social Self-Efficacy Questionnaire (CSSEQ) for Chinese students.

A mixed-method, multi-phase design was used. Phase 1 involved semi-structured interviews (n = 13) and open-ended surveys (n = 266) to explore the indigenous structure. Phase 2 included item generation, expert review, content validity, item analysis, and exploratory factor analysis (EFA; n = 572). Phase 3 performed confirmatory factor analysis (CFA; n = 1,011), reliability, validity, and common method bias tests.

The final 24-item CSSEQ exhibited a three-factor correlated model: Social Interaction Competence Confidence, Emotional Regulation Confidence, and Interpersonal Awareness Confidence. CFA showed excellent fit: χ ² /df = 2.59, RMSEA = 0.04, CFI = 0.96, TLI = 0.95, SRMR = 0.03. A higher-order model also fit acceptably. Reliability was excellent (Cronbach's α = 0.96, composite reliability = 0.95, test-retest = 0.96). Convergent validity (AVE > 0.50), discriminant validity (HTMT < 0.85), criterion validity (r = 0.88 with PSSE; r = 0.72 with social self-esteem), and incremental validity (ΔR ² = 0.124) were all supported. Content validity was excellent (I-CVI > 0.78). Common method bias was not substantial (Harman's single-factor: 28.6%). Measurement invariance across gender, grade, and major was supported (ΔCFI ≤ 0.01, ΔRMSEA ≤ 0.015).

The CSSEQ is a psychometrically rigorous, culturally grounded, and structurally robust instrument for assessing social self-efficacy among Chinese college students. Compared to the Western Perceived Social Self-Efficacy Scale (PSSE), the CSSEQ demonstrated significant incremental validity (ΔR ² = 0.124) and a correlation of r = 0.88 (below the redundancy threshold of 0.90), indicating that it captures culturally specific components not covered by existing Western measures. It captures culturally specific components missing from Western scales and integrates modern social contexts, making it suitable for cross-cultural research, mental health screening, intervention design, and educational assessment.

Low- and middle-income countries face a rapidly escalating, alcohol-related public health crisis spanning cancer, injury, liver disease, mental health disorders and the complications of human immunodeficiency virus infections. Despite compelling evidence that alcohol is a leading risk factor for premature death and disability, few countries include comprehensive alcohol control policies in their public health agenda. This gap between evidence and policy is critical because evidence-based interventions could decrease the alcohol-attributable disease burden by up to 30% within a decade. We conducted a policy analysis to synthesize evidence from low- and middle-income countries and propose a comprehensive multicomponent framework for alcohol control adapted from experience with tobacco control. Documented achievements show that simultaneously integrating alcohol control into the existing health-care system, introducing regulation, and building institutional capacity can reduce consumption and generate substantial economic returns. However, interference from the alcohol industry in policy, mirroring the historical approach of the tobacco industry, underscores the need for explicit protections. Evidence-based recommendations on implementing alcohol control policies are presented for international agencies, national governments, health-care systems and civil society. These recommendations also draw on global lessons from the World Health Organization's Framework Convention on Tobacco Control. Today, the convergence of robust scientific evidence, proven interventions, successful implementation models and growing political support present an opportunity to advance alcohol control in low- and middle-income countries. The question is not whether comprehensive alcohol control is feasible in resource-constrained settings but whether the global health community will act decisively on the evidence available.

Condom use resistance (CUR), which involves tactics to obtain condomless sex with a partner who wishes to use condoms, is a common sexual risk behavior among heterosexual men. CUR is associated with physical and mental health consequences for those who experience it. Prior research has identified adversarial heterosexual beliefs (AHB) as a trait-level risk factor that increases the likelihood of CUR engagement. However, little is known about how AHB interact with daily factors (e.g., daily emotion modulation, sex motives) to influence CUR in real-life. The current study examined how the interaction between AHB and daily emotion modulation difficulties and power- and coping-related sex motives was associated with CUR engagement. Using data from daily reports among men who have sex with women, a multilevel logistic model revealed that men were more likely to engage in CUR if they had higher average coping sex motives over the 32-day period and on days with higher power-related sex motives. Significant cross-level interactions emerged between AHB and both emotion modulation difficulties and coping sex motives. On days with greater emotion modulation difficulty, men with higher AHB reported increased CUR behavior. On days with higher coping sex motives, men with lower AHB reported increased CUR behavior. Results suggest that AHB amplify risk when coupled with impaired emotion modulation, while maladaptive coping motives represent an alternative pathway to CUR among men lower in AHB. Findings underscore the importance of examining both trait cognitive risk factors and daily emotion regulation and sex motives in understanding sexual risk behaviors.

Transcendental meditation (TM) is broadly trained mind-body intervention for its prospective benefits on physical and mental health. However, evidence exploring its effects on brain connectivity and cognitive performance remains inadequate.

This research aimed to evaluate the influence of TM on EEG functional connectivity and audiovisual reaction time in healthy adults.

This prospective single group study was undertaken after institutional ethical approval among 34 healthy adults aged between 25-50 years who completed a 12-week transcendental meditation intervention (20 minutes/day, 5 days/week). Physiological parameters including pulse rate and blood pressure were recorded using standardized protocols. Neurophysiological assessment was performed using a 32-channel EEG system and functional connectivity was analysed using Weighted Phase Lag Index (WPLI). Cognitive performance was assessed by audio-visual reaction time. Pre-post-intervention differences were analysed using paired t-test and effect sizes were calculated using Cohen's d.

TM practice significantly reduced systolic and diastolic blood pressure, along with significant reduction in pulse rate with a small effect size (p = 0.021, d = 0.29). EEG analysis showed increased functional connectivity across fronto-central and occipital regions. Visual and auditory reaction times improved significantly, with the largest effect observed in auditory reaction time.

TM enhances cardiovascular regulation, brain connectivity and cognitive processing speed, reflecting improved neural efficiency and autonomic balance. It may serve as a simple, non-pharmacological approach for improving cognitive performance and well-being.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited therapies, emphasizing the need for deeper understanding of disease pathogenesis. While more than 40 ALS-associated genes have been identified, their contribution varies significantly across populations and the data from the Indian population remains scarce. We aimed to comprehensively characterize the spectrum of coding DNA variations in ALS-associated genes and identify novel genetic contributors in an Indian cohort. Whole-exome sequencing on 761 ALS patients and 917 in-house healthy controls and repeat-primed PCR for expansions (C9orf72, ATXN2, NOTCH2NLC, NOP56) were performed. Variants were classified using ACMG guidelines, and rare variant association testing was conducted. Overall diagnostic yield was 15.90%, with pathogenic/likely pathogenic variants. Familial ALS showed higher diagnostic yield (36.95%) than sporadic ALS (12.96%). SOD1 dominated familial cases (53.85%), while OPTN, SOD1 and FIG4 were prevalent in sporadic cases. Homozygous SOD1 variants in six patients correlated with juvenile/young onset (< 30 years). C9orf72 expansions (4%) and ATXN2 repeats (1.7%) were identified at frequencies comparable with Asian cohorts. Rare variant analysis identified JAK2 as a novel genome-wide significant signal (FDR = 3.5 × 10^-5). This first large-scale genomic survey of Indian ALS patients showed SOD1 being the predominant cause of fALS, while OPTN, FIG4, and other genes drive disease amidst low C9orf72 frequency. The novel JAK2 association suggests a potential neuroinflammatory mechanism, highlighting the importance of studying diverse populations to uncover distinct genetic etiologies.

This paper takes an intersectional approach to explore the burdens of non-communicable diseases (NCDs) and their interactions with gendered inequities and poverty, in shaping health seeking practices. The study explores the lived experiences of men and women living with NCDs in three informal settlements in Freetown, Sierra Leone. As Low- and Middle-Income Countries (LMICs) grapple with increased NCD risk factors, evidence gaps limit understanding of the complex ways in which gendered vulnerabilities are shaped. This study provides insights into the multiple axes of inequity which shape NCD outcomes and healthcare access barriers and suggests ways to improve NCD services. This study therefore adapts and applies the Intersectional Gender Analysis Framework for Infectious Diseases of Poverty in an informal settlement context to understand how NCDs impact men and women differently and influence different health seeking and treatment outcomes. We conducted narrative interviews with 15 participants living with diabetes, hypertension, and disability related to stroke through three household visits for a period of 12 weeks. Findings highlight lived experience of NDCs, coping strategies and healthcare seeking patterns, influenced by poverty, gender inequities, and NCD comorbidities. Women's lived experiences of NCDs reflect historical and patriarchal disadvantages through their limited financial autonomy, barriers to healthcare decision making and treatment access, compounded by gendered impacts of conflict and migration. Men's experiences included an erosion of social status and financial autonomy, limiting access to healthcare and coping. Gender differences and patriarchal norms influenced household and healthcare decision making, reflecting the division of roles and access to resources by men and women, which shaped different care seeking pathways and treatment outcomes. Our study shows that the burden of NCDs and healthcare decision making are influenced by intersecting structural barriers, which requires that NCD healthcare must be approached from bio-social, rather than solely a biomedical perspective.

Patients with type 2 diabetes mellitus (T2DM) who survive myocardial infarction (MI) remain at high risk for recurrent cardiovascular events and heart failure (HF). Although glucagon-like peptide-1 receptor agonist (GLP-1 RA) reduces cardiovascular events in stable atherosclerotic disease, its impact among patients with established MI has not been comprehensively synthesized.

To evaluate the association between GLP-1 RA use and cardiovascular outcomes in patients with T2DM across MI-defined cohorts.

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Heterogeneity was evaluated using the I² statistic, and 95% prediction intervals (PIs) were calculated to estimate the expected range of true effects in future clinical settings. Outcomes included all-cause mortality, cardiovascular death, study-defined major adverse cardiovascular events (MACE), MI, stroke, and HF or hospitalization for HF. A sensitivity analysis using the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment was performed to account for the small number of included studies and substantial heterogeneity. Statistical analysis was performed using R software version 4.5.0.

Seven studies, including 37,393 patients with T2DM from MI-defined populations (9556 receiving GLP-1 RA), were analyzed. GLP-1 RA use was associated with lower all-cause mortality (HR, 0.67; 95% CI, 0.49-0.90; I² = 87.3%; PI, 0.27-1.63; P = 0.0085), reduced study-defined MACE (HR, 0.69; 95% CI, 0.56-0.84; I² = 55.6%; PI, 0.44-1.06; P = 0.0002), and fewer HF events or hospitalizations for HF (HR, 0.78; 95% CI, 0.62-0.98; I² = 77.6%; PI, 0.42-1.45; P = 0.0306). No significant associations were observed for cardiovascular death (HR, 0.85; 95% CI, 0.67-1.06; I² = 0%; PI, 0.42-1.69; P = 0.15), recurrent MI (HR, 0.82; 95% CI, 0.62-1.09; I² = 63%; PI, 0.41-1.63; P = 0.1753), or stroke (HR, 0.91; 95% CI, 0.68-1.22; I² = 61.2%; PI, 0.40-2.05; P = 0.5237). In the sensitivity analysis using the HKSJ adjustment, statistical significance was lost for all endpoints, including all-cause mortality (P = 0.05), study-defined MACE (P = 0.13), and HF or hospitalization for HF (P = 0.06).

In patients with T2DM across MI-defined populations, GLP-1 RA use showed signals toward lower all-cause mortality, study-defined MACE, and HF-related events; however, these findings remain exploratory because of substantial heterogeneity, wide PIs, and attenuation of statistical significance under HKSJ adjustment.

PROSPERO identifier no. CRD420251270326.

Mesenchymal stromal cell (MSC)-derived insulin-producing cells (IPCs) represent an emerging strategy for β-cell replacement in type 1 diabetes mellitus (T1DM) owing to their differentiation potential, intrinsic immunomodulatory properties, and lower tumorigenic risk compared with pluripotent stem cell-derived platforms. However, accumulating evidence indicates that differentiation-associated immunogenicity, context-dependent immune recognition, and recurrent autoimmune responses may substantially limit long-term graft survival and therapeutic durability following transplantation. This review critically examines the immunological barriers associated with MSC-derived IPCs, including altered MHC expression, susceptibility to alloimmune and autoimmune-mediated rejection, and potential reactivation of autoreactive immune memory. We discuss the application of CRISPR-based hypoimmunogenic engineering strategies targeting antigen presentation pathways, NK-cell activation, and immune checkpoint modulation to generate more immune-evasive MSC-derived IPCs while preserving β-cell functionality. By integrating insights from T1DM immunopathogenesis, MSC biology, genome editing, and translational immunology, we propose a framework linking immune engineering with controlled differentiation, functional maturation, and long-term safety evaluation. In parallel, we comparatively position MSC-derived IPCs alongside clinically advancing iPSC-derived β-cell platforms to highlight their distinct translational niche, including potential advantages related to safety, immunomodulatory capacity, manufacturing accessibility, and scalability, while acknowledging the superior functional maturity and clinical progression currently demonstrated by iPSC-derived systems. Finally, we discuss key translational challenges, including genomic stability, immune-evasion durability, GMP-compliant manufacturing, and the need for rigorous functional and immunological benchmarking prior to clinical application of hypoimmunogenic MSC-derived IPC therapies in T1DM.

Polygenic risk scores (PRS) stratify obesity risk in population cohorts, but their value within specialised paediatric obesity clinics-where genetic liability may already be saturated-remains unclear.

We analysed 246 European adolescents with overweight and obesity (mean ± SD age 13.3 ± 2.2 years; 51% female; BMI 31.6 ± 4.1 kg/m²) attending a tertiary clinic in Salzburg, Austria. BMI-PRS based on people with European ancestry (PGS000027) and two cardiometabolic PRS (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR], type 2 diabetes [T2D]) were computed from Axiom-array genotypes. Distributions were compared with a population-based adult cohort from the same region (n = 2044). Associations with BMI, insulin resistance (HOMA-IR ≥ 2.5), alanine aminotransferase (ALT) and oral-glucose-tolerance parameters were examined by linear and logistic regression adjusted for age and sex.

The adolescent cohort showed a right-shifted BMI-PRS distribution; the lowest quintile exceeded the adult mean (p < 0.001). Within the clinic sample, BMI-PRS neither correlated with BMI (r = -0.11; 95% CI -0.23 to 0.02) nor predicted other parameters investigated. PRS for HOMA-IR and T2D showed similarly null associations.

In a genetically enriched clinical cohort, polygenic scores lose discriminatory power, delineating their optimal use for population screening rather than intra-clinic risk stratification. These data underscore the strong hereditary architecture of paediatric obesity and support context-specific application of precision-medicine tools.