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PubMed2026

Polygenic risk scores in major depressive disorder: A systematic review across diagnostic, treatment, course/severity, and subtype domains.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous across diagnostic, treatment-related, course/severity, and subtype domains. Polygenic risk score (PRS) studies have examined these domains, but differences in PRS sources, samples, methods, and endpoint definitions have fragmented the evidence. We synthesised findings and examined potential contributors to heterogeneity. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science were searched for studies published from January 2016 through 25 November 2025. Result records were synthesised using SWiM, and certainty was assessed with an adapted GRADE framework. RESULTS: Sixty studies contributed 493 retained records; 450 were descriptively classified as positive, null, or reverse, although records were not independent. Positive findings accounted for 44/56 diagnostic, 61/273 treatment-related, 64/100 course/severity, and 14/21 subtype records. For MDD/depression-derived PRSs and case-control MDD status, all 10 contributing studies showed higher liability in cases (exploratory exact sign test p = 0.002; FDR q = 0.004). The same PRS group showed positive findings for overall depressive symptom severity (14/18), although the study-level test was imprecise (5/5 studies; p = 0.063). Pharmacological response/remission findings for these PRSs were mostly null or directionally mixed (10 positive, 18 null, and 9 reverse). Treatment-resistant depression (TRD) findings differed by operational definition. Atypical and psychotic subtype signals arose mainly from single-study PRS and endpoint contrasts. CONCLUSIONS: PRS evidence was clearest for MDD diagnostic status and showed a tentative pattern for overall symptom burden. Treatment and subtype findings were less consistent or less replicated. Larger, ancestrally diverse studies with standardised endpoints and transparent PRS methods are needed.

Humans↗

PubMed2026

Integrated multi-omics analyses identify an RAS-SLC11A2-associated molecular framework linking iron metabolism with PCOS-related cardiometabolic risk.

INTRODUCTION: PCOS is a common endocrine disorder with elevated cardiometabolic risk, yet the role of the renin-angiotensin system (RAS)-iron metabolism axis in this comorbidity remains unclear. We explored its underlying mechanisms and evaluated the therapeutic potential of gentiopicroside. METHODS: Integrated multi-omics analyses combining transcriptomics, single-cell RNA sequencing, Mendelian randomization, machine learning, molecular docking, and in vitro functional assays were performed to identify shared molecular pathways and therapeutic targets across PCOS, hypertension, NAFLD, and T2DM. RESULTS: SLC11A2 was consistently dysregulated in PCOS transcriptomic datasets, and associated with iron metabolism, inflammatory response and oxidative stress pathways. Genetic analyses validated RAS-related regulation in hypertension susceptibility and revealed shared genetic architecture between PCOS and cardiometabolic traits. Network and single-cell analyses characterized SLC11A2-associated molecular patterns in disease-relevant cell types; machine learning identified disease-classifying molecular signatures. Gentiopicroside alleviated inflammatory and oxidative stress phenotypes, including reduced IL-6 expression and reactive oxygen species accumulation. CONCLUSION: This study defines an RAS-SLC11A2 molecular framework linking iron metabolism dysregulation to PCOS-related cardiometabolic risk, elucidating the mechanisms connecting ovarian dysfunction, inflammation, oxidative stress and hypertension, and supports gentiopicroside as a promising therapeutic candidate.

Humans↗

PubMed2026

A systematic review and network meta-analysis of single nucleotide polymorphisms associated with oral submucous fibrosis risk.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic and insidious oral disease characterized by hyalinization of the subepithelial connective tissue and progressive fibrosis of the oral submucosa. It is a precancerous condition of oral squamous cell carcinoma. Studies have demonstrated that single nucleotide polymorphisms (SNPs) are closely associated with susceptibility to OSF. This study aims to comprehensively evaluate the association between SNPs and OSF risk and to rank the strength of the association between different genetic models and OSF susceptibility. METHODS: Literature related to OSF was comprehensively searched from PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wangfang databases up to July 2025. Full-text case-control studies with patients diagnosed with OSF were included. Quality assessment was performed to evaluate the risk of bias. RevMan 5.4, GeMTC 0.14.3, and STATA 17.0 were used for the pairwise and Bayesian network meta-analysis. RESULTS: A total of 24 studies with 2545 cases and 3772 controls, covering 13 SNPs in 11 genes, were included in our meta-analysis. We found that CYP1A1 rs4646903:T>C, CYP1A1 rs1048943:A>G, GSTT1 null genotype, GSTM1 null genotype, and XRCC3 rs861539:C>T were associated with an increased risk of OSF, while MMP2 rs243865:C>T and MMP3 rs3025058: 5A>6A were associated with a decreased risk of OSF. Further Bayesian network meta-analysis indicated the top 5 genetic models with the highest association with OSF risk in network group 1 were the dominant model, homozygous model, allelic model, and recessive model of CYP1A1 rs1048943:A>G (ranked 1-4), and the heterozygous/dominant model of CYP1A1 rs4646903:T>C (both ranked 5). While the allelic models of XRCC3 rs861539:C>T and MMP3 rs3025058: 5A>6A ranked first for predicting OSF in group 2 and group 3, respectively. CONCLUSION: Some specific SNPs are significantly related to the risk of OSF. Among them, the dominant model of CYP1A1 rs1048943:A>G may be the most strongly associated genetic model with OSF risk. Future large-sample, well-designed studies with detailed genotype data are needed to validate the roles of these SNPs in OSF risk.

Humans↗

PubMed2026

Atopic dermatitis and the risk of osteoporosis and fractures: a meta-analysis of cohort studies.

BACKGROUND: This meta-analysis aims to evaluate the risk of osteoporosis and fractures in patients with atopic dermatitis (AD) by synthesizing data from cohort studies. We also provide a comprehensive analysis of fracture risks across different severities of AD and anatomical sites. METHODS: Following the PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Embase, and the Cochrane Library up to May 30, 2025. Studies that investigated the relationship between AD and osteoporosis or fractures were included in the analysis. Data extraction and screening were performed independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was applied, alongside sensitivity and subgroup analyses. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Ten cohort studies, involving 368 to over 2 million AD patients, were included. NOS scores ranged from 7 to 8, indicating generally high study quality. The pooled analysis revealed a 56% increased risk of osteoporosis (OR = 1.56, 95% CI: 1.14-2.13; I2 = 99.9%, p < 0.0001) and an 8% increased risk of all-cause fractures (OR = 1.08, 95% CI: 1.05-1.10; I2 = 82.1%, p < 0.0001) in AD patients. Subgroup analyses demonstrated a progressive increase in fracture risk with the severity of AD. Specific risks were significantly higher for vertebral fractures (OR = 1.14, 95% CI: 1.08-1.20; I2 = 67.3%, p = 0.009) and lower limb fractures (OR = 1.11, 95% CI: 1.08-1.13; I2 = 65.0%, p = 0.014). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected (p = 0.316). CONCLUSION: AD is associated with an increased risk of osteoporosis and fractures, particularly among patients with severe AD and those experiencing vertebral or lower limb fractures. These findings highlight the importance of targeted bone health monitoring in the clinical management of AD patients.Registration: (PROSPERO: CRD420251066550).

Humans↗

PubMed2026

Cardiometabolic Multimorbidity Increases the Risk of Hip Fracture: A Longitudinal Cohort Study Based on CHARLS.

BACKGROUND: Cardiometabolic Multimorbidity (CMM) is defined as the co-occurrence of two or more conditions among heart disease, diabetes mellitus, stroke, and hypertension. Previous studies have shown associations between cardiometabolic diseases and fragility fractures; however, the relationship between CMM and hip fractures remains unclear in the Chinese population. This study therefore aims to investigate this association in a Chinese cohort to inform fracture prevention strategies. METHODS: This prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS) collected from 2011 to 2020. Participants from the 2011 baseline survey cohort were initially included. Subsequently, individuals were sequentially excluded if they were under 45 years of age, had incomplete baseline CMM information, had a history of hip fracture, lost to follow-up, or had missing data on confounders. Kaplan-Meier survival analysis, Cox proportional hazards regression, subgroup analyses, and sensitivity analyses were performed to evaluate the association between CMM and the risk of hip fracture. RESULTS: A total of 6314 participants aged 45 years and older were included, of whom 544 had CMM. Over a 9-year follow-up period, 287 incident hip fractures (4.55%) were identified. Among these, 36 participants had been diagnosed with CMM at baseline, whereas 251 had not. The incidence of hip fracture was significantly higher in participants with CMM than in those without CMM (13% vs. 8%, p = 0.015). After full adjustment for confounders, multivariable Cox regression showed that CMM was associated with a 70% increased risk of hip fracture (HR = 1.70, 95% CI: 1.318-2.47; p = 0.005). Subgroup analyses indicated that age and history of falls were significant effect modifiers. The association between CMM and hip fracture was more pronounced in participants under 60 years old (P for interaction = 0.048) and those with a history of falls (P for interaction = 0.014). CONCLUSION: These findings suggest that CMM increases the risk of hip fracture, particularly among relatively younger individuals and those with a history of falls.

Humans↗

PubMed2026

Genetic risk stratification of common diseases in breast cancer survivors: a population-based cohort study.

IMPORTANCE: Patients diagnosed with breast cancer (BCa) are at increased risk of multiple common diseases; however, the spectrum of these diseases and the contribution of inherited genetic susceptibility remain incompletely characterized. METHODS: We evaluated 15 common diseases and tested their associations with BCa exposure and disease-specific polygenic risk scores (PRS) in the UK Biobank (UKB; N = 254,736). Analyses were performed using cause-specific Cox proportional hazards models within a full-cohort framework, with time-updated BCa status, delayed entry at study recruitment, and age as the underlying time scale. RESULTS: After recruitment, incident BCa was diagnosed in 11,386 women (4.47%), including 2,742 (24.08%) with metastatic BCa. Patients with BCa had an increased risk of nine diseases spanning cardiovascular, metabolic, and neuropsychiatric domains (P<0.003, Bonferroni-corrected). Elevated risks were generally observed among patients with both early staged and advanced BCa. Inherited susceptibility further stratified disease risk, with the highest risks observed among patients with BCa with elevated disease-specific PRS. For example, compared with women without BCa, the hazard ratio (HR; 95% CI) for osteoporosis was 2.33 (2.15-2.52) among women with any BCa, 2.38 (2.18-2.59) among those with non-metastatic BCa, and 2.12 (1.78-2.54) among those with metastatic BCa; the HR was 4.48 (3.99-5.02) among patients with BCa in the highest quartile of osteoporosis-specific PRS (all P<0.001). In contrast, BCa was not significantly associated with risk of coronary artery disease. CONCLUSION: BCa and inherited genetic susceptibility jointly contribute to increased risk of multiple common diseases, supporting the integration of genetic risk stratification into survivorship care.

Complications↗

PubMed2026

Gout and allopurinol adherence in newly diagnosed patients and the risk of fractures: a nationwide cohort study.

INTRODUCTION / OBJECTIVES: The association between gout and fractures remains controversial due to the competing effects of uric acid's antioxidant properties and gout-induced chronic inflammation. Our study aimed to evaluate the risk of fractures in newly diagnosed gout patients and to analyze the impact of Allopurinol medication adherence on this risk. METHODS: This nationwide cohort study utilized the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database (2002-2019). We identified 4,107 patients newly diagnosed with gout who remained on continuous allopurinol therapy during the 24-month medication assessment period and matched them 1:3 with 12,321 non-gout controls using propensity score matching. Allopurinol adherence was assessed via the Medication Possession Ratio (MPR) over a 24-month period and categorized into three groups: MPR < 0.3, 0.3 ≤ MPR < 0.8, and MPR ≥ 0.8. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for fractures (vertebral, hip, and distal radius). RESULTS: Gout patients demonstrated a significantly higher risk of overall fractures compared to the non-gout group (aHR 5.52; 95% CI 4.19-7.26). A significant inverse linear relationship was observed between allopurinol adherence and fracture risk (P for trend < .001). The risk was highest in the low-adherence group (MPR < 0.3; aHR 5.91; 95% CI 4.40-7.93) and relatively lower in the high-adherence group (MPR ≥ 0.8; aHR 4.77; 95% CI 2.94-7.72). Consistent trends were observed for vertebral (aHR 5.68) and hip (aHR 4.22) fractures. These associations remained consistent across all subgroups, including age, sex, and comorbidities. CONCLUSION: Newly diagnosed gout is associated with a substantially increased risk of fractures. Higher adherence to Allopurinol therapy is correlated with a significant reduction in this risk, suggesting that consistent urate-lowering therapy may mitigate gout-related bone fragility. Key Points • Newly diagnosed gout patients have a significantly higher risk of major osteoporotic fractures compared to the non-gout population. • A significant inverse linear relationship exists between Allopurinol adherence and fracture risk, with the highest adherence group (MPR ≥ 0.8) showing a relatively lower risk. • Consistent urate-lowering therapy (ULT) may mitigate bone fragility in gout patients by reducing systemic inflammatory burden caused by urate crystal deposition.

Humans↗

PubMed2026

Suicidality risk of cancer caregivers: a systematic review and meta-analysis of observational studies.

BACKGROUND: The increase in the number of global cancer cases is expected to lead to a greater caregiving burden. However, few studies have investigated the risk of suicidality among cancer caregivers. OBJECTIVE: The aim of this systematic review was to explore the risk of suicidality among cancer caregivers. METHODS: For this systematic review, a comprehensive search of the PubMed, Embase, Cochrane, Web of Science databases, PsycINFO and Scopus databases was conducted from inception to 16 July 2025. A meta-analysis was performed to determine the odds ratios (ORs) for case-control and cross-sectional studies and the adjusted hazard ratios (aHRs) for cohort studies. RESULTS: Seven studies were included (four cohort studies, one case-control study and two cross-sectional studies), and 638,188 study subjects and 4,203,957 nonexposed subjects. The meta-analyses revealed that the ORs was 1.91 (95% confidence interval [CI]: 1.46-2.49) in the case-control study, cross-sectional studies, and one cohort study which reported ORs, and the aHRs was 1.32 (95% CI: 1.16-1.50) in the three cohort studies. Caregivers of patients with highly aggressive cancers had a greater risk of suicidality (aHR = 1.66; 95% CI: 1.48-1.86). Within the first 7 years following a patient's cancer diagnosis, the risk of suicidality among caregivers remained elevated (aHR = 1.42; 95% CI: 1.04-1.94). CONCLUSION: The results indicate the need for both clinical and societal awareness to reduce the risk of suicidality among cancer caregivers, especially those with highly aggressive cancers. TRIAL REGISTRATION: Registered prospectively in PROSPERO (https://www.crd.york.ac.uk/prospero/) with the registration number (PROSPERO CRD420251011926) and date of registration(15/03/2025).

Humans↗

PubMed2026

Microplastic contamination in South Asian commercially important seafood: A comprehensive assessment of occurrence, source, and human health risk.

Seafood is a cornerstone of global food security and human nutrition, serving as the primary source of animal protein for more than one-fourth of the global population, with South Asia representing one of the world's fastest-growing seafood-consuming regions. However, escalating microplastic (MP) pollution in marine ecosystems poses an emerging threat to seafood safety and human health, yet a comprehensive regional assessment of MP contamination in South Asian seafood remains lacking. This study presents the first region-wide systematic synthesis of the literature on MP contamination in commercially important seafood across South Asia, integrating occurrence patterns, human exposure assessment, polymer-specific hazard evaluation, and bibliometric analysis to address this critical knowledge gap. The meta-analysis estimated an average microplastic exposure of 145 particles/person/day through seafood consumption in South Asia, with fish contributing the highest intake (121 particles/person/day). The detected polymers were classified into PHI hazard levels I-IV, with polyvinyl chloride (PVC), polyurethane (PU), and polyacrylamide (PAM) representing the highest hazard categories. The mean pollution load index (PLI) was 7.71 (Category I), with crustaceans exhibiting the highest contamination (PLI = 10.07). Polypropylene was the predominant polymer, whereas fragments and blue particles were the most frequently reported microplastic characteristics. These findings provide the first regional baseline for assessing microplastic contamination, polymer-associated hazards, and human exposure through seafood consumption in South Asia, underscoring the need for standardized monitoring and targeted mitigation strategies to safeguard seafood safety and public health.

Animals↗

PubMed2026

The Impact of Hemoglobin Concentration on Prognosis in Patients With Diabetic Foot: A Systematic Review and Meta-Analysis of Risk Factors for Adverse Outcomes and Clinical Management.

BackgroundDiabetic foot (DF) complications, including diabetic foot ulcers (DFUs), lead to significant morbidity, disability, and economic burden. Hemoglobin (Hb) levels may influence the prognosis of DF patients, but their relationship with adverse clinical outcomes remains unclear. This systematic review and meta-analysis aimed to assess the association between hemoglobin concentration and the risk of adverse outcomes in diabetic foot patients, including amputation and mortality.MethodsWe followed PRISMA guidelines to conduct a systematic literature review. A meta-analysis was performed on observational studies assessing the impact of hemoglobin levels on amputation, mortality, and ulcer incidence. A random-effects model was applied, and risk bias was evaluated using the Newcastle-Ottawa Scale.ResultsA total of 22 observational studies involving 10,984 patients were included. Our meta-analysis revealed that lower hemoglobin levels were significantly associated with a higher risk of amputation (OR = 0.97, 95% CI: 0.94-0.99, P < .001), and lower hemoglobin concentrations were found in amputation cases compared to non-amputation cases (SMD = -0.14, 95% CI: -0.24 to -0.04, P < .01). However, no significant association was found between hemoglobin levels and mortality (OR = 0.99, 95% CI: 0.33-2.89, P > .05). Sensitivity and publication bias analyses indicated robust results.ConclusionLower hemoglobin levels were associated with higher odds of amputation in patients with diabetic foot. However, pooled effects were small and heterogeneity was substantial across studies; therefore, hemoglobin likely functions primarily as a marker of overall disease burden and perioperative risk rather than a proven modifiable target. Prospective interventional studies are needed to determine whether correcting anemia improves limb outcomes and survival.

Humans↗

PubMed2026

Enhanced risk stratification in hypertrophic cardiomyopathy through the integration of extracellular volume fraction on cardiovascular magnetic resonance.

AIMS: This study investigated the incremental prognostic value of cardiovascular magnetic resonance (CMR)-derived extracellular volume fraction (ECV), a marker of diffuse interstitial fibrosis, beyond late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We analysed 990 consecutive HCM patients (median age 58 years, male 68.3%) who underwent CMR between 2012 and 2024. LGE and global ECV were quantified, and their associations with the primary endpoint of HCM-related events-a composite of sudden cardiac death (SCD) events, heart failure (HF) events, and HCM-related death-were assessed. During a median follow-up of 3.2 years, 64 (6.5%) patients experienced the primary endpoint. While LGE (median 7.1%, IQR 2.3-16.9%) and ECV (median 29.0%, IQR 26.6-32.0%) were moderately correlated (R = 0.604, P < 0.001), both were significantly associated with increased risk of the primary endpoint and individual outcomes of SCD and HF events, and optimal cutoffs were determined as LGE ≥ 27% and ECV ≥ 35%. Patients with ECV ≥ 35% had more symptoms, a more severe phenotype with greater systolic and diastolic dysfunction, and more pathogenic gene variants. Notably, ECV remained a significant predictor of the primary endpoint (adjusted HR 1.08, 95% CI 1.02-1.15, per 1%) after adjustment for key disease variables, including left ventricular ejection fraction and LGE. Elevated ECV effectively identified high-risk individuals even among lower-risk subgroups, including those with low LGE burden. CONCLUSION: Increased ECV is an independent predictor of HCM-related outcomes. ECV may serve as a novel imaging biomarker to refine risk stratification in HCM patients who do not meet traditional LGE-based high-risk criteria.

Humans↗

PubMed2026

Beyond risk factors: A capacity framework for cancer survivorship research.

Cancer survivorship research has identified numerous biological, behavioral, psychosocial, health care, and structural factors that influence recovery. However, these factors are typically studied as separate determinants rather than interacting influences. This commentary proposes available survivorship capacity as a unifying framework that explains how these diverse determinants collectively shape recovery and survivorship outcomes. Concepts from geroscience, health care delivery, rehabilitation, occupational therapy, and human factors science were synthesized to develop a conceptual framework of available survivorship capacity. The framework conceptualizes recovery as a function of the capacity remaining after competing health care and life demands draw upon survivors' finite physical, cognitive, emotional, social, financial, temporal, and health care resources. It generates testable propositions for measurement, intervention research, health care delivery, and implementation science while positioning available survivorship capacity as a common mechanism linking diverse determinants of recovery and identifying actionable targets for intervention. Available capacity offers a unifying conceptual framework for understanding heterogeneity in survivorship outcomes and intervention effectiveness while generating a research agenda for future survivorship science. Measuring and strengthening survivors' available capacity, while reducing unnecessary demands, may improve engagement in care, health behaviors, and long-term recovery.

Humans↗

PubMed2025

Predictive Validity of Violence Screening Tools in Emergency and Psychiatric Services: A Systematic Review.

Violence against healthcare staff, including a threat or an act of violence toward people during their work, poses a physical and psychological risk to workers internationally. Screening is an important strategy in preventing violence against healthcare professionals. The aim of this systematic review was to synthesize evidence on the predictive validity of risk assessment tools used to screen for violence and aggression risk toward healthcare workers in emergency and psychiatric departments (PD). Primary studies that examined the predictive validity of risk assessment tools for workplace violence were identified via a systematic search of Medline, PsycINFO, Embase, and the Cochrane databases. There were 62 eligible studies, ten of which had a lower risk of bias (RoB). Those studies with high RoB were primarily due to a failure to present calibration measures as part of the analysis. All included studies adopted a longitudinal design and were conducted in PDs. The ten highest-quality studies reported on eight different instruments, four of which showed acceptable to outstanding predictive performance. The Dynamic Appraisal of Situational Aggression and the Brøset Violence Checklist showed the best predictive performance; they were also validated in emergency departments and are best suited for short-term risk prediction. We recommend that the selection of a risk assessment tool should consider the following: (a) the target population, (b) the violence operationalization, and (c) the purpose of the monitoring. We note that the use of a screening tool should be a part of a multicomponent strategy to ensure staff safety.

Humans↗

PubMed2026

Alcohol use disorder and childhood adversity in the association between polygenic risk and suicidality.

OBJECTIVE: Suicidal ideation (SI) and suicide attempt (SA) are both influenced by genetic, behavioral, and environmental factors. Alcohol use disorder (AUD) and adverse childhood experiences (ACEs) may mediate or moderate the effects of genetic liability for suicidality. METHODS: Using data from 10,275 participants (43.8% female; 47.2% African-like genetic ancestry [AFR], 52.8% European-like genetic ancestry [EUR]), we tested whether polygenic scores (PGS) for SI and SA predicted lifetime suicidality outcomes. We evaluated whether AUD partially accounted for these associations and ACEs moderated the direct and indirect associations. RESULTS: The SA PGS was significantly associated with SA (AFR: b = 0.36, SE = 0.01; EUR: b = 0.17, SE = 0.01; both ps < 2e-16), but the SI PGS was not associated with SI (p > 0.55). AUD statistically mediated the association between the SA PGS and SA, accounting for approximately 2% of the total association in AFR individuals and 10% in EUR individuals (both ps < 2e-16). Notably, the proportion of the association that was accounted for by AUD decreased as ACEs exposure increased, from 4.30% to 0.54% in AFR individuals and from 13.31% to 3.44% in EUR individuals. In contrast, there was only very modest mediation and no moderated mediation for SI. CONCLUSIONS: Particularly among individuals with lower ACEs exposure, AUD accounted for a meaningful proportion of the association between genetic liability to SA and lifetime SA. These findings highlight different correlates across suicidality phenotypes and suggest potential clinical relevance for AUD in the association between genetic liability and SA.

Adult↗

PubMed2026

Emerging hantavirus risks in mass gatherings: epidemiology, diagnostic challenges, and outbreak preparedness.

Hantaviruses are emerging rodent borne zoonotic pathogens of increasing global public health concern because of their high mortality, expanding ecological distribution, and potential for international dissemination. Although traditionally associated with sporadic rural outbreaks, recent ecological disruption, climate variability, urbanization, and increased global mobility have heightened concerns regarding hantavirus risks in mass gathering settings. This review critically examines the epidemiology, transmission uncertainty, diagnostic and surveillance challenges, and preparedness strategies related to hantavirus infections in the context of mass gatherings, including religious events, refugee settlements, cruise tourism, sporting events, and temporary accommodations. Particular emphasis is placed on the 2026 multinational cruise ship associated outbreak linked to the MV Hondius, which highlighted vulnerabilities related to delayed diagnosis, international passenger dispersal, and uncertainties surrounding possible human to human transmission of Andes virus. Current evidence indicates that hantavirus transmission occurs primarily through inhalation of aerosolized rodent excreta; however, controversies regarding limited interpersonal transmission, environmental persistence, and asymptomatic infections continue to complicate risk assessment and outbreak preparedness. Diagnostic limitations, underreporting, insufficient environmental surveillance, and lack of mass gathering specific preparedness frameworks remain major public health challenges, especially in resource limited settings. Strengthening proactive preparedness through integrated One Health approaches, ecological surveillance, genomic monitoring, AI driven epidemic intelligence, and coordinated international response systems is essential for mitigating future risks. The review emphasizes the urgent need for multidisciplinary research and evidence based policy development to improve global preparedness against emerging hantavirus associated threats in increasingly interconnected mass gathering environments.

Humans↗

PubMed2026

Machine learning-based prediction of unplanned readmission and construction of an online calculator for elderly patients with mild ischemic stroke.

OBJECTIVE: To screen for independent risk factors for unplanned readmission in elderly patients with mild ischemic stroke, and to construct and validate an online risk prediction calculator based on an interpretable machine learning model, thereby providing a promising practical tool for accurate clinical assessment of 30‑day all‑cause unplanned readmission risk in this population. METHODS: A prospective cohort study was conducted, including 1050 patients aged ≥ 60 years with mild ischemic stroke admitted between August 2023 and September 2024. Participants were randomly divided into a training set (840 cases) and a test set (210 cases) at a ratio of 8:2. Risk factors were screened by univariate analysis and multivariable Logistic regression. Four machine learning models, namely LightGBM, XGBoost, Random Forest, and K‑Nearest Neighbors (KNN), were developed and their performance was evaluated using AUC, accuracy, sensitivity, and specificity as metrics. The SHAP framework was used for interpretability analysis, and an online calculator was subsequently developed based on the optimal model. RESULTS: Univariate analysis showed significant differences (P < 0.05) in 13 factors including age, smoking, AIP, TyG index, HALP score, etc. Multivariable Logistic regression identified age (OR = 9.752), smoking (OR = 5.171), AIP (OR = 6.691), TyG index (OR = 4.393), HALP score (OR = 2.831), and ≥ 2 comorbidities (OR = 3.664) as independent risk factors. All four machine learning models demonstrated good predictive performance. Based on a comprehensive evaluation of multiple metrics and computational efficiency, the LightGBM model exhibited the best predictive performance (AUC = 0.884, accuracy = 0.829, sensitivity = 0.812, specificity = 0.875). SHAP analysis showed that age, AIP, TyG index, smoking, and HALP score were key predictors. An online calculator developed based on this model enables individualized risk predictions. CONCLUSION: Key risk factors associated with 30‑day unplanned readmission in elderly patients with mild ischemic stroke were identified. The LightGBM model demonstrated high predictive accuracy, and together with the interpretability analysis and online calculator, offers a practical tool to support clinical risk assessment. However, this tool requires future external validation.

Humans↗

PubMed2026

Risk Factors for Long-Term Health-Related Quality-of-Life and Mental Health Outcomes in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Traumatic brain injury (TBI) often leads to long-term disability, including persistent mental health issues and lower health-related quality of life (HRQoL). Early interventions can improve recovery, but because resources limit routine monitoring of all patients, trauma care remains largely symptom-driven. The combination of long-term disability and limited capacity for routine follow-up highlights the need for risk-stratified follow-up care and reliable evidence on early prognostic factors. However, the existing literature is sparse and methodologically heterogeneous, limiting the clinical applicability of findings. We therefore conducted a systematic review and meta-analysis to identify early risk factors for poorer long-term mental health and HRQoL outcomes. A systematic search of seven electronic databases identified studies of adult patients with TBI, with outcomes assessed at least 6 months postdischarge. Two authors independently screened the studies, assessed the risk of bias, and extracted the data. We pooled effect estimates using a random-effects meta-analysis and calculated 95% prediction intervals. A narrative synthesis was applied when meta-analysis was not feasible. The review was registered with PROSPERO (CRD42024576912) and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of the 8,104 articles screened, 64 studies met the inclusion criteria (n = 334,672). Most studies (58%) had a low risk of bias. Female sex, socioeconomic disadvantage, psychiatric history, assaultive-related injuries, and previous TBI were consistently associated with worse long-term outcomes. Across meta-analyses, assault-related injuries more than doubled the odds of post-traumatic stress disorder (odds ratio [OR] = 2.72; 95% confidence interval [CI]: 2.01-3.66, I2 = 0%). Higher odds were also observed among females (OR = 1.33; 95% CI: 1.11-1.59, I2 = 0%), individuals with prior TBI (OR = 1.56; 95% CI: 1.07-2.27, I2 = 0%), and those with psychiatric history (OR = 2.38; 95% CI: 1.83-3.10, I2 = 48%). We found that female sex (OR = 1.72; 95% CI: 1.38-2.16, I2 = 58%), prior TBI (OR = 1.52; 95% CI: 1.25-1.85, I2 = 0%), and psychiatric history (OR = 3.25; 95%CI: 1.86-5.69, I2 = 98%) were associated with higher odds of depression. Furthermore, higher pooled anxiety scores were observed in females and in individuals with a psychiatric history. The study identified several readily available factors present before or at discharge that are associated with poor long-term HRQoL and mental health outcomes. Leveraging these factors in follow-up protocols, prediction modeling, and clinical decision support systems may facilitate risk-stratified postdischarge care for TBI patients.

Humans↗

PubMed2026

Acute and chronic effects of mixed nuts on energy metabolism in women at cardiometabolic risk: a randomized clinical trial.

BACKGROUND AND AIMS: The effect of consuming a mix of Brazilian nuts on energy metabolism has not been explored. Thus, the present study aimed to evaluate the effects of acute and chronic consumption of mixed nuts on markers of energy metabolism in women with overweight/obesity. METHODS AND RESULTS: This is a randomized, controlled, and parallel clinical trial with adult women. In an acute study, participants received a beverage containing mixed nuts (30 g of cashew nuts + 15 g of Brazil nuts) or a control beverage, and energy metabolism markers were assessed for up to 3 h postprandially. For the chronic study, participants received 45 g of a mix of nuts/day and a -500kcal energy-restricted diet (MNG) or only a -500kcal energy-restricted diet free of nuts (CTG) for 8 weeks, and energy metabolism was assessed before and after the intervention period. In the postprandial period, fat oxidation was higher in the MNG than in the CTG (piAUC: 47.53 ± 5.78 mg/min vs. 27.93 ± 6.98 mg/min; p = 0.048). After 8 weeks of the intervention, fasting fat oxidation increased in the MNG (+16.0 ± 7.0 mg/min) and decreased in the CTG (-5.0 ± 6.0 mg/min), with no significant difference between groups. Other acute and chronic markers also showed no significant changes between groups. CONCLUSION: The acute consumption of mixed nuts increased postprandial fat oxidation, whereas chronic intake within an energy-restricted diet did not affect energy metabolism markers in women at cardiometabolic risk. REGISTRATION NUMBER FOR BRAZILIAN REGISTRY OF CLINICAL TRIALS: RBR-3ntxrm.

Humans↗