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PubMed2025

Efficacy of Janus kinase inhibitor combined with phototherapy in non-segmental vitiligo: systematic review and meta-analysis.

BACKGROUND: Vitiligo is a chronic autoimmune disease causing skin depigmentation and psychosocial issues. Non-segmental vitiligo often shows limited response to standard therapies. The IFN-γ-JAK-STAT pathway plays a key role, and combining JAK inhibitors with NB-UVB may improve repigmentation. AIM: To evaluate the efficacy of JAK inhibitors (baricitinib or tofacitinib) plus NB-UVB versus NB-UVB without JAK inhibitors in adult NSV. METHODS: PubMed, Cochrane, and ClinicalTrials.gov were searched till August 2024 for randomized controlled trials. Four studies, comprising 217 adults (121 in the combination group and 96 in the control group), were analyzed using RevMan 5.4. Bias was assessed via Newcastle-Ottawa, Cochrane ROB-2, and ROBINS-I tools. RESULTS: Combination therapy significantly reduced total VASI compared to controls (MD = -4.96, 95% CI [-9.29, -0.63], p = 0.02), with a greater effect on sensitivity analysis (MD = -6.84, p = 0.0007). Significant reductions were seen in face/neck (MD = -0.17, p = 0.002), trunk (MD = -3.62, p = 0.0001); acral (MD = -0.85, p = 0.0002) and extremity (MD = -4.61, p < 0.00001) regions after sensitivity analysis. Patients were more likely to achieve ≥50% (RR = 6.87, p < 0.00001) and ≥75% (RR = 15.13, p = 0.006) repigmentation. CONCLUSIONS: JAK inhibitor plus NB-UVB markedly improves the repigmentation in adult NSV compared to NB-UVB alone.

Humans↗

PubMed2026

Dynamic lysine acetylation and succinylation of platelet proteins regulates platelet storage lesion: mechanistic insights from multi-omics.

OBJECTIVES: Platelet storage lesion (PSL) severely impairs platelet function during storage, presenting a major hurdle in transfusion medicine; however, the dynamic interplay between global proteomic changes and post-translational modifications (PTMs) underlying these functional deteriorations remains insufficiently characterized. Here, we report the first comprehensive multi-omics analysis integrating global proteomics, acetylomics, and succinylomics to dissect the molecular dynamics during platelet storage. METHODS: We performed quantification of global proteomics, acetylome and succinylome based on TMT-labeled LC-MS/MS analysis, combined with antibody-affinity enrichment and purification. Dynamic molecular changes and functional transformation of platelet were also characterized under proper conditions stored for 1, 3, 5, 7 days, respectively. RESULTS: We systematically characterized 3,609 proteins, 1,308 acetylation sites, and 1,947 succinylation sites across multiple storage time points (D1, D3, D5, D7). We distinct temporal patterns of post-translational modifications, with succinylation showing more extensive coverage than acetylation in platelets. Pathway enrichment analysis revealed extensive metabolic reprogramming involving complement activation, energy metabolism, and cellular detoxification processes. The identification of specific motif patterns provided mechanistic insights into the functional specificity of these modifications. Random forest machine learning identified 20 core regulatory proteins representing critical nodes in PSL development. Furthermore, we employed real - time quantitative polymerase chain reaction (RT - QPCR) to measure the expression levels of key genes related to platelet function and PTM - associated pathways. CONCLUSION: By mapping the interplay between proteomic abundance shifts and PTM dynamics, this study provides a multidimensional understanding of PSL, establishing a foundational framework for optimizing storage protocols and enhancing transfusion safety.

Blood Platelets↗

PubMed2026

Medication safety in older adults in India: an integrative PhD synthesis of direct evidence and contextual implementation evidence.

BACKGROUND: Unsafe medication practices among older adults are an important global health concern, particularly in low- and middle-income countries where multimorbidity, fragmented care, self-medication, and informal healthcare provision intersect. OBJECTIVE(S): To synthesize direct evidence on medication safety among older adults in India and contextual evidence on deprescribing and community-level provider interventions relevant to safer medication use. METHODS: This PhD synthesis integrates four studies: a record-based cross-sectional study on polypharmacy and cardiovascular autonomic function in Kolkata; a six-city community study of 600 Indian older adults; a systematic review and meta-analysis on deprescribing preventive medications in frail or end-of-life older adults; and a systematic review of informal healthcare provider interventions in low- and middle-income countries. Studies I-II provided direct Indian older-adult evidence, while Studies III-IV provided indirect contextual evidence for their optimization and implementation. RESULTS: Polypharmacy was associated with higher anticholinergic burden and numerically higher cardiac autonomic neuropathy although residual confounding limits causal interpretation. In the multicity study, one-third had polypharmacy, while potentially inappropriate medications, prescribing omissions, and self-medication were common. Risks were higher with multimorbidity, recent hospitalization, care transitions, or living alone. Deprescribing showed no statistically significant increase in mortality, hospitalization, or major cardiovascular events, but heterogeneity was high and certainty low to very low. Informal-provider interventions showed the potential to improve knowledge, referral, case management, and medication-related practices. CONCLUSIONS: Medication safety among older adults in India requires an integrated continuum approach, but direct evidence supports only some components and implementation strategies that need prospective evaluation.

Humans↗

PubMed2026

Vaccine preferences and their role for vaccine confidence and uptake: a meta-ethnography.

Vaccine confidence and uptake are influenced by individuals' preferences regarding vaccine composition, quality, or administration pathways. However, literature synthesizing available qualitative insights into individuals' vaccine preferences remains limited. We therefore conducted a meta-ethnographic systematic review of the qualitative literature on vaccine preferences to identify opportunities for enhancing vaccine confidence and uptake. We implemented a comprehensive search strategy and screened 5,528 studies across seven research databases published between 2001 and 2023. We identified and synthesized 97 qualitative articles to delineate factors influencing consumers' vaccine preferences. Our findings revealed four primary domains shaping individuals' vaccine preferences: Product, Place, Price, and Promotion. First, individuals' preferences for vaccines often hinge on perceived quality and safety of the product itself, which can, for example, be associated with vaccine brand or origin, especially in the case of novel vaccines. Second, people prioritize convenience in terms of vaccination sites and delivery methods (wanting vaccinations offered at their doorstep or in local peripheral clinics); evidence regarding preferred groups to administer the vaccines was mixed. Third, the price of vaccines and the secondary costs associated with vaccination played a role in uptake considerations. Finally, both the sources of information (such as healthcare workers, community volunteers, and religious authorities) and the methods of promoting vaccine information (including face-to-face consultations during clinic visits and the distribution of leaflets or banners), emerged as crucial factors shaping decision-making processes. Overall findings highlight the importance of addressing multifaceted preferences to enhance vaccine confidence and uptake. By understanding individuals' vaccine preferences, strategic recommendations can be developed to optimize vaccination programs and ensure acceptability and utilization.

Humans↗

PubMed2026

Ceftriaxone for methicillin-susceptible Staphylococcus aureus bloodstream infections is associated with increased short-term mortality: a systematic review and meta-analysis.

BACKGROUND: Bloodstream infections (BSIs) by methicillin-susceptible Staphylococcus aureus (MSSA) are a significant cause of morbidity and mortality, traditionally treated with antistaphylococcal penicillins (ASPs) or cefazolin. Ceftriaxone has emerged as an alternative due to its once-daily dosing regimen and favourable safety profile; however, its efficacy compared to the standard of care (SoC) remains controversial. This evidence synthesis aimed to assess the role of ceftriaxone in treating MSSA-BSIs. METHODS: A systematic literature search was conducted in PubMed, Embase, and Scopus up to December 31, 2025 (PROSPERO protocol CRD42024595748). Studies comparing ceftriaxone to ASPs or cefazolin for MSSA-BSIs were included. Primary outcomes were 30-day and 90-day all-cause mortality . Pooled effect sizes with their 95% confidence intervals (CIs), were calculated using random-effects models, odds ratios (ORs) and mean differences (MDs) according to the type of outcome. RESULTS: Eleven studies totalling 2,568 patients were included. Ceftriaxone was associated with significantly increased 30-day mortality (OR 3.33; 95% CI: 2.17-5.10), although differences at 90 days were not significant (OR 1.71; 95% CI: 0.75-3.90). No significant differences were noted for clinical success (OR 0.49; 95% CI: 0.19-1.26), microbiological clearance (OR 1.66; 95% CI: 0.73-3.82). Adverse event rates were similar between groups. CONCLUSION: Given the availability of various alternatives and the consistent short-term mortality signal observed, routine use of ceftriaxone for MSSA-BSIs, especially as initial therapy, is not supported by current evidence. Only novel findings from randomized studies may change the place in therapy of the drug in this context.

Humans↗

PubMed2026

Lifestyle interventions to prevent gestational and type 2 diabetes among migrant women from low- and middle-income countries: a systematic review.

Migrant women from low- and middle-income countries (LMICs) living in high-income settings experience disproportionately high risk of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM). This review aimed to identify and synthesise culturally adapted lifestyle interventions for preventing or managing GDM and T2DM among migrant women from LMICs, focusing on intervention components, cultural adaptation strategies, and behavioural and metabolic outcomes. Five databases (PubMed, Embase, Scopus, CINAHL, Cochrane Central) were searched using Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 guidelines. Eligible studies included experimental designs involving lifestyle interventions delivered to migrant women from LMICs in high-income countries, reporting outcomes related to GDM or T2DM targeting behaviour change. Data were synthesised narratively; study quality was appraised using RoB2 for RCTs and a structured narrative approach for non-randomised designs. Certainty of evidence was evaluated using GRADE. Eight studies met the inclusion criteria. Sample sizes ranged from 28 to 641 participants. Intervention duration varied from 6 weeks to 12 months. Most interventions incorporated atleast one culturally tailored component, such as bilingual delivery, culturally adapted dietary education, or community-based engagement. Improvements were reported across dietary behaviours, physical activity, glycaemic measures, or diabetes-related knowledge; however, effect sizes were modest and inconsistent. Interventions combining dietary modification, physical activity, and culturally adapted delivery demonstrated greater improvements than exercise-only or digital-only programmes. Overall certainty of evidence ranged from low to moderate. Culturally adapted, multi-component lifestyle interventions show promise for improving behavioural and metabolic outcomes among migrant women from LMICs; however, the evidence base remains limited.

Humans↗

PubMed2026

Diagnostic performance of machine learning models for malignant and non-malignant pleural effusion: Systematic review and meta-analysis.

BACKGROUND: Accurately distinguishing malignant pleural effusion (MPE) from non-malignant pleural effusion is clinically important, but the generalisability and methodological quality of machine-learning (ML) models remain uncertain. METHODS: We searched eight databases to 23 April 2026. Diagnostic performance was pooled using random-effects and Reitsma bivariate models, and study quality was assessed using PROBAST+AI. RESULTS: Forty-two studies were included; 17 contributed to the AUC meta-analysis and 14 to the bivariate analysis. The pooled AUC was 0.90 (95 % CI 0.85-0.94; 95 % prediction interval 0.62-0.98), with sensitivity of 0.80 (95 % CI 0.77-0.83) and specificity of 0.87 (95 % CI 0.79-0.92). Only nine studies reported external, temporal or independent validation. Externally validated studies had a lower pooled AUC than studies without external validation (0.83 vs 0.92), with lower specificity observed in the two externally validated studies contributing sensitivity and specificity data. All 42 development assessments had high overall quality concerns, and all 42 model evaluations were judged at high risk of bias. CONCLUSIONS: ML models showed good apparent accuracy for distinguishing MPE from non-MPE, but the evidence was limited by substantial heterogeneity, high risk of bias and scarce external validation. The pooled estimates reflect the average performance of different selected models rather than the expected accuracy of a single clinical test. ML models should be regarded as adjuncts to existing diagnostic pathways until they are confirmed by rigorous multicentre prospective external validation and clinical-impact studies.

Humans↗

PubMed2026

Relationship between menopausal hormone therapy and incidence risk of breast cancer: systematic review and meta-analysis.

BACKGROUND: Menopausal hormone therapy (MHT) is widely prescribed for alleviating menopausal symptoms. Prior studies have mainly focused on individual hormone therapy formulations. This meta-analysis comprehensively synthesized evidence across various regimens to systematically evaluate the association between MHT and breast cancer risk. MATERIALS AND METHODS: We systematically searched CNKI, Wanfang, PubMed, and Web of Science from inception through August 2024. Eligible studies examining breast cancer risk following MHT were independently screened and assessed by two reviewers. The review and meta-analysis followed PRISMA guidelines. RESULTS: Thirty-four studies were included. The random-effects model showed a significant but heterogeneous overall association (OR = 1.15, 95% CI: 1.09-1.22; I² = 92.4%). Subgroup analysis identified hormone type, use status, and region as key determinants (P for interaction < 0.001). Stratification by hormone type resolved much of the heterogeneity, revealing risk confined to estrogen-progestin therapy (EPT; OR = 1.44, 95% CI: 1.26-1.64), while estrogen-only therapy (ET) showed no overall association (OR = 1.00, 95% CI: 0.91-1.10). Study type, region, and sample size were significant effect modifiers. For ET, randomized controlled trials demonstrated a protective effect (OR = 0.78, 95% CI: 0.70-0.87), contrasting with neutral findings from observational studies. CONCLUSIONS: MHT is associated with a modest but significant increase in breast cancer risk, primarily driven by EPT. This risk was not observed with ET in observational studies, though trials suggested a protective effect. Crucially, the association shows marked geographical heterogeneity, indicating risk is modified by regimen and regional factors.

Humans↗

PubMed2026

Plasma proteome profiling identifies XPNPEP3 as a novel biomarker associated with metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To identify plasma protein differences between type 2 diabetes mellitus (T2DM) patients with and without metabolic dysfunction-associated steatotic liver disease (MASLD), and to evaluate the diagnostic potential of X-prolyl aminopeptidase 3 (XPNPEP3) for identifying MASLD in T2DM patients. METHODS: Twenty T2DM inpatients were categorized into groups with and without MASLD and their plasma samples were analyzed using data-independent acquisition mass spectrometry, followed by bioinformatics analysis to identify differentially expressed proteins. The cohort was then expanded to 84 patients, and plasma XPNPEP3 levels were validated by enzyme-linked immunosorbent assay. Correlation between XPNPEP3 and clinical indicators were evaluated, and diagnostic performance was determined via receiver operating characteristic (ROC) analysis. Immunohistochemistry was employed to compare hepatic XPNPEP3 expression between the two groups. RESULTS: Proteomic analysis identified 176 differentially expressed proteins, with XPNPEP3 exhibiting the most significant down-regulation by fold change. In the validation cohort, plasma XPNPEP3 was significantly lower in T2DM+MASLD versus T2DM alone. XPNPEP3 levels were negatively correlated with diabetes duration, liver function markers, and triglyceride levels, and was identified as an independent factor inversely associated with MASLD in T2DM.ROC analysis demonstrated strong diagnostic performance for XPNPEP3, further enhanced when combined with BMI and diabetes duration.  Immunohistochemistry confirmed reduced hepatic XPNPEP3 expression in T2DM+MASLD patients. CONCLUSIONS: Lower plasma XPNPEP3 is independently associated with MASLD in T2DM patients and demonstrates strong diagnostic potential, positioning XPNPEP3 as a promising biomarker for diagnosing MASLD in T2DM patients and a novel target for non-invasive diagnostic tool development.

Humans↗

PubMed2026

A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.

INTRODUCTION: Cancer cell proliferation occurs within the context of persistent genomic instability. In this review, we propose the RS-CCD-CIN axis as a systems-level framework in which replication stress (RS), cell cycle deregulation (CCD) and chromosomal instability (CIN) form an interdependent triad that shapes tumour evolution. This axis represents a constrained metastable state in which genomic instability is tolerated and buffered. The objective of this review is to synthesize the current understanding of how the RS-CCD-CIN axis contributes to tumour heterogeneity, adaptability and therapy response. DISCUSSION: Evidence indicates that RS, CCD and CIN operate as a dynamic, interconnected network rather than as independent processes. Replication stress induces DNA damage and mutagenesis, while partial checkpoint disruption permits cells with unresolved lesions to proliferate. Chromosomal instability generates both structural and numerical alterations, contributing to intratumoural heterogeneity. Together, these processes facilitate adaptation to environmental and therapeutic pressures. Extrachromosomal DNA, micronuclei formation and cytosolic DNA signalling, including the cGAS-STING pathway, connect genomic instability to adaptive responses and immune modulation. Single-cell and spatial profiling reveal temporal and spatial variability in RS, CCD and CIN states, highlighting the limitations of static biomarkers. Therapeutically, targeting individual components often yields limited durability, whereas approaches that simultaneously perturb multiple aspects of the RS-CCD-CIN axis may improve clinical outcomes. CONCLUSIONS: This review highlights the RS-CCD-CIN axis as a fragile and metastable architecture that supports cancer evolution, while also being susceptible to collapse. A deeper understanding of this interconnected framework may inform the development of therapeutic strategies and enhance the management of resistance.

Humans↗

PubMed2026

Prognostic significance of NLRP-3 expression in solid cancers: a systematic review and meta-analysis.

BACKGROUND: The inflammasome is a critical immunological sensor comprised of NLRP-3, ASC, and CASPASE-1. Mutations in NLRP-3 are prevalent in inflammatory diseases. However, the role of NLRP-3 in cancer is controversial. This study investigates whether NLRP-3 expression is associated with clinical outcomes in patients with solid cancers. METHODS: PubMed (MEDLINE), Embase, Cochrane, and Google Scholar were searched for articles reporting NLRP-3 expression and disease outcome data in cancer patients. RevMan Review Manager was used to calculate pooled hazard ratios and Mantel-Haenszel pooled odds ratios. RNA sequencing datasets from the TCGA Pan-Cancer (PANCAN) were used for external validation. RESULTS: Patients with higher NLRP-3 expression showed a significant association with larger tumor size, advanced tumor grade, TNM stage, and presence of metastasis. High NLRP-3 expression has a significant association with poor OS (HR:2.12, 95% CI = 1.49-3.03), p < 0.0001) and DFS (HR:1.86, 95% CI = 1.30- 2.65, p = 0.0007). Subgroup analysis showed that higher NLRP-3 expression is associated with worse OS in head and neck cancer (HR: 2.77, 95% CI = 1.88-4.09, p < 0.00001), colorectal cancers (HR:2.14, 95% CI= 1.59- 2.87, p < 0.00001), and pancreatic cancer patients (HR: 3.19, 95% CI = 1.73-5.91, p = 0.0002). CONCLUSION: High NLRP-3 expression is associated with advanced disease and poor outcomes in many solid tumours.

Humans↗

PubMed2026

Risk prediction models for blood transfusion in patients undergoing total hip and knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and evaluate published risk prediction models for perioperative blood transfusion in patients undergoing total hip or knee arthroplasty (THA/TKA). METHODS: We systematically searched PubMed, Web of Science, the Cochrane Library, and Embase from inception to May 31, 2025. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability using the Prediction model Risk Of Bias Assessment Tool (PROBAST). The area under the receiver operating characteristic curve (AUC) values were pooled via a meta-analysis using Stata 18.0. RESULTS: d Fourteen studies containing 36 prediction models were included. The incidence of blood transfusion among THA/TKA patients ranged from 3.2% to 30.8%. Preoperative hemoglobin (Hb) level, tranexamic acid (TXA) use, operative duration, intraoperative blood loss, and age were the most frequently incorporated predictors. Model sensitivity ranged from 58% to 94.5%, and specificity ranged from 71.3% to 94%. Meta-analysis showed that the pooled AUC value of the 13 validated models was 0.87 (95% CI: 0.85-0.90), suggesting good discriminatory performance. All models were rated as having a high risk of bias. The applicability of four studies was rated as unclear. CONCLUSION: Although the included studies demonstrated promising discriminative ability of prediction models for blood transfusion in THA/TKA, all were assessed as having a high risk of bias using the PROBAST tool. Therefore, future research should prioritize the development of models with larger sample sizes, rigorous study designs, and multicenter external validation.

Humans↗

PubMed2026

Occupationally relevant vibrations and the brain: frequency-dependent proteomics signatures in a rat model.

INTRODUCTION: Occupational exposure to whole-body vibration (WBV), particularly in agricultural environments, has been associated with adverse cognitive and physiological effects. This study examined the neurophysiological impact of WBV in a rat model at 4 Hz and 30 Hz, frequencies representative of off-road and on-road vehicle operation. METHODOLOGY: Forty-four Sprague-Dawley rats were assigned to control (0 Hz), low-frequency (4 Hz), or high-frequency (30 Hz) vibration conditions. After three days of exposure, brain tissues were collected and analyzed using mass spectrometry-based proteomics to identify differentially expressed proteins. RESULTS: Proteomic profiling revealed distinct, frequency-dependent alterations in brain protein expression. Compared with controls, 32 cognition-related proteins were differentially regulated at 4 Hz and 29 at 30 Hz, with 13 differing between the two vibration conditions. Principal component analysis showed clear separation among groups, indicating unique proteomic signatures for each exposure frequency. Functional enrichment and protein-protein interaction analyses demonstrated involvement of synaptic plasticity, cytoskeletal organization, calcium regulation, and neurotransmitter release. Exposure to 4 Hz was associated with the upregulation of proteins involved in calcium homeostasis and synaptic integrity, suggesting potential disruption of cognitive processes. In contrast, 30 Hz increased the expression of proteins related to axonal guidance and neuroprotection, indicating a less clearly adverse response that may reflect adaptive or potentially beneficial effects. DISCUSSION: These findings provide new insight into biological mechanisms underlying WBV-induced cognitive changes and underscore the importance of vibration frequency in shaping neurophysiological outcomes. They also establish a foundation for future studies integrating proteomics with behavioural assessments in animals and humans.

Animals↗

PubMed2026

Nebivolol treatment improves hypertension-induced endothelial cell dysfunction by reducing TGF-β1-dependent senescence and normalizing mitochondrial indices.

OBJECTIVES: Serum from patients with hypertension (HT) causes endothelial cell (EC) damage, leading to senescence and dysfunctional phenotype. This study investigated whether serum from patients treated with the antihypertensive drugs could normalize EC activity. METHODS: This study involved 71 patients with newly diagnosed HT, who were randomly assigned to one of three groups based on the antihypertensive treatment: amlodipine, nebivolol, or perindopril. Serum samples collected before and 6 weeks after treatment were applied to ECs in vitro to assess their angiogenic activity, cellular senescence, mitochondrial metabolism, and oxidative stress. RESULTS: Results showed that exposure of ECs to serum from patients treated for 6 weeks significantly altered EC function, with varying effects among the drugs. Serum from nebivolol-treated patients produced the most consistent benefits, reducing EC proliferation and HIF-1α expression, likely due to lower levels of angiogenic factors such as angiopoietin-1, basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Additionally, this serum contained reduced levels of pro-inflammatory cytokines (E-selectin, P-selectin, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNFα)) and lower TGF-β1, which are linked to HT-related EC senescence. Nebivolol treatment decreased senescence biomarkers such as SA-β-Gal, 53BP1, and p16, with SA-β-Gal reduction comparable to that of TGF-β1 neutralizing antibodies. Oxidative stress was reduced, indicated by lower oxidized DNA product levels. CONCLUSIONS: Nebivolol was the most effective at reducing the factors, associated with HT induced cellular senescence of endothelium, through reducing TGF-β1.

Humans↗

PubMed2026

Psychological distress and incident cardiovascular disease independent of life's essential 8: a prospective cohort study.

BACKGROUND: Although psychological stress has emerged as an important determinant of cardiovascular disease (CVD) risk, it remains excluded from the recently updated cardiovascular health (CVH) metrics, known as Life's Essential 8 (LE8). This study aimed to examine the association between psychological distress and the incidence of CVD, independent of Life's Essential 8 metrics, in a large Korean adult population. METHODS: This study included 6,410 participants from the Korean Genome and Epidemiology Study Ansan-Ansung cohort, who had no history of CVD and had complete baseline data on psychological distress and Life's Essential 8 cardiovascular health (LE8 CVH) metrics. Psychological distress was assessed using the Psychosocial Wellbeing Index Short Form (PWI-SF). CVD events were identified based on participants' self-reports of physician-diagnosed conditions: myocardial infarction, stroke, coronary artery disease, and congestive heart failure. Cox proportional hazards models were used to examine the association between PWI-SF scores and incident CVD, adjusting for age, sex, residential area, educational attainment, household income, and LE8 CVH metrics. RESULTS: During a median follow-up of 13.8 years, 500 new cases of CVD were identified. Higher PWI-SF scores were independently associated with an increased risk of CVD after adjusting for LE8 CVH metrics and other potential confounders (hazard ratio: 1.321; 95% confidence interval: 1.067-1.636; p = 0.011). CONCLUSION: These findings suggest that higher levels of psychological distress are independently associated with an increased risk of CVD, even after accounting for established LE8 CVH metrics. Incorporating psychological distress into future CVH assessments may enhance risk stratification and prevention strategies.

Humans↗

PubMed2026

Association of ERBB4 and SHBG gene polymorphisms with polycystic ovarian syndrome in South Indian women: a case-control genetic analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinological disorder with a substantial genetic component. However, the role of genes involved in follicular development and androgen regulation remains incompletely understood, particularly in South Indian populations. This study aimed to evaluate how variations in the ERBB4 and SHBG genes affect PCOS risk. METHODOLOGY: A hospital-based case-control study was conducted among 400 South Indian women, comprising 200 women with PCOS and 200 age-matched healthy controls. Genomic DNA was extracted to study SNPs at ERBB4 (rs2178575 and rs1351592) and SHBG (rs1799941 and rs727428) using ARMS-PCR genotyping. The study compared genotype and allele frequencies between cases and controls while assessing their associations with allelic, homozygous, heterozygous, dominant, recessive, and over-dominant genetic models. Genotyping accuracy was confirmed by re-genotyping and Sanger sequencing of a subset of samples. RESULTS: The ERBB4 rs2178575 polymorphism demonstrated a significant association with PCOS, as the AA genotype and A allele combination increased risk across all three genetic models, including homozygous, recessive, and allelic models. The ERBB4 rs1351592 variant was associated with 3-fold higher risk of PCOS in heterozygous and GC carriers. The SHBG rs1799941 polymorphism showed a significant link to PCOS through its effects on heterozygous and allelic states, whereas rs727428 displayed no significant connection due to its monomorphic distribution. CONCLUSION: These findings suggest that polymorphisms in ERBB4 and SHBG may contribute to PCOS susceptibility in South Indian women in a locus- and model-specific manner, revealing the intricate genetic structure that defines this medical condition.

Humans↗

PubMed2026

Effect of transcutaneous auricular vagus nerve stimulation on postoperative pain in patients undergoing thoracoscopic partial lung resection: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Postoperative pain after thoracic surgery remains common and challenging. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique with potential analgesic effects. This study aimed to evaluate the efficacy and safety of taVNS for postoperative pain management in patients undergoing thoracoscopic partial lung resection. METHODS: Adults undergoing thoracoscopic partial lung resection were randomized to active or sham taVNS. The primary outcome was cough pain intensity at 48h post-surgery, assessed by Numeric Rating Scale (NRS). Secondary outcomes included cough pain at 24h and 72h, resting pain, moderate-to-severe pain incidence, opioid consumption, quality of recovery, postoperative pulmonary complications , chest tube duration, hospital stay, postoperative nausea/vomiting, and adverse events. RESULTS: Among 119 analyzed patients (active n = 60, sham n = 59), active taVNS reduced cough pain scores at 24h, 48h, and 72h postoperatively, as well as resting pain (p < 0.05). It also lowered the incidence of moderate-to-severe cough pain at 24h and 48h, reduced cumulative postoperative opioid use at 24h and 72h, and decreased rescue analgesia on postoperative day 3 (p < 0.05). Active taVNS was associated with a lower incidence of postoperative pneumothorax (p < 0.05). No serious adverse events occurred. CONCLUSION: Perioperative taVNS was associated with a modest analgesic benefit and reduced postoperative opioid requirements after thoracoscopic partial lung resection. The observed reduction in postoperative pneumothorax requires cautious interpretation, and further multicenter trials are needed to determine its clinical utility.

Humans↗

PubMed2025

Diagnostic and clinical utility of exome sequencing and chromosomal microarray in children with GDD/iD: a meta-analysis.

BACKGROUND: Global developmental delay/intellectual disability (GDD/ID) is among the most common neurodevelopmental disorders, with up to half of cases are attributed to genetic factors. Chromosome microarray (CMA) has traditionally been the primary genetic test for idiopathic GDD/ID. However, whole exome sequencing (WES) and whole genome sequencing (WGS) have recently emerged, substantially increasing diagnostic yields in these populations. METHODS: We conducted a comprehensive literature search of PubMed, Scopus, EMBASE, and the Cochrane Library from inception to April 29, 2025. Studies reporting the diagnostic utility of these tests in children with GDD/ID were included and analyzed. RESULTS: A total of 102 studies, comprising 55,752 children, were reviewed. The pooled diagnostic yield of WES was 0.37 (95% CI: 0.33-0.41; I2 = 93%), significantly higher than that of CMA at 0.19 (95% CI: 0.16-0.21; I2 = 95%). Subgroup analyses showed that WES yielded significantly higher diagnostic rates than CMA in both same-sample comparisons (OR = 2.27, 95% CI: 1.08-4.78) and different-sample comparisons (OR = 1.65, 95% CI: 1.15-2.37). Only one study evaluated WGS, reporting a diagnostic yield of 0.27. Meta-regression revealed a significant association between CMA diagnostic yield and the proportion of male participants (p < 0.01), but not with WES. No significant difference in diagnostic utility was observed between isolated GDD/ID and GDD/ID with comorbidities. CONCLUSION: In children with unexplained GDD/ID, WES demonstrates superior diagnostic and clinical utility compared to CMA. Incorporating WES as a first-line investigation in the diagnostic evaluation of GDD/ID may be warranted.

Humans↗