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PubMed2026

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n = 101) and a "Low Symptom Burden-Relieving (LSBR)" type (n = 88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P < 0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.  CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

Humans↗

PubMed2026

Searching for New Genes That Cause Usher Syndrome.

PURPOSE: The purpose of this project was to identify novel Usher syndrome (USH) candidate genes from phenotyping data of 9139 knockout (KO) mouse lines. METHODS: We evaluated phenotype data for concurrent retinopathy and hearing abnormalities in single-gene KO mice generated by the International Mouse Phenotyping Consortium (IMPC). A search was performed to determine whether each gene had been previously associated with retinopathy and/or deafness in humans. Bioinformatic tools were used to predict protein interactions, molecular functions, signaling pathways, and the expression of human orthologues of candidate genes in the retina and inner ear. RESULTS: We identified 18 single-gene KO lines exhibiting hearing abnormality and retinopathy after ear and eye examinations, respectively, and/or by histopathology. The molecular functions and signaling pathways of the human orthologues of the 18 candidate genes partially overlapped with those of USH genes. Particularly, FER and DYRK1B proteins were predicted to interact with proteins encoded by known ciliopathy genes. ADIPOR1, ATP8B1, and MPDZ were associated with retinal degeneration in humans. CHSY1 and IDUA may be pathogenic causes of hearing impairment in people. Furthermore, CHSY1, CSTB, and SPRED1 were located adjacent to unsolved genetic loci related to USH. CONCLUSIONS: A screen of 9139 KO mouse lines revealed 18 candidate genes exhibiting both retinal and inner ear abnormalities consistent with the principal clinical features associated with USH. As the observed phenotypes are attributed to gene deletion in mice, these genes warrant further study to determine the causation of retinal degeneration and hearing loss in patients.

Animals↗

PubMed2026

Comprehensive assessment of vasospastic angina using coronary computed tomography angiography: synergistic value of the presence of myocardial bridge, perivascular inflammation, and myocardial extracellular volume fraction.

AIMS: Coronary computed tomography angiography (CCTA) has evolved beyond anatomical assessment to include sophisticated tissue characterization. While an elevated perivascular fat attenuation index around the right coronary artery (FAI-RCA) is known to reflect coronary inflammation in vasospastic angina (VSA), recurrent vasospasms may also induce chronic subclinical myocardial injury and subsequent remodelling, potentially associated with an increased myocardial extracellular volume fraction (ECV). However, the diagnostic integration of ECV and FAI-RCA for identifying VSA in patients with angina with non-obstructive coronary arteries (ANOCA) remains to be elucidated. METHODS AND RESULTS: This study included consecutive ANOCA patients who underwent CCTA with a dedicated ECV protocol, followed by an invasive spasm provocation test. Comprehensive CCTA analysis quantified both FAI-RCA and the transmural ECV gradient (the difference between endocardial and epicardial ECV: ECVEndo - ECVEpi). Of the 100 patients analysed (mean age: 65.3 ± 11.8 years; 55% male), 27 were diagnosed with VSA. Multivariable logistic regression analysis identified transmural ECV gradient [odds ratio (OR): 1.12, 95% confidence interval (CI): 1.01-1.25], presence of myocardial bridging (MB) (OR: 3.49, 95% CI: 1.25-9.74), and high FAI-RCA (> -70.95 Hounsfield units [HU]) (OR: 5.79, 95% CI: 2.06-16.30) as significant independent predictors of VSA (all P < 0.05). Notably, the integration of transmural ECV gradient provided incremental diagnostic value beyond FAI-RCA and MB, as assessed by the Net Reclassification Improvement and Integrated Discrimination Improvement. CONCLUSION: A multi-parametric CCTA approach potentially identifies patients at high risk for VSA. The significant association of the transmural ECV gradient with VSA suggests that myocardial remodelling imaging provides a novel diagnostic window into the cumulative myocardial impact of vasospasm, independent of active adipose tissue inflammation and the presence of MB.

Humans↗

PubMed2026

Structural and tissue-specific organisation of endocrine Fgf19 and Fgf21 signalling in rainbow trout.

Endocrine fibroblast growth factors (FGF19 subfamily) play a key role in regulating metabolic homeostasis in vertebrates. However, their functional diversification in salmonids remains poorly understood. In this study, we conducted an integrative characterisation of Fgf19 and Fgf21 signalling in rainbow trout (Oncorhynchus mykiss) by combining phylogenetic, structural and expression analyses. Phylogenetic analyses revealed the conservation of single fgf19 and fgf21 genes, despite the extensive expansion of receptors post-Ss4R (salmonid-specific fourth-round whole genome duplication). Structural modelling and molecular dynamics simulations demonstrated the stable interactions of both ligands to multiple Fgfr isoforms, with receptor-specific energetic profiles and conserved core interaction residues. Tissue expression profiling revealed clear differences from mammalian models, such as predominant hepatic fgf19 expression and the absence of hepatic fgf21 under basal conditions. In addition, there were complex and tissue-dependent distributions of fgfr and klotho transcripts. These findings support a receptor-driven diversification model of endocrine Fgf signalling in salmonids, suggesting enhanced endocrine plasticity associated with the retention of receptors following post-genomic duplication. Taken together, our findings provide new insights into the structural and regulatory organisation of endocrine Fgf signalling, as well as its potential role in metabolic regulation in rainbow trout.

Animals↗

PubMed2026

Public health, public protest: The role of health burdens and healthcare access in protest mobilisation.

Health and politics are intertwined, yet few studies have examined the association between health and protest. This study examined whether population health burdens were associated with protest incidence and whether healthcare access modified these associations. Analysis was based on an unbalanced 2004-2023 country-year panel, combining protest counts from ACLED with rates for 22 GBD causes. Mixed-effects negative-binomial models estimated incidence-rate ratios (IRRs) with interactions for healthcare access (±1 SD). Two-way fixed-effects Poisson models were estimated as a benchmark to distinguish cross-national associations from within-country dynamics. Health burdens were systematically, but heterogeneously, associated with protest. Rates for several non-communicable burdens were associated with protest, notably musculoskeletal disorders (IRR 1.72, 95% CI 1.37-2.15), neoplasms (1.24, 1.06-1.44), substance-use disorders (1.32, 1.12-1.56) and HIV/AIDS and other STIs (1.24, 1.12-1.38). Higher healthcare access generally attenuated health-protest associations. Fixed-effects models confirmed several associations (e.g. HIV/AIDS, neoplasms) but revealed that others (e.g. maternal/neonatal disorders, enteric infections) were driven primarily by cross-national differences. Population health burdens were associated with cross-national variation in protest mobilisation. Chronic, non-communicable burdens were associated with heightened protest, whereas poverty-linked and early-life burdens were associated with lower mobilisation. Healthcare access was associated with attenuation of these relationships.

Humans↗

PubMed2026

Single-organ proteomics in Drosophila melanogaster larva.

The combination of genetic accessibility, organ complexity, evolutionary conservation, and cost-efficiency makes Drosophila melanogaster (Dm) a well-known model system for biomedical and fundamental biological research. Proteomic analysis of single organs enables the identification and quantification of proteins expressed in specific organs. This will help to uncover specific biological functions and unique protein profiles that are not detectable in whole-organism analyses. In this study we have isolated single organs form Dm larvae, and we have performed a deep proteomics mapping by following a minimal manipulation preparation procedure. The combined dataset across all organs comprised 9132 identified proteins. As anticipated, principal component analysis (PCA) revealed clear separation between the proteomes of most organs, confirming distinct protein profiles. These findings demonstrate the applicability of the sample preparation strategy for high-resolution proteomic characterization of individual organs in Drosophila. Given the extensive genetic tools available for this model organism, our approach has the potential to open new avenues for proteomic studies in Drosophila melanogaster and any other biological systems where the sample amount is limiting. SIGNIFICANCE STATEMENT: Drosophila melanogaster is a well-known model system for biomedical and fundamental biological research that serves as a valuable in vivo model organism due to its high degree of evolutionary conservation with higher vertebrates, tractable genetics, and logistical efficiency. However, the proteome of Drosophila at single organ level has been elusive to date, due to several factors like low sensitivity of previous generation mass spectrometers and sample preparation procedures, difficult isolation of some organs. In this study we have applied a compilation of advanced methods including minimal sample manipulation together with simple, straightforward and efficient protein extraction and digestion methods. Obtained peptides were minimally handled to be analyzed by applying specific and sensitive nLC methods coupled on-line to state-of-the-art MS/MS system. Altogether, the applied strategy allowed us to get the first single organ study to date for this animal. These datasets represent a significative resource for future genomic, transcriptomic and proteomic studies in Drosophila, as multi-omic integration requires deep proteomics to translate data into functional biochemistry, and serves as a critical bridge and an indispensable standalone resource across the genomic, transcriptomic, and proteomic landscapes.

Animals↗

PubMed2026

Artificial intelligence for dental caries detection: An umbrella review.

Artificial intelligence (AI) has been proposed as a tool to improve dental caries detection across imaging modalities; however, its clinical value remains uncertain. This umbrella review aimed to synthesize and critically appraise systematic reviews evaluating AI for caries detection and diagnosis. An umbrella review was conducted following PRIOR guidance (PROSPERO CRD420261340728). Searches were performed in MEDLINE, Embase, Scopus, Web of Science, and Google Scholar up to 15 March 2026. Methodological quality was assessed using AMSTAR 2, and overlap of primary studies was quantified using the corrected covered area (CCA). Seventeen systematic reviews were included, of which five reported diagnostic test accuracy meta-analyses using bivariate or HSROC models. Across these meta-analyses, pooled sensitivity ranged from 0.76 to 0.94 and specificity from 0.85 to 0.91. Most systems were based on deep learning models applied to bitewing radiographs and intraoral photographs. However, substantial heterogeneity was observed in imaging modalities, lesion thresholds, analytical tasks, and evaluation metrics. In addition, a high degree of overlap across reviews and recurrent methodological limitations, including reliance on retrospective datasets, limited external validation, and inconsistent reporting, substantially weaken the reliability of the evidence. Although AI models demonstrate high diagnostic performance under experimental conditions, current evidence does not support their use as stand-alone diagnostic tools. Their clinical applicability remains limited, and implementation should be restricted to decision-support contexts until robust prospective validation demonstrates meaningful impact on clinical decision-making and patient outcomes.

Dental Caries↗

PubMed2026

High-dose radiotherapy in patients with high-risk prostate cancers treated with long-term androgen deprivation therapy (GETUG AFU 18): a randomised, phase 3 trial.

BACKGROUND: For patients with high-risk prostate cancer, the role of dose-escalated radiotherapy in combination with long-term androgen deprivation treatment (ADT) is controversial, without any demonstrated benefit on cancer-specific or overall survival. We aimed to evaluate the effect of a 10 Gy dose increase, from 70 Gy to 80 Gy, on progression-free survival in men with high-risk prostate cancer. METHODS: In this multicentre, open-label, randomised, phase 3 trial, we enrolled patients with high-risk prostate cancer, defined as prostate-specific antigen of 20 ng/mL or more, Gleason score of at least 8, or clinical stage T3-T4, from 25 centres in France. Participants were randomly assigned (1:1) by minimisation, stratified by centre and previous pelvic lymph node dissection, to receive prostate-targeted dose-escalated external beam radiotherapy (80 Gy; 2 Gy per fraction for 8 weeks) or standard-dose external beam radiotherapy (70 Gy; 2 Gy per fraction for 7 weeks), combined with long-term ADT. Neither the participants nor the investigators were masked to the allocated treatment. The primary endpoint was 5-year progression-free survival defined as the time from randomisation to first biochemical (defined as prostate-specific antigen >nadir plus 2 ng/mL) or clinical (ie, local, regional, or metastatic) disease progression, analysed in the intention-to-treat population, with 197 events required. 5-year progression-free survival was the prespecified endpoint, and 10-year progression-free survival was additionally reported (post hoc) in view of the low number of events at 5 years. The trial is registered at ClinicalTrials.gov, NCT00967863, and is complete. FINDINGS: Between April 6, 2009, and Jan 24, 2013, 505 patients with high-risk prostate cancer were enrolled; 250 were assigned to receive dose-escalated radiotherapy (80 Gy) and 255 to receive standard dose radiotherapy (70 Gy). All participants were male and ethnicity data were not collected. At a median follow-up of 9·5 years (IQR 8·5-10·3), 5-year progression-free survival was 91·4% (95% CI 87·0-94·4) in the dose-escalation group versus 88·1% (83·2-91·6) in the control group, and 10-year progression-free survival was 83·6% (77·8-88·0) versus 72·2% (65·3-78·0; stratified HR 0·56, 95% CI 0·40-0·78, p<0·0001). Grade 3 or worse adverse events assessed at 6 months (acute toxicity) were observed in 60 (24%) of patients in the dose-escalation group and 62 (25%) in the control group. The most frequent grade 3 or worse adverse events were sexual disorders (28 [11%] in the dose-escalation group vs 20 [8%] in the control group) and bladder or urethra disorders (12 [5%] vs 19 [8%]). Adverse events assessed at 5 years (late toxicity) occurred in 118 (70%) of 168 in the dose-escalation group and 122 (73%) of 168 in the control group; grade 3 or worse late toxicities occurred in 19 (8%) participants in the dose-escalated radiotherapy group versus 17 (7%) participants in the control group. The most common late grade 3 adverse event was bladder or urethra disorders (seven [4%] vs three [2%], respectively). Serious adverse events occurred in nine (4%) patients in the dose escalation group and nine (4%) in the control group; none were considered to be treatment related. There were no treatment-related deaths. INTERPRETATION: For patients with high-risk prostate cancer, radiotherapy at a total dose of 80 Gy, in combination with long-term ADT, improved progression-free survival and could be a potential option in this situation. However, given the low number of events, further research is needed to consolidate and confirm the benefit in dose-escalation in prostate cancer-specific survival and overall survival. FUNDING: French National Cancer Institute and AstraZeneca.

Aged↗

PubMed2026

Adjuvant alectinib versus chemotherapy in resected ALK-positive non-small-cell lung cancer (ALINA): health-related quality-of-life and safety outcomes from a randomised, open-label, phase 3 trial.

BACKGROUND: For patients with resected, ALK-positive non-small-cell lung cancer (NSCLC), adjuvant alectinib significantly improved disease-free survival versus platinum-based chemotherapy in the global, phase 3, open-label, randomised ALINA trial. We report safety and health-related quality-of-life (HRQoL) outcomes from the ALINA trial. METHODS: Eligible patients aged 18 years or older with resected, ALK-positive, stage IB (≥4 cm)-IIIA NSCLC (per the American Joint Committee on Cancer and the Union for International Cancer Control Cancer Staging Manual 7th edition) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (1:1) via a block-stratified randomisation method to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy for four 3-week cycles. Randomisation was stratified according to disease stage and race. The primary endpoint, previously reported, was disease-free survival. Safety was a secondary endpoint and HRQoL was an exploratory endpoint. Safety was assessed by the investigator as per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5·0 until 28 days after the last alectinib dose or chemotherapy cycle. HRQoL was assessed via the Short-Form 36-item health survey version 2 (SF-36v2) questionnaire at baseline, every 3 weeks to week 12, then every 12 weeks until disease recurrence, consent withdrawal, death, or week 96. Norm-based scoring was applied; clinically meaningful changes were defined using the SF-36v2 manual. Safety was assessed in the safety-evaluable population and HRQoL in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT03456076) and is ongoing. FINDINGS: Between Aug 16, 2018, and Dec 8, 2021, 257 patients were assigned to receive alectinib (n=130) or chemotherapy (n=127). 123 (48%) patients were male and 134 (52%) were female; 143 (56%) were Asian. The safety-evaluable population comprised 128 patients who received alectinib and 120 patients who received chemotherapy; median duration of safety follow-up was 24·8 months (IQR 22·0-24·9) in the alectinib group and 3·7 months (IQR 3·7-3·8) in the chemotherapy group. The safety of adjuvant alectinib was generally consistent with its known profile. The most common grade 3-4 adverse events were blood creatine phosphokinase increased (eight [6%] of 128), alanine aminotransferase increased (two [2%] of 128), and blood bilirubin increased (two [2%] of 128) in the alectinib group, and neutrophil count decreased (12 [10%] of 120), neutropenia (ten [8%] of 120), and nausea (five [4%] of 120) in the chemotherapy group. Serious treatment-related adverse events occurred in two (2%; one each with appendicitis and pneumonitis) of 128 patients in the alectinib group and eight (7%) of 120 patients in the chemotherapy group ( most common were gastrointestinal disorders in three [3%] patients). No deaths due to adverse events were reported in either group. There were fewer discontinuations due to adverse events with alectinib (seven [5%]) versus chemotherapy (15 [13%]). A clinically meaningful difference in improvement from baseline was seen at week 12 for bodily pain, role physical, mental health, social functioning, and vitality SF-36v2 domains with alectinib; improvements in physical and mental HRQoL were maintained over 2 years of active treatment (at week 96, mean Mental Component Summary score: 49·9 [SD 10·4]; mean Physical Component Summary score: 48·8 [SD 7·2]) and reached levels similar to the general population (population norm: 50). INTERPRETATION: For patients with resected ALK-positive NSCLC, adjuvant alectinib had a manageable safety profile; HRQoL improved and was maintained over 2 years of active treatment. Together with the disease-free survival benefit seen in ALINA, these data support adjuvant alectinib as an important new standard-of-care for patients with resected ALK-positive NSCLC. FUNDING: F Hoffmann-La Roche.

Adult↗

PubMed2026

Integrated single-cell and bulk transcriptomic analysis identifies a novel senescent fibroblast subtype associated with poor prognosis in acral melanoma.

BACKGROUND: Acral melanoma (AM) exhibits significant intratumoral heterogeneity, but its tumor microenvironment (TME) and immune regulation remain unclear. This study aims to dissect TME heterogeneity and establish a prognostic model based on key cell subpopulations. METHODS: We collected AM single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Unsupervised clustering, CellChat, and Scissor analysis were performed to characterize cellular heterogeneity, cell-cell communication, and prognosis-related cell subpopulations. Kaplan-Meier analysis was used to assess the prognostic value of key genes, which were further validated by multiplex immunohistochemistry (mIHC). RESULTS: In AM, Mel_C2, C7, and C9 with high SEMA6A and KIT expression were strongly linked to poor prognosis. We further identified a senescent fibroblast subpopulation (sCAF_CDKN2A) characterized by high fibroblast senescence signature (FSS) scores. Integrating Scissor analysis of fibroblast subtypes with bulk prognostic data, we identified COL3A1, VCAN, and KIT as prognosis-associated genes upregulated in poor-outcome-related fibroblast subsets. Cell-cell communication analysis revealed that sCAF_CDKN2A engages in an immunosuppressive network, interacting with regulatory T cells (Tregs) via MIF signaling and receiving signals from exhausted CD8+ T cells through PPIA-BSG interactions. Using transcription factor expression patterns from these fibroblast subtypes, we constructed a prognostic model that effectively stratified patients into distinct risk groups with significant differences in overall survival (OS). mIHC confirmed significantly higher protein levels of SEMA6A and COL3A1 in tumor tissues compared to matched normal tissues. CONCLUSIONS: We established a novel prognostic model for AM and identified sCAF_CDKN2A as an immunosuppressive senescent fibroblast subpopulation driving poor prognosis.

Acral melanoma↗

PubMed2026

Redox Rewiring in Nicotine-Driven Gastric Carcinogenesis: Uncovering ROS-Dependent Oncogenic Circuits.

SIGNIFICANCE: Nicotine from tobacco products, secondhand smoke, and emerging delivery systems remains a major but underappreciated driver of gastric carcinogenesis (GC). Although reactive oxygen species (ROS) have long been implicated in tumor biology, current models incompletely explain how chronic nicotine selectively reprograms gastric epithelial signaling. This review advances the concept of redox rewiring, whereby nicotine establishes a persistent oxidative state that orchestrates multiple oncogenic programs via spatially compartmentalized NOX signaling. RECENT ADVANCES: We synthesize evidence for a unified model wherein nicotine activates nAChR/β-AR signaling, Ca2+ influx, PKC, and compartmentalized NOX-derived ROS to generate distinct oncogenic outputs. Beyond the established NOX/ROS/NF-κB/MAPK-driven IL-8 and MMP-9 axes, we integrate emerging evidence into three interconnected modules governing EMT/metastasis (ABL1/STAT3/COX-2/periostin), survival/chemoresistance (ERK/GLI1/Bcl-2), and invasion/immune evasion (miR-21/PDCD4). Collectively, these circuits suggest that ROS function not merely as damaging byproducts but as spatially organized signaling mediators dictating tumor behavior. CRITICAL ISSUES: A major challenge is distinguishing established mechanisms from incompletely validated models. The three proposed axes are testable hypotheses requiring experimental validation. Most data derive from in vitro studies with nonphysiologic nicotine concentrations, and artifacts from nonspecific ROS probes are common. Compensatory pathway activation and multi-target effects of natural products remain underexplored. FUTURE DIRECTIONS: We outline a precision-redox oncology roadmap linking pathway-specific biomarkers, mechanistically matched natural products, and biomarker-enriched trials. Priorities include genetic validation of the three axes, time-resolved ROS imaging, and pulsed natural product regimens. By reframing nicotine-driven GC as adaptive redox network remodeling, this review provides a framework for prevention, stratification, and next-generation therapy. Antioxid. Redox Signal. 00, 000-000.

gastric cancer↗

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

Adolescent health across Asia Pacific, 2000-23: a systematic analysis for the Global Burden of Disease Study 2023.

BACKGROUND: The Asia Pacific region is home to more than half of the world's 1·93 billion adolescents (aged 10-24 years). Addressing adolescent health in this region is of global importance, but to date a systematic analysis of key contributors to disease in adolescents has not been done, which is a barrier to responsive action. This systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 aims to provide a comprehensive assessment of adolescent health across the Asia Pacific region, at both the subregional and national levels, encompassing burden of disease, mortality, and prevalence of adolescent risk factors. METHODS: As part of GBD 2023, we obtained estimates for cause-specific mortality, disability-adjusted life-years (DALYs), and risk factor prevalence by sex for adolescents aged 10-24 years and 5-year age groups (10-14 years, 15-19 years, and 20-24 years) across 44 countries and territories (hereafter referred to collectively as Asia Pacific), grouped by seven UN subregions, from 2000 to 2023. We extracted GBD 2023 population counts and estimates of number and rate (per 100 000 population) for mortality and disease burden (DALYs). Risk prevalence estimates were obtained directly from the Institute for Health Metrics and Evaluation, and binge drinking estimates were sourced from WHO. Estimates are reported with 95% uncertainty intervals (UIs) where possible. UIs were estimated by running 250 draws of the posterior distribution, ordering the draws, and selecting the 2·5th and 97·5th percentiles for each metric. FINDINGS: In 2023, in adolescents across Asia Pacific, there were 637 496 deaths and a total disease burden of 115·8 million DALYs, representing 34·1% of global adolescent deaths and 40·6% of the global adolescent burden of disease. Non-communicable diseases (NCDs; particularly mental disorders) were the leading causes of disease burden and mortality (64·8% of DALYs and 43·9% of deaths). Unintentional and transport injuries were also leading causes of death (14·7% of deaths due to transport injury and 13·3% of deaths due to unintentional injury) and leading causes of disease burden particularly among males in south-eastern Asia. In Melanesia, Micronesia, and some parts of south-eastern Asia (Cambodia, Indonesia, Laos, the Philippines, and Timor-Leste), respiratory infections and tuberculosis remained important contributors. Southern Asia had the largest reduction (1·5% per year) in all-cause DALYs over the study period, and Australia and New Zealand (0·2% per year) had the smallest, with females in Australia and New Zealand showing a slight increase contrary to regional trends. Eastern Asia had the largest reduction (2·8% per year) in all-cause mortality rate and Melanesia (0·8% per year) the smallest. Risk factors generally had between-subregion and within-subregion variation; however, some regional trends stood out, with overweight and obesity increasing in all countries across the region, and binge drinking increasing in more countries than not. In 2023, prevalence of smoking in males exceeded that in females in every country, from 40% difference in Timor-Leste to less than 1% difference in Australia. Anaemia prevalence is decreasing in all countries, but female prevalence was higher and reducing at a slower rate than in males. Bullying prevalence was slightly higher in Polynesia, Micronesia, and Melanesia combined, Australia and New Zealand, and eastern Asia compared with southern and south-eastern Asian subregions. INTERPRETATION: Several patterns were consistent across the region: the dominance of mental disorders and NCDs, the universal rise in overweight and obesity (particularly high in Oceanic countries but increasing rapidly in south and south-eastern Asia), and persistent sex-specific challenges across subregions: unintentional injuries and smoking in males, and anaemia in females. Actions to tackle shared risk factors (while accounting for context-specific local health profiles, workforce deficits, cultural factors, and health system capacity) should not be forgone due to local variation. Future research could focus on subnational variation, intersecting inequalities, and multi-sectoral interventions targeting shared risk factors. Priority actions should include regional investment in adolescent mental health services and obesity prevention, targeted injury reduction strategies for high-risk populations, and sex-specific approaches to smoking cessation and anaemia reduction, delivered through local health systems with the capacity and cultural responsiveness to meet local needs. FUNDING: Gates Foundation and Australian Government.

Humans↗

PubMed2026

Selective monitoring of trace-level catechin and myricetin in herbal and aqueous matrices using magnetic MIP-DSPME: Optimization via design of experiments.

A novel dispersive solid-phase microextraction approach utilizing a magnetic molecularly imprinted polymer (MMIP) integrated with HPLC-UV detection was developed for the concurrent quantification of catechin and myricetin in herbal extracts and aqueous samples. The sorbent was engineered as a core-shell nanocomposite, consisting of a selective polymer layer deposited onto Fe3O4@SiO2-APTMS magnetic nanoparticles. Dual-template imprinting using catechin and myricetin generated complementary binding cavities within the polymer framework. Experimental variables influencing extraction were systematically screened and subsequently optimized. A Plackett-Burman design was first applied to identify the most influential factors, with pH and sorption time identified as the dominant variables. These parameters were subsequently fine-tuned using a central composite design, and the optimization process was completed in only 30 experimental runs. The sorption characteristics of the imprinted sorbent (MMIP) were compared with those of its non-imprinted counterpart (MNIP). The MMIP demonstrated markedly higher maximum binding capacities (Qmax), reaching 119.3 mg g-1 for myricetin and 112.1 mg g-1 for catechin, whereas the corresponding values for the MNIP were 32.55 and 32.08 mg g-1, respectively. Moreover, the affinity constants (KL = 0.760-0.950 L mg-1) were approximately 2.3-fold higher for the MMIP, confirming its stronger and more selective interactions with the target analytes. The selectivity coefficients for the targeted flavonoids relative to structurally related compounds, including ferulic acid, p-coumaric acid, melatonin, and curcumin, exceeded 3.5 for the MMIP, whereas the corresponding values for the MNIP were close to 1.1, demonstrating the high molecular recognition capability of the imprinted sorbent. Method validation demonstrated limits of detection (LODs) of 0.33-0.59 ng mL-1 and limits of quantification (LOQs) of 1.10-1.96 ng mL-1, and excellent linearity over the concentration range of 5.0-5500 ng mL-1 (R2 > 0.998). The method achieved recoveries of 93.96% to 105.69% with RSDs below 5.5%, while the preconcentration factors ranged from 209 to 229. Furthermore, the sorbent retained more than 95% of its extraction efficiency after four consecutive reuse cycles and more than 80% after six cycles, demonstrating excellent stability and reusability. The proposed method was successfully applied to the analysis of six medicinal plant extracts and water samples, showing negligible matrix interference and superior sensitivity, selectivity, and operational simplicity compared with conventional solid-phase extraction methods.

Flavonoids↗

PubMed2026

Association between cumulative social disadvantage, as measured by the social determinants of health score, and epilepsy: a cross-sectional study.

BACKGROUND: Social determinants of health (SDoH) shape access to care, health behaviors, and long-term outcomes, yet their cumulative relationship with epilepsy has not been well quantified. This study examined whether a composite SDoH score was associated with epilepsy in adults. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey 2013-2018. The SDoH score ranged from 0 to 8 and summarized eight unfavorable social conditions. Epilepsy was identified using medication-based ascertainment. Survey-weighted logistic regression models were applied to evaluate the association between SDoH score and epilepsy. Restricted cubic spline, subgroup, sensitivity, and receiver operating characteristic analyses were also performed. RESULTS: A total of 13,119 participants were included, of whom 114 had epilepsy. Participants with epilepsy had a higher mean SDoH score than those without epilepsy (3.41 ± 0.24 vs. 2.35 ± 0.06, P < 0.001). In the fully adjusted model, each 1-point increase in SDoH score was associated with 31% higher odds of epilepsy (OR 1.31, 95% CI 1.16-1.48). Compared with the low-score group (0-2), the adjusted odds ratios were 2.09 (95% CI 1.06-4.15) for scores of 3-5 and 2.67 (95% CI 1.34-5.33) for scores of 6-8. Spline analysis showed a significant overall association without evidence of nonlinearity. Adding SDoH components to demographic variables improved model discrimination (AUC 0.731 vs. 0.589, P for difference <0.001). CONCLUSION: Greater cumulative social disadvantage, as reflected by the SDoH score, was associated with higher odds of epilepsy.

Humans↗

PubMed2026

Insights into the fate and dynamics of antibiotic resistance in multidrug-resistant Bacillus cereus during in vitro simulated gastrointestinal digestion.

Bacillus cereus, an important pathogen responsible for causing foodborne diseases worldwide, releases pore-forming enterotoxins, which target host epithelial cells, leading to osmotic lysis and ultimately manifesting as diarrheal syndrome. Moreover, some B. cereus strains carry antimicrobial resistance genes that confer multidrug resistance against a spectrum of antibiotics. Characterizing the survival traits of multidrug-resistant (MDR) B. cereus strains in the intestinal microenvironment is essential for developing targeted strategies to effectively manage diarrheal foodborne diseases caused by this pathogen. This study used whole-genome sequencing (WGS) to evaluate the pre- and post-digestion toxigenic potential, antimicrobial resistance profiles, and genetic diversity of MDR B. cereus strains isolated from food samples in Guangdong Province, China. The four B. cereus isolates investigated in this study exhibited a genetic diversity, as determined by multilocus sequence typing analysis of WGS data. All four isolates produced the diarrheal toxins Hbl, Nhe, and CytK to varying levels, indicative of their potential to cause outbreaks of foodborne diseases. Each of the four isolates exhibited resistance to more than three classes of antibiotics, fulfilling the criterion for multidrug resistance. At an initial concentration of 9 log colony-forming units (CFU)/mL, the intestinal concentration of these four isolates crossed the threshold required to induce widespread diarrhea in the general population. Under rice slurry protection, all tested isolates maintained intestinal concentration beyond the threshold when the initial concentration was increased to ≥8 log CFU/mL. Moreover, the upregulations of genes associated with acid tolerance, bile tolerance and stress response were observed in the surviving MDR B. cereus isolates. Digestion markedly altered the antibiotic resistance profiles of the MDR B. cereus isolates. In the absence of a food matrix, the MDR isolates lost their resistance to imipenem, meropenem, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole post-digestion and was influenced by the initial concentration of the strains. In the presence of food matrix rice slurry, the effects of digestion on the antibiotic resistance of MDR B. cereus isolates can be mitigated, enabling them to maintain their antibiotic resistance to the greatest extent. Most remarkably, after digestion, the isolates Bce055 and Bce166 exhibited newly emergent resistance to cefotetan and trimethoprim-sulfamethoxazole, respectively. Our findings clarify the fate of MDR B. cereus isolates in the gastrointestinal tract and inform the development of prevention and control strategies for foodborne diseases caused by this pathogen.

Drug Resistance, Multiple, Bacterial↗

PubMed2026

Relational care in community mental health: Evaluating staff experiences in Intensive Community Care Services (ICCS) vs treatment as usual.

BACKGROUND: The quality of healthcare delivery relies heavily on building strong relationships between healthcare providers (HCPs) and clients. This study presents the results of a process evaluation for a Randomised Controlled Trial (RCT) examining the effectiveness of Intensive Community Care Service (ICCS) vs Treatment as Usual (TAU; inpatient or core community CAMHS). METHODS: Thirty-four semi-structured interviews were conducted with staff across various services, including 20 from ICCS and 14 other TAU services. A thematic decomposition analysis was conducted on the data, and specific themes relevant to staff experiences of young people's engagement with services and overall recovery. RESULTS: Three main themes were observed in the HCP data (1. Relational Ecologies: barriers and enablers to engagement, 2. flexibility of approach amidst systemic pressures and 3. the web of trust in the relationship-building process). HCPs highlighted the necessity of developing trust and rapport through non-clinical engagement strategies, such as informal visits and personalised interactions. HCPs emphasised that without trust, treatment effectiveness diminishes, necessitating a tailored approach rather than a one-size-fits-all model. The flexibility in duration of treatment and methods of engagement was noted as crucial in accommodating individual client needs and fostering an open, trusting environment necessary for long-term recovery. CONCLUSION: The findings highlight the vital importance of relational care models, especially ICCS, in addressing the complex needs of Children and Young People (CYP). Flexible, family-centred approaches improve trust, engagement, and long-term recovery outcomes. Recommendations include tackling systemic barriers and expanding relational care models within CAMHS to meet increasing mental health demands effectively. Further research should investigate scalable strategies for integrating these insights into wider mental health service frameworks.

Humans↗

PubMed2026

Discrimination, chronic stress, and multimorbidity in cohort of Black and Latina transgender women with HIV: Longitudinal findings from the LITE Plus study.

Black and Latina transgender women with HIV (BLTWH) are exposed to repeated, intersecting discrimination based on race, gender, and serostatus. Minority stress theory conceptualizes discrimination as minority-specific stressors that drive health inequities. Allostatic load theory posits a pathway between discrimination and chronic disease through multisystem physiological dysregulation caused by chronic stress. To test this pathway, a longitudinal cohort of 108 BLTWH, enrolled December 2020 - June 2022 in Boston, New York City, and Washington, DC, were followed for 24 months, with biomarkers measured at baseline, 12, and 24 months. Questionnaires administered every 6 months assessed anticipated discrimination, everyday discrimination, perceived stress, and other psychosocial factors. Multimorbidity was measured via self-reported non-HIV chronic conditions. In mixed-effects mediation models, allostatic load did not mediate relationships between multimorbidity outcomes and anticipated discrimination (β: -0.0004 [95% CI: -0.004, 0.003]) nor everyday discrimination (β: -0.002 [95%CI: -0.009, 0.003]). Perceived stress demonstrated indirect effects on multimorbidity in unadjusted models of anticipated discrimination (β: 0.024, [95% CI: 0.015, 0.081]) and everyday discrimination (β: 0.021 [95%CI: 0.016, 0.077]). Indirect effects remained significant, with attenuated effects (β: 0.020 for anticipated discrimination; β: 0.017 for everyday discrimination) after adjusting for social support, community connection, and resilient coping. Total effects were only significant for the adjusted model of everyday discrimination (β: 0.056 [0.014, 0.099]). Findings suggest discrimination impacted health through specific psychosocial pathways. Alongside efforts to eliminate intersectional discrimination, stress-lowering interventions and increased access to social support and community connection may be effective approaches to reducing multimorbidity in this highly marginalized group.

Humans↗