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PubMed2026

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent↗

PubMed2026

Azacitidine-Venetoclax or Induction Chemotherapy for Acute Myeloid Leukemia.

BACKGROUND: Induction chemotherapy has long been a key component of curative therapy for fit patients with acute myeloid leukemia (AML), despite its frequently severe side effects and substantial health care utilization. For patients who are ineligible for induction chemotherapy, hypomethylating therapy plus venetoclax is the standard treatment owing to its efficacy and side-effect profile. METHODS: In this multicenter, phase 2 trial, we randomly assigned, in a 1:1 ratio, previously untreated adults with AML who were eligible for induction chemotherapy to receive either azacitidine plus venetoclax or induction chemotherapy. Patients with core binding factor fusions, mutations in the gene encoding FMS-like tyrosine kinase 3 (FLT3), or mutations in the gene encoding nucleophosmin-1 (NPM1; unless the patient was ≥60 years of age) were excluded. The primary end point was event-free survival. RESULTS: A total of 172 patients underwent randomization, with 86 patients assigned to each group. The median age of the patients was 64 years. A total of 72% of the patients had adverse-risk disease according to the European LeukemiaNet 2022 classification. At a median follow-up of 21.9 months, the median event-free survival was 14.5 months (95% confidence interval [CI], 10.4 to 24.4) in the azacitidine-venetoclax group, as compared with 6.2 months (95% CI, 4.1 to 10.1) in the induction chemotherapy group, corresponding to a hazard ratio for event or death of 0.57 (95% CI, 0.39 to 0.84; P = 0.002 by the stratified log-rank test). Infection of grade 3 or higher occurred in 28% of the patients (95% CI, 19 to 39) receiving azacitidine-venetoclax and in 41% of those (95% CI, 30 to 52) receiving induction chemotherapy; hemorrhage of grade 3 or higher occurred in 2% (95% CI, 0.3 to 8) and 12% (95% CI, 6 to 20), respectively. CONCLUSIONS: In this phase 2, randomized trial, azacitidine-venetoclax therapy led to significantly longer event-free survival than induction chemotherapy among induction-eligible patients with AML. (Funded by AbbVie and others; PARADIGM ClinicalTrials.gov number, NCT04801797.).

Adult↗

PubMed2026

Validation of the newly introduced Deauville score 5a for patients treated for advanced-stage classic Hodgkin lymphoma.

The Lugano Imaging Committee recently refined the Deauville score (DS), subdividing DS5 into DS5a (>2× liver uptake without new lesions) and DS5b (new lesions). We investigated whether this improves prognostic discrimination at interim positron emission tomography (PET) after 2 cycles (PET-2) in patients with advanced-stage classical Hodgkin lymphoma (AS-cHL) treated in recent German Hodgkin Study Group randomized phase 3 trials. The primary analysis cohort was HD18 postamendment standard arms (uniform treatment with 6 cycles of escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [eBEACOPP]); sensitivity cohorts were HD18 intention-to-treat and HD21 eBEACOPP and brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone arms. Progression-free survival (PFS) was analyzed by landmark Cox models starting at PET-2. DS5a was infrequent (4%-6% across cohorts; 39/639, 67/1745, 33/568, and 29/560). In the primary cohort, DS5 was associated with inferior PFS vs DS1 to DS3 (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.25-7.23) and vs DS1 to DS4 (HR, 2.35; 95% CI, 1.01-5.50). Across sensitivity cohorts, DS5a remained adverse compared with DS1 to DS4 (HR range, 2.57-5.47), whereas DS4 according to the new definition did not consistently separate from DS1 to DS3, which is likely a result of PET-adapted treatment. Overall survival trends were concordant, but interpretation is limited by few events. To our knowledge, this is the first prognostic validation of the refined DS in prospectively randomized trial populations. The newly introduced DS5a isolates a small high-risk AS-cHL, which further supports risk assessment and adaptation using quantitative biomarkers from PET. The HD18 and HD21 trials were registered at www.clinicaltrials.gov as NCT00515554 and NCT02661503, respectively.

Humans↗

PubMed2026

Meta-PseU: A meta-classifier for robust prediction of RNA pseudouridine modification sites from long sequences.

BACKGROUND AND OBJECTIVES: Pseudouridine (Ψ) represents one of the most abundant and conserved RNA modifications. Ψ provides an additional hydrogen-bond donor that enhances RNA structural stability and modulates translation. It participates in diverse biological processes, including RNA-protein interactions, splicing, translational control, and stress responses. Aberrant pseudouridylation is implicated in cancer, neurodegenerative disorders, and autoimmune diseases. Despite its biological importance, experimental identification of Ψ sites remains time-consuming and costly, limiting the feasibility of transcriptome-wide profiling. Computational approaches have therefore become essential complements to experimental techniques. However, state-of-the-art machine-learning and deep-learning predictors often suffer from limited generalizability due to small training datasets. To overcome these issues, we aim at constructing new long-sequence datasets and developing a novel Ψ site predictor. METHODS: New long-sequence datasets were constructed as benchmarks for RNA Ψ-site prediction. The Ψ modification sites in RMBase 3.0 were mapped to the reference genomes across three species of human, mouse, and yeast, and the RNA sequences with a length of 201 were generated by extending the upstream and downstream from the mapped, central sites. To eliminate sequence redundancy, the sequences were clustered using CD-HIT with a 70% sequence identity threshold. We developed Meta-PseU, a logistic regression-based meta-classifier that considered 118 machine learning and deep learning classifiers. The datasets and programs are freely accessible at https://github.com/kuratahiroyuki/MetaPseU. RESULTS: By optimizing model configuration, we proposed the Meta-PseU model stacking 32 machine learning and deep learning classifiers out of 118 classifiers. Meta-PseU substantially improved model generalizability, overcoming a key limitation of existing approaches. It greatly outperformed state-of-the-art predictors and achieved increasing accuracy with increasing sequence length. CONCLUSIONS: Long-sequence datasets were newly constructed as benchmarks for RNA Ψ-site prediction. Meta-PseU offers a new framework for robust Ψ-site identification by using long sequences.

Pseudouridine↗

PubMed2026

Omics in hereditary optic neuropathies: A systematic review of clinical studies with an integrated point of view.

Hereditary optic neuropathies are characterized by bilateral visual loss due to the degeneration of retinal ganglion cells, resulting in optic nerve degeneration and atrophy. Although the genetic origin of the main isolated and syndromic hereditary optic neuropathies has been characterized, the clinical phenotypes exhibit significant and poorly understood variability in both penetrance and expressivity. Additionally, the genetic and environmental factors that influence the onset of these optic neuropathies remain poorly understood, with limited biomarkers to predict disease progression or as readouts for therapeutic trials. Data-driven omics strategies allow deep phenotyping to improve our understanding of pathophysiological mechanisms and to search for new biomarkers and therapeutic targets. We explore whether the omics strategies applied to patients with hereditary optic neuropathies have provided such new insights. MEDLINE, Web of Science and EMBASE databases were screened for studies with terms relating to hereditary optic neuropathies, transcriptomics, epigenomics, proteomics, metabolomics and lipidomics in clinical studies exploring patients' samples. Out of 1244 references identified, 22 articles were included after double-masked data curation. These articles focused only on the 3 main forms of hereditary optic neuropathies, namely, OPA1-related dominant optic atrophy (n = 4), Leber hereditary optic neuropathy (n = 13), and Wolfram syndrome (n = 5). While the methodological designs and results of these studies were highly heterogeneous, they revealed molecular alterations that we have attempted to discuss at the integrated multi-omics level. This data integration highlighted several common pathophysiological mechanisms such as energetic impairment, endoplasmic reticulum stress, proteotoxic and oxidative stresses, lipid remodeling and altered amino acid and purine metabolisms, while suggesting potential new biomarkers and therapeutic targets. These findings underscore the potential of integrated multi-omics approaches to deepen our understanding of the phenotypic complexity of hereditary optic neuropathies and to support the development of innovative diagnostic and therapeutic strategies.

Humans↗

PubMed2026

Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans↗

PubMed2026

Deciphering S-nitrosylation-regulated metabolic networks in postmortem beef based on label-free modificomics: Identification of ferroptosis as a novel quality-related pathway.

This study elucidated the molecular mechanisms of S-nitrosylation on postmortem beef metabolism and quality based on the label-free modificomics. Varying degrees of S-nitrosylation were exogenously induced in beef semimembranosus (SM) muscle. Results indicated that a high S-nitrosylation level significantly increased beef pH and Warner-Bratzler shear force (WBSF) while reducing centrifugal loss (P < 0.05). A total of 828 S-nitrosylated proteins and 1458 modification sites were identified, of which 114 sites on 81 proteins (DSNPs) exhibited differential modification abundance, representing an increase of 125% compared with previous proteomics studies. DSNPs were mainly involved in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, calcium signaling, cell structure, and ferroptosis. Notably, this study provides the first evidence in postmortem muscle that S-nitrosylation regulates key ferroptosis-related proteins, including ACSL, CP, and TF, offering new insights into the link between S-nitrosylation and the ferroptosis pathway in meat. Correlation analysis demonstrated that TF was significantly negatively correlated with pH and WBSF, but positively correlated with centrifugal loss (P < 0.05). Collectively, protein S-nitrosylation critically modulates postmortem beef quality through the coordinated regulation of multiple metabolic processes. More importantly, the identification of ferroptosis as a S-nitrosylation-sensitive pathway provides a new perspective for regulating meat quality through protein post-translational modifications.

Animals↗

PubMed2026

Depth-dependent microbial succession and interspecies hydrogen transfer drive pit mud maturation in Chinese strong-flavor baijiu fermentation.

Microbial communities in fermentation pit mud play a key role in determining the quality of Chinese strong-flavor baijiu (CSFB). However, the ecological processes underlying pit mud maturation across spatial and temporal scales remain unclear. In this study, amplicon sequencing and metagenomic analyses were employed to investigate the taxonomic succession, community assembly, and metabolic functions of bacterial and archaeal communities during the transition from fresh pit mud (FPM) to new pit mud (NPM) and old pit mud (OPM). A pronounced depth-dependent succession pattern was observed, with 4 cm representing a critical ecological boundary separating distinct community structures and maturation trajectories. During surface-layer maturation, community assembly shifted from stochastic to deterministic processes, accompanied by homogeneous selection and increasing network complexity. In contrast, stochastic processes remained dominant throughout deep-layer maturation. Metagenomic analyses revealed a functional transition from lactate and acetate production, primarily associated with Lactobacillus in FPM and NPM, to butyrate and caproate production associated with Clostridium and Caproiciproducens in OPM. This functional transition was accompanied by enhanced amino acid metabolism, which was associated with the enrichment of Proteiniphilum and Aminobacterium. Notably, methanogen-mediated interspecies hydrogen transfer (IHT) emerged as a key ecological feature during pit mud maturation. In OPM, IHT networks primarily involving Methanobacterium and Methanosarcina linked methanogenesis with reverse β-oxidation through diverse hydrogen-transfer pathways, reinforcing metabolic interactions underlying caproate production. These findings provide new insights into the ecological mechanisms underlying pit mud maturation and offer a theoretical basis for the directed cultivation of high-quality pit mud in CSFB production.

Hydrogen↗

PubMed2026

Chemotherapy-Induced Nausea and Vomiting in Early Breast Cancer Patients Receiving Adjuvant Chemotherapy With Fluorouracil, Epirubicin, Cyclophosphamide Followed by Docetaxel Versus an Anthracycline-Free Regimen With Docetaxel, Cyclophosphamide-Results From a Randomized Clinical Trial.

Chemotherapy-induced nausea and vomiting (CINV) remains an important side effect despite new antiemetic drugs. This study tried to understand the occurrence of CINV in patients receiving two different chemotherapy regimens. As part of the randomized controlled clinical trial SUCCESS C (NCT00847444), 1582 of the 3463 patients completed CINV diaries. Patients were randomized to receive either chemotherapy with FEC (5-fluorouracil, epirubicin, cyclophosphamide followed by docetaxel) or TC (docetaxel, cyclophosphamide). CINV was evaluated hourly using a specially designed questionnaire. Endpoints of the study were complete response (no emesis) and total control (no nausea and no emesis) and were assessed with Kaplan-Meier curves and Cox regression analyses over three chemotherapy cycles. Eight hundred fourteen patients received FEC and 768 received TC; patients and tumor characteristics were similar in both groups. Patients receiving FEC had significantly more nausea and vomiting, with the main difference in the first 12 h. In the first cycle, the 0-12-h nausea/emesis-free rates were 70%/41% for FEC and 91/76% for TC. By 24 h after chemotherapy, the rates were 65%/33% (FEC) and 85%/60% (TC). The differences were similar in cycles 2 and 3. The detailed analysis of CINV in the study is unique and paves the way for modern CINV analysis of new therapeutics such as antibody-drug conjugates.

Adult↗

PubMed2026

Precision Oncology in Hepatopancreatobiliary Cancer Surgery.

Advances in technology have allowed for the characterization of tumors at the genomic, transcriptomic, and proteomic levels. There are well-established targets for biliary tract cancers, with exciting new targets emerging in pancreatic ductal adenocarcinoma and potential targets in hepatocellular carcinoma. Taken together, these data suggest an important role for molecular profiling for personalizing cancer therapy in advanced disease and need for design of novel neoadjuvant studies to leverage these novel therapeutics perioperatively in the surgical patient.

Humans↗

PubMed2026

Neoplasms in prune belly syndrome: A novel case of early-onset metastatic bladder carcinoma and systematic review of reported tumors.

PURPOSE: Prune Belly Syndrome (PBS) is a rare congenital malformation complex characterized by cryptorchidism, urinary tract abnormalities and deficiency of the abdominal wall musculature. Although advances in neonatal and reconstructive care have substantially improved survival, the long-term risk of malignancy in this population remains poorly defined. We report a novel case of early-onset metastatic bladder carcinoma in a patient with PBS and perform a systematic review of all tumors described in association with the syndrome. METHODS: A systematic literature review was performed according to PRISMA guidelines and registered in PROSPERO (CRD420251072086). Databases searched through April 2025 included PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane, and SciELO. Reported tumor cases in PBS patients were identified and classified as either PBS-associated or not. We additionally describe a new case of invasive bladder carcinoma. RESULTS: Seventeen studies comprising 20 patients met inclusion criteria. Tumors directly related to the genitourinary tract accounted for half of the cases. Bladder carcinoma was the most frequent neoplasm (35%), followed by hepatoblastoma (25%). Bladder tumors occurred at markedly younger ages and often presented as advanced diseases. Our index case involved a 33-year-old man with PBS who developed metastatic muscle-invasive urothelial carcinoma and died shortly after diagnosis. DISCUSSION: Improved survival in PBS has led to recognition of new late complications, including malignancy. Tumorigenesis may be influenced by chronic urinary stasis, infection, catheterization, cryptorchidism, and underlying genitourinary developmental abnormalities. These findings should be interpreted as hypothesis-generating given the limited number of reported cases. CONCLUSION: Although uncommon, malignancies in PBS may occur earlier and behave more aggressively than in the general population. Given the current level of evidence, careful long-term follow-up with clinical awareness is warranted, rather than routine invasive screening for all patients.

Humans↗

PubMed2026

Effectiveness of artificial intelligence in nursing simulation education: A systematic review, meta-analysis and bibliometric visualization analysis.

OBJECTIVES: To synthesize the roles and core functions of AI in nursing simulation education for nursing students via systematic review, quantitatively evaluate its effects on students' knowledge and skill outcomes through meta-analysis, and map the research landscape and development trends of this field through bibliometric visualization analysis. DESIGN: Systematic review, meta-analysis and bibliometric visualization analysis. DATA SOURCES: Eight electronic databases: PubMed, Web of Science, MEDLINE, ERIC, Academic Search Complete, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Chinese Science and Technology Journal Database (VIP) were employed to search studies from the time of construction to 16 December 2025. REVIEW METHODS: Studies meeting the inclusion criteria were screened. The revised Cochrane Risk of Bias tool (ROB 2) and Joanna Briggs Institute (JBI) critical appraisal checklists were used for quality assessment. Meta-analysis was performed with Review Manager 5.4, and bibliometric visualization analysis was conducted using VOSviewer 1.6.20 and Bibliometrix (based on R4.4.3). RESULTS: A total of 61 studies were included. AI primarily played two roles in nursing simulation education: peer-type new subject (n = 24) and direct mediator (n = 22). Meta-analysis showed that AI interventions significantly improved nursing students' knowledge (SMD = 1.49, 95% CI [0.55,2.43], p = 0.002) and skills (SMD = 0.66, 95% CI [0.02,1.31], p = 0.04). Bibliometric analysis identified that the United States of America and China were the two main contributing countries in this field, and the key motor themes included generative artificial intelligence, virtual patients, and geriatric care. CONCLUSIONS: AI exerts positive effects on nursing students' knowledge acquisition and skill enhancement in simulation education, with peer-type new subject and direct mediator as the dominant roles. Future research should focus on expanding AI applications in multi-specialty simulation scenarios, activating the data-driven value of machine learning, and strengthening international collaboration and standardization construction, so as to promote the sustainable development of AI-integrated nursing simulation education.

Humans↗

PubMed2026

Short-term safety of dual versus single antiplatelet therapy in flow diversion for distal intracranial aneurysms: results from the DART trial.

BACKGROUND AND PURPOSE: Flow diverters (FDs) have become one of the primary treatments for intracranial aneurysms (IAs). However, their use in distal IA has been associated with higher complication rates compared with other techniques. The development of coated FDs, in combination with novel antiplatelet regimens, offers promising strategies to improve the safety profile of FDs in this context. This trial aimed to compare mono antiplatelet therapy (MAPT) using prasugrel versus dual antiplatelet therapy (DAPT) with aspirin and prasugrel for the treatment of distal IA using the p48 MW HPC FD (WallabyPhenox). METHODS: This was a multicenter, prospective, parallel-group, single-blind, non-inferiority randomized trial. Between February 2021 and February 2025, 140 patients were enrolled. After excluding 11 patients, 129 were included in the final analysis. The primary endpoint was the absence of new neurological deficits, defined as no shift in the modified Rankin Scale (mRS) score. The secondary endpoint was the incidence of any stroke. RESULTS: At the 30-day follow-up, 66 patients (98.5%) in the MAPT group and 59 patients (95.2%) in the DAPT group showed no new neurological deficits. With a predefined non-inferiority margin of 5%, the difference of 3.35% confirmed the non-inferiority of MAPT compared with DAPT (p=0.002). The incidence of any stroke was 4/67 (5.9%) in the MAPT group and 6/62 (9.6%) in the DAPT group (p=0.431). CONCLUSION: Prasugrel monotherapy for the treatment of distal IAs using the p48 MW HPC was non-inferior to DAPT within the first 30 days following treatment. CLINICAL TRIAL REGISTRATION: https://ensaiosclinicos.gov.br/rg/RBR-3q9zb73. UTN code: U1111-1290-2489. Research Ethics Committee of the Hospital das Clínicas de Ribeirão Preto - Universidade de São Paulo. CAAE number: 29848720.0.1001.5440.

Humans↗

PubMed2026

Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years.

BACKGROUND: Ponesimod demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) in 24-week phase-2 core study, further confirmed by an interim combined analysis of the core and open-label long-term extension (LTE) studies (NCT01093326; up to 8 years). Current study evaluated safety and efficacy of ponesimod using combined core and LTE studies data for up to 13 years. METHODS: Of 393 participants completing the core study, 353 (90%) entered LTE, having 3 treatment periods (TP). In TP1 (∼1.85 years), participants continued core treatment (ponesimod: 10, 20, or 40 mg QD) whereas placebo-treated participants were re-randomized (1:1:1) to respective ponesimod doses. In TP2 (TP2 and TP3 combined duration: ∼10.4 years), participants on 40 mg were re-randomized (1:1) to 10/20 mg, while others continued same dose; in TP3 all participants received 20 mg. Study outcomes included safety and efficacy (ARR, time-to 24-week confirmed-disability-accumulation [24-week CDA], total T1-weighted Gadolinium-enhanced (T1 Gd+) lesions, new/enlarging T2 lesions and Combined Unique Active Lesions [CUALs]). RESULTS: For 20 mg dose, total 92.4% participants experienced ≥1 TEAEs (73.1% mild/moderate severity) and 19 (13%) participants discontinued study. Mean (95% CI) ARR=0.14 (0.10-0.20); Kaplan-Meier estimate (95% CI) of confirmed relapse and 24-week CDA=52.5% (42.3-63.5) and 31.3% (22.6-42.3). Mean [SD] T1 Gd+ lesions decreased from ponesimod baseline (2.62 [7.06]) to 12.4 years (0.26 [1.48]), mean (95% CI) CUALs per participant/year=3.97 (2.75-5.73). CONCLUSION: Ponesimod treatment for up to 13 years was not associated with new safety concerns. Participants continued to experience low levels of disease activity consistently across clinical and MRI outcomes.

Humans↗

PubMed2026

Risk of neurodevelopmental disorders associated with paternal use of valproate during spermatogenesis: a living meta-analysis-version 1.

OBJECTIVE: To evaluate the association of paternal use of valproate during spermatogenesis compared with paternal use of lamotrigine or levetiracetam on offspring risk of neurodevelopmental disorders (NDDs). METHODS: Eligibility criteria: observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate vs lamotrigine or levetiracetam during spermatogenesis. INFORMATION SOURCES: the databases PubMed, Embase, Cochrane Library and Web of Science were systematically searched from January 1995 to October 2025.Synthesis of results and risk of bias: a random-effects model was used to estimate pooled HRs and 95% CI, with heterogeneity assessed using I2 statistic for any NDD.We present a meta-analysis of observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate versus lamotrigine or levetiracetam during spermatogenesis. Given the major regulatory implications of paternal valproate safety, the recent emergence of new population-based data, and the expectation of further large studies, we designed this work as a living systematic review and meta-analysis that will be updated as new eligible evidence becomes available. RESULTS: We identified three eligible studies based on data from (1) Norway and Sweden, (2) Norway and Taiwan and (3) Denmark. As two studies included Norwegian data, their results are referred to as 'Norway 1' and 'Norway 2' for clarity. In the meta-analysis of data from Denmark, Sweden and Norway 1, the pooled HR of offspring NDDs was 1.05 (95% CI 0.87 to 1.27; I2=0.0%), and in meta-analysis of data from Denmark, Sweden and Norway 2, it was 1.03 (95% CI 0.85 to 1.24; I2=0.0%).In the meta-analysis including Taiwan, Denmark, Sweden and Norway 1, the pooled HR was 1.06 (95% CI 0.88 to 1.27; I2=0.0%), and when including data from Taiwan, Denmark, Sweden and Norway 2, the pooled HR was 1.04 (95% CI 0.87 to 1.25; I2=0.0%). CONCLUSIONS: In this living meta-analysis, we found no evidence that paternal exposure to valproate compared with lamotrigine/levetiracetam during spermatogenesis was associated with increased risk of NDDs in offspring.

Humans↗

PubMed2026

Assessing the threat of Bacillus cereus: From toxin characterization to modern detection strategies.

Bacillus cereus is a spore-forming pathogen responsible for both diarrheal and emetic foodborne illnesses worldwide. Its significance in food safety has received growing attention. Recent advances, including the discovery of novel virulence factors and the development of emerging detection technologies, have provided new insights into its pathogenic mechanisms and surveillance strategies. This review critically examines the global burden of B. cereus infections, and molecular mechanisms of its major virulence factors, and the performance characteristics of current detection knowledge gaps such as the viable-but-non-culturable state and regulatory blind spots for emetic toxins, and discuss unresolved challenges in clinical management. By integrating epidemiological, microbiological, and technological perspectives with critical lens, this review aims to provide a valuable reference for future research and food safety practices.

Bacillus cereus↗

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

The identification of growth-promoting lncRNAs in oral cavity squamous cell carcinoma.

Oral Cavity Squamous Cell Carcinoma (OCSCC) is an aggressive tumor that develops within the mouth of patients. Tumor-suppressor gene loss and genomic arrangements fuel tumorigenesis and transcriptional reprogramming. Understanding how these alterations contribute to OCSCC growth and cell survival may identify new therapeutic vulnerabilities or biomarkers. We profiled the role of long non-coding RNAs (lncRNAs) in the growth of three OCSCC cell lines using a CRISPRi-screen and identified 19 lncRNAs that contribute to OCSCC proliferation. By comparing these lncRNAs to other screens, we find that these lncRNAs are uniquely required in OCSCC and not other malignancies. We show that these lncRNAs are abundantly expressed in OCSCC cells and tumors. Independent testing of candidate lncRNAs confirms their role in supporting OCSCC growth. Our results show that a novel subset of lncRNAs are required for the growth of OCSCC cancer cells and that these lncRNAs are cell lineage specific.

CRISPRi↗