Archives of Virology

Respectful maternity care [RMC] comprises the primary components of high-quality maternal health services. Evidence on RMC levels and determinants in Ethiopia is still inadequate. This study aimed to examine the reception and its determinants among postnatal women in government hospitals in the East Wallaga Zone, West Oromia. An institution-based cross-sectional study was conducted from June to October 2025, within seven days post-delivery. A structured questionnaire based on the WHO RMC tools was used. The total RMC score proved robust reliability [Cronbachs = 0.808] and was organized using the 75th-percentile threshold. Factor analysis revealed basic RMC dimensions, while logistic regression was used to identify predictors of a promising RMC experience. This study presented that only 46.8% of postpartum mothers received adequate RMC, with significant gaps in care. The main deficiencies comprised poor provider self-introduction, failure to call women by name, and infrequent communication and consent practices. Three key RMC dimensions were identified: privacy and consent, explanation and permission, and respectful communication. Using multivariate analysis, interpersonal caring practices were robust predictors of positive RMC experiences. Explaining procedures with possible events, maintaining privacy, obtaining consent, prompt responsiveness, provider self-introduction, and calling mothers by name were significantly associated factors. Sociodemographic and maternal reproductive factors were not significantly associated after adjusting for confounders. Finally, fewer than half [46.6%] of mothers experienced adequate RMC, which indicated major gaps in woman-centered care. Improving respectful interpersonal communication, informed consent, and maintaining privacy should be prioritized to boost the quality of maternal healthcare in the study area.

Background: Literature on the role of thermal discomfort (heat- and cold-stress) on in-vitro fertilization (IVF) outcomes are scarce and inconclusive. This multi-center research examines association between heat stress and IVF treatment outcomes in Andhra Pradesh, which is prone to year around chronic heat stress. Methods: IVF data were abstracted from clinical chart review of all patients from three IVF from centers 2019 to 2023, which included time-stamped data on each IVF procedure, demographics and pre-existing comorbidities. Weather data were acquired from the National Climatic Data Center (NCDC). IVF outcomes were modelled with respect to time-lagged exposure to ambient temperature stratified by hyper- and hypo-thermic conditions using Poisson and logistic regressions depending on the scale of IVF outcomes adjusting for confounders. Results: Heat stress peaked in June, which corresponded with elevated number of spontaneous abortions/miscarriage (SAM). Under hypo- and hyper-thermic conditions a unit increase ambient temperature was associated with an 11% higher and an 8% lower number of oocytes retrieved, respectively. Adjusting for confounders, a 10 degree F increase in two-day lag heat stress was associated with a 30% higher odds of SAM (odds ratio ~ 1.03; 95% CI = 1.001 to 1.068; p-value < 0.043), and odds of PTB were 3 times higher when three day-lagged heat index (HI) was greater than 35 degree C (odds ratio 1.13 to 7.99; p < 0.05). Conclusion. Our findings warrant strategies to engage IVF patients in mitigating their exposure to thermal discomfort before and during the treatment.

Background: Incomplete childhood vaccination undermines individual and herd immunity and increases vulnerability to vaccine-preventable diseases. Understanding local determinants of vaccination adherence is essential for targeted interventions. This study assessed routine immunization completion and dropout patterns among children aged 0-15 months in Bayelsa State, Nigeria. Objectives: To determine vaccination completion rates, identify factors influencing adherence, analyze temporal patterns across immunization milestones, and provide evidence-based recommendations for improving coverage. Methods: A comparative longitudinal study was conducted from March 2023 to July 2024 across three Local Government Areas (LGAs), representing each senatorial district. A total of 369 mother-child pairs (123 per LGA) were enrolled. Data were obtained from health facility immunization registers and supplemented with semi-structured questionnaires. Children were followed through the 6th week, 10th week, 14th week, 9th month, and 15th month immunization visits. Completion rates were analyzed using descriptive statistics and chi-square tests. Ethical approval was obtained from the State Ministry of Health, and informed consent was obtained from all mothers. Results: Completion rates varied across LGAs, with the highest in LGA C (86.2%) and lowest in LGA B (61.0%). Phone-based reminders achieved the highest adherence, outperforming routine and home visit strategies. Progressive attrition was observed along the immunization schedule, with dropout exceeding completion by the 15th month. Principal reasons for non-completion included forgetfulness, travel, and caregiver busyness. Maternal age, education, and occupation significantly influenced adherence, indicating disparities across LGAs. Conclusion: Vaccination adherence is shaped by maternal characteristics and operational strategies. While early-stage coverage is high, attrition increases at later milestones, particularly in LGAs with lower resource engagement. Recommendations: Implement targeted phone-based reminders, milestone-specific outreach, and community engagement programs to reduce dropout, enhance timely completion, and strengthen childhood immunity.

Background: Dengue is a major public health problem in Brazil, and Minas Gerais is one of the states with the highest burden. In January 2019, the Brumadinho dam collapse released about 12 million cubic meters of iron ore tailings into the Paraopeba River basin, causing environmental disturbance that could plausibly affect vector habitats and dengue transmission. We evaluated the spatiotemporal dynamics of dengue in Minas Gerais from 2014 to 2023 and tested whether the disaster was associated with changes in affected municipalities. Methods: We performed an ecological spatiotemporal analysis using dengue notifications from SINAN for all municipalities in Minas Gerais (2014-2023). Municipalities were classified as Paraopeba basin, regional controls, or state controls. Temporal similarity was assessed using Pearson correlation-based hierarchical clustering and non-metric multidimensional scaling (NMDS). Sources of variation were examined with PERMANOVA and principal component analysis (PCA). A linear mixed-effects model with municipality as a random effect was used to test changes after 2019, with pre/post contrasts estimated from marginal means. Results: Dengue showed strong temporal synchrony across the state, with major epidemic peaks in 2015-2016, 2019, and 2023. Health region explained 31.5% of the variation in temporal incidence profiles (p = 0.001), whereas Paraopeba basin status explained no significant variation (p = 0.998). No temporal cluster was enriched for municipalities in the Paraopeba basin. PCA identified 2023, 2019, and 2016 as the main years driving variability. In the mixed model, year was significant (p < 0.001), but Paraopeba basin status and its interaction with time were not. Incidence increased significantly after 2019 in non-exposed municipalities (p < 0.001), but not in basin municipalities (p = 0.088). Conclusions: Dengue dynamics in Minas Gerais were driven mainly by regional and state-wide epidemic processes, with no significant independent effect of the Brumadinho dam collapse on notified dengue patterns.

Filoviruses pose a threat to individuals and the global community as pathogens of pandemic potential. The scientific community faces an ongoing challenge of developing effective vaccines with unpredictable outbreaks concentrated in countries with lower healthcare resources. Given these limitations, it is important to ensure that existing filovirus research is used as efficiently as possible. To enable rapid identification and use of this research, we have developed evidence maps of existing filovirus publications to enable further analysis and synthesis. We systematically identified and categorised existing immunological and clinical publications on Bundibugyo (BDBV), Marburg (MARV), Sudan (SUDV) and Ebola (EBOV) viruses. We captured studies that reported on animal or human immune responses to infection, outcome of infection, or human vaccine safety data. Initial searches of PubMed, Embase and Europe PMC were run between November 2024 and January 2025 and the MARV, SUDV and EBOV searches were updated on 1 August 2025. A BDBV search was conducted on 18 May 2026 in response to the WHO declaration of a Public Health Emergency on 17 May 2026. The initial searches retrieved 208, 1646, 534 and 3963 manuscripts for BDBV, MARV, SUDV and EBOV, respectively. After screening using an a priori exclusion criteria, 49 BDBV, 198 MARV, 149 SUDV and 850 EBOV publications were included on each evidence map. These maps provide a comprehensive, transparent and reproducible structure to categorise existing studies of filovirus vaccination and immunity. They allow rapid identification of the totality of available evidence and the existing experimental tools to support vaccine development for these priority pathogens.

Summary Background Although CAIDE (Cardiovascular Risk Factors, Aging, and Dementia) score estimates 20 year dementia risk, prior studies have largely focused on global or composite measures. Only a few studies investigated on cognitive functions and structural neuroimaging markers, and the available structural neuroimaging evidence has largely been derived from subsamples or highly selected small cohorts rather than full population based cohorts. We therefore not only investigated associations between CAIDE score and cognitive performance but also explored structural neuroimaging markers in middle to older aged population. Methods Of 2,864 participants who were available for structural magnetic resonance imaging (MRI) data at baseline, we excluded 230 participants who have neurological and cardiovascular disease at baseline. We also further excluded 209 participants without having exposure, covariates, and cognitive assessments data, including 2,425 participants for the final analysis. The main exposure is CAIDE score (0 to 15) were calculated from age, sex, education, systolic blood pressure, body mass index, total cholesterol, and physical activity and categorized as low risk (<6), moderate risk (6 to 7), and high risk (7<) at baseline. The main outcomes were neuropsychological assessment battery included Story recall, Visual reproductions, Verbal fluency, Trail making, Digit symbol coding, and Stroop tests. Findings Of 2,425 healthy participants (mean age of 58.5 [6.5]; men 1,189 [49.0]), higher CAIDE risk groups were associated with poorer cognitive performance. Compared with low risk group, the high risk group showed significantly lower performance across all 12 cognitive assessments (all p <.001). The moderate risk group also showed lower performance in visual reproduction (immediate and delayed recall), digit symbol oding, and Stroop (word and color) reading tests. Interpretation This large based population study showed the highest risk group were independently associated with lower cognitive performance across all domains compare to the lowest risk group, suggesting the potential importance of managing these features for preserving neurological health in middle and older aged adults.

Gain-of-function variants (GOF) in SCN8A, which encodes the NaV1.6 sodium channel, lead to epilepsy syndromes ranging from drug-responsive self-limited (SeLIE) and intermediate epilepsy to drug-resistant developmental and epileptic encephalopathy (DEE). It is currently unclear why individuals with SCN8A GOF variants show variable responses to sodium channel blockers (SCBs). Here, we compared the clinical characteristics of 173 individuals with 25 different SCN8A GOF variants following the hypothesis that carriers of variants affecting activation gating respond less well to SCBs than those with variants affecting fast inactivation gating, given that use-dependent SCBs preferentially target inactivated channel states. We found that individuals with variants altering channel activation gating were more severely affected than those with variants altering inactivation properties: They had an earlier age at onset (3 vs. 5 months, P < 0.0001), higher prevalence of DEE (75% vs. 39%; P < 0.0001), and poorer response to SCBs (20% vs. 69% seizure free; P < 0.0001). We performed pharmacological studies on representative and recurrent variants from each group: two variants (F846S and M1760I) causing hyperpolarizing shifts of the voltage-dependent activation curves, and two variants (G1475R and N1877S) causing depolarizing shifts of the voltage-dependent fast inactivation curves. Phenytoin failed to suppress neuronal firing in neurons expressing activation-related variants, but showed good suppressing effects in neurons expressing inactivation-related variants. In contrast, PRAX-330, a new SCB, which showed much faster binding rates than phenytoin, was effective for both groups of variants by markedly reducing neuronal firing through rapidly and persistently stabilizing NaV1.6 in the inactivated state. Our findings provide new insights into the mechanism of drug-resistance in SCN8A-DEE and support PRAX-330 and compounds with similar pharmacological properties as a promising preclinical candidate for targeted therapies.

Objectives: To evaluate if direct access to a Pregnancy Early Access Center (PEACE) improves the timeliness and efficiency of pregnancy loss care. Methods: We conducted a retrospective cohort study of patients diagnosed with EPL from January 2017 to December 2022 within a single healthcare system. We included EPL patients treated with procedural or medication management who had been assessed for a related early pregnancy complaint in the thirty days prior. The exposure was direct utilization of PEACE (yes/no) between first EPL symptom visit and EPL management. The primary outcome was "care latency" defined as days from initial presentation for concerning early pregnancy symptoms to initiation of active management. Secondary outcomes included "care continuity," the number of care teams encountered, "care efficiency," the number of patient encounters, and the type of EPL management received. Results: The evaluable cohort included 2151 individuals, with 36.5% patients of Black race and 30.3% publicly insured. A total of 885 (41.1%) received any EPL care at PEACE and 246 (11.4%) initiated their care at PEACE. Patients initiating care through PEACE experienced a 5-day reduction in care latency compared to patients who did not access PEACE. Adjusting for age, race, and insurance type, patients whose index EPL visit was with PEACE initiated their treatment twice as quickly as those who never saw PEACE (aHR 2.36 [95% CI, 2.05-2.71]). Care efficiency (median 2 [1-3] encounters) and care continuity (median 4.5 [4-7] care teams) were also improved by an index visit with PEACE when compared with controls (3 [2-4] and 6 [4-8] p<0.01), respectively). Conclusions: The Pregnancy Early Access Center (PEACE) model is associated with reduced care latency and improved efficiency and continuity when compared with routine care. PEACE reduces barriers to timely, patient-centered early pregnancy care.

Background. Meningiomas exhibit well-established hormonal biology, yet no study has examined whether myeloid immune infiltration interacts with estrogen-responsive transcription in this tumor type. Methods. We applied three-method consensus immune deconvolution (EPIC, MCPcounter, CIBERSORTx) to 968 harmonized meningioma RNA-seq transcriptomes from five public datasets, stratified by Thirimanne et al. (2024) transcriptomic subtypes. Competitive gene set enrichment compared macrophage-high versus macrophage-low tertiles with sex-adjusted, purity-adjusted, and method-independent sensitivity analyses. Survival modeling tested both total macrophage burden and a decomposed microglia-to-macrophage ratio validated against single-cell ground truth (pseudo-bulk r = 0.77). Results. Macrophage-high tumors showed significant suppression of estrogen response gene sets (FDR = 4.9 x 10-5) despite paradoxical ESR1 upregulation (log2FC = +0.40, FDR = 2.5 x 10-26) and PGR downregulation (log2FC = -0.34, FDR = 2.7 x 10-3), indicating post-receptor transcriptional disruption. This signal strengthened after sex adjustment (FDR = 1.9 x 10-6) and was confirmed across a multi-layer sensitivity battery (eleven analyses including reference-matrix-independent, purity-adjusted, rotation-based self-contained, and empirical-null tests; all FDR < 3 x 10-4 in the relevant convergent tests). Myeloid infiltration was strongly subtype-dependent (Kruskal-Wallis p = 7.4 x 10-16) but grade-independent (p = 0.399), with CSF1R enriched in the macrophage-dominant Cluster B. Neither total macrophage score (HR = 0.90, p = 0.53; N = 102) nor a decomposed microglia/macrophage ratio (HR = 0.92, p = 0.46; N = 101) predicted recurrence-free survival. Conclusions. The pre-registered primary endpoint - macrophage infiltration score predicting recurrence-free survival - was not supported; the estrogen-immune dissociation emerged from secondary exploratory gene-set analysis and requires independent validation. Macrophage-infiltrated meningiomas exhibit a previously unreported dissociation between maintained ESR1 expression and suppressed estrogen-responsive transcription, with implications for hormonal therapy stratification.

Importance: Enfortumab vedotin (EV) is an antibody-drug conjugate approved for the treatment of locally advanced or metastatic urothelial cancer (la/mUC). Cutaneous adverse events (cAEs) are common during EV therapy, with prior studies suggesting an association between EV-related cAEs and improved survival; however, there is insufficient data to delineate the survival benefit of EV-induced cAEs from those associated with concurrent immune checkpoint inhibitors (ICIs). Objective: This study aims to evaluate the association of EV-induced cAEs and survival, and to characterize the timing and morphology of EV-induced cAEs. Design: We conducted a multi-institutional retrospective study of patients with la/mUC treated with EV between 2020 and 2025. Setting: Multicenter academic referral center. Participants: A total of 449 EV-treated patients were included. Patient characteristics were extracted manually, and likelihood scoring was used to attribute cAEs to either EV or other etiologies. Exposure: EV treatment. Main Outcomes and Measures: We estimated progression-free (PFS) and overall (OS) survival using Kaplan-Meier method. Multivariable time-varying and landmark Cox regression models were used to evaluate associations between EV-induced cAE and survival. Sensitivity analyses were performed at landmarks from 15 to 105 days. Results: Of 449 patients, 206 (45.9%) developed a cAE; 39 (18.9%) were high-grade and 127 (61.7%) were attributed to EV. The most common cAEs were pruritus (41.3%), unspecified and desquamating dermatitis (37.3%), and morbilliform dermatitis (27.7%). Across all treatment groups, survival was longer in patients with EV-induced cAEs. Developing an EV-induced cAE was protective across all examined landmark times, with hazard ratio (HR) 0.60 (95% CI: 0.43-0.82, p<0.001) for PFS and HR 0.46 (95% CI: 0.31-0.67, p<0.001) for OS at primary landmark time of 30 days. Early-onset EV-induced cAEs were protective at all landmark times and high-grade EV-induced cAEs were not associated with worse survival. Conclusions and Relevance: EV-induced cAEs were independently associated with improved PFS and OS in patients with la/mUC, even after accounting for immortal time bias and ICI exposure. Distinguishing EV-induced cAEs from other etiologies in timeline and morphology may help guide oncology and dermatology management.

Background Emerging evidence suggests irreversible electroporation (IRE) with standard-of-care (SOC) chemo-therapy may improve survival in patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) when compared to SOC alone. This study evaluates the overall survival (OS) and progression-free survival (PFS) of Stage 3 PDAC patients treated with SOC plus IRE with the NanoKnife System versus SOC alone. Methods This prospective, multicenter study included two cohorts from the DIRECT registry: an IRE cohort from sites offering IRE as part of clinical care, and a comparator SOC cohort of prospectively enrolled and contemporaneous retrospective patients. Enrollment spanned 08/05/2019 to 02/05/2023, with follow-up through at least 24 months, death, or loss to follow-up. Included were 137 patients (99 IRE; 38 SOC), aged [&ge;]18 years with Stage 3 PDAC and no progression after three months of SOC therapy. Results Median (interquartile range) time from diagnosis to enrollment was 8 (6-10) months for IRE and 4 (3-6) for SOC (p<0.0001). Median OS and PSF from enrollment were 18 (95% confidence interval [CI]: 15-24) months and 9 (95% CI: 7-12) months for IRE, and 10 (95% CI: 8-14) months and 6 (5-8) months for SOC, respectively (p<0.0001 and p=0.009). Adverse events occurred in 80% (79/99) of IRE patients and 95% (36/38) of SOC patients; 29% (29/99) of the IRE cohort experiencing an IRE-related adverse event. Conclusions IRE was associated with improved OS versus SOC alone and may be an effective consolidative treatment for Stage 3 PDAC after three months of induction chemotherapy.

Purpose: Beyond estrogen receptor (ER) positivity, no genomic biomarker reliably identifies ER+ breast cancer patients who derive differential benefit from endocrine therapy (ET). We performed an unbiased genomic screen to discover genes predicting ET response and characterized the top candidate across clinical settings, treatment modalities, and an independent validation cohort. Experimental Design: We screened 240 genes in 1,197 metastatic ET-treated patients from the MSK-CHORD clinical genomics database using Cox proportional hazards regression with false discovery rate (FDR) correction. The top candidate, core-binding factor subunit beta (CBFB), was characterized across four cohorts defined by disease setting (metastatic/adjuvant) and treatment (ET/chemotherapy), with multivariable adjustment, gene-by-treatment interaction testing, left-truncation sensitivity analysis for guarantee-time bias, and external validation in METABRIC (N = 1,499 ER+). Results: CBFB mutations (prevalence, ~5%) were the only gene associated with improved time to progression (TTP). In metastatic ET patients, CBFB-mutated tumors (n = 80) demonstrated significantly longer TTP (hazard ratio [HR], 0.44; 95% CI, 0.29-0.67; P = .0002, FDR q = .010) with no chemotherapy benefit (HR, 1.16; P = .65). The gene-by-treatment interaction was significant (HR, 0.37; P = .009). Effects were robust to multivariable adjustment (HR, 0.46-0.50), independent of histology, and preserved under left-truncated Cox regression (HR, 0.38). In the adjuvant setting, CBFB mutations predicted improved recurrence-free survival (HR, 0.52; 95% CI, 0.31-0.85; P = .010), with no effect under chemotherapy. In METABRIC, CBFB mutations predicted improved ER+ overall survival (HR, 0.52; P = 9.3e-5). Conclusions: CBFB mutations identify ~5% of ER+ breast cancers with exceptional ET benefit. As CBFB is included on all major cancer gene panels, this biomarker requires no additional testing infrastructure for clinical implementation.

Background: Lung cancer in never-smokers is rising, with a substantial proportion harboring the EGFR mutation. While fine particulate matter (PM2.5) is a recognized risk factor, other intervenable pollutants and built environmental factors remain unknown. Objectives: To identify urban characteristics associated with EGFR-mutant (vs. wild-type) lung cancer using high-resolution spatiotemporal data. Methods: We analyzed 2,699 lung cancer patients with documented EGFR status treated at a high-volume academic medical center in New York City. Patient residential addresses were linked to high-resolution (300m x 300m) 5-year cumulative exposures to 3 air pollutants and 26 urban features. We developed Light Gradient Boosting Machine (LightGBM) models to classify EGFR status, comparing a basic clinical model with established predictors (Asian, female, never-smoking status, and adenocarcinoma histology) to an extended model with additional urban factors. Predictive performance was assessed based on discrimination (AUC). Results: We included 2,699 patients, of whom 54.1% were female and 25.8% self-identified as Asian, 11.2% as Black, and 7.4% as Hispanic; and 29% had EGFR-mutated cancer. The extended model showed modest improvements in discrimination (AUC: 0.775 [95% CI, 0.739-0.809] vs. 0.768 [0.723-0.811]), compared to the clinical model. Newly identified factors for EGFR-mutant status included black carbon (BC), nitrogen dioxide (NO2), proximity to airports, reduced access to public transportation, elevated noise levels, and lead exposure. Conclusions: Traffic-related pollutants (BC, NO2) from diesel engines and motor vehicles, and proximity to airports, were among the novel spatiotemporal features associated with EGFR-mutant lung cancer. These results may inform policy interventions.

Importance: Abdominal pain causes roughly 10 million US emergency department (ED) visits annually, most resulting in discharge. Post-discharge courses vary, yet existing risk models predict only whether an ED revisit occurs, not what that revisit outcome will entail. Objective: To evaluate whether Curiosity, a generative medical event foundation model, can predict post-ED-discharge trajectories for adults with abdominal pain, differentiating the timing and severity of expected outcomes. Design: Retrospective cohort study; encounters January 1-December 31, 2022; 30-day follow-up; analysis conducted in 2026. Setting: Epic Cosmos research network (multicenter, population-based, de-identified electronic health record). Participants: Adults ([&ge;]18 years) discharged from the ED with abdominal pain, excluding training-set patients. Random sample of 3,000 drawn from 150,030 eligible patients (65.3% female; median age 47 years [IQR 36-60]). Exposure: ED discharge after evaluation for abdominal pain. Main Outcomes and Measures: Primary: Curiosity model vs. per-task, separately estimated XGBoost models on area under the receiver operating characteristic curve (AUROC) for ED revisit ending in admission (admit-revisit), ED revisit ending in discharge (DC-revisit), and any ED revisit at 72 hours, 7 days, and 30 days. Secondary: trajectory-level accuracy across 36 trajectory classes and edit distance vs XGBoost; calibration of simulated vs observed conditional path probabilities across 45 transitions. Results: Curiosity identified patients at high risk of revisit requiring admission more accurately than XGBoost and differentiated those likely to revisit without admission. Among 3,000 patients, Curiosity's 30-day admit-revisit AUROC was 0.83 (95% CI 0.79-0.87) vs 0.70 (95% CI 0.65-0.75) for XGBoost (DeLong P<.001), and admit-revisit AUC-PR was 0.37 (95% CI 0.29-0.46) against a 4.1% cohort base rate, vs XGBoost 0.13 (95% CI 0.09-0.19). Curiosity identified the most likely trajectory out of 36 possibilities for 45.9% of patients (XGBoost 41.0%; McNemar P<.001), with median edit distance 1.28 vs 1.40 (Wilcoxon P<.001). Median absolute calibration error across 45 transitions was 1.30 percentage points (95% CI 0.32-2.49). Conclusions and Relevance: A generative medical event foundation model produced calibrated trajectory-level predictions and discriminated admit-revisits more effectively than task-specific XGBoost baselines, separating patients that revisited and were admitted from those who revisited and were discharged.

The most recent Psychiatric Genomics Consortium (PGC) genome-wide association study of schizophrenia used the statistical fine-mapping tool FINEMAP to identify 70 genes that were likely to mediate common genetic variant associations with the disorder. Here, we extended that study by using two fine-mapping methods, SuSiE and FINEMAP, applying the methods to loci whose causal variant structure was considered too complex by the PGC, and optimising the proportion of posterior probability required by credible sets of causal SNPs for gene prioritisation. Prioritised gene sets were validated for schizophrenia relevance by testing for enrichment of loss-of-function mutation intolerance (LoFI), and for enrichment of rare deleterious coding variants associated with generalised cognition in UK Biobank, both known characteristics of schizophrenia associated genes. Concordance between FINEMAP and SuSiE was high, with most prioritised genes supported by both methods. Genes prioritised by both methods using a relaxed 80% posterior probability (PP) threshold for defining credible sets (N=98) were as enriched for LoFI and for rare deleterious missense variants associated with generalised cognition as genes prioritised using a more conservative 95% PP threshold (N=87). Loosening the credible set threshold combined with the joint application of SuSiE and FINEMAP increased the yield of prioritised genes by 40%, without reducing the orthogonal evidence for validity. Newly prioritised genes included calcium channel genes, CACNA1I and CACNB2, a glutamate receptor gene, GRM3, and TCF4, which has been previously implicated in schizophrenia.

Background: The choice of hand-drying method affects microbial contamination levels but its economic consequences have not been systematically quantified. Methods: By applying a quantitative microbial risk assessment framework, we translated the documented contamination differential between jet air dryers and paper towels into infection risk estimates, and embedded these into an established health economic model of healthcare-associated infections in NHS hospitals and an illustrative productivity analysis for the EU workforce. Results: The median estimated avoidable HCAI cost attributable to jet air dryer presence in UK NHS clinical areas was 58 million pounds per year, representing 2.1% of total HCAI expenditure for the affected hospital population, with a 50% certainty interval of 33-84 million pounds. Extended to the EU workforce, the same contamination differential implied a median of 1.7 billion euros in annual productivity gains, due to reduced absenteeism, for a shift to use of paper towels in public restrooms. Conclusions: These findings suggest that hand-drying method selection carries measurable economic implications that are not currently reflected in facility management practice. The evidence supports the prioritisation of paper towels in clinical and public settings as a cost-effective infection control measure

Background: Structuring oncology clinical notes into registry-grade variables is essential for research and care but remains labour-intensive and error-prone. Objective: To develop and evaluate a privacy-preserving large language model pipeline for oncology registry abstraction in a real-world clinical setting. Methods: We deployed an open-source Meta Llama 3.3 70B-based pipeline to extract over 50 variables from 6,700 oncology notes at a cancer centre in Singapore. Data were de-identified locally using a Hide-In-Plain-Sight approach, ensuring no identifiable data left hospital infrastructure. Performance was assessed on 200 randomly sampled notes with adjudicated ground truth. A structure-aware framework classified outputs as correct, missing, spurious, or incorrect. Results: F1 scores were high across variables, including diagnosis (97.2%), histology (95.8%), stage (92.6%), biomarkers (91.4%), and treatments (88.1%). Transferability testing on 50 external notes showed strong performance for core variables. Conclusions: Privacy-preserving LLMs can achieve near-human-level accuracy for oncology abstraction, with structure-aware evaluation enabling more clinically meaningful assessment. Keywords: Oncology Registry Abstraction, Privacy-Preserving Deployment, Clinical Information Extraction, Structure-Aware Evaluation, Large Language Models, Template-Filling Metrics

Background: Alzheimers disease (AD) is a multifactorial neurodegenerative disorder in which copper dyshomeostasis, mitochondrial stress, oxidative injury and immune dysregulation may contribute to pathogenesis. Cuproptosis, a copper-triggered regulated cell death pathway, has emerged as a potential mechanistic link to AD, but its therapeutic and biomarker implications remain incompletely defined. Methods: We integrated transcriptomic, machine learning, immune infiltration, QSFR, molecular docking, docking validation and ADME analyses using GEO blood- and brain-based AD cohorts. Differentially expressed genes were intersected with curated cuproptosis-related genes, followed by pathway enrichment, construction and validation of a hybrid ensemble classifier, CIBERSORT-based immune correlation analysis, QSFR-driven target prioritization, ligand docking, consensus docking validation and SwissADME profiling. Results: The transcriptomic analyses revealed reproducible AD associated signatures enriched in neurodegenerative, oxidative stress, mitochondrial and inflammatory pathways. Across multiple machine learning models, FDX1, PDHB, PDHA1, DLAT and DLD consistently emerged as the most important cuproptosis-related genes, with the hybrid ensemble achieving the best diagnostic performance. Immune profiling suggested that these genes are linked to distinct immune infiltration patterns. QSFR and docking prioritized FDX1 as a key target and Clioquinol, PBT2 and Ebselen showed the strongest and most consistent binding behavior. Docking validation confirmed reliable pose reproduction and enrichment over decoys, while ADME analysis supported Clioquinol, PBT2 and Ebselen as the most balanced candidates for further consideration. Conclusion: This integrated workflow identifies a cuproptosis-centered mitochondrial gene module as a robust AD signature and highlights Clioquinol, PBT2 and Ebselen as promising repurposing candidates. The findings provide a prioritized computational framework for future experimental validation of copper-linked therapeutic strategies in AD.

Background Smartphone ownership among UK adolescents is near universal. Teachers report phones increasingly being involved in classroom disruption, and misuse during school hours is among the more common serious behavioural issues in secondary schools. Evidence on whether restrictive policies improve behaviour, attainment, or wellbeing remains limited. Objectives The primary objective is to assess the impact of a lockable smartphone pouch on educational attainment and behaviour. Secondary objectives are to assess impacts on general functioning, psychological wellbeing, and school level indicators such as exclusions, and to examine whether effects differ for pupils who may be most at risk. Methods We will conduct a mixed methods cohort study in secondary schools across Northern Ireland and England during the 2025 to 2026 academic year. The quantitative component uses a serial cross sectional design. Students will complete an online questionnaire at 0, 4 weeks, and 8 weeks, covering homework completion, classroom disruption, participation in PE and extracurricular activities, peer interaction during break, and patterns of smartphone use. Measures include the Strengths and Difficulties Questionnaire (SDQ), the Revised Child Anxiety and Depression Scale (RCADS), the short form of the Smartphone Addiction Scale (SAS SV), and the Bergen Social Media Addiction Scale (BSMAS). Each participating school will also supply half termly aggregate data on exclusions, detentions, CAMHS referrals, counsellor visits, and parent visits between September 2023 and May 2026. Assuming 90% power, a two-sided type 1 error of 0.05, an intracluster correlation of 0.02, and 25% loss to follow up, we aim to recruit a minimum of 3,200 students from six or more schools to detect a small effect (Cohen's d = 0.2) on SDQ hyperactivity score. Continuous outcomes will be analysed with linear regression and binary outcomes with logistic regression. Prespecified subgroup analyses cover SEN or neurodivergent status, area level deprivation, and which phone policy is in place at each school. Qualitative analyses comprise focus groups with students and staff at each participating school and semi-structured interviews with school leads. Transcripts will be coded both inductively and deductively and analysed thematically with Braun and Clarke's six phase approach. Ethics and Dissemination The study has been approved by the King's College London Research Ethics Committee. A Data Protection Impact Assessment has been agreed with the Northern Ireland Department of Education. Findings will be published in peer reviewed journals and shared with participating schools, parents, and policy makers to inform smartphone policy in schools.

Background Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy that often requires prolonged corticosteroid therapy which is associated with adverse effects. Methotrexate is an affordable immunomodulatory agent with limited evidence for its use in ENL treatment. We evaluated whether weekly oral methotrexate in additional to prednisolone reduces the need for additional prednisolone in adults with severe ENL. Methods and Findings We performed an international, multicentre, double-blind, randomised, placebo-controlled trial conducted at five leprosy referral centres in Ethiopia, India, Indonesia, and Nepal. Adults aged 18-60 years with severe ENL were randomised to receive oral methotrexate and prednisolone, or matching placebo and prednisolone. All participants received an identical prednisolone regime over 20 weeks and were followed for 60 weeks. The primary outcome was time to first ENL flare requiring additional prednisolone, assessed over 24 and 48 weeks. Between January 2023 and June 2024, 231 individuals were screened and 137 were randomised (68 methotrexate and prednisolone; 69 placebo and prednisolone). By 24 weeks, 85/137 (62.0%) participants experienced an ENL flare requiring additional prednisolone; the adjusted hazard ratio (HR) for methotrexate versus placebo was 0.98 (95% CI 0.62-1.54). By 48 weeks, 102/137 (74.5%) experienced an ENL flare; adjusted HR 0.95 (95% CI 0.62-1.43). Secondary outcomes were similar: methotrexate did not reduce ENL severity at first flare, flare frequency, or severity of subsequent flares. Health-related quality of life improved substantially in both groups with no evidence of a differential treatment effect. Methotrexate was generally well tolerated. The trial was registered at ClinicalTrials.gov (NCT03775460). Conclusions Oral methotrexate added to prednisolone did not reduce the requirement for additional prednisolone or delay ENL flares compared to placebo and prednisolone, and our study does not support the use of methotrexate for severe ENL.