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Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12&#x202f;cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B)&#x202f;&#x2248;&#x202f;9, coefficient of variance (CV)&#x202f;<&#x202f;10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus

Molecular Diagnostics for WHO Priority Bacterial Pathogens: A Bibliometric Mapping of Diagnostic Platforms, Resistance Markers, and Antimicrobial Resistance Research Trends.

Antimicrobial resistance (AMR) constrains effective treatment and carries implications for infection control, surveillance, and public health. The World Health Organization (WHO) priority bacterial pathogen framework has intensified the need for diagnostic innovation by redefining research priorities around organisms combining high disease burden with complex resistance profiles. Molecular diagnostics have accordingly moved beyond culture-based workflows, integrating rapid pathogen identification, resistance-marker detection, genomic surveillance, and clinical decision support. The present study conducted a bibliometric mapping of the literature on WHO priority pathogens. Rather than addressing resistance at a general level or a single pathogen or technology, it integrates priority pathogens, molecular platforms, and resistance markers within a single framework, tracing their joint thematic and temporal evolution along an explicit pathogen-platform-marker axis. Scopus-indexed articles and reviews (2000-2025) were retrieved, yielding 1746 publications after screening adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analyses used Bibliometrix/Biblioshiny, R, and VOSviewer. The literature expanded markedly after 2018, led by China and the United States. Methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis, Enterococcus faecium, and the Enterobacterales-carbapenemase axis constituted the principal thematic cores, whereas conventional polymerase chain reaction (PCR)/nucleic acid amplification testing (NAAT) and whole-genome sequencing were the dominant platforms. Overall, the field has evolved from pathogen detection into an AMR-centered translational domain encompassing resistance prediction, genomic epidemiology, surveillance, and clinical decision support. Diagnostic development, stewardship, and surveillance depend on hybrid workflows coupling rapid marker-targeted assays with genome-based characterization, delivering actionable resistance within clinically meaningful timeframes, and extending coverage to underrepresented pathogens and platforms.

Humans

Social Responsiveness as a Mediator in Adapted Cognitive Behavioral Therapy for Autistic Youth with Maladaptive and Interfering Anxiety.

Numerous adaptations to interventions have been included in cognitive behavioral therapy (CBT) for autistic youth. This study examines the degree to which CBT adapted to the social needs of autistic youth confers significant benefit by promoting social responsiveness. A secondary analysis was conducted on a multisite randomized clinical trial (Wood et al. in JAMA Psychiatry 77:474-483, 2020) comparing adapted CBT with standard-of-practice CBT and treatment-as-usual (TA). Autistic youth (N&#x2009;=&#x2009;167; aged 7-13) with maladaptive and interfering anxiety participated. The adapted CBT (BIACA) uses a modular format, with an emphasis on supplementing common CBT practice elements (reframing and graded exposure) with social skill supports. The primary outcome measure was the Pediatric Anxiety Rating Scale. Social responsiveness was assessed with the Social Responsiveness Scale, Second Edition. Participants' general mental health was assessed as a secondary outcome using the Brief Problem Checklist. Mediation was tested using the SPSS PROCESS macro. Analyses suggested that the effect of adapted CBT on anxiety was mediated by its effects on social responsiveness, with a statistically significant indirect effect. Youth randomly assigned to adapted CBT exhibited better overall mental health at posttreatment compared to those randomized to the other conditions, and this effect was also mediated by improved social responsiveness. CBT adapted to address some of the social needs of autistic youth may enhance mental health outcomes by supporting social responsiveness, perhaps increasing the ease and effectiveness with which some youth can navigate potentially stressful situations such as entering and participating in group activities.

Humans

Self-selected goals outperform assigned goals in reducing mobile phone usage: Evidence from a randomized controlled trial.

Excessive smartphone use is increasingly recognized as a public-health concern, yet scalable approaches to help individuals regulate daily use remain limited. We examine whether allowing individuals to self-select reduction goals improves behavioral and psychological outcomes when incentives and average goal levels are held constant across conditions. In a twelve-week randomized controlled trial, (N&#x202f;=&#x202f;149; over 9000 person-day observations), participants were assigned to (i) a self-selected condition (choosing a 10%, 20%, or 30% reduction in daily phone use), (ii) an assigned condition (assigned a 14% reduction goal), or (iii) a no-goal control condition. Participants who selected their own goals reduced phone use by 26&#x202f;min more per day (73% larger reduction) and achieved their goals 11 percentage points more often than those assigned goals, despite identical incentives and average goal levels. Reductions in phone use and higher goal achievement were associated with improvements in perceived addiction, depressive, and anxiety symptoms. These psychological outcomes were secondary endpoints. Although the between-group estimates generally followed the same directional pattern as the behavioral outcomes, the sample size for these analyses was limited and the between-group differences were not statistically significant. These findings should therefore be interpreted with caution. Overall, the results provide causal field evidence that self-selection under this goal-setting design can improve behavioral outcomes. Allowing individuals to choose their own goals may strengthen engagement and support healthier digital behavior. Incorporating opportunities for goal-selection may represent a simple addition to digital-health and public-health interventions aimed at helping individuals moderate smartphone use and improve well-being.

Humans

Evaluating a coaching intervention for Dementia Care Practice Recommendations in care communities: a cluster randomized controlled trial.

BACKGROUND AND OBJECTIVES: Within care communities, including nursing home and assisted living settings, person-centered dementia care, outlined by the 2018 Alzheimer's Association Dementia Care Practice Recommendations (DCPR), is foundational to quality care and improving staff outcomes. This study evaluates the effectiveness of a 6-month Care Community Coaching Program in enhancing person-centered dementia care and staff outcomes in alignment with the DCPR. RESEARCH DESIGN AND METHODS: A cluster randomized controlled trial was conducted with 77 care communities and 434 staff members-227 from 38 intervention communities and 207 from 39 control communities. Outcomes included employee satisfaction (areas: job satisfaction, team building and communication, scheduling and staffing, training, and management and leadership), person-centered care practices (areas: workplace practices, individualized care and services, caregiver-resident relationships), and dementia care confidence, measured pre- and post-intervention and at 3-month follow-up. A generalized Estimating Equations model was used to estimate intervention effects. RESULTS: Care communities assigned to the coaching intervention showed statistically significant improvements in employee satisfaction and staff perceptions of workplace practices and individualized care. No statistically significant effects on staff perceptions of caregiver-resident relationships or on dementia care confidence were noted. DISCUSSION AND IMPLICATIONS: Findings provide direction for future research and intervention development, including examining coaching's impact on resident quality outcomes, and incorporating skills training into future models. Collectively, findings provide evidence of the effectiveness of a Care Community Coaching Program in improving staff outcomes and person-centered practices, offering a practical path towards improving the lived experience of residents and staff in care communities.

Humans

An introductory practical guide to secondary data analysis in pediatric urology.

INTRODUCTION: Secondary data analysis (SDA) has become an increasingly important approach in pediatric urology, enabling the study of long-term outcomes, care variation, and disparities in populations with chronic or congenital urologic conditions. With the growing availability of large datasets, a structured approach to designing and conducting SDA studies is increasingly relevant. OBJECTIVES: To provide an introductory, practical guide to SDA in pediatric urology by (1) summarizing commonly used data sources with representative studies, (2) outlining a stepwise approach to designing and executing SDA studies, and (3) highlighting key methodological considerations, limitations, and opportunities for future work. STUDY DESIGN: Narrative review of existing literature and commonly used datasets relevant to pediatric urology, including administrative claims, hospital encounter databases, clinical registries, electronic health record networks, and population-based surveys. RESULTS: Data sources differ in scope, clinical granularity, longitudinal follow-up, and representativeness, and each is suited to specific research questions. We present a practical workflow for SDA, including dataset selection, cohort definition, and analytic planning. Linkage across datasets can provide a more comprehensive view of care patterns and outcomes, although feasibility is influenced by legal, technical, and data-quality constraints. DISCUSSION: SDA enables population-level analyses and the study of rare conditions that are challenging to evaluate through single-center or prospective designs. However, careful cohort definition, feasibility assessment, and awareness of data limitations are essential to ensure validity and interpretability. CONCLUSION: SDA provides a scalable, cost-efficient framework for generating meaningful evidence in pediatric urology. Continued efforts to harmonize data elements, improve linkage infrastructure, and support cross-institution collaboration will enhance the quality and impact of future research. This article provides a practical framework and examples to support the design and execution of SDA studies.

Humans

Leading with Innovation: Maternal Health Transformation in New York City Health + Hospitals.

New York City's (NYC) maternal health crisis drew close attention in the late 2010s, driven by alarming data: Approximately 30 women died annually during childbirth in NYC, Black non-Hispanic women were 12 times more likely to die than white women, and more than 3,000 women experienced life-threatening birth complications each year. In response, NYC committed $12.8 million in July 2018 to reduce maternal mortality and eliminate racial disparities.NYC Health + Hospitals (H+H)-the nation's largest public health system, serving 1.1 million patients annually with roughly 15,000 births per year-became the primary vehicle for this initiative. With 80 percent of the system's deliveries covered by Medicaid and a patient population that is 51.2 percent Hispanic and 27.1 percent Black, H+H is uniquely positioned to lead the fight against maternal health inequity.Three flagship programs anchor H+H's response to the city's maternal mortality rate. The OB Simulation Program, launched in 2012 and expanded in 2018, was the first in the nation to use mannequins of color to train thousands of providers in obstetric emergencies. The Maternal Home Program, piloted at H+H's Kings County Hospital in 2019 and scaled system-wide by 2021, has served more than 10,341 patients, generating more than 33,000 referrals for social, behavioral health, and community resources. The Cardio-Obstetrics Program located at Kings County Hospital targets cardiovascular disease-the leading cause of maternal death among Black women-through screening, education, and community outreach. These programs are a health equity imperative, made more urgent by impending federal Medicaid cuts resulting from the H.R.1 One Big Beautiful Bill Act (passed on July 4, 2025).

Humans

Distinct molecular responses to acute cold exposure revealed by comparative transcriptomic and metabolomic profiling in the bay scallop Argopecten irradians.

Acute cold stress can elicit distinct molecular responses even when bay scallop populations show similar phenotypic outcomes. We compared a seventh-generation fast-growing bay scallop line (BS) with a commercial control population (CC) during a 72-h acute cold exposure at -1&#xa0;&#xb1;&#xa0;0.3&#xa0;&#xb0;C. RNA-seq was used as the discovery layer, representative BS cold-responsive genes were evaluated by qRT-PCR, and paired LC-MS profiles provided a comparative metabolic layer. At baseline, 138 genes differed between BS and CC; after cold exposure, 134 of these baseline differences disappeared and 61 of 65 cold-state differences newly emerged. BS showed a larger transcriptomic response magnitude than CC, with 1129 cold-responsive genes compared with 28 genes in CC, and this ordering remained robust across multiple sensitivity analyses. Survival after 72&#xa0;h was identical in BS and CC (83/90, 92.2% in each population). Biochemical responses were time-dependent and marker-specific: CAT, LZM, T-SOD and T-AOC showed population-by-time interactions, whereas GSH-Px and MDA did not, and the 72-h differences were not consistently favourable to BS. Metabolomic cold effects were strongly concordant between populations, and no feature showed a significant population-by-cold interaction. Features putatively assigned to arachidonic acid metabolism were enriched, but this provider-annotated pathway signal remains exploratory because authentic-standard confirmation was not performed. These findings indicate population-specific differences in molecular responsiveness but do not establish superior cold tolerance in BS.

Animals

Perioperative safety and survival outcomes of robot-assisted partial nephrectomy in elderly patients with localized renal cell carcinoma: an overlap-weighted Asian cohort study.

The value of robot-assisted partial nephrectomy (RAPN) in elderly Asian patients with localized renal cell carcinoma (RCC) remains insufficiently defined. We retrospectively analyzed 339 patients (&#x2265;&#x2009;70 years) with localized RCC treated at a single Asian center between 2015 and 2025, including 119 undergoing partial nephrectomy (PN) and 220 undergoing radical nephrectomy (RN). Propensity score overlap weighting (OW) was applied to compare PN versus RN and, within the PN cohort, RAPN versus laparoscopic partial nephrectomy (LPN). Three open partial nephrectomy cases were summarized descriptively and retained only in exploratory sensitivity analyses. Weighted logistic regression and Cox models with robust standard errors evaluated Clavien-Dindo grade&#x2009;&#x2265;&#x2009;II complications and overall survival (OS). After OW, PN was associated with better early postoperative renal functional preservation than RN but a greater incidence of grade&#x2009;&#x2265;&#x2009;II complications (36.4% vs. 17.6%; weighted p&#x2009;<&#x2009;0.001); OS was similar. Within the PN cohort, RAPN had longer operative time than LPN (weighted p&#x2009;=&#x2009;0.030), whereas warm ischemia time, early postoperative eGFR, and grade&#x2009;&#x2265;&#x2009;II complications (31.8% vs. 40.4%; weighted p&#x2009;=&#x2009;0.414) were not significantly different. Exploratory analyses favored RAPN, but only one death occurred in this group, and residual confounding remains possible. PN may preserve early renal function in selected older patients, while RAPN appears feasible in experienced centers; its survival association remains hypothesis-generating.

Humans

Comprehensive multi-post-translational modifications profiling reveals age-associated remodeling in skeletal muscle.

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a major hallmark of aging. Post-translational modifications (PTMs) play essential roles in regulating protein activity and cellular homeostasis; however, how multiple PTMs are remodeled during skeletal muscle aging remains incompletely characterized. Here, we performed comprehensive multi-layered proteomic profiling of skeletal muscle from young (3-month-old) and aged (24-month-old) mice, systematically quantifying the global proteome together with five major PTMs: acetylation, phosphorylation, N-glycosylation, O-glycosylation, and ubiquitination. In total, we identified 5 337 proteins and mapped thousands of PTM sites, generating an integrated atlas of age-associated proteomic and PTM remodeling in skeletal muscle. Pathway enrichment analyses revealed distinct modification-specific patterns: acetylation and phosphorylation were predominantly associated with metabolic and mitochondrial-related pathways; N-glycosylation was enriched in immune- and secretory pathway-related processes; O-glycosylation was associated with muscle contraction-related pathways; and ubiquitination was preferentially linked to cytoskeletal organization in muscle cells. Correlation analyses further uncovered diverse association patterns among different PTMs across protein- and modification-level datasets. Phosphorylation and ubiquitination exhibited consistent positive associations, whereas acetylation and ubiquitination showed both inverse and concordant co-variation patterns across subsets of proteins. Phosphorylation and O-glycosylation displayed heterogeneous association patterns across different proteins, and acetylation and phosphorylation demonstrated positive correlations with distinct age-associated directional changes across protein subsets. Together, these results provide a comprehensive, multi-dimensional view of age-associated remodeling of the skeletal muscle proteome and multiple PTM layers, offering a valuable resource for understanding molecular alterations accompanying muscle aging and sarcopenia.

Animals

Neighborhood Hostility is Associated With the Relationship Between Park Proximity and Physical Activity Among Youth: National Evidence From Chile.

PURPOSE: Physical inactivity among youth is highly prevalent worldwide. Although proximity to parks and recreational facilities is generally associated with higher physical activity (PA), unsafe or hostile neighborhood environments may limit their use. This study examined whether neighborhood hostility moderates the association between access to recreational facilities and adherence to World Health Organization PA guidelines among Chilean youth. METHODS: This cross-sectional study analyzed data from the 2024 National Physical Activity and Sport Survey of Chile, including 3,477 urban participants stratified into childhood (5-10 years), early adolescence (11-13 years), and late adolescence (14-17 years). Built environment exposures included perceived access to recreational facilities, a cumulative neighborhood hostility score (0-5). Logistic regression models were stratified by age group and adjusted for covariates. Interaction terms assessed moderation by neighborhood hostility, and causal mediation analyses were performed. RESULTS: Adherence to World Health Organization guidelines was low (41.9% in childhood, 43.8% in early adolescence, and 43.9% in late adolescence). Greater distance to recreational facilities was associated with lower odds of meeting activity guidelines. Higher neighborhood hostility was independently associated with lower PA levels. Among adolescents, neighborhood hostility substantially attenuated the association between proximity and activity. Mediation analyses indicated partial mediation, with effective park utilization emerging as the strongest mechanism, accounting for 21.8% of the association (p < .001), followed by psychological motivation (11.9%). DISCUSSION: Proximity to recreational infrastructure alone is insufficient to promote PA in hostile neighborhoods. Policy approaches should integrate infrastructure provision with strategies addressing neighborhood safety and promoting active engagement.

Humans

Robust optimisation for photon radiotherapy: A scoping review of models, paradigms, and reporting.

BACKGROUND AND PURPOSE: Robust optimisation offers an alternative to conventional margin-based photon radiotherapy planning by explicitly modelling uncertainty, but practice is variable and not standardised. MATERIALS AND METHODS: A scoping review was conducted to map robust optimisation for photon external beam radiotherapy. Electronic searches of Scopus, PubMed and Google Scholar (2000-2025, English language) identified planning studies that incorporated modelled uncertainties into the optimisation process and reported at least one robustness-related outcome. Data were charted on clinical context, uncertainty models, optimisation paradigms, robustness metrics and evidence for clinical implementation. RESULTS: Seventy-one studies were included. Most investigated prostate, breast or lung cancer and used intensity-modulated radiotherapy or volumetric-modulated arc therapy in commercial or research treatment planning systems. Scenario-based worst-case (minimax) optimisation was the dominant paradigm in clinically oriented work, while chance-constrained, conditional value at-risk, distributionally robust and adaptive formulations were confined to small methodological series. Uncertainty modelling focused mainly on rigid set-up error; fewer studies incorporated respiratory motion, inter-fraction anatomical change, dose-calculation uncertainty or biological variation. Robustness was evaluated with diverse scenario-based dose-volume metrics, probabilistic coverage measures, composite robustness indices and, less often, biological endpoints. Direct clinical implementation reports were scarce. CONCLUSION: Robust photon planning is technically feasible and generally maintains or improves target coverage and organ sparing compared with margin-based planning. However, heterogeneity in uncertainty models, optimisation configuration and robustness reporting limits comparison and synthesis. Pragmatic minimum standards are proposed to support future consensus and wider clinical adoption.

Humans

Saliva-based RT-LAMP assays support heat shock protein 70 as a promising transcript marker for estrus identification in buffaloes.

Buffaloes do not exhibit overt estrus signs particularly during summer, leading to a significant economic loss to farmers. Previous studies have identified several candidate transcripts (HSP70, TIMP1, TLR4 and HSD17B1), abundant in buffalo saliva during estrus stage. However, there is no widely applicable technology for estrus detection targeting these transcripts. Therefore, the present study aimed to develop reverse transcription loop mediated isothermal amplification (RT-LAMP) assays for these candidate transcripts using buffalo saliva. Saliva samples were collected from 10 cyclic buffaloes and RT-LAMP assays were optimized for salivary RNA as well as direct saliva. Among the four candidate transcripts, HSP70 showed a statistically significant colour change (p-value&#x2009;=&#x2009;0.0191) at the estrus stage compared to the diestrus stage. This abundance of HSP70 was also supported in large simulated population datasets (10,000 animals) generated using R. Further, the RT-LAMP assays were tested using direct saliva without RNA isolation, and the colour change in the samples during estrus suggested the feasibility of estrus identification using direct saliva, overcoming the tedious step of RNA isolation. The detection of HSP70 using either direct saliva or salivary RNA indicated its potential as a marker for estrus identification. Similarly, TLR4 appeared to be another potential biomarker for RT-LAMP reaction using direct saliva, but it needs further validation in both RNA and direct saliva samples. Overall, the proof-of-concept on RT-LAMP assays optimized for salivary transcripts in the present study would be useful for estrus identification in tropical production systems following further validation on a larger sample size.

Animals

Transcriptomic changes in the gut mucosa of fasting northern elephant seal pups reveal immune modulation during early microbiome establishment.

Fasting is an integral component of the life-history of many species. Following abrupt weaning, northern elephant seal pups (Mirounga angustirostris) undergo an extended post-weaning fast of approximately 60&#xa0;days. During this period, enteric bacterial diversity increases, suggesting that host immune regulation may facilitate the establishment of microbial communities. However, the molecular processes occurring within the intestinal mucosa during this transition remain poorly understood. To investigate these mechanisms, we characterized transcriptional changes in the enteric mucosa of male and female northern elephant seal pups sampled at weaning and after one month of fasting. Total RNA isolated from rectal swabs was sequenced and aligned to the Mirounga angustirostris reference genome. Differential gene expression and gene set enrichment analyses were used to identify genes and pathways associated with fasting and sex-specific responses. Fasting was accompanied primarily by transcriptional downregulation, including genes involved in antimicrobial defense, inflammation, protein turnover, and epithelial remodeling. In contrast, several genes associated with B-cell activity and immune recognition were upregulated. Gene Set Enrichment Analysis revealed coordinated activation of immune-regulatory pathways indicating dynamic modulation of intestinal immunity rather than generalized immune suppression. Pronounced sex-specific differences were also observed. Male pups exhibited transcriptional patterns consistent with enhanced immune tolerance, whereas females showed broader immune-pathway activation, including enrichment of pro-inflammatory and stress-response pathways. Several non-coding RNAs also displayed sex-specific changes in expression. Together, these findings suggest that fasting induces transcriptional remodeling of the gut and may contribute to immune regulation during a critical period of microbiome establishment in northern elephant seal pups.

Animals

Non-smoked cannabis consumption formats and Cannabis Use Disorder severity in an illicit setting: Evidence from Chile, 2020-2024.

BACKGROUND: Cannabis Use Disorder (CUD) has become an increasing public health burden, particularly in Chile. Non-smoked cannabis formats and products have been independently associated with CUD but remain understudied in the region. This study compares CUD severity among individuals aged 12 to 65 in Chile who consume cannabis via edibles, vaporization or both versus those who exclusively smoke it. METHODS: We obtained secondary data from three waves of the Chilean National Survey on Drugs in the General Population (ENPG), a three-stage stratified probabilistic sampling design study conducted in 2020, 2022, and 2024. Our pooled cross-sectional sample included individuals (n = 3543) who reported cannabis use in vaped, edible, both vaped and edible or exclusively smoked format in the past 12 months. We used a partial proportional odds model to estimate the association between CUD severity and consumption formats. RESULTS: Cannabis vaping group showed higher odds of presenting at least mild CUD (OR = 6.21 [95% CI: 3.75-10.3]), as did the edible group (OR = 1.73 [95% CI: 1.08-2.78]) and both group (OR = 5.92 [95% CI: 2.72-12.87]), compared to exclusive smokers. However, only the vaped group demonstrated higher odds for all severity levels. CONCLUSION: Compared with exclusive smokers, users of vaporizers and/or edibles showed a stronger association with CUD. This association may be explained by consumption patterns and total THC exposure. Further research is needed to characterize the average THC exposure by consumption format, acknowledging contextual confounders such as the legal framework.

Humans

Safety of early discharge and abbreviated nimodipine course in patients with good-grade aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular emergency associated with substantial morbidity and mortality. Current guidelines recommend 14-21&#xa0;days of inpatient monitoring and a 21-day course of nimodipine following aSAH. This retrospective study evaluates early outcomes early discharge (&#x2264;14&#xa0;days post-ictus) and an abbreviated nimodipine course in highly selected patients with good-grade aSAH managed under a standardized institutional protocol. Consecutive patients enrolled in the Vancouver Ruptured Aneurysm Database (VRAD) at Vancouver General Hospital between 2022 and 2025 were included. Inclusion criteria were good-grade aSAH (WFNS Grade I-III) and discharge home within 14&#xa0;days of ictus. The primary outcome was re-presentation to emergency care within 30&#xa0;days of discharge; secondary outcomes included hospital readmission and need for additional treatment. Of 333 total patients in VRAD, 49 patients met inclusion criteria. All patients received&#xa0;&#x2264;&#xa0;14&#xa0;days of nimodipine therapy. Forty-two patients (85.7%) were WFNS Grade I on presentation, 3 (6.1%) were WFNS Grade II, and 4 (8.2%) were WFNS Grade III. Radiographic vasospasm was reported in 18 cases (36.7%). No patients developed DCI or clinical vasospasm. Four patients (8.2%) re-presented to emergency care within 30&#xa0;days of discharge, and only one patient (2%) required hospital re-admission within 30&#xa0;days. While radiographic vasospasm was seen in over one third of patients, none developed clinical sequelae, supporting the premise that radiographic vasospasm alone may be insufficient to preclude early discharge in select good-grade patients.

Humans

Psychotherapy training in psychiatry: a systematic review and narrative synthesis on the supervision experiences of early-career psychiatrists.

BACKGROUND: Supervision is a fundamental component of psychotherapy training, transforming theoretical knowledge into clinical skills through real-world practice. Psychotherapy training practices vary widely between countries, training programs, and over time, including supervision. Our systematic review aimed to investigate and describe the experiences of psychotherapy supervision through early-career psychiatrists' (ECPs) views. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and PubPsych for survey-based studies on ECPs' experiences of psychotherapy supervision during or after their psychiatry training and reported our findings according to the PRISMA guidelines. Of 32,877 articles screened, 29 articles were included. Each article underwent quality assessment, and results were synthesized narratively. RESULTS: Included articles published between 2000 and 2025, were from Europe (N = 16, 55.1%), the Americas (N = 5, 17.2%), Western Pacific (N = 4, 13.7%), South-East Asia (N = 2, 7%), Eastern Mediterranean (N = 1, 3.5%), and Africa (N = 1, 3.5%), with a total of 4691 participants. Supervision access rates ranged from 26.2% in Nigeria to 85.5% in Russia, with significant variation across countries and psychotherapy modalities. Most ECPs received 50-100 total hours of supervision, frequently delivered in weekly sessions. While formats, individual, group, or mixed, varied by country and training scheme, supervision was generally provided by a psychiatrist-psychotherapist. Common learning techniques included oral consultations and case discussions, followed by audio recordings or transcripts. The need to self-fund psychotherapy supervision costs was identified as a prominent barrier. CONCLUSIONS: Psychotherapy supervision is inconsistent globally, with barriers including supervisor availability and cost. There is a large implementation gap between recommendations and evaluated practice. Digital tools and competency-based frameworks may improve access and quality.

Humans

Genomic characterization of a hypervirulent Aeromonas veronii NN0115 from Nile tilapia and head kidney transcriptome of infected fish reveals B-cell-dominated immune response with specific immunoglobulin downregulation.

Aeromonas veronii is a pathogen of multiple fish species, yet systematic understanding of its infection in Nile tilapia (Oreochromis niloticus) remains limited. A dominant strain, NN0115, was isolated from a natural outbreak and identified as A. veronii by 16S rRNA and whole-genome average nucleotide identity (ANI, 96.33%). Experimental infection revealed high virulence (LD50&#x202f;=&#x202f;3.41&#x202f;&#xd7;&#x202f;106&#x202f;CFU/mL, equivalent to 8.53&#x202f;&#xd7;&#x202f;104&#x202f;CFU/fish). The genome is 4.58&#x202f;Mb (58.57% GC) and encodes 4216 proteins. Virulence factor analysis identified 1253 genes, dominated by motility-related (264) and immune modulation (208) factors. Genomic island GI2 harbors 7 virulence genes and two dual-function resistance-virulence genes. The strain is resistant to 9 of 25 agents tested but carries three RND efflux pump genes whose predicted resistance was not phenotypically observed. The head kidney transcriptome of tilapia at 24&#x202f;h post-bacterial infection identified 773 differentially expressed genes; among them, 57 were immunoglobulin (Ig) genes, and 56 were down-regulated. Integration of published single-cell transcriptomic data showed that non-Ig B-cell marker genes were down-regulated by 32%, whereas Ig genes were reduced by 63%, indicating selective transcriptional suppression of Ig genes rather than a general decrease in B-cell transcriptional activity. Together, this study provides a comprehensive characterization of a highly virulent A. veronii from Nile tilapia and reveals that selective downregulation of B-cell Ig genes is the dominant transcriptional feature of the host head kidney response.

Animals