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Exploring hormonal influences on nicotine craving and use across the perinatal period: A prospective longitudinal study.

INTRODUCTION: Perinatal nicotine use is common despite well-documented adverse consequences. We examined associations between reproductive-related hormones with nicotine craving and use during the perinatal period to identify potential novel intervention points. METHODS: All participants reported use of nicotine during the perinatal period. Participants were enrolled at gestational week ≥ 36 and followed to postpartum week 12 via daily surveys (i.e., nicotine craving via 100-point scale, dichotomous use) and weekly hormone measurement in saliva (cortisol, oxytocin) or dried blood spots (progesterone, estradiol, testosterone, dehydroepiandrosterone sulfate). Bayesian mixed-effects models accounted for within-person correlation while estimating hormone effects. RESULTS: Participants (n = 46) were 28.9 ± 4.9 years old. During follow-up, exclusive combustible cigarettes (n = 20), electronic nicotine delivery systems (ENDS; n = 13), or dual (n = 2) use was observed, with variability in use and craving across participants and over time. During pregnancy, higher oxytocin was linked to greater craving (β=16.31, 95% CI: 3.71, 28.83). Greater peripartum declines in oxytocin were associated with more craving (β=8.71, 95% CI: 0.75, 16.93) and use (β=1.13, 95% CI: 0.05, 2.43). During postpartum, lower estradiol was linked to more craving (β=-1.17, 95% CI: -2.15, -0.18) and use (β=-0.40, 95% CI: -0.76, -0.03). In models simultaneously evaluating all postpartum hormones, the lone meaningful association was between estradiol and craving (β=-1.66, 95% CI: -2.84, -0.48). CONCLUSIONS: The results of this study suggest that oxytocin and estradiol may contribute to the risk of perinatal nicotine use. Additional research is needed to replicate our observations in more diverse study samples and explore implications for clinical intervention.

Bayesian

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1α axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

Humans

Artificial Intelligence for Diagnosing Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies.

PURPOSE: To identify, appraise, and synthesize the performance of artificial intelligence-based meibography reading as compared with human graders in diagnosing meibomian gland dysfunction. METHODS: We followed Cochrane methodology and reporting guidelines for diagnostic test accuracy reviews. To assess potential risk of bias and applicability, we used a modified Quality Assessment of Diagnostic Accuracy Studies-2 checklist. We applied bivariate logistic models to estimate summary sensitivity and specificity when appropriate and used the GRADE framework to rate the certainty of the evidence. RESULTS: We identified 14 eligible studies involving 5511 predominantly middle-aged participants (average age: 27-55 years) who were primarily female (≥54.5%). A total of 18,926 meibography images were obtained through noncontact infrared (11 studies) or in vivo confocal microscopy (three studies). Two studies reported external validation of deep learning models, 12 reported internally validated models, and one reported both. All but one study had high risk of bias in at least one domain; 12 studies raised high or intermediate concern about applicability. Based on three external evaluations, the summary sensitivity and specificity for diagnosing meibomian gland dysfunction from normal glands were 97.5% (95% confidence interval: 77.5%-99.8%) and 85.5% (95% confidence interval: 47.3%-97.5%). Sources of heterogeneity in internally validated models included study population, case mix, and others. The overall evidence was very low to low certainty because of imprecision, high risk of bias, and concerns about applicability. CONCLUSIONS: Artificial intelligence-based meibography grading appears less accurate than human graders. Future studies should adopt rigorous designs, including a more diverse participant pool (or image set), and external validation.

Humans

Privacy, security, and reliability risks of artificial intelligence in healthcare: a systematic review of empirical evidence.

BACKGROUND: Artificial intelligence (AI) is increasingly integrated into healthcare information systems, supporting clinical decision-making, imaging analysis, and predictive modeling. While these applications offer operational and clinical benefits, they also introduce emerging risks to patient privacy, data security, and system reliability. OBJECTIVE: To systematically review empirical evidence on privacy breaches, security vulnerabilities, and misuse associated with AI applications in healthcare settings. METHODS: PubMed, Embase, Web of Science, Scopus, IEEE Xplore, and ACM Digital Library were searched for empirical studies published between January 2015 and November 2025 that evaluated AI use or misuse in clinical diagnosis, treatment, or decision-making. Two reviewers independently screened studies and extracted data using a standardized form. Findings were synthesized narratively due to heterogeneity in study designs, AI methods, and reported outcomes. RESULTS: Of 7,285 records identified through database searches and 205 through citation screening, 22 empirical studies met the inclusion criteria, spanning multiple clinical domains and data modalities, predominantly medical imaging applications. Five recurring threat categories were identified: patient re-identification, membership inference, unauthorized access and adversarial exploitation, input manipulation, and misuse or overinterpretation of AI outputs. Across studies, AI models were shown to encode latent biometric signals across diverse data types, limiting the effectiveness of traditional anonymization and synthetic data approaches. Adversarial attacks and input manipulation were also shown to compromise diagnostic performance and system integrity. CONCLUSION: This systematic review provides empirical evidence suggesting that contemporary AI systems in healthcare introduce privacy and security risks that may challenge traditional assumptions about data protection. These findings underscore the need for privacy- and security-by-design approaches and governance frameworks that address risks across the AI lifecycle.

Humans

RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.

In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging predisposes neurons to dysfunction remain incompletely understood. While genomic instability, proteostasis decline, mitochondrial dysfunction, and chronic inflammation have dominated prevailing models, recent evidence highlights RNA dysregulation as a central component of age-associated decline. In this review, we summarize recent findings suggesting that aging progressively erodes RNA regulatory fidelity through alterations in RNA-binding protein abundance, localization, biophysical behavior, and RNA interactions. We argue that age-dependent RNA dysregulation represents an important mechanism that converges with genetic risk to drive neuronal vulnerability and neurodegeneration.

RNA dysregulation

Metabolomic and structural signatures of pigmented and non-pigmented Himalayan rice landraces.

BACKGROUND: This study investigated the anti-oxidant properties, starch composition, pasting behavior, structural properties, textural properties and non-targeted metabolomic profiles of pigmented and non-pigmented rice landraces as potential next-generation functional food ingredients. RESULTS: Pigmented rice demonstrated 1.34 times more anti-oxidant activity as compared to non-pigmented rice. Pigmented landraces showcased superior nutritional and functional attributes, including higher total dietary fiber and starch content. Fourier-transform infrared (FTIR) analysis revealed distinct molecular signatures with enhanced peak transmittance, while X-ray diffraction (XRD) indicated greater crystallinity ranging from 36-44.3% in pigmented rice compared with 30-40% in non-pigmented rice, suggesting improved digestibility and processing versatility. Pigmented rice recorded less amylose content hence tended to possess increased adhesiveness values whereas non-pigmented rice revealed greater amylose content hence was coupled with greater hardness values. Field-emission scanning electron microscopy (FE-SEM) images revealed that pigmented rice had densely packed and polygonal starch granules whereas non-pigmented rice had loosely packed starch granules with intergranular voids. Untargeted gas chromatography-mass spectrometry (GC-MS) profiling identified 84 metabolites, including unique compounds such as 3,3-dimethylbutanol and ethanoic acid, along with shared metabolites such as sucrose and linoleic acid, highlighting notable biochemical diversity. Multivariate statistical analyses using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping further differentiated the metabolomic landscapes, with variable importance in the projection (VIP) scores identifying key bioactive contributors. CONCLUSION: Pigmented rice landraces exhibited significant functional and nutritional advantages, making them promising candidates for functional food development and nutritional improvement programs. These findings support their potential role in advancing sustainable and health-oriented food systems. © 2026 Society of Chemical Industry.

Oryza

Robotic assistance in total hip arthroplasty: a systematic review and meta-analysis of leg length, cup orientation, and early outcomes.

This review examined whether robotic assistance alters postoperative leg-length discrepancy (LLD), acetabular cup orientation, or early hip-specific outcomes relative to conventional total hip arthroplasty (THA). We searched PubMed and Web of Science through May 2026 for comparative English-language reports. Study eligibility, data extraction, and methodological appraisal were undertaken independently by two reviewers. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated in Review Manager 5.4. Model selection was based on the target estimand and anticipated clinical and methodological diversity; leave-one-out and alternative-model sensitivity analyses were undertaken for heterogeneous outcomes. The protocol is registered with PROSPERO (CRD420261454043). The review included seven studies and 968 participants. Compared with conventional THA, robot-assisted THA yielded a smaller postoperative LLD (MD = -2.02, 95% CI -3.46 to -0.58; P = 0.006) and a higher Harris Hip Score (MD = 2.96, 95% CI 1.12 to 4.80; P = 0.002). Mean cup anteversion was lower in the robotic group (MD = -1.52, 95% CI -2.29 to -0.76; P < 0.0001), whereas cup inclination did not differ (MD = -0.71, 95% CI -3.26 to 1.83; P = 0.58). The robotic group also had higher Forgotten Joint Score (MD = 14.68, 95% CI 5.02 to 24.33; P = 0.003) and Oxford Hip Score values (MD = 2.61, 95% CI 0.71 to 4.51; P = 0.007). Robotic assistance was linked to a modest improvement in leg-length restoration and to higher scores on several early functional measures. The limited number of studies, predominance of nonrandomized designs, and marked heterogeneity in some analyses temper the certainty of these findings.

Humans

What's the meta now? More updates on the problems with systematic reviews.

BACKGROUND: Systematic reviews are intended to provide trustworthy evidence synthesis, yet previous iterations of this living review have identified numerous recurring problems in their conduct and reporting. This article presents the third version and second update of the living systematic review examining issues raised across the academic literature. METHODS: Using consistent eligibility criteria and methods from earlier versions, literature searches were updated to May 2025. Eligible meta-research and editorial articles describing problems with systematic reviews were analyzed to identify emerging themes. Additionally, four basic indicators of methodological quality of the included meta-research were presented across review versions. RESULTS: The update included 209 additional articles. Critically low methodological quality and absence of protocols remained among the most frequently reported issues in systematic reviews across disciplines and journals but notably in evidence underpinning clinical practice guidelines. Spin in abstracts and conflicts of interest continued to be common. Apparent improvements in reporting quality were inconsistent, with modest gains in some full-text reporting but persistent deficiencies in abstracts. Authorship diversity of systematic reviews improved in gender representation but remained geographically concentrated in high-income countries, and primary research included in reviews similarly lacked global representativeness. The issue of misalignment between systematic review evidence bases and global burden of disease bring the total number of problems with systematic reviews to 69. Emerging use of automation and artificial intelligence was variably reported. Descriptive comparison of meta-research articles over the three versions of this living review suggests a greater proportion meeting basic quality indicators in more recent updates. CONCLUSION: Across successive updates, problems with systematic reviews remain widespread and consistent rather than isolated. Incremental reporting improvements coexist with persistent concerns about transparency, bias, and representativeness. Future efforts should prioritize evaluating interventions and aligning research incentives to support genuinely trustworthy evidence synthesis.

Humans

Cross-kingdom dynamics of the subgingival bacteriome and mycobiome: A pilot study on the effects of a novel HA-H&#x2082;O&#x2082;-Glycine formulation to treat periodontitis.

OBJECTIVES: Traditional periodontal therapy primarily focuses on bacterial biofilm control; however, recent evidence also suggests a critical role for the oral mycobiome. This study evaluated the clinical and ecological impact of a novel mouthwash formulation containing hyaluronic acid (HA), hydrogen peroxide (H2O2), and glycine on periodontal patients METHODS: This prospective, randomized split-mouth trial included 13 adult participants with periodontitis treated with HA-H2O2-glycine formula (BMG0703A) used twice a day for seven days. Subgingival plaque samples were collected from periodontal pocket and healthy control sites at baseline (T0) and one-week post-treatment (T1). Microbial and fungal communities were characterized using Next-Generation Sequencing (NGS) of the 16S rRNA and ITS2 regions. Linear Mixed Models (LMM) and Spearman correlation were used to assess taxonomic shifts and cross-kingdom relationships. RESULTS: Sequencing revealed a promising ecological shift: the bacteriome shifted from anaerobic dominance (Olsenella, Peptostreptococcus) toward a health-associated aerobic profile, with Rothia near-doubling (11.91% to 22.68%). The mycobiome underwent a "normalization" effect: Candida abundance decreased significantly (22.8% to 9.1%), while fungal Shannon diversity in pockets returned to healthy-site levels. Inter-kingdom analysis identified antagonistic relationships between expanding commensal bacteria and opportunistic fungi, suggesting that the intervention may help re-establish a protective bacterial niche. CONCLUSIONS: The HA-H2O2-glycine formulation seems to facilitate a rapid, cross-kingdom modulation of the subgingival niche. By reducing anaerobic pathogens and normalizing the mycobiome it appear to induce short-term changes, suggesting potential as adjunctive strategy in periodontal management. CLINICAL SIGNIFICANCE: The present work underlines the possible cross-Kingdom effects of a novel compound.

Humans

Effect of urinary catheter securement band on meatal pressure injury in male intensive care patients: A randomized controlled trial.

OBJECTIVES: To investigate the effectiveness of a urinary catheter securement band in preventing meatal pressure injury (meatal-PI) in male ICU patients, and to identify associated risk factors and the timing of injury development. METHODS: A total of 248 adult male ICU patients were randomly allocated to an intervention group (n&#xa0;=&#xa0;124) or a control group (n&#xa0;=&#xa0;124) between December 2024 and April 2025. The intervention group received a catheter securement band in addition to standard care, while the control group received standard care alone. Meatal-PI was evaluated daily using a structured monitoring form and a validated staging system. RESULTS: The incidence of meatal-PI was significantly lower in the intervention group (6.5%) compared with the control group (16.1%) (p&#xa0;=&#xa0;0.016). Multivariate analysis identified catheter securement, use of silicone catheters, higher Braden Scale scores, and shorter ICU length of stay as independent protective factors, while advanced age was associated with increased risk. Additional factors significantly associated with meatal-PI included comorbidities, higher device burden, latex catheter use, dry skin, lower Glasgow Coma Scale and Braden scores, sedation, and perineal oedema (p&#xa0;<&#xa0;0.001). CONCLUSIONS: The use of a catheter securement band significantly reduces the incidence of meatal-PI in male ICU patients. Incorporating catheter securement devices into routine nursing care, prioritising silicone catheter use, and performing regular meatal assessments may enhance patient safety by reducing the risk of device-related pressure injuries. Further research comparing different catheter securement methods across diverse patient populations is warranted. IMPLICATIONS FOR CLINICAL PRACTICE: The use of catheter securement bands may reduce the incidence of meatal-PI in male ICU patients. Incorporating standardized catheter stabilization strategies into routine intensive care nursing practice may enhance patient safety and support pressure injury prevention efforts.

Humans

Genomic epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli across humans, poultry and wastewater sectors in Douala, Cameroon.

BACKGROUND: The global health threat of antimicrobial resistance involves the human, animal and environmental sectors. Data from Cameroon are scarce. OBJECTIVES: This study aimed to define extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) rates and associated risk factors across the three sectors in Douala, Cameroon, and to define molecular characteristics of isolates. METHODS: From June 2022 to May 2023, we collected blood cultures from hospitalized patients, rectal swabs from healthy pregnant women, caeca from broiler chickens and environmental wastewater. Samples were screened for ESBL-Ec using CHROMAgar&#x2122; ESBL and cefotaxime-supplemented Tryptone Bile X-glucuronide agar. Antimicrobial susceptibility testing was performed by disk diffusion following EUCAST guidelines. Whole-genome sequencing was carried out using Illumina technology. RESULTS: Of 628 samples, 374 yielded ESBL-Ec. Prevalence was 54.6% (131/240) in pregnant women, 70.4% (169/240) in chickens and 93.1% (67/72) in wastewater. The proportion of ESBL-Ec among E. coli-positive-blood cultures was 9.2% (7/76). Multi-family household living was independently associated with ESBL-Ec carriage among pregnant women (adjusted odds ratio&#x200a;=&#x200a;1.7, 95% CI 1.0-3.1, P&#x200a;=&#x200a;0.03). High co-resistance (>70%) was observed for tetracycline, ciprofloxacin and trimethoprim/sulfamethoxazole. Sequencing of 32 isolates revealed 45 distinct resistance genes, including blaCTX-M-15 (n&#x200a;=&#x200a;13, 40.6%), blaCTX-M-55 (n&#x200a;=&#x200a;11, 34.4%) and last-resort antibiotic resistance genes mcr-1 and bla OXA-181. High-risk sequence types included ST131 (pregnant women) and ST10 (chickens). Notably, ST48 was shared between pregnant women and chickens, and ST155 between pregnant women and wastewater. CONCLUSION: Cross-sectoral ESBL-Ec in Douala exhibits high genomic diversity and alarming resistance. The occurrence of last-resort genes requires immediate One Health surveillance and coordinated interventions.

Journal Article

Multi-omics reveal microbial functional traits and antifungal metabolites associated with lower Pseudogymnoascus destructans loads in bat cave soils.

White-nose syndrome, caused by Pseudogymnoascus destructans (Pd), is a major fungal disease threatening hibernating bats. Cave soils can serve as environmental reservoirs for Pd, yet the microbial and biochemical mechanisms underlying naturally low Pd burdens in some cave environments remain poorly understood. Here, we integrated soil microbiome profiling, metagenomics, metabolomics, multi-omics network analysis, and in vitro validation to investigate the ecological and functional basis of differential Pd loads in hibernating bat caves in Northeast China. The three caves shared cold, humid, and weakly acidic microenvironments, but differed significantly in electrical conductivity, soil water content, nutrient availability, and extracellular enzyme activities. Soil microbial communities showed significant inter-cave variation in composition, diversity, and niche breadth, with stochastic processes contributing substantially to community assembly. Environmental variables, particularly pH and Pd load, were important predictors of microbial community structure. Functional analyses revealed that the low-Pd Gezi Cave was enriched in genes associated with organic carbon degradation, nitrogen input and retention, and secondary metabolism. Metabolomic profiling further identified cave-specific metabolite signatures, among which Biochanin A, 4-Hydroxybenzaldehyde, Vanillin, and Arachidonic acid were negatively correlated with Pd loads. Integrated pathway and network analyses showed that differential genes and metabolites jointly mapped to secondary metabolite biosynthesis, aminobenzoate degradation, and flavonoid degradation pathways, forming a microbe-metabolite-functional gene coupling network involving key taxa such as Rhodococcus, Pseudorhodoplanes, and Rhodoplanes. In vitro assays confirmed that 4-Hydroxybenzaldehyde, Coumarin, and Vanillin inhibited Pd growth. Structural equation modelling further indicated that environmental heterogeneity was associated with variation in Pd loads through microbial functional attributes and metabolite profiles. These findings suggest that naturally low-Pd cave soils are associated with coordinated environmental filtering, microbial functional specialization, and antifungal metabolite production, providing mechanistic insight into microbial and biochemical constraints on Pd persistence in cave reservoirs.

Animals

Comparative genomic epidemiology of food- and patient-derived diarrheagenic Escherichia coli from sentinel surveillance in Southeast China.

Diarrheagenic Escherichia coli (DEC) remains an important foodborne pathogen, yet long-term comparative genomic surveillance data jointly characterizing food-derived and patient-derived isolates remain limited. This surveillance-based comparative study integrated antimicrobial susceptibility testing and whole-genome sequencing to characterize diarrheagenic Escherichia coli isolates recovered from food and patient sources in Lishui, Southeast China, during 2018-2025, with emphasis on occurrence, resistance profiles, genomic backgrounds, and plasmid replicon-associated features. Antimicrobial susceptibility testing was performed for 258 selected isolates, and whole-genome sequencing was conducted for a curated analytical subset of 204 isolates. The sequenced subset was used for diversity-oriented comparative genomic analysis rather than for unbiased prevalence estimation of the entire DEC collection. EAEC predominated in both sources, although food-associated occurrence was heterogeneous across categories, with the highest recovery rate observed in raw meat. Patient-derived isolates showed a broader overall resistance burden, whereas food-derived isolates retained substantial resistance to tetracycline, chloramphenicol, and florfenicol. Phylogenetic analysis showed partial overlap in genomic backgrounds between food-derived and patient-derived isolates, while representative resistance determinants displayed both broadly distributed and lineage-enriched patterns. Replicon-based plasmid profiling identified 42 plasmid types, including 12 detected in both sources, with IncF-related replicons predominating among these shared profiles. Several food-derived isolates carried multiple plasmid replicon types that were also observed in patient-derived isolates. Overall, food-derived and patient-derived DEC showed partial overlap in genomic backgrounds, resistance determinants, and replicon-defined plasmid profiles within this surveillance setting, while retaining source-associated heterogeneity. These findings should be interpreted as surveillance-based comparative evidence rather than as evidence of direct source attribution or transmission.

Humans

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

BACKGROUND AND OBJECTIVES: Pseudouridine (&#x3a8;) represents one of the most abundant and conserved RNA modifications. &#x3a8; 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 &#x3a8; 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 &#x3a8; site predictor. METHODS: New long-sequence datasets were constructed as benchmarks for RNA &#x3a8;-site prediction. The &#x3a8; 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 &#x3a8;-site prediction. Meta-PseU offers a new framework for robust &#x3a8;-site identification by using long sequences.

Pseudouridine

Educational interventions to improve medical students' bad news communication skills: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to both determine whether educational interventions improve medical students' ability and/or confidence in Bad News Communication (BNC), as well as assess the relative efficacy of instructional formats. METHODS: Performed according to the PRISMA guidelines, four databases were searched for articles describing education-based interventions to improve medical student's BNC ability and/or confidence, published in English between 2001 and 2024. Data on students' self-reported or observer-assessed level of competence/ability in BNC (primary outcome), and students' self-assessed confidence in BNC skills (secondary outcomes), were analysed. Meta regression explained the influence of several categorical moderators on heterogeneity in relation to intervention effects on competence/ability. RESULTS: 27 studies met the criteria for inclusion in the systematic review and 17 studies for the meta-analysis. Interventions described in controlled studies were associated with a moderate and significant increase in BNC ability (13 data sets; standardized mean difference [SMD] = 1.09, 95% CI = 0.52 - 1.66). Interventions detailed in pre-post design studies were associated with a significant increase in BNC ability (20 data sets; SMD = 0.92, 95% CI = 0.52 - 1.32), and student confidence/comfort in their BNC skills (12 data sets; SMD = 1.16, 95% CI = 0.57 - 1.75). Subgroup analysis demonstrated better skills/competence outcomes in studies that included simulation-based training (SBT). CONCLUSIONS: Educational interventions improve the BNC ability and confidence of medical students. Interventions should include an SBT element as this leads to greater improvements in BNC ability. Further research is needed to determine to what extent these interventions translate to positive patient outcomes. PRACTICE IMPLICATIONS: Diverse educational programme, especially those including simulation-based training, are effective in improving BNC skills, although the longetivity of these improvements is at present unclear. Therefore, we recommend that refresher courses or practice opportunities should be scheduled throughout students' medical education to ensure retention of BNC skills.

Humans

Emerging Principles in Spatial Functional Genomics.

Spatial transcriptomic and proteomic atlases have enabled mapping of gene programs within intact tissues, but these measurements remain largely descriptive and do not define the mechanisms controlling tissue biology. Pooled CRISPR screening provides scalable causal interrogation of gene function but remains largely confined to dissociated systems that lack spatial context. In vivo spatial functional genomics (SFG) bridges these approaches by integrating genetic perturbations with in situ transcriptomic and proteomic readouts to measure gene function within intact tissue ecosystems. By preserving spatial organization, SFG enables interpretation of perturbations through effects on cell-cell interactions, diffusible signals, multicellular niches, and tissue architecture. Here, we outline key design axes of SFG: perturbation strategy, barcoding strategy, and phenotypic readout. We discuss computational challenges, including spatial autocorrelation, neighborhood dependence, and context-aware null modeling, and highlight how SFG reveals non-cell-autonomous, architecture-dependent mechanisms of gene function, advancing toward predictive models of tissue organization and gene function.

Genomics

Long-term consequences of childhood sexual abuse: An umbrella review of diagnostic meta-analyses.

BACKGROUND: Childhood sexual abuse (CSA) is a public health issue with an estimated worldwide prevalence of 12.7%, potentially leading to a host of lifelong and significant mental, physical, and behavioral health. The aim of this study was to comprehensively map the long-term consequences of childhood sexual abuse on physical, psychiatric, and behavioral health outcomes. METHODS: An umbrella review of meta-analyses of observational studies, registered on PROSPERO, was conducted to examine the diverse repercussions of childhood sexual abuse on adult health. Three bibliographic databases (PsycINFO, PubMed and Scopus) were searched from the inception of the respective databases to November 1st, 2022. Thirty-eight meta-analyses representing about 20 million individuals were analyzed, revealing a range of long-lasting consequences associated with CSA. RESULTS: Among physical pathologies, cervical cancer and functional neurological syndromes emerged as the most prominent, exhibiting significantly elevated odds ratios (ORs) of 4.18 IC95% and 3.30 IC95%, respectively. Sleep disorders and borderline personality disorders were the most prevalent mental health disorders associated with CSA, with respective ORs of 16.17 IC95% and 5.96 IC95%. Early sexual initiation (OR=3.59 IC95%, sexual assault (OR=3.36 IC95%, and prostitution (OR=3.24 IC95%) emerged as the most common behavioral consequences. Notably, no significant differences in the consequences of CSA were observed between men and women, except for reproductive health outcomes. DISCUSSION: When faced with certain pathologies, clinicians should consider and discuss sexual abuse with their patients. The consequences of abuse have a multifactorial origin, which is a weakness, as are the problems of defining abuse. The strength of our study is that it lists the consequences published in high-quality studies. CONCLUSION: This umbrella review provides compelling evidence of the profound and far-reaching impact of childhood sexual abuse on a broad spectrum of physical, mental, and behavioral health issues.

Humans

Integrative genomic and transcriptomic analyses identify key regulators of skin pigmentation in Larimichthys crocea.

The yellow body coloration of large yellow croaker (Larimichthys crocea) constitutes a crucial economic trait, yet its underlying genetic regulatory mechanisms remain poorly understood. This study systematically elucidated the molecular basis of body color variation by integrating genome resequencing and skin transcriptome analyses, combined with the contextual analysis of key pigmentation-related genes and phenotypic histological validation. 200 phenotyped individuals (including yellow-selected lines, F1 progeny, and normal control groups, all derived from a well-characterized aquaculture stock) identified 39 significantly associated SNPs (-log&#x2081;&#x2080;(P)&#xa0;&#x2265;&#xa0;6), mapping to multiple candidate genes. These genes were significantly enriched in pathways related to pigment deposition (GO:0033059), melanosome organization (GO:0032438), melanogenesis, and tyrosine metabolism. Cross-developmental stage transcriptome analysis revealed 2395 differentially expressed genes (DEGs). Multi-omics integration identified eight overlapping candidate genes, including tyrp1, slc45a2, oca2, and dgat2, among which tyrp1 was prioritized for in-depth validation based on its core regulatory role in eumelanin synthesis, significant SNP association signal, and consistent downregulation in transcriptomic data. Experimental validation demonstrated that the g.895C&#xa0;>&#xa0;T mutation in exon 2 of tyrp1b was strongly significantly associated with the yellow phenotype: the frequency of mutant genotypes (TT/CT) reached 92.86%in the yellow-selected group, whereas the control group exclusively exhibited the wild-type genotype (CC). qPCR confirmed significantly downregulated tyrp1b expression in the skin of yellow individuals, consistent with the transcriptome trend. Histological and stereomicroscopic observations of skin tissues further validated the physiological basis of the yellow phenotype, revealing a significant reduction in melanophore number and abnormal melanosome morphology in yellow-phenotype individuals, accompanied by increased xanthophore density. These results suggest that tyrp1b mutation is strongly associated with the yellow phenotype. However, the presence of a wild-type CC individual in the yellow group indicates that this mutation is not strictly required for yellow coloration, suggesting that other genetic or environmental factors may also contribute to the phenotype, Additionally, downregulation of the carotenoid metabolism gene bco2 coupled with upregulation of xdh, together with the functional changes of slc45a2 and oca2, may synergistically promote xanthophore pigment deposition, contributing to the yellow phenotype. As melanin synthesis in large yellow croaker relies on the conserved tyrosinase pathway and transporter proteins, mutations in associated genes (tyrp1b, slc45a2, oca2) represent a primary underlying cause for the loss of melanin-based coloration and transition to a yellow phenotype in L. crocea. These findings provide key molecular targets and a theoretical foundation for molecular breeding of body color in this species, and also enrich the understanding of xanthism regulatory mechanisms in teleosts.

Animals