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One in three patients with positional obstructive sleep apnea does not benefit from positional therapy: Insights from a home-based trial.

PURPOSE: Positional obstructive sleep apnea (POSA) is the most common phenotype of obstructive sleep apnea, yet patient selection for positional therapy (PT) remains suboptimal. With this analysis we aimed to clarify how many patients with POSA may not require PT because they do not habitually sleep supine at home, and how many fail vibrotactile PT despite appropriate indication. METHODS: We conducted a retrospective observational study of consecutive adults with POSA evaluated at a tertiary sleep center between 2021 and 2024. All patients underwent a home-based trial with a neck-based vibrotactile positional therapy device (Night Shift™), consisting of monitoring mode followed by therapy mode. Outcomes included the proportion of non-supine sleepers at home, failure rate of vibrotactile PT, device compliance and differences in supine sleep time between diagnostic testing and home monitoring. RESULTS: Of 92 screened patients, 74 met inclusion criteria (mean age 60.3 ± 13.2 years; mean AHI 22.9 ± 13.3 events/h). Fifteen percent (11/74) did not habitually sleep supine at home, indicating no clinical need for PT, and an additional 14.8% (11/74) failed vibrotactile PT. Overall, 30% of patients were either unlikely to benefit from PT or failed therapy. Non-response was frequently associated with psychotropic or sedative medication use and neurological or sleep-related comorbidities. CONCLUSION: A substantial proportion of patients diagnosed with POSA either do not require or fail vibrotactile treatment in real-world conditions. Incorporating a brief home monitoring and therapy trial into routine clinical practice may optimize patient selection, reduce unnecessary costs, and improve personalized management of POSA.

Humans

Reinforcement learning-based dynamic ensemble for missense variant effect prediction and tiered prioritization of VUS.

BACKGROUND: Accurate classification of missense variants remains a challenging task despite major advances in genomics. Numerous computational models have been developed to assist in variant classification, but often require repeated integration and benchmarking efforts. Ensemble methods have been proposed to overcome the limitations of single predictors, but mostly rely on fixed, predefined weights that constrain their ability to capture interactions among predictive signals. METHODS: We present GenixRL, a dynamic ensemble framework that reformulates model fusion as a reinforcement learning optimization problem. GenixRL uses a Q-learning agent to learn a policy that dynamically weights the probabilistic outputs of complementary predictors, including BayesDel (addAF and noAF), ClinPred, and MetaRNN. Replacing static weighting with policy learning allows GenixRL to adaptively identify optimal weightings and substantially improve classification accuracy. RESULTS: In benchmark evaluation against 25 state-of-the-art predictors, GenixRL achieved an AUROC of 0.9644 on an independent ClinVar dataset. On saturation genome editing assays for BRCA1 and BRCA2, GenixRL achieved the best performance and ranked highest on 14 of 17 clinically significant genes in a zero-shot evaluation. Applied to uncertain and conflicting ClinVar variants, GenixRL enabled tiered, evidence-based prioritization of hundreds of thousands of variants as likely pathogenic or pathogenic with high confidence, supported by orthogonal population evidence from gnomAD. CONCLUSION: GenixRL advances pathogenicity prediction for missense variants and provides an adaptive ensemble that sorts variants of uncertain significance into tiered candidates for expert curation and functional validation.

Mutation, Missense

Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 × 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

Humans

The effect of monetary versus point-based rewards on effort-cost decision making in individuals at clinical high risk for psychosis.

OBJECTIVE: The dissemination of inexpensive computerized behavioral tasks indexing amotivation may enhance the assessment of clinical high risk (CHR) across settings. However, the impact of varying reward value in such tasks is unclear. If point-based rewards engage participants, this could improve the scalability of computerized assessments. We tested how point-based rewards versus money impacted effort-cost decision-making in CHR individuals. We further assessed how negative symptom severity and household income interacted with reward-type to impact behavior. METHODS: Participants completed the Effort Expenditure for Reward Task (EEfRT). Participants were randomly assigned to receive either money or points for their performance during the EEfRT. Data from a large sample of CHR (N = 233) individuals and healthy controls (HC; N = 157) were collected. RESULTS: Across diagnostic groups, we observed heightened effort expenditure when money was used as a reward (b = 0.13, p = 0.018). We did not find an interaction of CHR status (b = 0.07, p = 0.845) or negative symptoms (b = 0.01, p = 0.429) with reward-type. Within CHR individuals, heightened negative symptom severity was associated with reduced expended effort (b = -0.03, p = 0.016), regardless of reward type. In an exploratory analysis, we found that individuals in the money condition with relatively high household income expended less effort during high reward, high probability trials (b = -0.24, p = 0.046). CONCLUSIONS: Across CHR and HC individuals, individuals pursuing money expended greater effort. While we did not find a group by reward type interaction, CHR individuals with heightened negative symptom severity expended less effort across trials, replicating prior work. Present findings support further study of point-based rewards in tasks indexing amotivation.

Humans

A STORM-based protocol for nanoscale imaging and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber.

Stochastic Optical Reconstruction Microscopy (STORM) enables nanoscale mapping of molecular components beyond the diffraction limit; however, its reproducible implementation in hydrophobic polymer matrices remains challenging because fluorescence-labeling specificity, fluorophore photoswitching, three-dimensional localization, chromatic registration, and quantitative image analysis must be carefully controlled. This protocol presents a standardized experimental workflow for dual-color labeling, astigmatism-based three-dimensional STORM acquisition, and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber (NR). The workflow covers sample pretreatment, Cy5 NHS ester labeling of protein-associated primary amines, DiI labeling of phospholipid-rich domains, STORM imaging-buffer preparation, three-dimensional single-molecule localization, dual-channel registration, generation of standardized xy projections, aggregate-size analysis, and projected lateral spatial correlation assessment. Reproducibility is supported by defined acquisition and localization criteria, three independent sample preparations with at least five fields of view analyzed per condition, and unlabeled, single-color, dye-only matrix, and processing-associated Cy5 controls. Mean lateral localization precisions of 11.8 ± 2.3 nm for Cy5 and 13.5 ± 2.9 nm for DiI were obtained, while two-dimensional Fourier ring correlation analysis of the xy projections yielded effective lateral image resolutions of approximately 25 and 28 nm, respectively. Image-based particle segmentation and localization-coordinate-based density-based spatial clustering of applications with noise (DBSCAN) were applied to standardized xy projections as complementary quantitative approaches. Application of the protocol to untreated, centrifuged, and protease-treated NR samples demonstrated treatment-associated changes in the detected abundance and projected size distributions of protein- and phospholipid-associated aggregates, together with a non-monotonic change in their projected lateral spatial correlation. These observations describe alterations in nanoscale organization but do not, by themselves, establish stable protein-phospholipid complex formation. Unlike previous studies that primarily demonstrated the feasibility of STORM imaging in rubber materials, the principal contribution of this work is an end-to-end, step-by-step protocol incorporating defined controls, three-dimensional localization, image-quality metrics, chromatic-registration procedures, and complementary quantitative-analysis pipelines for non-expert users. The workflow may be adaptable to other hydrophobic polymers and soft-material systems after appropriate optimization and validation.

Rubber

Uce-based phylogeny and classification of Megachilini.

The generic-level classification of the bee tribe Megachilini (Megachilidae) has remained controversial due to poor phylogenetic resolution at the base of the group, particularly among the brood parasitic genera and the numerous dauber ("Chalicodoma s. l.") lineages. We present a phylogenomic analysis of Megachilini based on ultraconserved elements (UCEs), sampling 52 ingroup taxa with emphasis on the dauber lineages. We also present a combined UCE + six-gene analysis to improve taxon coverage, resulting in a dataset with 127 ingroup taxa. Maximum likelihood, coalescent, and Bayesian analyses of multiple UCE matrices recover largely congruent topologies with substantially improved support relative to previous studies. Our results strongly support the monophyly of Megachilini, the early divergence of Noteriades and Gronoceras, and a single origin of brood parasitism. All remaining non-parasitic Megachilini form a moderately supported clade sister to the brood parasitic lineage. The leafcutter bees are monophyletic and nested within dauber lineages. Several major dauber clades are consistently recovered, including an exclusively Australian clade corresponding to the Hackeriapis group of subgenera, while several recognized subgenera are paraphyletic. The lineage known as Morphella, previously placed in synonymy with the subgenus Callomegachile, was not closely related to that subgenus and is here treated as a valid subgenus. Divergence-time analyses place the crown age of Megachilini in the late Eocene to early Oligocene, with major extant lineages diversifying during the Miocene. Limited morphological diagnosability of several clades indicates that splitting non-parasitic lineages into numerous genera would result in an impractical classification that would widen the gap between taxonomists and non-specialists and exacerbate the taxonomic impediment in bees. We therefore advocate retaining a single genus Megachile for non-parasitic Megachilini (excluding Noteriades and Gronoceras), as the classification best supported by phylogenomic evidence and most robust to future taxon sampling.

Animals

Acceptability of alcohol-based hand rub during neonatal care in rural Ugandan households: a qualitative study nested within the BabyGel trial.

BACKGROUND: Poor access to water, sanitation and hygiene exacerbates the spread of infections among newborns. The BabyGel cluster randomised trial assessed the effectiveness of a community-level alcohol-based hand rub with a training component in reducing infection or death rates among newborns in Uganda. OBJECTIVE: Nested in the BabyGel trial, this study investigated the acceptability of the BabyGel intervention among mothers and household members in Eastern Uganda, using the Theoretical Framework of Acceptability. METHODS: In 2022, we conducted individual semistructured interviews with mothers, and group interviews with mothers and other household members, all recruited from intervention-arm clusters. Thematic analysis combined inductive and deductive coding, structured by the framework's seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy. RESULTS: Twenty mothers and 14 household members participated in 10 individual and 10 small group interviews. Participants found the intervention generally acceptable, appreciating its convenience and perceived protection against infection. Many described hand hygiene changes that persisted beyond the intervention period. However, concerns related to its harmful effects, spiritual beliefs and social tensions with visitors occasionally influenced its use. CONCLUSION: Alcohol-based hand rub combined with a training component was generally well accepted, driven by perceived health and practical benefits, although concerns related to safety, belief systems and social dynamics remained. Because data collection coincided with the COVID-19 pandemic, a period of heightened hygiene awareness, the acceptability observed could differ in nonpandemic periods. Culturally adapted education, community engagement and reinforcement of correct use may enhance acceptability and sustainability in similar settings.

Humans

Machine learning-based prediction of unplanned readmission and construction of an online calculator for elderly patients with mild ischemic stroke.

OBJECTIVE: To screen for independent risk factors for unplanned readmission in elderly patients with mild ischemic stroke, and to construct and validate an online risk prediction calculator based on an interpretable machine learning model, thereby providing a promising practical tool for accurate clinical assessment of 30&#x2011;day all&#x2011;cause unplanned readmission risk in this population. METHODS: A prospective cohort study was conducted, including 1050 patients aged&#xa0;&#x2265;&#xa0;60&#xa0;years with mild ischemic stroke admitted between August 2023 and September 2024. Participants were randomly divided into a training set (840 cases) and a test set (210 cases) at a ratio of 8:2. Risk factors were screened by univariate analysis and multivariable Logistic regression. Four machine learning models, namely LightGBM, XGBoost, Random Forest, and K&#x2011;Nearest Neighbors (KNN), were developed and their performance was evaluated using AUC, accuracy, sensitivity, and specificity as metrics. The SHAP framework was used for interpretability analysis, and an online calculator was subsequently developed based on the optimal model. RESULTS: Univariate analysis showed significant differences (P&#xa0;<&#xa0;0.05) in 13 factors including age, smoking, AIP, TyG index, HALP score, etc. Multivariable Logistic regression identified age (OR&#xa0;=&#xa0;9.752), smoking (OR&#xa0;=&#xa0;5.171), AIP (OR&#xa0;=&#xa0;6.691), TyG index (OR&#xa0;=&#xa0;4.393), HALP score (OR&#xa0;=&#xa0;2.831), and&#xa0;&#x2265;&#xa0;2 comorbidities (OR&#xa0;=&#xa0;3.664) as independent risk factors. All four machine learning models demonstrated good predictive performance. Based on a comprehensive evaluation of multiple metrics and computational efficiency, the LightGBM model exhibited the best predictive performance (AUC&#xa0;=&#xa0;0.884, accuracy&#xa0;=&#xa0;0.829, sensitivity&#xa0;=&#xa0;0.812, specificity&#xa0;=&#xa0;0.875). SHAP analysis showed that age, AIP, TyG index, smoking, and HALP score were key predictors. An online calculator developed based on this model enables individualized risk predictions. CONCLUSION: Key risk factors associated with 30&#x2011;day unplanned readmission in elderly patients with mild ischemic stroke were identified. The LightGBM model demonstrated high predictive accuracy, and together with the interpretability analysis and online calculator, offers a practical tool to support clinical risk assessment. However, this tool requires future external validation.

Humans

Impact of real-time respiratory function monitoring on neonatal mask ventilation training: a multicentre simulation-based crossover study.

OBJECTIVE: To evaluate whether visibility of respiratory function monitor (RFM) feedback improves mask ventilation performance and influences subsequent ventilation performance during neonatal resuscitation training. DESIGN: multicentre randomised crossover simulation study. PARTICIPANTS: Healthcare professionals involved in neonatal resuscitation training across participating centres. INTERVENTION: Participants performed positive pressure ventilation (PPV) on both term and premature manikins under two conditions: with visible RFM feedback and with the display masked. The order of feedback visibility was randomised. Each participant completed ventilation assessments in both conditions. MAIN OUTCOME MEASURES: Primary outcomes were expired tidal volume (Vte) and mask leak (%). The proportion of breaths within the target Vte range (4-8&#x2009;mL/kg) was calculated as a performance indicator. Secondary outcomes included variability in Vte and mask leak to assess ventilation stability between conditions. RESULTS: Visible RFM feedback was associated with lower mask leak and improved ventilation stability in the preterm manikin and with tidal volumes entering the target range in the term manikin. Participants initially ventilated with visible feedback maintained performance after feedback removal, suggesting a carry-over learning effect. CONCLUSION: In this multicentre crossover simulation study, visible RFM feedback was associated with changes in mask ventilation performance and evidence of a carry-over learning effect following feedback removal. Real-time visibility of respiratory parameters may strengthen neonatal resuscitation training.

Humans

Peripheral pain threshold, glycaemic status, and LAMP3 genetic variation: A community-based analysis.

Diabetic polyneuropathy is a common complication of diabetes, yet substantial inter-individual variation in peripheral pain perception suggests underlying genetic influences. This population-based study investigated clinical, metabolic, and genetic determinants of pain threshold using intraepidermal electrical stimulation in 906 participants from the Iwaki Health Promotion Project 2017. Genome-wide association analysis identified 12 loci showing suggestive associations, among which a missense variant in LAMP3 (rs482912) was prioritized as a biologically plausible candidate. Phenotype-stratified analyses showed that individuals carrying the CT or CC genotypes had lower PINT indices than those with the TT genotype, indicating reduced pain thresholds. Notably, the CC genotype retained an association with lower pain threshold using intraepidermal electrical stimulation under conditions of metabolic stress, including impaired glucose tolerance, elevated HbA1c, and obesity, whereas this association was attenuated in the presence of hypertension. Single-cell RNA sequencing analysis of human skin revealed that LAMP3-positive mature dendritic cells, enriched in immunoregulatory molecules, exhibited transcriptional enrichment of inflammatory, antigen-presenting, and nociception-related pathways, including NF-&#x3ba;B, JAK-STAT, cytokine signaling, and neuroimmune sensitization cascades. Autopsy-based skin analysis further demonstrated genotype-associated differences in dermal LAMP3-positive cell infiltration and CD8-positive T-cell abundance, while CD4-positive T-cell abundance and intraepidermal nerve fiber density remained unchanged across genotypes. Taken together, these findings suggest a potential association between LAMP3 variation and individual differences in peripheral pain threshold and provide biological context supporting a role for neuroimmune interactions in early sensory modulation under metabolic stress. Given the suggestive genetic evidence and indirect mechanistic data, these observations should be interpreted as exploratory and hypothesis-generating.

Humans

Effectiveness of an AI-based home exercise app for rehabilitation of rotator cuff-related shoulder pain: A randomized controlled trial.

BACKGROUND: Rotator cuff-related shoulder pain contributes to disability and healthcare use. Although therapeutic exercise is first-line treatment, limited supervision and adherence may reduce its effectiveness; digital rehabilitation with real-time feedback may address these limitations. OBJECTIVES: To evaluate the effectiveness of adding a digital rehabilitation program to standard physiotherapy on pain, function, fear-avoidance beliefs, and healthcare utilization. DESIGN: Single-center, assessor-blinded, randomized controlled trial with two parallel groups. METHOD: Forty-six adults (mean age 59 years) with rotator cuff-related shoulder pain were randomized to 12 weeks of conventional physiotherapy or physiotherapy plus an AI-based digital rehabilitation program using computer vision for real-time feedback and performance monitoring. Outcomes were assessed at baseline and at 2, 4, and 12 weeks. Pain intensity (NPRS) was primary outcome; secondary outcomes included upper limb function (QuickDASH), fear-avoidance beliefs (FABQ), and post-intervention healthcare utilization. Analyses followed an intention-to-treat approach. RESULTS: Pain reduction exceeded the MCID (1.3) at 4 and 12 weeks. Between-group differences favoured the intervention at Weeks 2 and 4 (MD -0.7; 95% CI -1.13 to -0.14 and MD -1.01; 95% CI -1.8 to -0.2, respectively). Upper limb function improved more at Week 4 (MD -7.3; 95% CI -12.3 to -2.2). FABQ scores decreased more at Week 12 (MD -7.6; 95% CI -14 to -0.5). Fewer participants in the experimental group required post-intervention healthcare (3 vs 10; p&#x202f;=&#x202f;0.02). CONCLUSION: Adding AI-based home exercise app to conventional treatment improve pain and may improve function and reduce healthcare utilization in rotator cuff-related shoulder pain.

Humans

Nanopore-based epigenomic profiling reveals the absence of widespread CpG methylation in the African swine fever virus genome.

DNA methylation is a critical epigenetic mechanism implicated in regulating replication and transcription in DNA viruses. However, the epigenetic landscape of African swine fever virus (ASFV), a large double-stranded DNA virus infecting pigs, remains controversial. Here, we systematically profiled the DNA methylome of the first ASFV strain isolated in Hong Kong (HK_NT_202103) using Oxford Nanopore Technologies (ONT) R10.4.1 sequencing. We employed a paired design: native whole-genome sequencing (WGS) against a methylation-free whole-genome amplification (WGA) control. Using conservative thresholds, we found no evidence of 5-methylcytosine (5mC), especially typical CpG methylation, across the viral genome. Importantly, clear CpG methylation signals were successfully detected in the host genome from WGS data, confirming the functionality of the workflow to detect 5mC at CG sites. While widespread 5mC seems absent, a small number of putative N6-methyladenine (6mA) loci were identified. A specific 6mA candidate exhibited raw ionic current disruptions and gene-level intersection with another ASFV isolate (CAS19-01/2019), although it lacked single-base consensus across different methylation callers or between the two isolates. Although our biological findings are restricted to a single isolate under specific experimental conditions, this study introduces a novel, highly rigorous ONT framework for viral epigenomics research. Furthermore, the absence of ASFV CpG methylation indicates that host CpG-depletion remains a viable strategy for viral metagenomic enrichment. Ultimately, our work offers a critical methodological baseline for ASFV surveillance and highlights the necessity of targeted experimental validation for rare viral modifications.

African Swine Fever Virus

Fungal drivers of mycotoxin contamination in wheat: Early warning and plasma-based control.

Mycotoxin contamination in wheat is a major food safety concern; however, quantitative evidence linking fungal community signals, mycotoxin exceedance risk, and wheat quality traits in naturally contaminated wheat remains limited. In this study, wheat samples were collected from mycotoxin-prone monitoring sites under unusually rainy conditions in 2022 to explore early-warning indicators and post-harvest mitigation strategies. According to the National Food Safety Standard of China GB 2761-2017, aflatoxin B1 (AFB1), deoxynivalenol (DON), and zearalenone (ZEN) exceeded the maximum limits in 52.24, 47.76, and 23.88% of samples, respectively; 38.81% exceeded the reference EU threshold for T-2 toxin, and 46.27% showed co-contamination with at least two mycotoxins above their respective thresholds. Although Alternaria, Cladosporium, and Epicoccum dominated the fungal community, Fusarium abundance was significantly associated with DON contamination and Fusarium-damaged kernels (FDKs). Mediation analysis identified DON as a significant mediator linking Fusarium abundance to FDKs, accounting for 68.41% of the total effect. In addition, Fusarium abundance above 3.70% showed strong predictive performance for DON exceedance, with an area under the curve of 0.906, indicating its potential as an early-warning indicator. Culture-based assays confirmed the toxigenic potential of Aspergillus and Fusarium isolates under simulated temperature and moisture conditions. After optimization using a toxin-spiked wheat flour model, dielectric barrier discharge cold plasma degraded AFB1, DON, and ZEN by 29.30-35.68%, disrupted the morphology of toxigenic fungi, and did not significantly affect wheat quality. This study provides practical insights into mycotoxin risk warning and post-harvest mitigation in wheat.

Triticum

Obstructive sleep apnea and long-term risk of site-specific cancers: A population-based cohort study.

BACKGROUND: Obstructive sleep apnea is common, but its long-term association with site-specific cancers remains unclear. In this study, we examined 15-year risks of site-specific cancers in people with obstructive sleep apnea compared with the general population and to people with overweight or obesity. METHODS: We conducted a nationwide population-based cohort study using Danish registries, 1995-2021. People diagnosed with obstructive sleep apnea were compared with the general population and to people with overweight or obesity. Adjusted (weighted) 15-year risks, risk differences, and risk ratios (RRs) were estimated using the Aalen-Johansen estimator. Confounding was addressed using standardized morbidity ratio weighting. RESULTS: The study included 114,264 people with obstructive sleep apnea, 115,497 members of the general population, and 113,034 with overweight or obesity. After weighting, the distributions of sex (74% male), age (median 53 years), and comorbidities were comparable across the three cohorts. Obstructive sleep apnea was associated with an increased risk of cancers of the brain (adjusted 15-year risk: 5.78 vs. 3.61 per 1,000 persons; aRR 1.60 [95% CI 1.43-1.78]) and spinal cord (1.65 vs. 1.17 per 1,000 persons; aRR 1.41 [95% CI 1.16-1.72]) compared with the general population. Associations persisted when the obstructive sleep apnea cohort was compared with those with overweight or obesity. No associations were observed for other site-specific cancers. CONCLUSION: Obstructive sleep apnea was associated with an increased risk of brain and spinal cord cancers. These findings highlight the importance of effective prevention of obstructive sleep apnea and the need for further research on treatment.

Cohort Study

Unconfined compressive strength prediction for the ordinary Portland cement-steel slag-silica fume ternary system based on response surface methodology.

This research was undertaken to address environmental concerns associated with industrial solid waste and to reduce cement consumption in geotechnical engineering. It specifically investigates the feasibility of using steel slag (SS) and silica fume (SF) as partial substitutes for ordinary Portland cement (OPC) in soil stabilization. The effects of SS, SF, OPC, and initial moisture content on the unconfined compressive strength (UCS) of stabilized soil were investigated through single-factor experiments and response surface methodology (RSM). The results show that SS and SF can synergistically enhance the strength of stabilized soil, although their interaction effect was not statistically significant within the investigated ranges. Compared with soil stabilized solely with OPC, the addition of 18 % SS and 10 % SF reduced OPC consumption by 3 % without compromising strength. Microstructural and compositional analyses further revealed that SS mainly supplied calcium- and silica-bearing components, while SF provided highly reactive silica and micro-filling effects, jointly promoting hydration reactions and improving the compactness of the stabilized soil matrix. As a result, more hydration products were formed in the OPC/SS/SF-stabilized soil than in the OPC-stabilized soil, which contributed to pore filling and strength enhancement. This study provides useful guidance for the sustainable utilization of industrial solid waste and the low-carbon development of soil stabilization materials.

Construction Materials

Revealing potential biomarkers and metabolic mechanisms of ovarian aging in hens during late laying period based on machine learning and metabolomics.

Ovarian function decline during the late laying period represents a major bottleneck for the economic efficiency of the global poultry industry. However, the underlying metabolic mechanisms and reliable early-warning biomarkers for ovarian aging remain poorly understood. In this study, we performed the first untargeted LC-MS/MS metabolomics analysis of ovarian tissues from Taihe silky fowls at peak laying (30&#xa0;weeks) and late laying (50&#xa0;weeks) stages, and employed an ensemble machine learning strategy integrating LASSO, random forest, and support vector machine (SVM) algorithms to identify high-confidence core biomarkers of ovarian aging. Gene expression analysis was further conducted to validate the potential molecular mechanisms. Our results showed that the metabolic profiles of ovarian tissues differed significantly between the two groups. A total of 6 core biomarkers were identified, 4 of which were long-chain acylcarnitines. Mechanistic analysis revealed that downregulation of key genes in the carnitine shuttle system led to impaired mitochondrial fatty acid &#x3b2;-oxidation, which in turn triggered excessive oxidative stress and compromised ovarian endocrine function. In conclusion, this study identifies long-chain acylcarnitines as potential metabolic biomarkers for ovarian aging in Taihe silky fowls. These findings provide novel insights into the metabolic basis of poultry ovarian aging and lay a theoretical foundation for the precise regulation of reproductive performance in indigenous poultry breeds.

Animals

Adolescents' Growing Sensitivity to Psychosocial Stressors: Evidence From Two Decades of Health Behaviour in School-aged Children (HBSC) Data in the Nordic Countries.

PURPOSE: We tested a perception-based explanation for rising psychosomatic complaints among adolescents in the Nordic countries. Specifically, we examined whether adolescents have become more sensitive to psychosocial stressors, reflected in stronger associations between stressors and psychosomatic complaints in 2022 than in 2002. METHODS: Data were drawn from the 2002 to 2022 waves of the Health Behaviour in School-aged Children survey among 15-year-olds in five Nordic countries (N = 7,263 in 2002 and 6,739 in 2022). Psychosomatic complaints were examined in relation to stressors in the following three domains: interpersonal relationships, school-related strain, and body- and activity-related factors. Moderated regression analyses tested whether associations between stressors and complaints differed between survey years. Sex and perceived family finances were included as covariates. RESULTS: Four of five psychosocial stressors showed stronger associations with psychosomatic complaints in 2022 than in 2002. Perceived poor family finances, although less prevalent in 2022, were more strongly related to complaints. Girls consistently reported higher levels of psychosomatic complaints, and the association between school pressure and complaints was stronger among girls. DISCUSSION: Although several psychosocial stressors declined in prevalence, their associations with psychosomatic complaints strengthened over time. These findings suggest that rising complaints may reflect changes in how psychosocial stressors are linked to adolescents' psychosomatic symptoms, rather than increases in exposure to those stressors. This shift highlights the importance of considering how adolescents interpret and respond to everyday stress when addressing population trends in mental health.

Humans

Proteomics-based analysis of the defense mechanisms of disease-resistant grass carp against Aeromonas veronii.

Sustainable aquaculture of grass carp (Ctenopharyngodon idella, GC) is consistently threatened by bacterial diseases, particularly those caused by Aeromonas veronii. A disease-resistant grass carp (DR-GC) has been developed by backcrossing female gynogenetic GC with normal male GC, exhibiting improved resistance. However, the systemic molecular mechanisms of DR-GC defending against Aeromonas veronii infection remain largely unexplored. Here, a label-free quantitative proteomics approach was employed to systematically compare proteomic profiles across five tissues (intestine, liver, muscle, skin, and kidney) in DR-GC and GC under healthy and infected conditions. The intestine was identified as the central defense tissue, exhibiting the highest number of differentially abundant proteins (DAPs). In DR-GC, A0A3N0YEK7 (small ribosomal subunit protein eS28), A0A3N0YGT8 (ATP synthase-coupling factor 6) and A0A3N0YNS7 (apolipoprotein A-I) were significantly upregulated in intestine, while D5KZW6 (GCHV-induced protein), A0A3N0Z0A1 and Q8JH84 (hemoglobin subunit alpha) were significantly dysregulated across multiple tissues, which playing the critical roles in defense mechanisms at the protein level. Furthermore, cytochrome P450-associated pathways, cytosolic DNA-sensing and RIG-I-like receptor signaling pathways were identified as crucial coordinators mediating immune and metabolic responses. This study provides the first comprehensive proteomic view of multi-tissue defense mechanisms in DR-GC, and identifies key DAPs and pathways for subsequent functional validation.

Animals