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Baseline serum oxytocin and OXTR rs53576 genotype are not predictive of escitalopram response in generalized anxiety disorder
Stemness and EMT profiles shift in xenografts derived from cisplatin-sensitive and cisplatin-tolerant ovarian cancer cells
The transcriptional alterations underlying epithelial-to-mesenchymal transition (EMT) in chemoresistant ovarian cancer remain a matter of debate, with emerging evidence pointing to tumour cell plasticity and subclone reprogramming. In this study, we developed a cisplatin-tolerant ovarian cancer model by treating the cisplatin-sensitive OVCAR-3 cell line with a single dose of cisplatin, generating the OVCAR-3 CP variant. These cisplatin-tolerant cells exhibited distinct EMT-related changes at both transcriptomic and protein levels, potentially regulated by epigenetic mechanisms. EMT profiling revealed that OVCAR-3 CP cells did not display a pronounced mesenchymal phenotype but rather retained epithelial characteristics and showed elevated expression of ALDH3A1 . In contrast, the parental chemosensitive OVCAR-3 cells expressed canonical mesenchymal markers ( CDH2, VIM, ZEB1/2, SNAIL, SLUG ) and lacked stemness marker expression. Upon xenografting, both OVCAR-3 and OVCAR-3 CP cells demonstrated phenotypic plasticity, with parental OVCAR-3 xenografts acquiring EMT-like features resembling to those observed in cisplatin-tolerant tumours. These findings suggest a decoupling of EMT from cisplatin-tolerance and instead underscore a stronger association between stemness traits and cisplatin tolerance. Our data further indicate that xenografting can induce significant cellular reprogramming. Comprehensive characterization of ovarian cancer cell-derived xenograft is therefore essential, as they represent a valuable translational platform for investigating therapy adapted ovarian cancer cells.
Integrated metabolomics and 16S rRNA sequencing reveal the mechanism of total flavones of Abelmoschus manihot (L.) Medic against liver fibrosis
Integrated environmental DNA analysis and population assessment revealed a biannual breeding season of the Korean clawed salamander (Onychodactylus koreanus)
Determining the breeding season of a species is key to understanding its life cycle and to ensuring efficient conservation. Determining the breeding season is challenging for subterranean breeders. Environmental DNA (eDNA) applications have been proposed alongside population surveys. In this study, larval influx, adult emergence, and eDNA detection of Onychodactylus koreanus , an external fertilizer, were investigated at underground cave breeding sites every 2 weeks from April 2024 to June 2025 to determine the breeding frequency and season. A major influx of 1-year-old larvae occurred in June and November. Adult emergence occurred in May–June and November–December, but was absent in July–September and February. The timing of major eDNA detection matched the pattern of adult emergence, but did not well reflect the larval influx. Major eDNA detection occurred twice, in April–June and November–December 2024. Three egg clutches were observed on December 23, 2024. On July 28, 2025, 110 eggs were counted at the same spawning site. Our combined results suggest that O. koreanus has two sperate breeding seasons each year, occurring April–June and November–December, and that eDNA detection along with population surveys can be useful to identify the breeding season of subterranean amphibians.
Fontan associated protein-losing enteropathy is linked to distinct metabolic and hepatic alterations
Abstract The univentricular Fontan circulation is associated with long-term multiorgan complications, including protein-losing enteropathy (PLE). While hemodynamic and lymphatic contributors to PLE have been described, its systemic metabolic signature remains incompletely characterized. We aimed to identify PLE-associated alterations in circulating metabolites using targeted serum metabolomics. Targeted serum metabolomic profiling was performed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) using the AbsoluteIDQ p180 kit. Forty-nine individuals were included: Fontan patients with PLE (FPLE, n = 10), Fontan patients without PLE (F, n = 30), and clinically stable biventricular controls (C, n = 9). Data were analyzed using MetaboAnalyst v6.0, including multivariate modeling (PLS-DA), univariate statistics with false discovery rate correction, correlation analyses, and receiver operating characteristic (ROC) analyses. Compared with controls, Fontan patients without PLE showed reduced concentrations of cholesterol, triacylglycerols, and several phosphatidylcholine (PC) species, whereas Fontan patients with PLE demonstrated relative increases in these lipid classes. Among 90 quantified PCs, 11 showed a consistent gradient with the lowest concentrations in F and the highest in FPLE. FPLE was further characterized by marked hypoalbuminemia and hypogammaglobulinemia, accompanied by elevated renin, aldosterone, and copeptin levels, indicating pronounced renal–neurohormonal activation of the renin-angiotensin-aldosterone system (RAAS) and vasopressin. Bile acid derivatives, including taurodeoxycholic acid and glycodeoxycholic acid, tended to be lower in FPLE and showed group-specific associations with both renin and selected PC species. Exploratory ROC-based screening identified the immunoglobulin G (IgG)-to-aldosterone and the albumin-to-PC ae C40:3 ratios as the most informative biomarker combinations distinguishing FPLE from non-PLE Fontan patients. These findings are exploratory and hypothesis-generating and require validation in independent cohorts. Fontan patients with PLE show a distinct metabolic phenotype integrating protein loss, lipid alterations, bile acid perturbations, and activation of the renin–angiotensin–aldosterone system. These findings suggest that metabolic and renal–neurohormonal pathways extend beyond lymphatic dysfunction in PLE and identify candidate biomarker patterns for further investigation rather than established diagnostic tools. Further studies are required to clarify causality, mechanistic links, and clinical generalizability.
The additive effect of IgE-mediated and pseudoallergic hypersensitivity in RBL-2H3 cells and guinea pigs
Drug hypersensitivity reactions (DHR) are commonly observed with various medications. However, some drugs, like Qingkailing (QKL), iodixanol, and vancomycin, previously classified as pseudoallergic, do not align with clinical observations, creating uncertainty in understanding DHR mechanisms and implementing prevention. In response, our research team hypothesized that IgE-mediated allergy and pseudoallergic hypersensitivity may synergistically lead to more severe reactions. We established an IgE-mediated hypersensitivity model using an anti-dinitrophenyl IgE monoclonal antibody in RBL-2H3 cells and employed ovalbumin (OVA) for guinea pigs. Compound 48/80 served as a positive control for non-immunologic hypersensitivity. We measured β-hexosaminidase and histamine released in cells and guinea pigs to focus on hypersensitivity responses from both IgE-mediated and pseudoallergic pathways. Results indicated that combining pseudoallergic drugs and IgE significantly increased the hypersensitivity response compared to IgE or separate compound 48/80 groups. This effect was mirrored in the OVA-induced model. Notably, the three pseudoallergic drugs exhibited a similar increase in IgE-mediated hypersensitivity. These findings highlight the additive effects of IgE-mediated and pseudoallergic hypersensitivity, suggesting a more potent DHR response. The study also measured several cytokines and developed a method to differentiate between allergic, pseudoallergic DHRs, and additive reactions, aiding in understanding and controlling serious DHR risks in clinical practice.
Comparative analysis of supervised and ensemble models with unsupervised exploration for alzheimer’s disease prediction
Streamlining psychosocial risk assessment: An exploratory adaptation of the COPSOQ III for Flemish healthcare workers
Background Healthcare workers are particularly vulnerable to psychosocial stress due to high emotional and cognitive demands, staffing shortages, and complex care responsibilities. The Copenhagen Psychosocial Questionnaire (COPSOQ III) is a widely used tool for assessing psychosocial risks at work, but its extended Flemish version has not been systematically evaluated in healthcare settings, and evidence on its psychometric performance in this context remains limited. Objective This exploratory study aimed to examine the factor structure and internal consistency of the extended Flemish version of the COPSOQ III among healthcare workers in Flanders, Belgium, and to provide initial psychometric evidence. Methods A cross-sectional survey was conducted among 242 employees across three healthcare institutions. Construct validity was examined through exploratory factor analysis (EFA) on polychoric correlations (oblimin rotation) to derive a revised factor structure of the extended Flemish COPSOQ III. Internal consistency of the resulting dimensions was assessed using Cronbach’s alpha, ordinal alpha, and McDonald’s omega (total and hierarchical). Multiple imputation was used in sensitivity analyses to evaluate the robustness of the factor structure and reliability estimates to missing data. A preliminary confirmatory factor analysis (CFA) was conducted as a supplementary, internal check of the proposed structure, rather than as a full confirmatory validation, given the limited sample size. Results EFAs supported retention of the original COPSOQ III domain framework while indicating meaningful within-domain refinements, including merged, split, and reallocated dimensions; the number of dimensions was reduced from 45 to 34. Most resulting dimensions showed acceptable internal consistency (ordinal α and ω_total generally ≥ 0.70), although a small number of brief scales showed lower reliability. Sensitivity analyses using multiple imputation yielded highly similar factor solutions and reliability estimates. Domain-specific CFAs provided preliminary support for the revised structures with acceptable fit on commonly used indices (e.g., CFI/TLI, RMSEA, SRMR), but these results should be interpreted cautiously as internal checks rather than definitive confirmation. Conclusion This exploratory study suggests that the extended Flemish version of COPSOQ III, with an adapted and more parsimonious structure, shows generally acceptable reliability and promising, though preliminary, evidence of construct validity for assessing psychosocial risks in healthcare settings. The adapted structure enhances its practical applicability while preserving theoretical integrity. Further research with larger and more diverse samples is recommended to confirm these findings in broader occupational contexts, test the stability of the proposed structure, and explore the utility of shorter versions in broader occupational contexts.
CD8+ T cell stemness precedes post-intervention control of HIV viraemia
Abstract Interventions to induce lasting human immunodeficiency virus (HIV) remission are needed to obviate the requirement for lifelong antiretroviral therapy. Durable post-intervention control (PIC) of viraemia has been achieved in a subset of people following administration of broadly neutralizing anti-HIV-1 antibodies (bNAb) and analytical interruption of treatment 1–4 . Previous studies support a role for CD8 + T cells in PIC 5–9 , but the precise features of CD8 + T cells involved remain unclear. Here we mapped and functionally profiled CD8 + T cell responses to autologous HIV epitopes using longitudinal samples from four analytical treatment interruption trials in bNAb recipients. PIC was associated with superior pre-intervention HIV-specific CD8 + T cell proliferative capacity, stem-cell-like memory phenotype and recall cytotoxicity against autologous HIV peptide-pulsed CD4 + T cells. CD8 + T cell stemness was increased further following bNAb administration without emergence of new clonotypes targeting defined HLA-optimal epitopes. Multi-modal single-cell analyses revealed molecular features associated with PIC and HIV-specific CD8 + T cell stemness, including signatures of metabolic fitness and reduced T cell exhaustion. These results identify immune features that precede subsequent PIC to inform the development of combination immunotherapies that will elicit durable HIV remission.
Potential of jute seeds crop waste for textile applications: a novel machine-based approach for sustainable resource utilization
Self-perceived far vision quality and night driving difficulties are not related to night myopia or visual acuity
This study aimed to psychometrically validate the Night Drive Questionnaire (NDQ), a new tool designed to assess self-reported far vision quality and difficulties related to night driving. Additionally, we evaluated the questionnaire’s potential for detecting and characterizing night myopia at an early stage. A total of 115 drivers, aged between 18 and 63 years (53% female), who regularly drove at night, completed the Night Drive Questionnaire (NDQ). Participants also had their refraction shift (night myopia) and visual acuity shift measured. Both refraction and visual acuity shift were calculated as the difference between the mesopic (low light) and photopic (normal light) measurements. We evaluated the 1) psychometric qualities through exploratory and confirmatory factor analyses, and 2) concurrent validity through correlations (Spearman) between the NDQ factors and night myopia and standard visual acuity shift and comparisons (Welch) between age groups, sexes, and night myopia levels. The NDQ displayed the best psychometric properties with a four-factor adjusted model, which includes: F1 – Quality of Far Vision, F2 – Difficulties in perceiving with central vision, F3 – Difficulties in perceiving with peripheral vision, and F4 – Difficulties in perceiving with the interaction of central and peripheral vision. This model demonstrated acceptable validity, consistency, and reliability indexes. Males compared to females reported fewer difficulties perceiving with central and peripheral vision and the combination of both (all p ≤ 0.011). There were no significant differences in driving difficulties based on age (all p ≥ 0.252) or night myopia groups (all p ≥ 0.242). Additionally, there were non-significant correlations between the factors and either night myopia or visual acuity shift (all p ≥ 0.092). In summary, the results indicate that the NDQ is a valid and reliable tool for measuring self-reported quality of far vision and the visual-related difficulties experienced during night driving, whether related to central, peripheral, or mixed vision. However, it is not effective in detecting or characterizing night myopia. Future studies should assess whether the NDQ is valid for identifying other visual function parameters that are more directly linked to night driving challenges.
Correction: In situ high temperature X-ray diffraction and dilatometric analysis of CGO–Cu composites for solid oxide devices
Teachers’ perspectives on barriers and motivators to physical activity participation in children from ethnic minority groups in Newcastle upon Tyne: A qualitative study
Physical inactivity among children in Western countries, especially children from ethnic minority groups, is a global health concern. Schools provide an ideal setting to address children’s physical activity needs, with teachers playing a major role. Therefore, the aim of this study was to explore teachers’ perspectives on barriers and motivators to physical activity participation in children from ethnic minority groups and to determine through their suggestions, how schools can be better supported to provide a physical activity-enabling environment. A purposive sample of eight primary school teachers in the Northeast of England, United Kingdom, participated in semi-structured interviews conducted through a combination of face-to-face and virtual settings. Reflexive thematic analysis identified seven barriers and nine motivators to physical activity, distributed across different levels of the socio-ecological theory. At the intrapersonal level, motivators included fun and wellbeing, whereas barriers included behavioural issues, and increased screen time. The interpersonal level encompassed influences of friends, parents, and teachers. At the institutional level, in-school activities were identified as motivators. At the community level, environmental influence and perceptions of safety were identified as barriers. At the public policy level, government/local council and resources were identified as both barriers and motivators. Notably, the teachers’ perspectives align with previous findings on barriers and motivators to physical activity among children from ethnic minority groups in the Northeast of England, while contributing to policy-level insights. These policy-level insights highlight the importance of staff training, government funding, and sports infrastructure improvements.
UCMSC-derived exosomes ameliorate dry eye disease pathogenesis by modulating neutrophils on Th17/Treg balance
Variant calling in genomics: A comparative performance analysis and decision guide
The accurate detection of genetic variants is critical for advancing genomics research and precision medicine. However, this task remains challenging due to pervasive sequencing errors and complex genomic regions. The choice of variant calling software significantly influences results, creating a need for clear, evidence-based guidance. This study aims to provide a performance evaluation and a clear, evidence-based guide for selecting variant callers by benchmarking seven widely used tools, GATK, FreeBayes, DeepVariant, Samtools, Strelka2, Octopus, and Varscan2, highlighting their algorithmic trade-offs. The well-characterized NA12878 genome from the Genome in a Bottle consortium was analyzed. High-coverage whole-genome sequencing data was processed with each variant caller, and the resulting variant calling files were benchmarked against a gold-standard reference. Performance was assessed using precision, recall, and F1-score on a chromosome 20 subset and on full whole-genome data. The analysis revealed that DeepVariant’s deep learning approach achieved the highest precision (0.7869) and F1-score (0.8754) on chromosome 20. For whole-genome analysis, Strelka2 excelled in precision (0.8326), while Octopus demonstrated superior recall (0.9838). FreeBayes exhibited high sensitivity but lower precision, underscoring a key trade-off. There is no universally superior variant caller; the optimal choice depends on the specific research objectives, whether prioritizing precision, recall, or computational efficiency. This study serves as a crucial evidence-based resource for researchers and clinicians, enabling informed tool selection.
Experimental study of microbial enhanced oil recovery in fractured porous media using the halophilic bacterium Haloferax mediterranei
Abstract Fractured reservoirs, comprising over 20% of the world’s oil reserves, present significant challenges to enhanced oil recovery (EOR). This study investigates the potential of the halophilic bacterium Haloferax mediterranei in microbial EOR (MEOR) for improving oil recovery in fractured porous media. Experiments using a heterogeneous glass micromodel were conducted at biomass concentrations of 5.07, 6.74, and 10.14 g/L. Results showed that the optimal biomass concentration (5.07 g/L) increased oil recovery by 23% through selective plugging. Higher biomass concentrations caused excessive polymer production, blocking communication pathways between the matrix and fractures, reducing oil recovery to 11.7% and 7.8%. Permeability reductions were evaluated in two core samples, achieving average reductions of 53.5%, 62.5%, and 73.5% for the respective biomass concentrations. Using the optimal biomass concentration (5.07 g/L), oil recovery in two similar core samples increased by 14% and 12.6%. These findings underscore the importance of optimizing biomass concentration to balance permeability reduction and oil recovery efficiency. The study highlights MEOR’s potential as a cost-effective, sustainable strategy for enhancing oil recovery in fractured reservoirs. It also provides valuable insights for improving future EOR operations, contributing to global energy resource sustainability.
Spatiotemporal aggregation and population distribution characteristics of HIV/AIDS in Nanchang city: A monitoring analysis from 2012–2021
AIDS is a major public health issue. As a transportation and economic hub in central China, Nanchang has frequent population mobility and unbalanced regional development, making it urgent to explore the prevalence characteristics of HIV/AIDS. Based on HIV/AIDS surveillance data in Nanchang from 2012 to 2021, this study innovatively integrates the Joinpoint regression model with spatiotemporal geographic information technology to construct an epidemiological analysis framework of “time-space-population”. The results show that a total of 3,789 HIV/AIDS infection cases were reported in the decade, with the growth rate of new cases (5.4%) significantly higher than the population growth rate (2.1%). There is a negative correlation between incidence and mortality, and men and the elderly (≥65 years old) are at prominent infection risk. Spatially, cases show significant heterogeneity, with “high-high” clustering areas concentrated in the city center and gradually expanding to surrounding areas, which is related to factors such as population density. The study provides a scientific basis for targeted interventions for men and the elderly, optimization of prevention and control strategies, and regional collaboration.
Correction: Model based noise correction enhances the accuracy of pancreatic CT perfusion blood flow measurements
A simplified two-dimensional culture system supports meiotic progression during mouse spermatogenesis in vitro
In vitro spermatogenesis (IVS) remains a major challenge due to its complexity and extended duration. Although organ culture of neonatal mouse testes can support complete spermatogenesis, its three-dimensional structure limits precise observation and control of culture conditions, resulting in heterogeneous oxygen and nutrient gradients. Two-dimensional (2-D) systems provide greater accessibility but often induce accelerated or abnormal meiosis. In this study, we present a simplified, serum free 2-D culture system that enables meiotic progression of mouse germ cells to the mid pachytene stage. Testicular cells from Acrosin ( Acr )-GFP transgenic mice (2.5 to 10.5 days postpartum : dpp) were enzymatically dissociated and cultured in APEL medium, a chemically defined and serum free basal formulation. The medium was supplemented with bovine pituitary extract (BPE), follicle stimulating hormone (FSH), and testosterone (BFT medium). Meiotic progression was monitored in real time by GFP fluorescence and further assessed by immunocytochemistry and nuclear spread analysis. Testicular cells consistently formed Sertoli cell monolayers and supported germ cell differentiation to mid pachytene stage. GFP-positive cells appeared around days 17.5 to 21.5 of culture, reflecting a modest delay compared to organ culture. GFP-positive cells were observed not only in 7.5 to 10.5 dpp cultures, but also in 2.5 to 6.5 dpp testes lacking preexisting spermatocytes, indicating de novo induction of meiosis. BFT medium, compared to APEL medium, increased the frequency of GFP-positive wells and the per-well duration of GFP expression, reaching statistical significance in the 9.5–10.5 dpp group (p = 0.021). Nuclear spread analysis confirmed synapsis through pachytene, although cells did not progress to diplotene. This simplified culture system offers a robust and accessible platform for studying early meiotic events and optimizing IVS.