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Nevin Manimala Statistics

Immune-related hub genes in intrauterine adhesions: a bioinformatics approach

PeerJ. 2025 Oct 3;13:e20035. doi: 10.7717/peerj.20035. eCollection 2025.

ABSTRACT

BACKGROUND: Intrauterine adhesions (IUA) are a leading cause of acquired female infertility that predominantly arises following surgical intrauterine interventions. Clinical strategies are available for managing IUA, however, the molecular pathogenesis of IUA, particularly the role of immune dysregulation in endometrial repair processes, has not been fully characterized, necessitating comprehensive mechanistic studies.

METHODS: We used computational biology methods to determine the molecular pathogenesis of IUA, the results of which were experimentally validated. (i) We systematically reanalyzed GSE224093, a publicly available endometrial transcriptomic dataset, using GEO2R. Differential gene expression was analyzed with stringent statistical thresholds; the results were immunologically contextualized via intersection with the ImmPort database. (ii) Multilayer functional annotation was conducted using Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway topology analyses. (iii) Weighted gene co-expression network analysis and scale-free topology optimization were used to identify conserved coexpression modules. (iv) Seven hub genes underwent quantitative real-time polymerase chain reaction (qPCR) validation in human and murine models, with four verified using immunohistochemistry (IHC).

RESULTS: Our integrated multiomics analysis identified seven hub genes associated with IUA pathogenesis through GO, KEGG, and GSEA enrichment analyses. The expression levels TUBB3, WNT5A, GDF7, IGF1, and BIRC5 were downregulated, and those of PTGDS and CCL14 were upregulated. The qPCR results confirmed these expression patterns in human and murine endometria (p < 0.05), with TUBB3 and PTGDS species-specifically diverging from the computational predictions. The IHC results provided the corresponding protein expression changes for IGF1, WNT5A, BIRC5, and GDF7 in IUA (p < 0.01). CCL14 could not be amplified in murine models due to technical constraints.

DISCUSSION: We identified seven immune-related gene signatures through integrative bioinformatics. We experimentally validated three genes (TUBB3, PTGDS, and CCL14) demonstrating species-specific expression patterns. We proposed four mechanistically plausible biomarkers (WNT5A, IGF1, BIRC5, and GDF7) for developing IUA diagnostic tools. The conserved dysregulation of WNT5A- and TGF-β-associated genes (GDF7 and IGF1) suggest therapeutic targets for preventing adhesion recurrence. This study advances our understanding of IUA pathogenesis. Single-cell transcriptomics should be examined in future studies to determine the cellular-subtype-specific contributions to IUA.

PMID:41059402 | PMC:PMC12499562 | DOI:10.7717/peerj.20035

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Current status of medical collaboration for persons with mental disabilities who use type-B continuous employment-support facilities

J Rural Med. 2025 Oct;20(4):282-293. doi: 10.2185/jrm.2025-035. Epub 2025 Oct 1.

ABSTRACT

OBJECTIVE: This study aimed to clarify the current status of collaboration between type-B continuous employment-support facilities and psychiatric care in Japan and determine the intention of these facilities toward medical collaboration.

METHODS: A self-administered anonymous questionnaire survey was conducted by mail. Basic descriptive statistics were calculated for the questions with multiple-choice responses. For the free descriptions of medical collaborations, we grouped sentences with similar meanings and generated categories.

RESULT: Of type-B employment continuation support offices, 76% collaborated with psychiatrists. However, only 6% incurred an additional fee for the medical collaboration system. They attempted to collaborate with medical care by contacting doctors and nurses and accompanying them during medical examinations. Some respondents stated that they did not need to collaborate with medical care. Type-B facilities often require support from doctors and nurses regarding support for psychiatric symptoms, guidance on medication, and other problems related to illnesses and treatment. Other opinions suggested that persons with mental disabilities should solve their problems themselves without intervention by doctors or nurses and that the support they want is absent. Among type-B continuous employment-support facilities that do not hire nurses, 25% would be unable to hire them, although desired, because of financial difficulties or other reasons, and 72% did not consider doing so.

CONCLUSION: Among the type-B continuous employment-support facilities, 76% collaborated with the psychiatric department. Some respondents indicated that medical collaboration was “Not required”. Among the types of support expected from doctors and nurses, those related to illness and treatment were the most commonly requested. But opinions emerged, including “No support is sought”. Many type-B continuous employment-support facilities that do not employ nurses, do not consider hiring nurses, and the most common reason is “Economically difficult to hire”.

PMID:41059372 | PMC:PMC12497983 | DOI:10.2185/jrm.2025-035

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Examining the Impact of Mesoporous Zinc Oxide Nanoparticle Inclusion on the Surface Microhardness and Roughness of Resin-Modified Glass Ionomer Cement: An In Vitro Analysis

Int J Dent. 2025 Sep 29;2025:5491727. doi: 10.1155/ijod/5491727. eCollection 2025.

ABSTRACT

AIM: Addressing the need for enhanced antibacterial properties in dental materials, this study investigated the impact of integrating zinc oxide nanoparticles (ZnO NPs) and mesoporous ZnO NPs into resin-modified glass ionomer cement (RMGIC) on microhardness and surface roughness.

MATERIALS AND METHODS: Seventy disk-shaped RMGIC specimens were allocated to seven experimental groups: RMGIC (control), RMGIC with 3 wt.% ZnO NPs, 5 wt.% ZnO NPs, 7 wt.% ZnO NPs, 3 wt.% mesoporous ZnO NPs, 5 wt.% mesoporous ZnO NPs, and 7 wt.% mesoporous ZnO NPs. Surface roughness and Vickers microhardness were quantified using a surface profilometer and Vickers microhardness tester, respectively. Statistical analysis was carried out with a significance level set at p < 0.05.

RESULT: Incorporating 5 wt.% of ZnO NPs or mesoporous ZnO NPs into the RMGIC yielded the highest microhardness values, while the control group exhibited the lowest microhardness values. Notably, the microhardness values of RMGIC with 3 and 5 wt.% ZnO NPs or mesoporous ZnO NPs were significantly higher than those of the 7 wt.% concentration. Regarding surface roughness, the control group displayed the highest roughness value, while RMGIC with 5 wt.% mesoporous ZnO NPs exhibited the lowest roughness values. Therefore, incorporating up to 5 wt.% ZnO NPs or mesoporous ZnO NPs led to decreased roughness values, with a notable increase observed at the 7 wt.% concentration, albeit still lower than the control group’s roughness values.

CONCLUSION: Incorporating 5 wt.% ZnO NPs or mesoporous ZnO NPs resulted in significantly enhanced microhardness values compared to the control group and the 7 wt.% concentration. The introduction of up to 5 wt.% NPs led to reduced surface roughness, with the 7 wt.% concentration showing a slight increase in roughness. These findings highlight the importance of optimizing NP concentrations, particularly mesoporous NPs, in RMGIC to enhance mechanical properties, offering valuable insights for the development of dental materials with improved performance characteristics.

PMID:41059355 | PMC:PMC12500347 | DOI:10.1155/ijod/5491727

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Genetic signatures of exceptional longevity: a comprehensive analysis of coding region single nucleotide polymorphisms (SNPs) in centenarians and supercentenarians

Hum Genomics. 2025 Oct 7;19(1):115. doi: 10.1186/s40246-025-00772-3.

ABSTRACT

Aging, a complex biological process, entails sequential changes in organisms that elevate the risk of frailty, disease, and mortality, affecting individuals at the level of cellular, organ, and organism. This process is influenced by genetic diversity, socioeconomic status, healthcare infrastructure, lifestyle choices, and cultural practices. Gerontology delves into the factors shaping longevity, aging processes, and aging from both evolutionary and individual perspectives. Centenarians and supercentenarians serve as models for studying exceptional longevity, offering insights into the aging process and resistance to age-related diseases. This research investigates common genetic variations (SNPs) shared among 3 centenarians and 18 supercentenarians, individuals aged 110 years or older. 754,520 SNPs were found to be common among all the 21 samples. Utilizing SNPnexus, a genetic variant annotation tool, we annotated coding variants and assessed potential disease susceptibilities associated with these variants. Ensembl was used as an annotation system, we annotated 1,607,122 variants, and found 11,348 coding variants. Among them, 4980 had non-synonymous variants, and 110 variants were observed to have deleterious effects. These deleterious SNPs were linked with 79 genes among them 16 novel variants were identified in 9 genes. The population frequency comparison using the 1000 Genomes Project and gnomAD revealed that a subset of these common, non-synonymous SNPs and deleterious SNPs had minor allele frequencies (MAF) below 1% or were absent entirely, suggesting potential rare variants specific to this cohort. In addition, we also found statistically significant (p < 0.05) 148 enriched pathways, among them the top enriched pathways such as extracellular matrix (ECM) remodeling, signal transduction, disease-associated pathways, sensory processing and metabolism of proteins and RNA. These preliminary findings may help prioritize candidate variants and genes for future studies on larger cohorts with appropriate controls can help in understanding the genetic basis of exceptional longevity.

PMID:41057961 | DOI:10.1186/s40246-025-00772-3

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Prevention and intervention against obesity and overweight in the military: a systematic review

J Occup Med Toxicol. 2025 Oct 7;20(1):32. doi: 10.1186/s12995-025-00480-7.

ABSTRACT

BACKGROUND: Overweight and obesity have a negative impact on health and have a detrimental effect on the operational readiness of soldiers. Different prevention and intervention measures against obesity include diet, physical activity, education, coaching or medication or a combination of several aspects have been investigated. This review systematically assesses the effectiveness of lifestyle, dietary, educational, and pharmacological interventions on weight, body composition, and military readiness in active-duty personnel.

METHODS: We carried out a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search was conducted in various electronic databases from 2000 to July 2024. The search strategy combined three concepts: military population, outcome terms, interventions or programs. For the review, 21 articles met the inclusion criteria (total n = 1696). Where possible, the effect size (ES) was calculated.

RESULTS: In studies that only examined exercise, minor effects were reported, e.g. a reduction in weight (-0.5 kg), Body Mass Index (BMI) (-0.3 kg/m²), waist circumference (-0.1 cm) and body fat percentage (-1.1%) without relevant statistical ES. Studies with nutritional programs reported low to moderate ES. Combined programs including dietary and exercise countermeasures showed to be more effective than programs based on diet or exercise alone. Combined programs with exercise and educational methods showed a moderate to large effect size (ES 0.6-1.3) for weight reduction. Pharmacological treatment for reducing fat intake resulted in a larger effect sizes for weight loss. The greatest efficacy (ES > 1.0) was observed for a combined intervention program consisting of lifestyle changing components based on individually tailored cognitive behavioral therapies, psychoeducation, exercise and nutritional interventions.

CONCLUSIONS: Effective countermeasure for reducing body weight found in this study were combined interventions, like education on lifestyle changes, dietary habits and promotion of physical activity in military personnel, as well as by ketogenic dietary interventions combined with physical activity and followed by pharmacological intervention approaches. Combined interventions appear promising in some studies, but future evaluations may focus on combinations of physical activity and exercise with new pharmaceutical approaches like Semaglutide or Bimagrumab medication in the long term for military personnel due to probable favorable body composition adaptations and military readiness.

PMID:41057950 | DOI:10.1186/s12995-025-00480-7

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Health-related quality of life in COVID-19 patients: a systematic review and meta-analysis of EQ-5D studies

Health Qual Life Outcomes. 2025 Oct 7;23(1):97. doi: 10.1186/s12955-025-02421-8.

ABSTRACT

BACKGROUND: COVID-19 has affected millions globally, with a significant proportion experiencing long-COVID and impaired health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to synthesize the existing literature on HRQoL in COVID-19 patients.

METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, Scopus, and the Cochrane Library for studies published between December 2019 and March 2025. Eligible studies were peer-reviewed and assessed HRQoL in COVID-19 patients using the EQ-5D instrument. Study quality and risk of bias were evaluated using the Newcastle-Ottawa Scale. Pooled health utility values were estimated using a random-effects model, and heterogeneity was assessed via I2 statistics. Predictors of poor HRQoL were qualitatively narrated.

RESULTS: Out of 3539 references, 187 studies with 116,525 participants were analyzed. The majority (80.2%) used the EQ-5D-5 L version. The pooled mean EQ-5D utility score was 0.76 (95% CI 0.74-0.79, I2 = 99.9%) while the mean EQ-5D Visual Analogue Scale (VAS) score was 70.76 (95% CI 68.48-73.04; I2 = 99.7%). Pain/discomfort and anxiety/depression were the most affected domains, reported by 51% and 46% of patients, respectively. Subgroup analysis showed significant differences in HRQoL based on national income status (p = 0.038) and geographic region (p < 0.001). Common predictors of lower HRQoL included older age, female gender, disease severity, comorbidities, and post-COVID-19 symptoms.

CONCLUSION: This systematic review demonstrates a substantial reduction in HRQoL among COVID-19 patients compared to the general population. The pooled utility values of COVID-19 contribute to understanding patients’ HRQoL and can assist in calculating Quality-Adjusted Life Years. This provides essential data for future economic evaluations and informs health policy decisions.

PMID:41057923 | DOI:10.1186/s12955-025-02421-8

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Genomic landscape of cancer driver genes in Omani breast cancers: a pilot study

Breast Cancer Res. 2025 Oct 7;27(1):172. doi: 10.1186/s13058-025-02133-3.

ABSTRACT

BACKGROUND: The global rise in breast cancer (BC) incidence is mirrored in the Sultanate of Oman, where the median age of diagnosis is strikingly young at 47 years. This pilot study represents the first in the region to examine the genetic alterations of Omani BC biopsies and resected tumors and their correlations with patient characteristics using a targeted pan-cancer panel.

METHODS: Utilizing the Oncomine Comprehensive Assay Plus, we profiled 40 BC biopsies alongside 22 matched post-neoadjuvant chemotherapy samples, identifying single-nucleotide variations (SNVs) and copy number variations (CNVs). Chi-Square and Fisher’s Exact tests were used for categorical variables. In contrast, the Independent T-test and Levene test were used for continuous variables. Comparative analyses were conducted using the METABRIC and TCGA datasets to place these findings in a global context.

RESULTS: The data revealed molecular patterns between early-onset (under 50 years) and late-onset (50 years and older) cases. Notably, SNVs were predominant in late-onset tumors, while CNVs were more frequent in early-onset cases. PIK3CA SNVs emerged as a hallmark of late-onset BC, which persists across pre- and post-treatment stages. NTRK1 mutations were linked to late-onset cases at pre-treatment, while OR6F1 CNV was exclusive to early-onset tumors. The five genes with the highest CNV prevalence in the cohort were CDK12, ERBB2, BRIP1, and BLM, and they closely mirrored those found in global datasets. Correlations with clinical features identified CHEK2 alterations associated with high-grade tumors and luminal and HER2 type, while TP53 mutations were predominantly found in TNBC cases. Mutations in CBFB and GATA3 were predominantly enriched in luminal subtypes, and TSC1 mutations corresponded with smaller tumors, whereas FGFR4 SNVs were linked to nodal (N) status. Additionally, we identified 19 new SNV variants distributed across seven genes that were not recorded in the public databases.

CONCLUSION: This study sheds light on the genetic landscape of BC driver genes in Oman and the shared molecular traits with Western populations while uncovering unique regional alterations in NTRK1, OR6F1, and FGFR4. These findings highlight the need for region-specific insights to inform targeted therapies and personalized care, advancing the global understanding of BC biology.

PMID:41057920 | DOI:10.1186/s13058-025-02133-3

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Exploring academic motivation across university years: a mixed-methods study at King Faisal University

BMC Psychol. 2025 Oct 7;13(1):1113. doi: 10.1186/s40359-025-03448-8.

ABSTRACT

This study explores how gender and year of study influence academic motivation among undergraduate students at King Faisal University, Saudi Arabia, an understudied non-Western, gender-segregated context in the motivation literature. By situating the research within this unique population, the study responds to calls for expanding motivational research beyond Western samples and contributes culturally grounded insights to the field. Using a mixed-methods approach, quantitative data were collected from 267 students (51.3% female, 48.7% male) via the Academic Motivation Scale, alongside qualitative insights from nine semi-structured interviews. Descriptive statistics showed that female students consistently scored higher in both intrinsic and extrinsic motivation, while male students reported significantly greater levels of amotivation. Motivation peaked in the first year of university and declined steadily in later years. Two-way ANOVA results revealed significant main effects of both gender and year of study across all seven academic motivation subscales (p < .05), though no significant interaction effects were found, suggesting stable gender-based differences across academic progression. Regression analysis further identified gender (β = 0.50, p = 0.013) and year of study (β = -0.75, p < 0.001) as significant predictors of motivation, particularly for intrinsic motivation to know. Thematic analysis reinforced the quantitative findings, highlighting external pressures, career concerns, and sociocultural expectations as key factors shaping students’ motivational experiences. These findings underscore the urgency of implementing targeted, gender-sensitive interventions, such as academic mentoring, psychological support, and flexible curricular pathways, to sustain motivation, particularly in later academic years. By contextualizing academic motivation within the Saudi higher education system, this study contributes novel empirical insights and practical implications for educators and policymakers aiming to enhance student engagement and persistence in culturally specific settings.

PMID:41057916 | DOI:10.1186/s40359-025-03448-8

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Comparative analysis of Chinese classical prescriptions and global traditional polyherbal formulations: insights from the database of global polyherbal formulation (GPFD)

Chin Med. 2025 Oct 7;20(1):169. doi: 10.1186/s13020-025-01145-7.

ABSTRACT

Polyherbal formulations (PHFs) serve as a cornerstone of traditional medical systems worldwide and remain integral to diverse therapeutic practices. The COVID-19 pandemic has reinvigorated scientific interest in PHFs, driving extensive investigations into their composition and pharmacological potential. In this study, we systematically analyzed PHFs across major traditional medical systems, including Traditional Chinese Medicine (TCM), Kampo, Ayurveda, and Unani. To facilitate comprehensive analysis, we developed the Global Polyherbal Formulation Database (GPFD), a repository documenting formulation names, sources, historical evolution, ingredient composition, dosages, medicinal origins, and therapeutic applications. Leveraging this extensive dataset, we conducted a cross-system comparative analysis of PHFs using statistical analysis and data integration approaches. Our investigation focused on plant usage frequency and co-occurrence patterns to uncover underlying principles of formulation design. This study establishes a research framework for PHFs, explores the relationship between species selection, and ecological distributions, and identifies key taxonomic differences in plant utilization across systems. Additionally, we reveal distinct preferences in herbal combinations within each system, highlighting both shared and unique formulation patterns. These findings provide critical insights into the cross-cultural utilization of PHFs and offer a data-driven foundation for integrating traditional botanical knowledge into modern pharmacological research and drug development.

PMID:41057911 | DOI:10.1186/s13020-025-01145-7

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Novel clinical and genetic insights into Gitelman syndrome from 95 Chinese patients

Hum Genomics. 2025 Oct 7;19(1):114. doi: 10.1186/s40246-025-00828-4.

ABSTRACT

BACKGROUND: Gitelman syndrome (GS) is a rare tubulopathy with clinical and genetic heterogeneity. This study aimed to investigate the characteristics of Chinese GS patients.

METHODS: The diagnosis of GS was established by combining clinical phenotypes with genetic testing, after which the clinical, biochemical, and genetic data were statistically analyzed.

RESULTS: We reported 95 Chinese GS patients aged 2-52 years. The younger group (≤ 16 years) had more frequent febrile episodes (20.4% vs. 4.3%, P = 0.028) and nausea/vomiting (12.2% vs. 0.0%, P = 0.027) but fewer paresthesia/numbness (20.4% vs. 43.5%, P = 0.026) and palpitations (8.2% vs. 37.0%, P = 0.001), along with higher serum potassium and magnesium levels (2.86 ± 0.45 mmol/L vs. 2.67 ± 0.38 mmol/L, P = 0.034; 0.65 ± 0.14 mmol/L vs. 0.58 ± 0.16 mmol/L, P = 0.031) than the older group (> 16 years). Moreover, serum potassium and magnesium levels were positively correlated and both were negatively correlated with age. Additionally, Among 170 detected SLC12A3 variants, 73 distinct variants were identified, including six novel ones. The compound heterozygous group exhibited higher serum magnesium levels compared to the heterozygous and homozygous groups (0.65 ± 0.17 mmol/L vs. 0.56 ± 0.09 mmol/L, P = 0.015; 0.65 ± 0.17 mmol/L vs. 0.51 ± 0.07 mmol/L, P < 0.001). Age at diagnosis was associated with variant types.

CONCLUSION: The study characterized the phenotypic and genotypic features of Chinese GS patients, highlighting age and mutation genotype as key factors influencing phenotype, underscoring the importance of standardized potassium and magnesium supplementation, and expanding the known mutation spectrum with novel variants.

PMID:41057907 | DOI:10.1186/s40246-025-00828-4