Category: Statistics

Aquat Toxicol. 2026 Apr 3;295:107819. doi: 10.1016/j.aquatox.2026.107819. Online ahead of print.

ABSTRACT

Microplastics (MPs) and antibiotics are emerging pollutants that frequently co-occur in aquatic environments, where their interactions intensify ecotoxicological risks and may accelerate the spread of antibiotics resistance. Experimental assessment of such sorption-driven environmental behavior of mixture is costly, time-intensive, and ethically constrained, underscoring the need for predictive computational approaches. We have reported a Partial Least Squares (PLS)-based quantitative Read-Across Structure-Activity Relationship (q-RASAR) framework to evaluate the sorption-driven toxicity of antibiotics-microplastics mixtures. The distribution coefficient (log K_d) was selected as the endpoint, reflecting partitioning between aqueous and plastic phases, a key determinant of environmental persistence and bioavailability. A curated dataset of antibiotics-microplastics mixtures was used to generate mixture descriptors based on additivity, squared, and norm-based rules. Descriptors reduction and q-RASAR integration yielded a final model with five hybrid descriptors (structural + similarity-based). The model exhibited strong internal robustness (Q²_LOO = 0.761) and high external predictivity (Q²_F1 = 0.832; MAE_test = 0.152). Applicability domain and Y-randomization confirmed statistical soundness. Mechanistic analysis indicated that hydrogen-bond donors, oxygen-based polar functionalities, and terminal unsaturation enhance adsorption, while steric hindrance and charge asymmetry reduce binding affinity. To address limited experimental data, we further designed 111 hypothetical mixtures and validated predictions using the Prediction Reliability Indicator (PRI) tool. Most predictions were classified as “Good” and within the applicability domain, confirming the framework’s scalability and reliability. By combining mechanistic interpretability with strong predictive power, the framework enables high-throughput virtual screening and supports early-stage environmental risk assessment, data-gap filling, and regulatory decision-making in line with OECD guidelines.

PMID:41967171 | DOI:10.1016/j.aquatox.2026.107819

Eur J Obstet Gynecol Reprod Biol. 2026 Apr 10;322:115116. doi: 10.1016/j.ejogrb.2026.115116. Online ahead of print.

ABSTRACT

BACKGROUND: Colpocleisis remains an effective yet often underutilised surgical option for advanced pelvic organ prolapse (POP), particularly in elderly women who no longer desire vaginal intercourse. Despite its long history, concerns persist regarding postoperative complications, urinary symptoms, and patient regret. This study aimed to evaluate the perioperative, long-term, and patient-reported outcomes of colpocleisis, and to identify predictors of persistent urinary incontinence.

METHODS: A retrospective single-centre cohort study was conducted including 66 women aged ≥60 years who underwent colpocleisis between January 2015 and January 2025. Perioperative data were obtained from a prospectively maintained database. Long-term follow-up was available for 40 patients, with a mean follow-up duration of 41.36 months. Outcomes included complications, prolapse recurrence, urinary symptoms, and patient satisfaction assessed using Patient Global Impression (PGI) questionnaires. Comparisons between partial and total colpocleisis were performed using risk ratios (RR), and univariate logistic regression was used to identify predictors of persistent urinary incontinence.

RESULTS: The mean age was 78 years. Overall perioperative complication rate was 9.1% (95% CI 4.2-18.5%). At long-term follow-up, anatomical success was achieved in 92.5% (95% CI 80.1-97.4%), with no patients requiring repeat prolapse surgery (0%, 95% CI 0-4.5%). Persistent urinary incontinence occurred in 30% (95% CI 18.1-45.4%), while no cases of de novo incontinence were observed. High patient satisfaction was reported by 81.4% (95% CI 63.0-92.1%), with a low regret rate of 3.7% (95% CI 0.7-18.3%). There were no statistically significant differences in outcomes between partial and total colpocleisis. On univariate analysis, urodynamic stress incontinence (OR 7.5, 95% CI 1.57-35.7, p = 0.01) and BMI ≥ 30 (OR 5.0, 95% CI 1.13-22.2, p = 0.03) were significant predictors of persistent urinary incontinence.

CONCLUSIONS: Colpocleisis is a safe and highly effective procedure for selected patients with advanced POP especially during the current emphasis on native tissues repairs for POP, offering durable anatomical outcomes, high satisfaction, and low regret rates. Preoperative urodynamic findings and obesity are important predictors of persistent urinary symptoms and should be considered during patient counselling and surgical planning.

PMID:41967161 | DOI:10.1016/j.ejogrb.2026.115116

Eur J Obstet Gynecol Reprod Biol. 2026 Apr 9;322:115110. doi: 10.1016/j.ejogrb.2026.115110. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of our study is to investigate the percentage of ovarian cancer (OC) patients with concomitant endometriosis and its distribution across histological subtypes, and to assess whether the presence of endometriosis influences overall survival (OS) and disease-free survival (DFS) in patients with clear cell and endometrioid OC.

METHODS: We conducted a retrospective observational study using patient’s medical records of two reference hospitals in Spain, including OC patients, with and without endometriosis. We analysed the frequency of the association between cancer and endometriosis, the differences in OS and DFS survival between patients with and without endometriosis and the influence of age, tumour size, histological subtype and grade.

RESULTS: Among the 257 patients included, 39 (15.2%) had concomitant endometriosis. This correlation was particularly strong in endometrioid (EC) and clear cell carcinoma (CCC) patients; 61.0% of whom have concomitant endometriosis. Survival analysis demonstrated that, in EC and clear CCC, endometriosis-associated patients had longer OS (HR = 0.1773 [IC95% 0.03053-1.019]) and DFS (HR = 0.02 [IC95% 0.0009266-0.5100]) than OC patients without endometriosis. The difference was statistically significant for OS (p = 0.0174) but not for DFS (p = 0.0525). Univariate analysis shows that age, BMI or cyst size did not significantly affect disease outcomes.

CONCLUSIONS: Endometriosis has a clear association with EC and CCC. Its presence improves OS in Ovarian Cancer patients. Further studies are needed to confirm the improvement in outcomes and to determine the nature of the putative protection.

PMID:41967157 | DOI:10.1016/j.ejogrb.2026.115110

J Natl Cancer Inst. 2026 Apr 9:djag108. doi: 10.1093/jnci/djag108. Online ahead of print.

ABSTRACT

BACKGROUND: Transcriptome-wide association studies (TWAS) integrate gene expression and genome-wide association studies (GWAS) to identify disease susceptibility genes. Because gene expression varies substantially across cell types within tissues, cell type-specific prediction models may enhance the power of TWAS.

METHODS: We conducted cell type-specific TWAS leveraging single-cell RNA sequencing data from the OneK1K cohort (14 immune cell types, 1.27 million cells) and GWAS summary statistics for seven cancers (>290,000 cases in total). To improve prediction accuracy, we developed a modeling framework that incorporates shared gene expression effects across cell types.

RESULTS: At a false discovery rate of 5% (Bonferroni 5%), we identified 106 (13) previously unreported loci for breast cancer, 51 (4) loci for prostate cancer, 11 (4) loci for lung cancer, 39 (5) loci for melanoma, 9 (1) loci for ovarian cancer, and 2 (1) loci for diffuse large B-cell lymphoma, with most genes exhibiting cell type specificity. Gene set analyses confirmed joint associations of unreported genes with breast and prostate cancer risk in UK Biobank data. Additional lung tissue scRNA-seq data with 113 individuals validated 18 of 32 (56.3%) significant genes for lung cancer. Across cancers, 139 significant genes were shared by at least two cancer types and were primarily enriched in specific immune cell types.

CONCLUSION: Cell type-specific TWAS improves the identification of novel cancer susceptibility loci and provides insights into the immune landscape of cancer etiology.

PMID:41967136 | DOI:10.1093/jnci/djag108

J Anim Sci. 2026 Apr 9:skaf308. doi: 10.1093/jas/skaf308. Online ahead of print.

ABSTRACT

Although several nutritional tables report Zn requirements for pigs, dietary Zn levels that exceed recommendations are commonly used to improve performance in nursery pigs. However, excessive Zn supplementation is a practice that has been recently regulated in different countries. Understanding the factors influencing Zn excretion is important for optimizing Zn utilization in swine production and mitigating regulations of its use. This review compiled data from 51 published studies to identify factors associated with Zn excretion using a principal component analysis and developed predictive models for fecal Zn excretion utilizing a meta-regression analysis. Because urine Zn excretion was negligible (around 2% of the total Zn excretion) fecal and total Zn excretion did not differ. The first two principal components (PC) accounted for 35.9% and 19.3% of the total database variance, respectively. Principal component 1 was primarily influenced by nutrient intake variables, including fiber, NE, nitrogen, and minerals such as P, Ca, and Fe, as well as body weight and feed intake. Principal component 2 was dominated by Zn-related variables including Zn intake, fecal Zn excretion, the difference between Zn intake and Zn requirements estimates from NRC (2012), and added dietary Zn. Variables such as Mn, Cu, and lactose intake moderately contributed to both components, whereas the use of antibiotics, exogenous enzymes other than phytase, and acidifiers had a low impact on the variation explained by both components. Stepwise selection indicated that when pigs were fed at or below their Zn requirement estimate, Zn, P, and Fe intake significantly influenced fecal Zn excretion. However, when Zn intake exceeds the requirement estimate, Zn sources and Zn intake were the most influential variables. Regardless of the scenario, Zn intake was the primary determinant of fecal Zn excretion. The meta-regression analysis indicated that when pigs are fed at or below their Zn requirement, 61% of Zn intake is excreted in feces, increasing to 82% when Zn intake exceeded requirements. In conclusion, while Zn excretion is affected by multiple dietary factors, their contribution under practical conditions is relatively low and Zn intake remains the primary determinant of fecal Zn excretion.

PMID:41967135 | DOI:10.1093/jas/skaf308

Eur J Cardiovasc Nurs. 2026 Apr 10:zvag101. doi: 10.1093/eurjcn/zvag101. Online ahead of print.

ABSTRACT

BACKGROUND: The foundation for future educational and job opportunities is laid during the crucial years of primary education. Navigating them while a parent has heart disease adds a potential stressor. We investigated whether childhood experience of parental heart disease was associated with I) primary and secondary education completion, and II) grade point average (GPA) in primary education.

METHODS AND RESULTS: This national register study included adolescents from the Danish Fertility Register born between 1979 and 2003. Through the National Patient Register adolescents were linked with their parents who either had ischaemic heart disease, arrhythmia, heart failure or heart valve disease. Statistical analyses included descriptive statistics, multivariate logistic and linear regression models. The population consisted of 102,829 adolescents with at least one parent diagnosed with heart disease. The matched reference population included 411,311 children without parental heart disease. Having a parent with heart disease was associated with lower odds of not completing primary education (OR: 0.56, 95% CI 0.52;0.62), corresponding to absolute risks of 0.6% among exposed and 1.9% among unexposed adolescents, and a lower GPA (estimate: -0.10, 95% CI: -0.12; -0.08) compared to peers. Parental ischaemic heart disease was associated with higher odds of not completing secondary education (OR: 1.31, 95% CI 1.17;1.47).

CONCLUSION: Exposure to parental heart disease was associated with lower odds of non-completion of primary education and slightly lower GPA, with small absolute differences, and showed no overall association with secondary education completion. Adolescents with a parent diagnosed with ischaemic heart disease had a lower completion of secondary education. These findings indicate diagnosis-specific differences in educational outcomes, with an overall limited impact on educational completion.

PMID:41967126 | DOI:10.1093/eurjcn/zvag101

Interdiscip Cardiovasc Thorac Surg. 2026 Apr 9:ivag106. doi: 10.1093/icvts/ivag106. Online ahead of print.

ABSTRACT

BACKGROUND: Uniportal video-assisted thoracoscopic surgery (U-VATS) has been increasingly adopted for anatomical segmentectomy because of its minimally invasive nature and favourable recovery profile. However, whether perioperative outcomes differ between complex and simple segmentectomy when performed via U-VATS remains uncertain. This study compared perioperative outcomes between complex and simple U-VATS segmentectomy.

METHODS: A systematic review and meta-analysis were conducted according to PRISMA 2020 and AMSTAR 2 guidelines, and the study was registered in PROSPERO (CRD420251151464). Six databases were searched for studies comparing complex and simple U-VATS segmentectomy for pulmonary lesions. Primary outcomes were operative time, intraoperative blood loss, and conversion to thoracotomy. Secondary outcomes included chest tube duration, hospital stay, and postoperative complications. Random-effects models were used for pooled analyses.

RESULTS: Five retrospective studies, including 1,051 patients (707 complex; 344 simple), were analysed. No statistically significant differences were detected in operative time (MD = 15.25 minutes, 95% CI: -1.25 to 31.75; P = 0.07; I2 = 88%), intraoperative blood loss (MD = -1.33 mL, 95% CI: -11.95 to 9.29; P = 0.81; I2 = 58%), or conversion to thoracotomy (OR = 0.46, 95% CI: 0.10 to 1.99; P = 0.30; I2 = 0%). Secondary outcomes also showed no significant differences, including chest tube duration (MD = -0.15 days, 95% CI: -0.41 to 0.11; P = 0.25; I2 = 26%), hospital stay (MD = -0.16 days, 95% CI: -0.73 to 0.40; P = 0.57; I2 = 66%).

CONCLUSION: No statistically significant differences were detected in key perioperative outcomes between complex and simple U-VATS segmentectomy; however, given substantial clinical heterogeneity and limited retrospective evidence, findings should be interpreted cautiously and are most applicable to selected patients treated in experienced, high-volume centres.

PMID:41967114 | DOI:10.1093/icvts/ivag106

Biostatistics. 2026 Jan 20;27(1):kxag007. doi: 10.1093/biostatistics/kxag007.

ABSTRACT

High-dimensional longitudinal data are increasingly available in biomedical research, especially from omics platforms, but pose substantial challenges for joint modeling with survival outcomes. These challenges include modeling complex temporal dynamics, accommodating cross-feature dependencies, and maintaining computational feasibility. We propose a novel joint modeling framework that addresses these issues using supervised low-rank functional tensor decomposition to capture latent structure in multivariate longitudinal data and proportional hazards modeling for time-to-event outcomes. The longitudinal process is represented as a multivariate functional tensor, with a low-rank approximation that incorporates supervision from baseline covariates. Estimation is performed using a likelihood-based Monte Carlo Expectation-Maximization algorithm, enabling coherent inference and individualized prediction. Our method produces dynamic predictions of both longitudinal feature trajectories and survival probabilities. Simulation studies demonstrate substantial improvements in estimation accuracy and predictive performance over a standard two-stage approach, particularly under high censoring and limited sample sizes. In application to the Alzheimer’s Disease Neuroimaging Initiative lipidomics data, the proposed model explains over 99% of variation with four components, and identifies significant subject-level latent predictors of dementia onset. This framework provides a scalable and interpretable strategy for integrating high-dimensional longitudinal biomarkers into joint models for disease progression and risk stratification.

PMID:41967112 | DOI:10.1093/biostatistics/kxag007

Can J Ophthalmol. 2026 Apr 8:S0008-4182(26)00129-8. doi: 10.1016/j.jcjo.2026.03.017. Online ahead of print.

ABSTRACT

OBJECTIVE: Glaucoma is the leading cause of irreversible blindness worldwide. No postmarketing study has comprehensively assessed Food and Drug Administration (FDA)-approved drugs for glaucoma risk by subtype, therapeutic class, and sex. This study sought to identify systemic and ophthalmic drugs associated with glaucoma-related adverse events (AEs).

DESIGN: Population-based pharmacovigilance analysis of FDA Adverse Event Reporting System (FAERS) reports (January 2004-December 2024).

PARTICIPANTS: All glaucoma-related AEs, including normal-tension glaucoma (NTG), open-angle glaucoma (OAG), and angle-closure glaucoma (ACG).

METHODS: Events were identified with the Medical Dictionary for Regulatory Activities Preferred Terms. Disproportionality was assessed using reporting odds ratios (RORs; 95% CI), Evans’ criteria (n > 2; χ² > 4, Proportional reporting ratio > 2) and Bayesian confirmation (information component, lower 95% bound [IC₀₂₅] > 0). Analyses were stratified by subtype and sex.

RESULTS: Among 13,237,811 FAERS reports, 2 165 involved glaucoma-related events: 67 NTG, 372 OAG, and 1 726 ACG. Ranibizumab showed the strongest NTG signal (ROR = 83.73; 95% confidence interval [CI] = 38.20-183.66), especially in females (ROR = 162.36; 95% CI = 62.14-424.21). In OAG, significant signals were found for ranibizumab (ROR = 27.13; 95% CI = 15.60-47.19), topiramate (ROR = 21.58; 95% CI = 12.14-38.37), duloxetine (ROR = 9.09; 95% CI = 4.85-17.03), alendronate (ROR = 13.52; 95% CI = 8.78-20.82), and female-specific methylphenidate (ROR = 42.57; 95% CI = 20.94-86.51). In ACG, top signals included tropicamide (ROR = 166.10; 95% CI = 105.18-262.30), topiramate (ROR = 109.19; 95% CI = 98.54-121.00), imipramine (ROR = 33.96; 95% CI = 20.05-57.53), phentermine (ROR = 25.25; 95% CI = 16.73-38.13), and chlorpromazine (ROR = 13.93; 95% CI = 7.69-25.21). Tropicamide, topiramate, and imipramine showed stronger ACG signals in males. All associations were statistically significant (p < 0.0001; IC₀₂₅ > 0).

CONCLUSIONS: This large-scale FAERS analysis provides the most comprehensive assessment of drug-associated glaucoma risk to date. It confirms known associations and identifies novel signals across anti-vascular endothelial growth factor, cardiovascular, psychiatric, and respiratory drugs. Subtype- and sex-specific patterns underscore the need for individualized risk assessment, targeted postmarketing surveillance, and cautious prescribing to reduce preventable glaucoma-related vision loss.

PMID:41967096 | DOI:10.1016/j.jcjo.2026.03.017

Eur J Prev Cardiol. 2026 Apr 9:zwag206. doi: 10.1093/eurjpc/zwag206. Online ahead of print.

ABSTRACT

AIMS: To examine the bidirectional association between myocardial infarction (MI) and depression and to summarize shared comorbidities and cardiovascular risk factors underlying their co-occurrence.

METHODS: PubMed, Embase, and PsycINFO were searched from inception to 31 December 2025 for prospective cohort and longitudinal studies reporting time-to-event estimates for either direction of the MI-depression association. Random-effects meta-analyses were used to pool adjusted hazard ratios (HRs), with heterogeneity assessed using the I2 statistic. Study quality was evaluated using the Newcastle-Ottawa Scale. Subgroup analyses by sex and age and sensitivity analyses restricted to high-quality studies and studies with only clinically diagnosed depression were performed. Antidepressant treatment class was examined exploratorily, and shared comorbidities and cardiovascular risk factors were synthesized descriptively.

RESULTS: Nine population-based cohort studies were included. Meta-analysis of two studies showed that MI was associated with an increased risk of subsequent depression (pooled adjusted hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.24-1.61; I2 = 0%). Eight studies examining depression as the exposure demonstrated an increased risk of incident MI (pooled adjusted HR 1.42, 95% CI 1.29-1.57), with substantial heterogeneity (I2 = 84.7%). Stratified estimates from individual studies suggested stronger relative associations among younger individuals and sex-specific differences according to the direction of the association. Sparse evidence indicated that tricyclic antidepressant use was associated with a higher observed risk of MI, whereas selective serotonin reuptake inhibitors were not. Cardiometabolic and mental comorbidities, including diabetes, hypertension, dyslipidaemia, coronary heart disease, stroke, anxiety, and post-traumatic stress disorder, alongside chronic kidney disease, were commonly reported across both temporal directions.

CONCLUSIONS: MI and depression show bidirectional associations, with each condition conferring an increased risk for the other. These associations are observed alongside demographic differences and shared cardiometabolic and mental comorbidities, stressing the importance of integrated cardiovascular and mental health assessment; however, these findings should be interpreted cautiously given the limited available evidence.

PMID:41967088 | DOI:10.1093/eurjpc/zwag206