Category: Statistics

Physiol Rep. 2025 Jul;13(13):e70455. doi: 10.14814/phy2.70455.

ABSTRACT

The present study compared acute testosterone (T), cortisol (C), epinephrine (EPI), norepinephrine (NE), and 22 kDa growth hormone (GH-22 kDa) responses following low-load resistance exercise with blood flow restriction (LL-BFR) and traditional high-load resistance exercise (HL-RE). Twelve resistance-trained men performed bouts of LL-BFR (30%1RM) and HL-RE (70%1RM), each consisting of four sets of bilateral seated leg extensions taken to momentary task failure with 60 s rest periods. A randomized crossover design was used with time of day matched within-subjects. Upon arrival between 1200 and 1800, 24 h dietary recalls were performed with post-exercise blood samples obtained within 60 s (IP) and 5 min post-exercise (+5 min) via intravenous cannulation. Greater total repetitions (d = 2.37, p < 0.001) and less volume-load (d = 2.86, p < 0.001) were performed during LL-BFR. No Condition × Time interaction effects were found for any hormonal analyte measured (p > 0.05). Both LL-BFR and HL-RE elevate the potent β₂ adrenergic receptor (β₂AR) agonist EPI (IP: 1.29 ± 0.44 and 1.35 ± 0.60 nmol·L^-1, respectively), and the androgenic steroid T (+5 min: 27.4 ± 12.9 and 29.0 ± 14.3 nmol·L^-1, respectively). Thus, acute skeletal muscle β₂AR phosphorylation may be comparable between conditions. When lower resistance exercise intensities (e.g., 30% 1RM) are desired, athletes may perform LL-BFR in place of HL-RE and experience no statistical difference in acute endocrine responses.

PMID:40631360 | DOI:10.14814/phy2.70455

Health Sci Rep. 2025 Jul 8;8(7):e70995. doi: 10.1002/hsr2.70995. eCollection 2025 Jul.

ABSTRACT

BACKGROUND AND AIM: Foodborne diseases pose serious health challenges in developing countries like Somalia, contributing to high rates of illness and death due to inadequate food safety practices, poor sanitation conditions, ineffective regulatory systems, and a lack of educational resources for food handlers. This study determined food handling practices and their associated factors among food handlers in Mogadishu, Somalia.

METHODS: A cross-sectional study was conducted with 304 food handlers in Mogadishu, Somalia, and data were gathered through direct interviews. Analysis was performed using SPSS Version 26, including descriptive statistics and logistic regressions (binary and multivariate). Adjusted Odds Ratios (AOR) and a significance level of p < 0.05 were employed to assess significant variables related to food safety measures.

RESULTS: The results show that only 27.3% of food handlers practiced proper food handling procedures. This means that the majority of those observed exhibited poor food handling practices. Various factors significantly influenced these practices, including age (AOR = 0.1; 95% CI: 0.05-0.21), marital status (AOR = 0.1; 95% CI: 0.06-0.27), work experience (AOR = 0.2; 95% CI: 0.10-0.44), and monthly income (AOR = 3.1; 95% CI: 1.56-6.21).

CONCLUSION: The study revealed that over two-thirds of participants practiced poor food handling, posing public health risks. Key factors included age, marital status, work experience, and income. Authorities should improve health education, strengthen environmental health services, and train food handlers to enhance safety and health outcomes in Somalia.

PMID:40631346 | PMC:PMC12235575 | DOI:10.1002/hsr2.70995

bioRxiv [Preprint]. 2025 Jul 4:2025.06.30.662443. doi: 10.1101/2025.06.30.662443.

ABSTRACT

Mismatches between interacting mitochondrial and nuclear gene products in hybrids have been proposed to disproportionately contribute to the formation of early species boundaries. Under this model, genetic incompatibilities emerge when mitochondrial haplotypes are placed into a cellular context without their coevolved nuclear-encoded mitochondrial (n-mt) proteins. Although there is strong evidence that mitonuclear coevolution has contributed to reproductive isolation in some cases, it is less clear how far-reaching the effects of mitonuclear incompatibilities are in speciation. Does disrupting co-adapted mitonuclear genotypes have broad, genome-wide effects with numerous n-mt loci contributing to reproductive isolation? We leverage a system with several hybridizing species pairs ( Xiphophorus fishes) that have known mitonuclear incompatibilities of large effect to ask whether a general signal of incompatibility is present when considering all n-mt genes. After dividing nuclear-encoded proteins into three classes based on level of interaction with mitochondrial gene products, we found only inconsistent statistical evidence for a difference between these classes in the degree of conserved mitonuclear ancestry. Our results imply that genome-wide scans focused on enrichment of broad functional gene classes may sometimes be insufficient for detecting a history of mitonuclear coevolution, even when strong selection is acting on mitonuclear incompatibilities at multiple loci.

PMID:40631220 | PMC:PMC12236695 | DOI:10.1101/2025.06.30.662443

bioRxiv [Preprint]. 2025 Jul 4:2025.06.30.662450. doi: 10.1101/2025.06.30.662450.

ABSTRACT

India is the most populous country globally, yet genetic studies involving Indian individuals remain limited. The Indian population is composed of many founder groups and has a mixed genetic ancestry, including an ancestral component not observed anywhere outside of India. This presents a unique opportunity to uncover novel disease variants and develop more tailored medical interventions. To facilitate genetic research in India, a crucial first step is to create a foundational resource that serves as a benchmark for future population studies and methods development. To this end, we have constructed the largest and most nationally representative linkage disequilibrium and genotype imputation reference panels in India to date, using high-coverage whole-genome sequencing data of 2,680 Indian participants from the Longitudinal Aging Study in India-Harmonized Diagnostic Assessment of Dementia (LASI-DAD). As an LD reference panel, LASI-DAD includes 69.5 million variants, representing 170% and 213% increases relative to the 1000 Genomes Project (1000G) and TOP-LD panels, respectively. Besides serving as an LD lookup panel, LASI-DAD facilitates various statistical analyses that rely on precise LD estimates. In a polygenic risk score (PRS) analysis, LASI-DAD improved the predictive performance of PRS by 2.1% to 35.1% across traits and studies. As an imputation reference panel, LASI-DAD improved the imputation accuracy by 3% to 101% (mean = 38%) compared to the TOPMed panel (Version R3) and by 3% to 73% (mean = 27%) compared to the Genome Asia Pilot (GAsP) panel across different minor allele frequencies. The LASI-DAD reference panel is publicly available to benefit future studies.

PMID:40631173 | PMC:PMC12236690 | DOI:10.1101/2025.06.30.662450

bioRxiv [Preprint]. 2025 Jul 5:2025.07.01.662655. doi: 10.1101/2025.07.01.662655.

ABSTRACT

DNA methylation is a compulsory and fundamental epigenetic mechanism, and its significant changes (i.e., differential methylation) regulate gene expression, cell-type specification and disease progression without altering the underlying DNA sequence. Differential methylation biomarkers were widely used as inputs for various downstream investigations, and differential methylation could be detected via existing statistical tools by comparing two groups of methyomes (i.e. whole-genome methylation profiles). However, few toolboxes were available to integrate robust detection, annotation and visualization of differential methylation to efficiently streamline methylation investigation. Also, differential methylation detected via tools has poor reproducibility and no tools were tested on long-read methylomes. To address these issues, we introduced DiffMethylTools, an end-to-end solution to eliminate analytical and computational difficulties for differential methylation dissection. Comparison on six datasets including three long-read methylomes demonstrated that DiffMethylTools achieved overall better detection performance of differential methylation than existing tools like MethylKit, DSS, MethylSig, and bsseq. Besides, DiffMethylTools supported versatile input formats for seamless transition from upstream methylation detection tools, and offered diverse annotations and visualizations to facilitate downstream investigations. DiffMethylTools therefore offered a robust, interpretable, and user-friendly solution for differential methylation investigation, benefiting the dissection of methylation’s roles in human disease studies.

PMID:40631172 | PMC:PMC12236622 | DOI:10.1101/2025.07.01.662655

bioRxiv [Preprint]. 2025 Jul 1:2025.06.27.661814. doi: 10.1101/2025.06.27.661814.

ABSTRACT

Pooled single-cell perturbation screens represent powerful experimental platforms for functional genomics, yet interpreting these rich datasets for meaningful biological conclusions remains challenging. Most current methods fall at one of two extremes: either opaque deep learning models that obscure biological meaning, or simplified frameworks that treat genes as isolated units. As such, these approaches overlook a crucial insight: gene co-fluctuations in unperturbed cellular states can be harnessed to model perturbation responses. Here we present CIPHER (Covariance Inference for Perturbation and High-dimensional Expression Response), a conceptual framework leveraging linear response theory from statistical physics to predict transcriptome-wide perturbation outcomes using gene co-fluctuations in unperturbed cells. We validated CIPHER on synthetic regulatory networks before applying it to 11 large-scale single-cell perturbation datasets covering 4,234 perturbations and over 1.36M cells. CIPHER robustly recapitulated genome-wide responses to single and double perturbations by exploiting baseline gene covariance structure. Importantly, eliminating gene-gene covariances, while retaining gene-intrinsic variances, reduced model performance by 11-fold, demonstrating the rich information stored within baseline fluctuation structures. Moreover, gene-gene correlations transferred successfully across independent experiments of the same cell type, revealing stereotypic fluctuation structures. Furthermore, CIPHER outperformed conventional differential expression metrics in identifying true perturbations while providing uncertainty-aware effect size estimates through Bayesian inference. Finally, most genome-wide responses propagated through the covariance matrix along approximately three independent and global gene modules. CIPHER underscores the importance of theoretically-grounded models in capturing complex biological responses, highlighting fundamental design principles encoded in cellular fluctuation patterns.

PMID:40631127 | PMC:PMC12236818 | DOI:10.1101/2025.06.27.661814

bioRxiv [Preprint]. 2025 Jul 6:2024.11.23.624995. doi: 10.1101/2024.11.23.624995.

ABSTRACT

Quantifying the inheritance of protein regulation during asymmetric cell division remains a challenge due to the complexity of these systems and the lack of a formal mathematical definition. We introduce ODEinherit, a new statistical framework leveraging ordinary differential equations (ODEs) to measure how much a mother cell’s regulatory network is passed on to its daughters, addressing this gap. ODEinherit first estimates cell-specific regulatory networks through ODE systems, incorporating novel adjustments for non-oscillatory trajectories. Then, inheritance is quantified by evaluating how well a mother’s regulatory network explains its daughter’s trajectories. We demonstrate that precise quantification of this inheritance relies on pruning and adjustment for the network density. We benchmark ODEinherit on simulated data and apply it to live-cell, time-lapse microscopy data, where we track the expression dynamics of six proteins across 85 dividing S. cerevisiae cells over eight hours. Our results reveal substantial heterogeneity in inheritance rates among mother-daughter pairs, paving the way for applications in cellular stress response and cell-fate prediction studies across generations.

PMID:40631107 | PMC:PMC12236845 | DOI:10.1101/2024.11.23.624995

Front Psychol. 2025 Jun 24;16:1622757. doi: 10.3389/fpsyg.2025.1622757. eCollection 2025.

ABSTRACT

INTRODUCTION: Current research shows that there is no vitiligo quality-of-life measurement instrument suitable for Chinese patients. At present, the DLQI scale commonly used with vitiligo patients in China includes symptom dimensions or items that are not applicable to vitiligo patients. Therefore, it is necessary to develop a quality-of-life scale specific to vitiligo patients in China.

METHODS: In this study, the item pool was created through a comprehensive review of relevant literature, focus group discussions, and brainstorming. Two rounds of Delphi expert consultation and a semi-structured interview were conducted to modify the item pool and form the draft scale. Two rounds of questionnaire investigations were used to select items and form the final scale. The reliability, validity, and discriminative ability were evaluated based on the third round of questionnaire investigation.

RESULTS: The scale contains 3 dimensions and 25 items, and the total cumulative variance contribution rate was 64.54%. The Cronbach’s α coefficient was 0.972; the split-half reliability coefficient was 0.950, and the test-retest reliability coefficient was 0.776. The Spearman correlation coefficient with the Dermatology Life Quality Index (DLQI) was 0.650. The scores of the scale or each dimension were correlated with patient characteristics, including gender, disease course, disease stage, Body Surface Area (BSA), and white spot area.

CONCLUSION: This study developed the Chinese Vitiligo Quality of Life Scale (CVQLS) to measure the quality of life of vitiligo patients in China. Compared to the commonly used DLQI, the CVQLS removed items related to skin disease symptoms while incorporating concerns specific to Chinese patients, such as the economic burden. The scale is thus tailored to the needs of Chinese vitiligo patients. Preliminary results indicate that the CVQLS has good reliability, validity, and discriminative ability.

PMID:40631062 | PMC:PMC12236179 | DOI:10.3389/fpsyg.2025.1622757

JTCVS Open. 2025 Apr 15;25:264-274. doi: 10.1016/j.xjon.2025.03.021. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is commonly observed after cardiac surgery and has been shown to be associated with increased morbidity and mortality. This study was conducted using the Kidney Disease Improving Global Outcomes (KDIGO) criteria to analyze potential perioperative biomarkers of CSA-AKI.

METHODS: Blood was collected from patients intraoperatively on entry into the pericardium and at 4, 12, 24, and 48 hours postoperatively. Repeated-measures, mixed-model analysis was conducted to determine which cytokines and/or chemokines were associated with postoperative CSA-AKI. LASSO regression and random forest modeling were used for variable selection and incorporation into a multivariable regression model.

RESULTS: There were no demographic or preoperative differences between patients with CSA-AKI and patients without CSA-AKI except for preoperative diabetes status, hemoglobin concentration, and CKD status. Additionally, there were no significant differences in preoperative medications between the 2 groups. Ten of the 40 biomarkers were statistically significant (P < .05) for the between-group main effect after repeated measures analysis: myoglobin, growth/differentiation factor 15 (GDF-15), neutrophil gelatinase-associated lipocalin (NGAL), haptoglobin, tumor necrosis factor alpha (TNFα), monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-1RA, IL-8, IL-6, and C-reactive protein. Multivariable stepwise regression showed the earliest independent predictors of postoperative AKI were 4-hour myoglobin (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.12-3.12; P = .036), 4-hour IL-1RA (aOR, 1.001; 95% CI, 1.000-1.001; P = .48), and 4-hour haptoglobin (aOR, 1.07; 95% CI, 1.03-1.18; P = .001).

CONCLUSIONS: Multiple cytokines were significantly elevated between the CSA-AKI group and the CSA-non-AKI group. Myoglobin, haptoglobin, and IL-1RA are potential blood biomarkers for AKI after cardiac surgery. Further research is needed to investigate the roles of these biomarkers and their associations with CSA-AKI.

PMID:40631034 | PMC:PMC12230585 | DOI:10.1016/j.xjon.2025.03.021

JTCVS Open. 2025 Apr 1;25:143-153. doi: 10.1016/j.xjon.2025.03.018. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Valvular heart disease (VHD)-associated heart failure (HF) remains an important and growing cause of morbidity and mortality. There are no contemporary data on the efficacy and safety of SGLT2 inhibitors in patients with a history of VHD.

METHODS: The EMPEROR-Pooled trial analyzed 9718 patients with HF who were enrolled in the randomized trials of empagliflozin versus placebo in HF with reduced left ventricular ejection fraction (HfrEF; EMPEROR-Reduced) and HF with preserved left ventricular ejection fraction (HFpEF; EMPEROR-Preserved). These trials evaluated a primary outcome of time to first HF hospitalization or cardiovascular death. Here we analyze outcomes of the EMPEROR-Pooled patients according to the presence and etiology of VHD history.

RESULTS: Of the 9717 patients enrolled in EMPEROR-Pooled with available data, 1484 (15.3%) had a history of VHD. Of the patients with VHD history, a history of isolated mitral disease (39.2%) was the most common subtype. In patients randomized to placebo, the risk of the primary outcome was higher among patients with VHD history (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.53; P < .01), and particularly those with a history of multivalvular disease (HR, 1.51; 95% CI, 1.13-2.04; P < .01) compared with no valvular disease. No heterogeneity was introduced by VHD history with respect to the efficacy of empagliflozin on all major clinical outcomes evaluated in EMPEROR-Pooled (P _interaction > .05).

CONCLUSIONS: We present the first large analysis of SGLT2i (empagliflozin) use in HF patients by history of VHD. Although VHD history was associated with worse outcomes in HF patients, empagliflozin demonstrated consistent safety, efficacy, and patient-reported outcomes across all categories of VHD history.

PMID:40631012 | PMC:PMC12230564 | DOI:10.1016/j.xjon.2025.03.018