Tag: pubmed

Eur J Psychotraumatol. 2025 Dec;16(1):2515683. doi: 10.1080/20008066.2025.2515683. Epub 2025 Jul 9.

ABSTRACT

Background: Even though evidence-based treatments are generally effective in reducing post-traumatic stress disorder (PTSD) in youth, many still experience elevated symptoms after treatment. A better understanding of how PTSD develops throughout treatment can increase efficiency and reduce residual symptoms.Objective: This study investigated which PTSD symptom clusters and symptoms within these clusters changed the most and least through trauma-focused cognitive behavioural therapy (TF-CBT), and identified common residual symptoms after treatment.Method: Latent growth curve modelling was used to identify differences in intercepts and slopes of symptoms, and residual symptoms were identified with McNemar tests in a sample of 517 youth (aged 6-19 years, 75.6% girls) receiving TF-CBT.Results: We found small but statistically significant differences in slopes across clusters. Avoidance both reduced the most and demonstrated most residual symptoms. Also, within clusters, many of the symptoms that reduced the most, such as psychological cue reactivity, persistent negative emotional state, and difficulties sleeping and concentrating, had the highest symptom levels before treatment and the most residual symptoms after treatment.Conclusions: Overall, symptoms of PTSD were reduced throughout TF-CBT. Symptoms rated highest at treatment start decreased the most but also tended to persist as common residual symptoms. Symptoms such as psychological cue reactivity, persistent negative emotional state, and negative beliefs that were common residual symptoms and are known to be central in the development and maintenance of PTSD are of particular clinical relevance. Research based on frequent symptom measurements during treatment could capture subtler changes, increasing understanding of the mechanisms of effective trauma treatment.

PMID:40631373 | DOI:10.1080/20008066.2025.2515683

Am J Med Genet B Neuropsychiatr Genet. 2025 Jul 9:e33043. doi: 10.1002/ajmg.b.33043. Online ahead of print.

ABSTRACT

Polygenic risk scores (PRSs), which sum the effects of SNPs throughout the genome to measure risk afforded by common genetic variants, have improved our ability to estimate disorder risk for Attention-Deficit/Hyperactivity Disorder (ADHD) but the accuracy of risk prediction is rarely investigated. In a study of 10,887 participants across nine cohorts, we performed gene set analysis of GWAS data to select gene sets associated with ADHD within a training subset. For each gene set, we generated gene set polygenic risk scores (gsPRSs), which sum the effects of SNPs for each selected gene set. We created gsPRS for ADHD and for phenotypes that are genetically correlated with ADHD. These gsPRS were added to the standard PRS as input to machine learning models predicting ADHD. On the test subset, a random forest (RF) model using PRSs from ADHD and genetically correlated phenotypes and an optimized group of 20 gsPRS had an area under the receiving operating characteristic curve (AUC) of 0.72 (95% CI: 0.70-0.74). This AUC was a statistically significant improvement over logistic regression models and RF models using only PRS from ADHD and genetically correlated phenotypes. Summing risk at the gene set level and incorporating genetic risk from disorders with high genetic correlations with ADHD improved the accuracy of predicting ADHD. Learning curves suggest that additional improvements would be expected with larger study sizes. Our study suggests that better accounting of genetic risk and the genetic context of allelic differences results in more predictive models.

PMID:40631367 | DOI:10.1002/ajmg.b.33043

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