Tag: pubmed

Brief Bioinform. 2026 Jul 3;27(4):bbag390. doi: 10.1093/bib/bbag390.

ABSTRACT

Variant-set association analysis is a powerful strategy for genetic studies of whole-genome sequence (WGS) data, especially for rare variants. By aggregating variant signals, variant-set analysis can improve statistical power, result interpretability, and study replicability. Motivated by the evidence that 3D genome architecture plays a critical role in regulating gene transcription, several works have incorporated 3D genome architecture into gene-based association tests and demonstrated great promise. In this work, we extend the idea of 3D-genome guided test from gene-centric to gene-agnostic, whole-genome testing by introducing an Hi-C informed kernel association test (i.e. HiC-KAT). We present a principled procedure that converts Hi-C contact confidence into borrowing weights and integrates these weights into genetic similarity kernels so that higher-confidence interacting loci contribute more to the association test of the target variant set. We use a controlling parameter to adaptively determine the appropriate degree of information borrowing from its interacting loci during association testing. We assess the performance of HiC-KAT using simulations and illustrate its advantage in detecting rare-variant sets using WGS data from the ARIC study in the Trans-Omics for Precision Medicine program.

PMID:42480046 | DOI:10.1093/bib/bbag390

Brief Bioinform. 2026 Jul 3;27(4):bbag384. doi: 10.1093/bib/bbag384.

ABSTRACT

Alternative splicing (AS) is a fundamental posttranscriptional mechanism that amplifies proteomic diversity and enables adaptive responses across eukaryotes. Current AS detection methods rely heavily on reference genomes, limiting their applicability to non-model organisms. Existing reference-free approaches suffer from inaccurate splice site prediction and treat detection and classification as separate processes, resulting in cascading errors. We present IRCAS, an integrated end-to-end framework for reference-free AS analysis, comprising three modules: identification, rectification, and classification. IRCAS employs colored de Bruijn graphs for AS detection, an attention-based convolutional neural network for splice site rectification, and a hybrid graph neural network combining graph attention network and Transformer layers for classification. Evaluation across four species demonstrates substantial improvements: splice site accuracy increased to 92%-96% versus 50%-55% for existing methods, and end-to-end inference accuracy reached 83.4% on rice (fine-tuned) compared to 44.7% for the previous best method. IRCAS establishes a new benchmark for reference-free AS detection in non-model organisms.

PMID:42480045 | DOI:10.1093/bib/bbag384

J Am Nutr Assoc. 2026 Jul 21:1-6. doi: 10.1080/27697061.2026.2705957. Online ahead of print.

ABSTRACT

OBJECTIVE: Available evidence indicates that fat-free mass and muscle mass positively associate with baseline urine specific gravity, particularly in physically active individuals and athletes. Relatively little, however, is known about the relationships between skeletal muscle mass and other hydration biomarkers in more diverse samples. This investigation sought to evaluate the associations between skeletal muscle mass and hydration status measured via urine specific gravity, urine osmolality, and saliva osmolality.

METHODS: Eighty-three adults (37 men, 46 women; 36.1 ± 13.2 yr, 170.6 ± 9.4 cm, 90.0 ± 17.9 kg; 27.9 ± 11.8% body fat) visited the laboratory once to complete body composition testing and provide spot urine and saliva samples. Urine and saliva were analyzed using a digital pocket refractometer, benchtop osmometer, and portable handheld saliva osmometer.

RESULTS: Urine osmolality and specific gravity were highly associated with one another (ρ = 0.98, p < 0.001; n = 81). In contrast, saliva osmolality showed no significant associations with urine specific gravity (ρ = 0.04, p = 0.726; n = 82) or urine osmolality (ρ = 0.03, p = 0.795; n = 81). Furthermore, urine specific gravity, urine osmolality, and saliva osmolality all showcased no statistically significant relationships with skeletal muscle mass, in either unadjusted or adjusted (age, past 4h fluid intake, and time of day) analyses.

CONCLUSIONS: The insignificant associations between muscle mass and hydration measures are possibly due to the diverse physical activity of participants, variations in sampling time of day, and limited control over pre-visit nutritional intake. In comparison to homogenous athlete samples, there may be less of a relationship between muscle mass and hydration measures in diverse populations, particularly when relatively unrestricted pre-testing controls are imposed.

PMID:42480042 | DOI:10.1080/27697061.2026.2705957

JMIR Form Res. 2026 Jul 21;10:e86899. doi: 10.2196/86899.

ABSTRACT

BACKGROUND: Depression carries the highest burden of mental health-related disability in the United States. Approximately 13% of military veterans report elevated rates of depression. Despite the availability of evidence-based treatments for depression, nearly 50% of veterans in need of mental health care remain untreated. Internet-based interventions show promise in reducing this gap; however, there are currently no standard self-guided internet-based interventions for depressive symptoms in veterans. Deprexis is one such intervention that leverages cognitive behavioral therapy to target depressive symptoms.

OBJECTIVE: This pilot study evaluated the feasibility, acceptability, and preliminary effectiveness of Deprexis, a fully self-guided internet-based intervention for depression, in US military veterans with mild to severe depressive symptoms.

METHODS: This open-label pilot trial recruited 19 veterans with mild to severe depression (mean age 55.5, SD 8.2 y; baseline Quick Inventory of Depressive Symptomatology-Self-Report [QIDS-SR]: mean 16.2, SD 4.1) for an 8-week course of Deprexis, with self-report assessments at baseline, posttreatment (8 wk), and follow-up (16 wk). Primary outcomes included depressive symptoms (QIDS-SR), functional disability (World Health Organization Disability Assessment Schedule 2.0), and symptom-related disability (Sheehan Disability Scale). Feasibility was assessed through recruitment and retention rates, and acceptability was measured using validated questionnaires (Credibility and Expectancy Questionnaire and Client Satisfaction Questionnaire). Multilevel models examined change over time, with effect sizes calculated using pooled SDs from unconditional models.

RESULTS: Recruitment and retention targets were met, with 15 out of 19 (79%) participants meeting the adherence criteria (ie, ≥60 min of active program use). Of these, 14 participants completed posttreatment questionnaires and were included in the completer analyses. The program received a positive acceptability rating: of the 18 participants who completed follow-up assessments, 78% (n=14) rated services as good or excellent and 72% (n=13) were satisfied with the amount of help received. No safety concerns were reported. Among completers (n=14), QIDS-SR scores decreased from baseline to posttreatment (estimate -2.22, SE 1.44; P=.14; d=-0.54, 95% CI -1.07 to 0.13) and follow-up (estimate -2.85, SE 1.19; P=.02; d=-0.70, 95% CI -1.21 to -0.08) with moderate-to-large effect sizes. Effect sizes were similar in the total sample. Functioning (World Health Organization Disability Assessment Schedule 2.0) improved among completers at follow-up (estimate -8.09, SE 3.80; P=.045; d=-0.41, 95% CI -0.96 to -0.05). Disability (Sheehan Disability Scale) did not significantly improve from baseline to posttreatment or follow-up.

CONCLUSIONS: This pilot trial demonstrates that Deprexis is feasible and acceptable for veterans with mild to severe depression, with preliminary evidence of effectiveness for depressive symptoms. The delayed emergence of functional improvements and sustained gains at follow-up support the potential of this scalable intervention. The results provide a strong foundation for the ongoing randomized controlled trial.

PMID:42480022 | DOI:10.2196/86899

JCO Oncol Pract. 2026 Jul 21:OP2501346. doi: 10.1200/OP-25-01346. Online ahead of print.

ABSTRACT

PURPOSE: Systematic integration of tobacco cessation treatment within cancer centers is needed to improve smoking cessation outcomes among cancer patients and survivors. The current study characterizes baseline rates of tobacco use, use of cessation support, and changes in tobacco use over time among 756 participants diagnosed with cancer and enrolled in 9 ECOG-ACRIN Cancer Research Group trials.

MATERIALS AND METHODS: Participants completed surveys at trial enrollment and at 3- and 6-month follow-ups. Descriptive statistics were used to characterize patient characteristics and selected items from the Cancer Patient Tobacco Use Questionnaire (C-TUQ). Generalized estimating equations were used to examine the time point effect on tobacco product use.

RESULTS: At baseline, 11% of participants (n = 740) currently smoked cigarettes. Among participants with data available at all time points (n = 443), prevalence of current smoking was stable over time, with 7.2% of participants (n = 32) reporting current smoking at baseline, 7.0% (n = 31) at the 3-month follow-up assessment, and 6.8% (n = 30) at the 6-month follow-up assessment. Most participants (n = 77/104) who smoked cigarettes within the year prior to their cancer diagnosis continued smoking after their diagnosis, and during (n = 44/72) and following completion (n = 30/46) of their treatment. Sixty-two percent of participants (n = 81) who were currently smoking at baseline reported using smoking cessation medication and 32.1% reported use of nonpharmacologic smoking cessation support since their cancer diagnosis. In longitudinal analyses, the odds of using cigarettes since their cancer diagnosis, 3-month follow-up, and 6-month follow-up was higher than the odds of using cigarettes for the past 30 days at baseline (odds ratio [OR] = 1.97, OR = 1.62, and OR = 1.50, respectively; all ps < .01).

CONCLUSION: Smoking persists over time among patients with cancer enrolled in therapeutic cancer trials. Findings highlight the importance of increasing access to integrated and longitudinal smoking cessation support.

PMID:42480004 | DOI:10.1200/OP-25-01346

Proc (Bayl Univ Med Cent). 2026 Jul 21:1-4. doi: 10.1080/08998280.2026.2699604. Online ahead of print.

ABSTRACT

BACKGROUND: The application of artificial intelligence (AI) in simulating detailed patient-doctor interactions for objective structured clinical examinations (OSCEs) remains emerging. This study aimed to evaluate an AI virtual patient (AIVP) innovation designed to support medical education through interactive patient simulations and feedback.

METHOD: This prospective mixed-methods pilot recruited final-year medical students during their critical care term. Two cohorts were examined: a volunteer AIVP group (n = 43) and an educational-support medical education enhancement training (MEET) group (n = 8). Participants completed pre- and postintervention OSCEs scored across communication, history and examination, management, and overall outcome domains. Students accessed nine emergency medicine scenarios featuring AI-driven dialogue, speech recognition, avatar interaction, and immediate feedback. Quantitative outcomes were analyzed using the Wilcoxon signed-rank test. Postintervention surveys (Likert scale) and focus groups provided qualitative data, which were analyzed thematically.

RESULTS: In the AIVP cohort, descriptive improvements were observed across domains; however, Wilcoxon testing identified no statistically significant changes. MEET students demonstrated significant improvement in overall OSCE outcomes (median 37 [IQR: 30-67] vs 67 [IQR: 47-75]; P = 0.03), with positive trends in all domains. Survey responses (n = 25) showed high agreement that AIVP enhanced confidence in history-taking (83%), differential diagnosis (78%), and management planning (78%). Thematic analysis from 10 students demonstrated that AIVP was experienced as a structured, exam-focused, and confidence-building learning tool that addresses gaps in workplace-based learning.

CONCLUSION: AIVP was feasible and well received, providing practice aligned with university OSCE standards. While the volunteer cohort showed modest gains, the MEET group demonstrated significant improvement, suggesting benefit for students needing structured support. Tailored feedback and alignment with OSCE standards highlight AIVP as a promising adjunct for training.

PMID:42480003 | DOI:10.1080/08998280.2026.2699604

Med Care Res Rev. 2026 Jul 21:10775587261467103. doi: 10.1177/10775587261467103. Online ahead of print.

ABSTRACT

We examined associations between hospital system market share, merger activity, 340B participation and operating margins using data for 2,226 U.S. hospitals. We calculated Metropolitan Statistical Area (MSA)-level health system market share, tracked merger activity from 2017 to 2022, and constructed a commercial price index for 1,336 hospitals with available prices. Hospitals with a greater share were significantly more likely to participate in the 340B Program. Among larger hospitals, a 20 percentage-point increase in MSA-level health system share was associated with a 7.6 percentage-point increase in the likelihood of participation. Recent mergers were linked to an 8.6 percentage-point higher likelihood of 340B participation; 340B participation was associated with 1.1-3.0 percentage-point higher margins for non-merged hospitals and 5.2-7.0 percentage-point higher margins for merged hospitals. Greater market share and outpatient revenues were associated with larger estimated 340B margin effects, consistent with the outpatient-focused design of the program.

PMID:42479453 | DOI:10.1177/10775587261467103

Angle Orthod. 2026 Jul 21:e011126-37.1. doi: 10.2319/011126-37.1. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the effect of plaque-disclosing tablet (PDT) instructions on periodontal parameters in patients with bonded lingual retainers (LR).

MATERIALS AND METHODS: Forty-two patients with bonded mandibular lingual retainers were randomly allocated to two groups. The traditional oral hygiene instruction (TOHI) group (n = 21; 17 females, four males) received conventional verbal and visual oral hygiene education. The plaque-disclosing tablet instruction (PDTI) group (n = 21; 18 females, three males) received the same instructions as the TOHI group plus specific education on the use of PDT. An additional control group without lingual retainers (n = 21; 14 females, seven males) received identical instructions as the TOHI group. Plaque index (PI), gingival index (GI), calculus index (CI), and bleeding on probing (BOP) were recorded on the mandibular anterior teeth immediately after retainer placement (T0), at 3 months (T1), and at 6 months (T2). Statistical analyses were performed using the Shapiro-Wilk test, one-way analysis of variance (ANOVA), least significant difference test, Tamhane T2 test, chi-square test, and repeated-measures ANOVA.

RESULTS: At T1, TOHI and PDTI groups exhibited significantly higher periodontal scores compared with the control group (eg, PI: TOHI 0.86 ± 0.65, PDTI 0.62 ± 0.65, control 0.27 ± 0.17; P < .05). At T2, periodontal parameters in the PDTI group were significantly lower than in the TOHI group whereas no significant differences were found between the PDTI and control groups (P > .05).

CONCLUSIONS: The use of plaque-disclosing tablets in patients with bonded lingual retainers may improve periodontal health.

PMID:42479443 | DOI:10.2319/011126-37.1

Online J Public Health Inform. 2026 Jul 21. doi: 10.2196/90241. Online ahead of print.

ABSTRACT

BACKGROUND: HEDIS Childhood Immunization Status (CIS) Combination 10 is a pediatric quality measure within a widely used health care performance framework; HEDIS is used by more than 90% of U.S. health plans, covering more than 190 million people in plans that report HEDIS quality results. Because HEDIS immunization measures support population-level monitoring and quality improvement, they are directly relevant to public health practice. However, aggregate reporting limits public health use by obscuring component-level drivers of noncompletion.

OBJECTIVE: To apply explainable machine learning as a public health informatics approach to identify vaccine components associated with CIS Combo 10 completion among U.S. children aged 24-35 months.

METHODS: We analyzed 2021-2023 National Immunization Survey-Child public-use files. The age-eligible cohort included 32,997 children; weighted modeling included 16,021 children. Survey-weighted logistic regression estimated national trends with 95% CIs, and Random Forest modeling with SHAP and cross-validation identified component-level predictors.

RESULTS: CIS Combo 10 completion declined from 53.7% in 2021 to 44.6% in 2023; the survey-weighted regression model was statistically significant (annual OR 0.83, 95% CI 0.831-0.834; P<.001). Influenza and rotavirus had the largest mean absolute SHAP values.

CONCLUSIONS: CIS Combo 10 completion declined substantially from 2021 to 2023. An explainable public health informatics approach identified influenza and rotavirus as actionable targets for immunization quality improvement.

PMID:42479442 | DOI:10.2196/90241

JAMA Netw Open. 2026 Jul 1;9(7):e2624727. doi: 10.1001/jamanetworkopen.2026.24727.

ABSTRACT

IMPORTANCE: According to the Neonatal Oxygenation Prospective Meta-Analysis, a higher oxygen saturation as measured by pulse oximetry (Spo2) target range, compared with a lower Spo2 target, may reduce mortality but increase the risk of treated retinopathy of prematurity (ROP). Choosing a target range at an individual center may depend on the local baseline risks and the value placed on prioritizing survival over the risk of severe retinopathy.

OBJECTIVE: To estimate trade-offs between mortality and treated ROP associated with Spo2 targeting and the association between variation in baseline risks and these trade-offs.

DESIGN, SETTING, AND PARTICIPANTS: This decision analytical modeling study used US national birth data and the Vermont Oxford Network database (2019-2023), incorporating gestational age (GA) and 16 performance subgroups (based on quartiles of center-specific mortality and retinopathy risks), to simulate an annual birth cohort of infants born extremely preterm (GA 23-27 weeks). The data were analyzed between January and August 2025.

EXPOSURE: High Spo2 (91%-95%) vs low Spo2 (85%-89%) target ranges.

MAIN OUTCOMES AND MEASURES: The primary outcome was the risk trade-off ratio (RTOR) of additional cases of treated ROP per death averted. Estimates of outcomes comparing universal adoption of the high or low Spo2 targets were summarized using results of a probabilistic sensitivity analysis. Scenarios were also included that incorporated selective adoption of high or low targets based on performance quartiles.

RESULTS: Among 19 050 simulated infants (2372 [12.5%] born at GA 23 weeks, 3253 [17.1%] at GA 24 weeks, 3809 [20.0%] at GA 25 weeks, 4357 [22.9%] at GA 26 weeks, and 5259 [27.6%] at GA 27 weeks), which approximated the distribution of extremely preterm births in the US, universal adoption of the higher Spo2 target range was associated with a mean of 638 fewer deaths (95% uncertainty interval [UI], -363 to -934 deaths) and a mean of 551 additional cases (95% UI, 435-659 additional cases) of treated ROP. The mean RTOR with the high Spo2 target range was 0.91 (95% UI, 0.61-1.43). Across performance subgroups, RTORs were 0.16 (95% UI, 0.00-0.40) in centers with the highest risk of mortality (4th quartile) and lowest risk of treated ROP (1st quartile) and 2.52 (95% UI, 1.39-4.72) for centers with the highest mortality (1st quartile) and lowest risk of treated ROP (4th quartile). Selective adoption of target ranges was favored in 50% of simulations if 2 cases of treated retinopathy per death averted were considered acceptable. Universal adoption of the high target range was favored in more than 90% of simulations if 4 or more cases of treated ROP were acceptable for each death averted.

CONCLUSIONS AND RELEVANCE: This decision analytical modeling study of a US cohort of extremely preterm infants found that the RTOR for treated ROP and mortality during Spo2 targeting varied by GA and local baseline risks. This decision analysis may help inform the choice of Spo2 target ranges in individual clinical centers.

PMID:42479429 | DOI:10.1001/jamanetworkopen.2026.24727