Tag: pubmed

Clin Transl Sci. 2026 Aug;19(8):e70694. doi: 10.1111/cts.70694.

ABSTRACT

Phase 2a trials in tuberculosis patients traditionally assess early bactericidal activity over two weeks, often using the time-to-positivity biomarker, followed by a phase 2b study typically lasting 8-week with time-to-event of culture conversion as the endpoint. This study investigated different machine learning models to predict the time-to-event of 2-month culture conversion in the REMoxTB trial with phase 2a time-to-positivity biomarker data and the impact of different phase 2a study lengths. Time-to-positivity at baseline and up to 14 days or 28 days after two moxifloxacin-containing regimens and one control regimen were analyzed using nonlinear mixed-effects modeling. The final models were used to predict individual baseline time-to-positivity and time-to-positivity differences between 0 and 14 days or 0 and 28 days. The individual predictions served as features in the following machine learning analysis. Statistical metrics and Kaplan-Meier plots informed model selection. Bi-exponential and exponential decay models described the 14-day and 28-day time-to-positivity data, respectively. In the machine learning analysis, baseline time-to-positivity and/or time-to-positivity differences were ranked as the most important features in all models. Statistical metrics and Kaplan-Meier plots indicated a good fit to culture conversion at 8 weeks using 4-week phase 2a information with a C-support vector classification model. Four-week time-to-positivity phase 2a data provided more information compared to the 2-week time-to-positivity data for the prediction of culture conversion. The workflow demonstrated the potential of machine learning to predict the time-to-event of phase 2b culture conversion up to 8 weeks using time-to-positivity phase 2a biomarker information in a clinical trial assessed with pharmacometric analysis.

PMID:42576151 | DOI:10.1111/cts.70694

Stat Med. 2026 Aug;45(18-19):e70691. doi: 10.1002/sim.70691.

ABSTRACT

Health risk behaviors, including smoking, poor nutrition, alcohol misuse, and physical inactivity (SNAP), are leading contributors to chronic disease burden and healthcare costs worldwide. Their prevalence is shaped not only by individual demographic characteristics but also by contextual factors such as socioeconomic and occupational environments. We develop a Bayesian topic-informed dynamic mixture model to analyze SNAP behaviors using data from the Italian health and behavioral surveillance system PASSI. Free-text occupational descriptions are integrated through structural topic modeling to define latent occupational groups that inform the mixture weights of a multivariate ordered probit model. Covariate effects are allowed to vary across occupational clusters and evolve over time. To enhance interpretability and facilitate variable selection, we incorporate non-local spike-and-slab priors on regression coefficients. We further develop a tailored online learning strategy based on sequential Monte Carlo, enabling efficient updating of inference as new surveillance data become available. The proposed approach provides a flexible and interpretable framework for monitoring how occupational contexts modulate the impact of socio-demographic factors on multiple health risk behaviors over time, supporting targeted public health interventions. More broadly, the methodology is applicable to other longitudinal health surveillance and clinical settings where complex contextual information is available in textual form.

PMID:42576150 | DOI:10.1002/sim.70691

J Int Med Res. 2026 Aug;54(8):3000605261476168. doi: 10.1177/03000605261476168. Epub 2026 Aug 10.

ABSTRACT

ObjectiveTo analyze the characteristics and risk factors of blood-borne occupational exposures among healthcare workers at Shaoxing Second Hospital from 2020 to 2025 and to inform targeted prevention and control strategies.MethodsA retrospective analysis was performed on 252 blood-borne occupational exposure events reported from January 2020 to December 2025. Occupational distribution, occurrence patterns, exposure routes, high-risk operations, pathogens, and postexposure prophylaxis data were statistically analyzed.ResultsThe annual standardized incidence of blood-borne occupational exposures increased year by year. Nurses and staff with <5 years of service were the highest-risk groups. Sharp instrument injuries accounted for 92.46% of exposures. Hepatitis B virus was the dominant known pathogen (25.78%), whereas the hepatitis B virus postexposure prophylaxis rate was only 21.21%.ConclusionsThese findings indicate that healthcare workers at this hospital exhibit distinct high-risk features for blood-borne occupational exposures. To mitigate occupational exposure risks, a systematic and precise prevention program, hierarchical management of high-risk groups, and regular hepatitis B virus immune monitoring are recommended.

PMID:42576147 | DOI:10.1177/03000605261476168

Orbit. 2026 Aug 10:1-7. doi: 10.1080/01676830.2026.2714930. Online ahead of print.

ABSTRACT

PURPOSE: To characterize nuclear expression of Yes-associated protein 1 (YAP1), a key effector of the Hippo pathway, in lacrimal gland adenoid cystic carcinoma (LG ACC) and explore potential associations with clinicopathologic features and clinical outcomes.

METHODS: A retrospective, multi-institutional study of 24 LG ACC specimens was performed. Immunohistochemistry (IHC) was used to assess nuclear YAP1 expression. Staining intensity and percentage expression were combined into a composite NY-SCORE. Exploratory analyses evaluated relationships between YAP1 expression scores, clinicopathologic features, and clinical outcomes.

RESULTS: Nuclear YAP1 expression was observed in all 24 LG ACC cases: 6 tumors showed moderate staining (NY-SCORE 5-6), 18 tumors showed high staining (NY-SCORE 7-8), and none were low-scoring. Exploratory analyses did not demonstrate statistically significant associations between YAP1 expression and clinicopathologic features or clinical outcomes.

CONCLUSIONS: Nuclear YAP1 expression was consistently present in LG ACC tissue, suggesting that YAP1 nuclear localization is a common feature of this malignancy and supports future investigation of Hippo pathway activation in LG ACC. While YAP1 expression did not distinguish clinicopathologic risk or outcomes in this cohort, its uniform presence provides a foundation for future studies evaluating its biological role and potential therapeutic relevance.

PMID:42576145 | DOI:10.1080/01676830.2026.2714930

Biol Trace Elem Res. 2026 Aug 11. doi: 10.1007/s12011-026-05270-8. Online ahead of print.

ABSTRACT

Blood lead levels were associated with increased mortality in cancer patients, with mediation analyses suggesting a partial role of oxidative stress and inflammation, and heterogeneity across cancer types linked to Hallmark pathway activity. We analyzed 2,689 cancer patients from NHANES (1999-2016) using Cox regression, restricted cubic spline, and mediation analyses. Over 22,151.5 person-years, 983 deaths occurred. Compared with the lowest quartile, the highest blood lead quartile was associated with increased all-cause mortality (HR = 2.44; 95% CI: 1.79-3.34) and cancer mortality (HR = 2.34; 95% CI: 1.20-4.46). Lipid-adjusted inflammation indicators-including uric acid-to-high-density lipoprotein ratio (UHR), monocyte-to-lymphocyte ratio (MLR), and systemic inflammatory response index (SIRI)-mediated 4.51-5.72% of the association, supporting partial mediation through oxidative stress and inflammation. The effect varied by cancer type and correlated with TCGA Hallmark pathway activities, including KRAS signaling (ρ = -0.95) and xenobiotic metabolism (ρ = 0.79), suggesting that molecular context modulates lead toxicity.

PMID:42576141 | DOI:10.1007/s12011-026-05270-8

Clin Teach. 2026 Oct;23(5):e70494. doi: 10.1111/tct.70494.

ABSTRACT

BACKGROUND: Explicit teaching of clinical reasoning to medical students can be difficult to achieve, though may be facilitated through structured clinical debrief sessions supporting student discussions of case studies and placement experiences. This study aimed to understand student perceptions of the value of clinical debrief throughout their curriculum.

APPROACH: A scaffolded series of clinical debrief sessions were incorporated into Years 1, 3 and 5 of a 5-year UK undergraduate medical programme. Sessions are increasingly complex across year-levels and continuously improved across academic years according to student feedback. Each session receives student feedback through Likert-scale and open-ended questions on the session and their facilitating tutor, which were consolidated and analysed using descriptive statistics and AI-assisted conceptual content analysis.

EVALUATION: From over 8000 responses across the three year-levels and nine academic years, clinical debrief was positively viewed across all cohorts, with increasing perceived value for Year 3 students, though some decrease in perceptions for Year 5 students. Earlier year students emphasised the value for their communication and clinical reasoning skills, while later year students valued the ethical and medico-legal skill development and preparing for practice as a doctor. Tutors across all year levels were perceived highly for their contributions to an inclusive and effective learning environment and reducing professional isolation.

IMPLICATIONS: Scaffolded clinical debrief is positively viewed by undergraduate medical students across year levels, with perceived contributions to skill development influenced by year level. Development and implementation of clinical debrief require design aligning to student experiences and expectations, with effective tutor training.

PMID:42576138 | DOI:10.1111/tct.70494

Cogn Affect Behav Neurosci. 2026 Aug 10. doi: 10.3758/s13415-026-01487-1. Online ahead of print.

ABSTRACT

The present study examined how social competition modulates motor response execution and inhibition using behavioral, signal-detection, and event-related potential measures. Forty-three participants completed a Go/NoGo (GNG) task under social-competition and control conditions while EEG was recorded. Relative to control, social competition shortened Go-trial reaction times (RTs) without reducing accuracy, and greater RT speeding was associated with larger increases in the rated importance of response speed. Competition also increased NoGo commission errors, reflecting reduced Go/NoGo discriminability (lower d’) and a more liberal response criterion (C). Neurally, NoGo trials elicited larger N2 and P3 amplitudes than Go trials, whereas competition enhanced both Go-P3 and NoGo-P3 amplitudes without reliably modulating the N2. Go-P3 amplitude, maximal over centro-parietal/parietal sites, was negatively associated with Go RTs in the control condition. Competition-related increases in Go-P3 amplitude were associated with greater Go-RT speeding and statistically mediated the effect of competition on Go RTs, suggesting greater engagement of an stimulus-response (S-R) mapping process that translates task-relevant stimulus features into the appropriate Go-response representation. NoGo-P3 amplitude, maximal over frontocentral/central sites, was not significantly associated with commission errors or d’ in the control condition. However, competition-related increases in NoGo-P3 amplitude were associated with increased commission errors and reduced d’ and statistically mediated both effects. This pattern suggests that enhanced NoGo-P3 amplitude reflects increased demands for reactive control under a heightened prepotent Go tendency. Overall, social competition preferentially modulated P3-indexed, time-resolved control processes during motor response execution and inhibition, facilitating faster but still accurate motor response execution while impairing response withholding.

PMID:42576125 | DOI:10.3758/s13415-026-01487-1

J Child Psychol Psychiatry. 2026 Aug 10. doi: 10.1111/jcpp.70217. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to compare the effects of atomoxetine (ATX) and methylphenidate (MPH) on emotional dysregulation (ED) in children with attention deficit/hyperactivity disorder (ADHD), and to explore potential neural correlates underlying treatment-related changes.

METHODS: A total of 152 children with ADHD were randomly assigned to receive ATX (n = 76) or MPH (n = 76). After individualized dose titration, participants received a stable dose for 4 weeks. Emotional lability (EL) was the primary outcome, while emotion regulation strategies, ADHD symptoms, and overall illness severity were secondary outcomes. Mixed-effects linear models were applied to examine group differences across three time points (baseline, post-titration, and endpoint). Resting-state functional MRI data were acquired at baseline and endpoint and analyzed using whole-brain functional connectivity (FC) analysis with six amygdala subregions as seeds.

TRIAL REGISTRATION: ChiCTR2200062905; approved on August 23, 2022.

RESULTS: In both ATX and MPH groups, EL scores decreased significantly over time (β = -1.54, p < .001), with treatment effects in a similar range and no statistically significant between-group difference (MPH: d = -1.46; ATX: d = -0.93). After controlling for ADHD symptom improvement, treatment effects remained significant (β = -0.75, p < .001), suggesting that EL improvement was not solely accounted for by ADHD symptom reduction. Increased FC between the right basolateral amygdala and left orbital middle frontal gyrus (r = -0.46, p = .043), and between the left superficial amygdala and left middle cingulate cortex (r = -0.48, p = .031), was associated with EL changes and remained significant after controlling for ADHD symptom changes. No significant changes were found in self-reported emotion regulation strategies.

CONCLUSIONS: ATX and MPH both alleviate ED in children with ADHD, and these effects are not solely accounted for by improvements in ADHD symptoms. Increased amygdala-centered FC may be associated with medication-related ED improvements.

PMID:42576119 | DOI:10.1111/jcpp.70217

Ann Surg Oncol. 2026 Aug 10. doi: 10.1245/s10434-026-20361-5. Online ahead of print.

NO ABSTRACT

PMID:42576116 | DOI:10.1245/s10434-026-20361-5

Surg Endosc. 2026 Aug 10. doi: 10.1007/s00464-026-13270-x. Online ahead of print.

ABSTRACT

INTRODUCTION: There is an increased risk of hazardous alcohol use following metabolic and bariatric surgery (MBS). Identifying risk factors of hazardous alcohol use, particularly factors that may differentiate risk among those with regular postoperative alcohol consumption, would inform postoperative monitoring.

METHOD: Participants (N = 100) who were up to 5 years post-MBS and were consuming alcohol at least 2-3 times per month completed an assessment as part of a larger study. Measures assessed hazardous alcohol use, drinking motives, psychiatric symptoms, and disordered eating behaviors.

RESULTS: Participants were primarily female (87.0%), White (49.0%) or Black (44.0%), with a mean age of 48 years. Approximately 1 in 5 met the threshold for hazardous alcohol use. In bivariate analyses, clinically significant symptoms of depression (OR = 4.88, p = .01) and anxiety (OR = 8.21, p < .001) were associated with the presence of hazardous alcohol use. All four types of drinking motives were associated with greater likelihood of hazardous alcohol use: social (OR = 1.10, p = .03), coping (OR = 1.33, p < .001), enhancement (OR = 1.24, p < .001), and conformity (OR = 1.25, p = .01). Emotional eating scores and the presence of a food addiction were not significantly associated with hazardous alcohol use (p > .05). In a multivariable analysis, only the coping drinking motive remained statistically significant (OR = 1.26, p = .003).

CONCLUSION: Drinking to cope with negative emotions may be a factor associated with increased risk of hazardous drinking among individuals who regularly consume alcohol after MBS. Interventions aimed at improving coping strategies could mitigate risk of hazardous alcohol use.

PMID:42576078 | DOI:10.1007/s00464-026-13270-x