Browse Articles

Three-dimensional ex-vivo visualization of normal and inflamed small intestine and colonic tissue using optical coherence tomography

Lifetime stressor exposure, executive functioning, and internalizing symptoms during emerging adulthood

Abstract Internalizing symptoms such as depression and anxiety rise dramatically during emerging adulthood. Although both childhood and adulthood adversity are associated with internalizing symptoms during this period, the underlying transdiagnostic processes connecting adversity to internalizing symptoms are unclear. To investigate this, we examined how childhood and adulthood adversity are related to internalizing symptoms during emerging adulthood via individual differences in executive functioning. In a cross-sectional study of 203 participants aged 18–24 years ( M age =20.36, SD age =1.73, 66.01% women/transwomen, 28.08% White–European/North American), lifetime stressor exposure was indexed using the Stress and Adversity Inventory, internalizing symptoms were measured using the Kessler Psychological Distress Scale, and executive functioning was measured as a latent factor indicated by multiple performance-based measures. Analyses were conducted using regression and path analyses. In separate models, both childhood and adulthood adversity exposure predicted greater internalizing symptoms, but when entered as competing predictors in the same model, only adulthood adversity continued to predict psychopathology. No evidence for an indirect association involving executive functioning was detected, although higher childhood adversity was associated with better executive functioning. These results highlight differential associations between adversity timing, internalizing symptoms, and executive functioning during emerging adulthood, with minimal evidence of executive functioning as an indirect path linking adversity to internalizing symptoms.

Deep learning-based visual algorithms for identity and action recognition in engineering practical courses

The development and validation of Direct and Indirect Prejudice Scales (DIPSs)

Emotion-specific regulation components differentially predict profiles of adolescent psychosocial dysfunction

Abstract Emotion regulation (ER) difficulties are a transdiagnostic risk factor for adolescent psychopathology, yet research is hampered by high intercorrelations among ER components. This study employed a data-driven approach to identify distinct profiles of adolescent dysfunction and select a parsimonious set of stable emotion-specific regulatory predictors. A sample of 795 Iranian adolescents (68.6% female; M age = 16.06) completed measures of emotion-specific ER across sadness, fear, and anger (CERSA), psychosocial adjustment (SDQ), pathological traits (PID-5-BF), and disability (WHODAS-12). Person-centered cluster analysis identified dysfunction profiles, and ordinal LASSO penalized regression selected stable ER predictors of cluster membership, with both steps embedded within a full-pipeline bootstrap. Three stable clusters emerged, reflecting a severity gradient: low-, moderate-, and high-dysfunction. This solution was independently replicated via latent profile analysis sensitivity analysis (84.4% agreement, weighted κ = 0.86). LASSO regression with full-pipeline bootstrap inference retained eight stable predictors from 21 candidates, with seven threshold-specific effects supported by unconditional 95% confidence intervals excluding zero. General dysregulation across all three emotions was the strongest maladaptive predictor. In addition to general deficits, specific strategies showed context-dependent effects: Rumination-Anger was associated with greater dysfunction, whereas Reappraisal-Anger and Support Seeking-Sadness predicted lower dysfunction severity. Some associations were specific to particular severity transitions (low to moderate or moderate to high dysfunction) rather than uniform across the dysfunction spectrum. Our findings indicate that general dysregulation may represent transdiagnostic vulnerability, whereas specific strategies show emotion–context dependency, supporting functionalist theories that adaptiveness depends on matching regulatory strategies to an emotion’s function.

Multi-strategy enhanced orchard algorithm for optimal integration of renewable energy sources and EV charging stations in microgrids

Modeling how penalty sequences influence decisive scoring in elite judo

Age-stratified trajectories of patient-reported outcomes and perioperative safety after robot-assisted radical prostatectomy: a prospective multicenter cohort study

Abstract As life expectancy increases, a growing number of older adults undergo radical prostatectomy for localized prostate cancer; however, longitudinal age-specific functional outcomes remain insufficiently characterized. We conducted a prospective multicenter cohort study evaluating age-stratified trajectories of patient-reported outcomes (PROs) assessed using the Expanded Prostate Cancer Index Composite (EPIC) and perioperative complications following robot-assisted radical prostatectomy (RARP). A total of 604 patients were categorized into three age groups (< 65, 65–74, and ≥ 75 years). PROs were assessed using the EPIC at baseline and at 1, 3, 6, and 12 months postoperatively, and longitudinal changes were analyzed using linear mixed-effects models. Urinary function declined transiently after surgery in all age groups and substantially recovered by 12 months, with no significant differences between men aged ≥ 75 years and younger patients. Sexual function decreased irrespective of age, although younger patients maintained higher absolute scores after nerve-sparing procedures. In contrast, sexual bother demonstrated an age-dependent pattern, with minimal change observed in men aged ≥ 75 years. Perioperative complication rates did not differ significantly across age groups. These findings suggest that chronological age alone should not preclude consideration of RARP in appropriately selected elderly patients and provide evidence supporting individualized surgical decision-making in an aging population.

Population pharmacokinetics and target attainment of pretomanid in rifampicin-resistant tuberculosis patients

Abstract Pretomanid is a key component of the bedaquiline, pretomanid, linezolid with or without moxifloxacin (BPaL/M) regimen recommended for treatment of rifampicin-resistant tuberculosis (RR-TB). To support dose optimization and efficacy interpretation, we developed a pretomanid population pharmacokinetic (PK) model and evaluated exposure and probability of target attainment (PTA). Ninety-four RR-TB patients received daily oral pretomanid at 200 mg, and plasma samples were collected at multiple time points. Pretomanid concentrations were quantified using high-performance liquid chromatography-tandem mass spectrometry and PK modeling was performed using nlmixr2 in R. A one-compartment model with first-order absorption and elimination, and fat free mass allometric scaling best described the data. Typical clearance was 3.10 L/h (32.9%CV), median AUC₀₋₂₄ was 64,000 (31,000– 140,000) ng·h/ml, and the median maximum inter-dose concentration (Cmax) was 3,000 (1,000– 6,000) ng/ml. Pretomanid MICs for Mycobacterium tuberculosis in the TB-PRACTECAL trial were consistently below the provisional critical concentration, with a median of 0.125 mg/L. PK-Pharmacodynamic (PD) simulations indicated that nearly all participants achieved drug exposures exceeding %fT > MIC target, consistent with the regimen’s clinical efficacy across the study population. However, the AUC/MIC target was not achieved. We developed a pretomanid population PK model and facilitated exploring robustness of PK-PD targets for PTA. Our study confirmed the clinical relevance of the time dependent index and target, but further investigation is needed to determine whether the 167 AUC/MIC target is valid in patients or using translational pre-clinical experiments, especially within the context of combination therapy. Trial registry : Clinical Trials.gov, TRN: NCT04081077, Registration date: 4 September 2019.

Neostigmine versus sugammadex on outpatient recovery among obese patients with obstructive sleep apnea: A randomized controlled trial

Abstract Patients presenting for outpatient surgery may have several comorbidities, including obesity and obstructive sleep apnea. The objective was to measure the efficacy of sugammadex (versus neostigmine) in reducing post-anesthesia care unit length of stay among obese patients with obstructive sleep apnea undergoing outpatient surgery. Furthermore, we aimed to assess differences in post- and pre-operative pulmonary function test and arterial blood gas metrics. We hypothesized that sugammadex would improve recovery times. This was a single institution randomized controlled double-masked clinical trial assessing the efficacy of sugammadex versus neostigmine in reducing length of stay among obese patients with obstructive sleep apnea undergoing outpatient surgery. Secondary outcomes included changes in pulmonary function test and arterial blood gas measurements postoperatively. Mann Whitney U test was the primary statistic used to compare primary and secondary outcomes. There were 90 subjects enrolled, divided equally into the neostigmine and sugammadex cohorts. The median [quartile] length of stay was 125 min [73, 186] versus 123 min [94, 169] in the neostigmine and sugammadex cohorts, respectively ( P  = 0.79). There were no statistically significant differences in proportional changes of pulmonary function tests (all P  > 0.05) nor arterial blood gas measurements (all P  > 0.05). This suggests that among patients with obesity and OSA undergoing low-to-moderate risk surgery in the outpatient setting, routine use of one reversal agent over the other would not affect overall PACU efficiency in an ambulatory surgery center. Trial registration: Clinicaltrials.gov NCT04570150, Principal investigator: Jerry Ingrande, Date of registration: 29/09/2020).

Body mass index (BMI) versus socioeconomic factors and physical activity in early childhood

PlantCLR: contrastive self-supervised pretraining for generalizable plant disease detection

From reductionism to complex systems: Paradigm shift and knowledge evolution in competitive sports research using BERTopic

Background and purpose With the exponential growth in the volume of competitive sports research, traditional bibliometric methods based on keyword co-occurrence struggle to accurately capture the field's deep semantic structure and evolutionary dynamics. This study aims to employ natural language processing (NLP) techniques to reconstruct the knowledge structure and evolutionary characteristics of competitive sports research from a micro-semantic perspective. Methods Utilizing the BERTopic topic modeling algorithm combined with dynamic regression analysis, we performed unstructured text mining on 24,659 core abstracts published between 2010 and 2024. Data were retrieved from the Web of Science, PubMed, and Scopus databases. Results The study reveals a distinct “monocentric, multi-dimensional” hierarchical structure in competitive sports research.Topic 0 (“Sports Injury and Load Management”) represents the largest volume and exhibits continuous, significant growth (“Hot”). It constitutes the field's epistemological foundation, demonstrating robust vitality driven by technological iteration. Meanwhile, the explosive growth of Topic 1 (“Sports Mental Health”) marks a profound paradigm shift from singular “physiological optimization” to “holistic psychophysical well-being."In contrast, Topic 4 (“Mega-event Management”) shows statistically non-significant growth, indicating that this sub-field has reached a stage of theoretical saturation. Furthermore, the evolution of the discipline can be categorized into three stages: the Budding Period (2010–2014), the Rapid Development Period (2015–2019), and the Multi-dimensional Transition Period (2020–2024). Conclusion Competitive sports science is currently in a critical transition period from reductionism to a complex systems perspective. Future research frontiers are likely to focus on the deep integration of biomedical technologies and humanistic psychology. This study provides a novel methodological perspective for understanding the evolutionary laws of the discipline.

Prevalence, perceptions and factors associated with non-adherence to hepatotoxicity monitoring among people living with HIV on tuberculosis preventive treatment at Mulago ISS clinic

Introduction Hepatotoxicity monitoring is recommended for people living with HIV (PLHIV) enrolled on tuberculosis preventive treatment (TPT). Despite a 7.3% hepatotoxicity incidence reported in a multi-country study, implementation and adherence to hepatotoxicity monitoring remains low. We aimed at determining the prevalence, patients’ and health workers’ perceptions, and factors associated with non-adherence to hepatotoxicity monitoring among adult PLHIV receiving TPT at Mulago ISS clinic. Methods A sequential explanatory mixed methods study was carried among health workers and adult PLHIV enrolled on TPT between 2022 and 2023 at Mulago ISS clinic. The quantitative and qualitative components utilized a cross-sectional and an exploratory descriptive design respectively. A data abstraction tool was used to obtain quantitative data from files and electronic medical records of a systematic random sample of 390 patients. The qualitative study utilized interview guides to conduct in-depth audio recorded interviews for five patients and five health workers. Descriptive statistics and modified Poisson regression analyses were performed for the quantitative data. Deductive thematic analysis based on the health belief model was utilized for the qualitative data. Results The prevalence of non-adherence to hepatotoxicity monitoring was 87.4% (95%CI: 83.7–90.4). The prevalence of non-adherence to hepatotoxicity monitoring was 85% lower in PLHIV that received primary TPT as compared to those on secondary TPT (aPR-0.15, 95% CI: 0.04–0.55). The qualitative findings revealed varied perceptions about non-adherence to hepatotoxicity monitoring that included awareness of associated risks, perceived benefits of monitoring, and confidence in taking action, while also identifying perceived barriers such as financial, knowledge and communication challenges. Conclusions The prevalence of non-adherence to hepatotoxicity monitoring was high within this pharmacovigilance sentinel site, given its clinical importance in HIV care and clear recommendations in the national HIV treatment guidelines. Health authorities should implement policies promoting hepatotoxicity monitoring in pharmacovigilance sentinel sites, especially for patients receiving secondary TPT, and allocate resources to support this initiative.

Understanding human arm stiffness modulation in overground pHRI: The roles of kinematics, perturbation, and trunk sway

This study examines human arm kinematics during overground physical human-robot interaction (pHRI). Previous work showed humans adjust arm stiffness with changing trajectory uncertainty, but the roles of arm kinematics and muscle activation remained unclear. Building on a preliminary study, we analyzed arm movements with more participants (10 individuals) to achieve more reliable findings and examined two potential influences that arose in the preliminary study: the robot’s perturbation effect (a brief hand push) and left-to-right trunk sway. Using a linear mixed-effects model, we evaluated the effects of participant, block, and trajectory condition on arm angles. Results showed minimal kinematic contribution to stiffness modulation, with inconsistent significance levels in the measured metrics. Perturbation presence also had no significant impact on voluntary posture, with the exception of the posture differences before and after the perturbation. Trunk sway was strongly correlated with elbow angle, with a mean correlation ( R 2 ) of 0.65 and a standard deviation of 0.24. Most variability arose from individual differences rather than experimental conditions. These findings might potentially allow for more flexible mechanical design in assistive and rehabilitation robots.

Deciphering the synergistic mechanism of a novel flavonoid-antioxidant combination for asthma by combining systems pharmacology and experimental validation

Asthma is a multifaceted disorder characterized by an intricate interplay of various pathophysiological processes, including airflow obstruction, bronchial hyperresponsiveness, and underlying inflammation. This complexity encompasses a multitude of genetic, molecular, and environmental factors, making it challenging to identify effective strategies for prevention and treatment. Research into the pathogenesis and treatment of asthma continues in the pursuit of more comprehensive and targeted therapeutic approaches. The asthma pathology has been shown to be influenced by the flavonoid 7,4′- Dihydroxyflavone (74DHF), which is extracted from the herb Rhizoma Glycyrrhizae (Gancao), while taking the antioxidant ascorbic acid (VC) daily through food or supplements contributes to the treatment of asthma related to immunomodulatory regulation. However, the potential molecular or systemic mechanism of the combination of 74DHF and VC in treating asthma has yet to be fully understood, despite the demonstrated individual benefits of each compound. The present study employed a systems pharmacology strategy, combining target identification, network analysis, data integration, Gene Ontology (GO) enrichment analysis, pathway analysis, and in vitro experimental validation to uncover the synergistic pharmacological mechanisms of 74DHF-VC combination for asthma therapy. The results identified 153 and 308 targets for 74DHF and VC, 37 overlapping targets and 20 hub targets among 74DHF, VC, and asthma. Based on the GO and pathway analysis, 10 optimal common GO processes and 10 key canonical pathways were enriched, which were closely related to the combination therapy of 74DHF and VC against asthma. In addition, the in vitro experiments validated that 74DHF and VC had synergistic effects on anti-inflammation and fibrosis. The combined treatment reversed the LPS induced inflammation in macrophages and TGF-β induced cell migration and fibrosis in lung epithelial cells. The current study not only successfully explains the synergistic mechanisms underlying the efficiency of 74DHF and VC against asthma but also proposes a viable and promising strategy to fasten the process of combination treatment.

Maternal smoking behaviour during pregnancy and the association of Sudden Unexpected Infant Death (SUID): A retrospective cohort study of births in the United States from 2017–2021

Background Maternal smoking during pregnancy is a significant risk factor for sudden unexpected infant death (SUID). However, the impact of variations in smoking behaviours, including timing, intensity, and cessation, remains understudied. This study examines the association between maternal smoking and SUID, incorporating detailed categorizations of smoking behaviours. Methods We conducted a population-based, retrospective cohort study of live births in the United States from 2017 to 2021 using the Centre for Disease Control Linked Birth-Infant Death files. Maternal smoking was categorized as non-smoking, pre-pregnancy smoking only, trimester-specific smoking, continuous or discontinuous smoking, and cessation before the third trimester, with stratification by smoking intensity. SUID was defined using ICD-10 codes. Multivariable logistic regression was used to estimate unadjusted (OR) and adjusted odds ratios (aOR) for SUID. Sensitivity analyses examined mediation by gestational age and infant birth weight. Results Heavy continuous smokers had the highest aOR for SUID (372.8 per 100,000 births; aOR 2.81, 95% CI 2.67–2.94), followed by light continuous smokers (395.6 per 100,000 births; aOR 2.47, 95% CI 2.19–2.78) and discontinuous heavy smokers (292.5 per 100,000 births; aOR 2.29, 95% CI 1.72–3.00) compared with non-smokers. Pre-pregnancy-only smokers had the lowest odds of SUID among all smoking categories (light: 188.2 per 100,000 births; aOR 1.77, 95% CI 1.48–2.10; heavy: 152.8 per 100,000 births; aOR 1.61, 95% CI 1.44–1.78). In the sensitivity analysis, the natural indirect effect (NIE) of continuous smoking throughout pregnancy on SUID through gestational age and infant birth weight were insignificant (gestational age: β = 1.01, 95% CI 0.99–1.03, p = 0.28, infant birth weight: β = 1.04, 95% CI 0.99–1.08, p = 0.10). Conclusions Maternal smoking significantly influences SUID, with earlier cessation exhibiting weaker associations. These findings emphasize the importance of early smoking cessation interventions to improve SUID outcomes.

Where do they come from and where do they go: Understanding the relationship between deprivation and the geographical journeys of trainee doctors in England

Having enough doctors to provide healthcare services is a concern internationally. In the UK, significant resources for education and training have been devoted to medical workforce management. Nevertheless, some areas of the country still struggle to recruit and retain staff compared with others. Solutions to this problem have focused on attracting students from backgrounds not traditionally represented in medicine to choose it as a career, and opening new medical schools in different areas of the country. The main objective of this paper is to examine medical student and doctor distribution in order to contribute to understanding the distribution of health and health service inequalities. We used a modelling approach to understand characteristics of medical students, medical schools and foundation schools to interpret and identify the relationship between geographic distribution and socio-economic deprivation. This geographical and statistical analysis aims to identify patterns in workforce distribution, layering these with data on deprivation and inequality. Analysis shows that there are fewer students who come from from more deprived areas, and that different patterns can be observed in geographic locations of training when considering gender and ethnicity. While there is greater diversity of the future workforce in terms of gender and ethnicity, there is evidence that fewer students from more deprived backgrounds are attending medical schools. This has implications for the future workforce, and medical schools may need to play a greater role in increasing access to medical education to overcome observed inequalities.

Activity constraints and the emergence of non-scale-free networks: Evidence from hip-hop and academia

Power-law distributions are widely used to characterize complex networks, yet recent work shows that scale-freeness is far less universal than once assumed, especially in social networks. We propose activity constraints—the finite time and effort required to complete collaborative ties—as a mechanism that limits hub growth and produces non-scale-free degree distributions. Using synthetic models and mathematical derivations, we show that imposing capacity limits on high-quality actors shifts degree distributions away from power laws and toward log-normal forms. We then examine degree saturation in two empirical settings: hip-hop featuring networks and academic coauthorship networks. In both cases, high-quality actors receive more ties, but their realized degree saturates relative to expectations, yielding sublinear or S-shaped quality-degree relationships. These findings demonstrate how micro-level workload constraints generate macro-level deviations from scale-free structure and highlight the importance of distinguishing activity-intensive from low-cost tie-formation processes when evaluating claims of scale-freeness in networks.

The effect of game-based education on adherence to treatment and anxiety level in type 2 diabetics started on insulin therapy

Background Insulin initiation in type 2 diabetes mellitus (T2DM) is often hindered by anxiety and poor treatment compliance. Although game-based learning may enhance patient engagement, evidence regarding its effectiveness in adult populations remains limited. Objective To evaluate the effect of a game-based education program on treatment compliance (primary outcome) and anxiety levels (secondary outcome) in adults with T2DM receiving insulin therapy. Methods This randomized controlled study included 72 adults with T2DM who were assigned to either a game-based education group (n = 36) or a standard lecture-based education group (n = 36). Treatment compliance was assessed using the Patient Compliance Scale for T2DM Treatment (primary outcome), and anxiety was measured using the Beck Anxiety Inventory (secondary outcome). Between-group differences were analyzed using baseline-adjusted ANCOVA, controlling for baseline scores, age, duration of diabetes, and employment status. Exploratory correlation analyses examined the association between anxiety and treatment compliance. Results Baseline demographic and clinical characteristics were comparable between the intervention and control groups (p > 0.05). Following the intervention, participants in the game-based education group demonstrated significantly higher treatment compliance compared with those in the control group. Baseline-adjusted ANCOVA revealed a significant between-group difference favoring the intervention group for total treatment compliance (F = 65.92, p < 0.001), indicating a substantial improvement associated with the intervention. Adjusted analyses also showed significantly lower post-intervention anxiety scores in the intervention group compared with the control group (F = 11.241, p < 0.001), with a large effect size (partial η² = 0.14). Improvements were observed across most treatment compliance sub-dimensions, with the exception of lifestyle change, which did not reach statistical significance. Exploratory correlation analyses further indicated that the negative association between anxiety and treatment compliance weakened following the intervention only in the game-based education group, whereas this relationship remained significant in the control group. Conclusion Game-based education is more effective than standard lecture-based education in enhancing treatment compliance and reducing anxiety among individuals initiating insulin therapy. Additionally, the intervention may attenuate the adverse impact of anxiety on adherence-related behaviors. Trial registration ClinicalTrials.gov NCT07195188