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461 papers

A 12-week Exercise Intervention Among Older Adults With Chronic Coronary Syndrome: Changes and Associations of Movement Behaviors and Cardiovascular Risk Factors.

Ullrich A et al. · Jul 1, 2026

Physical activity (PA) is key to improve the prognosis of patients with chronic coronary syndrome (CCS). This study investigated changes in movement behaviors (MB), obesity markers, cardiorespiratory fitness (VO 2peak ), cardiometabolic risk (CMR), and brain-derived neurotrophic factor (BDNF) and whether changes in MB are associated with VO 2peak , CMR, and BDNF from baseline to 9 months after a 12-week exercise intervention. In total, 35 CCS patients (M = 69.5 ± 6.4 years; 82.9% men) underwent a group-based intervention; including two 1-h exercise sessions per week Data was collected on anthropometrics, blood samples, cardiopulmonary exercise testing, and 7-day accelerometry at baseline, 3-month, and 12-month follow-up. Absolute changes were examined using paired t-tests. Mixed-effects linear regression models were applied to investigate associations of MB with VO 2peak , CMR, and BDNF over time. Intra-class correlations were calculated to estimate within-person variability. From baseline to 3-month follow-up, light PA (23.7 min/d ± 10.9) increased and body mass index (-0.3 kg/m 2 ± 1.2), glucose (-0.8 mmol/L ± 0.3), and diastolic blood pressure (-2.7 mmHg ± 1.3) decreased. From baseline to 12-month follow-up, there were no changes in any marker. Regression models revealed no associations between any measure of habitual movement behaviors and VO 2peak , CMR, and BDNF over time. To conclude, short-term but no long-term changes in MB and cardiovascular health markers were observed among CCS patients after a 12-week exercise intervention. Modeling the associations between MB and VO 2peak , CMR, and BDNF over time revealed considerable within-person variability in the data, which should be considered in future research. TRIAL REGISTRATION: NCT06178263, Retrospectively registered (20/12/2023).

Medicine

School Refusal and Parental Illness: A Narrative Review.

Villetorte S et al. · Jul 1, 2026

Introduction School refusal (SR) affects many young people and has short- and long-term consequences on their development. Early interventions improve SR prognosis. Among the risk factors studied, parental illness is often mentioned. This narrative review assesses the frequency and strength of the link between SR and parental illness and its specificities. Methods PsycInfo, PsycArticles, Google Scholar and PubMed were queried, resulting in the inclusion of 18 studies. Results This link exists, but the number of robust studies is limited. While often acknowledged, it is seldom considered the main topic and is more often found with parental mental illness than physical illness. Discussion This association, observed in both quantitative and qualitative studies, seems to correspond to clinical reality. This review highlights the lack of precise data on parental illnesses in the SR literature and the limited hypotheses put forward to explain this link. This relationship requires greater attention in order to better understand and improve support for these children and adolescents and their families.

Social Sciences

Knowing How to Ask About Digital Culture in Youth Mental Health Care: A Co-Designed Tool.

Paquin V et al. · Jul 1, 2026

Background With the digital cultures that youth are exposed to and participating in come potential risks and protective factors for their mental health. However, despite clear need there is a lack of guidance to help mental health professionals evaluate the role of social media, artificial intelligence, and other technologies in young people's mental health. Aims To co-design with young people the Digital Culture Interview, an interview tool to support the clinical assessment of digital cultural factors in mental health care. Method We recruited a diverse group of 12 participants aged 16-35 years (mean age 22 years) from outpatient mental health clinics in Montreal, Canada. Using the nominal group technique, they identified topics they found most relevant for exploring in a clinical assessment the experiences and practices involving digital technologies. Based on the topics that received the most votes from participants, we co-developed a list of interview questions and written guidance for their administration. Results Participants identified and ranked 48 themes. Drawing from these, 14 questions were developed for inclusion in the Digital Culture Interview, covering four topics: identity and worldview, negative experiences online, coping, and understanding of mental health. Participants emphasised that exploring digital culture in mental health care requires patients' trust and a baseline of knowledge. If done sensitively, this may enhance the patient-clinician alliance and improve mutual understanding. Conclusions The Digital Culture Interview has the potential to enhance rapport and reveal risk and protective factors that are salient to and actionable in mental health care.

Psychology

Automated Pharmacometric Model Development by Leveraging Low-Dimensional Neural ODEs and LASSO Regression.

Bräm DS et al. · Jul 1, 2026

Current pharmacometrics (PMX) model development is a manual process with iterative model building, fitting, and evaluation, which can be resource-intensive and time-consuming. Existing automated model development approaches utilize algorithms that still rely on iterative processes and perform model selection based on goodness-of-fit criteria. Recent advances in machine learning and artificial intelligence, particularly neural ordinary differential equations (NODEs), have demonstrated strong potential for characterizing complex pharmacokinetic (PK) and pharmacodynamic (PD) dynamics directly from data. However, NODEs are inherently black-box models, which limits their interpretability and their ability to provide mechanistic insights, both of which are essential in PMX. We recently presented a promising concept that proposes interpretable ODE-based structural models from NODEs but relied on manually identifying functional relationships, which can be challenging and prevents full automation. In this work, we present an automated model development approach that combines NODEs with least absolute shrinkage and selection operator (LASSO) regression to automatically propose structural models based on the dynamics learned by NODEs. The approach leverages LASSO's feature selection capability, thereby linking data-driven modeling with interpretable mechanistic structures. We demonstrate the applicability of this automated NODE-LASSO model development approach in three different scenarios: neonatal weight development, bi-exponential PK data, and warfarin PK/PD data. The results indicate that our automated NODE-LASSO model development approach can recover meaningful, mechanism-based structures while reducing the need for extensive iterative and manual model development. This highlights its potential as a resource-efficient and interpretable modeling strategy for PMX and its applications in model-informed drug development and clinical research.

Physics and Astronomy

Clinical Remission of an Unresectable Presumptive Haemangiosarcoma in a Dog Treated With Toceranib, Piroxicam, and Propranolol: A Case Report.

Park WD. · Jul 1, 2026

Haemangiosarcoma (HSA) is a highly aggressive vascular tumour in dogs, characterised by rapid growth, early metastasis, and poor prognosis despite conventional treatment with surgery and doxorubicin-based chemotherapy. A 14-year-old spayed female Maltese (4.14 kg) was presented with progressive abdominal distension and anorexia. Imaging revealed a large retroperitoneal mass, and computed tomography identified a 12.1 × 8.0 × 8.5 cm heterogeneous tumour. Exploratory laparotomy confirmed the lesion was unresectable, and biopsy findings were most consistent with presumptive haemangiosarcoma (HSA) due to the small, cautery-affected specimen. Medical therapy was initiated with toceranib phosphate (10 mg every other day), followed one week later by propranolol (0.3 mg/kg twice daily) and piroxicam (0.3 mg/kg once daily). The patient was monitored every 2-4 weeks with physical examination and serial haematology and serum biochemistry. Two months after initiating therapy, the abdominal ultrasonography demonstrated tumour reduction to 4.9 × 2.7 cm, and after 7 months the mass was no longer detectable on radiographic follow-up imaging (radiography and ultrasonography). Throughout treatment, haematologic and biochemical values remained within reference intervals, no clinically significant adverse effects were observed, and the owner reported resolution of abdominal distension with improved activity. This case demonstrates that combined therapy with toceranib, propranolol, and piroxicam achieved radiographic and clinically sustained remission of unresectable canine presumptive HSA while preserving quality of life. These findings suggest that multimodal therapy targeting angiogenesis and tumour growth pathways may represent a promising alternative strategy for managing this malignancy and warrant further clinical evaluation.

Medicine

Long-Term Cardiometabolic Outcomes in Children With Metabolically Healthy and Unhealthy Obesity.

Putri RR et al. · Jul 1, 2026

Importance Metabolically healthy obesity (MHO) in children has been considered a low-risk phenotype, potentially not requiring treatment. However, their long-term cardiometabolic outcomes remain unclear. Objective To compare the occurrence of type 2 diabetes, hypertension, dyslipidemia, and mortality up to young adulthood in children with metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), and general population peers, and to investigate the association between obesity treatment response and disease risk. Design, setting, and participants This was a prospective cohort study including children undergoing obesity treatment recorded in the Swedish Childhood Obesity Treatment Register (BORIS) between 1997 and 2020 and their general population comparators, linked with national registers. Children in the cohort with obesity were aged 7 to 17 years at obesity treatment initiation and had complete cardiometabolic data. General population comparators were matched (ratio 1:5) based on sex, birth year, and residential area. Study data were analyzed from February to March 2025. Exposures Exposures included metabolically healthy obesity (MHO), defined as the absence of high blood pressure, impaired fasting glycemia, elevated transaminases, elevated triglycerides, and low high-density lipoprotein cholesterol; otherwise, children were categorized as having metabolically unhealthy obesity (MUO). Main outcomes and measures Type 2 diabetes, hypertension, dyslipidemia, and mortality up to age 30 years. Results A total of 7275 children (median [first quartile {Q1}-third quartile {Q3}] age, 11.1 [9.1-13.5] years; 4004 male [55.0%]) were included, along with 35 636 general population comparators (median [Q1-Q3] age, 11.1 [9.1-13.5] years; 19 596 male [55.0%]). MHO at baseline was present in 3626 children (49.8%; median [Q1-Q3] age, 10.6 [8.8-12.8] years; 1981 male [54.6%]), and MUO was present in 3649 children (50.2%; median [Q1-Q3] age, 11.6 [9.4-14.0] years; 2023 male [55.4%]). By age 30 years, cumulative incidences were as follows: type 2 diabetes (MHO, 9.1%; MUO, 16.8%; general population, 0.5%), hypertension (MHO, 10.8%; MUO, 18.3%; general population, 3.7%), and dyslipidemia (MHO, 5.3%; MUO, 12.7%; general population, 0.9%). A reduction of at least 0.25 body mass index (BMI) z score was associated with reduced incidence rate ratio (IRR) of type 2 diabetes (IRR, 0.22; 95% CI, 0.14-0.35), hypertension (IRR, 0.56; 95% CI, 0.34-0.93), and dyslipidemia (IRR, 0.28; 95% CI, 0.14-0.57), with similar risk reduction for MHO and MUO. Conclusions and relevance Results of this cohort study reveal that a reduction in BMI z score of at least 0.25 was associated with similar risk reductions for both MHO and MUO. Children with MHO face a substantially increased cardiometabolic disease risk already as young adults compared with the general population. Hence, obesity treatment should be recommended for all children with obesity, regardless of initial metabolic status.

Medicine

Malignant Hyperthermia in Sweden: Clinical Presentations and Genetic Findings.

Hellblom A et al. · Jul 1, 2026

Introduction Malignant hyperthermia (MH) is a pharmacogenetic, hypermetabolic and potentially lethal reaction to potent volatile anaesthetics and the muscle relaxant succinylcholine. To improve the understanding of MH, the aim of this retrospective study was to describe the Swedish cohort with respect to clinical manifestations, demographics and genetic findings. Method The Swedish MH Registry covers a total of 2852 individuals belonging to 544 different families investigated for MH since 1980. For this study, the index case in each family was included for further description. Results In total, MH was confirmed in 1555 individuals. Among the 288 index cases with a history of an MH reaction and confirmed MH, 58% were male and 57% were Conclusions We found that MH reactions predominantly occur in young individuals and that case fatality has declined over recent decades, with no deaths reported in the past 20 years. Less than 40% of the genetically investigated MH families, corresponding to around 20% of all Swedish MH families, currently have an identified genetic diagnostic variant. Editorial comment This analysis of the national Swedish Malignant Hyperthermia patient registry presents case factors and outcomes from cases among recognised families from the last 45 years. Presenting symptoms and then case confirmation details are presented, along with results from cases and families where genetic variants has been assessed.

Biochemistry, Genetics and Molecular Biology

Childhood Material Hardship Linked to Adolescent Neurocognition: A Computational Modeling Approach.

Zhang YL et al. · Jul 1, 2026

Childhood material hardship, including insecurity in housing, utilities, food, and medical care, is a critical factor influencing cognitive functioning and mental health outcomes. However, past research on material hardship is limited by cross-sectional data and reliance on conventional behavioral measures of cognitive functioning that suffer from poor reliability and lack of specificity. To address these gaps, this study used a well-validated computational model of cognition to examine individuals' drift rate, which is hypothesized to be driven by the efficiency of evidence accumulation (EEA) for decision-relevant information, a key process that supports higher-order cognitive functioning. Here, we examined how material hardship during childhood was associated with adolescent drift rate, and whether drift rate was linked with attention difficulties. 187 adolescents recruited from the Future of Families and Child Wellbeing Study were included in the analyses. Adolescents exposed to greater material hardship showed lower drift rate, suggesting less effective processing. Growth curve modeling revealed that initial exposure to material hardship, but not changes across childhood, was associated with drift rate in adolescence. Lower drift rate was also associated with concurrent attentional problems and served as a significant indirect pathway linking material hardship to adolescent attention. This is the first longitudinal study that examined the associations among childhood material hardship exposure, adolescent drift rate, and attentional difficulties. Our results suggest that challenges to essential living conditions in childhood may impact cognitive processes underlying goal-directed behavior in adolescents. These findings highlight the application of computational models to reveal specific cognitive processes impacted by adversity. SUMMARY: Existing research on material hardship and cognitive functioning is limited by reliance on cross-sectional task-based performance, resulting in inconsistent findings. We applied the diffusion-decision model to decompose trial-wise performance into underlying cognitive processes, including drift rate, a key evidence accumulation process underlying goal-directed behavior. Greater cumulative childhood material hardship, beyond exposure to other adversity, is associated with lower drift rate, which is linked with greater attentional problems in adolescents. Findings were specific to drift rate, not average response time or accuracy, emphasizing the value of computational methods in capturing cognitive changes associated with material hardship.

Health Professions

Expansion of the Phenotypic and Genotypic Spectrum of MED13L-Associated Neurodevelopmental Disorder: A Case Report and Literature Review.

Wang Z et al. · Jul 1, 2026

Background Pathogenic variants in MED13L, including copy-number changes and sequence variants, cause MED13L syndrome. This rare neurodevelopmental disorder is characterized by global developmental delay, intellectual disability (ID), distinctive facial dysmorphism, hypotonia, and variable congenital heart defects. The phenotypic heterogeneity of MED13L syndrome underscores the significance of genotype-phenotype correlation analysis for improving clinical diagnosis and precise phenotypic characterization of affected individuals. Methods Venous blood samples anticoagulated with EDTA were collected from the patient and family members, followed by whole-exome sequencing analysis and subsequent validation using fluorescent quantitative PCR. Concurrently, a systematic search of the PubMed database was performed to summarize previously reported cases harboring MED13L copy number Variations (CNVs). Results Whole-exome sequencing revealed a de novo heterozygous single-copy duplication of a ~19-kb region within the MED13L gene (exons 8-16) in the proband. The patient presents phenotypic features consistent with MED13L syndrome and represents the first reported case exhibiting cleft lip. A literature review indicates that vision impairment, developmental delay, and congenital heart disease are widely observed phenotypes, while other less frequent manifestations vary between patients with duplications and deletions. Conclusion This study, integrating a case report and a literature review, provides important reference evidence for the clinical genetic counseling of MED13L syndrome.

Biochemistry, Genetics and Molecular Biology

Pulse‑level characterization of low monitor unit deliveries on a modern linear accelerator using a plastic scintillation detector.

White AJ et al. · Jul 1, 2026

Background Variability in low monitor unit (MU) deliveries has been previously documented, but the underlying pulse‑level behavior has not been fully described due to the integrating nature of most conventional detectors. A plastic scintillation detector (PSD) enables direct visualization of MU microstructure by isolating individual linac pulses. Purpose To use a high temporal resolution PSD to characterize pulse‑level MU substructure on a modern linac and quantify how variation in integral pulse magnitude and pulse count influence the reproducibility of low MU and fractional MU deliveries. Methods A Blue Physics Model 11 PSD was used to measure response from individual linac pulses of a Varian TrueBeam operating at energies of 6 MV, 6 MV FFF, 10 MV, and 10 MV FFF. Initial measurements benchmarked reproducibility in pulse count and dose per pulse by delivering 100 MU at a constant dose rate of 400 MU/min. Subsequent measurements focused on low MU cases, delivering 1-3 MU at dose rates of 5-2400 MU/min. Results The dose per pulse is variable during a single pulse train with a measured coefficient of variation (COV) of up to 13.3%. However, the average dose per pulse across multiple deliveries is stable ( Conclusions Time-resolved analysis shows that dose per pulse fluctuations and the limited number of pulses comprising low MU FFF deliveries lead to measurable variability in delivered MU. These findings characterize the pulsed MU substructure on a modern linac, in which each MU is composed of a finite number of discrete radiation pulses, and quantify the achievable precision of fractional MU delivery, which is fundamentally limited by the dose per pulse (∼0.1 MU for TrueBeam FFF beams).

Agricultural and Biological Sciences