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Abstract Circulating cell-free DNA (cfDNA) is emerging as an avenue for cancer detection, but the characteristics of cfDNA fragmentation in the blood are poorly understood. We evaluate the effect of DNA methylation and gene expression on genome-wide cfDNA fragmentation through analysis of 969 individuals. cfDNA fragment ends more frequently contained CCs or CGs, and fragments ending with CGs or CCGs are enriched or depleted, respectively, at methylated CpG positions. Higher levels and larger sizes of cfDNA fragments are associated with CpG methylation and reduced gene expression. These effects are validated in mice with isogenic tumors with or without the mutant IDH1, and are associated with genome-wide changes in cfDNA fragmentation in patients with cancer. Tumor-related hypomethylation and increased gene expression are associated with decrease in cfDNA fragment size that may explain smaller cfDNA fragments in human cancers. These results provide a connection between epigenetic changes and cfDNA fragmentation with implications for disease detection.

Introduction: Pyogenic liver abscess is a noteworthy health concern in North America, characterized by a mortality rate ranging from 2 to 12%. This condition is often polymicrobial, with Streptococcus species and Escherichia coli as the predominant causal pathogens in Western countries. Fusobacterium species, typically commensals of gastrointestinal, genital, and oral flora, have been implicated in the rare formation of tonsillar abscesses and Lemierre syndrome, including its gastrointestinal variant known as pylephlebitis. Case Presentation: We present the case of an immunocompetent male with a 2-week history of abdominal distention and pain. Abdominal magnetic resonance imaging revealed multiseptated cystic hepatic masses and portal vein thrombosis. A subsequent liver biopsy confirmed Fusobacterium nucleatum etiology. The patient was initiated on intravenous cefepime and oral metronidazole antibiotics. Unfortunately, the patient succumbed to cardiac arrest before a final diagnosis could be established. Conclusion: Fusobacterium species-associated liver abscess, coupled with the rare gastrointestinal variant of Lemierre syndrome (pylephlebitis), poses a significant mortality risk. This case underscores the rarity and clinical challenges associated with these conditions. Increased awareness among clinicians is crucial for early diagnosis and prompt intervention, potentially improving outcomes in such cases.

Abstract Background Combinations of movement behaviors (i.e., physical activity, sedentary behavior, sleep) are associated with health and developmental outcomes in youth. Youth vary in how they accumulate these behaviors, both in volume and specific domains (e.g., sedentary time spent on recreational screen activities vs homework). The aim of this study was to examine how youth’s combined general and domain-specific movement trajectories differ by socioeconomic position. Methods We conducted a longitudinal, group-based multi-trajectory analysis to identify general and domain-specific movement trajectory profiles for 2457 youth from age 10 to 14 years from the Longitudinal Study of Australian Children from 2014–2018. We used multinomial logistic regression to test if socioeconomic position predicted profile membership. Results We identified three general movement trajectory profiles for both sexes, four domain-specific profiles for males, and five for females. For general movement trajectories, females from lower socioeconomic positions were more likely to be a combination of less active and more sedentary than females from higher socioeconomic positions. Males across socioeconomic positions spend similar amounts of time in physical activity, sedentary time, and sleep. For domain-specific movement trajectories, youth from lower socioeconomic positions were likely to spend a combination of less time in education-based sedentary behavior and more time in recreational screen activities than their higher socioeconomic position peers. Conclusion Our results indicate that socioeconomic position predicted in which domains youth accumulate their movements. Future observational research and interventions targeting different socioeconomic groups should therefore consider domain-specific movement trajectories.

Population pharmacokinetic (pop-PK) models constructed for model-informed precision dosing often have limited utility due to the low number of patients recruited. To augment such models, an approach is presented for generating fully artificial quasi-models which can be employed to make individual estimates of pharmacokinetic parameters. Based on 72 concentrations obtained in 12 patients, one- and two-compartment pop-PK models with or without creatinine clearance as a covariate were generated for piperacillin using the nonparametric adaptive grid algorithm. Thirty quasi-models were subsequently generated for each model type, and nonparametric maximum a posteriori probability Bayesian estimates were established for each patient. A significant difference in performance was found between one- and two-compartment models. Acceptable agreement was found between predicted and observed piperacillin concentrations, and between the estimates of the random-effect pharmacokinetic variables obtained using the so-called support points of the pop-PK models or the quasi-models as priors. The mean squared errors of the predictions made using the quasi-models were similar to, or even considerably lower than those obtained when employing the pop-PK models. Conclusion: fully artificial nonparametric quasi-models can efficiently augment pop-PK models containing few support points, to make individual pharmacokinetic estimates in the clinical setting.

Abstract Background Psychopathology and side effects of antipsychotic drugs contribute to worsening physical health and long-term disability, and increasing the risk of mortality in these patients. The efficacy of exercise on these factors is not fully understood, and this lack of knowledge may hamper the routine application of physical activity as part of the clinical care of schizophrenia. Aims To determine the effect of exercise on psychopathology and other clinical markers in patients with schizophrenia. We also looked at several moderators. Method MEDLINE, Web of Science, Scopus, CINAHL, SPORTDiscus, PsycINFO, and Cochrane Library databases were systematically searched from inception to October 2022. Randomized controlled trials of exercise interventions in patients 18–65 years old diagnosed with schizophrenia disorder were included. A multilevel random-effects meta-analysis was conducted to pool the data. Heterogeneity at each level of the meta-analysis was estimated via Cochran’s Q, I2, and R2. Results Pooled effect estimates from 28 included studies (1,460 patients) showed that exercise is effective to improve schizophrenia psychopathology (Hedges’ g = 0.28, [95% CI 0.14, 0.42]). Exercise presented stronger effects in outpatients than inpatients. We also found exercise is effective to improve muscle strength and self-reported disability. Conclusions Our meta-analysis demonstrated that exercise could be an important part in the management and treatment of schizophrenia. Considering the current evidence, aerobic and high-intensity interval training exercises may provide superior benefits over other modalities. However, more studies are warranted to determine the optimal type and dose of exercise to improve clinical outcomes in people with schizophrenia.

Introduction Physical activity declines during adolescence, with the lowest levels of activity observed among those with disability. Schools are ideal settings to address this issue; however, few school-based interventions have been specifically designed for older adolescents with disability. Our aim is to investigate the effects of a school-based physical activity programme, involving high-intensity interval training (HIIT), on physical, mental and cognitive health in older adolescents with disability.Methods and analysis We will evaluate the Burn 2 Learn adapted (B2La) intervention using a two-arm, parallel group, cluster randomised controlled trial with allocation occurring at the school level (treatment or waitlist control). Secondary schools will be recruited in two cohorts from New South Wales, Australia. We will aim to recruit 300 older adolescents (aged 15–19 years) with disability from 30 secondary schools (10 in cohort 1 and 20 in cohort 2). Schools allocated to the intervention group will deliver two HIIT sessions per week during scheduled specialist support classes. The sessions will include foundational aerobic and muscle strengthening exercises tailored to meet student needs. We will provide teachers with training, resources, and support to facilitate the delivery of the B2La programme. Study outcomes will be assessed at baseline, 6 months (primary endpoint), and 9 months. Our primary outcome is functional capacity assessed using the 6 min walk/push test. Secondary outcomes include physical activity, muscular fitness, body composition, cognitive function, quality of life, physical literacy, and on-task behaviour in the classroom. We will also conduct economic and process evaluations to determine cost-effectiveness, programme acceptability, implementation, adaptability, and sustainability in schools.Ethics and dissemination This study has received approval from the University of Newcastle (H-2021–0262) and the New South Wales Department of Education (SERAP: 2021257) human research ethics committees. Findings will be published in peer-reviewed journals, and key stakeholders will be provided with a detailed report following the study.Trial registration number Australian New Zealand Clinical Trials Registry Number: ACTRN12621000884808.

[This corrects the article DOI: 10.1371/journal.pntd.0009808.].