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In recent years, children and adolescents have spent more time sitting and engaging in less physical activity than recommended by health authorities. Despite widespread efforts to promote physical activity through school-based programs, the impact of specific intervention programs often remains untested. Therefore, in this pilot study, the effects of a national school-based physical activity program were assessed. A sample of 80 first- and second-grade primary school students aged between 7 and 9 years (M = 7.95, SD = 0.44) of eight classes was cluster randomly assigned to either the experimental group (EG; classroom-based physical activity breaks) or the control group (CG; conventional school lessons). Primary outcomes included objective measurements of sedentary behaviour, step counts, and moderate-to-vigorous physical activity (MVPA) during the intervention. Secondary outcomes encompassed assessments of aerobic fitness performance, executive functions, academic achievement, and scholastic well-being before and after the 20-week intervention. The results indicate that students of the EG spent less time sedentary and took more steps during school mornings than their counterparts of the CG. The physical activity program resulted in a 630-step increase and a 10-minute reduction in sitting time daily. However, there were no effects on MVPA level, aerobic fitness performance, or cognitive functions (including executive functions and academic achievement). The implications of these findings are discussed in light of comprehensive school physical activity approaches.

Attention-deficit/hyperactivity disorder (ADHD) symptoms affect 40-60% of autistic children and have been linked to differences in adaptive behavior. It is unclear whether adaptive behavior in autistic youth is directly impacted by co-occurring ADHD symptoms or by another associated feature of both autism and ADHD, such as increased irritability. The current study examined relationships between irritability, ADHD symptoms, and adaptive behavior in 3- to 7-year-old autistic children. Results suggest that, after adjusting for co-occurring ADHD symptoms, higher levels of irritability are associated with differences in social adaptive behavior specifically. Understanding relationships between irritability, ADHD, and adaptive behavior in autistic children is critical because measures of adaptive behavior, such as the Vineland Scales of Adaptive Functioning, are often used as a proxy for global functioning, as well as for developing intervention plans and measuring outcomes as primary endpoints in clinical trials.

Some patients benefit from a treatment while others may do so less or do not benefit at all. We have previously developed a two-stage network meta-regression prediction model that synthesized randomized trials and evaluates how treatment effects vary across patient characteristics. In this article, we extended this model to combine different sources of types in different formats: aggregate data (AD) and individual participant data (IPD) from randomized and non-randomized evidence. In the first stage, a prognostic model is developed to predict the baseline risk of the outcome using a large cohort study. In the second stage, we recalibrated this prognostic model to improve our predictions for patients enrolled in randomized trials. In the third stage, we used the baseline risk as effect modifier in a network meta-regression model combining AD, IPD randomized clinical trial to estimate heterogeneous treatment effects. We illustrated the approach in the re-analysis of a network of studies comparing three drugs for relapsing--remitting multiple sclerosis. Several patient characteristics influence the baseline risk of relapse, which in turn modifies the effect of the drugs. The proposed model makes personalized predictions for health outcomes under several treatment options and encompasses all relevant randomized and non-randomized evidence.

Abstract Conventional navigation systems (CNS) in surgery require strong spatial cognitive abilities and hand-eye coordination. Augmented Reality Navigation Systems (ARNS) provide 3D guidance and may overcome these challenges, but their accuracy and efficiency compared to CNS have not been systematically evaluated. In this randomized crossover study with 36 participants from different professional backgrounds (surgeons, students, engineers), drilling accuracy, time and perceived workload were evaluated using ARNS and CNS. For the first time, this study provides compelling evidence that ARNS and CNS have comparable accuracy in translational error. Differences in angle and depth error with ARNS were likely due to limited stereoscopic vision, hardware limitations, and design. Despite this, ARNS was preferred by most participants, including surgeons with prior navigation experience, and demonstrated a significantly better overall user experience. Depending on accuracy requirements, ARNS could serve as a viable alternative to CNS for guided drilling, with potential for future optimization.

Abstract Background Prostate cancer ranks as the second most frequently diagnosed cancer in men worldwide. Recent research highlights the crucial roles IL6ST-mediated signaling pathways play in the development and progression of various cancers, particularly through hyperactivated STAT3 signaling. However, the molecular programs mediated by IL6ST/STAT3 in prostate cancer are poorly understood. Methods To investigate the role of IL6ST signaling, we constitutively activated IL6ST signaling in the prostate epithelium of a Pten-deficient prostate cancer mouse model in vivo and examined IL6ST expression in large cohorts of prostate cancer patients. We complemented these data with in-depth transcriptomic and multiplex histopathological analyses. Results Genetic cell-autonomous activation of the IL6ST receptor in prostate epithelial cells triggers active STAT3 signaling and significantly reduces tumor growth in vivo. Mechanistically, genetic activation of IL6ST signaling mediates senescence via the STAT3/ARF/p53 axis and recruitment of cytotoxic T-cells, ultimately impeding tumor progression. In prostate cancer patients, high IL6ST mRNA expression levels correlate with better recurrence-free survival, increased senescence signals and a transition from an immune-cold to an immune-hot tumor. Conclusions Our findings demonstrate a context-dependent role of IL6ST/STAT3 in carcinogenesis and a tumor-suppressive function in prostate cancer development by inducing senescence and immune cell attraction. We challenge the prevailing concept of blocking IL6ST/STAT3 signaling as a functional prostate cancer treatment and instead propose cell-autonomous IL6ST activation as a novel therapeutic strategy.

ABSTRACT: Mare milk has a unique protein composition that makes it a preferred option for adult and infant nutrition. Several functional properties have been attributed to this milk, but with little current evidence. In fact, knowledge on mare milk composition is still limited. In particular, studies addressing the performance of mare milk proteins during human gastrointestinal digestion are scarce, which limits the understanding of mare milk nutritional quality and functionality. For this reason, the present study describes the digestibility of mare milk proteins and the release of peptides as affected by management and lactation stage, factors which are known to affect milk composition. Mare milk samples from 3 different farms collected during 6 mo of lactation (n = 54) were subjected to a static in vitro gastrointestinal model to measure peptide release and protein digestibility. In the present study, a detailed description of protein and individual amino acid behavior during the digestion process was given. For the first time, digestion of the 2 equine β-lactoglobulin isoforms (I and II) was described individually. In addition, it was found that lactation stage and management system can significantly affect protein digestibility and peptide release during gastrointestinal digestion of mare milk. Presumably, differences in the composition of mare milk influence the protein structure and enzyme accessibility, which might have an impact on digestion behavior. Although no specific bioactive peptides were identified, several precursors of previously described bioactive peptides were found. These findings could support the idea of mare milk as a food with added value.

Malik Sallam,1– 3 Khaled Al-Salahat,1,3 Huda Eid,3 Jan Egger,4 Behrus Puladi5 1Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman, Jordan; 2Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman, Jordan; 3Scientific Approaches to Fight Epidemics of Infectious Diseases (SAFE-ID) Research Group, The University of Jordan, Amman, Jordan; 4Institute for AI in Medicine (IKIM), University Medicine Essen (AöR), Essen, Germany; 5Institute of Medical Informatics, University Hospital RWTH Aachen, Aachen, GermanyCorrespondence: Malik Sallam, Email malik.sallam@ju.edu.joIntroduction: Artificial intelligence (AI) chatbots excel in language understanding and generation. These models can transform healthcare education and practice. However, it is important to assess the performance of such AI models in various topics to highlight its strengths and possible limitations. This study aimed to evaluate the performance of ChatGPT (GPT-3.5 and GPT-4), Bing, and Bard compared to human students at a postgraduate master’s level in Medical Laboratory Sciences.Methods: The study design was based on the METRICS checklist for the design and reporting of AI-based studies in healthcare. The study utilized a dataset of 60 Clinical Chemistry multiple-choice questions (MCQs) initially conceived for assessing 20 MSc students. The revised Bloom’s taxonomy was used as the framework for classifying the MCQs into four cognitive categories: Remember, Understand, Analyze, and Apply. A modified version of the CLEAR tool was used for the assessment of the quality of AI-generated content, with Cohen’s κ for inter-rater agreement.Results: Compared to the mean students’ score which was 0.68± 0.23, GPT-4 scored 0.90 ± 0.30, followed by Bing (0.77 ± 0.43), GPT-3.5 (0.73 ± 0.45), and Bard (0.67 ± 0.48). Statistically significant better performance was noted in lower cognitive domains (Remember and Understand) in GPT-3.5 (P=0.041), GPT-4 (P=0.003), and Bard (P=0.017) compared to the higher cognitive domains (Apply and Analyze). The CLEAR scores indicated that ChatGPT-4 performance was “Excellent” compared to the “Above average” performance of ChatGPT-3.5, Bing, and Bard.Discussion: The findings indicated that ChatGPT-4 excelled in the Clinical Chemistry exam, while ChatGPT-3.5, Bing, and Bard were above average. Given that the MCQs were directed to postgraduate students with a high degree of specialization, the performance of these AI chatbots was remarkable. Due to the risk of academic dishonesty and possible dependence on these AI models, the appropriateness of MCQs as an assessment tool in higher education should be re-evaluated.Keywords: AI in healthcare education, higher education, large language models, evaluation

Abstract Background Patient-derived tumour organoids (PDOs) are highly advanced in vitro models for disease modelling, yet they lack vascularisation. To overcome this shortcoming, organoids can be inoculated onto the chorioallantoic membrane (CAM); the highly vascularised, not innervated extraembryonic membrane of fertilised chicken eggs. Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient – in vitro PDOs – in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns. Results The main liver metastasis of the CRC patient exhibited high 2-[18F]FDG uptake and moderate and focal [68Ga]Ga-Pentixafor accumulation in the peripheral part of the metastasis. Inoculation of PDOs derived from this region onto the CAM resulted in large, highly viable, and extensively vascularised xenografts, as demonstrated immunohistochemically and confirmed by high 2-[18F]FDG uptake. The xenografts showed striking histomorphological similarity to the patient’s liver metastasis. The moderate expression of CXCR4 was maintained in ovo and was concordant with the expression levels of the patient’s sample and in vitro PDOs. Following in vitro re-culturing of CAM-PDXs, growth, and [68Ga]Ga-Pentixafor uptake were unaltered compared to PDOs before transplantation onto the CAM. Although [68Ga]Ga-Pentixafor was taken up into CAM-PDXs, the uptake in the baseline and blocking group were comparable and there was only a trend towards blocking. Conclusions We successfully established an in vivo CAM-PDX model based on CRC PDOs. The histomorphological features and target protein expression of the original patient’s tissue were mirrored in the in vitro PDOs, and particularly in the in vivo CAM-PDXs. The [68Ga]Ga-Pentixafor uptake patterns were comparable between in vitro, in ovo and clinical data and 2-[18F]FDG was avidly taken up in the patient’s liver metastasis and CAM-PDXs. We thus propose the CAM-PDX model as an alternative in vivo model with promising translational value for CRC patients. Graphical Abstract

Abstract Background The coronavirus 2019 (COVID-19) pandemic impacted cancer health care in several countries, with delays in the detection and treatment of breast and cervical cancer. The objective of this study is to analyze and compare the screening, diagnosis and treatment of breast and cervical cancer in the pre-COVID period and during the COVID-19 period. Methods Cross-sectional study with secondary data collected from the Mortality Information System (SIM), Hospital Information System (SIH), Ambulatory Information System (SIA) and the Oncology Panel (PO) of breast cancer notifications with ICD C50.0 to C50.9 and cervix ICD C53.0 to C53.9, The analyzed period before the pandemic was from March 1 to October 1, 2019, and during the pandemic from March 1 to October 1, 2020. The period from 2013 to 2022 was also analyzed with the same information, including the number of diagnoses, treatments, and deaths from breast cancer and cervical cancer. The study population consisted of Brazilian women aged 25 to 70 years. In order to compare categorical variables between periods, the Chi-Square or Fisher’s Exact tests, and Mann-Whitney U tests were applied, and the Poisson Regression model was applied to model the number of reported cases of COVID-19 and the amount of procedures. Results There was a decrease in the number of mammograms and cytopathological exams during COVID-19, as well as a decrease in cases of breast and cervical cancer. The Poisson regression showed that the increase in the number of COVID-19 cases caused a decrease in the number of breast cytopathological examinations, cervical-vaginal cytopathological examinations/microflora and screening, diagnosis, initiation of treatment for breast cancer and deaths from this disease. Meanwhile, in some regions of Brazil, as the number of Covid-19 increased, there was a significantly increase in the number of mammograms performed and cervical cancer diagnoses. Conclusions The COVID-19 period in 2020 significantly impacted screening, diagnosis, treatment for breast and cervical cancer.

Abstract Background The positive effects of regular physical activity on children and adolescents’ physical and mental health are well-established. Despite these health benefits, most Swiss adolescents do not meet WHO’s recommended level of physical activity, which includes a daily minimum of 60 min of moderate-to-vigorous physical activity. Due to their inclusivity, schools are identified as a key setting to promote physical activity. Recently, the comprehensive school physical activity program (CSPAP), in which teachers as physical activity leaders (PALs) play a crucial role to advance comprehensive school-based physical activity promotion, has been discussed. However, such comprehensive approaches are still lacking in Switzerland, and specific PAL trainings do not exist. Therefore, the aim of this study is to implement and evaluate Active School, a comprehensive school-based physical activity program for Swiss secondary schools with integrated PAL training. Methods/design A cluster randomized controlled trial (RCT) involving 12 secondary schools (6 experimental, 6 waiting control schools) will assess baseline data and effectiveness of Active School at 12 and 24 months. Active School includes five components based on the CSPAP. Each school is encouraged to set individual physical activity goals in this regard. This process is guided by the PALs, who will participate in professional development training before and during Active School implementation. As a primary outcome, students’ moderate-to-vigorous physical activity will be assessed via accelerometers. As secondary outcomes, inactivity, light physical activity, step counts, aerobic fitness and coordination will be measured, and students’ general wellbeing, learning behavior, and multiple psychosocial measures related to physical activity will be assessed by questionnaires. The effectiveness evaluation is accompanied by a process evaluation that focuses on the implementation outcomes of dose of delivery, reach, feasibility, and sustainability. A mixed methods approach, including ripple effect mapping, will be employed to reconstruct and understand the implementation process. Discussion This study will be the first to implement and evaluate a CSPAP in the Swiss school system. The specific PAL training and the simultaneous application of effectiveness and process evaluation are considered strengths of the study. Trial registration German Clinical Trials Register (DRKS00033362). Date of registration: January 25, 2024. Retrospectively registered.

ABSTRACT: The effect of the horn status of cows on their milk composition and quality is a controversial research topic. In this study, 128 milk samples from 64 horned and 64 disbudded Brown Swiss and Original Braunvieh cows were collected from alpine farms where both horned and disbudded cows were grazing on mountain pastures. The samples were analyzed for their detailed composition and protein digestion in a simulated in vitro digestion (INFOGEST). To exclude probable influences on digestion, the β-CN genotype with its variants A1 and A2 was also included in the study. The effects of horn status and β-CN genotype were investigated in linear mixed models, which included additional influencing random factors such as Original Braunvieh blood proportion, stage of lactation, and farm. Horn status did not have any effect on milk composition or digestion. In contrast, milk from A1A1 cows showed a different protein digestion than milk of A1A2 and A2A2 cows in the gastric phase, including smaller amounts of β-casomorphin(BCM)21-associated peptides and larger amounts of BCM11-associated peptides. Abundances of BCM7 did not differ between β-CN genotypes. At the end of the intestinal phase, the digested milk of A1A1 and A2A2 β-CN genotypes did not differ.

We consider the dynamics of an elastic continuum under large deformation but small strain. Such systems can be described by the equations of geometrically nonlinear elastodynamics in combination with the St. Venant-Kirchhoff material law. The velocity-stress formulation of the problem turns out to have a formal port-Hamiltonian structure. In contrast to the linear case, the operators of the problem are modulated by the displacement field which can be handled as a passive variable and integrated along with the velocities. A weak formulation of the problem is derived and essential boundary conditions are incorporated via Lagrange multipliers. This variational formulation explicitly encodes the transfer between kinetic and potential energy in the interior as well as across the boundary, thus leading to a global power balance and ensuring passivity of the system. The particular geometric structure of the weak formulation can be preserved under Galerkin approximation via appropriate mixed finite elements. In addition, a fully discrete power balance can be obtained by appropriate time discretization. The main properties of the system and its discretization are shown theoretically and demonstrated by numerical tests.