Fine-tuning of Fgf8 morphogen gradient by heparan sulfate proteoglycans in the extracellular matrix.

Embryonic development is orchestrated by the action of morphogens, which spread out from a local source and activate, in a field of target cells, different cellular programs based on their concentration gradient. Fibroblast growth factor 8 (Fgf8) is a morphogen with important functions in embryonic organizing centers. It forms a gradient in the extracellular space by free diffusion, interaction with the extracellular matrix (ECM), and receptor-mediated endocytosis.

Digital Health Interventions for Informal Family Caregivers of People With First-Episode Psychosis: Systematic Review on User Experience and Effectiveness.

Background: First-episode psychosis (FEP) imposes a substantial burden not only on the individual affected but also on their families. Given that FEP usually occurs during adolescence, families overtake a big part of informal care. Early family interventions, especially psychoeducation, are crucial for informal family caregivers to best support the recovery of their loved one with FEP and to reduce the risk of a psychotic relapse as much as possible, but also to avoid chronic stress within the family due to the burden of care.

Inceptor binds to and directs insulin towards lysosomal degradation in β cells.

Blunted first-phase insulin secretion and insulin deficiency are indicators of β cell dysfunction and diabetes manifestation. Therefore, insights into molecular mechanisms that regulate insulin homeostasis might provide entry sites to replenish insulin content and restore β cell function. Here, we identify the insulin inhibitory receptor (inceptor; encoded by the gene IIR/ELAPOR1) as an insulin-binding receptor that regulates insulin stores by lysosomal degradation.

Causal inference concepts can guide research into the effects of climate on infectious diseases.

A pressing question resulting from global warming is how climate change will affect infectious diseases. Answering this question requires research into the effects of weather on the population dynamics of transmission and infection; elucidating these effects, however, has proved difficult due to the challenges of assessing causality from the predominantly observational data available in epidemiological research. Here we show how concepts from causal inference-the sub-field of statistics aiming at inferring causality from data-can guide that research.

Cardiovascular Risk Scores and Migraine Status.

Importance: A previous cohort study in the US found that women with higher cardiovascular risk were more likely to have a history of migraine but less likely to have active migraine. Extrapolating these results to men and European individuals is crucial to understanding the complex association between migraine activity status and vascular health in other populations.

Objective: To evaluate the association pattern between a cardiovascular risk score, the most recent European version of the Systematic Coronary Risk Evaluation 2 (SCORE2) risk estimation system, and migraine activity status in Dutch men and women.

Evaluation of easy-to-implement anti-stress interventions in a series of N-of-1 trials: study protocol of the anti-stress intervention among physicians study.

Background: Adverse effects of chronically high levels of stress on physical and mental health are well established. In physicians, the effects of elevated stress levels exceed the individual level and include treatment errors and reduced quality of patient-doctor relationships. Breathing and mindfulness-based exercises have been shown to reduce stress and could serve as an immediate and easy-to-implement anti-stress intervention among physicians.

Unravelling the Causal Relationship between Endometriosis and the Risk for Developing Venous Thromboembolism: A Pooled Analysis.

Objective:  To investigate the effect of endometriosis on venous thromboembolism (VTE) in oral contraceptive (OC) users. Pooled analysis on a harmonized dataset compromising international patient-centric cohort studies: INAS-VIPOS, INAS-SCORE, and INAS-FOCUS. Eleven European countries, the United States, and Canada.

Effect evaluation of outpatient long-term video EEGs for people with seizure disorders - study protocol of the ALVEEG project: a randomized controlled trial in Germany.

Background: Epilepsy and other seizure disorders account for a high disease burden in Germany. As a timely diagnosis and accurate treatment are crucial, improving the management of these disorders is important. Outside of Germany, outpatient long-term video EEGs (ALVEEGs) have demonstrated the potential to support the diagnosis and management of epilepsy and other seizure disorders.

Migraine and Risk of Parkinson Disease in Women: A Cohort Study.

Background And Objectives: Migraine and Parkinson disease (PD) are common neurologic disorders, which are hypothesized to share some pathophysiologic mechanisms. However, data on the association between migraine and risk of developing PD are sparse. We estimate the effect of migraine, migraine subtypes, and migraine episode frequency on the risk of developing PD in middle-aged and older women.

Rethinking animal attrition in preclinical research: Expressing causal mechanisms of selection bias using directed acyclic graphs.

Animal attrition in preclinical experiments can introduce bias in the estimation of causal treatment effects, as the treatment-outcome association in surviving animals may not represent the causal effect of interest. This can compromise the internal validity of the study despite randomization at the outset. Directed Acyclic Graphs (DAGs) are useful tools to transparently visualize assumptions about the causal structure underlying observed data.

Effect of elevated depressive symptoms during adolescence on health-related quality of life in young adulthood-a six-year cohort study with repeated exposure measurements.

Objectives: Depression is a major contributor of young people's burden of disease. In this study we aim to estimate the effect of elevated depressive symptoms on physical health-related quality of life.

Design: We used self-reported information from the prospective BELLA cohort study, which included adolescents selected from the general population in Germany.

Consequences of age and education correction of cognitive screening tests - A simulation study of the MoCA test in Italy.

Background: Cognitive screening tools are widely used in clinical practice to screen for age-related cognitive impairment and dementia. These tools' test scores are known to be influenced by age and education, leading to routine correction of raw scores for these factors. Despite these corrections being common practice, there is evidence suggesting that corrected scores may perform worse in terms of discrimination than raw scores.

Automated quantification of photoreceptor outer segments in developing and degenerating retinas on microscopy images across scales.

The functionality of photoreceptors, rods, and cones is highly dependent on their outer segments (POS), a cellular compartment containing highly organized membranous structures that generate biochemical signals from incident light. While POS formation and degeneration are qualitatively assessed on microscopy images, reliable methodology for quantitative analyses is still limited. Here, we developed methods to quantify POS (QuaPOS) maturation and quality on retinal sections using automated image analyses.

Health-related quality of life and impact of socioeconomic status among primary and secondary school students after the third COVID-19 wave in Berlin, Germany.

In the earlier phases of the COVID-19 pandemic, studies in Germany and elsewhere found an overall reduction in health-related quality of life (HRQoL) among students. However, there is little evidence on later pandemic stages as well as socioeconomic influencing factors. We aimed to (1) describe HRQoL in a Berlin student cohort at two time points in mid-2021, and to (2) analyze the effects of household income and education.

How to apply the broad toolbox of correlative light and electron microscopy to address a specific biological question.

Correlative light and electron microscopy (CLEM) is an approach that combines the strength of multiple imaging techniques to obtain complementary information about a given specimen. The "toolbox" for CLEM is broad, making it sometimes difficult to choose an appropriate approach for a given biological question. In this chapter, we provide experimental details for three CLEM approaches that can help the interested reader in designing a personalized CLEM strategy for obtaining ultrastructural data by using transmission electron microscopy (TEM).

SARS-CoV-2 Seroprevalence in a Berlin Kindergarten Environment: A Cross-Sectional Study, September 2021.

SARS-CoV-2 serology may be helpful to retrospectively understand infection dynamics in specific settings including kindergartens. We assessed SARS-CoV-2 seroprevalence in individuals connected to kindergartens in Berlin, Germany in September 2021. Children, staff, and household members from 12 randomly selected kindergartens were interviewed on COVID-19 history and sociodemographic parameters.

Purification of time-resolved insulin granules reveals proteomic and lipidomic changes during granule aging.

Endocrine cells employ regulated exocytosis of secretory granules to secrete hormones and neurotransmitters. Secretory granule exocytosis depends on spatiotemporal variables such as proximity to the plasma membrane and age, with newly generated granules being preferentially released. Despite recent advances, we lack a comprehensive view of the molecular composition of insulin granules and associated changes over their lifetime.