Developmental beta-cell death orchestrates the islet's inflammatory milieu by regulating immune system crosstalk.

While pancreatic beta-cell proliferation has been extensively studied, the role of cell death during islet development remains incompletely understood. Using a genetic model of caspase inhibition in beta cells coupled with mathematical modeling, we here discover an onset of beta-cell death in juvenile zebrafish, which regulates beta-cell mass. Histologically, this beta-cell death is underestimated due to phagocytosis by resident macrophages.

PROCEDURAL STATUS OF PERSONS SUFFERING FROM MENTAL DISORDERS: INTERNATIONAL STANDARDS.

Objective: The aim: To identify, group and analyze international standards in terms of regulating the criminal procedural status of persons su!ering from mental disorders.

Patients And Methods: Materials and methods: In preparing the article, the following issues were worked out: the provisions of international legal acts; legal positions of the European Court of Human Rights regarding the observance of the right to a fair trial of persons su!ering from mental disorders; scienti"c research to ensure the rights of persons su!ering from mental disorders in criminal proceedings. The methodological basis of the research is dialectical, comparative-legal, systemic-structural, analytical, synthetic, complex research methods.

A deep learning platform to assess drug proarrhythmia risk.

Drug safety initiatives have endorsed human iPSC-derived cardiomyocytes (hiPSC-CMs) as an in vitro model for predicting drug-induced cardiac arrhythmia. However, the extent to which human-defined features of in vitro arrhythmia predict actual clinical risk has been much debated. Here, we trained a convolutional neural network classifier (CNN) to learn features of in vitro action potential recordings of hiPSC-CMs that are associated with lethal Torsade de Pointes arrhythmia.

Metabolic Maturation Increases Susceptibility to Hypoxia-induced Damage in Human iPSC-derived Cardiomyocytes.

The development of new cardioprotective approaches using in vivo models of ischemic heart disease remains challenging as differences in cardiac physiology, phenotype, and disease progression between humans and animals influence model validity and prognostic value. Furthermore, economical and ethical considerations have to be taken into account, especially when using large animal models with relevance for conducting preclinical studies. The development of human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has opened new opportunities for in vitro studies on cardioprotective compounds.