The Human Phenotype Ontology in 2024: phenotypes around the world

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Wide-area low-energy surface stimulation of large mammalian ventricular tissue

The epicardial and endocardial surfaces of the heart are attractive targets to administer antiarrhythmic electrotherapies. Electrically stimulating wide areas of the surfaces of small mammalian ventricles is straightforward given the relatively small scale of their myocardial dimensions compared to the tissue space constant and electrical field. However, it has yet to be proven for larger mammalian hearts with tissue properties and ventricular dimensions closer to humans. Our goal was to address the feasibility and impact of wide-area electrical stimulation on the ventricular surfaces of large mammalian hearts at different stimulus strengths. This was accomplished by placing long line electrodes on the ventricular surfaces of pig hearts that span wide areas, and activating them individually. Stimulus efficacy was assessed and compared between surfaces, and tissue viability was evaluated. Activation time was dependent on stimulation strength and location, achieving uniform linear stimulation at 9x threshold strength. Endocardial stimulation activated more tissue transmurally than epicardial stimulation, which could be considered a potential target for future cardiac electrotherapies. Overall, our results indicate that electrically stimulating wide areas of the ventricular surfaces of large mammals is achievable with line electrodes, minimal tissue damage, and energies under the human pain threshold (100 mJ)