Primary Antibody Deficiencies: Curation Of Gene-Disease Relationships Using A ClinGen Validation Framework.

Background: The Clinical Genome Resource (ClinGen) is an international collaborative effort between scientists and clinicians, diagnostic and research laboratories as well as the patient community. Using a standardized framework, ClinGen has established guidelines to classify gene-disease relationships as Definitive, Strong, Moderate, and Limited based on available scientific and clinical evidence. When the genetic and functional evidence for a gene-disease relationship has conflicting interpretations or contradictory evidence, they can be Disputed or Refuted.

Site-Specific Ventricular Tachycardia Inducibility.

Background: Programmed electrical stimulation (PES) is an essential part of ventricular tachycardia (VT) ablation procedures, but VT is not always inducible, usually for reasons that are not clear.

Objectives: This study sought to review pacing site-specific failure of PES to induce scar-related VT and to provide a potential mechanistic explanation of the phenomena using a computer simulation.

Methods: Six patients in whom aggressive PES from traditional RV pacing sites failed to induce VT, but VT was easily inducible from a nontraditional site, were reviewed.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Heterogeneous Ribonucleoprotein K Is a Host Regulatory Factor of Chikungunya Virus Replication in Astrocytes.

Chikungunya virus (CHIKV) is an emerging, mosquito-borne arthritic alphavirus increasingly associated with severe neurological sequelae and long-term morbidity. However, there is limited understanding of the crucial host components involved in CHIKV replicase assembly complex formation, and thus virus replication and virulence-determining factors, within the central nervous system (CNS). Furthermore, the majority of CHIKV CNS studies focus on neuronal infection, even though astrocytes represent the main cerebral target.

Formation of a low-mass galaxy from star clusters in a 600-million-year-old Universe.

The most distant galaxies detected were seen when the Universe was a scant 5% of its current age. At these times, progenitors of galaxies such as the Milky Way were about 10,000 times less massive. Using the James Webb Space Telescope (JWST) combined with magnification from gravitational lensing, these low-mass galaxies can not only be detected but also be studied in detail.