Comprehensive evaluation of AlphaMissense predictions by evidence quantification for variants of uncertain significance.

Accurate variant classification is critical for genetic diagnosis. Variants without clear classification, known as "variants of uncertain significance" (VUS), pose a significant diagnostic challenge. This study examines AlphaMissense performance in variant classification, specifically for VUS.

Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection.

Genome-sequence-based newborn screening (gNBS) has substantial potential to improve outcomes in hundreds of severe childhood genetic disorders (SCGDs). However, a major impediment to gNBS is imprecision due to variants classified as pathogenic (P) or likely pathogenic (LP) that are not SCGD causal. gNBS with 53,855 P/LP variants, 342 genes, 412 SCGDs, and 1,603 therapies was positive in 74% of UK Biobank (UKB470K) adults, suggesting 97% false positives.

Model of superior semicircular canal dehiscence: asymmetrical vestibular dysfunction induces reversible balance impairment.

Background: Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems. We have developed an animal model of this human condition in the Mongolian Gerbil that uses surgically created SSCD to induce the condition.

Physical Activity and the Health of a Nation: A National Challenge and Collective Response.

Historic recruitment and retention challenges confront the U.S. military.