Paradoxical dominant negative activity of an immunodeficiency-associated activating variant.

encodes three regulatory subunits of class IA phosphoinositide 3-kinase (PI3K), each associating with any of three catalytic subunits, namely p110α, p110β, or p110δ. Constitutional mutations cause diseases with a genotype-phenotype relationship not yet fully explained: heterozygous loss-of-function mutations cause SHORT syndrome, featuring insulin resistance and short stature attributed to reduced p110α function, while heterozygous activating mutations cause immunodeficiency, attributed to p110δ activation and known as APDS2. Surprisingly, APDS2 patients do not show features of p110α hyperactivation, but do commonly have SHORT syndrome-like features, suggesting p110α hypofunction.

Barcode medication administration system use and safety implications: a data-driven longitudinal study supported by clinical observation.

Objectives: Barcode medication administration (BCMA) systems may improve patient safety with successful integration and use. This study aimed to explore the barriers and enablers for the successful use of a BCMA system by examining the patterns of medication and patient scanning over time and potential safety implications.

Methods: Retrospective longitudinal study informed by prospective clinical observations using data extracted from five hospital wards over the first 16 months after implementation to determine trends in medication and patient scanning rates, reasons for non-compliance and scanning mismatch alerts.

Finding a constrained number of predictor phenotypes for multiple outcome prediction.

Background: Prognostic models help aid medical decision-making. Various prognostic models are available via websites such as MDCalc, but these models typically predict one outcome, for example, stroke risk. Each model requires individual predictors, for example, age, lab results and comorbidities.

Differences in time to surgery and defect sizes after Mohs micrographic surgery for black versus white patients with cutaneous squamous cell carcinoma.

Few studies have examined outcomes for Mohs micrographic surgery (MMS) for cutaneous squamous cell carcinoma (cSCC) in Black versus White patients. We compared time to surgery and defect sizes after MMS between Black versus White patients with cSCC. Patients with biopsy-proven cSCC treated with MMS at the Hospital of the University of Pennsylvania were identified from a prospectively maintained database (2006-2023).

The Biorepository and Integrative Genomics resource for inclusive genomics: insights from a diverse pediatric and admixed cohort.

The Biorepository and Integrative Genomics (BIG) Initiative in Tennessee has developed a pioneering resource to address gaps in genomic research by linking genomic, phenotypic, and environmental data from a diverse Mid-South population, including underrepresented groups. We analyzed 13,152 genomes from BIG and found significant genetic diversity, with 50% of participants inferred to have non-European or several types of admixed ancestry. Ancestry within the BIG cohort is stratified, with distinct geographic and demographic patterns, as African ancestry is more common in urban areas, while European ancestry is more common in suburban regions.