Effects of RARα ligand binding domain mutations on breast fibroepithelial tumor function and signaling.

Point mutations in the ligand binding domain of retinoic acid receptor alpha (RARα) are linked to breast fibroepithelial tumor development, but their role in solid tumorigenesis is unclear. In this study, we assessed the functional effects of known RARα mutations on retinoic acid signaling using biochemical and cellular assays. All tested mutants exhibited reduced transcriptional activity compared to wild-type RARα and showed a dominant negative effect, a feature associated with developmental defects and tumor formation.

Potential Importance of Maximal Upper Body Strength-Generating Qualities and Upper Body Strength Training for Performance of High-Intensity Running and Jumping Actions: A Scoping Review.

Purpose: To investigate the influence of upper body (UB) strength qualities and UB strength training on the performance of high-intensity running and jumping actions and to identify gaps and recommendations for future research.

Methods: A systematic search using the PRISMA Scoping Review protocol was conducted in February 2024 using PubMed, Scopus, and ICTRP. Studies eligible for inclusion were those that reported associations between UB or trunk maximal strength qualities (e.

Construction and performance of a clinical prediction rule for ureteral stone without the use of race or ethnicity: A new STONE score.

Objectives: The original STONE score was designed to predict the presence of uncomplicated renal colic and the corresponding absence of alternate serious etiologies. It was retrospectively derived and prospectively validated and resulted in five variables: Sex (male gender), Timing (acute onset of pain), "Origin" (non-Black race), Nausea/vomiting (present), and Erythrocytes (microscopic hematuria). With recent increased awareness of the potential adverse impacts of including race (a socially constructed identity) in clinical prediction rules, we sought to determine if a revised STONE score without race could be constructed with similar diagnostic accuracy.

Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice.

Purpose: As part of the 100,000 Genomes Project, we set out to assess the potential viability and clinical impact of reporting genetic variants associated with drug-induced toxicity for patients with cancer recruited for whole-genome sequencing (WGS) as part of a genomic medicine service.

Methods: Germline WGS from 76,805 participants was analyzed for pharmacogenetic (PGx) variants in four genes (, , , ) associated with toxicity induced by five drugs used in cancer treatment (capecitabine, fluorouracil, mercaptopurine, thioguanine, irinotecan). Linking genomic data with prescribing and hospital incidence records, a phenome-wide association study (PheWAS) was performed to identify whether phenotypes indicative of adverse drug reactions (ADRs) were enriched in drug-exposed individuals with the relevant PGx variants.