Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Integrated Metagenomic and Metabolomic Analysis of In Vitro Murine Gut Microbial Cultures upon Bisphenol S Exposure.

Background: The gut microbiota are an important interface between the host and the environment, mediating the host's interactions with nutritive and non-nutritive substances. Dietary contaminants like Bisphenol A (BPA) may disrupt the microbial community, leaving the host susceptible to additional exposures and pathogens. BPA has long been a controversial and well-studied contaminant, so its structural analogues like Bisphenol S (BPS) are replacing it in consumer products, but have not been well studied.

Adjuvant therapy with pembrolizumab in renal cell carcinoma: real-world experiences from a retrospective, multi-institutional cohort.

Introduction: Adjuvant pembrolizumab versus placebo significantly improved disease-free survival (DFS) in renal cell carcinoma (RCC) patients at high risk of recurrence following nephrectomy in KEYNOTE-564 trial (NCT03142334). The objective of this study was to evaluate efficacy and safety of adjuvant pembrolizumab in a real-world setting.

Methods: In this multicenter retrospective study, RCC patients receiving adjuvant pembrolizumab between 01/22 and 10/23 at seven tertiary referral centers were included.

The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.

Orally bioavailable, synthetic nonpeptide agonists (NPAs) of the glucagon-like peptide-1 receptor (GLP-1R) may offer an effective, scalable pharmacotherapy to address the metabolic disease epidemic. One of the first molecules in the emerging class of GLP-1R NPAs is orforglipron, which is in clinical development for treating type 2 diabetes and obesity. Here, we characterized the pharmacological properties of orforglipron in comparison with peptide-based GLP-1R agonists and other NPAs.

Evaluation of deprescribing services in frail patients: a systematic review.

Background: Deprescribing, a process of dose reduction or withdrawal of inappropriate medication that no longer has benefit, is a proposed intervention in the care of older adults living with frailty.

Objective/aim: To evaluate the safety, effectiveness, and clinical impact of deprescribing services in frail patients.

Methods: A systematic literature search was performed in November 2023 using Scopus, CINAHL PLUS (EBSCO), MEDLINE (OVID and EMBASE), and Cochrane Library.