Validation, bias assessment, and optimization of the UNAFIED 2-year risk prediction model for undiagnosed atrial fibrillation using national electronic health data.

Background: Prediction models for atrial fibrillation (AF) may enable earlier detection and guideline-directed treatment decisions. However, model bias may lead to inaccurate predictions and unintended consequences.

Objective: The purpose of this study was to validate, assess bias, and improve generalizability of "UNAFIED-10," a 2-year, 10-variable predictive model of undiagnosed AF in a national data set (originally developed using the Indiana Network for Patient Care regional data).

DARPins as a novel tool to detect and degrade p73.

The concept of Targeted Protein Degradation (TPD) has been introduced as an attractive alternative to the development of classical inhibitors. TPD can extend the range of proteins that can be pharmacologically targeted beyond the classical targets for small molecule inhibitors, as a binding pocket is required but its occupancy does not need to lead to inhibition. The method is based on either small molecules that simultaneously bind to a protein of interest and to a cellular E3 ligase and bring them in close proximity (molecular glue) or a bi-functional molecule synthesized from the chemical linkage of a target protein-specific small molecule and one that binds to an E3 ligase (Proteolysis Targeting Chimeras (PROTAC)).

Effects of a Circuit Training Program on Myokine Levels in Insulin-Resistant Women: A Randomised Controlled Trial.

Circuit training is a form of body conditioning with endurance and resistance components. Given the function of skeletal muscle as an endocrine organ secreting various myokines involved in maintaining glucose metabolism homeostasis, our study focused on estimating the impact of the implemented training program on the direction of changes in myokines such as interleukin (IL)-6, IL-10, fibroblast growth factor 21 (FGF21), and irisin in women newly diagnosed with insulin resistance. This prospective controlled trial randomly divided 42 women into two groups.

Mechanopharmacology: in vitro techniques to advance drug discovery.

Mechanopharmacology is an emerging interdisciplinary field that investigates drug action using biomechanically appropriate in vitro systems to the relevant (patho)physiology. This review outlines emerging technologies and techniques which aim to bridge the gap between mechanical cues influencing cellular biology and conventional pharmacology. We delve into the impact of mechanopharmacology on drug development in cancers and fibrotic diseases.

A novel chitosan-peptide system for cartilage tissue engineering with adipose-derived stromal cells.

The natural healing process of cartilage injuries often fails to fully restore the tissue's biological and mechanical functions. Cartilage grafts are costly and require surgical intervention, often associated with complications such as intraoperative infection and rejection by the recipient due to ischemia. Novel tissue engineering technologies aim to ideally fill the cartilage defect to prevent disease progression or regenerate damaged tissue.