Covalent inhibitors of the RAS binding domain of PI3Kα impair tumor growth driven by RAS and HER2.

Genetic disruption of the RAS binding domain (RBD) of PI 3-kinase (PI3K) prevents the growth of mutant RAS driven tumors in mice and does not impact PI3K's role in insulin mediated control of glucose homeostasis. Selectively blocking the RAS-PI3K interaction may represent an attractive strategy for treating RAS-dependent cancers as it would avoid the toxicity associated with inhibitors of PI3K lipid kinase activity such as alpelisib. Here we report compounds that bind covalently to cysteine 242 in the RBD of PI3K p110α and block the ability of RAS to activate PI3K activity.

Hybrid performances in sport: Cybathlon spectatorship for critically imagining technologies for disability futures.

Disabled bodies have been historically marginalised in sporting arenas and spectacles. Assistive technologies have been increasingly featuring in, and changing, sporting landscapes. In some ways recent shifts have made disability more present and visible across many (para) sporting cultures, and yet sport continues to operate on a tiered system that assumes a normative able body.

Associations between dietary macronutrient composition and cardiometabolic health: data from NHANES 1999-2014.

Purpose: Dietary macronutrients significantly impact cardiometabolic health, yet research often focuses on individual macronutrient relationships. This study aimed to explore the associations between dietary macronutrient composition and cardiometabolic health.

Methods: This study included 33,681 US adults (49.

A Self-Administered Gamified Mobile Application for Secondary Prevention of Heart Disease in Patients Following a Cardiac Event (MyHeartMate): Process Evaluation from a Randomized Controlled Trial.

This study reports the process evaluation of a randomized controlled trial of the MyHeartMate app for patients with coronary heart disease (CHD). Data were collected on engagement in the intervention group from the app platform logs and self-reported usage and via interviews for perspectives of usefulness and acceptability. Participants' ( = 194) data logs showed 80.

Exercise Testing in Elite Athletes.

Exercise testing is frequently incorporated into management of patients with cardiovascular and/or pulmonary disease. A lifelong commitment to exercise promotes cardiac remodeling, leading to changes in structure and function of the atria and ventricles, commonly referred to as the "athletic heart." Stress testing is also incorporated into the management of athletes for a variety of reasons, such as identifying the cause of exertional symptoms, determining level of fitness and training zones, or assessing for acquired cardiomyopathies.