A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator.

Background: Adiposity is an established risk factor for colorectal cancer (CRC). The pathways underlying this relationship, and specifically the role of circulating proteins, are unclear.

Methods: Utilizing two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and colocalization, based on summary data from large sex-combined and sex-specific genetic studies, we estimated the univariable associations between: (i) body mass index (BMI) and waist-hip ratio (WHR) and overall and site-specific (colon, proximal colon, distal colon, and rectal) CRC risk, (ii) BMI and WHR and circulating proteins, and (iii) adiposity-associated circulating proteins and CRC risk.

Short Interval Repeat Colonoscopy After Inadequate Bowel Preparation Is Low Among Veterans.

Background: Adenoma detection rate and interval colon cancer rates are associated with bowel preparation quality. The US Multisociety Task Force recommends repeat colonoscopy for individuals with inadequate bowel preparation (IBP) within 1 year. However, little is known regarding the rate and associated factors of repeat colonoscopy after IBP.

Carbohydrate supplementation maintains physical performance during short-term energy deficit despite reductions in exogenous glucose oxidation.

Exogenous glucose oxidation is reduced 55% during aerobic exercise after three days of complete starvation. Whether energy deficits more commonly experienced by athletes and military personnel similarly affect exogenous glucose oxidation and what impact this has on physical performance remains undetermined. This randomized, longitudinal parallel study aimed to assess the effects of varying magnitudes of energy deficit (DEF) on exogenous glucoseoxidation and physical performance compared to energy balance (BAL).

Evaluation of Cereblon-Directing Warheads for the Development of Orally Bioavailable PROTACs.

PROTACs usually occupy physicochemical space outside the one defined by classical drug-like molecules, which often presents considerable challenges in their optimization and development for oral administration. We have previously reported phenyl glutarimide (PG)-based BET PROTAC SJ995973, with improved overall degradation and antiproliferative activities compared to its direct thalidomide-based analogue dBET1, but similarly poor pharmacokinetic profile. To further demonstrate the PG utility, we describe here optimization efforts that led to the discovery of an orally bioavailable BET-PROTAC SJ44236 (), and results of a comprehensive comparative study with analogues containing alternative CRBN-directing warheads.

Use of design thinking to develop a benchmarking tool to assess documentation procedures in a hospital pharmacy aseptic compounding unit: a case study.

Objectives: This paper combines the concepts of design thinking and benchmarking in an aseptic manufacturing context. Design thinking is a problem-solving approach that aims to understand user needs, generate ideas, prototypes and test solutions. There are no published examples in the Irish healthcare setting.