Systematic perturbation screens identify regulators of inflammatory macrophage states and a role for TNF mRNA m6A modification.

Macrophages exhibit remarkable functional plasticity, a requirement for their central role in tissue homeostasis. During chronic inflammation, macrophages acquire sustained inflammatory 'states' that contribute to disease, but there is limited understanding of the regulatory mechanisms that drive their generation. Here we describe a systematic functional genomics approach that combines genome-wide phenotypic screening in primary murine macrophages with transcriptional and cytokine profiling of genetic perturbations in primary human macrophages to uncover regulatory circuits of inflammatory states.

Accelerated drug-resistant variant discovery with an enhanced, scalable mutagenic base editor platform.

Personalized cancer therapeutics bring directed treatment options to patients based on their tumor's genetic signature. Unfortunately, tumor genomes are remarkably adaptable, and acquired resistance through gene mutation frequently occurs. Identifying mutations that promote resistance within drug-treated patient populations can be cost, resource, and time intensive.

A national qualitative study of surgical coaching: Opportunities and barriers for colorectal surgeons.

Background: Surgical coaching interventions have been recommended as a method of technological skills improvement for individual surgeons and lifelong occupational learning. Patient outcomes for laparoscopic colectomy vary significantly based on surgeon experience and case volume. As surgical coaching is an emerging area, little is known about how surgeons view coaching interventions.

A saturation mutagenesis screen uncovers resistant and sensitizing secondary mutations to clinical KRAS inhibitors.

Mutant-specific inhibitors of KRASG12C, such as AMG510 (sotorasib) and MRTX849 (adagrasib), offer the unprecedented opportunity to inhibit KRAS, the most frequently mutated and heretofore undruggable oncoprotein. While clinical data are still limited, on-target mutations in KRASG12C at position 12 and other sites are emerging as major drivers of clinical relapse. We identified additional mutations in KRASG12C that impact inhibitor sensitivity through a saturation mutagenesis screen in the KRASG12C NCI-H358 non–small-cell lung cancer (NSCLC) cell line.

Older Adults' Behavior Intentions Once a COVID-19 Vaccine Becomes Available.

Background: The purpose of this study was to examine the impact of antecedent variables on older adults' intention to get a CORONAVIRUS DISEASE-2019 vaccine. Older adults are at higher risk of severe illness from the disease and face an increasingly ageist general population who misrepresent the pandemic as an older adult problem. We use the Theory of Planned Behavior framework to examine vaccine behavior intention.