Modulation of the proteostasis network promotes tumor resistance to oncogenic KRAS inhibitors.

Despite substantial advances in targeting mutant KRAS, tumor resistance to KRAS inhibitors (KRASi) remains a major barrier to progress. Here, we report proteostasis reprogramming as a key convergence point of multiple KRASi-resistance mechanisms. Inactivation of oncogenic KRAS down-regulated both the heat shock response and the inositol-requiring enzyme 1α (IRE1α) branch of the unfolded protein response, causing severe proteostasis disturbances.

Introduction of medication review and medication report in Swedish hospital and primary care, using a theory-based implementation strategy.

Background: The development of routines regarding medication is important to avoid medication-related harm. Medication review and medication reports have earlier been found to be effective, but their implementation is not always successful. The aim of this study was to evaluate the introduction of medication review/medication report in hospital and primary care, in terms of perceptions of the implementation strategy, adoption and sustainability, in one Swedish county.

Lipidomic and biophysical homeostasis of mammalian membranes counteracts dietary lipid perturbations to maintain cellular fitness.

Proper membrane physiology requires maintenance of biophysical properties, which must be buffered from external perturbations. While homeostatic adaptation of membrane fluidity to temperature variation is a ubiquitous feature of ectothermic organisms, such responsive membrane adaptation to external inputs has not been directly observed in mammals. Here, we report that challenging mammalian membranes by dietary lipids leads to robust lipidomic remodeling to preserve membrane physical properties.

Curriculum Enrichment Across the Medical Education Continuum Using e-Delphi and the Community Priority Index.

Objective: To describe the use of the e-Delphi combined with the Community Priority Index (CPI) to support medical curriculum enrichment.

Methods: This mixed-methods study was conducted from December 2017 to May 2018 at Baylor College of Medicine in Houston, Texas. First, a nominal group identified a topical list.