Atomic-level mechanisms of abnormal activation in NRAS oncogenes from two-dimensional free energy landscapes.

The NRAS-mutant subset of melanoma is one of the most aggressive and lethal types associated with poor overall survival. Unfortunately, a low understanding of the NRAS-mutant dynamic behavior has led to the lack of clinically approved therapeutic agents able to directly target NRAS oncogenes. In this work, accurate local structures of NRAS and its mutants have been fully explored through the corresponding free energy surfaces obtained by microsecond scale well-tempered metadynamics simulations.

Unraveling atomic-scale mechanisms of GDP extraction catalyzed by SOS1 in KRAS-G12 and KRAS-D12 oncogenes.

The guanine exchange factor SOS1 plays a pivotal role in the positive feedback regulation of the KRAS signaling pathway. Recently, the regulation of KRAS-SOS1 interactions and KRAS downstream effector proteins has emerged as a key focus in the development of therapies targeting KRAS-driven cancers. However, the detailed dynamic mechanisms underlying SOS1-catalyzed GDP extraction and the impact of KRAS mutations remain largely unexplored.

Perception of antimicrobial stewardship interventions in Swiss primary care: a mixed-methods survey.

Background: With most of the antibiotic prescriptions occurring in primary care, antimicrobial stewardship (AMS) interventions must be known, welcomed, and used by primary care physicians (PCPs).

Aim: The main objective of this study was to evaluate the present awareness about, use of, and perceived acceptability, appropriateness, and feasibility of a broad range of interventions.

Design & Setting: A cross-sectional survey was distributed to Swiss PCPs from December 2023 to February 2024.

Monitoring equity in the delivery of health services: a Delphi process to select healthcare equity indicators.

Aims Of The Study: Health equity is a key component of quality of care and an objective for a growing number of quality improvement projects for deontological, ethical, public health and economic reasons. To monitor equity in the delivery of health services in Switzerland, there is a need to implement valid, measurable and actionable equity indicators, along with vulnerability stratifiers such as migrant status, which could lead to differences in quality of care. The aim of this study was to develop a set of healthcare equity indicators and stratifiers targeting inpatient and outpatient populations and to test their feasibility.

Evaluating the Economic Impact of the PedAMINES App in Reducing Medication Errors in Pediatric Emergency Care: Cost-Effectiveness Analysis.

Background: The administration of drugs in pediatric emergency care is a time-consuming process and is associated with a higher occurrence of medication errors compared with adult care. This is attributed to the intricacies of administration, which involve calculating doses based on the child's weight or age. To mitigate the occurrence of adverse drug events (ADEs), the PedAMINES (Pediatric Accurate Medication in Emergency Situations; Geneva University Hospitals) mobile app has been developed.