Autophagy-dependent alternative splicing of ribosomal protein S24 produces a more stable isoform that aids in hypoxic cell survival.

Cells remodel splicing and translation machineries to mount specialized gene expression responses to stress. Here, we show that hypoxic human cells in 2D and 3D culture models increase the relative abundance of a longer mRNA variant of ribosomal protein S24 (RPS24L) compared to a shorter mRNA variant (RPS24S) by favoring the inclusion of a 22 bp cassette exon. Mechanistically, RPS24L and RPS24S are induced and repressed, respectively, by distinct pathways in hypoxia: RPS24L is induced in an autophagy-dependent manner, while RPS24S is reduced by mTORC1 repression in a hypoxia-inducible factor-dependent manner.

Contraindications to use of neuraxial anesthesia for lower limb revascularization surgery in adults: a cross-sectional study.

Purpose: Nonrandomized and some randomized data suggest neuraxial anesthesia may improve outcomes after lower limb revascularization surgery. Nevertheless, the prevalence of contraindications to neuraxial anesthesia in vascular surgery patients is unknown. We aimed to identify the prevalence of patients with contraindications to neuraxial anesthesia, and to derive and validate a case ascertainment algorithm identifying individuals likely to have contraindications.

Analysis of Rates of Brain Metastases and Association With Breast Cancer Subtypes in Ontario, Canada.

Importance: Approximately 1 in 7 patients with metastatic breast cancer (MBC) will receive radiotherapy for brain metastases (BRM). Significant differences in cumulative incidence of BRM by breast cancer subtype may inform future BRM screening protocols.

Objective: To describe cumulative incidence of BRM among patients with de novo MBC.

mutated pancreatic cancer: A change is coming.

Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced disease. Recently, patients with germline mutations have received increased attention due to advances in the management of mutated ovarian and breast tumors. Germline mutations significantly increase risk of developing pancreatic cancer and can be found in up to 8% of patients with sporadic pancreatic cancer.