Subcutaneous administration of the sphingosine kinase 2 inhibitor ABC294640 has no metabolic benefits in high fat diet-induced obesity in male mice.

Aims: Experimental evidence suggests an important role for sphingosine-1-phosphate (S1P) and its generating enzymes sphingosine kinase 1/2 (SphK1/2) in obesity. We and others have shown that plasma S1P levels are elevated in obese mice and humans. Preclinical studies suggest that genetic SphK2 ablation in mice protects from age- and diet-induced obesity and metabolic dysfunction.

Impact of enhanced infection control and antimicrobial stewardship on infections by Clostridioides difficile, vancomycin-resistant enterococci, and third-generation cephalosporin-resistant Enterobacterales: A stepped-wedge cluster intervention study.

Objectives: Infection prevention and control (IPC) and antimicrobial stewardship (AMS) measures are critical to reduce transmission and infection by Clostridioides difficile (CDI) and other enteric pathogens. This study evaluated the impact of enhanced IPC and AMS on CDI and bloodstream infections (BSI) by vancomycin-resistant enterococci (VRE), and third-generation cephalosporin-resistant Enterobacterales (3GCREB).

Methods: The study was conducted in five German university hospitals from January 2016 to July 2019.

Triage of Stable Patients With Suspected Acute Myocardial Infarction and Left Bundle Branch Block: A Multicenter, Propensity Score-Matched Analysis.

Background: A pragmatic immediate invasive strategy is recommended in patients with ischemic symptoms and suspected left bundle branch block acute myocardial infarction (LBBB-AMI). It is important to identify patients with LBBB-AMI who do not need to be treated with the same strategy as those with ST-segment elevation myocardial infarction (STEMI). In this study, we aimed to compare the outcome of stable but symptomatic patients with suspected LBBB-AMI with that of matched STEMI patients.

Direct genetic transformation bypasses tumor-associated DNA methylation alterations.

Background: Tumors represent dynamically evolving populations of mutant cells, and many advances have been made in understanding the biology of their progression. However, there are key unresolved questions about the conditions that support a cell's initial transformation, which cannot be easily captured in patient populations and are instead modeled using transgenic cellular or animal systems.

Results: Here, we use extensive patient atlas data to define common features of the tumor DNA methylation landscape as they compare to healthy human cells and apply this benchmark to evaluate 21 engineered human and mouse models for their ability to reproduce these patterns.

HELLS is required for maintaining proper DNA modification at human satellite repeats.

DNA methylation regulation involves multi-layered chromatin interactions that require remodeling proteins like the helicase, lymphoid-specific (HELLS). Here, we generate HELLS and DNA methyltransferase 3A and B (DNMT3A/B) knockout human pluripotent stem cells and report telomere-to-telomere maps of whole genome bisulfite sequencing data combined with ATAC-sequencing. Disrupting HELLS induces a global loss of DNA methylation that is distinct from the DNMTs, in particular over peri/centromeric satellite repeats as defined in the telomere-to-telomere genome assembly.