Inferring DNA methylation in non-skeletal tissues of ancient specimens.

Genome-wide premortem DNA methylation patterns can be computationally reconstructed from high-coverage DNA sequences of ancient samples. Because DNA methylation is more conserved across species than across tissues, and ancient DNA is typically extracted from bones and teeth, previous works utilizing ancient DNA methylation maps focused on studying evolutionary changes in the skeletal system. Here we suggest that DNA methylation patterns in one tissue may, under certain conditions, be informative on DNA methylation patterns in other tissues of the same individual.

Understanding Health Care Provider Burnout When Caring for Patients With Refractory Epilepsy in the United States.

Background And Objectives: Among health care providers (HCPs), neurologists have one of the highest rates of burnout in the United States, compromising the quality and accessibility of patient care. Patients with refractory epilepsy are especially challenging to treat. This study aims to understand the burnout level in neurologists treating patients with refractory epilepsy and identify key contributing factors.

R-Loop Accumulation in Spliceosome Mutant Leukemias Confers Sensitivity to PARP1 Inhibition by Triggering Transcription-Replication Conflicts.

Unlabelled: RNA splicing factor (SF) gene mutations are commonly observed in patients with myeloid malignancies. Here we showed that SRSF2- and U2AF1-mutant leukemias are preferentially sensitive to PARP inhibitors (PARPi), despite being proficient in homologous recombination repair. Instead, SF-mutant leukemias exhibited R-loop accumulation that elicited an R-loop-associated PARP1 response, rendering cells dependent on PARP1 activity for survival.

PRC2-independent actions of H3.3K27M in embryonic stem cell differentiation.

The histone H3 variant, H3.3, is localized at specific regions in the genome, especially promoters and active enhancers, and has been shown to play important roles in development. A lysine to methionine substitution in position 27 (H3.

Medical and nursing home costs: From cognitively unimpaired through dementia.

Introduction: Efforts to model the cost-effectiveness of managing/modifying cognitive impairment lack reliable, objective, baseline medical, and nursing-home (NH) costs.

Methods: A stratified-random sample of Olmsted County, MN, residents ages 70-89 years (N = 3545), well-characterized as cognitively unimpaired, mild cognitive impairment (MCI), or dementia, were followed forward ≤1 year in provider-linked billing data and the Centers for Medicare & Medicaid Services NH assessments. Direct medical/nursing home/medical + NH costs were estimated.