Trametinib Sensitivity is Defined by a Myeloid Differentiation Profile in Acute Myeloid Leukemia.

Background And Objective: Acute myelogenous leukemia (AML) is a common blood cancer marked by heterogeneity in disease and diverse genetic abnormalities. Additional therapies are needed as the 5-year survival remains below 30%. Trametinib is a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor that is widely used in solid tumors and also in tumors with activating RAS mutations.

Initial investigation of molecular phenotypes of airway mast cells and cytokine profiles in equine asthma.

Equine asthma is a naturally occurring lung disease characterized by chronic, partially reversible airway obstruction, pulmonary remodeling, and lower airway inflammation. Asthma is currently divided into two major groups, mild to moderate asthma (mEA) and severe asthma (sEA), but further subtyping by phenotype (i.e.

AM Versus PM Postoperative Administration of Warfarin With a Mechanical Mitral Valve.

Currently, there are no guidelines regarding the optimal daily timing of inpatient warfarin administration. The purpose of this study was to determine whether dosing warfarin in the morning will have a significant impact on therapeutic international normalized ratio (INR) achievement compared with evening administration in mechanical mitral valve patients initiated on warfarin following cardiac surgery. This was a single-center, pre- and post-retrospective cohort conducted between 2014 and 2018.

Using Machine Learning on Home Health Care Assessments to Predict Fall Risk.

Falls are the leading cause of injuries among older adults, particularly in the more vulnerable home health care (HHC) population. Existing standardized fall risk assessments often require supplemental data collection and tend to have low specificity. We applied a random forest algorithm on readily available HHC data from the mandated Outcomes and Assessment Information Set (OASIS) with over 100 items from 59,006 HHC patients to identify factors that predict and quantify fall risks.

Genome-wide Identification of Structure-Forming Repeats as Principal Sites of Fork Collapse upon ATR Inhibition.

DNA polymerase stalling activates the ATR checkpoint kinase, which in turn suppresses fork collapse and breakage. Herein, we describe use of ATR inhibition (ATRi) as a means to identify genomic sites of problematic DNA replication in murine and human cells. Over 500 high-resolution ATR-dependent sites were ascertained using two distinct methods: replication protein A (RPA)-chromatin immunoprecipitation (ChIP) and breaks identified by TdT labeling (BrITL).

Loci associated with skin pigmentation identified in African populations.

Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near , , , , , and that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at was introduced into East Africa by gene flow from non-Africans.

Going global by adapting local: A review of recent human adaptation.

The spread of modern humans across the globe has led to genetic adaptations to diverse local environments. Recent developments in genomic technologies, statistical analyses, and expanded sampled populations have led to improved identification and fine-mapping of genetic variants associated with adaptations to regional living conditions and dietary practices. Ongoing efforts in sequencing genomes of indigenous populations, accompanied by the growing availability of "-omics" and ancient DNA data, promises a new era in our understanding of recent human evolution and the origins of variable traits and disease risks.

Whole-genome sequencing of uropathogenic Escherichia coli reveals long evolutionary history of diversity and virulence.

Uropathogenic Escherichia coli (UPEC) are phenotypically and genotypically very diverse. This diversity makes it challenging to understand the evolution of UPEC adaptations responsible for causing urinary tract infections (UTI). To gain insight into the relationship between evolutionary divergence and adaptive paths to uropathogenicity, we sequenced at deep coverage (190×) the genomes of 19 E.

Comparing variant calling algorithms for target-exon sequencing in a large sample.

Background: Sequencing studies of exonic regions aim to identify rare variants contributing to complex traits. With high coverage and large sample size, these studies tend to apply simple variant calling algorithms. However, coverage is often heterogeneous; sites with insufficient coverage may benefit from sophisticated calling algorithms used in low-coverage sequencing studies.