Systematic discovery of neoepitope-HLA pairs for neoantigens shared among patients and tumor types.

The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen-human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide-HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope-HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines.

Quartet RNA reference materials improve the quality of transcriptomic data through ratio-based profiling.

Certified RNA reference materials are indispensable for assessing the reliability of RNA sequencing to detect intrinsically small biological differences in clinical settings, such as molecular subtyping of diseases. As part of the Quartet Project for quality control and data integration of multi-omics profiling, we established four RNA reference materials derived from immortalized B-lymphoblastoid cell lines from four members of a monozygotic twin family. Additionally, we constructed ratio-based transcriptome-wide reference datasets between two samples, providing cross-platform and cross-laboratory 'ground truth'.

An immunodominant NP-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

NP-B*07:02-specific CD8 T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52).

Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia.

Background: Agitation is a common neuropsychiatric symptom of Alzheimer disease (AD). Data are scarce regarding agitation prevalence among community-dwelling patients with AD.

Objective: To estimate agitation prevalence in a sample of US patients with AD/dementia overall and by AD/dementia disease severity, using data from electronic health records (EHR).

Integrated Myocardial Perfusion Imaging Diagnostics Improve Detection of Functionally Significant Coronary Artery Stenosis by 13N-ammonia Positron Emission Tomography.

Background: Recent evidence suggests that the diagnostic accuracy of myocardial perfusion imaging is improved by quantifying stress myocardial blood flow (MBF) in absolute terms. We evaluated a comprehensive quantitative (13)N-ammonia positron emission tomography ((13)NH3-PET) diagnostic panel, including stress MBF, coronary flow reserve (CFR), and relative flow reserve (RFR) in conjunction with relative perfusion defect (PD) assessments to better detect functionally significant coronary artery stenosis.

Methods And Results: A total of 130 patients (307 vessels) with coronary artery disease underwent both (13)NH3-PET and invasive coronary angiography with fractional flow reserve (FFR) measurement.

Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats.

Simultaneous inhibition of the acetyl-CoA carboxylase (ACC) isozymes ACC1 and ACC2 results in concomitant inhibition of fatty acid synthesis and stimulation of fatty acid oxidation and may favorably affect the morbidity and mortality associated with obesity, diabetes, and fatty liver disease. Using structure-based drug design, we have identified a series of potent allosteric protein-protein interaction inhibitors, exemplified by ND-630, that interact within the ACC phosphopeptide acceptor and dimerization site to prevent dimerization and inhibit the enzymatic activity of both ACC isozymes, reduce fatty acid synthesis and stimulate fatty acid oxidation in cultured cells and in animals, and exhibit favorable drug-like properties. When administered chronically to rats with diet-induced obesity, ND-630 reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia.

Hospital costs associated with atrial fibrillation for patients with ischemic stroke aged 18-64 years in the United States.

Background And Purpose: Hospital costs associated with atrial fibrillation (AFib) among patients with stroke have not been well-studied, especially among people aged <65 years. We estimated the AFib-associated hospital costs in US patients aged 18 to 64 years.

Methods: We identified hospital admissions with a primary diagnosis of ischemic stroke from the 2010 to 2012 MarketScan Commercial Claims and Encounters inpatient data sets, excluding those with capitated health insurance plans, aged <18 or >64 years, missing geographic region, hospital costs below the 1st or above 99th percentile, and having carotid intervention (n=40 082).

Fe-chlorophyllin promotes the growth of wheat roots associated with nitric oxide generation.

Effects of Fe-chlorophyllin on the growth of wheat root were investigated in this study. We found that Fe-chlorophyllin can promote root growth. The production of nitric oxide in wheat root was detected using DAF-2DA fluorescent emission.