Inhibition of BRAF Sensitizes Thyroid Carcinoma to Immunotherapy by Enhancing tsMHCII-mediated Immune Recognition.

Context: Multiple mechanisms play roles in restricting the ability of T-cells to recognize and eliminate tumor cells.

Objective: To identify immune escape mechanisms involved in papillary thyroid carcinoma (PTC) to optimize immunotherapy.

Setting And Design: iTRAQ analysis was conducted to identify proteins differentially expressed in PTC samples with or without BRAFV600E mutation.

[Study on syndromic deafness caused by novel pattern of compound heterozygous variants in the gene].

To explore the pathogenic variants of a family with syndromic deafness by high-throughput sequencing. The family was from Puyang City, Henan Province, and had four members, including two with syndromic deafness. The proband and his sister had congenital deafness, and their parents had normal phenotypes.

Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complex disease triggered by the interaction between genetics and the environment, especially through the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, the available evidence shows that genetic diversity and environmental exposure cannot explain all the clinical characteristics and heterogeneity of RA. In contrast, recent studies demonstrate that epigenetics play important roles in the pathogenesis of RA, especially DNA methylation and histone modification.

ColoType: a forty gene signature for consensus molecular subtyping of colorectal cancer tumors using whole-genome assay or targeted RNA-sequencing.

Colorectal cancer (CRC) tumors can be partitioned into four biologically distinct consensus molecular subtypes (CMS1-4) using gene expression. Evidence is accumulating that tumors in different subtypes are likely to respond differently to treatments. However, to date, there is no clinical diagnostic test for CMS subtyping.

Allele Facilitates the Metastasis of KRAS-Mutant Colorectal Cancer.

Major histocompatibility complex (HLA) class I chain-related protein A (MICA) regulates immune surveillance through activation of NKG2D (natural killer group 2D) receptor. However, the genetic association, potential function, and predictive ability of MICA alleles with colorectal cancer (CRC) prognosis remain undefined. In this study, we characterized MICA alleles in tissue samples from 104 patients with CRC and 536 healthy controls and carried out genetic association studies by molecular and clinical CRC phenotypes.

Association of variants in selected genes mediating host immune response with duration of Staphylococcus aureus bacteremia.

Host genetic variation may be a contributing factor to variability in Staphylococcus aureus bacteremia duration. We assessed whether 28 single nucleotide polymorphisms (SNPs) in seven genes (TLR2, TLR4, TIRAP, IRAK4, TRAF6, NOD2, and CISH) that mediate host immune response were associated with S. aureus bacteremia duration.

Genome-wide DNA methylation profiles of low- and high-grade adenoma reveals potential biomarkers for early detection of colorectal carcinoma.

Background: Abnormal DNA methylation is a hallmark of human cancers and may be a promising biomarker for early diagnosis of human cancers. However, the majority of DNA methylation biomarkers that have been identified are based on the hypothesis that early differential methylation regions (DMRs) are maintained throughout carcinogenesis and could be detected at all stages of cancer.

Methods: In this study, we identified potential early biomarkers of colorectal cancer (CRC) development by genome-wide DNA methylation assay (Illumina infinium450, 450 K) of normal (N = 20) and pre-colorectal cancer samples including 18 low-grade adenoma (LGA) and 22 high-grade adenoma (HGA), integrated with GEO and ArrayExpress datasets (N = 833).

BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis.

The breast cancer susceptibility gene 1 () is a major tumor suppressor gene and is most frequently mutated in hereditary breast cancer. BRCA1 plays a critical role in many biological processes, especially maintaining genomic stability in the nucleus, yet its role in the cytoplasm remains elusive. Here, it is revealed that BRCA1 maintains a healthy mitochondrial network through regulating mitochondrial dynamics, including fission and fusion.

Noninvasive chimeric DNA profiling identifies tumor-originated HBV integrants contributing to viral antigen expression in liver cancer.

Background: Host genome integration of HBV sequence is considered to be significant in HBV antigen expression and the development of hepatocellular carcinoma (HCC).

Method: We developed a probe-based capture strategy to enrich integrated HBV DNA for deep-sequencing analysis of integration sites in paired patient samples derived from tumor, liver tissue adjacent to tumor, saliva and plasma, as a platform for exploring the correlation, significance and utility of detecting integrations in these sample types.

Results: Most significantly, alpha fetoprotein levels significantly correlated to the amounts of integrations detected in tumor.

Modeling of Effective Antimicrobials to Reduce Virulence Gene Expression Using a Two-Compartment Hollow Fiber Infection Model.

Toxins produced by community-associated methicillin-resistant (CA-MRSA) contribute to virulence. We developed a statistical approach to determine an optimum sequence of antimicrobials to treat CA-MRSA infections based on an antimicrobial's ability to reduce virulence. In an in vitro pharmacodynamic hollow fiber model, expression of six virulence genes (, , , , , and in CA-MRSA USA300 was measured by RT-PCR at six time points with or without human-simulated, pharmacokinetic dosing of five antimicrobials (clindamycin, minocycline, vancomycin, linezolid, and trimethoprim/sulfamethoxazole (SXT)).

A Polygenic and Phenotypic Risk Prediction for Polycystic Ovary Syndrome Evaluated by Phenome-Wide Association Studies.

Context: As many as 75% of patients with polycystic ovary syndrome (PCOS) are estimated to be unidentified in clinical practice.

Objective: Utilizing polygenic risk prediction, we aim to identify the phenome-wide comorbidity patterns characteristic of PCOS to improve accurate diagnosis and preventive treatment.

Design, Patients, And Methods: Leveraging the electronic health records (EHRs) of 124 852 individuals, we developed a PCOS risk prediction algorithm by combining polygenic risk scores (PRS) with PCOS component phenotypes into a polygenic and phenotypic risk score (PPRS).

Development of a vaccine against Staphylococcus aureus invasive infections: Evidence based on human immunity, genetics and bacterial evasion mechanisms.

Invasive Staphylococcus aureus infections are a leading cause of morbidity and mortality in both hospital and community settings, especially with the widespread emergence of virulent and multi-drug resistant methicillin-resistant S. aureus strains. There is an urgent and unmet clinical need for non-antibiotic immune-based approaches to treat these infections as the increasing antibiotic resistance is creating a serious threat to public health.

(5R)-5-Hydroxytriptolide (LLDT-8) induces substantial epigenetic mediated immune response network changes in fibroblast-like synoviocytes from rheumatoid arthritis patients.

Tripterygium is a traditional Chinese medicine that has widely been used in the treatment of rheumatic disease. (5R)-5-hydroxytriptolide (LLDT-8) is an extracted compound from Tripterygium, which has been shown to have lower cytotoxicity and relatively higher immunosuppressive activity when compared to Tripterygium. However, our understanding of LLDT-8-induced epigenomic impact and overall regulatory changes in key cell types remains limited.

Facilitating phenotype transfer using a common data model.

Background: Implementing clinical phenotypes across a network is labor intensive and potentially error prone. Use of a common data model may facilitate the process.

Methods: Electronic Medical Records and Genomics (eMERGE) sites implemented the Observational Health Data Sciences and Informatics (OHDSI) Observational Medical Outcomes Partnership (OMOP) Common Data Model across their electronic health record (EHR)-linked DNA biobanks.

Reduced Anti-Histone Antibodies and Increased Risk of Rheumatoid Arthritis Associated with a Single Nucleotide Polymorphism in PADI4 in North Americans.

Autoantibodies against citrullinated proteins are a hallmark of rheumatoid arthritis, a destructive inflammatory arthritis. Peptidylarginine deiminase 4 (PAD4) has been hypothesized to contribute to rheumatoid arthritis by citrullinating histones to induce neutrophil extracellular traps (NETs), which display citrullinated proteins that are targeted by autoantibodies to drive inflammation and arthritis. Consistent with this theory, PAD4-deficient mice have reduced NETs, autoantibodies, and arthritis.

Genome-Wide DNA Methylation Profiles Reveal Common Epigenetic Patterns of Interferon-Related Genes in Multiple Autoimmune Diseases.

Graves' disease (GD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are complex autoimmune diseases sharing common clinical, genetic and pathogenetic features. However, the commonalities of the DNA methylation profiles for these diseases are still unknown. We conducted an integrative analysis of the multiple-autoimmune disease methylation dataset including GD, RA, SLE, and SSc samples, to identify the common methylation patterns of autoimmune diseases.

Nonparametric collective spectral density estimation with an application to clustering the brain signals.

In this paper, we develop a method for the simultaneous estimation of spectral density functions (SDFs) for a collection of stationary time series that share some common features. Due to the similarities among the SDFs, the log-SDF can be represented using a common set of basis functions. The basis shared by the collection of the log-SDFs is estimated as a low-dimensional manifold of a large space spanned by a prespecified rich basis.

Identification of Hyper-Methylated Tumor Suppressor Genes-Based Diagnostic Panel for Esophageal Squamous Cell Carcinoma (ESCC) in a Chinese Han Population.

DNA methylation-based biomarkers were suggested to be promising for early cancer diagnosis. However, DNA methylation-based biomarkers for esophageal squamous cell carcinoma (ESCC), especially in Chinese Han populations have not been identified and evaluated quantitatively. Candidate tumor suppressor genes ( = 65) were selected through literature searching and four public high-throughput DNA methylation microarray datasets including 136 samples totally were collected for initial confirmation.

Polymorphism rs3819102 in thymidylate synthase and environmental factors: effects on lung cancer in Chinese population.

Purpose: Lung cancer is the leading cause of cancer death worldwide, and the predominant risk factor for its development is smoking. Thymidylate synthase (TYMS) is a key enzyme in DNA synthesis that catalyzes the conversion of deoxyuridine monophosphate to dTMP. Rs931794, a single nucleotide polymorphism located in the TYMS gene, was suggested to be associated with cancer risk.

LPA Variants Are Associated With Residual Cardiovascular Risk in Patients Receiving Statins.

Background: Coronary heart disease (CHD) is a leading cause of death globally. Although therapy with statins decreases circulating levels of low-density lipoprotein cholesterol and the incidence of CHD, additional events occur despite statin therapy in some individuals. The genetic determinants of this residual cardiovascular risk remain unknown.