Influence of social determinants of health and county vaccination rates on machine learning models to predict COVID-19 case growth in Tennessee.

Introduction: The SARS-CoV-2 (COVID-19) pandemic has exposed health disparities throughout the USA, particularly among racial and ethnic minorities. As a result, there is a need for data-driven approaches to pinpoint the unique constellation of clinical and social determinants of health (SDOH) risk factors that give rise to poor patient outcomes following infection in US communities.

Methods: We combined county-level COVID-19 testing data, COVID-19 vaccination rates and SDOH information in Tennessee.

Predictive Modeling of COVID-19 Case Growth Highlights Evolving Demographic Risk Factors in Tennessee and Georgia.

The COVID-19 pandemic has exposed the need to understand the unique risk drivers that contribute to uneven morbidity and mortality in US communities. Addressing the community-specific social determinants of health that correlate with spread of SARS-CoV-2 provides an opportunity for targeted public health intervention to promote greater resilience to viral respiratory infections in the future. Our work combined publicly available COVID-19 statistics with county-level social determinants of health information.

Illuminating an Invisible Epidemic: A Systemic Review of the Clinical and Economic Benefits of Early Diagnosis and Treatment in Inflammatory Disease and Related Syndromes.

Healthcare expenditures in the United States are growing at an alarming level with the Centers for Medicare and Medicaid Services (CMS) projecting that they will reach $5.7 trillion per year by 2026. Inflammatory diseases and related syndromes are growing in prevalence among Western societies.

Endogenous double-stranded Alu RNA elements stimulate IFN-responses in relapsing remitting multiple sclerosis.

Various sensors that detect double-stranded RNA, presumably of viral origin, exist in eukaryotic cells and induce IFN-responses. Ongoing IFN-responses have also been documented in a variety of human autoimmune diseases including relapsing-remitting multiple sclerosis (RRMS) but their origins remain obscure. We find increased IFN-responses in leukocytes in relapsing-remitting multiple sclerosis at distinct stages of disease.

Longitudinal changes in the expression of IL-33 and IL-33 regulated genes in relapsing remitting MS.

Objective: We tested the hypothesis that the expression of IL-33 in MS is dynamic and is likely to reflect the clinical and radiological changes during the course of RRMS.

Methods: MS with either clinical or radiological relapses were recruited for the study and followed for one year. IL-33 and a panel of genes was measured by q PCR and flow cytometry at different time points.

Divergent lncRNA Regulates Transcription in T-Helper 2 Cells.

Long non-coding RNAs (lncRNAs) possess a diverse array of regulatory functions including activation and silencing of gene transcription, regulation of splicing, and coordinating epigenetic modifications. is a divergent lncRNA gene neighboring . GATA3 is considered the master regulator of TH2 lineage commitment enabling TH2 effector cells to efficiently transcribe genes encoding cytokines IL-4, IL-5, and IL-13.

Profiles of Long Noncoding RNAs in Human Naive and Memory T Cells.

We employed whole-genome RNA-sequencing to profile mRNAs and both annotated and novel long noncoding RNAs (lncRNAs) in human naive, central memory, and effector memory CD4 T cells. Loci transcribing both lineage-specific annotated and novel lncRNA are adjacent to lineage-specific protein-coding genes in the genome. Lineage-specific novel lncRNA loci are transcribed from lineage-specific typical- and supertranscriptional enhancers and are not multiexonic, thus are more similar to enhancer RNAs.

Biogenesis and Transcriptional Regulation of Long Noncoding RNAs in the Human Immune System.

The central dogma of molecular biology states that DNA makes RNA makes protein. Discoveries over the last quarter of a century found that the process of DNA transcription into RNA gives rise to a diverse array of functional RNA species, including genes that code for protein and noncoding RNAs. For decades, the focus has been on understanding how protein-coding genes are regulated to influence protein expression.

Long noncoding RNAs in T lymphocytes.

Long noncoding RNAs are recently discovered regulatory RNA molecules that do not code for proteins but influence a vast array of biologic processes. In vertebrates, the number of long noncoding RNA genes is thought to greatly exceed the number of protein-coding genes. It is also thought that long noncoding RNAs drive the biologic complexity observed in vertebrates compared with that in invertebrates.

Long non-coding RNAs in innate and adaptive immunity.

Long noncoding RNAs (lncRNAs) represent a newly discovered class of regulatory molecules that impact a variety of biological processes in cells and organ systems. In humans, it is estimated that there may be more than twice as many lncRNA genes than protein-coding genes. However, only a handful of lncRNAs have been analyzed in detail.

Cutting Edge: Chronic NF-κB Activation in CD4+ T Cells in Rheumatoid Arthritis Is Genetically Determined by HLA Risk Alleles.

Of identified genetic variants, HLA polymorphisms confer the greatest risk for developing autoimmune diseases, including rheumatoid arthritis (HLA-DRB1*04). There are strong influences of HLA polymorphisms on cell type-specific gene expression in B cells and monocytes. Their influence on gene expression in CD4(+) T cells is not known.

Expression and functions of long noncoding RNAs during human T helper cell differentiation.

Long noncoding RNAs (lncRNAs) regulate an array of biological processes in cells and organ systems. Less is known about their expression and function in lymphocyte lineages. Here we have identified >2000 lncRNAs expressed in human T-cell cultures and those that display a TH lineage-specific pattern of expression and are intragenic or adjacent to TH lineage-specific genes encoding proteins with immunologic functions.

Defective structural RNA processing in relapsing-remitting multiple sclerosis.

Background: Surveillance of integrity of the basic elements of the cell including DNA, RNA, and proteins is a critical element of cellular physiology. Mechanisms of surveillance of DNA and protein integrity are well understood. Surveillance of structural RNAs making up the vast majority of RNA in a cell is less well understood.

Expression of IL-33 and its epigenetic regulation in Multiple Sclerosis.

We examined the expression of IL-33 as an indicator of an innate immune response in relapsing remitting MS (RRMS) and controls. Based on our previous studies we proposed a link between the expression of IL-33 and IL-33 regulated genes to histone deacetylase (HDAC) activity and in particular HDAC3, an enzyme that plays a role in the epigenetic regulation of a number of genes including those which regulate inflammation. Our studies showed that intracellular expressions of IL-33 and IL-33 regulated genes are increased in patients with RRMS.

Methotrexate-mediated inhibition of nuclear factor κB activation by distinct pathways in T cells and fibroblast-like synoviocytes.

Objectives: Nuclear factor κB (NF-κB) is a critical activator of inflammatory processes and MTX is one of the most commonly prescribed DMARDs for treatment of RA. We sought to determine whether MTX inhibited NF-κB activity in RA and in lymphocytes and fibroblast-like synoviocytes (FLSs) and to define underlying mechanisms of action.

Methods: An NF-κB luciferase reporter plasmid was used to measure NF-κB activation across experimental stimuli.

Methotrexate inhibits NF-κB activity via long intergenic (noncoding) RNA-p21 induction.

Objective: To determine interrelationships between the expression of long intergenic (noncoding) RNA-p21 (lincRNA-p21), NF-κB activity, and responses to methotrexate (MTX) in rheumatoid arthritis (RA) by analyzing patient blood samples and cell culture models.

Methods: Expression levels of long noncoding RNA and messenger RNA (mRNA) were determined by quantitative reverse transcription-polymerase chain reaction. Western blotting and flow cytometry were used to quantify levels of intracellular proteins.

Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937.

Introduction: Methotrexate (MTX) has been for decades a standard treatment in a wide range of conditions, from malignancies to rheumatoid arthritis (RA). Despite this long experience, the mechanisms of action of MTX remain incompletely understood. Reported immunologic effects of MTX include induction of increased production of some cytokines, an effect that seems to be at odds with the generally anti-inflammatory effects of this drug in diseases like RA.

Methotrexate increases expression of cell cycle checkpoint genes via JNK activation.

Objective: To assess defects in expression of critical cell cycle checkpoint genes and proteins in patients with rheumatoid arthritis (RA) relative to presence or absence of methotrexate (MTX) treatment, and to investigate the role of JNK in induction of these genes by MTX.

Methods: Flow cytometric analysis was used to quantify changes in levels of intracellular proteins, measure reactive oxygen species (ROS), and determine apoptosis in different lymphoid populations. Quantitative reverse transcription-polymerase chain reaction was used to identify changes in cell cycle checkpoint target genes.

Increased sensitivity to apoptosis induced by methotrexate is mediated by JNK.

Objective: Low-dose methotrexate (MTX) is an effective therapy for rheumatoid arthritis (RA), yet its mechanism of action is incompletely understood. The aim of this study was to explore the induction of apoptosis by MTX.

Methods: Flow cytometry was performed to assess changes in the levels of intracellular proteins, reactive oxygen species (ROS), and apoptosis.