The precision medicine process for treating rare disease using the artificial intelligence tool mediKanren.

There are over 6,000 different rare diseases estimated to impact 300 million people worldwide. As genetic testing becomes more common practice in the clinical setting, the number of rare disease diagnoses will continue to increase, resulting in the need for novel treatment options. Identifying treatments for these disorders is challenging due to a limited understanding of disease mechanisms, small cohort sizes, interindividual symptom variability, and little commercial incentive to develop new treatments.

Correlates of survival after autoantibody reduction therapy for acute IPF exacerbations.

Background: No medical treatment has proven efficacy for acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF), and this syndrome has a very high mortality. Based on data indicating humoral autoimmune processes are involved in IPF pathogenesis, we treated AE-IPF patients with an autoantibody reduction regimen of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin. This study aimed to identify clinical and autoantibody determinants associated with survival after autoantibody reduction in AE-IPF.

HLA-C and KIR permutations influence chronic obstructive pulmonary disease risk.

A role for hereditary influences in the susceptibility for chronic obstructive pulmonary disease (COPD) is widely recognized. Cytotoxic lymphocytes are implicated in COPD pathogenesis, and functions of these leukocytes are modulated by interactions between their killer cell Ig-like receptors (KIR) and human leukocyte antigen-Class I (HLA-Class I) molecules on target cells. We hypothesized HLA-Class I and KIR inheritance affect risks for COPD.

Development of An Individualized Risk Prediction Model for COVID-19 Using Electronic Health Record Data.

Developing an accurate and interpretable model to predict an individual's risk for Coronavirus Disease 2019 (COVID-19) is a critical step to efficiently triage testing and other scarce preventative resources. To aid in this effort, we have developed an interpretable risk calculator that utilized de-identified electronic health records (EHR) from the University of Alabama at Birmingham Informatics for Integrating Biology and the Bedside (UAB-i2b2) COVID-19 repository under the U-BRITE framework. The generated risk scores are analogous to commonly used credit scores where higher scores indicate higher risks for COVID-19 infection.

CD70 Activation Decreases Pulmonary Fibroblast Production of Extracellular Matrix Proteins.

Idiopathic pulmonary fibrosis (IPF) is a lethal, medically refractory syndrome characterized by intrapulmonary accumulations of extracellular matrix (ECM) proteins produced by fibroblasts. Activation, clonal expansion, and differentiation of lymphocytes are also frequently present in IPF. Activated T cells are known to exert several effects that promote ECM production, but opposing homeostatic actions, wherein T cells can inhibit fibrosis, are less well understood.

Glucose-Regulated Protein 78 Autoantibodies Are Associated with Carotid Atherosclerosis in Chronic Obstructive Pulmonary Disease Patients.

Atherosclerosis prevalence is increased in chronic obstructive pulmonary disease (COPD) patients, independent of other risk factors. The etiology of the excess vascular disease in COPD is unknown, although it is presumably related to an underlying (if cryptic) systemic immune response. Autoantibodies with specificity for glucose-regulated protein 78 (GRP78), a multifunctional component of the unfolded protein response, are common in COPD patients and linked to comorbidities of this lung disease.

Decrements of body mass index are associated with poor outcomes of idiopathic pulmonary fibrosis patients.

Background: The processes that result in progression of idiopathic pulmonary fibrosis (IPF) remain enigmatic. Moreover, the course of this disease can be highly variable and difficult to accurately predict. We hypothesized analyses of body mass index (BMI), a simple, routine clinical measure, may also have prognostic value in these patients, and might provide mechanistic insights.

Barx2 and Pax7 have antagonistic functions in regulation of wnt signaling and satellite cell differentiation.

The canonical Wnt signaling pathway is critical for myogenesis and can induce muscle progenitors to switch from proliferation to differentiation; how Wnt signals integrate with muscle-specific regulatory factors in this process is poorly understood. We previously demonstrated that the Barx2 homeobox protein promotes differentiation in cooperation with the muscle regulatory factor (MRF) MyoD. Pax7, another important muscle homeobox factor, represses differentiation.