Genetic risk factors for severe and fatigue dominant long COVID and commonalities with ME/CFS identified by combinatorial analysis.

Background: Long COVID is a debilitating chronic condition that has affected over 100 million people globally. It is characterized by a diverse array of symptoms, including fatigue, cognitive dysfunction and respiratory problems. Studies have so far largely failed to identify genetic associations, the mechanisms behind the disease, or any common pathophysiology with other conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that present with similar symptoms.

Genetic risk factors for ME/CFS identified using combinatorial analysis.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the genetic (and other) risk factors associated with the disease would begin to help to alleviate some of these issues for patients.

Methods: We applied both GWAS and the PrecisionLife combinatorial analytics platform to analyze ME/CFS cohorts from UK Biobank, including the Pain Questionnaire cohort, in a case-control design with 1000 cycles of fully random permutation.

Systematic indication extension for drugs using patient stratification insights generated by combinatorial analytics.

Indication extension or repositioning of drugs can, if done well, provide a faster, cheaper, and derisked route to the approval of new therapies, creating new options to address pockets of unmet medical need for patients and offering the potential for significant commercial and clinical benefits. We look at the promises and challenges of different repositioning strategies and the disease insights and scalability that new high-resolution patient stratification methodologies can bring. This is exemplified by a systematic analysis of all development candidates and on-market drugs, which identified 477 indication extension opportunities across 30 chronic disease areas, each supported by patient stratification biomarkers.

Combinatorial Analysis of Phenotypic and Clinical Risk Factors Associated With Hospitalized COVID-19 Patients.

Characterization of the risk factors associated with variability in the clinical outcomes of COVID-19 is important. Our previous study using genomic data identified a potential role of calcium and lipid homeostasis in severe COVID-19. This study aimed to identify similar combinations of features (disease signatures) associated with severe disease in a separate patient population with purely clinical and phenotypic data.

A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization.

The SARS-CoV-2 pandemic has challenged researchers at a global scale. The scientific community's massive response has resulted in a flood of experiments, analyses, hypotheses, and publications, especially in the field of drug repurposing. However, many of the proposed therapeutic compounds obtained from SARS-CoV-2 specific assays are not in agreement and thus demonstrate the need for a singular source of COVID-19 related information from which a rational selection of drug repurposing candidates can be made.

Per- and polyfluoroalkyl substances in Northern California cats: Temporal comparison and a possible link to cat hyperthyroidism.

The indoor environment and dietary intake are considered to be major human exposure pathways to per- and polyfluoroalkyl substances (PFASs). Cats have similar exposures to humans by sharing their residential environments, although they have different diet, body sizes, and indoor activities. In the present study, we report PFAS levels in the serum of 2 groups of Northern California cats (>10 yr old) collected during 2 time periods: 2008 to 2010 (n = 21) and 2012 to 2013 (n = 22).

High polybrominated diphenyl ether levels in California house cats: house dust a primary source?

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants that act as endocrine disruptors, affecting thyroid hormone homeostasis. As a follow-up to a recent study showing high PBDE levels in household cats and linking PBDE levels with cat hyperthyroidism, we measured PBDEs, polychlorinated biphenyls (PCBs), and organochlorinated pesticides (OCPs) in serum samples from 26 California household cats (16 hyperthyroid, 10 controls) using liquid-liquid extraction and high-resolution gas chromatography/high-resolution mass spectrometry. In the present pilot study, we found that PBDE levels in California house cats were extremely high (ΣPBDEs median = 2,904 ng/g lipid; range, 631-22,537 ng/g lipid).

An ESID case study at the federal level.

The D (dissemination) phase of the ESID model has been often overlooked in our efforts to create innovative and widespread social change. The process of replicating successful social innovations is both a prerequisite for dissemination (in order to assess the consistency of effects) and an obvious outcome of a successful dissemination effort. Fidelity, the extent to which a replicated program is implemented in a manner consistent with the original program model, is an important dimension of replication.