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Azagury, D.

Publications and source records attributed to Azagury, D..

2 recordsLinked to original sources

Extending the Boundaries of Cancer Therapeutic Complexity with Literature Data Mining

Drug combination therapy is a main pillar of cancer therapy but the formation of an effective combinatorial standard of care (SOC) can take many years and its length of development is increasing with complexity of treatment. In this paper, we develop a path to extend the boundaries of complexity in combinatorial cancer treatments using text data mining (TDM). We first use TDM to characterize the current boundaries of cancer treatment complexity and find that the current complexity limit for clinical trials is 6 drugs per plan and for pre-clinical research is 10. We then present a TDM based assistive technology, cancer plan builder (CPB), which we make publicly available and allows experts to create literature-anchored high complexity combination treatment (HCCT) plans of significantly larger size. We develop metrics to evaluate HCCT plans and show that experts using CPB are able to create HCCT plans at much greater speed and quality, compared to experts without CPB. We hope that by releasing CPB we enable more researchers to engage with HCCT planning and demonstrate its clinical efficacy.

bioinformatics↗

SARS-CoV-2 infects human adipose tissue and elicits an inflammatory response consistent with severe COVID-19

The COVID-19 pandemic, caused by the viral pathogen SARS-CoV-2, has taken the lives of millions of individuals around the world. Obesity is associated with adverse COVID-19 outcomes, but the underlying mechanism is unknown. In this report, we demonstrate that human adipose tissue from multiple depots is permissive to SARS-CoV-2 infection and that infection elicits an inflammatory response, including the secretion of known inflammatory mediators of severe COVID-19. We identify two cellular targets of SARS-CoV-2 infection in adipose tissue: mature adipocytes and adipose tissue macrophages. Adipose tissue macrophage infection is largely restricted to a highly inflammatory subpopulation of macrophages, present at baseline, that is further activated in response to SARS-CoV-2 infection. Preadipocytes, while not infected, adopt a proinflammatory phenotype. We further demonstrate that SARS-CoV-2 RNA is detectable in adipocytes in COVID-19 autopsy cases and is associated with an inflammatory infiltrate. Collectively, our findings indicate that adipose tissue supports SARS-CoV-2 infection and pathogenic inflammation and may explain the link between obesity and severe COVID-19. One sentence summaryOur work provides the first in vivo evidence of SARS-CoV-2 infection in human adipose tissue and describes the associated inflammation.

immunology↗