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Challenging molecular dogmas in human sepsis using mathematical reasoning

Ghazal, Peter ORCID:, Rodrigues, Patricia R.S. ORCID:, Chakraborty, Mallinath, Oruganti, Siva and Woolley, Thomas E. ORCID: 2022. Challenging molecular dogmas in human sepsis using mathematical reasoning. EBioMedicine 80 , 104031. 10.1016/j.ebiom.2022.104031

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Sepsis is defined as a dysregulated host-response to infection, across all ages and pathogens. What defines a dysregulated state remains intensively researched but incompletely understood. Here, we dissect the meaning of this definition and its importance for the diagnosis and management of sepsis. We deliberate on pathophysiological features and dogmas that range from cytokine storms and immune paralysis to dormancy and altered homeostasis setpoints. Mathematical reasoning, used to test for plausibility, reveals three interlinked cardinal rules governing host-response trajectories in sepsis. Rule one highlights that the amplitude of the immune response while important is not sufficient and is strictly dependent on rule two, specifying bioenergetic capacity and are together dynamically driven by rule three, delineating stability and alterations in setpoints. We consider these rules and associated pathophysiological parameters for guiding data-science and artificial intelligence mining of multi-omics and big-data for improving the precision of diagnostic and therapeutic approaches to sepsis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 2352-3964
Date of First Compliant Deposit: 6 May 2022
Date of Acceptance: 11 April 2022
Last Modified: 16 May 2023 17:17

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