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O papel da sinalização do eixo C5a/C5aR1 na fisiopatologia COVID-19

2022· dissertation· pt· W4319593600 on OpenAlexaff
Bruna Manuella Souza Silva

Bibliographic record

Venuenot available
Typedissertation
Languagept
FieldImmunology and Microbiology
TopicComplement system in diseases
Canadian institutionsInflamax Research (Canada)
Fundersnot available
KeywordsARDSPathophysiologyImmunologyInflammationPneumoniaC5a receptorMedicineContext (archaeology)Cytokine stormLungImmune systemProinflammatory cytokineComplement systemBiologyCoronavirus disease 2019 (COVID-19)PathologyInternal medicine

Abstract

fetched live from OpenAlex

Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that can progress to cytokine storm, organ dysfunction, consequently death.Considering that complement system factor 5a (C5a), through its cellular receptor C5aR1, exhibits potent pro-inflammatory actions, and plays immune and pathological roles in inflammatory diseases, we investigated whether the C5a/C5aR1 pathway might be involved in the pathophysiology of COVID-19.C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of severely ill patients with COVID-19 compared to patients with influenza pneumonia, supporting this previous data the lung of K18-hACE2 mice (Tg mice, susceptible to infection) infected with SARS-COV-2 showed increased C5a.Genetic and pharmacological inhibition of C5aR1 signaling improved lung immunopathology in infected mice.Mechanistically, C5aR1 signaling in the context of infection was found to drive the release of extracellular neutrophil trapping (NETs).These data confirm the pathophysiological role of the C5a/C5aR1 axis in amplifying inflammation in COVID-19 and propose as a therapeutic alternative to antagonize C5aR1.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.045
GPT teacher head0.351
Teacher spread0.306 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2022
Admission routes1
Has abstractyes

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