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Record W4200268628 · doi:10.12688/gatesopenres.13472.1

Investigating neutrophil cell death in TB pathogenesis

2021· preprint· en· W4200268628 on OpenAlexaff
Kimone L Fisher, Kerishka Rajkumar-Bhugeloo, Denelle Moodley, Thabo Mpotje, Duran Ramsuran, Thumbi Ndung’u, Mohlopheni J. Marakalala

Bibliographic record

VenueGates Open Research · 2021
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicNeutrophil, Myeloperoxidase and Oxidative Mechanisms
Canadian institutionsInstitute of Infection and Immunity
FundersDivision of Research Capacity DevelopmentMedical Research CouncilWellcomeSouth African Medical Research CouncilWellcome TrustBill and Melinda Gates Foundation
KeywordsNeutrophil extracellular trapsPathogenesisImmunologyProgrammed cell deathMycobacterium tuberculosisTuberculosisDiseaseBiologyPathologicalMedicineInflammationPathologyGeneticsApoptosis

Abstract

fetched live from OpenAlex

<ns4:p> <ns4:bold>Background:</ns4:bold> Neutrophils are one of the major early role players in antimycobacterial immunity. Upon infection, neutrophils can undergo NETosis, a cell death characterized by release of neutrophil extracellular traps (NETs). The role of NETosis in TB progression remains poorly characterized. We aim to characterize mechanisms underlying NETosis during TB pathogenesis by identifying genes that drive the cell death, and to determine their potential as markers of disease progression in high-risk individuals. Finally, we intend to evaluate neutrophil associated genes as targets for host directed therapy to reduce pathological damage caused by NETosis. <ns4:bold>Methods:</ns4:bold> Quantitative PCR will be used to quantify expression of specific genes identified in the blood of individuals with active lung disease (n=30), compared to those from healthy (n=30) and latently infected individuals (LTBI) (n=30). In addition, temporal events associated with NETosis will be measured using live microscopy in a neutrophil in vitro model of <ns4:italic>Mycobacterium tuberculosis</ns4:italic> (Mtb) infection. Candidate genes found to be associated with NETosis will be targeted with pharmaceutical inhibitors. <ns4:bold>Conclusion:</ns4:bold> Genes associated with neutrophil mediated cell death may serve as potential biomarkers of pathological damage and disease progression, as well as targets for host-directed therapy. </ns4:p>

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Open science, Research integrity, Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.018
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0030.011
Research integrity0.0010.004
Insufficient payload (model declined to judge)0.0020.001

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 head0.148
GPT teacher head0.374
Teacher spread0.225 · 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; both teacher heads agree on what is shown here.

Study designBench or experimental
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

Citations4
Published2021
Admission routes1
Has abstractyes

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