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Record W3061354765 · doi:10.1126/science.aay5356

Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy

2020· article· en· W3061354765 on OpenAlexafffund
François Binet, Gaël Cagnone, Sergio Crespo‐Garcia, Masayuki Hata, Mathieu Neault, Agnieszka Dejda, Ariel M. Wilson, Manuel Buscarlet, Gaëlle Mawambo, Joel P. Howard, Roberto Diaz-Marin, Célia Parinot, Vera Guber, Frédérique Pilon, Rachel Juneau, Rémi Laflamme, Christina Sawchyn, Karine Boulay, Séverine Leclerc, Afnan Abu-Thuraia, Jean‐François Côté, Grégor Andelfinger, Flávio Rezende, Florian Sennlaub, Jean‐Sébastien Joyal, Frédérick A. Mallette, Przemysław Sapieha

Bibliographic record

VenueScience · 2020
Typearticle
Languageen
FieldImmunology and Microbiology
TopicNeutrophil, Myeloperoxidase and Oxidative Mechanisms
Canadian institutionsMcGill UniversityCentre Hospitalier Universitaire Sainte-JustineMontreal Clinical Research InstituteUniversité de MontréalHôpital Maisonneuve-Rosemont
FundersFonds de Recherche du Québec - SantéNatural Sciences and Engineering Research Council of CanadaAgence Nationale de la RechercheCanadian Diabetes AssociationCanadian Institutes of Health ResearchMitacsHeart and Stroke Foundation of CanadaBurroughs Wellcome Fund
KeywordsDiabetic retinopathyClearanceNeutrophil extracellular trapsRetinopathyBlindnessInflammationRetinalExtracellularMedicinePathologicalPathologyBiologyCell biologyImmunologyDiabetes mellitusOphthalmologyEndocrinology

Abstract

fetched live from OpenAlex

In developed countries, the leading causes of blindness such as diabetic retinopathy are characterized by disorganized vasculature that can become fibrotic. Although many such pathological vessels often naturally regress and spare sight-threatening complications, the underlying mechanisms remain unknown. Here, we used orthogonal approaches in human patients with proliferative diabetic retinopathy and a mouse model of ischemic retinopathies to identify an unconventional role for neutrophils in vascular remodeling during late-stage sterile inflammation. Senescent vasculature released a secretome that attracted neutrophils and triggered the production of neutrophil extracellular traps (NETs). NETs ultimately cleared diseased endothelial cells and remodeled unhealthy vessels. Genetic or pharmacological inhibition of NETosis prevented the regression of senescent vessels and prolonged disease. Thus, clearance of senescent retinal blood vessels leads to reparative vascular remodeling.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
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 score0.052
Threshold uncertainty score0.664

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.025
GPT teacher head0.253
Teacher spread0.228 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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

Citations288
Published2020
Admission routes2
Has abstractyes

Explore more

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