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Inhibition of neutrophil elastase by the bacterial serine protease inhibitor ecotin in cystic fibrosis airway samples

2024· article· en· W4404173554 on OpenAlexaff
Yeongseo Son, Kayla Fantone, Harold Nothaft, Arlene A. Stecenko, Christine M. Szymanski, Balázs Rada

Bibliographic record

VenueThe Journal of Immunology · 2024
Typearticle
Languageen
FieldMedicine
TopicCystic Fibrosis Research Advances
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsCystic fibrosisNeutrophil elastaseElastaseSerine proteaseAirwayMedicineProteasesProtease inhibitor (pharmacology)ImmunologyMicrobiologyProteaseBiologyInternal medicineEnzymeBiochemistryInflammationVirusSurgery

Abstract

fetched live from OpenAlex

Abstract Cystic fibrosis (CF), a prevalent fatal genetic condition in North America, disrupts respiratory function by impeding chloride ion transport across mucosal surfaces. This leads to the thickening of mucus, resulting in constant lung inflammation and elevated levels of neutrophils. Neutrophil elastase (NE), a potent serine protease crucial for host defense, is released by these neutrophils. However, in excess, NE can cause detrimental host tissue damage. Abundant in CF airways, NE is a key predictor of lung disease progression. While past studies have explored targeting NE in CF, no optimal inhibitors have reached clinics. Our study tested ecotin, a bacterial periplasmic serine protease inhibitor, for its potential to impede NE activity in CF airway samples and curb NE release from human neutrophils. Results show that ecotin significantly reduces NE activity in sputum samples obtained from several CF patients. Additionally, we found that ecotin inhibits NE release from neutrophils exposed to CF lung stimuli like Staphylococcus aureus bacteria. These results establish ecotin as a promising NE inhibitor in CF with clinical potential.

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)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.011
GPT teacher head0.270
Teacher spread0.259 · 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 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

Citations1
Published2024
Admission routes1
Has abstractyes

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