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Bacterial peptidoglycan drives synovial inflammation in osteoarthritis

2024· article· en· W4404174541 on OpenAlexaff
Jacob A. Dickman, Meaghan Holub, Joseph R Rouse, Rebecca Danner, Amanda Wahhab, Brandon L. Jutras, Adam I. Edelstein, Robert B. Lochhead

Bibliographic record

VenueThe Journal of Immunology · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicAntimicrobial Peptides and Activities
Canadian institutionsWestern University
Fundersnot available
KeywordsPeptidoglycanOsteoarthritisInflammationMedicineMicrobiologyBacteriaBiologyImmunologyPathologyGenetics

Abstract

fetched live from OpenAlex

Abstract Peptidoglycan (PG) is a potent inflammatory mediator. We have previously demonstrated that PG is present in the synovial tissue of osteoarthritis (OA) patients but its role in OA inflammation remains unknown. We hypothesized that PG in synovial tissue drives inflammation in OA. Intraoperative synovial tissue and synovial fluid samples were obtained from 56 consecutive patients with OA, with no prior history of infection. PG in synovial tissue was detected by immunohistochemical (IHC) staining of serial sections of 10 mm2 of tissue with anti-PG antiserum. PG was found in 33/56 (59%) of the tissue samples using IHC, with a median of eight PG occurrences per 10 mm2 in PG-positive samples. Tissue inflammation and fibrosis were assessed by histopathology. Cellular localization was further characterized in three PG-positive tissue samples by immunofluorescent microscopy (IFM). PG was localized to cells demonstrating mononuclear and fibroblastic morphology primarily in and around areas of vascularization and inflammation. CD68+ macrophages and to a lesser degree CD90+ synovial sublining fibroblasts. In multiplex assay analysis of synovial fluid cytokine levels, IL-6 and PG abundance were positively correlated. Fibroblasts and macrophages stimulated with PG in vitro secreted high levels of innate cytokines, paricularly IL-6 when measured by supernatant cytokine quantification. Together these data support the hypothesis that PG in synovial tissue drives joint inflammation in OA.

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)0.001
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 score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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 head0.007
GPT teacher head0.214
Teacher spread0.208 · 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

Citations0
Published2024
Admission routes1
Has abstractyes

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