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Record W4409902418 · doi:10.1016/j.healun.2025.03.010

Persistent and progressive acute lung allograft dysfunction is linked to cell compositional and transcriptional changes in small airways

2025· article· en· W4409902418 on OpenAlexaff
Elsa Brunet‐Ratnasingham, Ruyin Guo, R. Mohanty, Allen Duong, Nicholas A. Kolaitis, Steven R. Hays, Rupal Shah, Aida Venado, J. Maheshwari, Mary Ellen Kleinhenz, Lorriana E. Leard, John F. McDyer, Tereza Martinu, Alexis J. Combes, Daniel R. Calabrese, Jonathan Singer, John R. Greenland

Bibliographic record

VenueThe Journal of Heart and Lung Transplantation · 2025
Typearticle
Languageen
FieldMedicine
TopicTransplantation: Methods and Outcomes
Canadian institutionsUniversity Health Network
FundersResearch and DevelopmentNational Heart, Lung, and Blood InstituteUniversity of California, San FranciscoCystic Fibrosis FoundationCook Family FoundationNational Institutes of HealthOffice of Research and DevelopmentU.S. Department of Veterans Affairs
KeywordsLungMedicineCellImmunologyPathologyCardiologyInternal medicineBiologyGenetics

Abstract

fetched live from OpenAlex

BACKGROUND: ) decline concerning for chronic lung allograft dysfunction (CLAD) onset. Novel diagnostic tools are needed to identify those with ALAD who will progress to CLAD and to target appropriate therapies. We hypothesized that progressive ALAD would be associated with changes in small airway cell composition and cell-specific transcription. METHODS: decline. Cell compositional changes, pseudobulk Reactome pathways, and the AI2 score, previously linked to CLAD in airway brush transcriptomes, were assessed as a function of ALAD outcome group. RESULTS: Across 68,140 cells, the distribution of cell composition was linked to ALAD outcome group (PERMANOVA, p = 0.004). Worse ALAD outcomes correlated with loss of basal cells, changes in club and ciliated subsets, a loss of macrophages, and expansion of cytotoxic T cells. The AI2 gene score was positively associated with ALAD outcome group, particularly in epithelial cell subsets (p < 0.001). Pathway analysis showed increased interferon signaling and inhibition of cell proliferation in epithelial cells. CONCLUSIONS: In this pilot study, persistent and progressive ALAD was associated with changes in bronchiolar cell composition and transcriptional programs. Molecular phenotyping may help identify and characterize individuals with ALAD at increased risk for progression.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

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)0.0020.000

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 head0.015
GPT teacher head0.293
Teacher spread0.278 · 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

Citations9
Published2025
Admission routes1
Has abstractyes

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