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Record W4206129249 · doi:10.1101/2022.01.17.22269397

EXTRACELLULAR MATRIX REMODELING IN ATOPIC DERMATITIS HARNESSES THE ONSET OF AN ASTHMATIC PHENOTYPE AND IS A POTENTIAL CONTRIBUTOR TO THE ATOPIC MARCH

2022· preprint· en· W4206129249 on OpenAlexafffund
Patrick Graff, Jenny Wilzopolski, Anne Voß, Travis M. Blimkie, January Weiner, Olivia Kershaw, Preety Panwar, Tillie‐Louise Hackett, Dieter Brömme, Lucie Loyal, Andreas Thiel, Dieter Beule, Robert E. W. Hancock, Achim D. Gruber, Wolfgang Bäumer, Sarah Hedtrich

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldMedicine
TopicDermatology and Skin Diseases
Canadian institutionsSt. Paul's HospitalUniversity of British Columbia
FundersCanadian Institutes of Health ResearchKillam TrustsStudienstiftung des Deutschen VolkesDeutsche ForschungsgemeinschaftBC Children's Hospital
KeywordsAtopic dermatitisImmunologyExtracellular matrixCrosstalkAsthmaFibronectinPhenotypeMedicineBiologyCell biologyGeneticsGene

Abstract

fetched live from OpenAlex

Abstract The development of atopic dermatitis (AD) in infancy, and subsequent allergic rhinitis, food allergies, and asthma in later childhood, is known as the atopic march. The mechanism is largely unknown, yet the course of disease indicates the contribution of inter-epithelial crosstalk, through to the onset of inflammation in the skin and progression to another mucosal epithelium. Here, we investigated if and how skin-lung epithelial crosstalk could contribute to the development of the atopic march. First, we emulated this inter-epithelial crosstalk through indirect co-culture of bioengineered atopic-like skin disease models and three-dimensional bronchial epithelial models triggering an asthma-like phenotype in the latter. A subsequent secretome analysis identified throm-bospondin-1, CD44, complement factor C3, fibronectin, and syndecan-4 as potentially relevant skin-derived mediators. As these mediators are extracellular matrix (ECM)-related proteins, we then studied the involvement of the ECM, unveiling distinct proteomic, transcriptomic, and ultrastructural differences in atopic samples. The latter indicated ECM remodeling triggering the release of the above-mentioned mediators. In addition to pro-inflammatory effects in lung tissue, the ECM mediators also exert distinct effects on CD4 + T cells. In vivo mouse data showed that exposure to these mediators over seven days dysregulated activated circadian clock genes which have been previously discussed in the context of atopic diseases and asthma development. We hypothesize the existence of a skin-lung axis that could contribute to the atopic march driven by skin ECM remodeling. One Sentence Summary Atopic skin harbors the progression of atopic diseases to lung tissue through a skin-lung axis that contributes to the atopic march via extracellular matrix 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 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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

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 integrity0.0000.001
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 head0.016
GPT teacher head0.291
Teacher spread0.275 · 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

Citations2
Published2022
Admission routes2
Has abstractyes

Explore more

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