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Record W2021369167 · doi:10.1007/s12079-012-0160-8

Egr-ly awaiting a “personalized medicine” approach to treat scleroderma

2012· article· en· W2021369167 on OpenAlexaff
Andrew Leask

Bibliographic record

VenueJournal of Cell Communication and Signaling · 2012
Typearticle
Languageen
FieldMedicine
TopicSystemic Sclerosis and Related Diseases
Canadian institutionsWestern University
Fundersnot available
KeywordsScleroderma (fungus)MedicineLocalized SclerodermaFibrosisDiseasePrecision medicineInflammationPersonalized medicineImmunologyCancer researchBioinformaticsPathologyBiology

Abstract

fetched live from OpenAlex

Scleroderma, an autoimmune disorder characterized by skin and organ fibrosis, has no treatment. Although over the past decade valuable insights into the molecular mechanisms underlying scleroderma have been generated, results in clinical trials have been disappointing. This issue is likely to arise due to the heterogeneity of scleroderma. Molecular insights into the heterogeneity of this disease have been provided by genome-wide expression profiling. In a recent paper, Bhattacharyya and colleagues (PLOS One 6:e23082, 2011b) to show that the overexpression of a range of "fibroproliferative" genes in diffuse cutaneous scleroderma patients are likely to be caused by the overexpression of transcription factor Early growth response (Egr)-1. Only a minority of Egr-1-regulated genes were also found to be regulated by TGF-ß. Moreover, Greenblatt and colleagues (Am J Pathol., 2012) have shown that the overexpression of "inflammatory" genes overexpressed in "localized" scleroderma and a small subset of limited and diffuse scleroderma patients is likely to be due to the activity of interleukin-13 (IL-13). Intriguingly, at a gene expression level, murine sclerodermatous graft-versus-host disease (sclGVHD) approximates this inflammatory subset of scleroderma. These data suggest that targeting Egr-1 expression/activity might be a novel therapeutic strategy to control fibrosis in a subset of diffuse scleroderma patients, and further emphasize that notion that elevated canonical TGFβ signaling is insufficient to explain the fibrosis observed in scleroderma. Moreover, targeting IL-13 expression/activity might be a novel therapeutic strategy to target the inflammation leading to "localized" scleroderma.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.610
Threshold uncertainty score0.326

Codex and Gemma teacher scores by category

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

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 head0.055
GPT teacher head0.290
Teacher spread0.235 · 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

Citations2
Published2012
Admission routes1
Has abstractyes

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