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Record W3208167843 · doi:10.1016/j.ebiom.2021.103660

Perspectives on the translation of in-vitro studies to precision medicine in Cystic Fibrosis

2021· review· en· W3208167843 on OpenAlexafffund
Marie‐Pier Dumas, Sunny Xia, Christine E. Bear, Félix Ratjen

Bibliographic record

VenueEBioMedicine · 2021
Typereview
Languageen
FieldMedicine
TopicCystic Fibrosis Research Advances
Canadian institutionsUniversity of TorontoHospital for Sick Children
FundersCanadian Institutes of Health ResearchCystic Fibrosis CanadaGenome Canada
KeywordsCystic fibrosisMedicineClinical trialIn vivoPrecision medicinePopulationTranslational medicineBioinformaticsDiseaseIn vitroPersonalized medicineTranslation (biology)Translational researchIn vitro toxicologyComputational biologyPathologyInternal medicineBiologyBiotechnologyGenetics

Abstract

fetched live from OpenAlex

Recent strides towards precision medicine in Cystic Fibrosis (CF) have been made possible by patient-derived in-vitro assays with the potential to predict clinical response to small molecule-based therapies. Here, we discuss the status of primary and stem-cell derived tissues used to evaluate the preclinical efficacy of CFTR modulators highlighting both their potential and limitations. Validation of these assays requires correlation of in-vitro responses to in-vivo measures of clinical biomarkers of disease outcomes. While initial efforts have shown some success, this translation requires methodologies that are sensitive enough to capture treatment responses in a CF population that now predominantly has mild lung disease. Future development of in-vitro and in-vivo biomarkers will facilitate the generation of new therapeutics particularly for those patients with rare mutations where clinical trials are not feasible so that in the future every CF patient will have access to effective targeted therapies.

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)0.002
metaresearch head score (Gemma)0.009
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.975
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.009
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0040.000
Bibliometrics0.0020.003
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.100
GPT teacher head0.448
Teacher spread0.348 · 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.

Study designOther design
Domainnot available
GenreReview

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

Citations21
Published2021
Admission routes2
Has abstractyes

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