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Record W2224037267 · doi:10.3389/fphar.2015.00303

Hepatoprotective and Anti-fibrotic Agents: It's Time to Take the Next Step

2016· review· en· W2224037267 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueFrontiers in Pharmacology · 2016
Typereview
Languageen
FieldMedicine
TopicLiver physiology and pathology
Canadian institutionsnot available
FundersRWTH Aachen UniversityDeutsche ForschungsgemeinschaftGovernment of Canada
KeywordsCirrhosisMedicineDiseaseEuropean unionPharmacologyAnimal testingMode of actionAnimal modelMember statesDrugBioinformaticsPathologyToxicologyInternal medicineBiologyBusiness

Abstract

fetched live from OpenAlex

Hepatic fibrosis and cirrhosis cause strong human suffering and necessitate a monetary burden worldwide. Therefore, there is an urgent need for the development of therapies. Pre-clinical animal models are indispensable in the drug discovery and development of new anti-fibrotic compounds and are immensely valuable for understanding and proofing the mode of their proposed action. In fibrosis research, inbreed mice and rats are by far the most used species for testing drug efficacy. During the last decades, several hundred or even a thousand different drugs that reproducibly evolve beneficial effects on liver health in respective disease models were identified. However, there are only a few compounds (e.g., GR-MD-02, GM-CT-01) that were translated from bench to bedside. In contrast, the large number of drugs successfully tested in animal studies is repeatedly tested over and over engender findings with similar or identical outcome. This circumstance undermines the 3R (Replacement, Refinement, Reduction) principle of Russell and Burch that was introduced to minimize the suffering of laboratory animals. This ethical framework, however, represents the basis of the new animal welfare regulations in the member states of the European Union. Consequently, the legal authorities in the different countries are halted to foreclose testing of drugs in animals that were successfully tested before. This review provides a synopsis on anti-fibrotic compounds that were tested in classical rodent models. Their mode of action, potential sources and the observed beneficial effects on liver health are discussed. This review attempts to provide a reference compilation for all those involved in the testing of drugs or in the design of new clinical trials targeting hepatic fibrosis.

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.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.651
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.001

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 head0.048
GPT teacher head0.352
Teacher spread0.304 · 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