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Record W7133044944

Targeting Acid Ceramidase to Attenuate Kidney Fibrosis

2022· dissertation· W7133044944 on OpenAlexaff
Seung Hyun Ki

Bibliographic record

VenueTSpace · 2022
Typedissertation
Language
FieldBiochemistry, Genetics and Molecular Biology
TopicHippo pathway signaling and YAP/TAZ
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsKidneyPathogenesisFibrosisKidney diseaseSphingolipid
DOInot available

Abstract

fetched live from OpenAlex

Chronic kidney disease (CKD) affects nearly 1 in 10 Canadians, a condition that in its end-stage has a worse prognosis than most cancers, and results in an annual healthcare cost of $40 billion. Despite fibrosis driving the progression of most forms of CKD, its pathogenesis remains poorly understood. Emerging evidence suggests the important role of acid ceramidase in regulating fibrosis across several organs, including the lung and liver. However, the role of acid ceramidase in the pathogenesis of kidney fibrosis remains largely unknown. Here we demonstrate that acid ceramidase mRNA is increased in fibrotic kidneys, and that inhibition of acid ceramidase with Carmofur reduces renal fibrosis. Furthermore, we provide evidence that acid ceramidase inhibition with Carmofur inhibits the activity of YAP and TAZ, two key pro-fibrotic transcription co-factors. Taken together, these data suggest that acid ceramidase inhibition might be a novel strategy to reduce kidney 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.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

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)0.0020.000

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 head0.011
GPT teacher head0.306
Teacher spread0.295 · 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 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

Citations0
Published2022
Admission routes1
Has abstractyes

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