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Abstract 16993: An Antisense Inhibitor of Apolipoprotein C-III Significantly Decreases Nonesterified Fatty Acid Levels in Severe Hypertriglyceridemic Patients

2014· article· en· W1608752774 on OpenAlexaff
Veronica Alexander, Diane Brisson, JoAnn Flaim, Steve Hughes, W. S. Singleton, Richard S. Geary, Daniel Gaudet

Bibliographic record

VenueCirculation · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Lipids, and Metabolism
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsNEFAHypertriglyceridemiaFibrateInternal medicineMedicineEndocrinologyApolipoprotein BTriglycerideInsulin resistanceInsulinHyperlipidemiaFatty acidDiabetes mellitusCholesterolChemistryBiochemistry

Abstract

fetched live from OpenAlex

Background: Apolipoprotein C-III (apoC-III), a CV risk factor, plays a pivotal role in regulating plasma triglyceride (TG) levels. Elevated TG and its nonesterified fatty acid (NEFA) derivatives are associated with insulin resistance and type 2 diabetes. ISIS-APOCIII Rx selectively inhibits apoC-III protein synthesis in the liver and studies show it may improve insulin sensitivity in patients with type 2 diabetes. Treatment with ISIS-APOCIII Rx results in significant dose-dependent decreases in apoC-III and TG levels (Table) in patients with severe hypertriglyceridemia (SHTG) as monotherapy or add on to a stable dose of fibrate. The present study assessed the potential resulting change in NEFA levels in these patients. Methods: Adult patients with SHTG treated or untreated with fibrate were enrolled in a double-blind Phase 2 study to receive ISIS-APOCIII Rx (up to 300 mg) or placebo as weekly SC injections for 13 weeks. Baseline and end-of-treatment fasting serum samples were analyzed for NEFA levels. Results: Results show significant reductions in NEFA levels in line with reductions in TG levels at the 300 mg/week dose (the Phase 3 dose) of ISIS-APOCIII Rx (Table). ISIS-APOCIII Rx was generally safe and well tolerated. There were no clinically meaningful changes in liver tests or other laboratory values. Conclusions: Treatment with ISIS-APOCIII Rx reduces NEFA levels together with decreases in TG in patients with treated or untreated SHTG suggesting the potential for improvement in peripheral insulin sensitivity in these patients.

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: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
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)0.0030.001

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 head0.017
GPT teacher head0.245
Teacher spread0.229 · 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 designNon-randomized trial
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
Published2014
Admission routes1
Has abstractyes

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