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Record W2131010086 · doi:10.1161/circ.104.19.2263

Tolerance to the Organic Nitrates

2001· editorial· en· W2131010086 on OpenAlexaff
John D. Parker, Tommaso Gori

Bibliographic record

VenueCirculation · 2001
Typeeditorial
Languageen
FieldMedicine
TopicNitric Oxide and Endothelin Effects
Canadian institutionsMount Sinai Hospital
Fundersnot available
KeywordsMedicineSoluble guanylyl cyclaseNitric oxideSecond messenger systemGuanylate cyclaseReceptorInternal medicinePharmacology

Abstract

fetched live from OpenAlex

itroglycerin (NTG) and other organic nitrates continue to be important drugs that are often used in cardiovascular medicine.All organic nitrates undergo denitrification, releasing nitric oxide (NO) through a biotransformation process that remains poorly understood to date.NO activates the enzyme soluble guanylyl cyclase in smooth muscle cells, causing increased levels of the second messenger cGMP.Finally, cGMP activates a cGMPdependent protein kinase.This enzyme mediates vasorelaxation through inhibitory phosphorylation of different proteins involved in the regulation of intracellular Ca 2ϩ levels. See p 2338All of the organic nitrates have potent short-term vascular, hemodynamic, and clinical effects.A critical limitation in their clinical application is the development of tolerance, whereby their initial effects are rapidly lost during sustained administration.Although there seems to be little doubt that NO, or some NO adjunct, mediates the pharmacodynamic effect of nitrates, the mechanism(s) underlying the development of tolerance remain an important and vexing problem for cardiovascular pharmacology.

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)0.001
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Editorial · Consensus signal: Editorial
Teacher disagreement score0.007
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.004
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0070.008
Insufficient payload (model declined to judge)0.0020.001

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 head0.010
GPT teacher head0.267
Teacher spread0.257 · 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 designNot applicable
Domainnot available
GenreEditorial

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
Published2001
Admission routes1
Has abstractyes

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