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Record W2159341638 · doi:10.1126/sageke.2002.36.nw126

NO-aspirin, No Atherosclerosis

2002· article· en· W2159341638 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.

aboutThe title or abstract carries a Canadian signal from the geographic lexicon.
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

VenueScience of Aging Knowledge Environment · 2002
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEicosanoids and Hypertension Pharmacology
Canadian institutionsnot available
Fundersnot available
KeywordsAspirinMedicineAortaPlaceboInflammationPharmacologyInternal medicinePathology

Abstract

fetched live from OpenAlex

Modern twists on old favorites sometimes make them better. According to a new study, a redesigned aspirin molecule that delivers nitric oxide battles atherosclerosis, at least in rodents. The modified molecule keeps fatty plaques from accumulating in blood vessels and choking circulation. The study suggests that the compound, already being tested as a gut-sparing painkiller, might double as an effective plaque-buster. The signaling molecule NO relaxes blood vessels and soothes inflammation. Previous work suggested that NO also protects blood vessels from fatty buildup: Atherosclerosis-prone mice accumulate more plaques when treated with compounds that block NO production. But whether adding NO could prevent atherosclerosis was unclear. To further explore NO's plaque-preventing prowess, Napoli and colleagues used an old standby with a new twist: an aspirin molecule with NO attached. Researchers at NicOx, a biotech company in Sophia Antipolis, France, had designed the compound in hopes of finding a painkiller that doesn't irritate the stomach, as regular aspirin does. Napoli and colleagues wondered whether the NO-aspirin combo might also squelch fat buildup in blood vessels. The team tested NO-aspirin in mutant mice that develop extensive atherosclerosis when fed a high-cholesterol diet. These mice received regular aspirin, NO-aspirin, or a placebo for 12 weeks; the researchers then killed the animals and analyzed their blood and aortas. Fatty deposits covered 40% less of the aorta's lining in mice given NO-aspirin than in either aspirin-dosed animals or the placebo group. In NO-aspirin treated animals, blood vessels also contained fewer macrophages: immune cells that infiltrate blood vessels and gobble cholesterol, launching atherosclerosis (see "Purging Plaques" ). Furthermore, low-density lipoproteins suffered less oxidative damage in NO-aspirin-treated animals than in controls; such marring of these cholesterol-carrying proteins appears to exacerbate atherosclerosis by weakening plaques, increasing the likelihood that they will shatter and block blood vessels. The results suggest that providing the animals with supplementary NO alleviates atherosclerotic damage. "I am very impressed with the magnitude of improvement they saw," says pharmacologist John Wallace of the University of Calgary in Alberta, Canada, a member of NicOx's scientific advisory board. Because the aspirin derivative releases NO slowly, he adds, it might approximate physiological amounts of NO more closely than do other compounds. Molecules that generate high concentrations of NO, such as nitroglycerin, can cause headaches and dangerously low blood pressure. Pharmacologist Colin Funk of the University of Pennsylvania in Philadelphia is more circumspect. "If it really reduces plaque accumulation by 40%, that would be significant," he says. But recent studies have hinted that aspirin alone curtails plaque formation, says Funk, an effect that the new study doesn't replicate. Study co-author and molecular pharmacologist William Sessa of Yale University stands by the data, however, saying that little evidence supports the idea that aspirin by itself foils plaques. Trials to assess NO-aspirin's safety in humans are already under way. Perhaps the new take on the old painkiller will provide a high-performance tool for cleaning our arteries. --R. John Davenport C. Napoli, E. Ackah, F. de Nigris, P. Del Soldato, F. P. D'Armiento, E. Crimi, M. Condorelli, W. C. Sessa, Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes, and atherogenesis in hypercholesterolemic mice. Proc. Natl. Acad. Sci. U.S.A., 3 September 2002 [e-pub ahead of print]. [Abstract] [Full Text]

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 categoriesInsufficient payload (model declined to judge)
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 score0.193
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.019
GPT teacher head0.247
Teacher spread0.228 · 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