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Record W4307778508 · doi:10.1038/s41467-022-33776-x

Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium

2022· article· en· W4307778508 on OpenAlexaff
Ivan Cokic, Shing Fai Chan, Xingmin Guan, Anand R. Nair, Hsin‐Jung Yang, Ting Liu, Yinyin Chen, Diego Hernando, Jane Sykes, Richard Tang, John Butler, Alice Dohnálková, Libor Kovarik, Robert Finney, Avinash Kali, Behzad Sharif, Louis‐S. Bouchard, Rajesh Gupta, Mayil Singaram Krishnam, Keyur Vora, Balaji Tamarappoo, Andrew G. Howarth, Andreas Kumar, Joseph Francis, Scott B. Reeder, John C. Wood, Frank S. Prato, Rohan Dharmakumar

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldMedicine
TopicCardiovascular Function and Risk Factors
Canadian institutionsNOSM UniversityUniversity of CalgaryLawson Health Research InstituteWestern University
FundersPacific Northwest National LaboratoryBiological and Environmental ResearchOffice of ScienceU.S. Department of Health and Human ServicesNational Institutes of HealthSiemens HealthineersNational Heart, Lung, and Blood InstituteU.S. Department of Energy
KeywordsMedicineCardiologyMyocardial infarctionInternal medicineHeart failureVentricular remodelingDegeneration (medical)Pathology

Abstract

fetched live from OpenAlex

Sudden blockage of arteries supplying the heart muscle contributes to millions of heart attacks (myocardial infarction, MI) around the world. Although re-opening these arteries (reperfusion) saves MI patients from immediate death, approximately 50% of these patients go on to develop chronic heart failure (CHF) and die within a 5-year period; however, why some patients accelerate towards CHF while others do not remains unclear. Here we show, using large animal models of reperfused MI, that intramyocardial hemorrhage - the most damaging form of reperfusion injury (evident in nearly 40% of reperfused ST-elevation MI patients) - drives delayed infarct healing and is centrally responsible for continuous fatty degeneration of the infarcted myocardium contributing to adverse remodeling of the heart. Specifically, we show that the fatty degeneration of the hemorrhagic MI zone stems from iron-induced macrophage activation, lipid peroxidation, foam cell formation, ceroid production, foam cell apoptosis and iron recycling. We also demonstrate that timely reduction of iron within the hemorrhagic MI zone reduces fatty infiltration and directs the heart towards favorable remodeling. Collectively, our findings elucidate why some, but not all, MIs are destined to CHF and help define a potential therapeutic strategy to mitigate post-MI CHF independent of MI size.

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 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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.526
Threshold uncertainty score0.494

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.014
GPT teacher head0.273
Teacher spread0.259 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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

Citations43
Published2022
Admission routes1
Has abstractyes

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