Thanatogenomic Investigation of the Hydroxymethylome and Mitochondrial Genome of Cadaveric Cardiomyocytes: Proposal for a Proof-of-Concept Study
Notice bibliographique
Résumé
BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of death in the United Arab Emirates (UAE). One of the common CVDs is hypertrophic cardiomyopathy (HCM). Recent studies conducted in heart cells of mice have shown that this condition involves a chemical modification called hydroxymethylation of the DNA of heart cells. OBJECTIVE: Objectives of the proposed research are to profile the distribution of 5-hydroxymethylation in the cardiomyocyte (CMC) genome of cadaveric cardiac tissue and cardiac biopsy specimens; to compare the hydroxymethylome of cadaveric CMCs with that of cardiac biopsy specimens from HCM patients and/or cardiac transplant patients (control) undergoing cardiac catheterization; to histologically appraise sarcomere distribution and mitochondrial morphology of CMCs in the presence of HCM; to correlate the mitochondrial genome with the HCM phenotype; and to integrate anatomy with biochemistry and genetics into the instructional design of HCM in the core medical curriculum at Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU). METHODS: Normal and hypertrophic heart specimens will be obtained from 8 whole-body cadavers (2/8, 25% control and 6/8, 75% HCM). Myocardial biopsy specimens will be obtained from cardiothoracic and transplant units at the Cleveland Clinic in Abu Dhabi, UAE. As this is a proof-of-concept study, we plan to recruit 5 patients with HCM, where HCM has been diagnosed according to the guidelines of the 2014 European Society of Cardiology Guidelines. Patients with valvular heart disease, history of myocarditis, regular alcohol consumption, or cardiotoxic chemotherapy will be excluded. The control biopsy specimens will be obtained from patients who had received heart transplants. Three investigational approaches will then be employed: (1) gross anatomical evaluation, (2) histological analysis, and (3) profiling and analysis of the hydroxymethylome. These investigations will be pursued with minor modifications, if required, to the standard protocols and in accordance with institutional policy. The objective associated with the education of health professionals will be addressed through a strategy based on Graham's knowledge translation model. RESULTS: This study is at the protocol-development stage. The validated questionnaires have been identified in relation to the objectives. The MBRU and the Cleveland Clinic Abu Dhabi Institutional Review Board (IRB) are reviewing this study. Further clarification and information can be obtained from the MBRU IRB. There is funding in place for this study (MBRU-CM-RG2019-08). Currently, we are in the process of standardizing the protocols with respect to the various molecular techniques to be employed during the course of the study. The total duration of the proposed research is 24 months, with a provision for 6 months of a no-cost extension. CONCLUSIONS: The spectrum of CVDs has recently received significant focus from the public health sector in the UAE. HCM is a common familial heart disease, contributing to the sudden increase in the mortality rate of young Emiratis in the UAE. Incorporating artificial intelligence into the identification of epigenetic risk factors associated with HCM will promote accurate diagnosis and lead to the development of improved management plans, hence, positive patient outcomes. Furthermore, integration of these findings into the instructional design of undergraduate, postgraduate, and continuous professional development medical curricula will further contribute to the body of knowledge regarding HCM. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/17241.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».