Abstract 15584: Metabolomic Signature of Fontan Circulation
Bibliographic record
Abstract
Introduction: Patients born with a range of cardiac defects, not amenable to biventricular repair are palliated with establishment of Fontan circulation. Although majority of patients with Fontan circulation survive childhood, eventually they experience multi-system dysfunction, mainly frailty, impaired exercise capacity, blunted exercise-augmented hemodynamics, progressive liver fibrosis, and shortened survival. Fontan circulation associated biochemical abnormalities have not been well described. Materials and Methods: Twenty adult patients with Fontan circulation and 20 age- and sex-matched healthy subjects underwent a non-targeted metabolomics assessment using an LC-QTOF-MS system to detect potential Fontan-related biomarkers. These study participants were also investigated for markers of frailty, cardiopulmonary exercise testing, and resting as well as exercise-augmented hemodynamic evaluation. Results: A total of 1679 known plasma metabolites were detected in electrospray positive and negative modes among which 37 metabolites were significantly different (T-Test Unpaired (p<0.05) followed by a multiple testing correction of p values (Benjamini-Hochberg)). These metabolites belonged to several classes of compounds including lipids, bile acids, amino acids, and derivatives. Several bile acids such as chenodeoxycholic acid glycine conjugate, glycoursodeoxycholic acid, and deoxycholic acid glycine conjugate were upregulated in patients with Fontan while 8-hydroxyguanine, N-arachidonoyl glycine, uracil, and cysteine were down-regulated in comparison to healthy subjects. Conclusion: In-depth plasma metabolomic analysis demonstrated metabolic pathways activation involved in bile acid formation, markers of oxidative stress, damage of DNA, whereas lower concentrations of several amino acids in patients with Fontan.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".