Regional changes in cellular and molecular pathology in children with end-stage dilated cardiomyopathy: Correlation with regional and global cardiac performance
Bibliographic record
Abstract
Abstract Background Paediatric dilated cardiomyopathy (DCM) carries a poor prognosis. We previously identified regional heterogeneity and patterns of left ventricular (LV) dysfunction that correlated with outcomes. In this project, we aimed to describe associations of regional myocardial performance with fibrosis and molecular signalling. Methods We prospectively studied children undergoing heart transplantation for DCM. Pre-transplant clinical and echocardiographic features were correlated with regional histological and molecular findings from explanted hearts. Ten LV and one right ventricular (RV) regions were assessed for fibrosis, myocyte area, and protein expression related to hypertrophy and fibrosis signalling (p38, ERK, phospho-JNK, phospho-GSK3β, SMA, cadherin, ILK), contractile function (myosin heavy chain), and calcium handling (SERCA2a, phospho-CamKII, phospholamban [PLN], and phospho-PLN). Results Eight children were included [median age 2.0years (0.3–15.1years)], of whom six required mechanical circulatory support. There was no difference in fibrosis burden or myocyte area between LV segments, and between ventricles. LV dimensions, ejection fraction and diastolic parameters were not related to fibrosis, myocyte area or molecular signalling. Tricuspid annular systolic plane excursion was related to myocyte volume (r=0.89, p<0.01). There was an inverse relationship between fibrosis and segmental longitudinal strain for LV basal and mid-posterior segments (basal posterior, r=0.96, p<0.01; mid-posterior, r=0.74, p=0.05). Global longitudinal strain was related to expression of ILK (r=0.78, p=0.02) and SERCA2a (r=0.71, p=0.04). Conclusion In paediatric end-stage DCM, regional cardiac function is associated with interstitial fibrosis and expression of calcium-cycling and contractile proteins. Phenotypic and molecular expression is variable. The RV shows similar injury and protein expression to the LV despite better myocardial function. These findings suggest that even with severely reduced LV function, paediatric DCM is a highly heterogeneous disease involving both ventricles.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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".