Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue
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Bibliographic record
Abstract
Torsade de Pointes (TdP) is a lethal arrhythmia that is often drug-induced, thus there is an urgent need for development of models to test or predict the drug sensitivity of human cardiac tissue. Here, we present an in vitro TdP model using 3D cardiac tissue sheets (CTSs) that contain a mixture of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and non-myocytes. We simultaneously monitor the extracellular field potential (EFP) and the contractile movement of the CTSs. Upon treatment with IKr channel blockers, CTSs exhibit tachyarrhythmias with characteristics of TdP, including both a typical polymorphic EFP and meandering spiral wave re-entry. The TdP-like waveform is predominantly observed in CTSs with the cell mixture, indicating that cellular heterogeneity and the multi-layered 3D structure are both essential factors for reproducing TdP-like arrhythmias in vitro. This 3D model could provide the mechanistic detail underlying TdP generation and means for drug discovery and safety tests.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it