Abnormal cardiac inflow patterns during postnatal development in a mouse model of Holt-Oram syndrome
Bibliographic record
Abstract
Tbx5(del/+) mice provide a model of human Holt-Oram syndrome. In this study, the cardiac functional phenotypes of this mouse model were investigated with 30-MHz ultrasound by comparing 12 Tbx5(del/+) mice with 12 wild-type littermates at 1, 2, 4, and 8 wk of age. Cardiac dimensions were measured with two-dimensional and M-mode imaging. The flow patterns in the left and right ventricular inflow channels were evaluated with Doppler flow sampling. Compared with wild-type littermates, Tbx5(del/+) mice showed significant changes in the mitral flow pattern, including decreased peak velocity of the left ventricular (LV) early filling wave (E wave), increased peak velocity of the late filling wave (A wave), and decreased or even reversed peak E-to-A ratio. The prolongation of LV isovolumic relaxation time was detected in Tbx5(del/+) neonates as early as 1 wk of age. In Tbx5(del/+) mice, LV wall thickness appeared normal but LV chamber dimension was significantly reduced. LV systolic function did not differ from that in wild-type littermates. In contrast, the Doppler flow spectrum in the enlarged tricuspid orifice of Tbx5(del/+) mice demonstrated increased peak velocities of both E and A waves and increased total time-velocity integral but unchanged peak E/A. In another 13 mice (7 Tbx5(del/+), 6 wild-type) at 2 wk of age, significant correlation was found between Tbx5 gene expression level in ventricular myocardium and LV filling parameters. In conclusion, the LV diastolic function of Tbx5(del/+) mice is significantly deteriorated, whereas the systolic function remains normal.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| 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".