The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later
Bibliographic record
Abstract
Congenital diaphragmatic hernia (CDH) is a severe birth defect and a major cause of neonatal respiratory distress. Impacting ~2-3 in 10,000 births, CDH is associated with a high mortality rate, and long-term morbidity in survivors. Despite the significant impact of CDH, its etiology remains incompletely understood. In 2003, Greer et al. proposed the Retinoid Hypothesis, stating that the underlying cause of abnormal diaphragm development in CDH was related to altered retinoid signaling. In this review, we provide a comprehensive update to the Retinoid Hypothesis, discussing work published in support of this hypothesis from the past 20 years. This includes reviewing teratogenic and genetic models of CDH, lessons from the human genetics of CDH and epidemiological studies, as well as current gaps in the literature and important areas for future research. The Retinoid Hypothesis is one of the leading hypotheses to explain the etiology of CDH, as we continue to better understand the role of retinoid signaling in diaphragm development, we hope that this information can be used to improve CDH outcomes. IMPACT: This review provides a comprehensive update on the Retinoid Hypothesis, which links abnormal retinoic acid signaling to the etiology of congenital diaphragmatic hernia. The Retinoid Hypothesis was formulated in 2003. Twenty years later, we extensively review the literature in support of this hypothesis from both animal models and humans.
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How this classification was reachedexpand
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 | 0.006 | 0.010 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.004 |
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 teacher head, 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".