A collagen-based laboratory model to mimic sex-specific features of calcific aortic valve disease
Bibliographic record
Abstract
Calcific aortic valve disease (CAVD) shows in the deposition of calcium phosphates in the collagen-rich layer of the valve leaflets. This stiffens the leaflets and eventually leads to heart failure. Recent research suggests that CAVD follows sex-specific pathways: at the same severity of the disease, women tend to have fewer and less crystalline calcifications, and the phases of their calcifications are decidedly different than those of men; namely, dicalcium phosphate dihydrate (DCPD) - one of the mineral phases in CAVD - occurs almost exclusively in females. Furthermore, the morphologies of heart valve calcifications might be sex-specific, but the sex dependence of the morphologies has not been systematically investigated. Herein, we first show that male CAVD patients have more compact and less fibrous calcifications than females, establishing sex-dependent morphological features of heart valve calcification. We then build a model that recapitulates the sex differences of the calcifications in CAVD, which is based on a collagen gel that we calcify in simulated body fluid with varying fetuin A concentrations. With increasing fetuin A concentration, the calcifications become less crystalline and more fibrous, and more DCPD deposits in the collagen matrix, resembling the physicochemical characteristics of the calcifications in female valves. Lower fetuin A concentrations give rise to a model that replicates male-specific mineral characteristics. The models could be used to develop sex-specific detection and treatment methods for CAVD. STATEMENT OF SIGNIFICANCE: Although calcific aortic valve disease (CAVD) affects ∼10 million people globally, researchers have only discovered recently that the disease follows sex-specific pathways, and many of its sex-specific features remain unknown. To further our understanding of sex differences in CAVD and to develop better detection and treatment methods, there is an urgent need to establish models for CAVD that account for its sex-specific manifestations. In this study, we first show that CAVD calcifications in men and women take on different morphologies. Second, we present a model that can replicate physicochemical calcification characteristics of male or female valves, including morphology, and that can help to develop sex-specific detection and treatment methods for CAVD.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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) | 0.000 | 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 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".