Understanding the Mechanisms and Treatment of Heart Failure: Quantitative Systems Pharmacology Models with a Focus on SGLT2 Inhibitors and Sex-Specific Differences
Bibliographic record
Abstract
Heart failure (HF), which is a major clinical and public health challenge, commonly develops when the myocardial muscle is unable to pump an adequate amount of blood at typical cardiac pressures to fulfill the body's metabolic needs, and compensatory mechanisms are compromised or fail to adjust. Treatments consist of targeting the maladaptive response of the neurohormonal system, thereby decreasing symptoms by relieving congestion. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, which are a recent antihyperglycemic drug, have been found to significantly improve HF complications and mortality. They act through many pleiotropic effects, and show better improvements compared to others existing pharmacological therapies. Mathematical modeling is a tool used to describe the pathophysiological processes of the disease, quantify clinically relevant outcomes in response to therapies, and provide a predictive framework to improve therapeutic scheduling and strategies. In this review, we describe the pathophysiology of HF, its treatment, and how an integrated mathematical model of the cardiorenal system was built to capture body fluid and solute homeostasis. We also provide insights into sex-specific differences between males and females, thereby encouraging the development of more effective sex-based therapies in the case of heart failure.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| 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".