Increases in dietary phosphate levels can augment atrial arrhythmias
Bibliographic record
Abstract
Increases in dietary phosphate levels can augment atrial arrhythmiasAtrial fibrillation (AF) is a rapid, irregular supraventricular tachycardia, which is now the most commonly occurring cardiac arrhythmia worldwide.1 The incidence of AF and its clinical impact, including stroke, heart failure, and other morbidities are increasing, in part due to the aging of populations worldwide.2,3 In spite of expanded efforts to identify the basic underlying mechanisms in animal models, 4 and improve clinical detection, diagnoses and treatment modalities, significant knowledge gaps remain concerning how AF is initiated and maintained.2,3 An interesting, significant manuscript in this volume of Acta Physiologica 5 provides important new information concerning the intracellular signaling pathways through which a high phosphate diet, administered to healthy adult mice, can result in remodeling of the atria of these hearts, while also producing an increased tendency for the myocardium to exhibit AF-like high-frequency firing.In this study, 5 either sham (control) or nephrectomized adult mice (a model of chronic kidney disease) were fed high phosphate diets for 10 weeks, and resulting increases in plasma levels of phosphate were measured.Animals were then sacrificed to allow the two main constituents of the atrial myocardium (myocytes and fibroblasts) to be isolated, maintained in short-term culture, and then analyzed using rigorous biochemical, molecular, and bioinformaticsbased methods.Based on the resulting extensive and informative datasets, the authors conclude that even when phosphate levels are increased by as little as 1 mM (from normal, approximately 2.5 mM, to approximately 3.5 mM, see Table 1) specific intracellular signaling pathways involving STAT3/NF-κB were activated and consistent signs of mitochondrial stress and associated redox imbalance 6 were observed.Additional insights were obtained using a cell line (HL-1), that mimics many of the properties of atrial myocytes.Specifically, alterations in the levels of proteins that are involved in contraction and intracellular calcium release provided the basis for the conclusion that a primary driver of the phosphate-induced effects in mouse atria is mitochondrial impairment, manifested in
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".