Metabolic Oversupply and Mitochondrial Dysfunction as a Cause of Diaphragmatic Failure after Mechanical Ventilation
Bibliographic record
Abstract
Mechanical ventilation (MV) unloads the diaphragm and leads to ventilator‐induced diaphragmatic dysfunction (VIDD). The cellular basis of VIDD is poorly understood, but oxidative stress is involved. A known cause of oxidative stress and skeletal muscle impairment is mitochondrial dysfunction, which can result from altered cellular energy metabolism. Therefore, we investigated indices of mitochondrial function and energy metabolism in human diaphragm after MV. Compared to controls, MV diaphragms had abnormal intramyocellular lipid accumulation (+219%, p<0.01), de‐phosphorylation of the cellular metabolic sensor AMPK (−64%, p<0.01), and downregulation of SIRT1 (−50%, p<0.01). Mitochondrial biogenesis and antioxidant gene systems were globally downregulated, as indicated by gene expression profiling. Consequently, whole muscle mitochondrial enzyme activities were decreased by 35–70%. MV diaphragms contained abnormally high levels of mitochondrial cytochrome c oxidase (COX) deficient myofibers that co‐localized with intracellular lipid accumulation, and which contained high levels of clonally‐expanded mtDNA deletions. MV‐induced contractile inactivity results in an overabundance of energy substrate supply relative to demand, a potent metabolic imbalance that triggers mitochondrial ROS production, and may lead to compromised diaphragmatic function.
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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) | 0.000 | 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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".