Clinical risk factors of intensive care unit acquired weakness predicted by human muscle microtissue response to humoral factors
Bibliographic record
Abstract
1. Abstract ICUAW is an acquired phenomenon in the critically ill patient that is characterized by severe muscle weakness and atrophy. It results from both myopathic and neuropathic injury and is associated with heightened patient morbidity and mortality. Critical illness survivors exhibit variable functional outcomes following ICUAW, ranging from full recovery to persistent weakness with a significant negative impact on quality of life. Despite clinical importance, the mechanistic understanding of ICUAW remains incomplete, in part due to a paucity of tractable, species-specific experimental models. Previous studies have suggested a potential causative role of bloodborne factors, though this remains a matter of debate. To address these technological and knowledge gaps, we leveraged a 3-D human skeletal muscle microtissue (hMMT) culture platform to investigate the ability of humoral factors to directly impact pathogenesis of the myopathic component of ICUAW; critical illness myopathy (CIM). Blood serum collected from ICU patients within 72 hours of ICU admission was used to treat hMMTs for 6 days starting at a time-point when the myotubes were multinucleated, striated, and capable of generating force. hMMTs treated with serum from patients that survived the ICU stay exhibited several hallmarks of CIM including; significant reductions in myotube diameter (atrophy) and striation density, alongside functional declines in calcium release, peak force, and force kinetics. The in vitro profiles of ICU serum treated hMMTs displayed significant associations with known ICUAW and CIM clinical risk factors (e.g. age, length of ICU stay) such that individual patient risk factors could be predicted from serum-induced hMMT responses. An evaluation of hMMT responses enabled delineation of ICU non-survivors from healthy control and ICU survivors. This study offers an enabling technology for studies of CIM biology in the context of human cells while also delivering compelling evidence that humoral factors directly influence ICU-associated skeletal muscle pathogenesis. Together, these advances may inform strategies for preventing or treating ICUAW.
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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 | 0.001 |
| 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".