PB1425 High Cell-free (cf)DNA in Patients with Myelofibrosis (MF) is Associated with Adverse Clinical Outcomes, Activation of the AIM2 Inflammasome and Elevated Levels of Inflammasome-Related Cytokine IL-18
Bibliographic record
Abstract
Background: Hyperglycemia is a common complication in the intensive care unit and is associated with increased morbidity and mortality.The causes of hyperglycemia during critical illness include pre-existing conditions (e.g., diabetes mellitus) as well as the host response to severe stress (e.g., sepsis, trauma).Individuals with hyperglycemia also carry an additional risk of developing sepsis, a dysregulated host response to infection associated with a prothrombotic state.However, the precise mechanisms by which hyperglycemia modulates host response to sepsis remains unclear.The objective of this project is to investigate the host response to infection in hyperglycemic and normoglycemic mice.Aims: Investigate time-dependent changes in markers of coagulation, anticoagulation, inflammation, and the formation of neutrophil extracellular traps (NETs) in a streptozotocin (STZ)-induced model of hyperglycemia in mice.Methods: 5-week-old C57Bl/6 mice from both sexes were administer 10 rounds of STZ to induced hyperglycemic (blood glucose >15 mmol/L).At 11-12 weeks of age the mice are given an IP injection of rat fecal slurry (0.6 mg/g) to induce sepsis.The mice were monitored for 48 h and euthanized at the humane or study endpoint.Additionally, ELISAs on collected plasma were performed to measure coagulation, anticoagulation, inflammation, and NET formation.Results: The 48 h survival was similar in male and female hyperglycemic mice.There is a significant decrease in endogenous protein C in hyperglycemic mice that died during sepsis.Levels of IL-6, TAT, cfDNA, and MPO were not significantly different between hyperglycemic and normoglycemic mice.We also observed that acquired hypoglycemia in normoglycemic mice (defined as < 3.1 mM) may be a useful predictor of poor outcomes in sepsis.Conclusion(s): Our data suggests that exposure to sepsis in a hyperglycemic state impairs endogenous anticoagulation mediated by protein C.An acquired deficiency of protein C may contribute to a prothrombotic state associated with hyperglycemia in sepsis.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.003 | 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".