Systemic release of high mobility group box 1 (HMGB1) protein is associated with severe and fatal Plasmodium falciparum malaria
Bibliographic record
Abstract
BACKGROUND: Severe falciparum malaria (SM) pathogenesis has been attributed, in part, to deleterious systemic host inflammatory responses to infection. High mobility group box 1 (HMGB1) protein is an important mediator of inflammation implicated in sepsis pathophysiology. METHODS: Plasma levels of HMGB1 were quantified in a cohort of febrile Ugandan children with Plasmodium falciparum infection, enrolled in a prospective observational case-controlled study, using a commercial enzyme-linked immunosorbent assay. The utility of HMGB1 to distinguish severe malaria (SM; n = 70) from uncomplicated malaria (UM; n = 33) patients and fatal (n = 21) versus non-fatal (n = 82) malaria, at presentation, was examined. Receiver operating characteristic curve analysis was used to assess the prognostic accuracy of HMGB1. The ability of P. falciparum-parasitized erythrocytes to induce HMGB1 from peripheral blood mononuclear cells was assessed in vitro. The effect of an anti-HMGB1 neutralizing antibody on disease outcome was assessed in the experimental Plasmodium berghei ANKA rodent parasite model of SM. Mortality and parasitaemia was assessed daily and compared to isotype antibody-treated controls. RESULTS: Elevated plasma HMGB1 levels at presentation were significantly associated with SM and a subsequent fatal outcome in paediatric patients with P. falciparum infection. In vitro, parasitized erythrocytes induced HMGB1 release from human peripheral blood mononuclear cells. Antibody-mediated neutralization of HMGB1 in the experimental murine model of severe malaria failed to reduce mortality. CONCLUSION: These data suggest that elevated HMGB1 is an informative prognostic marker of disease severity in human SM, but do not support HMGB1 as a viable target for therapeutic intervention in experimental murine SM.
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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) | 0.000 | 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) | 0.000 | 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".