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Record W4394893028 · doi:10.1093/jbcr/irae036.002

2 Differential Transcriptomic Responses Among Burn Injury Outcomes Related to Morality and Hospital Length of Stay

2024· article· en· W4394893028 on OpenAlexfundno aff
Burook Misganaw, Benjamin Levi, Desiree Pinto, Tuan Le, Anthony E. Pusateri, Arti Gautam, Lauren T. Moffatt, Jeffrey W. Shupp, Rasha Hammamieh

Bibliographic record

VenueJournal of Burn Care & Research · 2024
Typearticle
Languageen
FieldMedicine
TopicBurn Injury Management and Outcomes
Canadian institutionsnot available
FundersMcGill UniversityUniversity of Texas Southwestern Medical CenterUniversity of WashingtonUniversity of Southern California
KeywordsMedicineEmergency medicineTranscriptomeMoralityBurn injuryIntensive care medicineMedical emergencySurgeryGeneGenetics

Abstract

fetched live from OpenAlex

Abstract Introduction Severe burn injury induces a profound systemic molecular response. Yet, the various molecular mechanisms mediating clinical outcomes after burn injury are not well characterized. Using longitudinal global gene expression data, we investigate the evolution of transcriptomic responses to thermal injury. We hypothesized that burn patients with differing clinical outcomes will show diverging transcriptomic alterations over time. Methods This prospective observational study included patients from a regional burn center from 2013 to 2017. Patient demographics, burn injury characteristics, and blood samples for mRNA extraction and microarray whole genome gene expression profiling were collected at admission and set timepoints until 30 days. Patients were divided into 4 groups based on mortality status and hospital length of stay (LOS); G1 - died within 7 days, G2 - died after 7 days, G3 - discharged after 7 days, and G4 - discharged within 7 days. Transcriptomic abundances were compared between groups to identify differences in gene profiling. Pathway enrichment analysis was performed to determine the top significant pathways in each group. Results A total of 116 patients were analyzed. Most patients were male (72.4%) with a median age of 39 and TBSA of 12.3%. Overall mortality rate was 12.9%. The distribution of patients in G1 to G4 was 8%, 5%, 60%, and 27% respectively. A total of 1,245 blood samples and 17,289 transcripts were quantified. At admission, genes were differentially expressed in G1, G2 and G3 compared to G4 (FDR-corrected P < 0.05 and magnitude of log fold-change > 1). Significant gene sets were largely nonoverlapping, with only a few immune response related genes being activated across all groups. Pathway enrichment analysis showed significant up-regulated protein folding pathways in G1, and significant up-regulated pathways related to oxidative stress and temperature homeostasis in G3. Intra-individual transcriptomic changes from admission to 30 days showed distinct group- and time-dependent patterns. G4 showed the least pronounced transcriptomic response without any noticeable change over time, while G3 mounted a transcriptomic response that increased over time. Conclusions We identified transcriptomic alterations associated with distinct outcomes related to mortality and hospital LOS after burn injury. Alterations among groups were present at admission and persisted for 30 days. Connecting transcriptomic alterations to molecular mechanisms continues to evolve. Applicability of Research to Practice Enhanced understanding of transcriptomic alterations and molecular mechanisms of burn injury trajectories will allow for the development of early biomarkers, prognostic tools and novel intervention strategies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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.

Opus teacher head0.035
GPT teacher head0.394
Teacher spread0.359 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

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Citations0
Published2024
Admission routes1
Has abstractyes

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