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Record W4249035566 · doi:10.21203/rs.3.rs-384297/v1

A Novel Blood-Based Assay for Treatment Monitoring of Tuberculosis

2021· preprint· en· W4249035566 on OpenAlexaff
A. Zimmer, Samuel G. Schumacher, Erik Södersten, Anna Mantsoki, Romain Wyss, David H. Persing, Sara Banderby, Linda Strömqvist Meuzelaar, Jacqueline Prieto, Devasena Gnanashanmugam, Purvesh Khatri, Stefano Ongarello, Morten Rühwald, Claudia M. Denkinger

Bibliographic record

VenueResearch Square · 2021
Typepreprint
Languageen
FieldMedicine
TopicTuberculosis Research and Epidemiology
Canadian institutionsMcGill University
FundersNational Institutes of HealthMinisterie van Buitenlandse ZakenDepartment of Foreign Affairs and Trade, Australian GovernmentU.S. Department of DefenseAustralian GovernmentNational Institute of Allergy and Infectious DiseasesBill and Melinda Gates FoundationBundesministerium für Bildung, Wissenschaft, Forschung und TechnologieUniversidad Peruana Cayetano HerediaDr. Ralph and Marian Falk Medical Research Trust
KeywordsGeneXpert MTB/RIFMedicineTuberculosisInternal medicineGene signatureTb treatmentSputumGeneGene expressionPathologyBiology

Abstract

fetched live from OpenAlex

Abstract ObjectivesA novel 3-gene host transcriptional signature (GBP5, DUSP3 and KLF2) that has been validated for TB diagnosis. The signature was recently translated by Cepheid into a prototype cartridge-based test that can be run on the GeneXpert instruments. In this study, we prospectively evaluated the change in the expression of the cartridge-based 3-gene signature with time following treatment initiation among pulmonary TB patients who were microbiologically cured at the end of treatment. ResultsOur results show that the 3-gene signature expression level (TB score) changes significantly over time with respect to baseline levels. The greatest increase in TB score occurred within the first month of treatment (median fold-increase in TB score: 1.08 [IQR 0.54-1.52]) and plateaued after 4 months of treatment (median TB score: 1.97 [IQR: 1.03-2.33]. The rapid and substantial increase of the TB score in the first month of treatment holds promise for the early identification of patients that respond to TB treatment. The plateau in TB score at 4 months may indicate early clearance of disease and could direct treatment to be shortened. These hypotheses need to be further explored with large prospective treatment monitoring and test of cure studies.

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)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.155
GPT teacher head0.461
Teacher spread0.305 · 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 designBench or experimental
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".

Quick stats

Citations0
Published2021
Admission routes1
Has abstractyes

Explore more

Same venueResearch Square→Same topicTuberculosis Research and Epidemiology→French-language works237,207→