MétaCan
Menu
Back to cohort
Record W2894410744 · doi:10.1002/acn3.637

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

2018· article· en· W2894410744 on OpenAlexaff
Bardia Nourbakhsh, Pavan Bhargava, Helen Tremlett, Janace Hart, Jennifer Graves, Emmanuelle Waubant

Bibliographic record

VenueAnnals of Clinical and Translational Neurology · 2018
Typearticle
Languageen
FieldNeuroscience
TopicTryptophan and brain disorders
Canadian institutionsUniversity of British Columbia
FundersNational Institute of Neurological Disorders and StrokeRace to Erase MSNational Multiple Sclerosis Society
KeywordsMedicineKynurenineMetaboliteInternal medicineOdds ratioHazard ratioProportional hazards modelGut floraPhysiologyMicrobiomeTryptophanMetabolomicsConfidence intervalBioinformaticsImmunologyBiologyGeneticsAmino acid

Abstract

fetched live from OpenAlex

OBJECTIVE: To determine if altered tryptophan (Trp) metabolism is associated with MS risk or disease severity in children. METHODS: Participants with pediatric-onset MS and clinically isolated syndrome (CIS) within 4 years of disease onset and healthy controls underwent collection of serum. Longitudinal disability and processing speed measures and relapse data were collected in cases. Global metabolomics were conducted in 69/67 cases/controls. Targeted Trp measurement was performed in a discovery group (82 cases, 50 controls) and a validation group (92 cases, 50 controls), while functional gut microbiome analysis was done in 17 cases. Adjusted logistic, linear and negative binomial regression and Cox-proportional hazard models were used. RESULTS: Using global metabolomics data, higher relative abundances of Trp and indole lactate, a known gut microbiota-derived Trp metabolite, were associated with lower risk of MS. In cases, higher relative abundances of gut microbiota-derived Trp metabolites were associated with lower disability and higher processing speed scores and higher relative abundance of kynurenine was associated with higher relapse rate. Using targeted tryptophan measures, in the discovery and validation groups, each 1 mcg/mL increase in serum Trp level was associated with 20% (95% CI: 4-34%) and 32% (95% CI: 16-44%) decrease in adjusted odds of having MS, respectively. A lower relative abundance of gut microbial genes involved in Trp catabolism was associated with higher relapse risk. INTERPRETATION: Trp metabolism by the gut microbiota and the kynurenine pathway may be relevant to the risk of MS in children as well as MS activity and severity.

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation 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 score0.019
Threshold uncertainty score0.466

Codex and Gemma teacher scores by category

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

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 head0.149
GPT teacher head0.354
Teacher spread0.205 · 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 teacher head, 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".

Quick stats

Citations92
Published2018
Admission routes1
Has abstractyes

Explore more

Same venueAnnals of Clinical and Translational NeurologySame topicTryptophan and brain disordersFrench-language works237,207