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The role of Th17 lymphocytes in drug-resistant epilepsy

2019· article· en· W4313359027 on OpenAlexaff
Oumarou Ouédraogo, Hélène Jamann, Audrey Daigneault, Marie-Laure Clénet, Boaz Lahav, Anick Bérubé, Patrick Cossette, Mark R. Keezer, Dang Khoa Nguyen, Catherine Larochelle

Bibliographic record

VenueThe Journal of Immunology · 2019
Typearticle
Languageen
FieldMedicine
TopicDrug Transport and Resistance Mechanisms
Canadian institutionsUniversité de MontréalCentre Hospitalier de l’Université de Montréal
Fundersnot available
KeywordsEpilepsyPeripheral blood mononuclear cellCD8Immune systemMedicineImmunologyCytokineImmunosuppressionFlow cytometryTumor necrosis factor alphaEx vivoIn vivoBiologyIn vitro

Abstract

fetched live from OpenAlex

Abstract Epilepsy is a chronic neuronal disorder affecting ~65 millions people throughout the world. 1/3 of patients suffer from drug-resistant epilepsy (DRE). Objective to assess the relationship between different Th17 markers and the clinical course of epilepsy to uncover new potential immune biomarkers and therapeutic targets of interest for DRE. Approach Subjects between 19–55 years old with a focal diagnosed epilepsy were recruited at the CHUM epilepsy clinic. The profile of peripheral blood T lymphocytes from DRE patients (n=48) is compared to well-controlled epilepsy (WCE; n=30) and healthy controls (n=35). Peripheral blood mononuclear cells (PBMCs) were isolated by gradient density centrifugation before ex vivo analysis of surface markers (flow cytometry). Total CD4 T lymphocytes were magnetically isolated from PBMCs and stimulated overnight before analysis of cytokine expression or processed for RNA extraction before analysis of transcription factors expression by qRT-PCR. Results Our data suggest that antiepileptic drugs are associated with a relative ‘immunosuppression’, more pronounced in WCE. Epilepsy is associated with an altered distribution of immune cell populations with a higher CD4:CD8 ratio. A higher proportion of CD4 T lymphocytes from DRE subjects express CCR6 and CD161 compared to WCE. The proportion of CD4 T cells expressing pro-inflammatory cytokines from Th17/1 lineage (IL-17A, IL-22, IFN-γ, GM-CSF, TNFα) is higher in DRE than WCE, while anti-inflammatory cytokines (IL-4, IL-10) tend to be lower. Conclusion Our preliminary results suggest an increased frequency of pro-inflammatory Th17/1 lymphocytes and their related cytokines in DRE. Pro-inflammatory CD4 T cells could play a role in DRE.

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)0.000
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
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
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 head0.004
GPT teacher head0.210
Teacher spread0.206 · 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".

Quick stats

Citations3
Published2019
Admission routes1
Has abstractyes

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