Cell-Based Screening Test for Idiopathic Scoliosis Using Cellular Dielectric Spectroscopy
Notice bibliographique
Résumé
In Brief Study Design. A cell-based assay was developed to identify asymptomatic children at risk of developing idiopathic scoliosis (IS) and to stratify IS patients at an earlier stage in order to better predict their clinical outcome. Clinical validation of this assay was performed by testing IS patients at different stages, healthy control subjects, and asymptomatic offspring, born from at least one scoliotic parent, who are considered at risk of developing this disorder. Objective. Our goal was to develop and validate a clinical test for IS using cellular dielectric spectroscopy (CDS) and peripheral blood mononuclear cells (PBMCs). Summary of Background Data. We have previously demonstrated the occurrence of a melatonin signaling dysfunction in osteoblasts obtained from severely affected IS patients using a cAMP assay. This led us to stratify IS patients into 3 functional subgroups. Methods. A group of 44 patients with IS was compared with 42 healthy control subjects and 31 asymptomatic at-risk children. PBMCs were obtained after centrifugation on a Ficoll-gradient. Melatonin signal transduction was measured by CDS in the presence of varying concentrations of melatonin or iodomelatonin. Results. Osteoblasts from distinct functional subgroups were retested using CDS, allowing their classification into the same functional subgroups with both ligands as initially demonstrated using a cAMP assay. Clinical data obtained with CDS and PBMCs showed 100% specificity and 100% sensitivity because melatonin signaling impairment was observed only in IS patients and not in healthy controls. Assessment of the risk of developing a scoliosis in asymptomatic children was determined by CDS in 33% of asymptomatic children at risk, which was confirmed clinically within 24 months. Conclusion. This cell-based assay can serve as a presymptomatic screening test to identify asymptomatic children at risk of developing IS and may be used to improve stratification of patients, which in turn allow clinicians to predict their clinical outcome. Moreover, this functional blood test is advantageous because it can be performed without prior knowledge of specifically mutated genes causing IS. A cell-based assay was performed to assess melatonin signal transduction in peripheral blood mononuclear cells obtained from patients with IS and asymptomatic children using cellular dielectric spectroscopy. This functional blood test allowed the stratification of IS patients into 3 functional subgroups. Similar analysis with asymptomatic children led to the identification of individuals at risk of developing scoliosis before onset.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».