Cell-Based Screening Test for Idiopathic Scoliosis Using Cellular Dielectric Spectroscopy
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".