Imaging Correlates of Leukocyte Accumulation and CXCR4/CXCL12 in Multiple Sclerosis
Bibliographic record
Abstract
OBJECTIVE: To compare leukocyte accumulation and expression of the chemokine receptor/ligand pair CXCR4/CXCL12 in magnetic resonance imaging-defined regions of interest (ROIs) in brains from patients with chronic multiple sclerosis. We studied the following ROIs: normal-appearing white matter (NAWM); regions abnormal only on T2-weighted images (T2 only); and regions abnormal on T2- and T1-weighted images with an abnormal magnetization transfer ratio (T2/T1/MTR). DESIGN: Case-control study. SETTING: Cleveland Clinic. PATIENTS: Brain tissue was acquired from 5 patients with secondary progressive multiple sclerosis (MS) and 5 nonneurological controls. INTERVENTION: Magnetic resonance imaging pathological correlations were performed on the 5 cases. Based on imaging characteristics, 30 ROIs were excised. MAIN OUTCOME MEASURE: Using immunohistochemical analysis, we evaluated myelin status, leukocyte accumulation, and CXCR4/CXCL12 expression in the MS ROIs and white matter regions from the 5 nonneurological controls. RESULTS: Eight of 10 T2/T1/MTR regions were chronic active or chronic inactive demyelinated lesions, whereas only 2 of 10 T2-only regions were demyelinated and characterized as active or chronic active lesions. Equivalent numbers of CD68+ leukocytes (the predominant cell type) were present in myelinated T2-only regions as compared with NAWM. Parenchymal T cells were significantly increased in T2/T1/MTR ROIs as compared with T2-only regions and NAWM. Expression of CXCR4 and phospho-CXCR4 were found on reactive microglia and macrophages in T2-only and T2/T1/MTR lesions. CXCL12 immunoreactivity was detected in astrocytes, astrocytic processes, and vascular elements in inflamed MS lesions. CONCLUSIONS: Inflammatory leukocyte accumulation was not increased in myelinated MS ROIs with abnormal T2 signal as compared with NAWM. Robust expression of CXCR4/CXCL12 on inflammatory elements in MS lesions highlights a role of this chemokine/receptor pair in central nervous system inflammation.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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".