Angiogenesis biomarkers discriminate multiple sclerosis phenotypes
Bibliographic record
Abstract
Abstract Background: Multiple Sclerosis is a neuroinflammatory/neurodegenerative disease characterized by a state of “virtual hypoxia” in the central nervous system. Angiogenesis, one of the main homeostatic responses to hypoxia, has been implicated in the pathophysiology of multiple sclerosis; and angioneurins (angiogenic molecules released by/exerting effects on neural cells) are reported to have conflicting roles in perpetuating or ameliorating disease. This study aimed to determine whether angiogenic molecules are dysregulated in the serum and central nervous system of multiple sclerosis patients. Methods: Serum samples were obtained from 317 multiple sclerosis participants (n=130 with relapsing-remitting multiple sclerosis; n=187 with progressive multiple sclerosis; n=43 controls) followed at the multiple sclerosis clinic in Calgary, Alberta, Canada. A proportion of participants were in trials of domperidone and hydroxychloroquine. Angiogenic factors were measured using the Human Angiogenesis Array & Growth Factor Array® multiplex (Eve Technologies). A meta-analysis of publicly available transcriptomic databases was performed to explore if the differences seen in serum were similar to those within the central nervous system. Results: Several angioneurins were dysregulated in multiple sclerosis serum compared to healthy controls with increased expression of epidermal growth factor (p<0.01) and leptin (p<0.05). Further, multiple sclerosis phenotypes had distinct angiogenic signatures: epidermal growth factor was significantly higher in the sera of relapsing-remitting multiple sclerosis compared to progressive multiple sclerosis (p<0.0001), while endoglin was elevated in primary progressive (p<0.001) and secondary progressive (p<0.01) compared to relapse-remitting multiple sclerosis. Follistatin levels were exclusively higher in primary progressive compared to both relapse-remitting (p<0.001) and secondary progressive (p<0.0001) multiple sclerosis. Distinct angiogenic patterns were observed histologically in lesions and normal appearing brain tissue similar to what is seen in serum, with elevated epidermal growth factor across phenotypes, and elevated endoglin/follistatin in progressive multiple sclerosis lesions. Further, bone morphogenetic protein-9, endoglin, and follistatin were positively correlated with age and disability, while epidermal growth factor was negatively corresponded. Conclusion: Angiogenesis is dysregulated in multiple sclerosis and across phenotypes. Angiogenesis may play complex roles in multiple sclerosis pathophysiology and be a relevant pathway, both in understanding disease mechanisms and as a possible therapeutic target.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".