Bibliographic record
Abstract
Background and Objective(s): Current research into the mechanism by which abnormal neurologic input results in muscular dysfunction in cerebral palsy (CP) is limited by the available human muscle samples (clustered in ages 9-12).To allow for a mechanistic evaluation of this disease process, we aimed to develop a surgically-induced mouse model of CP and validate this model for its associated muscle changes. Study Participants & Setting:Wild type (WT) C57BL/6 5day old mouse pups (perinatal human equivalent age) were included for study.Materials/Methods: We surgically-induced a hypoxic/ischemic injury in WT mice.Through a midline neck incision, bilateral carotid arteries were temporarily occluded utilizing smooth venous hemostatic clips (5 min).Control mice received anesthesia and a midline "sham" incision only.CP mice were subsequently placed in a hypoxia chamber (8% O2) (20min).Rear grip-strength was tested at 40 days of age (peri-adolescent equivalent age) to demonstrate analogous physical decline.Mice were sacrificed and hindlimb muscle samples were interrogated for analogous structural and compositional alterations (muscle fiber cross-sectional area, relative satellite cell abundance, collagen I and laminin content).Results: Eight CP mice and 10 WT mice were included for study.Hind-limb grip strength was significantly reduced in CP mice compared to WT (1.22 vs 0.90 grams of force, p = 0.0165).Hamstring -a muscle classically affected by spasticity -samples were compared between groups.There was no significant difference in myofiber cross-sectional area comparing CP to WT (1596.60 vs 1278.77μm 2 , p = 0.07).However, there was a significant decrease in satellite cell ratio in CP samples (0.041 vs 0.059, p = 0.01).Collagen I content was increased in CP (1.29 vs 1.0 mean G integration, p = 0.02), as was laminin content (1.78 vs 1.0, p = 0.001).Conclusions/Significance: Initial testing of this surgicallyinduced small-animal model of CP demonstrates clinical decline and muscular pathology analogous to what has been demonstrates in human CP skeletal muscle, making this model the first small-animal model validated for CP-associated muscular pathology.The validation of this model allows for exploration into the timing and mechanism by which CP muscle deviates from healthy muscle's developmental trajectory, is fundamental for testing the efficacy of established therapeutic interventions, surgeries, and spasticity control and is requisite to the safe development and testing of biological treatments that could potentially rebuild strength, prevent contracture and restore function to this patient population.
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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 | 0.002 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.009 | 0.004 |
| Open science | 0.003 | 0.005 |
| Research integrity | 0.004 | 0.002 |
| Insufficient payload (model declined to judge) | 0.844 | 0.781 |
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; the direct Gemma label and the distilled Codex classifier agree on what is shown here.
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".