Abstracts of the 13th International Conference on Cachexia, Sarcopenia and Muscle Wasting, 11‐13 December 2020
Bibliographic record
Abstract
Introduction: The physiologic mechanisms that drive functional changes due to cachexia are poorly understood.Existing cachexia models limit our ability to address these mechanisms because they either express a rare tumour type or cause rapid death.Such models are not amenable to multi-domain functional analysis of rehabilitation protocols, which typically require 6-8 weeks.The goal of this study was to develop and functionally characterize a longitudinal model of cancer-associated cachexia.Methods: The "KPC orthotopic injection" pancreatic cancer mouse model was selected for optimization.We tested multiple cell clones, cell doses, and vehicle types in order to maximize survival.Ex vivo analysis included skeletal and cardiac muscle mass.Functional characterization included: hind-limb grip strength for muscle function; open-field arena for ambulation and anxiety; Y-maze for spatial memory; and Morris Water Maze and Rotarod for endurance.Results: Serial dilution of multiple KPC clones yielded optimal conditions for extending median survival, from 3 weeks up to 8.5 weeks post-injection using the KPC orthotopic model (p < 0.0001).In weekly ex vivo analysis, the optimized model resulted in progressive skeletal and cardiac muscle mass loss at 5 weeks post-injection and continued through 9 weeks (p < 0.01).Starting 5 weeks post-injection, animals had 8% decline in grip strength (p < 0.01) and a sustained decrease in distance ambulated and gait speed of 30-50% (p < 0.05).Animal subjects retained spatial memory similar to controls, indicating that functional deficits were not confounded by behavioural change.There was also a trend towards decreased motor endurance (p = 0.07) at 5 weeks and increased open-field anxiety (p = 0.06) at 8 weeks.Conclusion: This optimized model of cancer-associated cachexia demonstrates progressive loss of muscle and function in multiple domains while accounting for potential confounding factors of cognition and behaviour.The model is tailored for longitudinal studies and sets the stage for mechanistic and translational studies of cachexia rehabilitation.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.170 | 0.086 |
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".