Examining the Utility of a Catalytic Antioxidant in Islet Transplantation.
Bibliographic record
Abstract
Islet transplantation has been demonstrated as an effective modality to treat type-1 diabetes. However, long-term function has been limited, in part to the availability of viable donor pancreata. Oxidative stress is a mechanism associated with disease states marked by inflammatory processes including islet graft dysfunction. The ability to modulate redox reactions within a cell may control signaling cascades necessary for generating inflammation, providing therapeutic targets to down regulate immune function. Catalytic antioxidants (CA) scavenge a broad range of oxidants, decreasing the production of free radicals and inflammatory cytokines. This may have a positive impact on islet function post-transplant and reduce the prevalence of primary non-function, increasing the incidences of insulin independence from single islet infusions. We hypothesize that CA may allow for the utilization of islets isolated from donation-after cardiac death (DCD) donors, increasing the number of patients that can receive an islet transplant. We established a DCD islet transplantation model in diabetic mice, where islets harvested in the presence of vehicle (Control) or CA during organ procurement and islet isolation. Islet yields for control and CA treated pancreata were 42.9±5.8 and 45.9±9.0 islets per pancreas, respectively, which varied from a non-DCD islet yield of 170±31.3. In a syngeneic, marginal islet mass transplant model, approximately 60% of recipients returned to euglycemia when transplanted with CA-harvested islets, as compared to approximately 40% of control mice. CA recipients established a mean euglycemic restoration time of 15.5±7.2days, while controls restored in 33.3±8.7days. Glucose tolerance tests performed 60days post-islet transplant revealed an impaired glucose response in control animals, while this effect was ameliorated in CA recipients. Interestingly, this response mirrored that exhibited by non-DCD control animals. Altogether, these results suggest that the use of CA in a DCD islet isolation and transplantation model may play a critical role in improving islet function, with the prospect of increasing organ donor availability.Figure: No Caption available.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.001 |
| 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".