Mind the Gaps: Increased Density of Epithelial Gaps Observed in the Terminal Ileum of Patients with Inflammatory Bowel Disease Using Confocal Endomicroscopy
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Bibliographic record
Abstract
Purpose: Epithelial cells within the small intestine undergo shedding resulting in the formation of epithelial gaps (spaces between cells). The cytokine TNF-α has been shown to accelerate this process by 20-fold. Epithelial gaps can be observed within human small and large intestine through the use of confocal endomicroscopy, and increased epithelial gap density within the duodenum has been previously reported in patients with inflammatory bowel disease (IBD). Given the role of TNF-α in the pathogenesis of IBD, we hypothesize that epithelial gap density is increased in the terminal ileum of IBD patients compared to controls. Methods: Probe-based confocal laser endomicroscopy (pCLE) is a new modality which allows in-vivo histopathologic evaluation of the intestinal mucosa. Use of the ColoFlexTM UHD miniprobe (Cellvizio, Mauna Kea Technologies, Paris, France) provides a resolution of 1.4 μm (for comparison, the diameter of a RBC is 7 μm) thus allowing visualization of epithelial cells and gaps. After intravenous injection of 5 mL of 10% fluorescein, pCLE of the terminal ileum of consecutive patients undergoing colonoscopy was performed. Controls were patients undergoing colonoscopy for non-IBD related indications; IBD patients were those with a history of biopsy-proven Crohn's disease or ulcerative colitis. We imaged endoscopically normal mucosa in the terminal ileum, as areas with visible erosions and ulcerations had significant architectural distortions making quantitative analysis of cells and gaps impossible. Over 3000 images were acquired for each patient. Gap density was defined as the number of epithelial gaps found per 1000 cells counted. Results: The experimental cohort consisted of 20 controls (9 males; mean age=51±12 years) and 15 IBD patients (9 males; mean age=39±13 years). Of the 15 IBD patients, 10 had Crohn's disease and 5 had ulcerative colitis. Endoscopically normal terminal ileal mucosa was imaged in both groups. The images were reviewed by two blinded reviewers. A minimu m of 3 confocal images with the highest epithelial gap density were analyzed for each patient; epithelial cells and gaps were manually counted. Gaps were ascertained in at least three different sequential images. The mean gap density (± SD) was 15±2 gaps per 1000 cells counted for controls versus 100 ± 8 gaps/1000 cells counted for IBD patients (p<0.0001). Conclusion: Confocal endomicroscopy revealed significantly increased epithelial gap density in endoscopically normal-appearing terminal ileum of IBD patients as compared to controls.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it