A79 CHARACTERIZATION OF VIPOMA-MEDIATED INTESTINAL EPITHELIAL CELL SECRETION
Bibliographic record
Abstract
A 3-year old female with a history of chronic watery diarrhea was diagnosed with a suprarenal vasoactive intestinal peptide (VIP)-secreting neuroblastoma (‘VIPoma’). Neuroblastomas are one of the most common malignancies in children aged 0–5 years, while VIP is a gastrointestinal neuropeptide that can act upon epithelial cells, neurons, and immune cells. Secretory diarrhea and hypokalemia are classic symptoms of a VIPoma, however the precise mechanism remains unknown. To define in the pathway of VIP-mediated ion secretion using intestinal organoids. Prior to diagnosis, supplemental KCl was given (3 mmol/kg) to address the low potassium. Following this, serum and stool samples were collected daily for 8 days to measure electrolyte (Na+, K+, Cl-) levels and stool osmolal gap. Intestinal organoids were cultured from a sigmoid colon biopsy of a non-inflamed control patient. Organoids were labelled with calcein AM dye and assessed every 12 min for 1–2 hrs by microscopy, with luminal ion secretion assessed by the increase in organoid size over time. The patient’s serum potassium levels were consistently below the normal range and the stool osmolal gap was <50 mmol/L (indicative of secretory diarrhea). Supplemental KCl increased [K+] in the blood but failed to improve the diarrhea. VIP levels at the time of diagnosis were 7.3X above the upper limit of the normal range. To test this in vitro, VIP was applied to intestinal organoids in vitro; concentrations above the normal range (10-10 and 10–9 M) but not within the normal limits (10–11 M) induced a swelling response in normal human enteroids. This swelling was completely abolished in isotonic K+-deficient buffer, and dependent on Ca+ for maximal effect. The use of the non-specific potassium channel blocker tetraethylammonium chloride (TEA; 1–10 mM) did not significantly reduce the organoid swelling response when applied 30 min prior to VIP stimulation. Increased intake of potassium improved serum [K+] levels but did not relieve the diarrheal symptoms. A significant swelling response occurs in intestinal organoids when stimulated with VIP in the absence of a neural or immune network. More studies are needed to further characterize the signalling pathway and ion channels through which this secretory response occurs in the intestinal epithelium. CIHRHelmsley Charitable Trust
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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".