P041 Differences in NOTCH signalling between stricturing and penetrating behaviour in Crohn’s disease
Bibliographic record
Abstract
Fibrosis and fistula development constitute the main complications associated to Crohn’s disease. Notch signalling has been implicated in lung, kidney, liver, and cardiac fibrosis and in various disease conditions such as scleroderma. We aim to analyse here the pattern of NOTCH ligands, receptors, and effectors expression in surgical resections from stenotic and fistulizing CD patients and to determine the potential role of these ligands in favouring fistula and fibrosis. CD patients (n = 41) were categorised according to Montreal classification (age at diagnosis, location, and behaviour). mRNA was isolated from resections of patients presenting a stricturing (B2, n = 26) or a penetrating (B3, n = 15) behaviour or from unaffected mucosa of patients with colorectal cancer (control, n = 15). The expression of Notch ligands, receptors, and effectors (HES1 and MATH1) was determined by RT-PCR or WB. Correlations between data were analysed using Pearson’s correlation coefficient (*p < 0.05). A higher mRNA expression of NOTCH3 and NOTCH4 receptors was detected in CD patients compared with controls; in addition, the expression of these markers was higher in the fistulizing than in the stenotic behaviour (Table 1). The fistulizing group presented a generalised overexpression of NOTCH ligands (JAG2, DLL3, and DLL4) compared with controls and among them, only DLL3 expression was up-regulated in the stenotic group (Table 1). Similar levels of HES1 and MATH1 mRNA expression were detected between different groups while protein levels of HES1 were higher in the fistulising group than in control or stenotic groups (3.4 ± 0.1 A.U*#, 2.8 ± 0.2 A.U and 2.0 ± 0.1 A.U, respectively). The expression of DLL3 significantly correlated with FSP1 (r = 0.77, p = 0.04*), DESMIN (r = 0.80, p = 0.03*), and SNAIL1 (r = 0.59, p < 0.04*), only in intestinal tissue from the fistulizing CD group. Relative mRNA expression of NOTCH ligands and receptors vs. the housekeeping gene β-ACTIN in intestinal mucosa. Significant differences vs. the respective Non-IBD patients are shown by *p < 0.05 or **p < 0.05 and vs. B2 CD patients by #p < 0.05. Activation of the Notch signalling pathway is detected in Crohn’s disease patients presenting a penetrating (B3) behaviour compared with those with a structuring (B2) phenotype and it may be involved in fistula development over fibrosis.
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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 | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".