bluuebunny/crossref_metadata_2025_split huggingface dataset:
P126 Differential granulocyte populations as therapeutic targets in fistula
Authors: Becker M , Koelink P , Buskens C , Wildenberg M 
Published: January 2024

Abstract

Background
Despite the recent increase in therapeutic options in IBD care, treatment of perianal disease and in particular fistula remains highly challenging. Specific targeted medical therapy is not currently available, and a majority of patients fails to respond to surgical intervention. In contrast, cryptoglandular fistula show much higher response rates with closure in up to 80-90% of patients. Interestingly, the most present cell type in fistula, the granulocyte, is also the least studied due to their fragile nature. To fill this void, we evaluated granulocytes in perianal fistula and those present in the blood.

Methods
Curettage material of 18 fistula (Crohn n=15 and cryptoglandular n=5) was obtained and processed by mass cytometry. Two additional samples were obtained (1 Crohn, 1 cryptoglandular) together with matching blood samples and assessed by single cell RNASeq.

Results
As expected, granulocytes formed the majority of all cells in all fistula (mean 64%). Cryptoglandular fistula displayed significantly more granulocytes than Crohn’s related fistula. Single cell analysis showed 4 subsets: Subset 1 was the main subset in blood, and expressed high levels of LAMTOR4. Interestingly, although found both in blood and fistula, abundance was much higher in blood (80 vs 10%) and signaling cascades differed. In blood, activity was associated with degranulation, IL8 activity and migration. In fistula, a very strong IFNa/b signature was present. Subset 2 expressed high MMP9, and showed degranulating activity. Subsets 3 and 4 were almost exclusively found in the fistula tracts, and were defined by expression of PI3 and LRG1 respectively. Pathway analysis showed the PI3+ population to have strong cytokine signaling but little degranulating or migratory activity. Conversely, the LRG1+ population showed little cytokine activity, but stronger degranulating activity and integrin signaling. The two populations also expressed distinctive chemokine receptors, with PI3+ cells expressing high levels of CXCR4, while LRG1+ express CXC1 and CXCR2, suggesting differntial recruiment and potential modulation. In that light, it is interesting to note the proportion of PI3+ and LRG1+ cells differed between patients, with the majority of Crohn derived cells being PI3+ while the cryptoglandular fistula mainly contained LRG1+ cells.

Conclusion
Granulocytes form the main cellular component of fistula tracts in both Crohn and cryptoglandular fistula. Four different subsets of granulocytes could be identified, of which the two main subtypes in fistula tracts appear to differ significantly both in phenotype, activity and method of recruitment. This data may be a starting point for specific interventions in this highly abundant but often overlooked cell type.
P134 Characterization for the similarity assessment between proposed biosimilar SB17 and ustekinumab reference product using state-of-the-art analytical method
Authors: Yang S Y , Lee C , Hwang K , Lee J , Lee J , Hong J , Jung S 
Published: January 2024

Abstract

Background
SB17 is being developed as a proposed biosimilar to ustekinumab reference product (RP), a human monoclonal antibody (IgG1 kappa immunoglobulin) that binds to the common p40 subunit of cytokines interleukin (IL)-23 and IL-12. Binding to this subunit prevents interaction with their receptor, resulting in modulation the immune system responses which play a key role in the inflammatory disease. The objective of this study was to demonstrate structural, physicochemical, and biological similarity between ustekinumab RP and SB17 using various state-of-the-art analytical methods.

Methods
Comprehensive analytical characterization was conducted with side-by-side comparison of SB17 with the EU and US ustekinumab RP using various analytical methods. Comparisons included purity, product-related impurity, charge heterogeneity, primary structure, post-translational modification, higher order structure, quantity, Fab-related biological activities (potency and binding activity), and Fc-related biological activities.

Results
Based on the analytical similarity assessment, the structural, physicochemical, and biological characterization results demonstrated that SB17 is highly similar to the EU and US ustekinumab RP. In the structural aspects, it was confirmed that there is no clinically meaningful difference between post-translational modification profiles and higher order structures of SB17 compared to the ustekinumab RP. Product-related impurities in the form of aggregates were also confirmed to be similar. SB17 has a lower of acidic and basic peaks compared with ustekinumab RP, due to the difference in producing cell line. Ustekinumab RP is expressed in an Sp2/0 cell line, whereas SB17 is expressed in CHO cell line. However, the difference between SB17 and ustekinumab RP in the charge variants is not considered clinically meaningful since equivalent biological activity was observed. In case of mechanism of action (MoA)-related biological activities, SB17 is highly similar to the EU and US ustekinumab RP with respect to overall critical and non-critical quality attributes analyzed. Moreover, similarity or lack of activity in Fc-related biological activities was also confirmed. Based on these results, SB17 is expected to have highly similar safety and efficacy as compared to ustekinumab RP.

Conclusion
In summary, the overall analytical characterization and similarity assessment results show that SB17 is highly similar to the EU and US ustekinumab RP in terms of structural, physicochemical, biophysical, biological attributes.
P158 Expression of IL-19 and IL-24 in intestinal mucosa of inflammatory bowel disease: An immunohistochemical study
Authors: Toskas A , Milias S , Papamitsou T , Meditskou S , Dellis G , Sioga A 
Published: January 2024

Abstract

Background
Interleukins are considered as targets for future inflammatory bowel disease ( IBD) treatments. IL-19 and IL-24 are members of IL-10 family and through the JAK-STAT pathway induce proinflammatory cytokine production. A retrospective single center study was performed to study the IL-19 and IL-24 expression in 121 patients with moderate to severe IBD, before and after treatment with biologics.

Methods
A retrospective study of 121 patients with moderate to severe IBD was performed using immunochemistry between 1999 and 2017. This study included 72 patients with Crohn's disease (CD), 49 with Ulcerative Colitis (UC) and 20 healthy controls. The age, gender, disease extent, severity and treatment choice were recorded. Endoscopy reports before and after 12 months of treatment were retrieved. Intestinal biopsy samples were retrieved from the Histopathology Lab before and 1 year after treatment with biologics. A signed consent was received from all the patients involved and the study was approved by the Bioethics Committee of Aristotle University of Thessaloniki.
The histological specimen were stained for IL-19 and IL-24 before and one year after treatment with biologics. The results were analysed using SPSS for each of the IBD groups (CD, UC) and further to subgroups depending the biologic treatment they received, anti-Tumor Necrosis Factor alpha(anti-TNFa), Vedolizumab (VDZ), Ustekinumab (USK).

Results
A statistically significant increase was found in IL-19 and IL-24 patients in IBD patients versus healthy controls (P&lt;0.05). On the biologics treated group and the anti-TNFa subgroup, there was statistically significant increase in IL-24 expression post treatment (P&lt;0.01). In UC patients, the IL-24 expression was significantly increased after a successful treatment in relation with Mayo score ( P&lt;0.01). On the CD group, a reverse statistically significant correlation was found between the pre-treatment IL-19 expression and the Harvey Bradshaw Index (H.B.I.) score reduction in the anti-TNFa and the VDZ subgroups (p&lt;0.05).

Conclusion
A possibly proinflammatory role of IL-19 was found on the CD group. This can be used as a tool in the future to assess the disease activity and support the diagnosis as a diagnostic biomarker, as IL-19 was found normal in healthy controls. An anti-inflammatory role of IL-24 was found especially in the UC group and in relation with the activity index score post-treatment. This can be used potentially as a marker of response to treatment in active UC, assisting the clinical management. Further research is needed to delineate the exact role of these interleukins in intestinal inflammation.
P178 Changes in composition and structure of ileal mucus in Crohn’s disease patients compared to healthy controls
Authors: Kramer C , Rulff H , Kuppe A , Addante A , Fentker K , Ziegler J , Bischoff P , Gradzielski M , Mertins P , Mall M , Glauben R , Siegmund B 
Published: January 2024

Abstract

Background
Crohn’s disease (CD) is a chronic transmural disease that can affect any part of the gastrointestinal tract. Typically, the terminal ileum is impacted. The pathogenesis of this disease results from a complicated interaction of multiple factors, with the intestinal barrier playing a critical role. The intestinal barrier in the ileum is comprised of epithelial cells that are coated with a mucus layer. This barrier is permeable to nutrient absorption and microbiota. Detailed analyses of human ileal mucus are currently absent. Our study aimed to comprehend the function of mucus and the biophysical and biochemical stimuli that exist in the mucus layer during ileal inflammation, in contrast to the healthy state.

Methods
We enrolled 28 patients diagnosed with Crohn’s disease (CD) and 27 healthy individuals as part of our study. Mucus and biopsies from the terminal ileum were collected during a colonoscopy. The extent of clinical, endoscopic and histologic inflammation in the terminal ileum at the time of collection was evaluated using the Harvey-Bradshaw Index, Simple Endoscopic Score, and modified Naini and Cortina score. The disease trajectory and dietary behaviors of all patients and healthy controls were documented. Samples were processed following protocols for various analyses, including rheology, proteomics and scanning electron microscopy (SEM).

Results
Our study presents the first data on the rheology and viscoelastic properties, of human ileal mucus. Interestingly, we discovered notable variations in the viscoelastic properties of mucus in CD patients compared to healthy individuals. Furthermore, the mucus mesh size and structure differed in CD patients in comparison to healthy controls. The SEM pictures also displayed these quantitative changes. We further assessed clinical characteristics, encompassing duration of disease, and observed certain variations, although their significance is not yet statistically established.
A distinct profile was detected in CD patients compared to healthy controls using proteomic analysis. The ileal mucus of CD patients demonstrated elevated levels of ITGB2 and S100 proteins, which are involved in inflammatory pathways. Moreover, a correlation was found with histologic inflammation at the time of the collection.

Conclusion
In our study, significant changes in mucus composition and structure were found in the terminal ileum of CD patients, compared to healthy controls. This preliminary analysis provides a basis for further investigations to establish correlations between mucus composition and viscoelastic properties, and the subsequent effects on the underlying epithelial barrier.
P183 Therapeutic Effects of Curcumin and Ginsenoside Combination in a Animal Model of Radiation Proctitis
Authors: Kim S E , Kim M S , Lee R A , Yang S J , Lim H , Lee T Y , Woo S Y 
Published: January 2024

Abstract

Background
Although various preventive and therapeutic modalities have been proposed to manage radiation-induced proctitis, there are no universally accepted preventive measures for effective treatment. This study aimed to investigate using an animal model whether the combination of curcumin and ginsenoside could be an effective treatment or preventive agent for progressive rectal inflammation caused by radiation.

Methods
C57BL/6 mice were exposed to gamma irradiation at 27 Gy (3 Gy/min) in the lower abdominal (rectal) region, establishing an animal model with acute radiation proctitis. A combination hydrogel containing 5 mM curcumin and 1 mM ginsenoside Rh1 was prepared and administered into the inflammed rectum of the murine model. This administration was repeated every 2 to 3 days after radiation exposure for a total of 6 times. Two weeks after radiation exposure, the mice were sacrificed to obtain the irradiated tissue samples. The histological and molecular evaluations were performed using H&E staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis, Proliferating Cell Nuclear Antigen (PCNA) staining, immunohistochemistry, and qPCR.

Results
The murine group treated with the combination hydrogel of curcumin and ginsenoside showed significant restoration of the damaged rectal mucosa induced by radiation, including recovery of the mucosal layer and villi, mitigation of epithelial loss, and repair of crypt damage, compared to control group. Additionally, at the cellular level, a comparative analysis of apoptosis and proliferation within the tissues through TUNEL and PCNA staining demonstrated the combination hydrogel not only significantly inhibited cell death but also significantly increased cell proliferation. The gene expression of inflammatory cytokines in rectal tissue, including IL-6 and IFN-γ was significantly decreased in the treatment group. The infiltration of immune cells including T cells (CD4) and macrophages (CD68), which are important components in the pathogenesis of radiation proctitis, as shown by immunohistochemistry of tissue samples, was significantly reduced in the treatment group compared to the control group.

Conclusion
These promising results suggest that the combination of curcumin and ginsenosides has therapeutic potential for the management of radiation proctitis and provide valuable insights into new therapeutic strategies in clinical applications.
P185 Food avoidance and dietary restrictions in patients with Inflammatory Bowel Disease
Authors: Norman E , Hoque S 
Published: January 2024

Abstract

Background
Nutrition has a key role in IBD, more so in Crohn’s disease (CD) than ulcerative colitis (UC) and studies have shown that patients restrict or avoid certain dietary items; not necessarily due to medical advice. This could be detrimental to nutritional status by causing weight loss, disordered eating and nutritional deficiencies.

Methods
An online survey was carried out amongst IBD patients attending a teaching hospital in an urban area in the UK. Ten questions were asked and the survey was sent to 100 patients with their consent.

Results
The total survey response rate was 38%. Only 8% of patients had a long diagnosis due to diagnosis when a child, and although all restricted their diet still, this did not seem to show significance (p = 0.597). There was no significant difference between IBD type and whether the patient restricted their diet or not (p = 0.107). Notably, we did find that the most common reason for avoiding dietary items was patients ‘feel it helps symptoms’ (less so the ‘advised by clinician’ choice), however there was no significant difference between types of IBD and dietary exclusion reasons (p = 0.721). The most common dietary avoidances were spicy foods, followed by caffeine and fibre. There was a significant difference between CD and UC patients and the dietary groups they limited (p = 0.006), with there being a difference between CD and UC patients specifically for fibre (p = 0.027), for gluten/wheat (p = 0.0002) and for dairy (p = 0.077), however the latter did not reach significance. Of note, there is no difference in how long patients avoided dietary items, showing restriction is widespread irrespective of disease status (active or in remission).

Conclusion
Our survey indicates that food avoidance is commonplace among IBD patients, and the common foods avoided are spicy foods, caffeine and fibre, more so with CD than UC. These appear self-induced without medical advice, and this could have a detrimental impact on nutritional status. This is important information which merits further studies, perhaps with a larger sample size.
P208 Personalized Machine Learning Algorithm to Predict Ulcerative Colitis Disease Activity from Wearable Data
Authors: Saleh A , Abraham B 
Published: January 2024

Abstract

Background
Due to its ease of use and ability to determine complex information, wearables have been gaining popularity over the last decade. Smart rings such as OuraTM present the ability to track metrics such as sleep quality, resting heart rate, body temperature, and daily activity. This is not only useful for the predicting disease activity in inflammatory bowel disease (IBD), but also to understand behavior changes that can be associated with disease activity. This study aimed to evaluate potential use for wearable data in IBD management.

Methods
Daily OuraTM ring data of a patient with ulcerative colitis (UC) was collected from OuraTM ring application programming interface from 2019 to 2023. Days were classified as “active disease” or “remission” based on patient symptoms, colonoscopies, and fecal calprotectin levels. Data was collected on the patient’s sleep metrics, activity levels, and daily vitals. Variables with &gt;50% null values were not included in model training. A univariate analysis was conducted to determine features that correlated with flaring periods (p-value &lt;0.3) [ABPM1] [AS2] to be included in model training. An XGBoost classifier was selected with the target variable being flare status. Boosting parameters were then hypertuned to optimize model performance. After hypertuning and kfold cross-validation, the model’s mean accuracy, mean logarithmic loss, and AUC was reported. Further analysis was conducted comparing remission, active disease and pre-diagnosis data.

Results
963 days were collected. 444 days were determined to be “flare” based on reported symptoms, 4 fecal calprotectin levels, 2 colonoscopies, and 1 intestinal ultrasound confirming disease activity. Remission was determined by no reported symptoms, 2 normal fecal calprotectin levels and a normal intestinal ultrasound. Generally, worse sleep quality, increased resting heart rate, increased respiratory rate, and deviations in activity levels were positively associated with disease activity. After model training with XGBoost classifier and 10-fold stratified cross-validation, the mean accuracy was 0.92 ± 0.08, mean logarithmic loss of 0.134 ± 0.11, and a mean AUC was 0.94 ± 0.02. The patient’s mean biometric values such as heart rate and respiratory appeared to recover to pre-diagnosis levels with the exception of heart rate.

Conclusion
Data from the OuraTM ring demonstrated the potential application of wearables in IBD management in a single patient with UC. The high accuracy and AUC of our XGBoost model demonstrates how individualized wearable data can be used to predict IBD flares. Prospective studies with multiple patients could be useful to consider wearables as an additional adjunct disease monitoring device in IBD.
P212 Evaluation of the accuracy of MR-Enterography and CT-Enterography in the preoperative measurement of small bowel segments affected by Crohn's Disease: a single center experience
Authors: Sacchetti F , Larosa L , Minordi L M , Balzano D , Caprino P , Pastena D , Pugliese D , Scaldaferri F , Sofo L 
Published: January 2024

Abstract

Background
The surgical treatment of Crohn's Disease (CD) must deal with heterogeneous intra-operative scenarios, multiple disease locations and the risk of short bowel syndrome related to repeated surgery. A precise preoperative assessment of the exact extension of the disease is essential to avoid extensive surgeries and to plan the best strategy.
The aim of our study is to evaluate the accuracy of the pre-operative radiological assessment for predicting the intra-operative measurement of the affected bowel.

Methods
Consecutive patients underwent either first or repeated surgeries for ileocecal or ileal CD from November 2017 to April 2023 with an available preoperative radiological assessment trough (at most 3 months before) MR-Enterography (MR-E) or CT-Enterography (CT-E) were retrospectively included. Radiological examinations were performed according to standard protocols and each of them was independently reviewed by two experienced radiologists and the length of pathological small bowel segments were measured using a vessel analysis software. Radiological measurements were compared, using Pearson correlation coefficient, with those acquired by a single surgeon intra-operatively on the still vascularized pathologic small bowel segment.

Results
We included 81 patients (44% male), with a median age of 42 years [range 18-81], undergoing first (92%) or repeated surgery for fistulizing (34%) or stenosing CD.
The median length of radiological measurements was 27 cm [range 3-205] while the median length of intra-operative measurements was 30 cm [range 5-165].
Pearson correlation coefficient was used to analyze the variation between the measurements and there was a statistically significant positive correlation between radiological measurements and intra-operative in-vivo small bowel lenght (r2 = 0.962; p &lt; 0.01).

Conclusion
MR-E and CT-E allow precise and accurate measurements of the extent and location of intestinal tracts involved by CD. Such information is extremely important to properly plan the surgical strategy and to be able to quantify the risk of short bowel syndrome in cases of extensive disease or repeated surgery.