bluuebunny/crossref_metadata_2025_split huggingface dataset:
P151 Characterization of platelet activation profile in Inflammatory Bowel Disease
Authors: Rueda Garcia J L , Martín Arranz E , Ramírez García L , Suárez Ferrer C , Sánchez Azofra M , Poza Cordón J , Amiama Roig C , Noci Belda J , Perosanz L , Cubillo García C , García-Rojas C , Silva K , Monzón Manzano E , Arias-Salgado E G , Acuña P , Butta N , Martín Arranz M D 
Published: January 2024

Abstract

Background
Platelet-related markers associated with a procoagulant state have been described for Immune-mediated Inflammatory Diseases (IMIDs), but a broader profiling of these abnormalities in Inflammatory Bowel Disease (IBD) is lacking.

Methods
Cross-sectional study to describe and compare platelet biomarkers of IBD outpatients, both Crohn’s Disease (CD) and Ulcerative Colitis (UC), vs healthy controls (HC).
Patients over 18 years old with a diagnosis of CD or UC according to the European Crohn’s and Colitis Organization (ECCO) criteria were included. Fecal calproctectin (Fcal) &gt;=150ug/g was used as a cutoff level for active disease. Exclusion criteria for IBD patients are listed under Table 1.
Fibrinogen (FBG) receptor on platelet’s surface was determined with anti-CD41 and anti-CD61 monoclonal antibodies (mAbs); and von Willebrand factor receptor with anti-CD42a and anti-CD42b mAbs.
Platelet activation markers [TRAP and ADP-induced activation of fibrinogen (FBG) receptor, and P-selectin (Psel) and CD63 exposure] were determined, respectively, through binding of PAC1, anti-P-selectin and anti-CD63 (mAbs).
All variables were determined by flow cytometry.

Results
55 patients (27 CD, 28 UC) and 75 HC have been included. 43 IBD patients had active disease (21 CD, 22 UC). Complete baseline characteristics of the IBD population are described in Table 1.
Basal Psel (% of positive cells) was increased in CD vs UC (median [IQR]: 5.64 [4,4-10,4] vs 2,9 [1,8-6,8], p=0,02) and vs HC (3,5 [1,4-6,8], p=0,008). ADP-induced Psel was increased in CD vs HC (mean, SD: 49.92, SD 12.75 vs 41.943, SD13.15, p=0,007). Basal CD63 (% of positive cells) was significantly higher in active IBD vs HC (W = 1143, p = 0.02) and inactive IBD vs HC (W = 528, p= 0.006). CD42a (% of positive cells) was decreased in IBD vs HC (W = 1128.00, p=0.007) and CD vs HC (W = 777.00, p =0.04). CD42b (% of positive cells) was also decreased in IBD vs HC (mean, SD: 106.9 SD, 17.32 vs 115.7, SD 28.42, p=0,01) and CD vs HC (104.06 SD 14.49, p=0,03). No differences in basal or TRAP/ADP induced PAC binding, and in CD41 or CD61 expression were observed among groups. Multiple linear regression showed association of Fcal with basal Psel in IBD patients (p=0,02); and Spearman’s correlation showed negative moderate correlation between Fcal and basal Psel (r=0,3; p=0,003)

Conclusion
Features of platelets in IBD suggest increased platelet degranulation and reduced vWF receptor with regards to healthy controls, specially in CD, but no differences in FBG-related receptors. Inverse moderate correlation between Fcal and Psel in IBD patients suggests depletion of intra-platelet granules at higher levels of gut inflammation.
P154 Histological disease progression and ALK5i therapeutic efficacy in a chronic DSS-induced mouse model of IBD with intestinal fibrosis
Authors: Nielsen M H , Zachariassen L , Sárvári A K , Madsen M R , Hansen H B , Fink L N , Fuchs B C , Papazyan R , Aymeric R , Feigh M 
Published: January 2024

Abstract

Background
Inflammatory bowel disease (IBD) comprises a group of intestinal disorders, including ulcerative colitis and Crohn's disease. Intestinal fibrosis, as a result of chronic inflammation, is a common complication in IBD. Many patients do not respond or do not have a sustained response to existing treatments, highlighting the large unmet need for more effective drugs in the management of IBD. Translational animal models demonstrating chronic, progressive colonic fibrosis are important tools in preclinical drug discovery for IBD. The aim of the present study was to characterize histological disease progression and therapeutic efficacy of a TGF-β type I receptor inhibitor (ALK5i) in a novel chronic DSS-induced mouse model of IBD.

Methods
10 week old male C57BL/6JRj mice received 3 cycles of DSS (2% w/v) administration in the drinking water (DSS-IBD) or normal water (CTRL). Study groups were terminated at week 1, 3 or 6. Groups terminated at week 6 received twice daily oral dosing with vehicle or ALK5i (30 mg/kg, BID). Terminal endpoints included distal colon morphometry, quantitative histological markers of inflammation and fibrosis as well as colon transcriptomics.

Results
Compared to healthy controls, the chronic DSS-IBD mouse model demonstrated clinical and histological hallmarks of progressive IBD, including mild-to-moderate weight loss, colonic hypertrophy with sustained inflammation and fibrosis in the mucosa and submucosa areas. ALK5i treatment increased colon weight/length ratio while significantly reducing fractional (%) area of alpha-1 type I collagen in the colonic mucosa and submucosa. The histopathological phenotype was supported by corresponding regulations in gene expression markers of colonic inflammation including ptprc (cd45), tnf and nos2. Alk5i therapy did not influence gene expression markers of fibrosis, suggesting that improved relative (%) levels of collagen were driven by Alk5i-stimulated tissue volume increases. Further studies are needed to establish if TGF-beta inhibitors have antifibrotic effects in the chronic DSS model of IBD complicated by fibrosis.

Conclusion
The DSS-IBD mouse model is a preclinical model with features of progressive IBD suitable for testing novel anti-fibrotic drug therapies targeted for IBD patients.
P161 The use of Novel Natural Treatments for Inflammatory Bowel Diseases
Authors: Najafzadeh M , Najafzadeh Mojgan , Adoul Zahra , Jafarinejad Shohreh , Baumgartner Adi , Reynolds Domenic , Isreb Mohammad , Ghaderi Rojan , Sefat Farshid , Heidari Saeed , Anderson Diana 
Published: January 2024

Abstract

Background
Background: Free radicals and reduced antioxidant levels lead to oxidative stress, which plays a role in causing Inflammatory Bowel Disease (IBD). IBD is a chronic gastrointestinal autoimmune condition that involves an abnormal immune response. This includes Crohn's disease (CD) and ulcerative colitis (UC). In the previous studies, we demonstrated the antioxidant effect of Inonotus obliquus (IO) and flavonoids such as quercetin and epicatechin on lymphocytes from IBD patients. In vitro studies have shown that Chaga extract is effective in reducing oxidative stress in lymphocytes of both healthy individuals and those with IBD. This suggests that Chaga extract may be a useful supplement for anyone looking to inhibit oxidative stress.

Methods
Methods: In our current study, Cord Blood Stem Cells -derived Exosomes (CBSC Exo) and their synthesised miRNAs were investigated as antioxidant/anti-inflammatory elements on lymphocytes and 3D intestinal epithelial model. There were seven miRNAs found in CBSCs Exo, and among them were two miRNAs that were identified as novel. The Peripheral Blood Monocyte Cells (PBMCs) from IBD patients and healthy individuals after challenging with H2O2 or Interleukin 6 were treated with CBSCs Exo, transfected with miRNA novels or both. The treatment method also was applied to the EpiltestinalTK 3D model from Mattek. Various techniques were utilised, including the Comet assay, Fast Microplate DNA damage assay, and CCK8.

Results
The findings of the study indicate that the administration of CBSC-derived Exo, Let-7c-mimic miRNA, Let7bSb miRNA, as well as Novel 1 and Novel 2 miRNAs on the 3D model intestine, significantly decreased the level of DNA damage when compared to the positive control H2O2 and IL6, as well as the untreated samples.

Conclusion
Conclusions: In conclusion, certain natural substances like flavonoids, Inonotus obliquus, and exosomes derived from CBSCs may have an advantage in decreasing significantly oxidative stress and DNA damage in IBD Peripheral Blood Mononuclear Cells (PBMCs) and inflamed intestinal 3D models.
P167 Remodelling of the colonic molecular landscape in patients failing anti-TNF therapy highlights dysregulation of the extracellular matrix in ulcerative colitis
Authors: Cozzetto D , Thomas J , Saifuddin A , Powell N 
Published: January 2024

Abstract

Background
In patients with ulcerative colitis (UC) who previously failed anti-TNF therapy, subsequent treatment with other advanced therapies is generally less effective than they are in anti-TNF naïve patients. Since anti-TNF drugs are frequently used first-line in UC, drug sequencing depreciation poses a major clinical challenge. To understand potential underlying mechanisms, we compared the clinical and molecular phenotype of UC patients who failed anti-TNF therapy with those who were anti-TNF naïve.

Methods
Clinical information and mucosal gene expression profiles were collected from 262 anti-TNF naïve and 275 anti-TNF exposed individuals with moderate to severe UC enrolled in the UNIFI clinical trial programme. We assessed differences between the groups in terms of clinical parameters, gene expression levels, pathway and transcription factor activity, as well as cellular composition.

Results
Anti-TNF exposed patients had significantly increased disease duration (p=0. 000009), CRP (p=0.03), and histological severity[PN1] (p=0.002). After adjusting for these factors, we identified 1,592 genes differentially expressed (FDR &lt; 0.05), although the expression changes were quite modest. Pathway analysis linked previous anti-TNF exposure to significant downregulation of TNF and NFkB signalling and up-regulation of extracellular matrix components, stroma-related signatures, and growth factor receptor (EGFR, MAPK, PI3K) and TGFb signalling. These data were in line with results from cellular deconvolution methods, which showed an increase in stromal cell abundance and T cell depletion following anti-TNF failure. Gene regulatory network inference suggested that the observed gene expression differences were driven by increased activity of many transcriptional regulators, including those downstream of RUNX1 and RUNX3.

Conclusion
In patients with active UC, prior anti-TNF failure is associated with molecular remodelling of the colon characterised by dysregulated ECM organisation and shifts in stromal compartments. These data provide new insights into potential mechanisms of drug sequencing depreciation and could inform novel strategies to overcome this challenging clinical phenomenon.
P170 SLC7A5 promotes the progression of Ulcerative Colitis by regulating amino acid transport and intestinal epithelial autophagy
Authors: Shi Y , Wang F , Hou L , Zhou H , Wu T , Li R , Li X , Liu X , Fan Z , Zhang T , Da Y , Liang J 
Published: January 2024

Abstract

Background
IBD has become a common chronic intestinal disease in China. Considering the important role of amino acid metabolism in inflammatory diseases, inhibition amino acid metabolism of inflammatory sites may be effective in alleviating UC (ulcerative colitis). SLC7A5 is involved in the progression of UC, but the mechanism of its functional regulation still needs to be investigated. In this study, we aimed to clarify the link among SLC7A5 expression in UC, mTOR pathway activation and immunoregulation.

Methods
We previously discovered through high-throughput screening that SLC7A5, as a cellular amino acid transport carrier, is significantly elevated in the colonic tissues of UC patients; in vivo experiments have demonstrated for the first time that JPH203, a specific inhibitor of SLC7A5, alleviates DSS-induced intestinal inflammation and inhibits mTOR pathway activation to promote intestinal autophagy. This study utilized model animals, transcriptomics, amino acid-targeted metabolomics assays, and macro-genome sequencing to elucidate the mechanism of SLC7A5-regulated amino acids in mTOR pathway activation and intestinal autophagy dysfunction.

Results
SLC7A5 expression is increased in the colon of UC patients and DSS-induced mice lesions. SLC7A5 inhibitor (JPH203) restrained the inflammatory responses induced by DSS. SLC7A5 deletion or inhibition dampens the release of IL-1β, IL-18, and IL-23 and the production of ROS in the LPS-induced FHC and RAW264.7 cells. Moreover, upregulating SLC7A5 expression induces mTOR signaling pathway activation in FHC cells. Deletion or inhibition of SLC7A5 efficiently blocks the SLC7A5-dependent amino acid transport, inhibits the mTOR activation, and results in the activation of autophagy.

Conclusion
Targeting SLC7A5-mediated amino acid uptake is a potentially useful immunosuppressive strategy to regulate colonic inflammation through mTOR pathway and autophagy. This study is expected to reveal the intrinsic factors of metabolic disorders promoting the UC progression from the perspective of amino acid metabolism, and to lay a new theoretical and experimental foundation for potential UC treatment.
P171 Rescuing Intestinal Stem Cells via TMEM219 inhibition promotes mucosal healing in Crohn’s disease
Authors: D'Addio F , Canducci F , Marin V , Assi E , Maestroni A , Nardini M , Petrazzuolo A , Loretelli C , Usuelli V , Moufida B N , Sampietro G , Ardizzone S , Fiorina P 
Published: January 2024

Abstract

Background
Intestinal mucosa regeneration is disrupted in inflammatory bowel disease as Chron’s disease, but whether this relies on a defect in intestinal stem cells remains to be established.

Methods
Transcriptome and receptome profile in Crohn’s disease bioptic samples demonstrated a defect in intestinal stem cells (ISCs). The TMEM219 knockout mouse, in which TMEM219 expression is abrogated on ISCs was tested in dextran sulfate sodium (DSS) acute colitis model. DSS-induced chronic colitis was also used to confirm in vivo relevance for TMEM219 blockade in mucosal recovery.

Results
An increased intestinal stem cells death and dysfunction in colonic samples obtained from patients with Crohn’s disease was observed, which is controlled through the death factor TMEM219. Based on a receptome analysis, we documented large alterations in the expression of the death receptor TMEM219 in patients with Crohn’s disease, particularly in those with refractory disease and/or non responders to conventional therapy, which were paralleled by altered peripheral levels of the TMEM219 ligand, insulin-like growth factor binding protein 3 (IGFBP3). Pharmacological blockade of the IGFBP3/TMEM219 axis restored the self-renewal abilities of mini-guts generated from patients with Crohn’s disease in vitro, ameliorated DSS-induced colitis in vivo and favored mucosal healing. Genetic deletion of TMEM219 in intestinal stem cells in newly generated TMEM219flflLGR5cre mice restored mucosal regenerative abilities both in vitro and in vivo.

Conclusion
Our findings demonstrate that genetic and pharmacological TMEM219 blockade re-establishes intestinal self-renewal properties and offers a therapeutic opportunity for mucosal healing in inflammatory bowel disease.
P180 Novel biomarkers associated with inflammatory bowel disease
Authors: Baldan-Martin M , Lloro I , Azkargorta M , Orejudo M , Ramírez C , Soleto I , Mercado J , Suárez-Trujillo F , Sánchez-Sánchez C , Gordillo-Vélez C H , Riestra S , Rivero M , Gutiérrez A , Rodríguez-Lago I , Fernández-Salazar L , Ceballos D , Benítez J M , Aguas M , Bastón Rey I , Bermejo F , Casanova M J , Lorente R , Ber Y , Royo V , Esteve M , Elortza F , Gisbert J P , Chaparro M 
Published: January 2024

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic multi-factorial disease characterized by inflammation of the gastrointestinal tract. Currently, the mechanisms underlying the disease are far from being elucidated. Thus, the study of proteins involved in its pathogenesis would allow further insights into the molecular mechanisms underlying IBD.

Methods
The serum and intestinal mucosa (ileum and left colon) proteomic profiles of patients with Crohn´s disease (CD) and ulcerative colitis (UC) and healthy controls (HC) were analyzed using a label-free quantitative proteomics approach (Table 1). Data mining and pattern recognition techniques were performed to identify hidden relationships that are not detectable using classical linear classifiers, and thus identify potential markers able to discriminate between the different study groups. Six candidate biomarkers were selected for further validation using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in serum and intestinal tissue samples, respectively (Table 2).

Results
Comparison of serum proteins between UC patients and HC revealed statistically lower levels of protein 1 and 2 and higher levels of protein 3. The comparison of potential biomarkers between CD and HC group showed lower levels of protein 1 and higher levels of protein 3. In addition, protein 4 was differentially upregulated in CD patients compared to UC (Figure 1A). Regarding the intestinal biopsies, protein 5 showed higher intensity in the IHC staining of ileum from CD patients compared to HC, whereas protein 6 was significantly decreased in left colon and ileum from CD and UC patients compared to HC (Figure 1B). These proteins are involved in thyroxine transport, regulation of chemotactic chemokine activity, inflammatory processes, triglyceride homeostasis, oxidative stress and regulation of NF-kappa-B activation in the cytosol.

Conclusion
In this study, we have identified a panel of six potential biomarkers that could help to elucidate mechanisms involved in IBD pathogenesis. Their roles in the pathophysiology need to be clarified in further experiments.
P189 Lifestyle and psychosocial factors in IBD; prevalence and patients’ perspective
Authors: Demers K , Hendrix E M B , Rezazadeh Ardabili A , Bredero Q M , van Bodegraven A A , van der Horst D , Jonkers D M A E , Kimman M L , Mujagic Z , Romberg-Camps M J , Römkens T E H , Scherpenzeel M P , Schroevers M J , Stassen L P S , West R L , Dijkstra G , Pierik M J 
Published: January 2024

Abstract

Background
Lifestyle and psychosocial factors impact mucosal inflammation and subjective well-being in Inflammatory Bowel Disease (IBD) patients. Better understanding of the relevancy of these factors within the IBD population, including prevalence and patients' perspective, may enhance systematic implementation of lifestyle interventions in regular care. This collaborative study with the Dutch patient organisation aimed to estimate the prevalence and patients’ perspectives on lifestyle and psychosocial factors in an outpatient cohort of IBD patients.

Methods
A multicentre cross-sectional study was conducted, enrolling IBD patients who utilized the remote monitoring platform myIBDcoach in 2022. Patients reported on clinical disease activity, lifestyle and psychosocial factors on this platform. A nationwide online survey was distributed by the Dutch patient organisation for IBD in April 2022 to assess patients’ perspectives regarding the impact of lifestyle and psychosocial factors on intestinal complaints, motivation to make changes, and need for and satisfaction with support in this regard from the hospital.

Results
In the multicentre myIBDcoach cohort (n=460), 16.3% adhered to a specific diet (Table 1). Two third (67.4%) did not comply with the Dutch healthy exercise norm and smoking was prevalent in 9.3%. About one-third experienced at least regularly poor sleep (33.8%), at least occasionally emotional distress (33.9%), and high perceived stress (36.7%). In the nationwide survey (n=1148), most (58.3-75.7%) patients believed that stress, unhealthy food, poor sleep, minimal or no exercise, and symptoms of anxiety and depression could lead to intestinal complaints (Fig. 1A). Around 70% of patients were taking action or were motivated to do so regarding their diet, stress, and physical activity (Fig. 1B). About 30% had no intention of addressing social support, and 22.8% were unwilling to change their alcohol use. Less than one-fifth received support from the hospital regarding these various factors (Fig. 1C). When support was received, most patients expressed satisfaction. Although desired, approximately 20% lacked support concerning stress, physical activity, diet, and sleep.

Conclusion
There is considerable scope for improvement in lifestyle and psychosocial factors among individuals with IBD, highlighting the need for systematic integration of these factors into clinical care. From the patient's viewpoint, widespread recognition of the impact of these factors emerged, with most expressing openness to initiating changes across various areas. These insights emphasize the potential for implementing targeted interventions, particularly in areas where patients indicated a need for additional support.
P229 Comparison of Different Histological Scoring Systems for Ulcerative Colitis [Nancy Histological Index, Robarts Histopathology Index and IBD-DCA (Inflammatory Bowel Disease-Distribution, Chronicity, Activity Score)] Among Specialists in GI Pathology and General Pathologists Pre- & Post Workshop
Authors: Loong S , Chen X F , Zhang X , Wan W K , Leow W Q , Kieran S , Lim T K H , Wang L M 
Published: January 2024

Abstract

Background
Histopathology is an emerging treatment target and an important parameter in predicting clinical outcomes of patients with ulcerative colitis (UC). Histological scoring indices Nancy Histological Index (NHI) and Robarts Histopathology Index (RHI) have been developed and validated for UC. We aim to compare the inter-observer reliability of NHI, RHI and the recently described Inflammatory Bowel Disease-Distribution, Chronicity, Activity (IBD-DCA) Score among gastrointestinal (GI) pathologists versus general pathologists pre- and post-workshop to determine the scoring system with the best reproducibility.

Methods
Digital whole slide images of 20 H&E-stained biopsies of ulcerative colitis (UC) cases are scored independently by 6 GI pathologists and 44 general pathologists that attended the Singhealth GI Pathology Course 2023 using NHI, RHI and IBD-DCA on the digital Pathpresenter platform. The 44 course participants performed the scoring before the course and again after attending a 3-hour IBD workshop on the assessment of histological remission using these 3 scoring systems. Data tabulation using “Free Online Surveys” platform is collated and intraclass correlation coefficient (ICC) of each component of the scoring indices is calculated. The ICC values of &lt;0.5, 0.5–0.75, 0.75–0.9, and &gt;0.9, indicate ‘poor’, ‘moderate’, ‘good’, and ‘excellent’ agreement, respectively.

Results
There is good inter-observer reliability for IBD-DCA ‘Activity’ component (ICC 0.85) and NHI (ICC 0.83) among GI pathologists while lBD-DCA ‘Distribution’ component (ICC 0.395) has the poorest agreement. Poor to moderate inter-observer reliability for all 3 scoring systems (ICC 0.4 – 0.6) is seen among the 44 participants pre-workshop with an observed post-workshop improvement, achieving best agreement for the NHI, ‘lamina propria neutrophils’ component of RHI and IBD-DCA ‘activity’ component (ICC 0.7).

Conclusion
GI pathologists are generally consistent in assessing disease activity in UC with good inter-observer reliability for NHI (a scoring system with an emphasis on activity grade) and only the ‘activity’ component of the IBD-DCA. Our study confirms NHI as a reliable scoring system for UC with the best reproducibility and favour its application to assess histological response in routine clinical practice to help gastroenterologists better manage patients with UC. We have also demonstrated that improvement in NHI scoring reproducibility can be achieved after training workshop for pathologists less familiar with the application of IBD histological scoring.