bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the construction of green transport network for construction waste
Authors: Zhang Saisai
Published: May 2021

With the rapid development of my country’s construction industry, soil, groundwater damage and environmental pollution caused by construction waste are becoming more and more serious. Therefore, research on the location, classification and treatment of construction waste is very important to conserve resources and protect the environment. Starting from the construction of a construction waste green operation network, this paper first briefly analyzes the operation characteristics of construction waste logistics, including the positioning, classification, treatment mode and treatment process of construction waste, by consulting a large number of literature materials. Then, from the perspective of supply chain and green sustainable development, a green transport network of construction waste is set up to provide a foundation for the disposal of construction waste and the protection of environmental resources.
Harm and countermeasure of indoor air pollution
Authors: Wang Yingchun , Zhang Zijing
Published: May 2021

Due to the rapid development of the economy, the consumption of coal, oil and other fossil fuels increases year by year, resulting in the problem of air pollution is also increasing. Economic development has also brought about people’s pursuit of quality of life, air pollution on the comfort of life and even human health, will affect. Therefore, not only outdoor air pollution, but also indoor air pollution has gradually received attention [1]. According to the investigation results of the U.S. Environmental Protection Administration, the concentration of indoor air pollutants is at least 2-5 times that of outdoor pollutants, and sometimes can even reach 100 times that of outdoor pollutants [2]. These particles are usually smaller than 10μm in size and can enter the respiratory tract during breathing. Smaller particles can even enter the alveoli and then enter the bloodstream. In addition, these tiny particles are likely to be carriers of bacteria and fungi, and may enrich heavy metals, organic pollutants and acid oxides, which will cause great harm to the human body [3]. All in all, it is of great significance to study indoor air pollution.
Research on structure optimization of overflow orifices in Hydropower Station
Authors: Xue Yang , Xu Jianrong , Peng Yu , Zhang Weidi
Published: May 2021

With the characteristics of large flood discharge and high water head, the flood discharge and energy dissipation structures of the dam body of A Hydropower Station are composed of overflow orifice, deep orifices, pond behind the dam and the second dam. In order to reduce the impact of the flood tongue on the cushion pond behind the dam, the method of stratified flow and air collision are adopted in the design of overflow orifice and deep orifice. The hydraulic model test is carried out to analyze body structure parameters such as diversion pier of overflow orifice, trajectory angle of outlet and so on, finally put forward the recommended structure design of overflow orifice. The model test showed that The setting of the diversion pier reduces the collision effect, therefore, it is not advisable to set the diversion pier. The structure of great differential drop and tongue without diversion pier are put forward, which can achieve the effect of layering the water tongue into the water, and colliding water tongue fully. The recommended structure can control the peak pressure of the cushion pond behind the dam within the allowable range.
Research on electric power distribution network operation and evaluation under energy saving and emission reduction environment
Authors: Zhang Geli , Zhang Heng , Zheng Yan , Wang Hongjin
Published: May 2021

This paper puts forward a four-step evaluation method based on data mining directly from information system under energy saving and emission reduction environment, including taking data, finding problems and putting forward measures. Through distribution network core indexes, an example was given to prove the method is scientific and practical.
Using deep learning to protect the diversity of the ecological environment Based on the prevention and control of alien species
Authors: Han Huijin
Published: May 2021

Ecological environmental protection has gradually changed from the original protected species to the protection of the entire ecosystem, controlling the destruction of biological resources and the ecological environment. The protection of the diversity of the ecological environment is one of the important measures to prevent the destruction of the ecological environment, and the invasion of alien species is one of the important reasons for the destruction of the ecological diversity. The expansion of invasive alien species not only brings various disturbances or damages to the native ecosystem, but also pays a great price for human health and economic and social development. This article uses deep learning related models and methods to identify alien species to help strengthen the prevention and control of alien species. Based on the data of 3000 reporters of the Asian Hornet invading the United States, this paper trains and uses the Bi-LSTM model and the CNN model to identify the pictures of the Asian Hornet reporter’s explanation and feedback, and makes full use of the above two models through XGBoost The output identification results and the temperature, humidity, air pressure and other parameters of the corresponding area were finally successfully screened out of the invalid reports of sightings of the Asian Hornet reported by the masses. Compared with the 1,386 test data, the accuracy rate was as high as 0.956. The results can effectively identify and Prevent and control new species and protect ecological diversity.
Study on Monitoring the ecological environment by SAR model
Authors: Han Huijin
Published: May 2021

Global environmental problems include environmental pollution and the destruction of ecological balance that transcend national boundaries. With the continuous development of human life, economy, trade, and technology, the intrusion into the environment has continued to deepen, causing extensive destruction of forests and other vegetation, large-scale killing of organisms, environmental pollution, and invasion of alien organisms. This has led to a sharp decline in biodiversity and a serious imbalance in the ecological environment. At the same time, the continuous improvement of information technology capabilities and the introduction of big data management and related detection models have brought new methods to the detection and governance of the global ecological environment. Based on the data related to the spread of Asian Hornet in the United States, this paper proposes a method and model for monitoring the number and distribution of new species based on the SAR model. Based on the spatial relationship and the distribution data of the Asian Hornet in the United States from May 2020 to October 2020, and taking into account environmental and climatic factors such as temperature, humidity, and air pressure, this paper conducts time series predictions to obtain the extent of the spread of the Hornet in the United States. The average RSME is 91.27, and a relatively ideal prediction result has been obtained, which proves that this model and method have a good effect on the control and management of alien species and the maintenance of ecological diversity.
Lost Dynamics and the Dynamics of Loss: Longitudinal Compression of Brain Signal Variability is Coupled with Declines in Functional Integration and Cognitive Performance
Authors: Garrett Douglas D , Skowron Alexander , Wiegert Steffen , Adolf Janne , Dahle Cheryl L , Lindenberger Ulman , Raz Naftali
Published: May 2021

Reduced moment-to-moment blood oxygen level-dependent (BOLD) signal variability has been consistently linked to advanced age and poorer cognitive performance, showing potential as a functional marker of brain aging. To date, however, this promise has rested exclusively on cross-sectional comparisons. In a sample of 74 healthy adults, we provide the first longitudinal evidence linking individual differences in BOLD variability, age, and performance across multiple cognitive domains over an average period of 2.5 years. As expected, those expressing greater loss of BOLD variability also exhibited greater decline in cognition. The fronto-striato-thalamic system emerged as a core neural substrate for these change–change associations. Preservation of signal variability within regions of the fronto-striato-thalamic system also cohered with preservation of functional integration across regions of this system, suggesting that longitudinal maintenance of “local” dynamics may require across-region communication. We therefore propose this neural system as a primary target in future longitudinal studies on the neural substrates of cognitive aging. Given that longitudinal change–change associations between brain and cognition are notoriously difficult to detect, the presence of such an association within a relatively short follow-up period bolsters the promise of brain signal variability as a viable, experimentally sensitive probe for studying individual differences in human cognitive aging.
Provider Satisfaction With Infectious Diseases Telemedicine Consults for Hospitalized Patients During the Coronavirus Disease 2019 (COVID-19) Pandemic
Authors: Canterino Joseph E , Wang Kaicheng , Golden Marjorie
Published: May 2021

During the coronavirus disease 2019 (COVID-19) pandemic, our institution transitioned infectious diseases (ID) consultations on hospitalized patients to telemedicine. We evaluated satisfaction with telemedicine among referring providers and ID consultants. Respondents were satisfied with telemedicine consults for hospitalized patients, although there were significant differences in perceptions of quality and timeliness between consultants and referring providers.
Neutralization Heterogeneity of UK and South African Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants in BNT162b2-Vaccinated or Convalescent Coronavirus Disease 2019 (COVID-19) Healthcare Workers
Authors: Marot Stéphane , Malet Isabelle , Leducq Valentin , Abdi Basma , Teyssou Elisa , Soulie Cathia , Wirden Marc , Rodriguez Christophe , Fourati Slim , Pawlotsky Jean-Michel , Boutolleau David , Burrel Sonia , Calvez Vincent , Marcelin Anne-Geneviève , Jary Aude
Published: May 2021

There are concerns about neutralizing antibodies’ (NAbs’) potency against severe acute respiratory syndrome coronavirus 2 variants. Despite decreased NAb titers elicited by BNT162b2 vaccine against VOC202012/01 and 501Y.V2 strains, 28/29 healthcare workers (HCWs) had an NAb titer ≥1:10. In contrast, 6 months after coronavirus disease 2019 mild forms, only 9/15 (60%) of HCWs displayed detectable NAbs against 501Y.V2 strain.
DOP02 αEβ7 positive γδ T cells are associated with mucosal healing in Ulcerative Colitis and have a homeostatic immunophenotype
Authors: Dart R , Zlatareva I , Irving P , Hayday A
Published: May 2021

Background

α4β7 blockade is a well-established therapy in ulcerative colitis (UC), acting in part by preventing lymphocyte ingress into the mucosa. The β7 unit of the α4β7 heterodimer is shared by α Εβ7, which is expressed on both tissue resident memory cells and γδ intra-epithelial lymphocytes (IEL). It was hypothesised that targeting both α4- and α Εβ7 might be more efficacious; however mixed results from phase III studies of β7 blockade asks questions of the biological relevance of different α Eβ7 expressing cells.

Methods

Colonic biopsies were obtained during endoscopy from >40 subjects. Lymphocytes were isolated using short term culture or digested from whole tissue. RNA sequencing was performed on α Εβ7pos and α Εβ7neg colonic γδ T cells from 4 donors and findings were validated by flow cytometry.

Results

α Εβ7 is widely expressed on TCRαβ CD8 cells and γδ IEL in both non-IBD controls and the uninflamed mucosa in UC, but its expression is significantly reduced on analogous subsets harvested from inflamed UC. On further study, the capacity of TCRαβ CD8 T cells to make TNFα and IFNγ on stimulation is similar between α Εβ7pos and α Εβ7neg cells, whereas in the γδ T cell compartment α Εβ7neg cells produce significantly more pro-inflammatory cytokine than their homeostatic α Εβ7pos counterparts. To examine the cells’ biology further, γδ T cells were isolated according to their α Εβ7 status and RNAseq undertaken. This revealed a distinct signature with α Εβ7neg cells demonstrating an activated phenotype high in markers such as CD18, CD5 and lymphoid homing receptor CCR7 whereas α Εβ7pos cells demonstrate a homeostatic tissue-resident phenotype, expressing immune checkpoints TIGIT and CD101 and gut-homing marker CCR9. On culturing tissue from non-IBD controls in pro-inflammatory cytokines, IL-12 and IL-18, the γδ T cell compartment down-regulated α Εβ7 and TIGIT and upregulated CD18, in part recapitulating a disease phenotype. On examining previously affected mucosa of patients who have achieved mucosal healing, α Eβ7 expression of the γδ T cells returned to a profile resembling non-IBD controls whereas the expression levels in the inflamed mucosa remained predictably low.

Conclusion

This study demonstrates that α Εβ7 expression is low in active UC but restored in mucosal healing. α Εβ7neg cells are proinflammatory with a distinct phenotype which may in part be recapitulated by inflammatory cytokines in vitro; whereas α Εβ7pos cells demonstrate a homeostatic phenotype, which may both reflect and maintain steady state barrier integrity. Hence in terms of γδ T cells, pharmacological β7 blockade has potential to interfere with the homeostatic roles of α Εβ7 expressing cells while having little effect on a potentially pathogenic subset of tissue α Εβ7neg γδ cells.
DOP25 Association of Enterobacteriaceae with Crohn’s Disease subtypes during remission
Authors: Pisani A , Rausch P , Ellul S , Bang C , Tabone T , Marantidis Cordina C , Zahra G , Ellul P , Franke A
Published: May 2021

Background

Members of the Enterobacteriaceae have been associated with active Crohn’s Disease (CD), possibly as a result of intestinal inflammation via production of a lipopolysaccharide that can trigger TLR4 signalling. This study aims to assess whether this association persists in remission of CD patients and whether correlation with disease phenotype is present.

Methods

Stool samples of 32 CD patients in remission and 97 healthy controls were analyzed by 16S rRNA sequencing. High quality Amplicon sequence variants (ASV) were derived and classified via DADA2.

Results

ASV 6-Escherichia/Shigella uncl. was found to be more abundant in CD (padj=0.0003) while ASV 24, another member of the Escherichia/Shigella cluster was identified as being an indicator species for CD (padj=0.09). Differential abundance analysis according to phenotype as per Montreal classification revealed that, compared to patients with the B1 phenotype, patients with the B2 and/or B3 have a higher abundance of Escherichia/Shigella uncl. (ASVs 13, 31, 282 and 422), Klebsiella uncl. (ASVs 75 and 101) and Enterobacter uncl. (ASV 219) (Figure 1). Furthermore, patients with L3 involvement had higher abundances of Klebsiella uncl. (ASVs 75 and 101) and Parasutturella uncl. (ASVs 22, 53, 120, 199, 249 and 510), the latter being a Proteobacteria, compared to patients with L1 and/or L2 involvement. No significant association with “Age of Onset” was identified. In addition, network analyses revealed a strongly correlated group of Enterobacteriaceae ASVs (Klebsiella, Escherichia/Shigella, Enterobacter, Citrobacter) which appear to collectively associate to CD.

Abstract DOP25 – Figure 1: Heatmap visualizing significant differentially abundant ASVs in CD patients with respect to behaviour subgroups

Conclusion

Enterobacteriaceae persist in the faecal microbiota in significantly higher levels than controls despite remission and furthermore are associated with the more severe phenotypes of stricturing and penetrating disease. Further studies might indicate whether microbiota assessment on diagnosis might predict CD subtypes and therefore influence therapeutic choices.
DOP58 Non-white race is associated with decreased efficacy of tumor necrosis factor antagonist therapy in Ulcerative Colitis: A post-hoc analysis of individual level data from golimumab clinical trials
Authors: Greywoode R , Petralia F , Ullman T , Colombel J F , Ungaro R
Published: May 2021

Background

Observational studies suggest non-white patients with inflammatory bowel disease (IBD) have worse clinical outcomes.1 There are limited data on whether race impacts response to biologic therapy. We therefore aimed to evaluate the efficacy of the tumor necrosis factor (TNF) antagonist golimumab comparing white to non-white participants, using individual participant level data from phase 2/3 randomized clinical trials of TNF antagonist therapy in ulcerative colitis (UC).

Methods

We conducted a pooled analysis of individual-level data from the induction and maintenance trials of golimumab in UC accessible through Yale University Open Data Access Project (YODA). There were insufficient non-white participants in infliximab studies accessible through YODA, precluding meaningful analysis. We analyzed patients in the placebo and treatment arms separately. Our primary outcome was clinical response and secondary outcomes were clinical remission and endoscopic healing according to clinical trial definitions. We compared white and non-white (defined as Black, Asian, or Other race) participants using multivariable logistic regression a priori adjusting for age, sex, treatment group, baseline Mayo score, immunomodulator and corticosteroid use. Effect estimates were expressed as adjusted odds ratios (aOR) and 95% confidence intervals (95% CI).

Results

A total of 1,006 participants were included in the induction trial (PURSUIT-SC; 18% non-white) and 783 participants in the maintenance trial (PURSUIT-M; 17% non-white). Non-white participants had significantly lower odds of week 6 clinical response (aOR 0.43, 95%CI 0.28–0.66), clinical remission (aOR 0.41, 95%CI 0.22–0.77) and endoscopic remission (aOR 0.48, 95%CI 0.30–0.74) compared to white participants (Figure). Non-white participants also had a lower adjusted odds of week 30 clinical response (aOR 0.64, 95%CI 0.40–1.01), clinical remission (aOR 0.45, 95%CI 0.28–0.74), and endoscopic remission (aOR 0.62, 95%CI 0.41–0.96). By week 54, the lower odds of these outcomes among non-whites were no longer statistically significant (Figure).

Conclusion

Non-white UC patients were less likely to achieve clinical response, clinical remission, and endoscopic healing with golimumab compared to white patients in these clinical trials. Further studies are needed to understand these differences and whether they are observed with other drugs or outside the context of clinical trials.

Reference
DOP70 Exosomes derived from human umbilical cord mesenchymal stem cells to attenuate colitis through repairing intestinal mucosal barrier
Authors: Yang S , Liang X , Liu A , Zhang X
Published: May 2021

Background

Inflammatory bowel diseases (IBD) is a chronic intestinal disease characterized by persistent intestinal inflammation and mucosal damage. Mesenchymal stem cells (MSCs) transplantation is a promising therapy in IBD and other autoimmune diseases. Recent studies indicated that exosomes are the main therapeutic vectors of MSCs in treatment of IBD, but the therapeutic mechanism of exosomes derived from MSCs (MSCs-EXO) remains to be explored. The aims of our research is to explore whether MSCs-EXO have a protective effect on the intestinal barrier.

Methods

The serum-free cell culture supernatant of Human umbilical cord MSCs (hUC-MSCs) cultured for 48 hours was collected to extract exosomes. Two separate mouse models of IBD induced by dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzenesulfonic acid (TNBS) were administered MSCs-EXO intraperitoneally. The effects of MSCs-EXO on intestinal inflammation, colon barrier function and proportion of T cells were investigated.

Results

Intraperitoneal injection of MSCs-EXO significantly ameliorated colitis, especially reduced disease activity index and mortality, and inhibited inflammatory cells infiltration. The protective effect of MSCs-EXO on intestinal barrier was demonstrated by reducing the loss of goblet cells and the intestinal mucosa permeability, improving the destruction of tight junctions (TJs) structures and microvilli, and increasing the expression of TJs proteins ZO-1, Claudin-1, and Occludin. MSCs-EXO administration downregulated the level of proinflammatory cytokines, including CXCL14, IL-1β, IL-11, and IL-12 and upregulated the anti-inflammatory cytokine IL-4 and TGF-β in colon tissue. MSCs-EXO also modulated the response of Th2 cells and Th17 cells in mesenteric lymph nodes (MLN).

Conclusion

Our findings suggested that MSCs-EXO promoted mucosal barrier repair and maintained intestinal immune homeostasis in murine colitis model.
DOP72 Perianal Crohn’s Disease in the biologic era: A population-based cohort study
Authors: Jenkinson P , Plevris N , Lyons M , Siakavellas S , Arnott I , Jones G R , Watson A , Lees C
Published: May 2021

Background

Peri-anal Crohn’s disease (pCD) significantly affects quality of life in patients with CD. The natural history of pCD in the era of biologic therapy is poorly understood. Perianal surgery includes examination under anaesthesia (EUA), drainage of peri-anal sepsis, seton instertion and fistula manipulation. EUA forms part of the standard of care at diagnosis of pCD and therefore can be used as a proxy for incidence of pCD.

Methods

CD patients were identified from the Lothian IBD registry, a physician validated registry of all IBD cases within Lothian which has been shown to be 94.3% complete. Prospectively collected coding data was used to identify peri-anal surgery, which was validated by review of the electronic health record. Biologic prescription data was extracted from the Lothian biologics database; a physician validated, prospectively collected registry. Time trend analysis was performed for the period 2000 to 2017 by 1) calculating annual incidence rates of peri-anal interventions for all patients with CD and estimating annual percentage change and 2) by calculating cumulative incidence of pCD and biologic prescription in newly diagnosed CD and 3) stratifying by era of diagnosis (Cohort 1: 2000–2008 and Cohort 2: 2009–2017.

Results

2937 patients with CD were identified in the study period, with 1108 operations for pCD performed on 381 patients. Rates of surgery fell from 5.1 to 2.0 operations per 100 CD patients per year between 2000 and 2017 (p<0.001) giving an annual percentage change of -3.4% (-4.9% to -1.9% 95% CI) (fig 1).

1753 new diagnoses of CD were made of whom 247 developed pCD. 5 year risk of pCD was 12.8% (9.5–16.6%) with no significant difference identified between cohort 1 (11.5%) and cohort 2 (13.8%) (p=0.116) (fig 2). The 5 year incidence of biologic prescription for patients with pCD increased from 11.2% in cohort 1 to 58.1% in cohort 2 (p<0.001) (fig 3).

Figure 1: Number of peri-anal interventions per 100 CD patients per year (multiple procedures per patient included).

Figure 2: Kaplan Meier curves showing cumulative incidence of pCD stratified by era of diagnosis.

Figure 3: Kaplan Meier curves showing cumulative incidence of biologic prescription in patients with CD stratified by era of diagnosis and presence of pCD.

Conclusion

The incidence of pCD remains unchanged over time. Although we cannot ascribe causality, the overall decrease in surgery for pCD has been paralleled by a marked increase in the use of biologic medication.
N02 PREVIEW study: Factors associated with willingness to switch from intravenous to subcutaneous formulations of CT-P13 and vedolizumab in patients with Inflammatory Bowel Disease
Authors: Asnong K , Hoefkens E , Lembrechts N , Van de Schoot I , Pouillon L , Bossuyt P
Published: May 2021

Background

Subcutaneous (SC) formulations were recently approved for CT-P13 and vedolizumab (VED). No insights in the willingness of patients with Inflammatory Bowel Disease (IBD) to switch from intravenous (IV) to SC maintenance therapy with CT-P13 and VED are available. The aims of this study were (1) to evaluate the percentage of patients with IBD in favour of switching to SC formulations, (2) to define the factors influencing this decision, and (3) to explore the role of the IBD nurse in the process of switching.

Methods

This was a monocentric study in patients with IBD on maintenance IV CT-P13 or VED. All patients attending the infusion unit were invited to complete a survey exploring the willingness to switch to SC formulations. Prior to completing the survey, patients were informed on the new SC formulations and the accompanying care pathway. The survey was performed prior to the market introduction of SC CT-P13 and VED. Demographics, patient reported outcomes, willingness to switch and reason for IV vs. SC preferences were captured.

Results

In total, 183 (91%) patients completed the survey (m/f: 84/99; CD/UC/IBD-U: 120/57/6; median age 45 IQR 34–59; remission CD/UC: 67%/75%). The majority of patients preferred switching to SC (56% yes, 12% no, 32% doubt). The main driver to switch was an anticipated decrease in hospital visits (90%); the main reason to continue IV was fear of change (61%). Patients doubting to switch had a lower stool frequency compared with patients making a definite decision (p=0.012). Factors significantly associated with the willingness to switch in the univariate analysis were younger age (p<0.0001), experience with SC therapy (p=0.03), full time work occupancy (p=0.001), younger age at start IV therapy (p=0.001), shorter disease duration (p=0.012), and compliance level (p<0.0001). Multivariate analysis retained younger age as the only independent factor. For patients doubting to switch, an electronic alert (71%), an information brochure (69%), and a personal teaching moment (60%) were recognised as valuable support. An information package should cover patient-focused efficacy and safety data of SC therapy, therapeutic options in case of disease worsening, and practical concerns including information about administrative issues and travelling.

Conclusion

This is the first study exploring the willingness to switch from IV to SC maintenance therapy with CT-P13 and VED in patients with IBD. The majority prefers to switch to a SC formulation, with willingness to switch being most likely in younger patients. Further studies are required to investigate the impact of nurse led interventions on the willingness to switch, patient satisfaction, and treatment compliance.
OP21 Predictive value of Milan Ultrasound Criteria in Ulcerative Colitis: A prospective observational cohort study
Authors: Allocca M , Dell’Avalle C , Furfaro F , Craviotto V , Zilli A , D’Amico F , Peyrin-Biroulet L , Fiorino G , Danese S
Published: May 2021

Background

Endoscopic remission is associated with better outcomes in ulcerative colitis (UC). However, colonoscopy (CS) is invasive and poorly tolerated by patients. Recently, we developed and externally validated non-invasive ultrasonography based criteria [Milan ultrasound criteria (MUC)] to assess and grade endoscopic activity in UC. We also confirmed that a MUC score > 6.2 is a valid cut-off to discriminate endoscopic activity, defined by a Mayo endoscopic subscore > 2.

Aim of this study was to assess the predictive role of MUC on disease course in a prospective cohort of UC patients.

Methods

UC consecutive patients were followed for at least 12 months after performing baseline bowel US. UC-related outcomes, including need of treatment escalation (defined as the need of corticosteroids or change/optimization of immunosuppressants), hospitalization and surgery, were assessed at 1 year by logistic regression analysis, and were analyzed after long term follow-up (5 years) using Kaplan-Meier survival analysis.

Fig. 1A and 1B. Kaplan–Meier curves for the cumulative probability of hospitalization and surgery in patients with Milan ultrasound criteria (MUC) < 6.2 (solid line) or MUC > 6.2 (dotted line). (p= 0.046; p= 0.023; respectively).

Fig. 1C and 1D. Kaplan–Meier curves for the cumulative probability of hospitalization and surgery in patients with Mayo endoscopic subscore 0–1 (solid line) or 2–3 (dotted line). (p= 0.035; p= 0.071; respectively).

Results

87 UC consecutive patients were included in the study, 31 (36%) were in endoscopic remission (Mayo endoscopic subscore 0–1) and 56 (64%) in endoscopic activity (Mayo endoscopic subscore 2–3). MUC and Mayo endoscopic subscore significantly correlated at baseline (Spearman’s rank correlations [rho]= 0.642; 95% confidence interval (CI) 0.499 to 0.751; p < 0.001). The multivariable analysis identified as independent predictors of need of treatment escalation throughout the 12-month period as being: MUC > 6.2 (OR: 5.95, 95% CI: 1.32–26.76, p < 0.020) and a partial Mayo score (PMS) > 2 (OR: 26.88, 95% CI: 5.01–144.07, p < 0.001). Kaplan-Meier survival analysis of long-term follow up demonstrated a lower cumulative probability of need for surgery and hospitalization in patients with MUC < 6.2 compared to MUC > 6.2 (Fig. 1A and 1B), as well as in patients with a Mayo endoscopic subscore of < 1 compared to Mayo endoscopic subscore of 2–3 (Fig. 1C and 1D).

Conclusion

MUC is a novel non invasive tool that predicts the course of UC in the short and long term follow-up.
OP30 Lyophilised orally administered faecal microbiota transplantation for Active Ulcerative Colitis (LOTUS study)
Authors: Haifer C , Saikal A , Paramsothy S , Borody T J , Ghaly S , Kaakoush N O , Leong R
Published: May 2021

Background

Faecal microbiota transplantation (FMT) administered via the lower GI tract effectively induces remission in ulcerative colitis (UC). Orally administered FMT capsules may improve patient tolerability and facilitate maintenance therapy while it is unclear if pre-FMT antibiotics enhance therapeutic efficacy.

Methods

We performed a dual-centre randomised, double blind, placebo-controlled trial of oral lyophilised FMT in adults with mild-moderately active UC (total Mayo 4–10). All subjects received 2-weeks of pre-FMT antibiotics (amoxycillin, metronidazole and doxycycline) before 1:1 randomisation to either oral FMT (0.35g stool content per capsule from 1 of 2 healthy donors) or identical placebo for 8 weeks. Enforced tapering and cessation of corticosteroids was mandated. The primary endpoint was week 8 steroid-free clinical remission with endoscopic remission or response (total Mayo score ≤2 with subscores ≤ 1 for rectal bleeding, stool frequency and endoscopic appearance, and ≥1-point reduction from baseline in endoscopy subscore). Responders to FMT induction were re-randomised to either continue maintenance FMT or withdrawal of FMT with final outcomes assessed at week 56.

Results

Recruitment was paused due to the COVID-19 pandemic. 37 patients were randomised. Baseline patient and disease characteristics were balanced between the randomised groups. The primary outcome was achieved in 8/16 (50%) receiving FMT versus 3/19 (16%) receiving placebo (OR: 4.63; 95%CI: 1.74–12.30; P=0.002). Steroid-free clinical remission rates and endoscopic remission rates were 69% vs 26% (P=0.012) and 44% vs 16% (P=0.074) in the FMT and placebo arms, respectively. Reported SAE were worsening colitis (2 FMT, 1 placebo) and PR bleeding relating to previous anal surgery (placebo). Ten patients entered the maintenance withdrawal study. Steroid-free clinical, endoscopic and histologic remission was achieved in 4/4 patients who continued daily oral FMT, with all 6 patients randomised to FMT withdrawal having a flare of disease with a median time to relapse of 6 months.

Conclusion

Oral lyophilised FMT following antibiotic pre-treatment for mild-moderately active ulcerative colitis was associated with a significant increased rate of clinical remission with endoscopic remission or response versus antibiotic treatment alone at week 8. Pre-treatment antibiotics had an additive impact upon treatment efficacy compared with previous studies utilising FMT. Maintenance FMT therapy was associated with sustained clinical, endoscopic and histologic remission at week 56. Treatment was well tolerated and there were no new safety signals related to FMT therapy.
P022 Pathologic involvement of the farnesoid X receptor/fibroblast growth factor 19 axis to the Crohn’s disease early postsurgical recurrence
Authors: Suau R , Garcia-Jaraquemada A , Lorén V , Torres P , Jou E , Llaves M , Aterido A , Julià T , Zabana Y , Lozano J J , Domènech E , Mañosa M , Manyé J
Published: May 2021

Background

Crohn’s disease (CD) is a chronic inflammatory bowel disease that normally requires bowel surgical resection due to intra-abdominal inflammatory complications such as fistulae and stenosis. However, 90% of patients that underwent surgery and did not receive prophylaxis, suffer from postsurgical endoscopic recurrence within one year.

Methods

The objective of this study is to understand the de novo postsurgical lesion formation in order to stablish a potential mechanism of action and its derived predictive signals to devise preventive strategies. To achieve it, transcriptome analyses of the inflamed and macroscopically unaffected zone of the ileocecal resection from 20 patients from a hospital cohort and 10 controls were performed. Patients were classified for early postsurgical recurrence by means of Rutgeerts index (i0<i1<i2<i3<i4) and transcriptome was analysed using different comparatives and clustering strategies. In order to replicate the results from the transcriptome analyses, the statistically significant genes and rationally related genes have been tested by qPCR in a corroboration cohort formed by 24 different patients.

Results

The transcriptome results showed there were no differences neither between i0, i1 and i2a (anastomotic lesions) nor when comparing i2b (non-anastomotic lesions) vs ≥i3. However, when comparing i0+i1+i2a vs. i2b+i3+i4 there were differently expressed genes highlighting ADIPOQ in the inflamed zone and the FXR/FGF19 axis in the unaffected zone. When replicating the results in the corroborative cohort, we identified FXR and other xenobiotic nuclear receptors as the genes differentially expressed in i2a vs i2b, i3 and/or i4, mainly in the macroscopically unaffected zone. Specifically, the differentially expressed genes were: MOGAT2, PXR, FXR and AHR (i2a vs i4), PPARα and FXR (i2a vs i3), TMIGD1, PPARα, FXR and AHR (i2a vs i3+i4) and FXR (i2a vs i2b+i3+i4).

Conclusion

Nuclear receptor FXR is activated in the ileum by bile acids action and it is key in the lipid metabolism regulation and in the bile acids production by means of FGF19. Moreover, ileal FXR, as well as other xenobiotic nuclear receptors, actively participates in the enhancement of the intestinal barrier function and in the innate immunity regulation. In conclusion, the results obtained in this study suggest a link between bowel xenobiotic metabolism and the de novo lesion formation in previously unaffected areas in the postsurgical recurrence in CD.
P046 Disease modelling of Inflammatory Bowel Disease by human colon organoids
Authors: Molnár T , Jójárt B , Resál T , Szántó K , Kata D , Földesi I , Molnár T , Maléth J , Farkas K
Published: May 2021

Background

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastrointestinal tract which is associated with the imbalanced pro- and anti-inflammatory cytokines. Anti-TNF-α is widely used as a therapeutic agent, but 10–30% of the patients are not responding to the treatment or in time it become less affective. In vitro organoid cultures generated from stem cells can mimic the cellular diversity and function of the organ of origin and might be used as a predictive tool for patient specific response. However, the in vitro cytokine expression pattern of the IBD colon organoid cultures have never been determined or compared with the cytokine expression of the colon mucosa.

Methods

Our aim was to determine and compare the cytokine profiles of the colon biopsy samples in IBD patients and organoid cultures generated from these biopsies.

In this study samples from 5 IBD patients were used. Biopsies were taken during colonoscopy from inflamed part of the colon. Crypts were isolated from the biopsy samples to start colon organoid culture. Total protein was isolated from the biopsies and the organoids. Cytokine Array was used to determine the cytokine patterns in both samples. ELISA was used to measure the TNF-α concentrations and immunofluorescence staining to localize it in the organoids.

Results

We determined the cytokine profile of the biopsy samples and the colon organoid cultures. The cytokine patterns were remarkably similar until the first passage. The major pro-inflammatory cytokines, IL-1β, IL-6, IL-8, were detected in the organoids after the first passage. After the second passage the cytokine expression decreased or disappeared. ELISA revealed that TNF-α was also expressed in the organoid cultures, however a similar decrease in the expression was observed, which was also confirmed by immunofluorescence staining. TNF-α positive cells were present in the organoids, but it decreased after every passage.

Conclusion

Our results suggest that the colon organoid cultures maintain the cytokine profile of the tissue of origin until a limited time (until the first passage). Therefore, organoids might be used to determine patient specific therapy for drug tests.
P066 Exploration of critical molecules for optimizing treatment by analyzing in flammatory cytokines in the intestinal mucosa of patients with Inflammatory Bowel Disease
Authors: Yokoyama Y , Yamakawa T , Hayashi Y , Kazama T , Hirayama D , Nakase H
Published: May 2021

Background

Inflammatory cytokines initiate and sustain the perpetuation of processes leading to chronic inflammatory conditions such as inflammatory bowel diseases (IBD). Research into the cytokine biology of IBD has nurtured the dogmatic view that distinct immunotypes characterize different IBD subtypes. Recently, many biologics have emerged as the treatment options for IBD patients. Still, it is challenging to establish biomarkers for predicting their effectiveness because the cytokines that determine the IBD clinical phenotype vary in individual patients. Therefore, this study aims to explore critical molecules for optimizing treatment by analyzing inflammatory cytokines in the intestinal mucosa of IBD patients.

Methods

From September 2019, to February 2020, patients with ulcerative colitis (UC) and Crohn’s disease (CD) who underwent colonoscopy or flexible sigmoidoscopy, and the control group, patients who received colorectal polypectomy at our institution, were enrolled in the study. We took biopsies from inflamed ileal or colonic mucosa. We analyzed the gene expression of various inflammatory cytokines by real-time PCR using RT2 Profiler PCR Array (96-Well Format) Human Inflammatory Cytokines & Receptors (QIAGEN). Cytokines not included in this array were subjected to real-time PCR separately. Based on these data, we investigated the relationship between mucosal cytokines and clinical characteristics.

Results

The total number of patients was 23 (control 5, UC 12, CD 6) cases, the median age was 51 years (18–78), genders were fifteen males and eight females. Disease phenotype was divided into extensive colitis/ left-sided colitis/proctitis (10/1/1) in UC patients, and A1/A2/A3 (2/3/1), L1/L3 (2/4), B1/B1+p/B2/B3 (3/1/1/1) in CD patients. Seven patients were steroid-dependent, and six patients were refractory to the anti-TNFα agent. The higher gene expressions of CCR2/CXCL1/CXCL3/CXCL13, IL-8, IL-33, and SPP1 in inflamed mucosa of UC compared to those of CD (p<0.05). The positive correlation between Mayo score and IL-1R1 expression in intestinal mucosa was observed (r=0.68, p=0.028). The expression of IL-1β, IL-6, IL-8, and oncostatin M (OSM) was higher in steroid-dependent UC patients, and the primary non-responders to anti-TNFα therapies had higher expressions of IL-7 in colonic mucosa than the secondary non-responders in UC.

Conclusion

Our results suggest that UC exhibits different cytokine patterns in the intestinal mucosa from CD as reported previously. Exploration of cytokine expressions in the intestinal mucosa may lead to predicting refractory IBD. The identification of molecules that can predict therapeutic effectiveness helps to optimize IBD treatment in the future.
P072 The involvement of extracellular Nicotinamide Phosphoribosyltransferase (eNAMPT) and Nicotinate Phosphoribosyltransferase (eNAPRT) in inflammatory bowel disease
Authors: Colombo G , Ribaldone D G , Caviglia G P , Genazzani A , Travelli C
Published: May 2021

Background

Nicotinamide phosphoribosyltrasferase (NAMPT) is a pleiotropic enzyme which catalyses the first and rate-limiting step in the biosynthesis of NAD. It is present in two different forms: an intracellular form, called iNAMPT, (Chiarugi et al., 2012), and an extracellular form, eNAMPT. eNAMPT is considered an important factor for granulocyte-colony stimulating factor-(G-CSF)-induced myeloid differentiation, with paracrine and autocrine effects on different cell types (i.e. immune and cancer cells), binding TLR4. NAMPT is structurally and functionally related to the enzyme nicotinate phosphoribosyltransferase (iNAPRT), which is rate-limiting in the NAD salvage pathway that starts from nicotinic acid. The NAD biosynthetic pathways controlled by NAMPT and NAPRT are closely interconnected and can compensate for each other. Also, NAPRT is identified as an extracellular ligand (eNAMPRT) for TLR4 and a mediator of inflammation (Managò et al., 2020).

Importantly, iNAMPT and eNAMPT levels are increased in several pathologies, included inflammatory bowel disease (IBD). It has been reported that serum eNAMPT levels correlate with the stage of the pathology: in an active state of the disease the levels of NAMPT are very high, however its levels are partially reduced in a remission stage (Moschen et al., 2007).

Methods

First, we investigated the role of eNAMPT and eNAPRT in murine IBD models (especially in DNBS and DSS model). We took into account phenotypic effect as weight loss and colon shortening, but also the reduction of mRNA of inflammatory genes with RT-PCR, tissue damage with H&E and IHC analysis and systemic and local production through colon explant. Secondly, we determined serum eNAMPT and eNAPRT levels in a cohort of adult IBD patients.

Results

Both eNAMPT and eNAPRT have been found elevated in 180 IBD patients, as proinflammatory marker of the pathologies. These levels are also elevated in serum and colonic explant of DSS and DNBS preclinical models, associated to an active state of the disease, as a pro-inflammatory response developed locally and systemically.

Moreover, we performed ELISA analysis on sera of 100 IBD patients, eligible for anti-TNF treatment, both pediatric and adults. Serum eNAMPT levels are increased before the treatment, responsive patients verified a reduction of these levels, while no-responsive ones verified higher levels.

Conclusion

eNAMPT and eNAPRT could be considered pro-inflammatory markers of IBD and possible druggable targets.
P096 Which patients with known Crohn’s disease after an ileo-colonoscopy will benefit most from small bowel capsule endoscopy?
Authors: Viazis N , Mountaki A , Koustenis K , Veretanos C , Arvanitis K , Georgiadi T , Karampekos G , Manolakis A , Archavlis E , Christidou A , Mela M , Mantzaris G
Published: May 2021

Background

Ileo-colonoscopy with biopsies is considered the gold standard for the diagnosis and management of Crohn’s disease (CD). In contrast, the role of small bowel capsule endoscopy (SBCE) is limited currently in cases where ileo-colonoscopy and imaging techniques raise doubts on the diagnosis or cannot explain certain clinical manifestations of Crohn’s disease. The aim of our study was to determine whether there are patients with endoscopically confirmed established CD who could get additional benefit by SBCE.

Methods

Retrospective analysis of prospectively collected data from 6301 patients subjected to SBCE in our department from 1st March 2003 to 18th February 2021. Patients with CD diagnosed by ileo-colonoscopy or total colonoscopy only (because the ileo-caecal valve could not be intubated) prior to SBCE were included in the study and biopsies. SBCE had been performed only in patients who lacked any clinical and/or imaging (CT/MRE) evidence of bowel obstruction. The presence and extent of mucosal lesions, namely local and/or diffuse erythema, erosions and ulcers (aphthous, superficial and/or deep) throughout the small intestine, which may be difficult to identify by traditional imaging, could either explain clinical manifestations unrelated to the findings of colonoscopy or led onto reassessment of applied treatments were sought by SBCE.

Results

The study sample consisted of 1002 patients (males/females: 511/491, mean age ± SD: 52.6±27.3). Among these, CD had been diagnosed with colonoscopy (and not ileo-colonoscopy) in 293 (29.2%) subjects and small bowel involvement was seen in 104 (35.5%) patients. The vast majority of these patients had lesions only in the terminal ileum (n=81, 77.8%), while the remaining patients (n=23, 22.2%) had additional lesions in more proximal parts of the small bowel. Among the 709 (70.8%) patients in whom CD had been diagnosed by ileo-colonoscopy, lesions in the terminal ileum were found in 407 (57.4 %) patients; SBCE revealed more proximal lesions in 104 patients (25.5%). In the remaining 307 patients (43.3%) in whom ileo-colonoscopy did not reveal terminal ileum involvement, more proximal small bowel lesions were seen in 35 (11.4%) patients. These lesions were mainly apthoid ulcers or larger ulcers, findings that led to a change in therapeutic management in 17 patients (48.6%).

Conclusion

SBCE identifies more proximal small bowel lesions in a substantial number of patients with CD established by traditional endoscopic techniques. When these lesions are more severe and extensive they may lead onto re-evaluation of the personalized therapeutic strategies.