bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Factors of Failure Risk in Refill Drinking Water Quality by Using Ishikawa Diagram
Authors: Hidayah E.N. , Veronica G. , Cahyonugroho O. H.
Published: May 2021

The owner of refill drinking water stores (RDWS) have a big opportunities to expand their business since most of people need drinking water with the cheaper price than bottled drinking water. However, some issues regarding the quality of refill drinking water (RDW) have been arised recently, such as issue of pathogen existence in the treated water of RDW. This study aims are to measure the RDW quality and to identify the factors of failure risk of RDWS in treating RDW by using Ishikawa diagram. Study was carried out in 23 RDWS in Gunung Anyar District of Surabaya City. Sample was taken and measured for pH, turbidity, total dissolved solid (TDS), total coliform and Eschericia coli concentration. Ishikawa diagram was applied to reveal risk failure factors of RDW treatment processes. The results show that microbiology parameters was not fulfilled the drinking water quality standard. Ishikawa diagram found that man, material, method, machine, monitoring and evaluation for environment were the factors of failure risk. Therefore it is necessary to provide recommendations to reduce the failure risk of microbiology parameters through UV or Ozone contact time of at least 4 minutes, routine monitoring of treatment units, preparing procedure operational standard.
Design of Fuzzy Sugeno Controller for Anti-Roll Stabilizer Using Flywheel
Authors: umam Faikul , Widyaningrum Vivi Tri , Budiarto Hairil
Published: May 2021

Ship stabilizers are still an interesting issue to develop. The ship changes a lot like the rolling motion caused by the waves. The scrolling effect of the ship causes passenger inconvenience and collisions. Therefore, a stabilizer is needed to reduce rolling so that the ship stays balanced. This stabilizer is mounted on the center of the ship to effect the rolling ship effect. This research developed an anti-roll stabilizer by utilizing the flywheel. The flywheel rotates on the stabilizer shaft producing Direction force and value magnitude. To control the flywheel speed, a fuzzy logic controller is used. The results of the study showed that the Anti-roll stabilizer was able to reduce rolling vessels by 26% from the front and rear directions of the ship, and 56% from the left and right directions.
Investigation of Groundwater Potential Based On Vertical Electrical Sounding Methode On Gosoma District In North Halmahera
Authors: Sahdar I , Rauf I , Gaus A
Published: May 2021

Population growth has encourage an increasing of clean water needs as a basic human necessity, both in terms of quality and quantity. River water and rain water are sources of raw materials for these elementary needs, however global climate change has indirectly affected the hydrological characteristics of the last few decades. Thus, the use of ground water is a solution in meeting these needs. The research aims to identify the potential presence of ground water that can be used as a source of fresh water in the village of Gosoma, Tobelo, North Halmahera Regency. This potential fresh water investigation was carried out using a Mc Ohm Mark-2 OYO resistivity meter, while the Schlumberger configuration was the measurement method used. The length of the track geoelectric extends as far as 1,060 m, while for transverse profiles as far as 560 with a total number of measurement points of 6 points. The results of geoelectric measurements show that there are 2 layers that have the potential as deep aquifers. First groundwater layers predicted at a depth that varies between 21.10 m - 83.00 m and secondary groundwater layer may exist deeper than 95.90 m above the surface. This result were indicated by resistivity values measured at the observed points, where the values varies from 18.10 ohms to 91.30 ohms. Those resistivity value illustrates that lithology of the soil layer were indicated as a layer of sand and sandy tuff, where both of the rock lithologies layer have a potential as a layer of ground water.
Installation of Handphone Signal Booster Antennas at 900 MHz Frequency in Onggari Village Merauke Regency
Authors: Murniani  , Corputty Roberto , Letsoin Vinsensius , Ponadi Acep
Published: May 2021

The importance of cellular communication demands to improve the quality of good and quality services in all regions including rural areas. The limitations of BTS signal propagation in Kumbe village have disrupted cellular communication services in Onggari village. By using the Yagi antenna 13 elements as a cellular signal amplifier that is modified by using a repeater so that the handphone signal can be accessed at a greater distance from the BTS location. The results obtained after mounting the signal amplifier antenna is very good where the signal increase is at 4 Barr, the signal strength is -75 dBm at a distance of 1 meter with “excellent” sound quality, while the results of the measurement of signal strength and signal quality for sunny weather are better than when it rains.
Design Of Monitoring Robot Based On Bogie Rocker System
Authors: Sukri Hanifudin , Dafid Ach.
Published: May 2021

The system using CCTV cameras (Closed Circuit Television) that are currently in use still has many shortcomings. This is what underlies the making of a monitoring robot using a rocker bogie system and a camera that can be adjusted as desired and can display the situation in the room through a smartphone connected to a WiFi network. The transfer process uses IP cameras, nodeMCU, relays, DC motors and servo motors so that the monitoring process can run well. IP camera is used as a camera that will take pictures of the state of the room being monitored, this camera uses a wifi network connection to connect with other devices. nodeMCU is used as a controller while connecting the system with a wifi network. Control and navigation using smartphone applications connected to the same WiFi network. With the robot, the remote monitor becomes wider because of the movement process that can walk and climb stairs easily.
Comparative assessment of green ball-manufacturing alternatives using Green Productivity Index (GPI)
Authors: Findiastuti W , Mualim  , Aminawati D N
Published: May 2021

This paper compares three alternatives of green ball-manufacturing to replace existing ball-manufacturing. Using Green Productivity Index (GPI), alternatives were evaluated on their total productivity to its environmental pressure. Productivities were measured as their selling price per production cost, while environmental pressures were determined as their seven green-waste analysis through the manufacturing. The result showed that alternative 3 has the highest GPI which is combination of solid waste and water waste utilization.
Exergy Modeling of Monocrystalline Silicon Solar Cells with Spectral Irradiation Variations
Authors: Hariyanto  , Parenden D , Wullur C W , Sariman F
Published: May 2021

Exergy modeling was made to analyze the work performance of monocrystalline silicon solar cells. Analysis is done by making modeling and simulation of the equation and parameter data that affect the amount of photon energy and the exergy rate at PV. The incident radiation source used varies on the (0.05, 0.1, 0.3 and 0.5 Suns) in the AM1.5G spectral response standard. Calculation analysis with the model made shows that the PV module photonic energy is greater than the photonic exergy, this is related to the irreversibility of the PV module conversion system.
Simulation and kinematic analysis of KUKA KR5 Arc robot
Authors: Jha Aparna , Soni Manoj , Suhaib Mohd
Published: May 2021

Nowadays robots have become an indispensable part of manufacturing systems, for gripping needs manipulators are needed. Trade sector is touching industry 4.0 and asks for a much-advanced automation process. In which commercial robots play an essential role in automating the methods such as material handling, palletizing, painting, assembly lines, and numerous applications. With the increase in demand and need to have more research on engineering robots, artificial intelligence, and machine learning. A systematic design and analysis study is needed to get the best output for a specific robot. In India, there is scarcity of Indian based robot manufacturers to satisfy the rising need. Hence, there is more influence of foreign robot manufacturer in Indian markets. Due to the deficient information in robotics, robot part and resources are unavailable. More and more open source and easily access information regarding industrial robot is needed. So, this work emphasis on the developing and designing six degrees of freedom robotic arm and its kinematic analysis particularly forward and inverse kinematics. This paper gives an idea of the Denavit Hartenberg method for forward and inverse kinematics of a 6 axis KUKA KR5 Arc robot and uses RoboAnalyzer simulation software. The Robo Analyzer is simulation software that is used for design, kinematics, and dynamic analysis.
Aerodynamics Characteristics of Compound Delta Wing at Sea Level
Authors: Gupta Gaurav , Tiwari Pranav , Vatsa Bhanu Pratap , Sahay Aashish Anand , Srikanth K S , Vidya Shrikant
Published: May 2021

Compound delta-wing aircraft are in the top tier for great maneuverability and satisfactory take-off and landing speeds and low distance as delta wing have a property of vortex generation at different speeds, during flight the property of vortex generated depends on factors like the coefficient of lift, coefficient of drag and shock wave impact absorption upon varying speed from subsonic speed and supersonic speed with changing attack angle is studied by flow visualization of the wing in Ansys Fluent using ’k-ε 2nd equation model’ to simulate mean flow characteristics for turbulent flow conditions. Vortex generation is studied for flow physics at Subsonic speed and Supersonic speed at sea level over Pressure and Density based respectively. The flow velocity at Subsonic is 260m/s and 686m/s for Supersonic. During the experiment, we observed that the vortex flow generation of observable output starts forming at 5° angle of attack following a powerful vortex at 10° leading to a shortfall powerful vortex at 15° for both subsonic and supersonic speeds but as velocity is more in the supersonic state the vortex is denser and more stable and provides better shock absorption while transitioning on higher attack angle and lift force is very sensitive for the supersonic state as drag is substantially increased with speed.
Study on the effect of heat exchange tube structure on waste heat recovery capacity of the internal combustion engine in the freshwater distillation system
Authors: Minh Dien Vu , Vu Quang Khong , Duy Tien Nguyen , Toi Le Manh
Published: May 2021

In the Internal Combustion Engine (ICE) working operation, fuel is fed into the combustion chamber, where it is burnt in air to convert the chemical energy of fuel into heat according to the first law of thermodynamics. However, the amount of energy transformed into actual power is only 21-33% and 25-40% for gasoline engines and diesel engines, respectively. Consequently, about two-thirds of the remaining energy is lost due to the heat transfer to the surrounding environment, in which the heat energy removed by the exhaust occupies the largest proportion (about 30-35%). Therefore, utilizing the regenerative heat from the exhaust gases is a potential solution to improve the ICE’s efficiency. This paper presents the simulation results of the effect of heat exchange tube structure on waste recovery capacity in the system, which utilizes the heat of exhaust gases and cooling water of ICE based on Ansys Fluent. In addition, the boundary conditions, the flow, and exhaust temperature are determined by simulating the engine’s working process using AVL-Boost. This research shows that the heat utilization efficiency of exhaust energy can be achieved up to 34%, corresponding to a reasonable structure. This research’s study outcomes are the foundation to implement the complete design of the heat waste recovery system of ICE.
The deterioration of 100 years old coated steel bridges
Authors: Paglia C. , Antonietti S. , Mosca C.
Published: May 2021

Steel bridges have been widely built from the beginning of the XIX century. The structures were protected from the uniform atmospheric corrosion through Lead-containing coatings. These exhibited over the decades a very good resistance to degradation. Generally, a similar reduced corrosion was also observed for the rivets, which linked the structural elements. The degradation was mainly located in the regions directly exposed to rainfall or water flux. The formation of craters or exfoliation was only locally found. The enrichment of organic deposits promoted the permanence of humidity, which in turn, had an adverse effect on the steel conservation. Generally, the total coating thickness slightly decreased, and the long-therm protection was no longer attained. The content of Lead has a detrimental effect on the environment. Thus, the restoration works must consider the pollutant effect during its elimination and disposal.
Quantum autoencoders with enhanced data encoding
Authors: Bravo-Prieto Carlos
Published: May 2021

We present the enhanced feature quantum autoencoder, or EF-QAE, a variational quantum algorithm capable of compressing quantum states of different models with higher fidelity. The key idea of the algorithm is to define a parameterized quantum circuit that depends upon adjustable parameters and a feature vector that characterizes such a model. We assess the validity of the method in simulations by compressing ground states of the Ising model and classical handwritten digits. The results show that EF-QAE improves the performance compared to the standard quantum autoencoder using the same amount of quantum resources, but at the expense of additional classical optimization. Therefore, EF-QAE makes the task of compressing quantum information better suited to be implemented in near-term quantum devices.
Peel learning for pathway-related outcome prediction
Authors: Li Yuantong , Wang Fei , Yan Mengying , Cantu III Edward , Yang Fan Nils , Rao Hengyi , Feng Rui
Published: May 2021

Motivation

Traditional regression models are limited in outcome prediction due to their parametric nature. Current deep learning methods allow for various effects and interactions and have shown improved performance, but they typically need to be trained on a large amount of data to obtain reliable results. Gene expression studies often have small sample sizes but high dimensional correlated predictors so that traditional deep learning methods are not readily applicable.

Results

In this article, we proposed peel learning, a novel neural network that incorporates the prior relationship among genes. In each layer of learning, overall structure is peeled into multiple local substructures. Within the substructure, dependency among variables is reduced through linear projections. The overall structure is gradually simplified over layers and weight parameters are optimized through a revised backpropagation. We applied PL to a small lung transplantation study to predict recipients’ post-surgery primary graft dysfunction using donors’ gene expressions within several immunology pathways, where PL showed improved prediction accuracy compared to conventional penalized regression, classification trees, feed-forward neural network and a neural network assuming prior network structure. Through simulation studies, we also demonstrated the advantage of adding specific structure among predictor variables in neural network, over no or uniform group structure, which is more favorable in smaller studies. The empirical evidence is consistent with our theoretical proof of improved upper bound of PL’s complexity over ordinary neural networks.

Availability and implementation

PL algorithm was implemented in Python and the open-source code and instruction will be available at https://github.com/Likelyt/Peel-Learning.

Supplementary information

Supplementary data are available at Bioinformatics online.
Quartet-based inference is statistically consistent under the unified duplication-loss-coalescence model
Authors: Markin Alexey , Eulenstein Oliver
Published: May 2021

Motivation

The classic multispecies coalescent (MSC) model provides the means for theoretical justification of incomplete lineage sorting-aware species tree inference methods. This has motivated an extensive body of work on phylogenetic methods that are statistically consistent under MSC. One such particularly popular method is ASTRAL, a quartet-based species tree inference method. Novel studies suggest that ASTRAL also performs well when given multi-locus gene trees in simulation studies. Further, Legried et al. recently demonstrated that ASTRAL is statistically consistent under the gene duplication and loss model (GDL). GDL is prevalent in evolutionary histories and is the first core process in the powerful duplication-loss-coalescence evolutionary model (DLCoal) by Rasmussen and Kellis.

Results

In this work, we prove that ASTRAL is statistically consistent under the general DLCoal model. Therefore, our result supports the empirical evidence from the simulation-based studies. More broadly, we prove that the quartet-based inference approach is statistically consistent under DLCoal.

Supplementary information

Supplementary data are available at Bioinformatics online.
DOP54 Real-world effectiveness of thiopurine monotherapy in Crohn’s Disease: Is there still a place for thiopurines in the biological era?
Authors: Rezazadeh Ardabili A , Jeuring S F G , Mujagic Z , Romberg-Camps M J L , van Bodegraven A A , Jonkers D M A E , Pierik M J
Published: May 2021

Background

In current guidelines, thiopurines are still recommended as first-line maintenance therapy for patients with Crohn’s disease (CD). Due to their lack of immunogenicity, oral administration route and low costs, thiopurines are an attractive first-line treatment option. However, in recent studies the position of thiopurine monotherapy in CD has been questioned as a result of relatively lower overall effectiveness rates compared to ulcerative colitis. Real-world long-term effectiveness data substantiating the use and position of thiopurines in CD management remain sparse. We assessed long-term effectiveness of thiopurine monotherapy in CD using the population-based IBD South-Limburg (IBDSL) cohort.

Methods

All CD patients in the IBDSL cohort starting thiopurine monotherapy as first-line maintenance therapy between 1991–2014 were included. Thiopurine monotherapy was defined effective if either: (1) no escalation to biological treatment, (2) no course of corticosteroids, (3) no resective surgery or, (4) no hospitalization for active disease was required whilst on thiopurine treatment. Patients with early treatment discontinuation (i.e. <3 months) were identified, including reason of discontinuation. Long-term effectiveness was assessed adjusting for differences in follow-up between patients using Kaplan-Meier analysis. Potential risk factors for therapy failure were identified using Cox regression.

Results

In total, 643/1162 (55.3%) CD patients (median follow-up: 8.5 years IQR 5.0–13.2) received first-line thiopurine monotherapy after a median of 9.7 months (IQR 3.2–31.3) after diagnosis. Therapy was discontinued within three months in 164 patients (25.5%), mainly due to adverse events [Figure 1]. Thiopurine monotherapy was effective for the duration of treatment in 229/479 (35.6%) patients, corresponding to estimated effectiveness rates of 62.9%, 43.9% and 31.2% after 1, 5 and 10 years, respectively [Figure 1–2]. No significant difference in effectiveness was observed after stratifying for era of thiopurine initiation (pre-biological (1991–1998) vs. biological (>1999) era, p=0.84). Factors associated with thiopurine failure were stricturing disease (aHR 1.41, 95%CI 1.01–1.96) and upper GI involvement (aHR 1.52, 95%CI 1.02–2.28) at diagnosis. During follow-up, 40/229 patients with a durable response discontinued treatment due to quiescent disease. Of these, 35 patients (87.5%) remained without treatment 24 months after discontinuation.

Conclusion

Real-world data from this population-based study demonstrate that thiopurine monotherapy remains an effective and durable first-line treatment option for CD, even in the biological era. These results should be considered in the ongoing discussion regarding the position of thiopurine therapy.
OP06 5-aminosalicylates are not associated with adverse outcomes in Inflammatory Bowel Disease patients with COVID-19: Analysis from an international registry
Authors: Ungaro R , Brenner E , Agrawal M , Gearry R B , Kaplan G G , Kissous-Hunt M , Ng S C , Rahier J F , Reinisch W , Steinwurz F , Zhang X , Lewis J D , Kappelman M D , Colombel J F
Published: May 2021

Background

Prior data have suggested that 5-aminosalicylates (5-ASA) may be associated with an increased risk of severe COVID-19 among inflammatory bowel disease (IBD) patients. We aimed to evaluate the association of 5-ASA with severe COVID-19 in a large cohort of IBD patients.

Methods

We analyzed data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, a large, international database of IBD patients with confirmed COVID-19. The primary outcome was severe COVID-19, defined as intensive care unit admission, ventilator use, and/or death. Hospitalization due to COVID-19 was a secondary outcome. We performed multivariable regression modeling with a generalized estimating equation accounting for country as a random effect to analyze the association of 5-ASA with severe COVID-19. Models a priori included age, sex, race, disease phenotype (CD or UC/IBD-U), corticosteroid use, azathioprine/6-mercaptopurine use, TNF antagonist use, disease activity by physician global assessment, number of comorbidities, and days from SECURE-IBD inception to reporting. We constructed three models examining 5-ASA use as binary covariate using 1) all patients, 2) only patients on any biologic, and 3) only patients on TNF antagonists.

Results

5,174 patients were included with 212 (4.1%) severe COVID-19 events. At the time of COVID-19 infection, 1,504 patients were taking 5-ASA. 5-ASA patients were older (mean age 44 vs. 38.3 years, p<0.001), more likely to have UC (70.7% vs. 27.7%, p<0.001), less likely to be in remission (49.6% vs. 57.2%, p<0.001), and more likely to have at least one comorbidity (33.6% vs. 26.7%, p<0.001) compared to patients not on 5-ASA. 3,325 patients were on any biologic and 2,216 were on a TNF antagonist. Among all patients, 5-ASA was not associated with severe COVID-19 (adjusted OR [aOR] 1.14, 95% confidence interval [CI] 0.86–1.52) (Table 1). Prior associations of age, comorbidities, TNF antagonists, and corticosteroids with severe COVID-19 were similar to prior analyses (Table 1). In analyses restricting to those on any biologic or only TNF antagonists, there was also no significant association between 5-ASA and severe COVID-19 (aOR 0.76, 95% CI 0.38–1.50 and aOR 0.99, 95% CI 0.43–2.32, respectively). Use of 5-ASA was not associated with risk of COVID-19 related hospitalization in any analysis.

Conclusion

In an analysis of updated data from the SECURE-IBD registry, 5-ASA use was not associated with worse outcomes among IBD patients with COVID-19.
OP23 Efficacy and safety of upadacitinib as induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from phase 3 U-ACCOMPLISH study
Authors: Vermeire S , Danese S , Zhou W , Pangan A , Greenbloom S , D’Haens G , Panes J , Juillerat P , Lindsay J O , Loftus Jr E V , Sandborn W J , Reinisch W , Sanchez Gonzalez Y , Huang B , Xie W , Liu J , Weinreich M A , Panaccione R
Published: May 2021

Background

Upadacitinib (UPA) is a selective and reversible Janus kinase inhibitor.U-ACCOMPLISH is one of two phase 3 induction trials that evaluated the safety and efficacy of UPA 45 mg once daily (QD) in adults with ulcerative colitis (UC).

Methods

U-ACCOMPLISH was a multicentre, randomized, double-blind, placebo-controlled trial (NCT03653026) that enrolled patients with moderate-to-severe UC (defined as adapted Mayo score 5–9 with centrally read endoscopic score 2–3) who had inadequate response, loss of response, or intolerance to aminosalicylates, immunosuppressants, corticosteroids and/or biologics. Patients were randomized 2:1 to UPA 45 mg QD or placebo (PBO) for 8 weeks. At week 8, responders entered the maintenance phase and non-responders entered the extended treatment period to receive open-label UPA 45 mg QD for additional 8 weeks.The primary endpoint (clinical remission per adapted Mayo Score) and ranked secondary endpoints including symptomatic, endoscopic– histologic evaluations from the 8-week PBO-controlled period are reported here. Non-responder imputation incorporating multiple imputation for missing data due to COVID-19 are reported.

Results

522 patients were randomized (UPA, n=345; PBO, n=177); the intent-to-treat population included 341 patients in UPA and 174 patients in PBO group. Baseline demographics and disease characteristics were similar between groups; 50.7% and 51.1% were biologic inadequate responders in UPA and PBO groups, respectively (Table 1). A significantly higher proportion of patients receiving UPA 45 mg QD (33.5%) versus PBO (4.1%) achieved the primary endpoint (adjusted treatment difference: 29.0% [23.2, 34.7]; P<0.001). A significantly higher proportion of patients receiving UPA versus PBO also achieved all ranked secondary endpoints (all P<0.001; Figure 1).Serious adverse events were reported by 3.2% and 4.5% of patients in UPA and PBO groups, respectively (Table 2). Similar rates of serious infection were observed in both groups (0.6%); 2 events each of herpes zoster and opportunistic infection were reported in UPA group. No active tuberculosis, malignancy, adjudicated major adverse cardiovascular events, or deaths were reported in the study. One patient with venous thromboembolism (deep vein thrombosis and pulmonary embolism) and 1 patient with gastrointestinal perforation were reported in the placebo group.

Conclusion

In U-ACCOMPLISH, 8-week UPA 45 mg QD induction treatment led to statistically significant improvements in clinical, endoscopic, and combined endoscopic-histologic endpoints. The treatment was well tolerated, and the safety profile and AE prevalence was comparable with previous studies of UPA with no new safety signals identified.
OP33 Oral ritlecitinib and brepocitinib in patients with Moderate to Severe Active Ulcerative Colitis: Data from the VIBRATO umbrella study
Authors: Sandborn W , Danese S , Leszczyszyn J , Romatowski J , Altintas E , Peeva E , Vincent M , Reddy P , Banfield C , Banerjee A , Gale J , Hung K
Published: May 2021

Background

The efficacy and safety of oral ritlecitinib (JAK3/TEC inhibitor) and brepocitinib (TYK2/JAK1 inhibitor) were assessed in a 32-week Phase 2b induction-maintenance umbrella study (VIBRATO) in participants with moderate to severe active ulcerative colitis who had inadequate or loss of response, or intolerance to corticosteroids, immunosuppressants, or biologic therapies. We report efficacy and safety results from the 8-week induction period of the VIBRATO study.

Methods

Adult participants with Total Mayo Score ≥6 and centrally-read Mayo endoscopic subscore ≥1 were randomised to receive oral ritlecitinib 20, 70, or 200 mg; brepocitinib 10, 30, or 60 mg; or placebo once-daily (QD) for 8 weeks. Participants then continued in their respective treatment cohorts to receive ritlecitinib 50 mg or brepocitinib 30 mg QD for 24 weeks. The proportions of patients who achieved remission (Total Mayo Score ≤2; no individual subscore >1; rectal bleeding subscore 0), modified remission (Modified Mayo Score: Total Mayo without Physician’s Global Assessment; stool frequency subscore ≤1; rectal bleeding subscore 0; endoscopic subscore ≤1), or endoscopic improvement (Mayo endoscopic subscore ≤1) were analysed.

Results

319 participants were randomised: baseline mean (standard deviation [SD]) age 40.3 (13.8) years; mean (SD) Total Mayo Score 9.0 (1.5); and median (range) disease duration 4.8 (0.24, 36.5) years. Ritlecitinib and brepocitinib were generally safe and well tolerated. At Week 8, a dose–response relationship was observed across all efficacy endpoints for ritlecitinib and brepocitinib. The proportions of participants achieving remission were significantly higher (P<0.05) with ritlecitinib 70 and 200 mg and brepocitinib 30 and 60 mg vs placebo (Figure 1). The proportions of participants achieving endoscopic improvement and modified remission were significantly higher in all ritlecitinib and brepocitinib groups vs placebo (Figures 2 and 3).

Conclusion

Ritlecitinib 70 and 200 mg QD and brepocitinib 30 and 60 mg QD demonstrated significant improvement in remission, modified remission, and endoscopic improvement in participants with moderate to severe active ulcerative colitis.
P035 Potential biomarkers for diagnosis through proteomics, in patients with Inflammatory Bowel Disease
Authors: Muñoz-Villafranca C , Aresti Goiriena U , Ispizua N , Irigoyen Muñoz M , Rivera Garcia N A , Ortiz de Zárate J , Arreba Gonzalez P , Calderón García Á J
Published: May 2021

Background

Currently,endoscopy,an invasive medical procedure, is the gold standard for diagnosis of inflammatory bowel disease (IBD) and to determine mucosal activity.Our main goal was to identify biomarkers in saliva samples that can be used as a screening tool for the diagnosis of ulcerative colitis(UC) and Crohn`s disease(CD).

Methods

100 saliva samples were collected from: healthy individuals(20), UC-active stage(10),UC-remission stage(31),CD-active stage(7) and CD-remission stage(32) patients. The samples were thawed on ice and centrifugated at 10,000g for 15 min at 4ºC.The supernatants were aliquoted and stored at -80ºC.

The protein extracts were digested with trypsin and peptides resulting from digestion were loaded onto a nano Acquity UPLC chromatograph and analysed in a nano Elute coupled on-line to a timsTOF Pro(Bruker).The data obtained was then processed and loaded onto the Progenesis LC-MS software (Nonlinear Dynamics) for Orbitrap data and PEAKS(Bioinformatics Solutions Inc.) for timsTOF Pro data. Finally, this information was converted to deregulation patterns at protein level and relative quantification was done.

Saliva protein levels were compared between healthy (always as control) and CD remission,UC remission,UC active and CD active stages respectively.The identification of potential biomarkers was carried out with classical statistic methods(p value<0,05 and ratio> 1,5) and data Mining mathematical model(p-value<0,05, balanced accuracy ≥ 70, sensitivity ≥ 60 and specificity ≥ 60).

Results

We have chosen the most relevant classifiers according to statistical and biological criteria, based on their biological function and the pathogenesis of UC or CD(figure 1).

We have identified 152 classifiers(biomarkers),118 single and 34 dual, defined by one or two proteins of a list of 135 proteins(table 1).The classifiers are shown for each cohort compared to healthy control:42 biomarkers were found in Active UC,16 in Remission UC, 99 in Active CD and 13 in Remission CD,all of them compared to healthy controls.

Conclusion

Multiple potential biomarkers have been identified in saliva in relation to IBD.

Biomarkers with significant value have been found for identifying and classifying UC as well as CD, compared to controls.The number of biomarkers found in CD has been higher than in UC.

The simple biomarker option(versus dual) is recommended,since its application involves fewer errors.
P036 MicroRNA composition of colon crypt-top and crypt-bottom epithelial cells in Ulcerative Colitis
Authors: Inčiūraitė R , Juzėnas S , Ramonaitė R , Skiecevičienė J
Published: May 2021

Background

Ulcerative colitis (UC) is a chronic relapsing large intestine condition of inflammatory origin1. One of the most common features of UC is the injury of the intestinal barrier, which is composed primarily of colonic epithelial cells (CEpCs)2. The aim of this study was to identify UC-induced miRNA markers in CEpCs by determining the miRNA expression profile changes in crypt-top and crypt-bottom CEpC populations during active (aUC) and inactive (iUC) UC.

Methods

Crypt-top and crypt-bottom CEpCs were sorted from biopsies of healthy control (HC) individuals (n=19), patients with aUC (n=17) and iUC (n=15) using FACS technology. Total RNA was extracted, small RNA sequencing libraries were prepared and sequenced using Illumina platform. Sequencing data was processed with nextflow-core/smrnaseq pipeline. Differential expression, correlation, miRNA-target interactions, gene set enrichment analyses and data visualisation were performed using Rstudio software packages DESeq2, isomiRs, multimiR, SingleCellExperiment, clusterProfiler, ReactomePA, etc. The miRNAs with an adjusted p-value < 0.05, and absolute value of log2 fold change > 1 were considered to be significantly differentially expressed.

Results

432 unique miRNAs were identified in samples. Changes of expression profile during aUC were identified in crypt-bottom CEpCs (compared to: (i) HC - 23 miRNAs, (ii) iUC - 22 miRNAs), as well as in crypt-top CEpCs (compared to: (i) HC - 28 miRNAs, (ii) iUC - 9 miRNAs). Also, 7 miRNAs were differentially expressed in crypt-bottom CEpCs and 3 miRNAs in crypt-top CEpCs during iUC compared to HC. 5 miRNAs were identified to be differentially expressed during aUC, 2 miRNAs - during iUC, and 11 miRNAs in HC when comparing expression profiles of crypt-bottom and crypt-bottom CEpCs. We also identified 16 and 14 miRNAs which expression in crypt-bottom and crypt-top CEpCs moderately (0.5<rho<0.7) correlated with Mayo score, respectively. Finally, the gene sets of pathways revealed the involvement of several miRNAs in biological processes and molecular functions associated with UC pathogenesis.

Conclusion

The changes of expression profiles of miRNAs revealed that crypt-top and crypt-bottom CEpCs respond to inflammation differently, the expression of these miRNAs reflects disease activity and modulates the processes of UC pathogenesis.

References
P107 Monitoring inflammatory bowel disease in clinical practice using gut microbial markers in faecal samples. Prospective study in a clinical cohort
Authors: Miquel Cusachs J O , Bahí Saavedra A , Vila Currius M , Lliròs Dupre M , Leal Validivieso C , Aldeguer Manté X
Published: May 2021

Background

The gut microbiota(GM) plays a pivotal role in the pathogenesis of inflammatory bowel disease (IBD) which includes Crohn’s disease (CD) and ulcerative colitis(UC). The degree of IBD activity, and therefore of inflammation, modifies GM composition towards an altered pattern called dysbiosis This IBD-dysbiosis pattern is different from healthy individuals(HI). The degree of dysbiosis is a good indicator of IBD activity and could be useful in monitoring IBD. The AIM of this study is to quantify the degree of IBD dysbiosis of the GM, and determine the utility as a biomarker for monitoring IBD disease compared with HI.

Methods

80 IBD patients from 2 tertiary hospitals have been included. We included patients with clinical Remission (R), defined as Faecal Calprotectin (FC) levels <250 µg/gr., and Activity (A) (FC >250 µg/gr.) with mild to moderate disease. A blood sample (to determinate RCP, albumin and hemoglobin (Hb) levels) and stool sample (to determinate Faecal calprotectin (FC) and GM analysis) has been collected. DNA was extracted from fecal samples, using real-time qPCR techniques and 3 bacterial groups (Faecalibacterium prausnitzii (FP), Escherichia coli (EC), and total eubacteria (TE) that are highly representative of GM dysbiosis degree were analyzed. In regards to these bacteria, an index called FEI has been created to quantify GM dysbiosis. GM and FEI data has been collected in order to compare with standards analytical markers (Hb, Alb, RCP, FC). The duration of this study is 6 months with samples every three months (T0, T1 and T2).

Results

35 UC and 45 CD patients were included. Initial treatment in 76,25% of cases were biological drugs. 55 % of patients were in remission at first sample. The analysis of clinical data showed that only PCR and CP had significantly differences between R and A (p=0,0037) and type of disease (p=0,018) and temporal evolution (p=0,004). Higher levels of FP are been observed in UC (p=0,0013) and higher levels of EC in CD (p=0,003) in all 3 samples. FEI values are higher in UC (p=0,001) and different between CD and UC and HI (p=0,015) indicating FEI ability to differentiate between 2 disease subtypes and HI. FEI cut-off point has been set at 1,869 (S 0,44 and E0,82; AUC 0,658) in T0. The IBD-GM compared with HI-GM showed lower FP abundance (p=0,002) and higher TE abundance (p=0,0001) with increased non-significant EC abundance. The A and R abundances for FP,FEI and TE showed significant differences between CD, UC and HI, indicating capacity to differentiate between activity and remission in T0.

Conclusion

Microbiological markers and FEI allow to differentiate between IBD subtypes and HI, and between A and R. The combination if RCP, FC and FEI can become a potential biomarker of IBD activity.
P138 Platelet-to-lymphocyte ratio index: a reliable tool for non-invasive assessment of endoscopic activity in small bowel Crohn’s Disease
Authors: Macedo Silva V , Freitas M , Xavier S , Cúrdia Gonçalves T , Boal Carvalho P , Dias de Castro F , Rosa B , Moreira M J , Cotter J
Published: May 2021

Background

The platelet-to-lymphocyte ratio (PLR) index has been a recent focus of investigation as a reliable marker of inflammation. This score was recently shown to have a good accuracy upon predicting endoscopic remission in patients with colonic Crohn’s Disease (CD). We aimed to assess the discriminative power of PLR index in patients with isolated small bowel CD.

Methods

Single center study of consecutive patients with isolated small bowel CD (L1 ± L4 disease according to Montreal classification) who underwent small bowel capsule endoscopy (SBCE) for assessment of endoscopic activity between January 2019 and December 2020. Only complete SBCEs were considered. CD endoscopic activity was classified according to the Lewis score (LS) value. Complete blood count, C-reactive protein and fecal calprotectin values were collected within 1 month of SBCE.

Results

Final sample included 49 patients, 35 (71.4%) of them females, with a mean age of 35.1±11.8 years. SBCE reported mucosal healing (LS<135) in 30.6% of the patients; mild activity (135≤LS<790) in 42.9% and moderate-to-severe activity (LS≥790) in 26.5% of the patients.

PLR index positive correlation with LS was significant and moderate (k=0.597; p<0.001). This correlation was stronger than the one seen between fecal calprotectin (k=0.525; p=0.001) or C-reactive protein (k=0.321; p=0.029) and the LS score.

In particular, PLR index presented an excellent accuracy for predicting patients with a moderate-to-severe endoscopic activity (AUC=0.908; 95%CI=0.816–0.999; p<0.001), with an optimal cut-off of PLR above 157 (sensitivity 92.3%; specificity 82.9%). The accuracy for prediction of mucosal healing was good (AUC=0.743; 95%CI=0.600–0.887; p=0.007), with an optimal cut-off of PLR below 126 (sensitivity 66.7%; specificity 80.0%).

Conclusion

PLR index demonstrated an excellent acuity for predicting patients with moderate to severe disease in small bowel CD. Moreover, it also demonstrated good acuity for predicting mucosal healing on this set of patients. These results come from a significant correlation of PLR index with endoscopic activity in small bowel CD. Our findings establish this index as a promising and easy-to-apply tool for non-invasive and regular follow-up of patients with small bowel CD.
P166 Impact of consultation frequency and time to diagnosis on subsequent Inflammatory Bowel Disease outcomes
Authors: Jayasooriya N , Saxena S , Blackwell J , Petersen I , Bottle A , Creese H , Pollok R
Published: May 2021

Background

The impact of length of time between the point of initial contact, at symptom onset, with a health-care provider and diagnosis of inflammatory bowel disease (IBD) on subsequent disease outcomes, is unclear. Diagnosis can be challenging and delay common, with an excess of gastrointestinal (GI) symptoms reported 3 years before the diagnosis of IBD compared to the background population.1

We describe the impact of time to diagnosis and frequency of consultation amongst individuals with GI symptoms who later go on to develop ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

Using the Clinical Practice Research Datalink, a nationally representative research database, incident cases of IBD were identified between 2003 and 2016. GI symptoms were defined as abdominal pain, diarrhoea, or rectal bleeding. The proportion of individuals consulting for incident GI symptoms within 3 years prior to IBD diagnosis was identified. Using a multivariable regression model we evaluated the association between time to diagnosis from incident consultation and consultation frequency for GI symptoms on disease outcomes (corticosteroid (CS) and thiopurine (TP) use, hospitalisation and major abdominal surgery) 5 years after IBD diagnosis.

Results

Six thousand nine hundred and sixty-seven incident cases of IBD were identified during the study period. Within 3 years prior to IBD diagnosis, 2,645 (38%) patients had an incident presentation with GI symptoms in primary care (782 CD, 1,863 UC). Presentation with GI symptoms occurred >3 years before IBD diagnosis in 2,842 (41%) of patients. There was no recorded primary care consultation for 1,480 (21%) patients.

Time to diagnosis from initial consultation was not associated with worse subsequent disease outcomes. However, amongst patients later diagnosed with UC, ≥3 prior consultations for GI symptoms was associated with an increased subsequent risk of CS use (HR 1.19, 95% CI 1.05 -1.36), CS dependency (HR 1.50, 95% CI 1.10 -2.05), TP use (HR 1.60, 95% CI 1.22 – 2.11) and colectomy (HR 1.91, 95% CI 1.21 – 3.04). Amongst patients with CD, ≥3 prior consultations were associated with an increased subsequent risk of major abdominal surgery (HR 1.75, 95% CI 1.22 -2.5) and hospitalisation (HR 1.58, 95% CI 1.18 -2.11)

Conclusion

Frequent primary care consultation with GI symptoms, but not symptom duration prior to IBD diagnosis, was associated with worse subsequent disease outcomes. Steps are needed to expedite IBD diagnosis to reduce the risk of adverse disease outcomes.

Reference
P226 Does faecal Calprotectin help differentiate inflammatory from fibrous stenosis in Crohn’s disease?
Authors: Ben Farhat F , Sabbah M , Ben Abid M , Bibani N , Bellil N , Aoun K , Bouratbine A , Gargouri D
Published: May 2021

Background

Digestive stenosis is the most common complication of Crohn’s disease. It can be either inflammatory or fibrous. The clinical, biological and especially morphological characteristics of the stenosis can help differentiate inflammatory stenosis from fibrous stenosis. The aim of our study was to evaluate the performance of fecal calprotectin (FC), a marker of intestinal inflammation, in identifying the type of stenosis.

Methods

A prospective study including all patients followed for Crohn’s disease in the Gastroenterology Department of Habib Thameur Hospital over a 6-month period from July 2020 to December 2020 was performed. Clinical, biological, endoscopic and radiological data were collected. The inflammatory nature of the stenosis was mainly retained according to radiological activity signs objectified by cross-sectional imaging. All patients were given a FC assay at the time of inclusion. FC was dosed by using the Bulhmann® FCAL ELISA technique. The statistical study was carried out using the SPSS software version 22.0 (p value significant if lower than 0.05).

Results

Fifty patients were included in our study (mean age 40.54 years [18–67] and sex ratio (M/F) = 1.77). The average evolution time of the disease was 8 years [6 months- 27 years]. The disease was ileal in 16 patients, colic in 4 patients and ileocolic in 30. Twenty patients (40%) had an intestinal stenosis whose location was: ileocaecal anastomosis (n=9), ileal (n=8) and colic (n=3). Multiple stenoses (colic and ileal) were noted in 3 patients. Fifteen patients were on medical treatment at the time of inclusion: 7 patients were on Infliximab, 5 were on azathioprine and 3 were on 5ASA. Digestive symptoms such as diarrhoea or subocclusive syndromes were noted in 7 patients. A biological inflammatory syndrome (CRP >10mg/L) was noted in 8 patients. Of the 20 stenoses included, 8 were of the inflammatory type (40%). In the presence of stenosis, the mean level of FC was 224.9 μg/g. A high level of FC was associated with the inflammatory type of stenosis (p<0.001). A cut-off of 135 µg/g had a sensitivity 100% and a specificity of 90%. CRP did not differentiate between inflammatory stenosis and fibrous stenosis (p=0.4).

Conclusion

According to our study, FC is a good marker of intestinal inflammation allowing to differentiate an inflammatory from a fibrous stenosis during Crohn’s disease better than the usual biological markers. These results should be confirmed by larger studies.
P253 A qualitative study exploring meaningful improvement in bowel urgency among adults with moderate to severe Ulcerative Colitis
Authors: Newton L , Guobyte A , McFadden S , Symonds T , Delbecque L , Donaldson J , Naegeli A
Published: May 2021

Background

Ulcerative Colitis (UC) is a chronic disease with periods of relapse and remission. Bowel urgency, the sudden or immediate need for a bowel movement, is one of the most bothersome symptoms experienced by patients with UC. This study explored how patients define urgency severity and what would be a meaningful improvement based on a numeric rating scale (NRS).

Methods

In-depth interviews were conducted in the United States with 19 adults with clinician-confirmed moderate to severe UC. Participants were asked to define levels of bowel urgency severity using an 11-point NRS (where 0 = no urgency and 10 = worst possible urgency) and to describe what would be a meaningful improvement based on how this change would impact their daily life. Interviews were audio-recorded, transcribed, and coded using thematic coding in NVivo.

Results

Mild bowel urgency was described as ranging between 0 to 3 on the 11-point scale by most UC patients (n=16, 84%). Mild was described as “almost normal” or “normal urgency” (n=6, 32%) and being able to make it to the bathroom with ease (n=5, 25%). Most participants (n=15, 79%) rated moderate urgency between 4 to 6 on the 11-point scale. At this level, participants commented that they would need to ensure they are close to a bathroom (n=7, 37%). Finally, ratings for severe urgency clustered between 6 to 8 (n=7, 37%) and 8 to 10 (n=12, 63%). Severe bowel urgency was described as an immediate or uncontrollable need (n=8, 42%) which impacts their ability to leave the home (n=7, 37%). When asked about what change on the urgency NRS would be meaningful, n=10 (53%) participants reported that a 1-point change would be meaningful, with most stating that any change was an improvement. Participants commented that a 1-point change would reflect improved emotional well-being and greater confidence to leave the home. In contrast, 9 (47%) participants wanted improvements of more than 1-point change; 5 (26%) indicated that a 2-point improvement was required to consider the change meaningful and 4 (21%) felt a 3-point change or more was needed. With this greater level of change, participants described having a significant improvement in urgency, with less frequent urges and improved emotional well-being.

Conclusion

This qualitative study revealed that UC patients largely agreed regarding ratings of ‘mild’ and ‘moderate’ bowel urgency on an 11-point severity scale. ‘Severe’ bowel urgency was split between two ranges suggesting the existence of ‘very severe’ bowel urgency. In addition, the majority of UC patients perceived a 1 or 2-point reduction on the urgency NRS as a meaningful change in their lives.