bluuebunny/crossref_metadata_2025_split huggingface dataset:
Achyranthes aspera (devil's horsewhip).
Authors: Rojas-Sandoval Julissa , Acevedo-Rodríguez Pedro 
Published: May 2021

Abstract

Physiology and Phenology: A. aspera is a coarse herb or shrub, sometimes growing in arable land as an annual, but under suitable conditions lasting for a number of years and reaching a height of 4 m. There are sun and shade adapted types (Vora et al., 1989). Reproductive Biology: In germination studies of desert plants, Khan et al. (1984) noted little seed dormancy in this species. Associations: A. aspera displays anti-feedant activity against gram pod borer (Helicoverpa armigera; Singh et al., 2001).
Objective performance assessment on trainees of a VATS simulation program: A prospective single center study
Authors: Koliakos E , Bedat B , Caput B , Hasenauer A , Federici S , Ojanguren-Arranz A , Gonzalez M , Krueger T , Perentes J Y 
Published: May 2021

Abstract

Objective
A prospective single center study to assess the objective impact on motion performance of a VATS simulation program on thoracic surgery trainees.

Methods
We developed a 6-month VATS simulation training program including exercises of progressive complexity on 3 different black box simulators: a 2D and 3D lobectomy model (Stupnik®) and a 3D perfused lobectomy model (Crabtree®). Between November 2019 and 2020, all consecutive thoracic surgery residents (study group) were prospectively enrolled in this weekly training program that was supervised by a board certified thoracic surgeon. We compared an objective performance evaluation of the study group before and after the training program by assessing movement parameters (distance in cm, time in sec) and absence of shock/extreme motion (%) on 3 simple standardized thoracoscopic exercises (peg placement on a board, rope insertion in loops and precision circle cutting) using the Simball®. Also, we determined the objective performance 6 months apart of 5 final year medical students (unexperienced controls) that were not trained.

Results
There were 7 residents (2 female and 5 male, median age: 29 [range: 26-34] years) who completed the 6-month VATS simulation training program. Five residents were in their first year while two had &gt;3 year experience. The study group's objective performance improved significantly for all three movement parameters in all standardized exercises (Figure 1) after the training program. The objective performance of the unexperienced control group was comparable to the study group before training, but it remained unchanged at 6 months (p &gt; 0.05). When comparing unexperienced and advanced residents, we observed that the training program had more impact on improving the performance for unexperienced residents (p &lt; 0.05).

Conclusion
This study suggests that the implementation of a VATS simulation training program improves the objective performance of trainees compared to controls. Such programs could be interesting adjuncts for residents.
Why Does Social Work Work? A Proposal for a Social Work Understanding of Causality
Authors: Dollinger Bernd 
Published: May 2021

Abstract
In a critical examination of evidence-based approaches, the contribution argues for the development of a concept of causality that is sustainable for social work in order to explain why it has an impact. Two special features of social work are important in this respect: it is confronted with relatively high complexity and service users shape the effects of social work in their interactions with professionals. A social work conceptualisation of causality should consider both aspects, and it should be analytically grounded in interactions between professionals and service users. However, their interrelated practices do not stand alone. Interactions are always reflexively accompanied by the participants. The awareness and expectation that social work measures (should) have consequences is part of the practice of social work and its effects.
Uncertainty and general equilibrium: an evaluation of Professor Knight’s contributions to economics
Authors: Brooke Geoffrey T F , Cheung Lydia 
Published: May 2021

Abstract
One hundred years ago Frank Hyneman Knight made a distinction between risk and uncertainty. The distinction, and the theories of profit and entrepreneurship that followed from it, are widely considered his most important contributions to economic theory. In this paper, we ask why they have not had more impact on economic theory and whether they are indeed his most important contributions. The distinction between risk and uncertainty has been of limited use; in making it, Knight overlooked all forms of partial information. The uncertainty theory of profit in turn has been superseded by theories of imperfect competition based on oligopoly and monopolistic competition. Rather than these innovations, Knight’s real contribution to economics was promoting the model of perfect competition.
DOP07 Ulcerative Colitis associated single nucleotide polymorphisms found in transcription factor binding sites effect key pathogenesis pathways and facilitate patient stratification
Authors: Modos D , Brooks-Warburton J , Sudhakar P , Madgwick M , Fazekas D , Szalay-Beko M , Thomas J P , Verstockt B , Watson A , Tremelling M , Parkes M , Vermeire S , Bender A , Carding S R , Korcsmaros T 
Published: May 2021

Abstract

Background
Ulcerative Colitis (UC) associated single nucleotide polymorphisms (SNP) are mostly in non-coding regions of the genome. Because of that, it has been challenging to determine their role in the disease onset and severity. We have previously developed an integrative workflow (termed iSNP) to understand better how these SNPs are involved in the pathogenesis of UC. Here we present a recent update both in the methodology and new results, including a new player for prediction of therapeutic escalation in UC.

Methods
From immunochip data of 376 UC patients of an East-Anglian, UK cohort, the SNPs were filtered for only the UC-associated ones. Then we predicted the SNPs’ effect on regulatory interactions using two complementary transcription factor-target gene prediction methods, RSAT and FIMO. SNPs were considered if the SNP was located in the promoter region of a gene or in an enhancer region of a gene defined by the HEDD database. We considered a gene ‘SNP-affected’ if the risk allele and the non-risk allele had different transcription factor binding sites detected by any of the two methods. The proteins encoded by the SNP-affected genes were mapped to the integrated and high-confidence signaling network resource OmniPath. We also identified the direct physical interactors (first-neighbours) of these SNP affected genes/proteins. We created networks for each patient separately using their individual SNP-profiles. Finally, based on these patient-specific networks, we clustered patients in an unsupervised manner.

Results
We found 15 UC-associated SNPs which affected transcription factor binding sites, which in turn were modulating 54 genes. From these 54 SNP affected genes, 29 coded proteins that were present in the OmniPath signaling network. The patients formed five clusters, which were significantly correlated with therapeutic escalation defined by mesalazine or other more advanced therapy (p &lt;0.05). Patients requiring immunomodulatory treatment have a greater prevalence of SNP RS943072 (G), corresponding to the transcriptional regulation of VEGF (vascular endothelial growth factor). VEGF is elevated in UC and stimulates angiogenesis, which is involved both in tissue regeneration and inflammation. VEGF is upregulated in the presence of this risk SNP causing increased inflammatory phenotype.

Conclusion
We updated the iSNP method by including enhancer regions and multiple transcription factor binding site prediction methods, and were able to predict that those UC patients who have a VEGF-affecting SNP require therapeutic upscaling.
DOP50 Recommencement of Inflammatory Bowel Disease medications following colectomy for Ulcerative Colitis
Authors: Ledder O , Lujan R , Orlanski-Meyer E , Friss C , Loewenberg Weisband Y , Greenfeld S , Kariv R , Lederman N , Matz E , Focht G , Yanai H , Ollech Y , Dotan I , Turner D 
Published: May 2021

Abstract

Background
Total colectomy (TC) is often considered a curative procedure for patients with chronic refractory ulcerative colitis (UC) or acute severe colitis. Chronic pouchitis and de novo Crohn’s disease (CD) are well recognized sequelae following TC, yet the true incidence of these are poorly characterized in large population models. We assessed the rate of subsequent utilization of IBD medications as a proxy marker of clinically significant pouchitis or de novo CD following TC for UC.

Methods
This study utilized data from the Epi-IIRN project, a meta-database incorporating patient data from all four health maintenance organisations (HMO) in Israel, representing 98% of the population. We included all patients identified in the prevalence cohort with an initial diagnosis of UC who underwent TC from January 2000, with ≥ 6 month follow-up. Primary outcome was utilization of IBD medications (including thiopurines, methotrexate, infliximab, adalimumab, vedolizumab, ustekinumab and tofacitinib) following TC. Secondary outcomes were time to commencement of medications, hospitalizations and repeated surgery. Potential predictors of IBD medication use were identified using multivariable models.

Results
Overall 23,506 patients with UC were identified in the prevalence cohort of whom 456 patients underwent TC for UC and were included in our analysis. 51% of our sample were female, with a median follow up of 8.5 years (IQR 3.8–13.2) and 3956 patient-years. Median age at UC diagnosis was 44.1 (26.5–56.2) years and at TC was 50.2 (34.2–61.7). IBD medications were commenced in 88 (19%) of patients, including 54 (12%) biologics, 56 (12%) immunomodulators and 3 (1%) tofacitinib. A diagnosis of CD was formally assigned to 65 (75%) of these patients. The need for IBD medications was gradual (figure 1).
Patients recommenced on IBD medications were younger at diagnosis (30.3 years (18.3–49.7) vs 41.4 (24.2–55.6), p&lt;0.001), at colectomy (34.3 (21.5–54.1) vs 47.5 (30.4–60.6), p&lt;0.001) and with shorter interval from UC diagnosis to TC (2.2 years (1.0–3.3) vs 2.8 (1.4–5.1), p=0.03). TC during childhood was performed in 33 (7%) patients and these had higher utilization of IBD medications post TC (16/33 (49%) vs 72/423 (17%), p=0.001).

Conclusion
In this nationwide analysis we show that almost 20% of patients require ongoing IBD medications following TC for UC. Younger age is associated with higher rate of subsequent medication use. Patient expectations need be adjusted to account for the potential ongoing requirement of long-term medication following TC.
DOP57 Predictive modelling to examine long term treatment effectiveness of darvadstrocel in patients with complex perianal fistulas in Crohn’s Disease
Authors: Maruszczak M , Genenz K , Turkstra E , Fenu E , Hantsbarger G , Gilaberte I , Karki C , Panes J 
Published: May 2021

Abstract

Background
Darvadstrocel (DVS) was approved in 2018 by EMA for treatment of complex perianal fistulas in Crohn’s disease (CPF-CD)1, with evidence on long-term effectiveness still accruing. The objective of this study was to synthesize clinical trial data and real-world evidence (RWE) using robust statistical methodologies to predict absolute and relative long-term effectiveness of DVS vs. standard of care (SoC) in patients with CPF-CD.

Methods
Data was pooled from the pivotal phase 3 trial ADMIRE-CD (n=212; ≤ 2 years data), INSPECT (n=89; chart review study of patients completing ≥52 weeks in ADMIRE-CD, 2-year follow-up post-trial) and PREFACE (n=313; chart review study of patients undergoing SoC treatment, median follow-up of 4 years). Individual anonymized patient data from these studies were combined and analysed with shared covariates of interest included in regression analyses. Weighting procedures were used to adjust for bias due to differences in distribution of outcomes among patients included in INSPECT. Key outcomes were clinical remission, clinical and patient-centric remission (CPC remission), and relapse. Missing values were imputed using a multi-level Bayesian approach. Predictive statistical models extrapolated clinical outcomes beyond the observed follow-up time using parametric curves which were fitted to the defined study populations for each treatment arm and outcome. The models were then implemented within a semi-Markov model, to obtain the resultant number of patients in remission.

Results
Adult patients with CPF-CD from ADMIRE-CD and PREFACE were similar in age, number of internal and external openings of the perianal fistulas. However, the median CD disease duration was 9.5 vs 6.5 years and prior biologic exposure: 79.5% vs 46.0% for patients in ADMIRE-CD and PREFACE respectively. Patients included in INSPECT were comparable to the overall ADMIRE-CD patients for the covariates of interest. Percentage of patients in CPC remission at 24 months was 39% vs 32% for DVS and SoC respectively for ADMIRE-CD+INSPECT. However, after adding PREFACE data to the predictive model and adjusting for outcome bias, the predicted percentage of patients in CPC remission increased in DVS and SoC groups to 48% vs 35%, respectively. There were small differences by 48 months, after which the remission rates stabilized (Figure).

Conclusion
In this pooled analysis, we used predictive modelling to examine the effectiveness of DVS vs. SoC over a longer time. Inclusion of RWE to the model indicates possible maintenance of the disease-modifying effect of DVS over a longer time period.

Reference
1. Panés et al. Gastroenterology 2018;154:1334–42
Sponsor: Takeda Pharmaceuticals USA, Inc.
DOP68 Assessment of patients’ understanding of Inflammatory Bowel Diseases (IBD): Development and validation of a questionnaire (U-IBDQ)
Authors: Ostromohov G , Fiebelman M , Hirsch A , Ron Y , Aviv Cohen N , Kariv R , Deutsch L , Anbar R , Maharshak N , Fliss Isakov N 
Published: May 2021

Abstract

Background
Education of inflammatory bowel disease (IBD) patients regarding their disease, therapeutic aims and options, is important for patients’ empowerment and commitment to disease management. Currently, there is no standardized and validated tool for assessment patients’ knowledge of their disease. Therefore, we aimed to develop a questionnaire to evaluate IBD patients’ understanding of disease pathophysiology and treatment.

Methods
We have developed the Understanding IBD Questionnaires (U-IBDQ), consisting of multiple-choice questions in two version [for Crohn’s disease (CD) and ulcerative colitis (UC)]. U-The U-IBDQ is composed of 36 questions covering 8 IBD topics. Each question received a similar weight, and total score ranges between 0–100. Questionnaires were tested for: content validity by an independent multidisciplinary stirring committee using the content validity index, face validity, readability and responsiveness on a pilot group of IBD patients. Convergent validity was assessed by correlating scores of the U-IBDQ with physician’s subjective assessment of disease understanding and knowledge. Discriminant validity was assessed by comparison to healthy controls (HC), patients with chronic gastrointestinal (GI) conditions other than IBD, and to GI nurses. A test-retest reliability was assessed among a sub-population of IBD patients which were asked to fill-in the U-IBDQ twice. Multivariate analysis was used to determine associated factors of a high level of disease understanding.

Results
Study population consisted of IBD patients (n=106), HC (n=35), chronic GI disease patients (n=38) and GI nurses (n=19). Mean U-IBDQ score among IBD patients was 56.5±21.9, not differing between CD and UC patients (P=0.941). There was a strong correlation between the U-IBDQ score and the physician’s subjective score (r=0.747, P&lt;0.001). The U-IBDQ showed strong discriminant validity with mean score of IBD patients significantly higher than that of HC and chronic GI disease patients, and was lower than that of GI nurses (P&lt;0.001). The U-IBDQ is reliable as determined by Cronbach’s alpha = 0.872.
Independent factors associated with high U-IBDQ scores included academic education (OR=1.21, 95% CI 1.10–1.33, P&lt;0.001), biologic therapy experience (OR=1.24, 95% CI 1.01–1.53, P=0.046), and IBD diagnosis before the age of 21 years (OR=2.97, 95% CI 1.05–8.87, P=0.050).

Conclusion
We have developed and meticulously validated the U-IBDQ. This is a short, self-report questionnaire that has demonstrated good reliability and validity in measuring understanding of disease pathophysiology and treatment in IBD.
DOP80 Automatic detection of ulcers and erosions in PillCam™ Crohn’s capsule using a convolutional neural network
Authors: Saraiva M , Ribeiro T , Afonso J , Cardoso H , Ferreira J , Andrade P , Parente M , Jorge R , Lopes S , Macedo G 
Published: May 2021

Abstract

Background
Capsule endoscopy (CE) plays a central role in the management of patients with suspected or known Crohn’s disease (CD). It is indicated for the diagnosis, classification, monitoring of the response to treatment, and prognostic prediction. In 2017, PillCam™ Crohn’s Capsule (PCC) was introduced. It has demonstrated greater accuracy in detecting and evaluating the extent of lesions in these patients. However, this new tool produces thousands of images, whose revision is time-consuming and prone to errors, since lesions can be restricted to a small number of images. In the last decade, several Artificial Intelligence (AI) algorithms were developed, and demonstrated potential to mitigate some of the drawbacks of CE. Among AI tools, Convolutional Neural Networks (CNN) display the best performance for imagery analysis. This study aims to develop an AI algorithm based on an CNN for the automatic detection of ulcers and erosions of the small intestine and colon in PCC images.

Methods
A total of 8 085 PCC images were extracted from a single tertiary centre between 2017–2020. This pool of images was constituted by 2 855 images depicting ulcers, 1 975 erosions; the remaining with normal enteric and colonic mucosa. For the automatic identification of these findings, this pool of images was split into training and validation datasets. A CNN model with transfer learning using tensorflow and keras tools was constructed. The performance of the network was subsequently assessed in an independent test set.

Results
After optimizing the different layers of the CNN, our model was able to detect and distinguish small intestinal or colonic erosions or ulcers with a sensitivity and specificity of 90.0% and 96.0%, respectively. The precision and accuracy of this model were 97.1% and 92.4%, respectively (Figure 1). Particularly, the CNN detected ulcers with a sensitivity of 83% and specificity of 98%, and erosions with sensitivity and specificity of 91% and 93%, respectively.

Conclusion
Our group developed, for the first time, a CNN capable of automatically detecting ulcers and erosions of the small intestine and colon in PCC images with high sensitivity and specificity. These findings are extremely important since they pave the way for the development of systems for the automatic detection of clinically significant lesions, optimizing diagnostic performance and efficiency of monitoring CD activity.
DOP83 Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 3 Years: UNIFI Long-term Extension
Authors: Abreu M T , Danese S , Sandborn W J , Miao Y , Tikhonov I , Zhang H , Panaccione R , Hisamatsu T , Scherl E J , Leong R W , Rowbotham D S , Arasaradnam R P , Afif W , Peyrin-Biroulet L , Sands B E , Marano C 
Published: May 2021

Abstract

Background
Ustekinumab (UST) is an IL-12/23p40 antagonist used to treat pts with moderate-to-severe ulcerative colitis (UC). The ongoing UNIFI long-term extension (LTE) evaluates subcutaneous (SC) 90mg UST maintenance therapy, with efficacy (wk152) and safety (wk156) results reported here.

Methods
523 intravenous UST induction responders were randomized to SC maintenance therapy (175 SC placebo [PBO]; 172 UST 90mg every 12 weeks [q12w]; 176 UST 90mg q8w). 284 UST pts who completed wk44 entered the LTE. PBO pts were discontinued after wk44 unblinding. Starting at wk56, randomized pts with UC worsening could adjust to q8w. Symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0) was evaluated in randomized pts. Safety was evaluated for all 588 pts treated in the LTE, including the randomized and nonrandomized populations; 188 received PBO and 457 received UST. The nonrandomized population included responders to PBO induction and UST induction nonresponders at wk8 who received SC UST, responded 8 wks later and received UST 90mg q8w.

Results
Among all pts randomized to UST at maintenance baseline (intent-to-treat population with nonresponder imputation for missing data and treatment failure criteria), 55.2% were in symptomatic remission at wk152 (biologic naïve, 66.1%; biologic failures, 43.5%; Table 1); 96.4% (185/192) of pts in symptomatic remission at wk152 were corticosteroid-free. Overall, 20.1% (39/149 biologic failure, 16/149 biologic naïve) of pts who were randomized to UST and treated in the LTE discontinued treatment between wks44 and 156. Among randomized pts treated with UST in the LTE, 67.6% were in symptomatic remission at wk152; 76.4% of those in clinical remission at wk44 were in symptomatic remission at wk152; and 84.1% of pts with observed data at wk152 were in symptomatic remission.
From maintenance wk0-156, combined UST and PBO pts had 1281.6 and 425.0 pt-years of follow-up, respectively; and safety events per 100 pt-years of follow-up for combined UST vs PBO were AEs: 235.81 vs 204.48, SAEs: 7.73 vs 7.53, and serious infections: 2.34 vs 2.35 (Table 2). From wks96-156, there were no reported deaths or major adverse cardiovascular events. One UST-treated pt with fair skin and a prior history of basal cell carcinoma (BCC) reported 2 BCC. One 90 mg q8w UST pt receiving concomitant 6-MP reported SAEs of neutropenic sepsis and oral herpes SAE; the latter events were considered potential opportunistic infections. The dose of 6-MP was reduced, pt recovered and continued UST.

Conclusion
The efficacy of UST in pts with UC was sustained through 3 years. No new safety signals were observed.