bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classification Model on Big Data in Medical Diagnosis Based on Semi-Supervised Learning
Authors: Wang Lei , Qian Qing , Zhang Qiang , Wang Jishuai , Cheng Wenbo , Yan Wei 
Published: January 2020

Abstract
Big data in medical diagnosis can provide abundant value for clinical diagnosis, decision support and many other applications, but obtaining a large number of labeled medical data will take a lot of time and manpower. In this paper, a classification model based on semi-supervised learning algorithm using both labeled and unlabeled data is proposed to process big data in medical diagnosis, which includes structured, semi-structured and unstructured data. For the medical laboratory data, this paper proposes a self-training algorithm based on repeated labeling strategy to solve the problem that mislabeled samples weaken the performance of classifiers. Aiming at medical record data, this paper extracts features with high correlation of classification results based on domain expert knowledge base first, and then chooses the unlabeled medical record data with the highest confidence to expand the training set and optimizes the performance of the classifiers of tri-training algorithm, which uses supervised learning algorithm to train three basic classifiers. The experimental results show that the proposed medical diagnosis data classification model based on semi-supervised learning algorithm has good performance.
OP20 The gut microbiota during biological therapy for inflammatory bowel disease
Authors: Caenepeel C , Viera-Silva S , Verstockt B , Machiels K , Davani N A , Sabino J , Ferrante M , Raes J , Vermeire S 
Published: January 2020

Abstract

Background
The expansion of therapeutic options in IBD brought forward a need to personalise treatment. Gut inflammation in inflammatory bowel disease (IBD) patients has been associated with reduced microbial richness and abundance of SCFA producers. We aimed to explore the longitudinal impact of treatment on the inflammatory burden and faecal microbiota in patients with CD and UC, treated with anti-tumour necrosis factor (anti-TNF) therapy, vedolizumab (VDZ) or ustekinumab (UST).

Methods
We analysed faecal samples from 349 IBD patients (112 UC, 237 CD) initiating biological therapy (anti-TNF; VDZ; UST), regardless baseline disease activity, between 2010 and 2019 at a tertiary referral centre. Samples were collected at week 0, 14 and 24. Microbiota phylogenetic profiling was conducted by 16S rRNA gene sequencing and faecal cell counts were determined using flow cytometry. Moisture levels were measured using lyophilisation. Disease activity and response were assessed by faecal calprotectin (FCal). Statistics were performed in R, v3.5.1. Enterotyping was based on the Dirichlet multinomial mixtures approach.

Results
Faecal microbiota profiles showed high diversity, with samples classified into all four enterotypes (Fig1), although Bact2 was 6- to 10-fold more prevalent in patients compared with controls (Fig2). The variation in faecal microbiota composition was explained (multivariate dbRDA) by diagnosis (R2 = 1.2%, p = 1.00E−04), timepoint (R2 = 0.52, p = 0.006), significantly by age, gender and faecal moisture. The full model only explained 2.85% of the microbiota variation.

A slight non-significant decrease in the Bact2 enterotype prevalence was observed in the CD, but not in the UC cohort, during treatment.

A significant decrease in FCal concentrations (w0 vs. 14, UC p = 5.12E-08, CD p = 2.56E−08; week 0 vs. 24: CD p = 4.86E-08) was observed with treatment, accompanied by a significant increase in cellcounts (w0 vs. 14: UC p = 0.024, CD p = 0.0022; week 0 vs. 24: CD p = 0.0201) (Figure 3). No significant change in Bact2 prevalence was found during treatment.

Only treatment-associated variables—week of treatment (p = 2.4E−18), diagnosis (0.0005) and timepoint (p = 0.0073)—were significant predictors for response, while microbiota-associated variables (enterotype, cell counts and faecal moisture) not. Baseline samples were associated with higher FCal levels. This suggests that the response time of the microbiota to treatment may be higher than the host inflammatory response.

Conclusion
The prevalence of the inflammatory Bact2 enterotype was 5- to 10-fold higher in CD and UC patients as compared with controls. Although initiation of biological therapies leads to a decrease in inflammation levels as witnessed by faecal calprotectin and increase in microbial richness, a shift in enterotypes did not occur.
OP30 The interplay of microbiome dysbiosis and immune system deregulation in patients with Crohn’s disease
Authors: Seyed Tabib N S , Caenepeel C , Machiels K , Verstockt S , Verstockt B , Ardeshir Davani N , Sabino J , Ferrante M , Vermeire S 
Published: January 2020

Abstract

Background
The perturbation of composition, function, and structure of the gut microbiota known as dysbiosis is a key factor in inflammatory bowel disease (IBD) pathogenesis. There is a crosstalk between the microbiota and the gut immunological niche. To better understand this interaction, we characterised the degree of dysbiosis and dysregulation of the immune proteome in Crohn’s disease (CD) patients to see whether subtypes of patients could be identified.

Methods
We collected faecal and serum samples of 146 CD patients and 63 healthy controls (HC) (Figure 1), and studied microbiota phylogenetic (16S rRNA gene sequencing) and serum proteomic (91 inflammatory proteins OLINK). Microbial dysbiotic index (MDI), defined as the logarithm of the sum of [abundance in organisms increased in CD] over the [abundance of organisms decreased in CD] was calculated and patients were ranked from Q1 (the least dysbiotic state) to Q4 (the most dysbiotic state). For the proteomic score, 32 proteins that correlated (adj. p ≤ 0.01) with faecal calprotectin (FC) were selected. A penalised logistic regression model was trained on these proteins, to distinguish HC from super active (defined as FC ≥ 1800 μg/g). We next developed an inflammatory proteomic score (IPS) defined as the weighted sum of the serum level of inflammatory proteins, using the coefficient value of the regression model as the protein’s weight. Using the IPS score, patients were clustered from Q1 (the least inflammatory state) to Q4 (the most inflammatory state). Statistical analyses were performed in R 3.5.2.

Results
The MDI did not correlate with standard phenotypic subgroups based on the Montreal classification but did positively correlate with C-reactive protein (CRP) and FC level (p ≤ 0.001). The regression model identified 14 proteins [including CCL20, CXCL1, IL-7, IL-17A, FGF-19] distinguishing super active CD patients from HC with accuracy, sensitivity, and specificity of 95.6%, 92.3%, 100%, respectively. IPS positively correlated with CRP and FC level (p ≤ 0.001). Likewise, MDI and IPS-based clusters were significantly different in CRP and FC levels. Different components of the microbiome correlated with the proteome in a subset of samples. For example, fibroblast growth factor 19 (FGF-19) positively correlated with Faecalibacterium and negatively with Fusicatenibacterium. Of note, we observed a significant positive correlation between MDI and IPS (r = 0.33, p ≤ 0.001) (Figure 2).

Conclusion
We were able to define clusters of patients based on molecular characterisation of different players in IBD pathogenesis such as microbiota and proteome. This molecular clustering in a given patient could be considered as a novel therapeutic and personalised approach to IBD. Further validation in larger cohorts is required.
OP37 Fibrogenesis in chronic DSS colitis is driven by an innate lymphoid cell-independent innate immune response
Authors: Creyns B , Cremer J , De Hertogh G , Boon L , Ferrante M , Vermeire S , Van Assche G , Ceuppens J , Breynaert C 
Published: January 2020

Abstract

Background
Obtaining insights in the pathogenesis of intestinal fibrosis is a priority for improving outcomes in inflammatory bowel diseases (IBD). Studies in murine models and human organ fibrosis indicate a role for innate immunity pathways in fibrosis. The aim of this study was to dissect the role of innate lymphoid cells (ILC) in chronic intestinal inflammation and fibrosis.

Methods
A chronic 3-cycles dextran sulphate sodium (DSS) model was induced in wild-type (WT), recombinant activating gene (RAG)-deficient (lacking adaptive immunity), RAG−/− common γ-chain (ɣc)−/− (lacking ILC) and anti-CD90.2 treated (ILC depleted) C57Bl/6 RAG−/− mice. One cycle of DSS comprised 1 week of DSS administration followed by 2 weeks of recovery with normal drinking water. Colonic lamina propria cells were isolated and CD45+Lineage−CD127+CD90.2+ ILC, Ly6C+ monocytes and Ly6G+ neutrophils were identified after staining by flow cytometry. Inflammation and fibrosis were scored by macroscopic and HE and Martius Scarlet Blue staining and fibrosis was evaluated by hydroxyproline quantification. For analysis Kruskal–Wallis testing with multiple Dunn’s comparisons was performed.

Results
In RAG-1−/− mice chronic inflammation and fibrosis developed similarly as in WT mice, with elevated KLRG-1+ ILC2 (68.90 vs. 48.00% of ILC, p = 0.012) after repeated DSS exposure as compared with control mice (Figure 1). Chronic colitis could also be induced in RAG−/−ɣc−/− or ILC depleted RAG−/− mice (ILC: 0.99 vs. 25.70% of CD45+ cells, p = 0.029), with no attenuation of fibrosis (p &gt; 0.99) as compared with chronic DSS exposed RAG-1−/− mice despite the absence of ILC (Figure 2). Colon length decrease was more pronounced in RAG−/−yc−/− as compared with RAG-1−/− mice after chronic DSS colitis (7.15 vs. 8.30 cm, p = 0.046), while hydroxyproline levels and thickness of mucosa and muscularis propria were not different in RAG−/−yc−/− as compared with RAG-1−/− mice after chronic DSS. Moreover, after the second cycle of DSS a slower recovery of weight was seen in RAG−/−yc−/− mice as compared with RAG-1−/− mice (d31: 88.64 vs. 111.0% of initial weight, p &lt; 0.001; d35 p = 0.001; d39 p = 0.006 and d42 p = 0.002) (Figure 3). In absence of ILC, RAG−/−yc−/− mice increased lamina propria neutrophils (19.10 vs. 5.91% of CD45+ cells, p = 0.004) and monocytes (11.80 vs. 3.25% of CD45+ cells, p = 0.004) may represent an alternative source of inflammation.

Conclusion
These data argue against a pro-fibrotic role of ILC in the induction of fibrosis in chronic DSS colitis, and suggest a protective and recovery-enhancing role of ILC after repeated intestinal injury.
DOP24 Patient-reported health-related quality-of-life outcomes with vedolizumab vs. adalimumab treatment of ulcerative colitis: Results of the VARSITY trial
Authors: Loftus E V , Schreiber S W , Danese S , Peyrin-Biroulet L , Colombel J F , Sands B E , Wang S , Chen J , Lirio R A 
Published: January 2020

Abstract

Background
Patients with ulcerative colitis (UC) experience substantial impairment in quality of life (QOL). Patient QOL endpoints are important measures of treatment outcome. We evaluated the effects of intravenous vedolizumab vs. adalimumab on QOL in VARSITY, the first head-to-head trial comparing the efficacy and safety of biologics in patients with moderately to severely active UC.

Methods
VARSITY was a phase 3b, double-blind, double-dummy, randomised trial (NCT02497469; EudraCT 2015-000939-33). QOL was assessed using the inflammatory bowel disease questionnaire (IBDQ) at baseline, Week (Week) 30, and Week 52. Endpoints included clinically meaningful IBDQ improvement (defined as an increase in total score of ≥16 points from baseline to Week 52), IBDQ remission (defined as a total score of &gt;170 points at Week 52) and change from baseline in IBDQ-specific domain scores (bowel symptoms, systemic symptoms, emotional function, and social function) at Week 30 and Week 52. Serum C-reactive protein (CRP) and faecal calprotectin (FCP) were also assessed as indicators of disease activity.

Results
Among randomised patients, 383 (vedolizumab) and 386 (adalimumab) patients received ≥1 dose of study drug (N=769). At Week 52, clinically meaningful IBDQ improvement was observed in 52.0% (vedolizumab) vs. 42.2% (adalimumab) of patients (treatment difference 9.7%; 95% confidence interval [CI], 2.7% to 16.7%), while IBDQ remission was achieved by 50.1% (vedolizumab) vs. 40.4% (adalimumab) of patients (treatment difference 9.6%; 95% CI, 2.8% to 16.5%). Mean (standard deviation [SD]) changes in IBDQ total score from baseline for observed cases favoured vedolizumab over adalimumab (Week 30: 61.3 [39.8] vs. 52.6 [42.8]; Week 52: 66.1 [41.8] vs. 60.4 [42.2]; Figure 1). IBDQ subscores showed similar favourable trends for vedolizumab (Figure 2). At Week 52, mean (SD) changes from baseline in CRP for patients treated with vedolizumab vs. adalimumab were –50.9 (174.8) nmol/l vs. –37.2 (169.2) nmol/l and for FCP were –2187.3 (7440.4) µg/g vs. –1846.6 (4560.6) µg/g (Figure 3). Among patients with FCP &gt;250 µg/g at baseline, the proportion of patients achieving FCP ≤250 µg/g was 33.9% vs. 24.5% at Week 30 and 35.2% vs. 28.9% at Week 52 for patients treated with vedolizumab vs. adalimumab, respectively.

Conclusion
Based on IBDQ total score and subscores, more patients with UC treated with vedolizumab than with adalimumab achieved clinically meaningful improvement and clinical remission. Reduced inflammation, as indicated by improvements in CRP and FCP, was consistent with improvements in QOL.
DOP30 Multi-‘omics profiling in patients with quiescent inflammatory bowel disease identifies biomarkers predicting relapse
Authors: Borren N , Plichta D , joshi A , Bonilla G , Sadreyev R , Vlamakis H , Xavier R , Ananthakrishnan A 
Published: January 2020

Abstract

Background
Inflammatory bowel diseases (IBD) are characterised by intermittent relapses and their course is heterogeneous and often unpredictable. The ability of protein, metabolite, or microbial biomarkers to predict relapse in patients with quiescent disease is unknown.

Methods
This prospective study enrolled patients with quiescent Crohn’s disease (CD) and Ulcerative colitis (UC) defined as absence of clinical symptoms (HBI &lt; 4, SCCAI &lt; 2) and a colonoscopy within the 1 year prior with endoscopic remission. The primary outcome was relapse within 2 years, defined as symptomatic worsening accompanied by elevated inflammatory markers resulting in a change in therapy, or IBD-related hospitalisation or surgery. Metabolomic and proteomic profiling was performed on serum samples and stool samples underwent shotgun metagenomic sequencing on Illumina HiSeq platform. Biomarkers were tested in a derivation cohort and their performance examined in an independent validation cohort.

Results
Our prospective cohort study included 164 patients with IBD (108 CD, 56 UC). Upon follow-up for a median of 1 year, 22 patients (13.4%) experienced a relapse. Three protein biomarkers (IL-10, GDNF, and CD8A) and four metabolomic markers (propionyl-l-carnitine, carnitine, sarcosine, and sorbitol) were associated with relapse in multivariable models at p &lt; 0.05. Proteomic and metabolomic risk scores, defined as the tertile sum of the serum levels of these biomarkers independent predicted relapse with a combined AUC of 0.83. This risk score clearly differentiated relapsers from those who remained in remission in both the derivation and validation cohort (Figure 2). A high proteomic risk score (OR 9.11, 95% CI 1.90–43.61) or metabolomic risk score (OR 5.79, 95% CI 1.24–27.11) independently predicted higher risk of relapse over 2 years. Faecal metagenomics from 85 patients demonstrated increased abundance of Proteobacteria (p = 0.0019, q = 0.019) and Fusobacteria (p = 0.0040, q=0.020) and at the species-level Lachnospiraceae_bacterium_2_1_58FAA (p = 0.000008, q = 0.0009) among relapses. Proinflammatory changes in the microbiome correlated with the metabolomic and proteomic perturbations associated with relapse.

Conclusion
Proteomic, metabolomic, and microbial biomarkers identify a pro-inflammatory state in quiescent IBD that predisposes to clinical relapse.
DOP41 Low-grade dysplasia prognosis and predictive factors for advanced neoplasia progression in the 21st century: A large multi-centre retrospective cohort study
Authors: Kabir M , Curtius K , Al-Bakir I , Hartono J , Johnson M , East J E , Lindsay J O , Vega R , Thomas-Gibson S , Hart A , Graham T , Wilson A 
Published: January 2020

Abstract

Background
Recent advances in ulcerative colitis (UC) endoscopic surveillance such as high-definition imaging and greater chromoendoscopy (CE) use have led to an increase in detection and resection of visible dysplasia. An updated study of prognosis of low-grade dysplasia (LGD) is needed to address uncertainty as to the accuracy of progression rates based on historical studies.

Methods
This retrospective cohort study involved four UK IBD centres. Hospital and endoscopy pathology databases were searched between 1 January 2001 and 30 December 2018 to identify adult patients with UC who had their first LGD diagnosis diagnosed within the extent of colitis. Only patients followed up with at least one colonoscopy or colectomy by 30 August 2019 were included. The study endpoint was time to high-grade dysplasia (HGD) or cancer (CRC), i.e. advanced neoplasia (AN), or end of follow-up. Survival analyses were performed using Kaplan–Meier estimation and Cox proportional hazards (PH) models.

Results
In total, 460 patients met the inclusion criteria and were followed up for a median of 4.1 years (IQR 6), equating to 2,232 patient-years. A mean of 3.7 (range 0–17) subsequent colonoscopies was performed per patient. Seventy-seven per cent of patients had CE surveillance. Complete endoscopic resection was achieved in 94% and 64% of the polypoid and non-polypoid LGD, respectively. There was progression to AN in 88 cases (19%) during follow-up. There was no significant difference in AN progression between centres. Unresectable non-polypoid or invisible LGD carried the greatest risk of AN development (Figure 1).

On univariate Cox PH analysis, CE use was protective against AN progression (HR 0.5; 95% CI 0.3–1.0; p = 0.04). However, only highly significant predictors of LGD progression to AN on univariate analysis (Bonferroni adjusted p &lt; 0.003), were entered into the multivariate model:
Cumulative risk of AN increased with the number of risk factors (Figure 2).

Conclusion
This is the largest study examining prognosis of LGD, based on endoscopic features, in this century. Five-year cumulative incidence of AN is low after complete endoscopic resection of visible LGD without surrounding dysplasia. Lesion size of 1 cm or more, invisibility, multifocality and unresectability of LGD are significant risk factors for progression to AN. These factors should be taken into consideration when discussing management options with patients.
DOP54 Integrated network analysis using patient-specific single-nucleotide polymorphism profiles uncovers new pathways involved in ulcerative colitis pathogenesis
Authors: Modos D , Brooks J , Sudhakar P , Verstockt B , Alexander-Dann B , Zoufir A , Fazekas D , Vermeire S , Korcsmaros T , Bender A 
Published: January 2020

Abstract

Background
Genome-wide association studies have deciphered the single nucleotide polymorphisms (SNPs) which are responsible for ulcerative colitis (UC) susceptibility. However, to understand how these SNPs are involved in UC, additional methods are necessary. One such approach is in silico network propagation modelling, which can discover how the effects of SNPs in UC can affect the whole cell. A complementary approach is weighted gene co-expression network analysis (WGCNA), where co-regulated genes are identified using transcriptomic data. Integrating these two methods can shed light on how SNPs are affecting the transcriptome of UC patients.

Methods
We used immunochip profiles of 941 UC patients and focussed on UC-associated SNPs altering regulatory regions. Based on these regions, we identified affected genes. To understand how their corresponding proteins rewire transcriptional regulation, we predicted the path between these proteins and relevant transcription factors (TF) using the OmniPath signalling network (http://omnipathdb.org). From the TFs, we propagated the signal further to target genes using TFlink (https://tflink.net) and GTRD (http://gtrd.biouml.org). To evaluate the predicted network propagation signal, we conducted WGCNA with transcriptomics data from 46 matching patients’ (GEO ID: GSE48959). To interpret the results, we used Gene Ontology Biological Process annotations of the target genes, and we compared the function and regulation of affected genes and the determined WGCNA modules.

Results
We found 9 predominant signalling pathways, some already known from other studies to be involved in UC pathogenesis, including NFkB signalling, chemokine signalling, Notch pathway, JAK/STAT signalling. Downstream of these pathways we identified potential key TFs regulate the UC phenotype, for example NFKB1, GATA3, GTF2I. The targets of these TFs were enriched in the WGCNA modules of the patients. The WGCNA modules and the transcriptionally affected genes had enriched processes including cell migration, TGF-β signalling, exocytosis, adaptive T- and B-cell-specific immune responses and tight junctions. We also found myogenetic development specific TFs affected transcriptionally such as MyoD, MEF2A, MEF2D. We are currently validating these results through patient-specific biopsies.

Conclusion
In silico methods bring us closer to understanding UC pathogenesis. Our results suggest that in a well-defined set of patients, weakened tight junctions and insufficient immune response can lead to dysfunctional epithelial barrier, resulting in poor wound healing in UC. We hope the developed workflow will provide novel diagnostic and therapeutic options in UC.