bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural Processing of Taste Information
Authors: Fontanini Alfredo , Czarnecki Lindsey
Published: January 2023

The gustatory system has evolved to detect molecules dissolved into the saliva. It is responsible for the perception of taste and flavor, for mediating the interaction between perception and internal homoeostatic states, and for driving ingestive decisions. The widely recognized five basic taste categories (sweet, salty, bitter, sour, and umami) provide information about the nutritional or potentially harmful content in what is being consumed. Sweetness is typical of sugars that are carbohydrate dense; saltiness is the percept of ions which are necessary for physiological function and electrolytic homeostasis; bitterness is associated with alkaloids and other potential toxins; sourness is the percept of acidity signaling spoiling foods; and umami is the sensation associated with amino acids in protein-rich foods. In addition to taste, the act of eating also engages sensations of temperature, texture, and odor—the integration of all these sensations leads to the unitary percept of flavor. These same senses, and others such as vision and audition, are also engaged before an ingestive event. Sights, sounds, and smells can alert organisms to the presence of food as well as inform the organism as to the specifics of which taste(s) to expect. As such, the neurophysiology of taste is necessarily intertwined with that of other senses and with that of cognitive and homeostatic systems.
Ceramics and Archaeology in Southern Africa
Authors: Fredriksen Per Ditlef
Published: January 2023

Pottery has been part of daily life in southern Africa for the last two millennia. The frequent occurrence at settlement sites and its resistance to decay makes pottery the most common proxy for past food-producing communities (farmers and livestock herders), who made containers for cooking, serving, and storing foods and liquids. Provided that pots and sherds have enough diagnostic features to indicate décor patterns and vessel shape, trained eyes can get an instant and literally cost-free peek into past movement and interaction. Various material sciences offer high-precision dating and insights into less visible characteristics, and ethnographic insights are helpful for understanding more intangible aspects, such as the organization of production, pots’ roles in social practices and belief systems, and the transmission of knowledge and skills through apprenticeship. Potting has been a highly gendered activity, and attention to social identity is instrumental in widening the range of lenses through which archaeologists view past material culture. In this manner, by focusing on skilled craft networks dominated by women, ceramic research can provide a critical corrective alternative to more traditional top-down narratives that trace the evolution and interaction of (male) elites.

However, the European and North American legacy of archaeological classification in southern Africa cannot be overlooked. Ceramic classification may still unwillingly project a Western-centered understanding of the human condition, mobility, and social change. While unacceptable labels that refer to outmoded notions of tribalism have long been replaced by more neutral terms, this does not mean that ceramics provide archaeology with a neutral “tracking device.” A continual key challenge for practitioners in southern Africa is to situate ceramic analysis within a wider thematic and disciplinary nexus in order to construct convincing deep time narratives while also exploring new pathways to insights that can give voices to otherwise silent or subaltern members of past societies.
Behavioral Development Economics
Authors: Hoff Karla , Demeritt Allison
Published: January 2023

Economics, like all behavioral sciences, incorporates premises about how people think. Behavioral economics emerged in reaction to the extreme assumption in neoclassical economics that agents have unbounded cognitive capacity and exogenous, fixed preferences. There have been two waves of behavioral economics, and both have enriched development economics. The first wave takes into account that cognitive capacity is bounded and that individuals in many situations act predictably irrationally: there are universal human biases. Behavioral development economics in this first wave has shown that low-cost interventions can be “small miracles” that increase productivity and well-being by making it easier for people to make the rational choice. The second wave of behavioral economics explicitly takes into account that humans are products of culture as well as nature. From their experience and exposure to communities, humans adopt beliefs that shape their perception, construals, and behavior. This second wave helps explain why long-run paths of economic development may diverge across countries with different histories. The second wave also suggests a new kind of intervention: Policies that give individuals new experiences or new role models may change their perceptions and preferences. New perceptions and preferences change behavior. This is a very different perspective than that of neoclassical economics, in which changing behavior requires ongoing interventions.
Indigenous Health and Connection to Country
Authors: Thorpe Alister , Yashadhana Aryati , Biles Brett , Munro-Harrison Emily , Kingsley Jonathan
Published: January 2023

There are an estimated 370 million Indigenous peoples living in more than 70 countries. Indigenous populations are defined as the First Peoples occupying countries or regions at times of colonization, with distinct cultural, religious, and social practices that distinguish them from other populations. Indigenous peoples across the globe have deep, intimate, holistic, localized, and reciprocal relationships and connections to their “Country” (as it is known in Australia), which includes elements of the land, sea, waterways, sky, stars, and living and nonliving entities. This relationship is largely unacknowledged through Western biomedical models of health, which tend to focus on individual risk behaviors and disease outcomes, thereby situating Indigenous health inequities in terms of deficiency and ignoring the ongoing impacts and trauma of colonization. Indigenous concepts of health are holistic, encompassing emotional, physical, cultural, and spiritual health. Country is central to health and is steeped in the harmonized interrelationships that constitute cultural well-being. Models for measuring and understanding health outcomes for Indigenous peoples need to respectfully incorporate the full range of determinants that are relevant to their health that understand the importance of connection to Country.
Teaching about Gender and Sexuality in the International Relations Classroom
Authors: Sjoberg Laura , Whooley Jon
Published: January 2023

Feminist pedagogy considers the scholarship on and practices of teaching gender and sexuality in global politics. Humans narrativize (tell stories about) their lives, creating stories about the world that they see in order to make sense of their complicated realities. As such, there are multiple story lines of the ways that a feminist curiosity can affect approaches to teaching, strategies for teaching feminist curiosity, the role that genders and sexualities play in constituting the international relations (IR) classroom, and approaches to teaching material related to genders and sexualities in global politics. There are six story lines that reveal the distinctive features of feminist pedagogy: foregrounding an explicitly feminist politics, treating knowledge as situated, reimagining the purpose and structure of the classroom, recognizing and combating alienation, broadening the view of texts available for teaching and learning, and including explicitly activist components in teaching strategies. Across these story lines, feminist teaching is an important part of feminist academic practice, where pedagogy with a feminist curiosity foregrounds the politics of feminisms and the politics of pedagogy.
SMURF: embedding single-cell RNA-seq data with matrix factorization preserving self-consistency
Authors: Pu Juhua , Wang Bingchen , Liu Xingwu , Chen Lingxi , Li Shuai Cheng
Published: January 2023

The advance in single-cell RNA-sequencing (scRNA-seq) sheds light on cell-specific transcriptomic studies of cell developments, complex diseases and cancers. Nevertheless, scRNA-seq techniques suffer from ‘dropout’ events, and imputation tools are proposed to address the sparsity. Here, rather than imputation, we propose a tool, SMURF, to extract the low-dimensional embeddings from cells and genes utilizing matrix factorization with a mixture of Poisson-Gamma divergent as objective while preserving self-consistency. SMURF exhibits feasible cell subpopulation discovery efficacy with obtained cell embeddings on replicated in silico and eight web lab scRNA datasets with ground truth cell types. Furthermore, SMURF can reduce the cell embedding to a 1D-oval space to recover the time course of cell cycle. SMURF can also serve as an imputation tool; the in silico data assessment shows that SMURF parades the most robust gene expression recovery power with low root mean square error and high Pearson correlation. Moreover, SMURF recovers the gene distribution for the WM989 Drop-seq data. SMURF is available at https://github.com/deepomicslab/SMURF.
A subsampling perspective for extending the validity of state-of-the-art bootstraps in the frequency domain
Authors: Yu Haihan , Kaiser Mark S , Nordman Daniel J
Published: January 2023

Bootstrapping spectral mean statistics has been a notoriously difficult problem over the past 25 years. Many frequency domain bootstraps are valid only for certain time series structures, e.g., linear processes, or for special types of statistics, i.e., ratio statistics, because such bootstraps fail to capture the limiting variance of spectral statistics in general settings. We address this issue with a different form of resampling, namely, subsampling. While not considered previously, subsampling provides consistent variance estimation under much weaker conditions than any existing bootstrap in the frequency domain. Mixing is not used, as is often standard with subsampling. Rather, subsampling can be generally justified under the same conditions needed for original spectral mean statistics to have distributional limits in the first place. This result has impacts for other bootstrap methods. Subsampling then applies to extending the validity of recent state-of-the-art bootstraps in the frequency domain. We nontrivially link subsampling to such bootstraps, which broadens their range, as moment and block assumptions needed for these are cut by more than half. Essentially, state-of-the-art bootstraps then require no more stringent assumptions than those needed for a target limit distribution to exist, which is unusual in the bootstrap world. We also close a gap in the theory of subsampling for time series with distributional approximations, in addition to variance estimation, for frequency domain statistics.
Implementing brief and low-intensity psychological interventions for children and young people with internalizing disorders: a rapid realist review
Authors: Roach Anna , Cullinan Sophie , Shafran Roz , Heyman Isobel , Bennett Sophie
Published: January 2023

Introduction

Many children fail to receive the mental health treatments they need, despite strong evidence demonstrating efficacy of brief and low-intensity psychological interventions. This review identifies the barriers and facilitators to their implementation.

Sources of Data

PsycInfo, EMBASE and Medline were searched and a systematic approach to data extraction using Normalization Process Theory highlighted key mechanisms and contextual factors.

Areas of Agreement

Ten interventions from 9 papers, including 371 young people, were included. Studies identified organizational demands, lack of implementation strategy and stigma as barriers to implementation, and clear training and plans for implementation as facilitators.

Areas of Controversy

No standardized implementation outcomes were used across papers so meta-analysis was not possible.

Growing Points

Barriers and facilitators have been clearly identified across different settings.

Areas Timely for Developing Research

Longitudinal studies can identify methods and processes for enhancing long-term implementation and considers ways to monitor and evaluate uptake into routine practice.
DiscolobiumandRiedeliella(Fabaceae – Faboideae – Dalbergieae clade): leaflet anatomy, secretory structures and their systematic implications
Authors: Bento João Pedro Silvério Pena , Rosa Marcus Paulo Gonçalves , Sartori Ângela Lúcia Bagnatori
Published: January 2023

Discolobium and Riedeliella, exclusively South American genera, have been shown in phylogenetic analyses to be the sister group to the Pterocarpus clade. The species of the two genera can be confused when reproductive structures are absent, resulting in taxonomic misunderstandings in botanical collections. This study aimed to investigate the anatomical characters of leaflets of representatives of Discolobium and Riedeliella in terms of their diagnostic value at the genus and species levels and to provide information about the type, location and histochemistry of their secretory structures, and their usefulness for the systematics of the genera. The taxa were analysed using light microscopy and scanning electron microscopy. Unistratified epidermis, epidermal cell contour and fibre bundles of the main vein are features shared by the two genera. The position of the stomata and of the tector trichomes and the shape of the epidermal cells and of the mucilaginous idioblasts are diagnostic anatomical features at the genus level. Epidermal mucilaginous idioblasts are confirmed for all species studied. Phenolic idioblasts are present in Riedeliella and Discolobium, and secretory trichomes are found only in Discolobium. The anatomical characters of the leaflets are useful for the taxonomy of all species studied. Furthermore, our dataset shows novelties for the systematics of Fabaceae.
Floral development of one of the oldest dioecious lineages of Arecaceae reveals different stages of dicliny in pistillate and staminate flowers
Authors: Reis Sarah Barbosa , Mello Ana Caroline Marques Pereira , Rech André Rodrigo , Oliveira Denise Maria Trombert
Published: January 2023

Arecaceae subtribe Mauritiinae are a lineage of Neotropical dioecious species in subfamily Calamoideae, the earliest diverging and most diverse group of palms regarding sexual systems. Ontogenetic and anatomical studies of reproductive structures contribute to the understanding of evolutionary relationships, but there is a lack of detailed information. We describe the anatomical floral development of Lepidocaryum tenue, Mauritia flexuosa and Mauritiella armata (subtribe Mauritiinae) using standard light microscopy techniques. Three central moments in the development of pistillate and staminate flowers were identified: the initial phase of development of the floral meristem; the phase of determination of the whorls that will compose the pistillate and staminate flowers; and the phase of differentiation (pre-anthesis) of these whorls. Although the pre-anthetic flowers are diclinous, they are initially monoclinous, suggesting a hermaphrodite ancestor for Mauritiinae. The development is asynchronous since, in pre-anthesis, the pistillate flowers have staminodes that produce non-viable pollen grains, whereas the staminate flowers do not even have a pistillode. Staminodes may have a secondary function in attracting floral visitors.
Systemic sclerosis and primary biliary cholangitis share an antibody population with identical specificity
Authors: Favoino Elvira , Grapsi Ettore , Barbuti Giovanna , Liakouli Vasiliki , Ruscitti Piero , Foti Caterina , Giacomelli Roberto , Perosa Federico
Published: January 2023

Anti-centromere (ACA) and antimitochondrial antibodies (AMA) are specific for limited-cutaneous systemic sclerosis (lcSSc) and primary biliary cholangitis (PBC), respectively, and can coexist in up to 25 and 30% of SSc and PBC patients. Here, we evaluated whether anti-centromeric protein A (CENP-A) antibodies cross-react with mitochondrial antigens. To this end, sera from two lcSSc patients (pt1 and pt4), one of them (pt4) also affected by PBC, were used as the source of ACA, previously shown to recognize different groups of amino acids (motifs) in the CENP-A region spanning amino acids 1–17 (Ap1–17). Pt1 and pt4 Ap1–17-specific IgG were purified by affinity-chromatography on insolubilized Ap1–17-peptide column and tested by western blotting with nuclear and cytoplasmic protein extract from HeLa cells. Immunoreactive proteins were identified by mass spectrometry and validated by immunodot. The results showed that affinity-purified SSc/PBC pt4 anti-Ap1–17 and not SSc pt1 anti-Ap1–17 Ab, specifically cross-reacted with the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen in PBC. Sequence homology analysis indicated that the motif A-x-x-P-x-A-P recognized by pt4 anti-Ap1–17 IgG and shared by CENP-A and PDC-E2, is also expressed by some members of the Human Herpesvirus family, suggesting that they may trigger the production of these cross-reacting antibodies.
OP03 Highly stable epigenome-wide peripheral blood DNA methylation signatures accurately predict endoscopic response to adalimumab, vedolizumab and ustekinumab in Crohn’s disease patients: The EPIC-CD study
Authors: Joustra V , Li Yim A , Hageman I , Levin E , Noble A , Chapman T , McGregor C , Adams A , Satsangi J , de Jonge W , Henneman P , D’Haens G
Published: January 2023

Background

Despite the proven efficacy of biological treatments in Crohn’s disease (CD), many patients fail to respond or lose response over time. Therefore, predictive biomarkers for treatment efficacy would be of extreme value. Previous epigenome-wide association studies associated differential DNA methylation with CD-specific phenotypes, suggesting a potential use in classification and prediction of response to treatment.

Methods

We prospectively collected and measured longitudinal peripheral blood DNA methylation profiles of 184 adult CD patients prior to (T1) and after a median of 28 weeks (T2) following biological treatment with Adalimumab (ADA), Vedolizumab (VEDO) or Ustekinumab (USTE) in a discovery (n=88) and independently collected internal validation cohort (n=96) using the Illumina EPIC BeadChip array. Response (R) was defined as the combination of endoscopic response (≥50% reduction in SES-CD score) and steroid-free clinical response (≥3 point drop in HBI or HBI ≤4 AND no systemic steroids) and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Biomarker identification and classification analyses were performed using stability selection gradient boosting on samples taken at T1 whereas samples taken at T2 and intraclass correlation (ICC) data were used to assess long-term stability of our identified CpG loci1.

Results

A total of 58 ADA-patients (NR=29, NNR=29), 64 VEDO-patients (NR=36, NNR=28) and 62 USTE-patients (NR=30, NNR=32) were included. Prior to treatment, at T1, we identified distinct panels of 100 ADA-, 22 VEDO- and 68 USTE-associated CpG loci that, in combination, predict clinical- and endoscopic response with high accuracy (AUC ADA=0.73, VEDO=0.89 and USTE=0.94) upon validation. Notably, for these CpG loci, methylation levels did not significantly differ between T1 and T2, implicating stability during both induction and maintenance treatment, irrespective of inflammatory status and therapeutic intervention. In addition, the majority of these CpG loci (>60%) demonstrated long-term hyper stability (ICC-values ≥0.90). Furthermore, genes annotated to the CpGs of interest suggest drug specific involvement in TNF-signaling, endothelial cell-cell adhesion, integrin dependent T-cell homing, the innate immune system and Th17/Treg differentiation, corroborating to the mode of action of each drug.

Conclusion

Here, we report on 3 validated panels of highly stable, epigenetic biomarkers that predict clinical and endoscopic response in CD patients treated with ADA, VEDO or USTE. Additional external- and clinical validation as part of EPIC-CD and the OMICROHN clinical trial are currently ongoing.
OP09 Long-term Colectomy rates of Ulcerative Colitis over 40-year of Different Therapeutic eras – Results from a Western Hungarian Population-based Inception Cohort between 1977–2020
Authors: Lakatos PhD P L , Gonczi L , Lakatos L , Golovics P A , Pandur T , David G , Erdelyi Z , Szita I
Published: January 2023

Background

Few population-based studies have investigated the long-term colectomy rates of ulcerative colitis (UC). The present study is a continuation of the Veszprem IBD population based cohort with a follow-up of the incidence and disease course for over 40 years. We aimed to assess the colectomy rates over 40 years of different therapeutic eras in a prospective population-based inception cohort from Veszprem Province, Western Hungary.

Methods

Patient inclusion lasted between January1,1977 and December31, 2018. Patient follow-up ended December 31,2020. Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. Disease extension was evaluated based on the Montreal classification. Colectomy rates and disease course were examined in three different eras based on the time of UC diagnosis; cohort-A(1977-1995),cohort-B(1996-2008), and cohort C(2009-2018).

Results

Data of 1,370 incident UC patients were analyzed (male/female: 702/668; median age at diagnosis: 37 years(y) [IQR: 26-51]), with a median of 17y (IQR 9-24) follow-up. Table 1. The overall colectomy rate was 76/1,370 patients during the total follow-up. The proportion of extensive colitis at diagnosis increased over time (24.2% / 24.3% / 34.9% in cohorts A/B/C; p=0.001). Overall immunosuppressive therapy exposure was increasing in the cohorts (11.3% / 20.9% / 34.4%; p<0.001), as well as the probability of biological therapy initiation within 5 years of diagnosis (0.0±0% / 3.3±0.7% / 13.9±1.8%; pLogRank<0.001). Figure 1. There was no significant difference in the cumulative probability of proximal disease progression from proctitis (E1) to left-sided colitis/extensive colitis (E2/E3) or from left-sided colitis (E2) to extensive colitis (E3) over time in cohorts A, B, and C (Long-rank=0.482). Figure 2. The cumulative probability of colectomy in the total population was 4.1±0.6% after 10 years, 6.3±0.8% after 20 years, and 8.8±1.2% after 30 years. There were no statistically significant differences in the cumulative probability of colectomies between cohorts A/B/C: 1.7±0.7% / 2.2±0.6% / 3.7±1.0% after 5 years; 3.5±1.0% / 3.9±0.8% / 4.5±1.2% after 10 years; and 6.9±1.4% / 5.3±1.0% (cohorts A/B) after 20 years [pLogRank=0.447]. Figure 3. Extensive disease (HR 2.3;95%CI 21.60-3.37) and continuous uncontrolled disease activity (HR 6.89;95%CI 4.15-11.46) were independent predictors for colectomy. Table 2.

Conclusion

No differences in proximal disease progression and colectomy rates have been observed in the incident UC patients over 40 years despite increasing use of immunomodulators and biological therapies.
OP25 Prevalence of IBD in the Netherlands: development and validation of machine learning models for administrative data
Authors: Van Linschoten R , van Leeuwen N , Hazelzet J A , van der Woude C J , van Noord D , West R L
Published: January 2023

Background

Treatment of IBD has improved with the introduction of biologics and small molecules, yet this has come with a considerable increase in healthcare costs. Due to the increasing cost burden, reliable nationwide epidemiological data on the prevalence of IBD is necessary to inform health policy makers, especially as the prevalence of IBD is forecasted to double between 2010 and 2030. We aimed to develop a model for identifying prevalent IBD cases in administrative data and to determine prevalence of IBD in the Netherlands.

Methods

Data on hospital care came from the Dutch National Hospital Care Basic Registration (Landelijke Basisregistratie Ziekenhuiszorg). This database contains data on all hospital admissions (since 1991), outpatient clinic visits (since 2017), and dispensations of biologics and small molecules (since 2015) of all hospitals in the Netherlands. Data on pathology reports were retrieved from the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), this database contains coded pathology reports of all Dutch hospitals since 1991. These datasets were combined with a reference cohort with a verified IBD diagnosis (yes/no) and demographics for all patients. Models were trained to optimise the F-score and evaluated using five-times repeated ten-fold cross-validation. The best performing model from cross-validation was applied to assess IBD prevalence in the Netherlands.

Results

The reference cohort consisted of 10,155 patients, of which 3,381 were diagnosed with IBD. All models performed well in the cross-validation procedure, with F-scores of 0.870 and higher. The use of more flexible models led to improved performance, with gradient boosted trees performing best in the cross-validation procedure (Table 1). When applying the gradient boosted trees model to the general population, a prevalence of 691 per 100,000 was found for IBD in the Netherlands on 31-12-2020. Cases are unevenly distributed throughout the Netherlands (Figure 1), with the highest incidence in the south (Middle Limburg: 936 per 100,000 inhabitants) and the lowest in the northwest (Amsterdam: 545).

Conclusion

Prevalent IBD cases can be identified from administrative data using a gradient boosted trees model. Using this model, we have shown that prevalence of IBD in the Netherlands is increasing. However, while prior studies have predicted a growth in prevalence of 50% over the last 10 years, we found that IBD prevalence has only increased by 12% in that time range. The lower increase in prevalence may be predictive of a transition to the fourth epidemiological stage of IBD, aptly named Prevalence Equilibrium.
DOP09 Eosinophils exert a pro-inflammatory role in a chronic DSS colitis model without an impact on fibrosis
Authors: Jacobs I , Deleu S , Cremer J , De Hertogh G , Vermeire S , Breynaert C , Vanuytsel T , Verstockt B
Published: January 2023

Background

Eosinophils might play a pro-inflammatory role in inflammatory bowel disease (IBD). However, the role of eosinophils in intestinal fibrosis remains poorly understood, although a pro-fibrotic function has been hypothesized based on data outside the gastrointestinal tract. Therefore, we aimed to unravel the role of eosinophils in chronic intestinal inflammation and fibrosis and to explore eosinophil depletion as a potential therapeutic target.

Methods

A 3-cycles chronic dextran sodium sulphate (DSS) model was induced in 6-8-week-old C57BL/6 wild type mice. Mice received 3 DSS cycles (1.5% - 2.00% - 2.00%) in which 1 DSS cycle consisted of 1 week of DSS administration followed by 2 weeks of recovery. During the 3 cycles, and starting 3 days prior to colitis induction, anti-CCR3 antibody or isotype injections were given twice weekly to study the effect of the eosinophil depletion (total of 18 injections). The disease activity index (DAI; weight loss, stool consistency and presence of blood) was determined twice weekly. At sacrifice, colonic damage was scored macroscopically (presence of hyperaemia, adhesions and length and degree of colon affected by inflammation) and colonic single cells were isolated and fluorescently stained for flow cytometry. Eosinophils were thereby identified as CD45+ CD11b+ Siglec-F+ CD117- cells. Lastly, a histological active disease score was determined comprising of the sum of neutrophil infiltration, mononuclear cell infiltration, changes in mucosal architecture, goblet cell loss and epithelial defects (Creyns et al., 2019). Intestinal fibrosis was assessed via colon weight/length ratio, COL1A1 gene expression and collagen deposition with a Martius Scarlet Blue (MSB) staining and a colorimetric hydroxyproline assay.

Results

Blood and colonic eosinophil depletion via anti-CCR3 injections was confirmed via flow cytometry (figure 1). The DAI in the eosinophil depleted group was decreased compared to the isotype injected group (area under the curve 115.4 ± 29 vs 160.6 ± 28; p=0.02). A similar trend was seen in the macroscopic damage score (2.0 ± 1.3 vs 3.9 ± 2.1; p=0.08). Furthermore, a lower histological active disease score was found in the mice in which the eosinophils were depleted compared to the isotype injected mice (8.8 ± 0.8 vs 12.8 ± 1.5; p=0.002) (figure 2). Lastly, no differences in the parameters for fibrosis between the anti-CCR3 injected and isotype injected groups were observed (figure 3).

Conclusion

Eosinophil depletion via intraperitoneal anti-CCR3 injections resulted in partial protection from intestinal inflammation in chronic DSS, and could therefore be further explored as a potential therapeutic agent. In contrast, eosinophil depletion does not seem to have any anti-fibrotic effect
DOP16 Anti-integrin αvβ6 autoantibodies predate Ulcerative Colitis diagnosis by up to 10 years and are associated with adverse disease-related outcomes
Authors: Livanos A , Dunn A , Fischer J , Ungaro R C , Turpin W , Lee S H , Rui S , Del Valle D M , Jougon J J , Martinez-Delgado G , Riddle M S , Murray J A , Laird R M , Torres J , Agrawal M , Magee J S , Dervieux T , Gnjatic S , Sheppard D , Sands B E , Porter C K , Croitoru K , Petralia F , Colombel J F , Mehandru S ,   CCC-GEM Project Research Consortium and OSCCAR Consortium
Published: January 2023

Background

Biomarkers for predicting the development of Ulcerative Colitis (UC) and disease-related complications are lacking. Anti-integrin αvβ6 IgG autoantibodies (anti-αvβ6) have been recently described in patients diagnosed with UC. Here, we sought to determine if anti-αvβ6 autoantibodies predate UC development and to study associations between anti-αvβ6 and disease outcomes in newly diagnosed UC patients.

Methods

In a unique pre-clinical IBD cohort from the PRoteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS), anti-αvβ6 were measured in longitudinal pre-diagnosis serum samples from 82 subjects who later developed UC as well as in 82 matched subjects that did not develop IBD (HC). Sample A was at the time of UC diagnosis, Sample B was at a median of 2 years before Sample A, Sample C was at a median of 4 years before Sample A and Sample D was at a median of 10 years before Sample A. In a distinct, external validation cohort (the Crohn’s and Colitis Canada Genetics Environment Microbial (GEM) Project), we tested samples from 12 subjects who later developed UC and compared those with 49 matched subjects who remained asymptomatic. Further, anti-αvβ6 were measured in 2 incident IBD cohorts (COMPASS, n=55 and OSCCAR, n=104 UC subjects) and associations between anti-αvβ6 and adverse UC-outcomes were defined using Cox proportional-hazards model.

Results

Anti-αvβ6 were significantly higher in the PREDICTS cohort among individuals who developed UC compared to HC up to 10 years prior to diagnosis (Figure 1A). The anti-αvβ6 seropositivity was 12.2% 10 years before diagnosis and increased to 52.4% at the time of diagnosis in subjects who developed UC compared with 2.7% in controls across the 4 timepoints. Additionally, the predictive performance of anti-αvβ6 autoantibodies as assessed via area under the receiver operator curves (AUROC) with 10-fold cross validation was at least 0.8 up to 10 years before diagnosis (Figure 1B). Elevated levels of anti-αvβ6 in pre-clinical UC samples were further validated in the GEM cohort (Figure 1C). Finally, high anti-αvβ6 were associated with a composite of adverse UC-outcomes including hospitalization, disease extension, colectomy, systemic steroid use and/or escalation to biologic therapy in both incident cohorts (Figure 1D).

Conclusion

Anti-integrin αvβ6 autoantibodies precede the clinical diagnosis of UC by up to 10 years and are associated with adverse UC-related outcomes.
DOP20 The impact of early life antibiotics on the occurrence of paediatric inflammatory bowel disease - a nationwide study from 1995 – 2018
Authors: Jawad A , Jansson S , Malham M , Wewer V ,   Copenhagen Center for Inflammatory Bowel Disease in Children- Adolescents and Adult
Published: January 2023

Background

Early–life antibiotic exposure has been associated with a decreased richness of the microbiome, which is associated with the development of inflammatory bowel disease (IBD). The aim of this study was to assess the risk of developing paediatric-onset IBD (pIBD) after being exposed to systemic antibiotics during the first five years of life.

Methods

We identified all patients < 18 years old diagnosed with pIBD in Denmark between 1995-2018 in the National Patient Registry. Data on antibiotic prescriptions during first five years of life were retrieved from the National Prescription Register. PIBD patients were matched with up to ten healthy controls. Risk estimates were presented by Hazard ratios (HR).

Results

We identified 1,808 patients with pIBD (989 Crohn’s disease [CD]/819 ulcerative colitis [UC]) and 17,234 matched controls. An increased risk of developing pIBD was associated with prescription of antibiotics during first five years (HR = 1.32 [95%CI: 1.2-1.5], p= <0.0001), and risk was further increased if the patient had ≥ 4 antibiotic prescriptions compared to no antibiotic prescription (HR = 1.43 [95%CI: 1.2-1.6], p= <0.0001). Prescription of broad-spectrum antibiotics increased the risk of pIBD compared to prescription of only narrow-spectrum antibiotics (HR: 1.19, [95%CI 1.0-1.4], p=0.04). When stratified by IBD subtypes, only CD was significantly associated with exposure to antibiotics (HR = 1.43 [95%CI: 1.2-1.7], p=0.0003).

Conclusion

In this nationwide registry-based study, we found that antibiotic exposure during first five years of life, was associated with an increased risk of pIBD. Repeated antibiotic exposures increased risk estimates.
DOP89 Impact of biologics on the risk of early postoperative complications in Crohn’s disease: a French nationwide study
Authors: Fumery M , Nancey S , Nachury M , Allez M , Rouillon C , Boureille A , Altwegg R , Serrero M , Vuitton L , Bouguen G , Abitbol V , Boualit M , Biron A , Panis Y , Laharie D , Amiot A , Simon M , Caillo L , Hébuterne X , Vidon M , Benezech A , Elgharabawy Y , Peyrin-biroulet L ,   GETAID
Published: January 2023

Background

While the effect of anti-TNFs on postoperative outcomes in patients with Crohn’s disease (CD) has been widely studied, the impact of vedolizumab and ustekinumab on the risk of postoperative complications remains poorly known.

Methods

All consecutive patients who underwent intestinal resection for CD between July 2014 and April 2022 within 22 French centers were included in a retrospective cohort. The risk of early post-operative complications (≤30days) in patients exposed to biologics was compared to patients not exposed by logistic regression and propensity score-matched analysis adjusted for age, previous intestinal resection, corticosteroids or immunosuppressants exposure, disease activity, presence of abscess, urgent surgery and initial stoma (preoperative contra-indication to anastomosis).

Results

Among the 1201 patients included, respectively 491 (41%), 76 (6.3%) and 57 (4.7%) were exposed to anti-TNFs, ustekinumab, or vedolizumab within six months before surgery. A total of 317 (26.4%) patients had at least one complication of which 123 (38%) were considered as severe (DINDO III/IV). New surgery was necessary in 69 (5.7%) patients and secondary stoma in 23 (1.9%). Three deaths were observed (0.25%). The rates of overall complications in patients not exposed to biologics, exposed to anti-TNFs, ustekinumab or vedolizumab were respectively 26.1%, 25.1%, 34.7% and 29.8%. The risks of intra-abdominal infectious complications in these four groups were respectively 13.5%, 11.1%, 13.3% and 8.8%. In multivariate analysis, age [OR, 1.02 (1.01-1.04); p=0.004], disease activity [OR, 8.36 (1.79 – 149); p=0.037], the presence of an abscess [OR, 2.01 (1.25-3.20); p=0.004] and initial stoma [OR, 1.70 (1.10 –2.61); p=0.016] were significantly associated with intra-abdominal infectious complications. Conversely, preoperative enteral nutrition [OR, 0.12 (0.01 -0.59); p=0.040] was associated with a reduction in this risk. Exposure to anti-TNFs [OR, 0.80 (0.51-1.24); p=0.31], ustekinumab [OR, 1.17 (0.39-3.51); p=0.78] and vedolizumab [OR, 1.28 (0.32-5.17); p=0.72] within the 3 months before surgery were not associated with the risk of intra-abdominal infectious complications. Similar results were observed in patients exposed to these treatments in the month before surgery.

Conclusion

In this large cohort, a quarter of patients operated on for CD presented an early postoperative complication and 10% a severe complication. Preoperative exposure to anti-TNFs, vedolizumab or ustekinumab was not associated with an increased risk of early postoperative complications. Preoperative enteral nutrition was associated with a reduced risk of intra-abdominal infectious complication.
P175 Burden of Inflammatory Bowel Disease in Mexico: RISE-MX, a Multi-center, Retrospective, 3-Year Data Study
Authors: Yamamoto-Furusho J K , Martinez-Vazquez M , Miranda-Cordero R , Bosques.Padilla F ,   RISE-MX Study Group
Published: January 2023

Background

The incidence and prevalence of inflammatory bowel disease (IBD) has increased significantly in the last decade in Mexico. This work describes the burden of disease in terms of healthcare resources utilization and costs (direct and indirect) related to the management of patients (pts) diagnosed with moderate/severe ulcerative colitis (UC) and Crohn’s disease (CD), over 3 years.

Methods

This multicenter, retrospective, non-interventional study enrolled 335 IBD pts. Upon written consent for eligible pts, data regarding disease activity, treatment patterns and burden of disease were collected (Fig 1). Direct costs calculation was obtained by a micro-cost analysis and cross-sectional indirect costs (human capital/income) by proportional hours of absence/productivity, based on Work Productivity and Activity Impairment score. Unitary costs were taken from institutional data: Groups Related to the Diagnosis (GRD-IMSS) 2017 updated with the INEGI explosion factor in the middle of the year 2022 and IMSS Unit Costs 2022, the price of the drugs used was from the Annual Acquisitions, Leasing and Services Program updated to September 2022. Direct costs were obtained by multiplying resource use with relevant unit costs. Unit costs for each resource items were collected in Mexican reliable administrative databases or other sources. All data were descriptively analyzed.

Results

There were 335 pts enrolled and 326 eligible. 95 (29.1%) had CD and 231 (70.9%) had UC. In the CD group, 52 pts had remission/mild activity and 43 had moderate/severe activity. A total of 26.3% (25/95) disease–related hospitalizations were reported in CD pts and 15.6% (36/231) for UC pts. The mean of hospitalization duration was 11.7 days for pts with moderate/severe CD and 8.5 days for pts with moderate/severe UC. The absenteeism in CD pts was 19.9% for moderate/severe and 17.3% for remission/mild activity, while in UC pts was 9.8% for moderate/severe and 10.6% for remission/mild activity. Considering comorbidities, extraintestinal manifestations, previous treatments, medical appointments, hospitalizations and other medical procedures, the annual direct costs per-patient impact in CD was US$19,026 (moderate/severe) and US$12,126 (remission/mild). Furthermore, in pts with UC, the cost was US$11,516 (moderate/severe) and US$8,952 (remission/mild). The indirect costs represent US$1,191 for CD and US$376 for UC (Fig 1F).

Conclusion

The disability rate of CD is 25% [20-34%], this study reports 18.4%. CD was associated with higher rates of hospitalization and increase in cost of health care resources, compared to UC patients.
P207 Colonic location at diagnosis of pediatric-onset Crohn’s disease is associated with a pejorative disease course: a two decades population-based study
Authors: Fumery M , Savoye G , Ley D , Dupont-Lucas C , Bertrand V , Wils P , Guillon N , Sarter H , Gower-Rousseau C , Turck D , Leroyer A ,   EPIMAD
Published: January 2023

Background

Crohn's disease (CD) location would influence the risk of complications and therapeutic strategies. The objective of this study was to compare the clinical presentation at diagnosis and the natural history of colonic CD in comparison to ileal CD and ulcerative colitis (UC) in pediatric-onset inflammatory bowel disease.

Methods

All children (< 17 years) with a diagnosis of CD or UC made between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. Presentation at diagnosis, risks of complicated disease, surgery, hospitalization and exposure to treatments in ileal CD (L1), colonic CD (L2) and UC were compared. Disease location was defined at diagnosis. In case of extension of the disease (L1 or L2 to L3), follow-up was censored.

Results

A total of 215 L1 patients, 234 L2 patients and 337 UC patients were included. At diagnosis, the proportion of males (L1 53.5%; L2 53.4%; UC 42.7%; p=0.012), age at diagnosis (15.0; 13.7; 14.0 years; p=0.003), family history of IBD (12.6%; 12.7%; 5.0%; p=0.005), diagnostic delay (3.0; 3.0; 2.0 months; p=0.001) and smoking prevalence (11.6%; 8.1%; 5.6%; p=0.041) were different between the three groups. Bloody stool and diarrhea at diagnosis was observed in respectively 14.9%, 44.4%, and 91.1% (p < 0.001) and 47.0%, 71.8%, and 65.0% (p < 0.001) of L1, L2 and UC. At diagnosis, granuloma was identified in 12.6% of L1 patients and 31.2% of L2 patients (p<0.001). The risk of extension to L3 was significantly higher in the L2 group than in the L1 group (at 5 years - 37% vs. 14%, p<0.001). Compared to L1 location, L2 was associated with a lower risk of luminal fistula (HR 0.41 [0.21-0.79], p=0.008) but a higher risk of anoperineal lesion (HR 2.11 [1.29-3.45], p=0.003). The prevalence of extra-intestinal manifestations, articular (p<0.001) and cutaneous (p<0.001) was higher in L2. While the risk of surgery was significantly higher in case of L1 (at 5 years – L1 37%, L2 13% and UC 13%; p<0.001), the risk of hospitalization (at 5 years - 22%, 39% and 33%; p=0.01), exposure to corticosteroids (at 5 years - 55%, 69% and 67%; p<0.001), immunosuppressants (at 5 years - 47%, 61% and 42% - p<0.001) and anti-TNF (at 5 years - 16%, 35% and 22%; p<0.001) were higher in case of L2.

Conclusion

The clinical presentation at diagnosis and natural history of ileal and colonic CD differ significantly. Colonic location is associated with a high risk of perianal CD, extra-intestinal manifestations, hospitalization as well as exposure to steroids, immunosuppressants and anti-TNF. These differences may justify different therapeutic strategies in the future.
P247 Oncostatin M and its receptor are markers of endoscopic and histological disease activity in Inflammatory Bowel Disease
Authors: Nguyen A , Sturm G , Plattner C , Trajanoski Z , Atreya R , IBDome Consortium I C , Siegmund B , Hegazy A N ,   IBDome Consortium
Published: January 2023

Background

Oncostatin M (OSM) and its receptor (OSMR) have been associated with active disease in patients with inflammatory bowel disease (IBD). This study compared the expression of OSM and OSMR in intestinal tissue according to clinical, endoscopic, and histological disease activity.

Methods

A multi-centre IBD database containing RNA-sequencing datasets, was used to analyse OSM and OSMR expression in ileal and/or colonic tissue, expressed as transcripts per million (TPM). Clinical scoring systems included the Harvey Bradshaw Index for Crohn’s disease (CD) and partial Mayo score for ulcerative colitis (UC). Endoscopic scoring systems included the simple endoscopic score for CD (SES-CD) and UC endoscopic index of severity (UCEIS). Histological scoring included the modified Naini and Cortina, and Riley scores. Graphs were presented in log transformed TPM+1 values.

Results

155 patients (108 CD, 47 UC) and 38 controls were included. For IBD patients, 49% were men, median age was 35 years and intestinal tissue was collected at endoscopy (73%) and surgery (27%). Compared to controls, patients with CD and UC had significantly elevated median expression of OSM (0.08, 0.29 and 0.34 TPM respectively) and OSMR (1.21, 1.69 and 3.53 TPM respectively). OSMR expression was higher in UC patients than CD (p<0.001). There was no difference in OSM or OSMR between Harvey Bradshaw Index categories (0-4 vs 5-7 vs 8-16) or partial Mayo scores (0 vs 1-3 vs 4-7). Endoscopically, OSM was higher for SES-CD scores of 16-51 (1.11 TPM), compared to SES-CD scores of 0-3 (0.14 TPM, p=0.003) and controls (0.08 TPM, p<0.0001). Median OSMR increased non-significantly with increasing SES-CD scores (score 0-3: 1.59 TPM; score 4-15: 1.90 TPM; score 16-51: 2.04 TPM). There was no difference in OSM and OSMR expression between UCEIS scores, but the most severe disease (UCEIS score 5-8) had higher expression than controls for both OSM (3.92 vs 0.08 TPM, p<0.001) and OSMR (6.10 vs 1.21 TPM, p<0.0001). Increasing expression of OSM and OSMR was found with increasing histological scores, see Figure. Using the modified Naini and Cortina score for CD, OSM and OSMR were most expressed in the highest scores compared to the lowest scores (OSM: 1.48 vs 0.09 TPM, p<0.001; OSMR: 5.50 vs 1.27 TPM, p=0.003). For the modified Riley score for UC, both OSM and OSMR were also able to differentiate between the highest and lowest score groups (OSM: 3.14 vs 0.12 TPM, p=0.0001; OSMR: 6.61 vs 1.58 TPM, p<0.0001).

Conclusion

This study showed that OSM and OSMR expression in intestinal tissue is associated with inflammation both histologically and endoscopically. Further investigations are needed to confirm our observations and explore the OSM pathway’s relevance in intestinal inflammation.