bluuebunny/crossref_metadata_2025_split huggingface dataset:
A217 DEFINING THE RELATIONSHIP BETWEEN DIETARY FIBERS AND INFLAMMATORY RESPONSE IN PEDIATRIC INFLAMMATORY BOWEL DISEASES
Authors: Mander I K , Jerasi J , Dickner R , Carroll M W , Huynh H Q , Armstrong H , Wine E 
Published: February 2020

Abstract

Background
The incidence rates of inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC) are increasing in children. Although the etiology of IBD is poorly understood, factors such as urban lifestyle, diet, increased hygiene, and reduced microbial biodiversity have been implicated as risk factors. Compositional changes and reduced microbial biodiversity have been linked to therapy failure in pediatric IBD. Non-digestible dietary carbohydrates, such as fiber, must undergo fermentation by gut microbiota within the large bowel, producing short chain fatty acids (SCFAs). Animal studies have shown that dietary fibers can inhibit IBD-associated inflammation, and clinical trials have demonstrated that SCFAs can prevent intestinal atrophy and allow for tissue recovery in IBD patients. In disease settings with altered gut microbes, fermentation of dietary fibers may be greatly affected. Unfermented fibers interact with receptors on host immune cells and can induce proinflammatory immune response, production of oxygen species and inflammation, or an inhibition of proinflammatory receptors.

Aims
Based on this rationale, we hypothesize that dysbiosis in the IBD gut leads to decreased fiber fermenting microbes, resulting in reduced SCFA production. This contributes to increased inflammatory responses both in in vitro cell lines, as well as ex vivo patient biopsies. Because intact fibers can bind to host cell receptors, this promotes inflammatory response and continued dysbiosis.

Methods
To assess effects of intact fiber on immune cells, macrophage and T-cell in vitro cultures were used to measure cytokine response to inulin (5mg/mL) and oligofructose (5mg/mL) through ELISAs/qPCR. These cell lines and ex vivo patient biopsies were treated with whole fibers and IL-1β secretion was measured. Fibers were also pre-fermented with microbes of interest or whole microbe patient intestinal washes and used to treat cell lines and patient biopsies.

Results
Whole fibers induced a pro-inflammatory response in macrophage cells but not T-cells, and this pro-inflammatory response was mitigated by pre-fermenting the fibers. Intestinal washes from severe IBD patients were unable to successfully ferment oligofructose or reduce fiber-associated inflammation in macrophage cell lines, whereas washes from remission or non-IBD samples reduced IL-1β. Oligofructose was found to increase IL-1β secretion in UC and CD patient biopsies, but not in non-IBD specimens. This increase was also correlated with disease severity.

Conclusions
These results indicate that a lack of fiber-fermenting microbes and presence of whole fibers can lead to pro-inflammatory responses, both in cell lines and patient biopsies. However, the presence of appropriate fermenting microbes can reduce fiber-associated inflammation.

Funding Agencies
CCCWCHRI, Weston Foundation
A231 UNDERSTANDING THE IMPACT OF TNF-ALPHA ANTAGONISTS ON THE SEVERITY OF NON-MELANOMA SKIN CANCER IN INFLAMMATORY BOWEL DISEASE AND THE CONSEQUENCES FOR THERAPY
Authors: Townsend C M , Khanna R , Wilson A 
Published: February 2020

Abstract

Background
Non-melanoma skin cancer (NMSC) accounts for at least 40% of all new cancer diagnoses in Canada annually and presents a significant cost to the health care system due to the volume of cases. The incidence of NMSC in patients with Inflammatory Bowel Disease (IBD) is higher when compared to the general population. Generally, in a non-IBD population, the risk of further NMSC progression is low, however, little data exists that highlights differences in clinical course of patients diagnosed with NMSC who have IBD and are TNF-α antagonist exposed. It is unclear if TNF-α antagonist therapy should be discontinued in this patient population.

Aims
Our goal is to determine whether TNF-α antagonist exposure in IBD is associated with a high risk NMSC presentation at diagnosis, as defined by the National Comprehensive Cancer Network (NCCN) stratification. Our secondary objectives include presence of positive margins following resection, presence of metastatic disease on initial presentation, requirement of additional therapy to treat NMSC, number of patients who had TNF-α antagonist therapy discontinued following diagnosis of NMSC and number of individuals with recurrent NMSC.

Methods
Four hundred and twenty-four IBD patients seen at London Health Sciences Centre were reviewed. We have identified 22 patients who were diagnosed with NMSC. Twelve patients had a pre-NMSC TNF-α antagonist exposure while 10 patients who developed an NMSC and had no TNF-α antagonist exposure prior to NMSC diagnosis.

Results
Preliminary results of the primary outcome demonstrate that fifty-percent (6/12) of patients who have been exposed to TNF antagonist therapy presented with a high risk NMSC lesion at diagnosis compared to 40% (4/10) who were not exposed (OR 5.16, 95%CI 0.47–57.00; p = 0.181). Preliminary results of the secondary outcomes suggest that 25% (3/12) of patients exposed to TNF-α antagonist had positive margins compared with 0% (0/10) of patients who were not exposed. No patients in either group presented with metastatic disease. Twenty-five percent (3/12) of patients in the exposed group received more advanced treatment compared with 0% (0/10) in the non-exposed group. Eight percent (1/12) of patients in the TNF-α antagonist group had their IBD therapy changed from a TNF-α antagonist to an alternative biologic class, and 17% of patients (2/12) in the TNF-α antagonist group had recurrent NMSC lesions.

Conclusions
In conclusion, preliminary results suggest that TNF-α antagonist exposure may be associated with higher risk NMSC lesion at presentation. Further expansion of the sample size is required to explore these hypotheses further.

Funding Agencies
None
A244 MATERNAL THIOPURINE AND ANTI-TUMOR NECROSIS FACTOR THERAPY DURING PREGNANCY IS ASSOCIATED WITH AN INCREASED RISK OF PLACENTAL-RELATED DISEASES
Authors: Tandon P , Lee E , Hitz L , Huang V 
Published: February 2020

Abstract

Background
Though previous studies have suggested that most therapies for inflammatory bowel disease (IBD) are safe during pregnancy, the effect of these medications on placental-related diseases remain unknown.

Aims
To determine the effect of gestational medication exposure on pregnancy-related outcomes in patients with IBD.

Methods
We retrospectively reviewed the University of Alberta and University of Toronto pregnancy databases to identify patients (age &gt; 18) who underwent routine assessment by a gastroenterologist at least once during pregnancy (first trimester (T1), second trimester (T2), and third trimester (T3). Pregnancy-related outcomes (maternal, obstetrical, and neonatal) were recorded from obstetrical records. Low-birth weight (LBW) was defined as an infant weight &lt; 2500g at birth. Pre-term delivery was defined as birth &lt; 37 weeks gestation. Medication exposure, such as 5-aminosalicylates (5-ASA), thiopurines, steroids, and anti-tumor necrosis factor (TNF) therapy was recorded for each trimester. Categorical variables were statistically compared using the Chi-square (x2) test through the SPSS software.

Results
A total of 84 patients were included. Compared to those not exposed to thiopurines, patients exposed to thiopurine therapy during T2 had an increased risk of pre-term birth (26.7% vs. 7.7%, p=0.046) and pre-eclampsia (13.3% vs. 0%, p=0.008) and a trend towards an increased risk of placental abruption (6.7% vs, 0%, p=0.061). Furthermore, compared to those not treated with corticosteroids, those prescribed corticosteroid therapy during any trimester had an increased risk of pre-term birth (T1 exposure: 50% vs. 10.2%, p=0.024; T2 exposure: 37.5% vs. 8.5%. p=0.018; T3 exposure: 42.9% vs. 8.8%, p=0.008) and infants born with LBW (T1 exposure: 50.0% vs. 7.8%, p=0.009; T2 exposure: 37.5% vs. 8.2%, p=0.015; T3 exposure: 57.1% vs. 8.6%, p=0.0005). Those exposed to corticosteroids in T3 only had an increased risk of PPROM (60.0% vs. 7.5%, p=0.0003) and chorioamnionitis (14.3% vs. 0%, p=0.002). Finally, anti-TNF therapy in T2 was associated with an increased risk of pre-eclampsia (9.1% vs. 0%, p=0.040. 5-ASA therapy was not associated with an increased risk of any adverse pregnancy-related outcome. No medication increased the risk of other maternal (i.e. gestational diabetes, emergency Cesarean-section delivery) and neonatal (intensive care unit admission, congenital anomalies) outcomes.

Conclusions
Placental related diseases, such as pre-eclampsia, appear to be increased with maternal exposure to thiopurine and anti-TNF therapy during pregnancy. Larger studies are required to confirm these associations.

Funding Agencies
None
A254 IGA-MEDIATED WARM AUTOIMMUNE HEMOLYTIC ANEMIA IN A PATIENT WITH CROHN’S DISEASE ON VEDOLIZUMAB
Authors: Cheah M S , Khanna R 
Published: February 2020

Abstract

Background
Iron deficiency anemia and anemia of chronic disease are relatively common manifestations of Crohn’s disease. Autoimmune hemolytic anemia, however, is quite rare with few reported cases.

Aims
To present a rare case of IgA-mediated warm autoimmune hemolytic anemia in Crohn’s Disease.

Methods
A chart review and literature search were performed in preparation of this case report.

Results
A 21-year-old male with a recent diagnosis of Crohn’s disease on Vedolizumab presents to infusion clinic with generalized weakness, coke-colored urine and weight loss. Physical examination was remarkable for tachycardia and jaundice. Laboratory investigations revealed profound anemia with IgA-mediated DAT positivity. The patient remained admitted in hospital for a prolonged period. Bone marrow biopsy, CT imaging and infectious workup were negative. Vedolizumab was held and treatment with both high-dose corticosteroids and rituximab was required. Eventually, the anemia would stabilize and Vedolizumab was safely resumed as an outpatient.

Conclusions
Here we report a both rare and challenging case of IgA-mediated DAT positive autoimmune hemolytic anemia in a patient with Crohn’s disease who was successfully treated with corticosteroids and rituxumab.

Funding Agencies
None
A262 DIFFERENTIAL PHENOTYPES AND LOCALIZATION OF CD8+ T CELL RESPONSES TO ACUTE AND CHRONIC ENTERIC VIRAL INFECTION
Authors: Hardman B K , Osborne L C 
Published: February 2020

Abstract

Background
Human Norovirus infection is the most common viral cause of gastroenteritis globally and the second most reported viral infection in Canada after the common cold. Most infections are acute, symptomatic, and rapidly cleared but some cases persist asymptomatically or induce post-infectious irritable bowel syndrome. Despite the global burden of these infections, no vaccine to prevent disease exists nor is the mechanism for persistence understood. MNV-CW3 and MNV-CR6 are murine noroviruses which demonstrate distinct biological behaviors that correlate with differential quantity and quality of antiviral CD8+ T cell responses. MNV-CW3 causes acute systemic infections initiated in the small intestine and cleared by day 8 due to a robust antiviral CD8+ T cell response. In contrast, MNV-CR6 causes chronic infections localized to the colonic intestinal epithelium and induces fewer antiviral CD8+ T cells with reduced effector molecule expression.

Aims
This research interrogates the mechanisms underlying strain-specific differential antiviral CD8+ T cell responses.

Methods
At days 3, 4, 5 and 8 post-infection, the phenotype and quantity of adoptively transferred MNV specific CD8+ T cells in the spleen, mesenteric lymph node (MLN), and the small and large intestine are analyzed by flow cytometry. Concurrently, immunofluorescent microscopy is used to determine whether CD8+ T cells are broadly disseminated throughout the intestines or localize in acute clusters of antiviral response. Combining these complementary techniques provides novel insight into mechanisms governing intestinal antiviral T cell responses.

Results
Activated MNV-specific CD8 T cells first accumulate in the MLN following oral infection with both MNV-CW3 and CR6, suggesting this is the site of immune activation. Supporting this hypothesis, preliminary data indicates that preventing T cell egress from activation sites by treatment with the S1PR1 agonist FTY720 leads to an enrichment of activated CD8+ T cells in the MLN following CW3 infection. Notably, the earliest stages of CD8+ T cell activation to CR6 infection is delayed compared to that elicited by CW3. Furthermore, at the peak of CD8+ T cell expansion (day 8 post-infection), CR6-elicited CD8+ T cells preferentially develop into short-lived effector populations rather than memory precursor populations.

Conclusions
These data reveal previously unknown differences in early events in CD8+ T cell activation following infection with two highly related viral strains that correlate with long-lasting effects on T cell differentiation and function. We are currently investigating the hypothesis that MNV-CW3 and CR6 may induce activation of distinct populations of, or pathways in, APC populations that would drive these differences. These results may have broad impacts on our understanding of how non-latent, chronic viral infections persist within a host.

Funding Agencies
CIHR
A270 AMPULLARY MORPHOLOGY PREDICTS SUCCESS AND POST-PROCEDURE COMPLICATIONS IN PRIMARY NEEDLE-KNIFE FISTULOTOMY FOR BILIARY CANNULATION IN ERCP: RESULTS OF A PROSPECTIVE CASE SERIES
Authors: Hew S , Taylor C , Hookey L , Bechara R 
Published: February 2020

Abstract

Background
Biliary cannulation is often the most challenging component of successful ERCP. Needle-knife fistulotomy (NKF) involves incising directly into the intra-duodenal portion of the bile duct, away from the native orifice, to achieve direct biliary access. This technique is usually performed when standard cannulation is unsuccessful, however recently, has been shown by our group to be a potentially effective and safe method to achieve biliary access as the primary approach. It has also been demonstrated that ampullary morphology influences cannulation success.

Aims
This study aims to assess the impact of ampullary morphology on the success and complications of NKF.

Methods
A retrospective visual analysis was performed of the ampullary morphology collected prospectively as part of our original NKF study (NCT03698266). Endoscopic videos and photos were reviewed to classify the ampulla into one of four types, as per a validated classification system. Ampullas were either Type 1 (regular), Type 2 (small), Type 3 (protruding or pendulous) or Type 4 (creased or ridged). Outcomes examined included: time to cannulation, proceduralist-perceived difficulty and complications.

Results
Of the 71 patients enrolled in the NKF study, 66 had video or photographs of the ampulla to facilitate classification. There were 35 (52%) Type 1 ampullas, 16 (24%) Type 2 and 14 (21%) Type 3 and one (1%) Type 4 ampullas. 65 out of the 66 (98.4%) patients had successful biliary access after primary NKF. The mean time to cannulation in all patients was 5.3 minutes (range 0.25–27 minutes). There were 3 cases of post-ERCP pancreatitis (PEP) (4.5%) and 3 cases of post-ERCP bleeding (4.5%).
Compared to Type 1 ampullas, there was a no significant increase in time to cannulation in Type 2 and Type 3 ampullas using NKF (Type 1 4.7 vs. Type 2 7.1 vs. Type 3 6.4 minutes, p = NS). Only one patient with a Type 2 ampulla was rated as ‘low difficulty’ by the proceduralist performing NKF. Nevertheless, successful NKF was achieved in 15 out of 16 Type 2 ampullas (93.8%). There was 100% success rate in biliary access for Type 3 ampullas, previously shown to more challenging using conventional cannulation techniques. All cases of PEP occurred in patients with Type 2 ampullas.

Conclusions
As with the impact on conventional cannulation, ampullary morphology may influence outcomes of NKF. It appears that small, Type 2 ampullas with a short intra-duodenal segment makes NKF more challenging and may be associated with a higher rate of PEP. Unlike conventional cannulation, Type 3 ampullas are similar to Type 1 ampullas in ease of NKF access.

Funding Agencies
None
Rudolph M. Schindler
Authors: Sheine Judith 
Published: February 2020

R. M. Schindler (b. 1887–d. 1953) was born in Vienna, Austria, and received architecture degrees from the Vienna Polytechnic University (Technische Hochschule) in 1911 and the Academy of Fine Arts (Akademie der bildenden Kunste) in 1913. While influenced by the Viennese architects Otto Wagner and Adolf Loos, Schindler was exposed to the work of the American architect Frank Lloyd Wright through his Wasmuth portfolio and was inspired to go to the United States in March 1914, shortly before the outbreak of World War I. In the United States, he found work in February 1918 with Wright, who sent him to Southern California in December 1920 to work on a project for his client, Aline Barnsdall. Schindler began his independent practice there, designing and building his own house and studio in 1921–1922. He had intended to return to Vienna, however, due to the difficult postwar economic conditions in Europe, he settled for the rest of his life in Southern California, with its mild climate, promising economic future, and openness to experimentation. Throughout his career Schindler wrote articles on architectural theory, designed over 500 projects—more than 150 of which were built, almost entirely in Southern California—and acted as his own contractor on the vast majority of his commissions. He has been identified as the first modern architect in Southern California, introducing innovative ideas and construction techniques, along with his contemporary and fellow Viennese architect Richard Neutra, who came to Southern California at Schindler’s invitation in January 1925. Schindler distinguished his own individual approach to architecture from that of the so-called International Style, proclaiming that architecture should be about “space” rather than focusing on any particular style or material. Throughout his career, Schindler experimented with a wide variety of materials and building techniques, resulting in buildings that, while they looked very different, retained their focus on a consistent set of spatial principles along with specificity to their site, climate, and client. In part due to his unorthodox approach to modern architecture, while his early projects were published with some frequency, the later works were published increasingly less and Schindler did not receive the large commissions for which he had hoped. After his death, with the postmodern reevaluation of the direction of architecture starting in the mid-1960s, Schindler’s work began to receive renewed critical attention, with books and exhibits devoted to his career, and recognition continues to grow in the present day.
A quantum-corrected approach to black hole radiation via a tunneling process
Authors: Hajebrahimi Milad , Nozari Kourosh 
Published: February 2020

Abstract
In the language of black hole physics, Hawking radiation is one of the most controversial subjects about which there exist lots of puzzles, including the information loss problem and the question of whether this radiation is thermal or not. In this situation, a possible way to face these problems is to bring quantum effects into play, also taking into account self-gravitational effects in the scenario. We consider a quantum-corrected form of the Schwarzschild black hole inspired by the pioneering work of Kazakov and Solodukhin to modify the famous Parikh–Wilczek tunneling process for Hawking radiation. We prove that in this framework the radiation is not thermal, with a correlation function more effective than the Parikh–Wilczek result, and the information loss problem can be addressed more successfully. Also, we realize that quantum correction affects things in the same way as an electric charge. So, it seems that quantum correction in this framework has something to do with the electric charge.
Creating Reflective Space for Reflective and “Unreflective” Medical Students: Exploring Seminal Moments in a Large-Group Writing Session
Authors: Campbell Bruce H. , Treat Robert , Johnson Benjamin , Derse Arthur R. 
Published: February 2020

Problem
Reflection is a critical skill for all physicians, but some busy medical students describe themselves as “unreflective.” The authors sought to provide all third-year medical students at the Medical College of Wisconsin (MCW) with opportunities to explore seminal clinical and personal moments through reflective writing during workshops on preparing a personal statement for the Electronic Residency Application Service.

Approach
The authors developed and facilitated semiannual 1.5- to 2-hour sessions (January and June) for MCW third-year medical students (about 200 per class), pairing information on personal statements with reflective writing and group reflection activities. Students wrote reflectively but were not required to share their writing with peers or faculty. They discussed insights gleaned during the writing process in small groups and with the class. They completed pre- and postsession questions on an anonymous questionnaire.

Outcomes
Eight all-class sessions were held between January 2015 and June 2018. Students completed 1,139 of 1,600 questionnaires (completion rate of approximately 71%). They misperceived their peers’ views of reflective activities. Twice as many students agreed their peers felt writing, reflective, and narrative exercises were a waste of time as they themselves did (39% vs 19%). While 42% entered the session comfortable with creative writing, 57% were surprised by the amount, quality, and/or insight of their writing during the session and 77% agreed the session helped them think more clearly about clinical encounters. Students who believed reflective writing was a waste of time were more likely to believe their peers felt that also, and they were less likely to believe the session helped them reflect on clinical experiences. Most written comments were positive.

Next Steps
To expose students to narrative medicine techniques, the authors added a close-reading exercise and shortened the reflective writing activity in 2019, hoping this would better equip all students for their journeys.
Ethics of HIV and hepatitis B cure research
Authors: Sugarman Jeremy 
Published: February 2020

Purpose of review
Achieving a cure for HIV or hepatitis B virus (HBV) is expected to have a range of salutary effects including eliminating the need for continued treatments, minimizing risk to sexual and injecting partners, reducing prevalence, and decreasing stigma. Nevertheless, conducting research to achieve such laudable goals is necessarily associated with a broad set of ethical challenges. This review aims at describing key findings from selected peer-reviewed literature published in the last 2 years (2018–2019) that enhance understanding of some of these issues.

Recent findings
A variety of ethical issues in HIV cure research have been informed by recent conceptual and empirical scholarship. These include: analytical treatment interruptions; attitudes towards participation; responsibilities to nonparticipants; consent and terminology; and selected other issues.

Summary
Understanding of the ethical issues in HIV cure research has been enhanced by sustained normative and empirical scholarship with a range of stakeholders. This work has crucial implications for HBV cure research, but there is also a pressing need for directed work on HBV cure research. In both HIV and HBV cure research, such scholarship promises to help ensure that critically important research efforts are ethically sound.