bluuebunny/crossref_metadata_2025_split huggingface dataset:
REGULATION OF HUMAN INTESTINAL ORGANOID REACTIVE OXYGEN SPECIES PRODUCTION AND MITOCHONDRIAL FUNCTION BY DUOX2 GENETIC VARIATION AND MICROBIAL PRODUCTS
Authors: Jurickova Ingrid , Novak Elizabeth , Angerman Elizabeth , Bonkowski Erin , Mollen Kevin , Denson Lee 
Published: January 2021

Abstract

Introduction
The DUOX2 intestinal epithelial NADPH oxidase is upregulated in Crohn’s Disease (CD), and DUOX2 mutations are associated with increased CD risk. Oxidative stress and loss of mitochondrial function disrupt the intestinal barrier promoting inflammatory responses to commensals. The relative impact of DUOX2 mutations and microbial products in this regard is poorly understood.

Hypothesis
We hypothesized that DUOX2 genetic variation would be associated with differences in cellular reactive oxygen species (ROS) production and mitochondrial function in a Human Intestinal Organoid (HIO) model system.

Methods
Induced pluripotent stem cell lines derived from pediatric CD patients with and without combined DUOX2 missense mutations(R701Q, P982A, and H678R) were used to generate wild type (WT) and DUOX2mut HIOs. Reactive oxygen species (ROS) production was measured using the two-color ROS-ID® Total ROS/Superoxide detection kit, and the mitochondrial membrane potential (MMP) was measured using JC1 staining by flow cytometry in HIO EpCAM+ epithelial cells and CD90+ stromal cells. Expression of inflammatory and mitochondrial genes which varied with DUOX2 mutation carriage in CD patent ileal biopsies was measured by RT-PCR. HIO mitochondrial complex I and II activity was measured using an Oroboros respirometer.

Results
Epithelial ROS production was reduced in DUOX2mut HIO under basal conditions; this difference was not observed following pyocyanin stimulation (Fig. 1A). A profound suppression of epithelial ROS production was observed following butyrate treatment. Butyrate did not alter stromal cell ROS production. Under these conditions, induction of ROS by pyocyanin was abrogated in WT, but not DUOX2mut HIO epithelial cells (Fig. 1B). Butyrate increased expression of core genes regulating the mitochondrial respiratory chain and DNA synthesis (COX5B, NDUFA1, POLG2, SLC25A27) and HIF1A implicated in barrier function, independent of genotype (p&lt;0.05). The epithelial and stromal cell mitochondrial membrane potential (MMP) (Fig. 2A), and HIO mitochondrial complex I activity (Fig. 2B), were reduced in DUOX2mut HIO under basal conditions. This was specific, as mitochondrial complex II activity did not vary with DUOX2 genotype.

Conclusions
We confirmed epithelial effects of DUOX2 genotype and butyrate exposure on ROS production in the HIO model system. Genotype dependent effects on basal ROS production were largely abrogated by the microbial products pyocyanin and butyrate, although butyrate inhibition of pyocyanin induced ROS production was dependent on intact DUOX2 function. Data suggest a previously unanticipated effect of DUOX2 genetic variation on the epithelial and stromal cell MMP and cellular respiration. This may have implications for mechanisms by which DUOX2 regulates barrier function and inflammatory responses to commensals in CD.
EVALUATING THE ROLE OF GOBLET CELL ASSOCIATED ANTIGEN PASSAGES (GAPS) IN THE DEVELOPMENT OF MUCOSAL IMMUNE TOLERANCE IN THE CFTR KO INTESTINE
Authors: Young Sarah , McDonald Keely , Newberry Rodney , Clarke Lane 
Published: January 2021

Abstract
Greater than 70,000 individuals worldwide are living with the monogenetic disease cystic fibrosis (CF). The development of chronic intestinal inflammation, with clinical signs resembling inflammatory bowel disease-like conditions, is a common yet poorly understood occurrence in CF patients. This inflammation is typically neutrophilic in human and animal models with a heightened basal pro-inflammatory cytokine release. Prior research utilizing intestinal organoids (enteroids) cultured from Cftr knockout mice has shown that goblet cells in the CF mouse intestine demonstrate defective clearance of mucin granules and abnormal mucus retention. Goblet cell-associated antigen passages (GAPs), located in the small intestine and colon, deliver intraluminal antigens to antigen-presenting dendritic cells in the submucosa. This mechanism serves as an important step in the development and maintenance of tolerogenic dendritic cell populations expressing receptors to luminal antigens with involvement of regulatory T cell activation and release of IL-10. We hypothesized that mucus plugging of goblet cells in the CF intestine leads to defective GAP formation and a consequent decrease in the expansion of tolerogenic dendritic cells. To test this hypothesis, Cftrtm1Unc (Cftr KO) and wild type (WT) sex-matched littermate pairs (n=2) maintained on a commercially available liquid diet (Peptamen®) were anesthetized with ketamine/xylazine for a laparotomy to inject a luminal fluorescent 10kD dextran dye into the mid-jejunum. After 30 min, the mice were euthanized with CO2, and the intestine was collected for immunofluorescent staining to evaluate GAP formation. In the WT intestine, the dextran dye was observed within goblet cells outlined by CK18 immunofluorescence, a goblet cell marker. Punctate dextran dye was observed in the submucosa, suggestive of dendritic cell uptake. In contrast, the Cftr KO mice demonstrated defective GAP formation, i.e., without dye penetration of goblet cells, and the lack of punctate dextran fluorescence in the submucosa. To evaluate the population of tolerogenic dendritic cells, small intestinal segments from Cftr KO-WT sex-matched littermate pairs (3-female and 2-male pairs) were collected for FACS sorting of submucosal CD103+ (tolerogenic) and CD103- (pro-inflammatory) dendritic cells. The WT mice had a significantly higher population of CD103+ tolerogenic dendritic cells compared to the CF mice (WT: 20.5+/-2, CF: 9.2+/-3, P &lt; 0.006). A trend towards an increase in CD103- dendritic cells was seen in the CF intestine. In summary, the CF mice were found to have defective intraluminal antigen transfer through the GAP pathway and a significant decrease in tolerogenic dendritic cells in the intestine.
VALIDATION OF HPTM-001, A HUMANIZED CANDIDATE THERAPEUTIC ANTIBODY FOR PROMOTING MUCOSAL WOUND HEALING IN IBD
Authors: Liang Tony , Presta Leonard , Brazil Jennifer , Parkos Charles , Cheng Jennifer 
Published: January 2021

Abstract
A hallmark of the clinical course of patients with Inflammatory Bowel Disease (IBD) is poorly healing erosions and ulcers in the intestinal mucosa. Despite the adverse clinical consequences of non-healing mucosal wounds in IBD, current front-line therapies that selectively target mucosal wound healing are not available.
Recent studies revealed an association between colonic inflammation and aberrant glycosylation of epithelial CD44v6. Under conditions of inflammation, epithelial CD44v6 was shown to be decorated with the terminal glycan sialyl Lewis A. Importantly, targeting sialylated Lewis glycans on CD44v6 with a murine antibody GM35 was shown to promote mucosal wound healing in cell lines and in biopsy based wounding assays as well as dextran sodium sulfate (DSS) induced murine colitis models.
We sequenced CDRs from GM35 and produced a humanized antibody. Eight candidate human IgG1 clones were produced and screened. hPTM-001.4772 was selected from the eight candidates based on glycan affinity and selectivity compared to GM35. In vitro wound healing studies revealed that PTM-001.4772 was as effective as GM35 in promoting repair of scratch wounds with human intestinal epithelial cells. Furthermore, intraperitoneal injection of mice with hPTM-001.4772 during induction of DSS colitis resulted in reduced weight loss compared to control IgG. These results suggest that hPTM-001.4772 is well-positioned as a unique potential candidate therapeutic for IBD that can be used to selectively promote healing of mucosal wounds and ulcers.
INCIDENCE AND RISK FACTORS FOR NEOPLASIA IN INFLAMMATORY BOWEL DISEASE
Authors: Garcia Joana Lemos , Rosa Isadora , Moleiro Joana , da Silva João Pereira , Pereira António Dias 
Published: January 2021

Abstract

Introduction and goals
Inflammatory Bowel Disease (IBD) patients may have an increased risk of neoplasia due to IBD itself or its therapy. The aim of this study was to evaluate the incidence of malignant neoplasia in IBD patients in a portuguese hospital, the associated risk factors and the therapy adjustments made.

Methods
Unicentric retrospective cohort study. All patients followed for IBD in a tertiary portuguese hospital and oncological center during 2015–2020 were included. Demographic and clinical data were registered.

Results
A total of 318 patients were included: female n=175(55.0%), age at diagnosis=37.24(±15,28)years-old, Crohn’s disease (CD) n=168(52.8%), Primary Sclerosing Cholangitis n=7, family history of cancer n=12, previous diagnosis of neoplasia n=23(7.2%), smokers n=49 (15.4%). A total of 42 cancers were diagnosed in 36 patients (11.3%) - median of 12.0(IQR=8.0–21.0) years after IBD diagnosis. Most affected organs: skin (n=15 in 11 patients; melanoma=1), colon and rectum (n=8 in 6 patients), prostate (n=4), breast (n=3) and anal canal (n=2). In those with non-melanoma skin cancer, 6 patients were under active treatment with azathioprine and 2 had stopped it for more than two years. In both univariate/multivariate analysis, the occurrence of neoplasia was associated with tobacco exposure (p=0.0.29/p=0.004), age (p&lt;0.001/p=0,003) and IBD duration (p=0.001/p=0.017). There was no association with IBD therapy. In 9 cases, the cancer treatment was different because of the IBD (type of surgery n=6, drugs used n=2, radiotherapy not used n=1); IBD treatment was changed in 9 patients; clinical remission was lost in 1 patient in whom azathioprine treatment was halted after cancer. In the last follow-up, 3 patients remained with active oncological disease and 5 had died, 3 of which with active cancer. In those affected by cancer, in the univariate analysis, its cure/remission was negatively associated with tobacco exposure (p=0.003) and positively with salicylates use (p=0.016) and IBD remission before cancer diagnosis (p=0.008). In the multivariate analysis, the statistical significance was lost. Overall survival was lower in smokers with or without neoplasia (p&lt;0.001) and in those who developped cancer (p=0.003).

Conclusion
In IBD patients, cancer mostly affected the skin and the lower digestive system. As in the general population, age and tobacco exposure were risk factors for the development of neoplasia. Tobacco is globally associated with lower survival rates and may be associated with a lower cure/remission rate, while salicylates and IBD remission may have a beneficial effect.
RISK OF ADVERSE OUTCOMES IN HOSPITALIZED PATIENTS WITH AUTOIMMUNE DISEASE AND COVID-19: A MATCHED COHORT STUDY FROM NEW YORK CITY
Authors: Faye Adam , Lee Kate , Laszkowska Monika , Kim Judith , Blackett John , McKenney Anna , Krigel Anna , Giles Jon , Wang Runsheng , Bernstein Elana , Green Peter , Krishnareddy Suneeta , Hur Chin , Lebwohl Benjamin 
Published: January 2021

Abstract

Objective
To examine the impact of autoimmune disease on the composite outcome of intensive care unit admission, intubation, or death, from COVID-19 in hospitalized patients.

Methods
Retrospective cohort study of 186 patients hospitalized with COVID-19 between March 1st–April 15th, 2020 at New York-Presbyterian Hospital/Columbia University Irving Medical Center. The cohort included 62 patients with autoimmune disease and 124 age- and sex- matched controls. The primary outcome was a composite of intensive care unit admission, intubation, and death, with secondary outcome assessing time to in-hospital death. Baseline demographics, comorbidities, medications, vital signs, and laboratory values were collected. Conditional logistic regression and Cox proportional hazards regression were used to assess the association between autoimmune disease and clinical outcomes.

Results
Patients with autoimmune disease were more likely to have at least one comorbidity (25.8% vs. 12.9%, p=0.03), take chronic immunosuppressive medications (66.1% vs. 4.0%, p&lt;0.01), and have had a solid organ transplant (16.1% vs. 1.6%, p&lt;0.01). There were no significant differences in intensive care unit admission (14.2% vs. 19.4%, p=0.44), intubation (14.2% vs. 17.7%, p=0.62) or death (17.5% vs. 14.5%, p=0.77). On multivariable analysis, patients with autoimmune disease were not at an increased risk for a composite outcome of intensive care unit admission, intubation, or death (adjOR 0.79, 95%CI 0.37–1.67). On Cox regression, autoimmune disease was not associated with in-hospital mortality (adjHR 0.73, 95%CI 0.33–1.63).

Conclusion
Among patients hospitalized with COVID-19, individuals with autoimmune disease did not have an increased risk of a composite outcome of intensive care unit admission, intubation, or death.

Kaplan-Meier curve examining death, stratified by the presence or absence of autoimmune disease in all 186 patients, with 16 patients censored as of 4/29/2020
RECENT APPROACHES FOR SMOKING CESSATION IN CROHN’S DISEASE: A QUALITATIVE REVIEW
Authors: Moon Jooyoung , Moon Hanna 
Published: January 2021

Abstract

Background
The clinical practice guideline for Crohn’s disease (CD) management strongly recommends the avoidance and cessation of smoking. However, no standardized smoking cessation (SC) program exists for CD patients. Results from a nationwide survey among U.S. gastroenterologists have shown that SC counseling occurs irregularly and that almost half are not comfortable discussing SC strategies with their patients. These findings suggest that systematization and improvements in approaches for SC are necessary. This study aimed to provide a comprehensive review on recent developments and recommendations in SC care for CD patients.

Methods
A systematic literature review was conducted using PubMed, Google Scholar, and Web of Science databases for articles published from years 2016 to 2020. Two researchers independently screened and reviewed data. Inclusion criteria included peer-reviewed, published scientific articles written in the English language that examined SC in CD patients. Only studies with adults (≥18 years old) and those with more than 10 subjects were included. No geographic limitations were applied. A total of 12 articles met our inclusion criteria.

Results
CD patients were found to have a significantly lower rate of SC when compared to the average population. Initial diagnosis of CD served as a strong motivator to quit, suggesting that SC education and intervention should begin on the first visit. Other significant positive predictors for SC in previous smokers included male gender, older age, and higher BMI. Adoption of a standardized program with a systematized process of questioning, documenting, and educating patients on SC resulted in an increase in discussion of SC strategies. Studies which expressed concerns regarding the deleterious effects of passive smoking on CD suggested that SC counseling be more broadly applied to include a patient’s cohabitants. For those who require more intervention, addiction medicine consultation has been shown to reduce smoking use by a substantial margin of 27%. In order to increase the success of SC, a recent trial has taken a personalized approach that involves measuring an individual’s nicotine metabolite ratio to recommend a matching medication. Results have been promising with high rates of satisfaction of 85%.

Conclusions
Gastroenterologists should provide SC counseling more often and on a more regular basis, especially for patients who receive an initial diagnosis of CD. As existing SC strategies have limitations, new approaches are being actively explored, but further studies are desperately needed. Development of standardized and personalized SC programs should be considered so that SC counseling can become a routine and integral part of care for CD patients.
TELEMEDICINE IN IBD: GOOD TRUST FROM OUTPATIENTS DURING THE COVID-19 PANDEMIC IN MILAN (LOMBARDY)
Authors: Costantino Andrea , Noviello Daniele , Mazza Stefano , Berté Roberto , Vecchi Maurizio , Caprioli Flavio 
Published: January 2021

Abstract

Background and Aim
During the recent COVID-19 pandemic, telemedicine has enabled many IBD patients worldwide to get access to remote assistance. Some positive reports on the use of telemedicine among patients and healthcare providers have been published1-4, but a patient’s trust perspective is not available yet.
The aim of our study was to verify IBD patients’ trust in telemedicine. This study was approved by our local Ethics Committee.

Material and Methods
At our Gastroenterology Unit in Milan (Italy), 123 video-consultations were delivered to IBD patients with mild or moderate disease, in place of follow-up visits scheduled but not provided during the general lockdown (March-April 2020).
Video-calling solutions from Google (Hangouts or Meet) or Microsoft Teams were used according to the patient’s preference.
The patients’ trust in telemedicine was assessed through an adapted version of the PAtient Trust Assessment Tool (PATAT) questionnaire.5
The primary endpoint was expressed as a &gt;75% percentage of patients giving a score of at least 4 out of 5 in a Likert Scale for three selected key statements: “I can trust video-consultation”, “I can trust that possible problems with the telemedicine service will be solved properly” and “I feel at ease when working with this website”.
The questionnaire was formulated through the EUSurvey platform, widely used for clinical research questionnaires in Europe.

Results
One-hundred-fifteen (93.4%) video-consultations were performed out of the 123 scheduled. Among the 115 consultations, 100 questionnaires were completed (86.9%). The primary endpoint of trust in the telemedicine service was achieved in 95%, 90% and 84% of patients for the three selected key statements about the trust in the telemedicine service, its capability to solve clinical problems and its ease to use.
While clinical outcomes were beyond our intentions, we reported no drugs withdrawal in this cohort nor major events.

Conclusion
Our results showed that during the COVID-19 pandemic most of our IBD patients accepted to receive a video-consultation in spite of the traditional in-person visit and trusted the video-consultation.
References:
1. Bezzio C. et al. Gut 2020;69:1213–1217
2. George L.A., Raymond K. Current Gastroenterology Reports (2020) 22: 12
3. Lees C. W. et al. Gastroenterology 2020; 2020 May 28
4. Allocca M et al. Clin Gastroenterol Hepatol 2020;18:1882–1883
5. Velsen, L. V. et al, H. Int. J. Med. Inform 2017;97:52–58.
ANALYSIS OF ONLINE INFORMATION ON SUPPORT GROUP MEETINGS FOR CROHN’S DISEASE PATIENTS
Authors: Moon Jooyoung , Moon Hanna 
Published: January 2021

Abstract

Background
In 2018, the American College of Gastroenterology published guidelines for Crohn’s disease management that emphasized the importance of addressing the patient’s quality of life (QOL). Due to the unique challenges that they face, afflicted patients and their families benefit from support groups that provide psychosocial support. Hospitals have traditionally preferred in-person support group meetings, but there has recently been a great increase in the need for online meetings amidst the COVID-19 pandemic. With increasing usage of the Internet for health advice and assistance, it is important to assess the availability of information on support groups online.

Methods
Two independent investigators queried the terms “Crohn’s support group” using the Google search engine. The first 100 websites were analyzed and categorized into either informational websites (IW) or professional websites (PW) depending on their association. The mode of support group meetings was categorized as either online or in-person. Websites that included outdated events, were inaccessible, did not specify the mode of meeting, required additional contact, or were irrelevant were excluded. Statistical analyses were performed using the chi-squared test of independence with significance level at p&lt;0.05.

Results
A total of 56 websites (33 IW, 23 PW) met our inclusion criteria. IW offered online meetings more often than PW (60.6% and 39.1%, respectively; p=0.11). In contrast, PW offered in-person meetings more often than IW (73.9% and 69.7%, respectively; p=0.73). Excluded websites (30 IW, 14 PW) were further analyzed for their reason for elimination. For IW, the most frequent causes of exclusion in descending order were as follows: irrelevance (30.0%), outdated (26.7%), inaccessible (20.0%), did not specify the mode of meeting (13.3%), and redirected for further information (10.0%). Listing of outdated sessions was the most common reason for exclusion of PW from the study (57.1%), and the proportion was significantly higher than IW (26.7%) (p=0.01).

Conclusion
Crohn’s disease patients face unique challenges that require special attention. Support groups are an important means of alleviating stress, depression, and anxiety in order to improve their QOL. Yet, due to the COVID-19 social distancing policies, many are refrained from participating in in-person sessions. This study illustrates that more online support group meetings are needed and that professional websites should improve on making regular updates for future meeting sessions.
PATIENTS’ JOURNEY THROUGH INFLAMMATORY BOWEL DISEASE (IBD): A QUALITATIVE STUDY
Authors: Omprakash Tina Aswani , Reilly Norelle , Bhagwakar Jan , Carrell Jeanette , Woodburn Kristina , Breyer Abby , Close Frances , Wong Gabriel 
Published: January 2021

Abstract

Background
Inflammatory bowel disease (IBD) is a debilitating intestinal condition, manifesting as Crohn’s disease (CD), ulcerative colitis (UC) or indeterminate colitis (IC). The patient experience is impacted by a lack of awareness from other stakeholders despite growing global disease prevalence. To gain deeper insight of the patient experience, promote quality care, and enhance quality of life, we performed a qualitative study of the patient journey starting from pre-diagnosis through treatment.

Methods
U.S. patients with IBD were recruited via UC/CD support groups and organizations, social media platforms, blog followers, and personal networks. Participants were screened via an emailed survey and asked to self-identify as medically diagnosed on the basis of reported diagnostic testing. Interviews were conducted by qualitative researchers by phone or web conferencing. Open-ended questions were developed to support and gather information about our learning objectives—primarily, our desire to understand the unique experiences of UC/CD patients in their journey from symptom onset through diagnosis, treatment and maintenance (e.g. “Upon diagnosis, what were your immediate thoughts about the condition?”). This qualitative data were analyzed using Human-Centered Design methodology, including patient typologies (personas), forced temporal zoom (journey maps), forced semantic zoom (stakeholder system mapping), and affinity mapping for pattern recognition of unmet needs.

Results
A total of 32 patients were interviewed: N=17 CD patients, N=13 UC patients and N=2 IC patients. The interviewed population reflected regional, demographic, and disease-related diversity (Table 1). Five unique, mutually exclusive journeys were identified to understand and classify patient experiences: (1) Journey of Independence, (2) Journey of Acceptance, (3) Journey of Recognition, (4) Journey of Passion and (5) Journey of Determination (Figure 1). Patients with IBD expressed a need for increased awareness, education, and training for providers to shorten the path to diagnosis. Mental health support was found to be a critical gap in care, particularly for major treatment decisions (e.g., surgery). The inclusion of emotional support into the treatment paradigm was perceived as essential to long-term wellness. Patient attitudes and self-advocacy varied on their individual journeys; understanding these journeys may accelerate time to diagnosis and treatment.

Conclusion
Better understanding of patient journeys can help healthcare providers improve their approach to patient care and coordination.