bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACONITATE DECARBOXYLASE 1 IS A KEY REGULATOR OF COLITIS
Authors: McNamara Kara , Latour Yvonne , Smith Thaddeus , Barry Daniel , Allaman Margaret , Delgado Alberto , Piazuelo M Blanca , Washington Mary , Zhao Shilin , Coburn Lori , Gobert Alain , Wilson Keith 
Published: January 2023

Abstract

INTRODUCTION
Aconitate decarboxylase 1 (ACOD1; also known as IRG1) is highly expressed in activated macrophages and converts cis-aconitate to itaconate, which contributes to the antimicrobial activity of macrophages. The role of ACOD1 in intestinal inflammation remains unknown. Therefore, we investigated the role of ACOD1 during colitis induced by Citrobacter rodentium (C. rodentium), a murine bacterial pathogen used to model the pathogenesis of enteropathogenic Escherichia coli, and dextran sulfate sodium (DSS) a model of epithelial injury-mediated inflammation.

METHODS
The GEO database was utilized to examine ACOD1 mRNA levels in ulcerative colitis (UC) and Crohn’s disease (CD) patients, and normal controls. C57BL/6 wild-type (WT) and Acod1–/– mice were infected with C. rodentium for 14 days or given 4% DSS for 5 days and then normal drinking water for 5 days. Mice were weighed daily. Histology was analyzed by H&E staining on colon Swiss rolls using a 0-21 scale for C. rodentium infection and a 0-40 scale for DSS. DNA was extracted from stool to use for 16S microbiome analysis from 5 naïve WT and 5 Acod1–/– mice.

RESULTS
ACOD1 expression is increased in the colon of UC and CD patients compared to normal controls (GEO GSE16879). Further ACOD1 is significantly increased in active UC compared to inactive (P=0.0256) (GEO GSE75214). C. rodentium-infected Acod1–/– mice lost significantly more body weight compared to infected WT mice (P&lt;0.0001). There was a significant increase in histologic injury score in the infected Acod1–/– mice (12.07 ± 0.93; n=19) compared to infected WT mice (7.65 ± 1.04; n=20; P=0.0087). In the DSS model, we observed a significant decrease in body weight (P=0.0002) in Acod1–/– mice compared to controls. A significant decrease in colon length, commonly associated with colitis in mice, was observed in the DSS-treated Acod1–/– animals (6.07 ± 0.29 cm compared to 7.22 ± 0.32 cm; P=0.0164). This was accompanied by a significant increase in histologic injury score (23.89 ± 2.14) compared to treated WT mice (13.47 ± 2.03; P=0.0004), which was driven by inflammation, epithelial injury, and crypt damage. 16S microbiome analysis on naïve mice from each genotype revealed significant differences in both the phylum and genus. Acod1–/– mice had significantly more Bacteroidetes (P=0.03) and Proteobacteria (P=0.03), specifically more Alloprevotella (P=0.029) and Prevotellaceae (P=0.029).

CONCLUSION
While ACOD1 is increased in human IBD tissues, our data indicates that this enzyme has a protective role in experimental colitis. Notably, Acod1 deletion is associated with an altered microbiome. Together our findings suggest that enhancement of ACOD1 activity may represent a new therapeutic strategy for IBD.
BUTYRATE AMELIORATES PANETH CELL DEFECTS, TOTAL INFLAMMATION, AND EPITHELIAL CELL APOPTOSIS DURING MITOCHONDRIAL DYSFUNCTION DRIVEN BY PROHIBITIN 1-DEFICIENCY
Authors: Alula Kibrom , Dowdell Alexander , Lee Joseph , Colgan Sean , Theiss Arianne 
Published: January 2023

Abstract

INTRODUCTION
Prohibitin 1 (PHB1) is a mitochondrial chaperone protein important for maximal activity of the electron transport chain. PHB1 deficiency in intestinal epithelial cells (IECs) or specifically in Paneth cells (PCs) induces epithelial mitochondrial dysfunction, PC defects, gut microbiota dysbiosis, and spontaneous ileitis in mice by 20 weeks-of-age. Dysbiotic gut microbiota has been implicated in inflammatory bowel diseases and is associated with the decreased abundance of short chain fatty acids (SCFAs; acetate, propionate, and butyrate)-producing bacteria. SCFAs play a significant role in reducing intestinal inflammation and epithelial barrier dysfunction. We tested the hypothesis that luminal SCFA levels were decreased in mice with PHB1 deficiency and that supplementation of SCFAs will ameliorate intestinal inflammation during mitochondrial dysfunction driven by loss of PHB1.

METHODS
Ileal luminal contents were collected from Phb1fl/fl (control) and Phb1iΔIEC (Phb1-deficient in IECs) mice at 20 weeks of age and SCFAs were measured by gas chromatography-mass spectrometry. Phb1iΔIEC and Phb1fl/fl littermate mice were treated with 20 mM butyrate dissolved in their drinking water from 16 to 20 weeks-of-age and PC defects were measured by antimicrobial peptide expression (Lysozyme, Cryptdin 3, Cryptdin 5, and Ang4) and Lysozyme staining allocation into secretory granules. Ileitis was measured by histological scoring and pro-inflammatory cytokine expression. To test epithelial intrinsic responses, ileal crypt enteroids derived from Phb1iΔIEC and Phb1fl/fl littermate mice were treated with 200 µg/ml healthy ileal stool lysates (from Phb1fl/fl mice) or dysbiotic stool lysates (from Phb1iΔIEC mice) for 16 hours with or without 0.05 mM butyrate, 0.5 mM propionate, 0.5 mM acetate, alone or in combination. Enteroid viability and apoptosis were measured by morphological change and cleaved Caspase 3 expression.

RESULTS
Butyrate was significantly decreased in ileal stool of Phb1iΔIEC mice. Butyrate supplementation in Phb1iΔIEC mice protected against ileitis and PC defects. Dysbiotic stool lysate decreased viability and increased apoptosis in Phb1-deficient enteroids that were prevented by butyrate supplementation.

CONCLUSION
Mitochondrial health in IECs cells is crucial for healthy gut microbiota composition and for epithelial defense when the microbiome becomes dysbiotic. Butyrate rescues IECs from insults caused by dysbiotic gut microbiota during mitochondrial dysfunction driven by PHB1 deletion.
COMMENSAL GUT BACTERIA REGULATE HIF ACTIVITY TO PROMOTE INTESTINAL HOMEOSTASIS
Authors: Dowdell Alexander , Mahjoob Omemh , Colgan Sean 
Published: January 2023

Abstract
Inflammatory bowel disease (IBD) is a disorder marked by chronic, relapsing inflammation of the gastrointestinal tract. Although the precise etiology of IBD is unclear, pathogenic immune response to the gut microbiota is considered a contributing factor. The importance of the gut microbiota in the development of intestinal inflammation has been previously shown through associative studies that correlate dysbiosis of the gut microbiota with active IBD, particularly through the loss of fiber-fermenting obligate anaerobes, an increased presence of pathobionts, and an overall decrease in microbial species diversity. Although the gut microbiota clearly plays an essential role in the development and progression of IBD, the mechanisms by which these micro-organisms regulate gut homeostasis remain to be fully elucidated.
Previously, we found that Salmonella Typhimurium (STm), a model invasive pathogen, activated hypoxia inducible factor-1α (HIF-1α) in intestinal epithelial cells (IECs) to regulate anti-bacterial autophagy. HIF-1α is a member of a transcription factor family that senses and responds to environmental stressors, in particular low oxygen tensions. Such stressors stabilize HIF-1α in the cytoplasm and prevent its usual oxygen-dependent degradation. Of note, HIF-1α has been previously shown to be essential for intestinal homeostasis in animal models of IBD, and stabilization of HIF has been demonstrated to be protective during various models of colitis in mice.
As an extension of these studies, we asked whether bacterial stabilization of HIF was unique to STm in the intestinal epithelium. We found that stabilization of HIF in IECs was not restricted to STm but was, surprisingly, recapitulated by a wide variety of bacteria, including bacteria rendered non-invasive by genetic manipulation and nonpathogenic/commensal enteric bacterial isolates. Further, we observed that stabilization of HIF was dependent on live bacteria and not due to a secreted factor, suggesting an innate HIF response by the intestinal epithelium to enteric bacteria. Finally, we found modulation of HIF signaling by enteric bacteria including regulation of numerous genes previously implicated in gut homeostasis. These results, taken together, suggest that commensal bacteria regulate intestinal homeostasis through activation of the transcription factor HIF.
THE PRECIOUS STUDY: A PROSPECTIVE, OBSERVATIONAL STUDY OF CD8+ BIOMARKER BASED PROGNOSTIC TEST IN NORTH AMERICAN IBD PATIENTS
Authors: Chen Lea Ann , Sultan Keith , Weidner Melissa , Lukin Dana , Axelrad Jordan , Saubermann Lawrence , Deepak Parakkal , Oneto Caterina , Yu Huimin , Damas Oriana , Sauk Jenny , Oliva-Hemker Maria , Sheibani Sarah , Hills Karen , Ardolli Lediona , Lee James 
Published: January 2023

Abstract

BACKGROUND
The clinical course of IBD varies considerably among patients1. One barrier to personalized medicine in IBD is the lack of a reliable prognostic assay that can be used at diagnosis to guide effective therapy for each patient, to optimize clinical outcomes and minimize complications. To address this need, a whole-blood qPCR-based prognostic assay was developed to divide IBD patients into two subgroups2. This transcriptional signature yields CD8 T-cell exhaustion level data that correlated with disease outcomes among IBD patients in UK2. Here, we aimed to determine if this prognostic assay could stratify an ethnically diverse North American cohort of IBD patients at diagnosis into low and high-risk subgroups.

METHODS
PRECIOUS (Predicting Crohn’s & Colitis Outcomes in the United States) is a multi-centre, observational, double-blinded study of patients with active IBD, who are not receiving systemic steroids, immunomodulator, advanced small molecules or biologics. The study is recruiting up to 200 patients between 16-80 years of age, from 14 centres across the US and Canada. Patients are prospectively followed for &gt;12 months after enrolment to monitor disease course, including the requirement for IBD-related surgery or treatment escalations. Patients and clinicians are blinded to the biomarker results and patients are treated according to local practice.

RESULTS
Of 120 patients recruited to date, 86 have reached the 12-month follow-up timepoint (Table 1). Of the 102 patients with complete race and ethnicity data (Table 1), 63.5% are non-Hispanic Whites, 13.7% identified as Hispanic/Latino, 11.8% Asian and 9.8% Black/African American. Biomarker results were obtained for 80 (88.8%) of the 90 samples tested to date – 10 (11.1%) of samples failed quality control. Of these 80 results, 38 patients (47.5%) were identified as high risk for disease progression and 42 (52.5%) as low risk – a similar breakdown to that seen in the UK cohort2.

DISCUSSION
This is the first trial of a prognostic biomarker for patients with CD and UC in North America. This patient population was significantly more diverse than the UK cohort which had ~98% White. This diversity is not generally reflected in clinical trials performed in the United States in which approximately 90% of participants for all conditions are White whereas non-Hispanic Whites represent approximately 60% of the U.S. population. 4,5. Our enrolment of only 63.5% non-Hispanic White subjects speaks to our targeted efforts to recruit a representative level of diversity into our study population to that represents the diversity of patients with IBD that are being diagnosed globally6.
NON-MEDICAL SWITCHING FROM INFLIXIMAB TO A BIOSIMILAR IN ADOLESCENTS AND YOUNG ADULTS WITH INFLAMMATORY BOWEL DISEASE
Authors: McNicol Megan , Abdel-Rasoul Mahmoud , Morris Grant , Boyle Brendan , Dotson Jennifer , Michel Hilary , Maltz Ross 
Published: January 2023

Abstract

BACKGROUND
Studies in adults with inflammatory bowel disease (IBD) have demonstrated that a one-time switch from the originator to a biosimilar has not resulted in loss of response, increased side effects, or antibody development. Data describing non-medical switching is limited in adolescents and young adults. The objective of this study was to evaluate clinical outcomes of one-time switches from the originator to a biosimilar in adolescents and young adults with IBD.

METHODS
Patients with IBD that underwent a non-medical switch from infliximab originator to a biosimilar were retrospectively reviewed. Demographic data, physician global assessments (PGA), and laboratory values (albumin, hemoglobin, sedimentation rate (ESR), c-reactive protein (CRP), anti-TNF level, and anti-TNF antibody level) were recorded up to one year prior to the switch and up to one year after the switch. Rates of continuation on the biosimilar was reported at 6 and 12 months post-switch. Linear mixed effect models with random intercepts accounting for within patient correlation were used to compare continuous lab values before and after switching.

RESULTS
A total of 53 patients completed a switch from infliximab originator to a biosimilar. The mean age at the time of the switch was 18 (+/- 2.86) years old. Fifty-three percent of those undergoing a switch were female, 74% had Crohn’s disease, and 96% were switched to the biosimilar infliximab-dyyb. At the time of the switch, 52 (98%) patients had quiescent disease activity based on PGA and 1 (2%) patient had mild disease. At follow up after receiving at least 2 biosimilar infusions, 51 (96%) patients had quiescent disease and 2 (4%) patients had mild disease based on the PGA. At 6 months post switch, 48 (90%) patients were still on the biosimilar. Three (6%) patients switched back to the originator due to worsening symptoms, one (2%) patient developed worsening psoriasis, and one (2%) patient had ongoing issues with IV access. Of the 33 patients who had a full 12 months of follow-up data, 91% (30/33) remained on the biosimilar, one patient switched back to the originator due to worsening symptoms, and two switched to adalimumab due to the development of psoriasis and an underlying social situation, respectively.
There was no statistically significant difference in albumin, hemoglobin, ESR, CRP, or anti-TNF levels when comparing pre- and post- switch values. The mean anti-TNF level prior to the switch was 17.3 ug/ml (95% CI: 13.7 -19.0) and 15.1 ug/ml (95% CI: 12.5 - 17.8) after the switch. No patients developed anti-drug antibodies or infusion reactions.

CONCLUSION
A one-time non-medical switch to an infliximab biosimilar in an adolescent and young adult cohort had no significant effect on clinical remission rates, laboratory markers of inflammation, serious adverse events, anti-TNF levels, or anti-drug antibodies.
IMPACT OF NON ST- ELEVATION MYOCARDIAL INFARCTION (NSTEMI) ON PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Suga Herman , Chhoun Christopher , Patel Rahul , Blair Brian , Dasu Neethi , Khalid Yaser , Joo Lucy 
Published: January 2023

Abstract

INTRODUCTION
Inflammatory Bowel disease is a long-term illness which can lead to numerous hospital admissions and accounts for a large amount of health care costs. IBD is a pro-inflammatory state and these patients have known elevated inflammatory markers and thus there is a known association between IBD and cardiovascular disease. The aim of this study was to evaluate the economic burden and hospital outcomes associated with IBD in patients with concomintant NSTEMI.

METHODS
Patients aged 18 years with IBD and NSTEMI versus IBD alone were identified from the US Nationwide Inpatient Sample (NIS), from the years 2015-2019. ICD 10 codes were utilized Multivariate regression analysis was used to estimate the odds ratios of in-hospital mortality, average length of hospital stay, and hospital charges, after adjusting for age, gender, race, primary insurance payer status, hospital type and size (number of beds), hospital region, hospital teaching status, and other demographic characteristics. Weighted analysis utilizing Stata 17 MP was performed.

RESULTS
This study identified approximately 447,300.04 patients with either UC or Crohn’s disease (IBD) from the years 2015 to 2019. Of these patients, 89,460 had a concomitant diagnosis of an NSTEMI. Mean age of patients was 56.61 years. The analysis revealed that mortality (OR 2.16, p= 0.003, CI: 1.29- 3.66), length of stay (LOS) (+2.25, p= 0.002, CI: 0.82- 3.67), and total hospital charges (THC) were all increased ($42,710.89 , p=0.000, CI: $21,379.01-$ 64,042.77) for patients with IBD and NSTEMI compared to patients with only IBD. Independent positive predictors of mortality, LOS, and increased total hospital charges were sepsis, AKI, malnutrition, and an aspiration event.

CONCLUSIONS
Our study revealed that patients with IBD and NSTEMI had higher mortality, hospital LOS, and total hospital charges compared to patients with only IBD. Common and overlapping inflammatory pathways contribute to that both IBD and NSTEMI which likely increases the risk for complications and mortality for these patients and demonstrated by our study. A mutli-discplinary approach should be utilized on treating patients with IBD and NSTEMI due to the significant morbidity and mortality. Further studies are needed to further evaluate the impact of NSTEMI on IBD.
TREATMENT PREFERENCES IN CROHN’S DISEASE PERIANAL FISTULA: PERSPECTIVES OF HEALTHCARE PROFESSIONALS
Authors: Jiang Jeanne , Cazzetta Susan , Chen Lily , Athavale Amod , Edelblut Josiah , Fan Tao , Hadker Nandini , Nazarey Pradeep 
Published: January 2023

Abstract

INTRODUCTION
Crohn’s perianal fistulas (CPFs) are a common complication of Crohn’s disease and treated with both medical and surgical interventions. This study aimed to characterize the experience and satisfaction of healthcare professionals (HCPs) with current CPF treatments and assess HCP preferences for future CPF treatment attributes.

METHODS
A US observational study recruited gastroenterologists (GEs) and surgeons who managed at least three patients with CPF in the past 12 months and spent ≥ 70% of their professional time treating patients. Using a web-enabled questionnaire, HCP satisfaction with CPF treatments and attitudes towards CPF care were rated using a 1–9 scale (1 = not at all satisfied/strongly disagree, 9 = extremely satisfied/strongly agree). A discrete choice experiment (DCE) evaluated HCP preferences for future treatment attributes. Data were analyzed using descriptive statistics and hierarchical Bayesian modeling for DCE.

RESULTS
In total, 137 HCPs were recruited (GEs, n = 77; surgeons, n = 60) with a mean (standard deviation [SD]) of 15.6 (7.8) years in active clinical practice. The mean (SD) number of patients with CPF per HCP was 29.4 (16.7), and 41% of patients had moderate disease severity.
Overall, HCPs reported moderate satisfaction with current CPF treatment (medication or surgical) attributes (Table). HCP satisfaction scores for each CPF medication and surgical procedure were low to moderate (mean range [SD]: 3.4 [2.1]–6.7 [1.5]; 4.2 [2.2]–5.7 [1.6], respectively) with biologics rated highest for medications (4.7 [2.2]–6.7 [1.5]), and short- or long-term seton placement highest for surgical procedures (mean [SD]: 5.7 [1.6] and 5.5 [1.7], respectively).

HCP attitudes towards current CPF interventions (mean score [SD]) revealed a need for better treatments (7.4 [1.5]), a concern for CPF recurrence despite treatment (7.2 [1.4]), that current treatments may not reduce risk of fecal incontinence (FI) (6.8 [1.4]), and that setons are a good short- but not long-term solution for CPF (6.5 [1.8]).
Achieving fistula closure was the most important treatment goal for HCPs (57%), with improvement in quality of life (mean score [SD]: 7.7 [1.3]), low chance of symptom recurrence (7.5 [1.4]), minimal risk of FI (7.5 [1.4]) and sustained efficacy post treatment (7.5 [1.5]) the main attributes influencing treatment decisions.
The DCE identified symptom control and/or fistula closure and low FI rates as the most important future CPF treatment attributes (Figure).

CONCLUSIONS
HCPs were unsatisfied with current CPF treatments, highlighting a need for better treatments. From an HCP’s perspective, future CPF therapies should control symptoms, promote fistula closure, and low rates of FI.
EXPLORING RELATEDNESS AS SOUGHT BY ADOLESCENTS AND YOUNG ADULTS IN AN ONLINE INSTAGRAM INFLAMMATORY BOWEL DISEASE SUPPORT COMMUNITY
Authors: Malloy Caeli , Mravec Michelle , Miller Wendy 
Published: January 2023

Abstract

INTRODUCTION
Individuals with chronic conditions have flocked to social media as a source of information, connection, and support. Online social groups are particularly salient for individuals with isolating or stigmatized conditions such as inflammatory bowel disease (IBD). IBD self-management is complex, ongoing, and highly individualized. Adolescents and young adults (AYAs) often struggle with IBD self-management, resulting in increased risk for poor health outcomes. AYAs with IBD are active on social media sites, but little is known about the possible drivers of motivation for AYAs to engage in online support communities.
Self-Determination Theory proposes that behavior is intrinsically motivated by an individual’s need for autonomy, competence, and relatedness. Relatedness has been defined as a sense of group belonging and has been theorized as a key component of behavior change. However, little is known about the way in which online communities may fulfill the need for relatedness for people with chronic conditions. In this study, we aim to explore the way AYAs with IBD find relatedness in an Instagram IBD support community.

METHODS
We extracted public Instagram posts published between January and December 2019 in a popular IBD support group. In this group, Instagram users sent questions about IBD to the group account owner via direct message. The owner screenshotted user messages and posted these anonymous screenshots to the group, allowing other users to leave comments. We extracted posts about IBD self-management from users who indicated that they had IBD and that they were 13-24 years old or in middle school, high school, or college. Eighty-three posts were included. Then, we screenshotted and transcribed comments under each post, resulting in 1,110 unique comments. Using thematic analysis, three investigators have begun familiarizing themselves with the data, independently coding comments, and identifying emerging themes. Themes will continue to be refined through an iterative process.

RESULTS
From preliminary analysis, five themes have emerged: Validation, Autonomy Support, Well Wishes, Shared Identity, and Connection Within and Beyond Illness. Instagram users connected with AYAs with IBD in a variety of ways by validating their concerns, supporting their autonomy in making self-management decisions, providing online human connection, and uplifting them in their illness journeys.

CONCLUSION
Relatedness is a critical component of behavioral interventions, but is poorly understood in reference to self-management support in AYAs with IBD. As AYAs seek relatedness online, it is crucial to understand this population’s needs for relatedness in developing future interventions that are effective, sustainable, and tailored to the self-management needs of AYAs with IBD.