bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADIOLOGIST PERFORMANCE AND RELIABILITY OF MR SCORING SYSTEMS IN PERIANAL FISTULIZING CROHN’S DISEASE: RETROSPECTIVE ANALYSIS IN A REAL-WORLD CLINICAL PRACTICE
Authors: Devi Jalpa , Abushamma Suha , Arora Jyoti , Deepak Parakkal , Ballard David H , Ravella Balakrishna , George Alvin , Hickman John , Zulfiqar Maria , Ludwig Daniel R , Shetty Anup , Ganapathy Aravinda , Miller Philip , Elumalai Anusha , Bishop Grace 
Published: January 2024

Abstract

BACKGROUND
Perianal fistulizing Crohn’s disease (CD-PAF) is difficult to treat, and several MR scoring systems have been developed to assess treatment response.

OBJECTIVE
To assess the relationship between CD-PAF MR scoring systems and radiologists’ subjective assessment of CD-PAF severity and treatment response on baseline and follow-up pelvic MR.

METHODS
Retrospective single-institution study of consecutive symptomatic CD-PAF patients who underwent pelvic MR before and ≥3 months after initiating biologic therapy during a 10-year period (December 2011 to December 2021). One of four radiologists interpreted baseline and follow-up MRs. Scoring systems included variables in the modified Van Assche index (mVAI), magnetic resonance novel index for fistula imaging in CD (MAGNIFI-CD), and pediatric MR-based perianal Crohn’s disease (PEMPAC) index. For initial and follow-up MR, a 5-point Likert scale assessed severity (1=mild, 3=moderate, 5=marked). On follow-up MR, radiologists evaluated fistula response as 1-improved, 3-stable, or 5-worsened CD-PAF severity. All four study radiologists scored the baseline MR in 20 patients to calculate inter-reader agreement statistics. Interrater reliability was assessed with the Krippendorff α coefficient for categorical variables and intraclass correlation coefficient (ICC) for continuous variables.

RESULTS
The cohort included 96 CD-PAF patients (50 men; mean age=33.0 years) with 192 baseline and follow-up MRs. Agreement between radiologists was moderate to substantial for the MAGNIFI-CD, mVAI, PEMPAC, and Likert scores, with ICC values of 0.716, 0.756, 0.535, and 0.679, respectively. Individual components of MR scoring systems had fair to substantial agreement (Alpha: 0.195 to 0.730). Significant univariate associations were found between MR scoring systems and radiologists’ Likert severity assessments (p&lt;.001, Pearson correlation coefficients ≥.820). In patients meeting criteria for change in disease severity (n=17), all scoring systems demonstrated AUC values ≥.93.

CONCLUSION
The MR scoring systems for CD-PAF (MAGNIFI-CD, mVAI, and PEMPAC) demonstrated strong associations with radiologists’ subjective assessments of severity and treatment response on baseline and follow-up pelvic MR. These scoring systems demonstrated better inter-reader agreement compared to individual MR factors.

CLINICAL IMPACT
The introduction of new medical therapies for CD-PAF and the growing utilization of MR fistula response in CD-PAF highlight the importance of a standardized approach in defining changes in CD-PAF severity on MR.

Table 1 Inter-reader reliability perianal Crohn’s disease MR scoring systems and length of fistula tract
MORTALITY IN INFLAMMATORY BOWEL DISEASE: A LONGITUDINAL POPULATION-BASED STUDY IN THE UNITED STATES
Authors: Maas Laura , Weber Andrew , Sauk Jenny , Parian Alyssa , Limketkai Berkeley 
Published: January 2024

Abstract

INTRODUCTION
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract. Data are limited regarding how longevity in IBD compares to the general population. The aim of this study was to compare the mean age of death and causes of mortality between patients with IBD and the general population in a nationally representative cohort.

METHODS
A retrospective study using 2010-2019 data from the National Readmissions Database (NRD) was performed. We identified hospitalized patients with CD and UC using International Classification of Diseases (ICD) codes. We compared the mean age of death and most common causes of mortality in CD, UC, and non-IBD patients.

RESULTS
The mean age of in-hospital death was significantly lower in the CD group (64.60 years) compared to the UC and non-IBD groups (67.43 and 67.07 years, respectively, p&lt;0.01). Among all age groups, the highest death rates were among those ages 71 through 80 years of age (p&lt;0.01). The UC group had significantly higher rates of death associated with cardiovascular causes, including myocardial infarction, congestive heart failure and cardiovascular disease, and infectious causes, including Clostridioides difficile infection and sepsis. Death rates did not significantly differ among the groups for those with diagnoses of leukemia and lymphoma (p=0.20 and p=0.19, respectively). UC patients had the highest in-hospital rate of death per year from 2010-2019, followed by the CD and non-IBD groups. Common diagnoses associated with death across all ages in the CD, UC, and non-IBD groups included fluid/electrolyte imbalance, respiratory failure, anoxic brain injury, sepsis, and renal failure.

CONCLUSION
While those with UC had higher in-hospital death dates, those with CD were more likely to die younger compared to the general population. UC patients were more likely to die if diagnosed with cardiovascular disorders or infections. Investigation of factors that drive premature mortality in CD patients and higher rates of mortality in UC patients is crucial to guide practice improvements and for management of co-morbid conditions.

Table 1 Patient demographics and hospital characteristics.

Figure 1 Death rates comparing non-IBD, CD and UC groups with specific inpatient diagnoses. * p &lt; 0.05.
RISING INCIDENCE, MORTALITY, AND DISABILITY-ADJUSTED LIFE YEARS OF INFLAMMATORY BOWEL DISEASE IN THE UNITED STATES: A SYSTEMIC ANALYSIS OF THE GLOBAL BURDEN OF DISEASE STUDY
Authors: Pan Chun-Wei , Attar Bashar , Nieto-Dominguez Alejandro 
Published: January 2024

Abstract
INTRODUCTION: In North America, Inflammatory Bowel Disease (IBD) poses a significant burden, yet detailed data on its incidence, mortality, and disability-adjusted life years (DALYs) within the United States is scarce. Our study aims to systematically analyze these aspects of IBD while considering gender, age, and state-level variations. Methods: Utilizing the Global Burden of Disease database, we systematically analyzed IBD incidence, mortality, and DALYs in the United States from 1999 to 2019. We further stratified these metrics by gender and age groups (25-49 years, 50-75 years, and 75+ years) and calculated annual percentage changes (APC) using linear regression. Results: Between 1999 and 2019, IBD incidence cases increased from 65,555 to 85,388. The incidence rate per 100,000 person-years rose from 23.5 (95% UI: 21.4-26.2) to 26.0 (95% UI: 23.8-28.9), with APC of 1.0. Females consistently had higher incidence rates, increasing from 34,236 (95% UI: 31,052-38,351) in 1999 to 43,882 (95% UI: 39,953-48,871) in 2019. Incidence rates also rose, with males at 0.6% APC and females at 0.4%. In 2019, the 24-49 years age group had the highest incidence rate at 35.1 (95% UI: 30.3-40.1) per 100,000, with a 0.5% APC increase from 1999 to 2019.Mortality increased, with 5,910 IBD-related deaths in 2019. The mortality rate per 100,000 population rose from 1.1 (95% UI: 1.0-1.3) to 1.8 (95% UI: 1.4-2.0), reflecting a 2.4% APC. Although females had a higher mortality rate in 2019 (2.2 per 100,000), males had a 2.7% APC increase from 1999 to 2019. Geographically, notable differences in APC for incidence rates across states were observed. The highest increases were seen in Ohio (1.06%), North Dakota (1.04%), and Maine (0.96%), while Nevada had a slight decrease in APC (-0.02%). Mortality rate changes also varied by state, with substantial increases in Alaska (3.75%), Vermont (3.19%), and Tennessee (3.13%). Regarding DALYs, significant APC rate changes were observed in New Mexico (1.53%), Vermont (1.38%), and Mississippi (1.37%), while the lowest changes were seen in the District of Columbia (0.24%). Conclusions: This comprehensive analysis of IBD in the US from 1999 to 2019 reveals trends and disparities. IBD incidence steadily increased during this period, with notable rises in cases and rates. Gender-wise, females had higher incidence rates, while males displayed a slightly steeper increase. Geographic disparities were evident, with varying trends in incidence and mortality rates across states. Ohio, North Dakota, and Maine had the highest incidence increases, while Alaska, Vermont, and Tennessee saw significant mortality rate increases. Our study highlights the changing epidemiology of IBD and the need for targeted intervention to address changes in incidence and disease burden.

Fig 1. * Denotes P
THE IMPORTANCE OF PATIENT ENGAGEMENT IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASE (IBD)
Authors: Kosinski Lawrence , Singh Sachin , Shahab Omer , Henderson Richard , Athmer Leslie 
Published: January 2024

Abstract

BACKGROUND
IBD constitutes a diverse and progressive spectrum of chronic illnesses, presenting formidable management challenges for both patients and healthcare providers. Due to the inherent unpredictability of disease progression, proactive monitoring strategies are crucial for optimal IBD management.
The linchpin of proactive monitoring in IBD is patient engagement, which is necessary for continuous monitoring of disease activity. GI practices using SonarMD, a technology-driven care coordination company specializing in IBD, have consistently maintained an enrollment and engagement rate exceeding 80%. This study demonstrates the disparity in clinical outcomes between an engaged patient population utilizing SonarMD’s platform and an unengaged cohort within a single large gastrointestinal (GI) practice under a value-based agreement with a major health plan.

METHODS
The study cohort was composed of a population of 1173 patients attributed by the heallth plan on the basis of ICD-10 Codes who had a diagnosis of Crohn's Disease (K50) or ulcerative colitis (K51). 939 (80%) enrolled in the program and 234 (20%) remaining unenrolled. Demographic and clinical characteristics of the patient groups are detailed in Table 1. The enrolled and unenrolled groups exhibited similar metrics with regard to: age, gender, average risk score (AVG), disease type, stricturing/fistulizing disease, and history of behavioral health diagnoses. The enrolled group did demonstrate a 10% higher utilization of biologics. The SonarMD platform was only deployed into the enrolled group.
Claims data (including pharma claims) from a single health plan, which insured all cohort patients, was the source for the utilization data analysis. The study period was the calendar year 2022 with a claim runoff period of 3 additional months.

RESULTS
The IBD specific Inpatient hospitalization rate and ED Visit rate for each group is shown in table 2. There is a 10X statistically significant difference in both hospital inpatient admission rate and ED visit rate between the engaged and unengaged populations. (p = 0.02). Two thirds of the INPT/ED admissions for the entire attributed population were driven by the unenrolled group.

CONCLUSIONS
This study highlights the influential role of proactive patient engagement in the management of IBD, exemplified by the utilization difference for inpatient care and ED usage and its potential to optimize clinical outcomes. Proactive patient engagement is critical in population management of symptomatic chronic disease. An unengaged population represents a significant risk for unnecessary morbidity and healthcare cost. Provider-payer-industry partnerships can help build the infrastructure necessary to accomplish high rates of engagement. You can’t manage the patient you don’t engage.
UNRAVELING THE CONNECTION: RACIAL INFLUENCE ON THE DEVELOPMENT OF ULCERATIVE COLITIS AFTER BARIATRIC SURGERY
Authors: Mohan Raj Mohan Ram , Joy Melvin , Magam Sai Greeshma , Magam Sai Reshma , Natt Dilman , Desai Jiten , Mustacchia Paul 
Published: January 2024

Abstract

INTRODUCTION
Bariatric surgery is an effective treatment for obesity and aids in enhancing metabolic health. However, it has been observed that there's a heightened occurrence of Ulcerative Colitis (UC), especially following Roux-en-Y gastric bypass surgery. This study aims to ascertain whether racial differences influence the risk of developing Ulcerative Colitis in patients who have undergone bariatric surgery. Illuminating this relationship is key to improving patient outcomes and refining care following surgery.

METHODS
Our retrospective analysis reviewed patients who underwent bariatric surgery at our facility between 2009 and 2022. We collected data concerning comorbidities, insurance statuses, types of surgical procedures, colonoscopy, pathology reports, and baseline characteristics, employing ICD and CPT codes. We monitored patients who manifested Ulcerative colitis (UC) after surgery until 2023, categorizing them by gender, race, and the time elapsed. To balance baseline characteristics, we used propensity score matching. Patients with a history of UC before surgery were omitted from the study. We utilized Kaplan-Meier survival analysis and Cox proportional hazards models to determine the timing of UC onset across different racial groups. We applied odds ratios to discern independent factors impacting the study's outcomes.

RESULTS
Between 2009 and 2022, our facility performed 960 bariatric surgeries. Of these procedures, 24 patients (or 0.02%) were diagnosed with UC, typically identified around 80±14.2 months post-surgery. The mean age of the participants was approximately 46±11.8 years, and females constituted 54.2% of the cohort. When examining racial breakdowns, 38.39% were African Americans, 24.4% were whites, 21% were Asians, and 16.21% were Hispanics. Notably, Hispanic patients manifested UC within a considerably shorter duration than other racial groups (Breslow: 11.836, p=0.022). Additionally, a heightened risk of UC was observed among individuals from the lowest income bracket (OR: 3.15, P=0.041), emphasizing the influence of socioeconomic status on health outcomes.

DISCUSSION
This research contributes to bridging the knowledge deficit regarding the influence of race on the occurrence of UC following bariatric surgery. Our retrospective examination of 960 surgeries from 2009 to 2022 indicated a 0.02% incidence of UC, usually identified approximately 45 months after surgery. Importantly, Hispanic patients experienced the onset of UC in a notably shorter period compared to other racial groups, with those in lower income brackets encountering elevated risk levels. Continued studies in this domain can facilitate the development of interventions to diminish these risks, thereby improving health outcomes for a broad spectrum of patient demographics.
PROTEOLYSIS TARGETING CHIMERAS (PROTACS) AS ATTRACTIVE THERAPEUTICS IN IBD THROUGH THE REGULATION OF HYPOXIA-INDUCIBLE FACTORS
Authors: Ornelas Alfredo , Countess Jacob , Welch Nichole , Cartwright Ian , Colgan Sean 
Published: January 2024

Abstract
Inflammatory bowel disease (IBD) represents a group of chronic mucosal inflammatory disorders, including Crohn’s disease (CD) and ulcerative colitis (UC). Many IBD patients have limited therapeutic options. Accumulating literature has implicated a prominent role for O2 metabolism and hypoxia in innate immunity of healthy intestinal tissue (“physiologic hypoxia”) and shifts associated with active inflammation (“inflammatory hypoxia”). Reduction of oxygen levels triggers the temporal stabilization of the transcription factors hypoxia-inducible factors HIF1a and HIF2a, which are essential in intestinal homeostasis. HIF-1/2α are regulated by a family of prolyl hydroxylases (PHDs). Inhibition of PHDs results in transient stabilization of HIF-1/2α, and thus, PHD inhibitors (PHDi) have become attractive targets for the therapeutic treatment of IBD and are reported as protective in mouse models of colitis. We have pursued the development of PHDi using proteolysis targeting chimeras (PROTACs), heterobifunctional compounds that contain a protein of interest ligand, a linker, and a E3 ubiquitin ligase ligand. PROTACs hold advantages over small-molecule inhibitors, including enhanced specificity, higher potency, and sustained pathway inhibition. In ongoing studies, we have synthesized and tested a panel of PHD targeting PROTACs. In cultured intestinal epithelial cells, we have observed PROTAC activity at the nanomolar concentrations in vitro, representing a 2-3 log increase in potency compared to PHDi small molecules. For these purposes, we monitor PHD protein degradation and HIF1/2α stabilization through immunoblotting. We have confirmed HIF transcriptional activity in intestinal epithelial cells exposed to these PROTACs through the induction of various HIF target genes. In parallel, we have established a stably transduced GFP-PHD cell line as a high-throughput assay to monitor PHD degradation in real time. Thus, PHD-targeted PROTACs hold promise as viable alternatives to small molecules for the stabilization of HIF in intestinal epithelial cells.
ZINC RESTRICTION BY INTESTINAL E. COLI - PRODUCED YERSINIABACTIN ACTIVATES HIF-1α IN MACROPHAGES TO PROMOTE CD-ASSOCIATED FIBROSIS
Authors: Ahn Ju-Hyun , Lopez Lacey , Tibbs Taylor , Yu Yen-Rei , Tighe Robert , Denson Lee , Arthur Janelle 
Published: January 2024

Abstract
Intestinal fibrosis is a significant complication in Crohn’s disease (CD) patients, causing severe intestinal strictures and obstructions that are ultimately relieved by surgical bowel resection. Mechanisms driving CD-associated fibrosis are poorly understood but implicate the microbiome, especially adherent-invasive E. coli (AIEC). Previously, our work demonstrated that AIEC production of the metallophore yersiniabactin (Ybt) promotes fibrosis in the well-established gnotobiotic Il10-/- CD mouse model. These pro-fibrotic effects do not require bacterial uptake/utilization of Ybt, suggesting Ybt directly targets the host. Here we show that CD11b+ F4/80+ MHCIIlow macrophages are abundant in the submucosa and muscularis of fibrotic lesions in our mouse model. Similarly, CD68+ macrophages are abundant in strictures, not adjacent margins, of ileocolonic CD patients. We hypothesized that Ybt targets host macrophages to drive fibrosis. A critical metal-dependent pathway for immune cell function during inflammation is HIF-1α. We demonstrate that AIEC infection activates HIF-1α in macrophages, which is dependent upon Ybt production. Importantly, in fibrotic lesions of CD mouse models and resected strictures of ileocolonic CD patients, HIF-1α is activated and localized in nuclei of F4/80+ or CD68+ macrophages. We identified that zinc sequestration by Ybt is responsible for HIF-1α activation, a novel mechanism of HIF-1α stabilization. Furthermore, Ybt-producing AIEC induce potent pro-fibrotic gene expression in macrophage:fibroblast co-cultures, a process dependent on macrophage HIF-1α. This implies that Ybt induces pro-fibrotic macrophages, activating adjacent fibroblasts and fostering intestinal fibrosis. In summary, our findings suggest that as intestinal macrophages encounter AIEC, Ybt sequesters zinc, causes an accumulation of nuclear HIF-1α, and this imbalance of metal homeostasis drives pro-fibrotic macrophage and fibroblast activation. Ultimately, effective fibrotic remodeling fails and leads to intestinal fibrosis in CD patients.
PHYSICAL ACTIVITY AND SOCIAL COGNITIVE THEORY CORRELATES AMONG POSTOPERATIVE PERSONS WITH CROHN'S DISEASE: PRELIMINARY RESULTS FROM A CROSS-SECTIONAL ANALYSIS
Authors: Neal Whitney , Chu Daniel , Motl Robert , Pekmezi Dori 
Published: January 2024

Abstract

INTRODUCTION
There is increasing research and clinical interest in physical activity (PA) behavior among persons with Crohn's disease (CD), but little is known regarding PA and its correlates among postoperative persons with CD. This is important as most patients with CD will require surgery within 10 years of diagnosis which may drastically alter PA levels and its benefits for CD. As found in past studies with other patient populations (e.g., colorectal cancer survivors), understanding the cognitive and behavioral factors associated with PA engagement among postoperative adults with CD is useful for informing the development of PA behavior change interventions for this population. This cross-sectional study examined self-reported PA levels and its associations with social cognitive theory (SCT) variables among postoperative persons with CD.

METHODS
Participants included 30 persons with CD who completed an online survey between November 2022 and June 2023. Of those participants, 18 reported a history of CD-related surgery. The survey assessed demographic and clinical characteristics, disease activity (Harvey-Bradshaw Index), leisure time exercise (Godin Leisure-Time Exercise Questionnaire and International Physical Activity Questionnaire), and related SCT variables (exercise self-efficacy, social support, outcome expectations, goal setting, and planning). Analyses included independent sample t-tests and non-parametric bivariate correlations (rs) for comparing PA levels and SCT survey scores among participants with and without a history of surgery.

RESULTS
There were differences in PA and SCT variables based on surgical history. Postoperative participants engaged in significantly more PA (t = 2.17, p = 0.04) and reported greater outcome expectations (t = 2.45, p = 0.02) and goal setting (t = 2.22, p = 0.04) scores compared with CD participants without a history of surgery. Among postoperative participants, only exercise goal setting was significantly correlated with PA (rs = .53, p = 0.03) such that postoperative participants with greater exercise goal setting behaviors reported higher levels of PA. None of the SCT variables were significantly associated with PA in the sample of participants without a history of surgery.

CONCLUSIONS
This study yielded novel findings regarding PA behavior and its SCT correlates in a small sample of postoperative persons with CD. The results suggest the need for further research into exercise goal setting as a potential target of behavior change interventions for increasing PA among postoperative persons with CD.
Full operator preconditioning and the accuracy of solving linear systems
Authors: Mohr Stephan , Nakatsukasa Yuji , Urzúa-Torres Carolina 
Published: January 2024

Abstract
Unless special conditions apply, the attempt to solve ill-conditioned systems of linear equations with standard numerical methods leads to uncontrollably high numerical error and often slow convergence of an iterative solver. In many cases, such systems arise from the discretization of operator equations with a large number of discrete variables and the ill-conditioning is tackled by means of preconditioning. A key observation in this paper is the sometimes overlooked fact that while traditional preconditioning effectively accelerates convergence of iterative methods, it generally does not improve the accuracy of the solution. Nonetheless, it is sometimes possible to overcome this barrier: accuracy can be improved significantly if the equation is transformed before discretization, a process we refer to as full operator preconditioning (FOP). We highlight that this principle is already used in various areas, including second kind integral equations and Olver–Townsend’s spectral method. We formulate a sufficient condition under which high accuracy can be obtained by FOP. We illustrate this for a fourth order differential equation which is discretized using finite elements.