bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIPEP-IBD; A SYNTHETIC PEPTIDE TARGETING NOVEL MOLECULE, INTEGRIN BETA 1, TO RESTITUTE INTESTINAL EPITHELIAL CELLS FOR INFLAMMATORY BOWEL DISEASE (IBD) TREATMENT
Authors: Kim Deogil , Lee Dong Woo , Jeong Eui Kyun , Lee Hoo Cheol , Park Yoon Shin , Lee Jue Yeon , Chung Chong Pyung , Park Yoon Jeong 
Published: January 2022

Abstract
Under Inflammatory bowel disease (IBD), impaired intestinal barrier from lumen is highly associated with ongoing IBD symptoms and it also contributes as a precursor for IBD. Current IBD therapeutics lack on mucosal regeneration, which the unmet needs could be the next first in class therapeutics for IBD. Here, we propose NIPEP-IBD, a synthetically modified peptide that promotes adhesion, migration, and differentiation of intestinal epithelial cells via interaction of integrin beta 1. From NIBEC’s specialized peptide discovery platform screening, specifically sequenced peptide has been selected for regenerative functional peptide, termed NIPEP-IBD. NIPEP-IBD selectively targeted and bound to integrin beta 1 protein, and its interaction was also verified in vitro, using immunoprecipitation and immunofluorescence assays on epithelial cells. Consequently, NIPEP-IBD increased integrin beta 1 expression, followed by phosphorylated FAK and RhoA proteins. As FAK-RhoA signaling pathway is known to modulate cytoskeletal rearrangement and maturation of epithelial cells, tight junction markers and rapid wound closure of epithelial cells was accelerated by NIPEP-IBD induction. The effect of NIPEP-IBD was further analyzed in vivo IBD model. DSS-induced colitis mouse model was used to analyze therapeutic effect of NIPEP-IBD in each IP and PO administration, and impaired mucosa layer by DSS was recovered by NIPEP-IBD, verified with H&E staining. Moreover, NIPEP-IBD treated mice showed reduced immune cell infiltration in colon tissue and reduced pro-inflammatory cytokines in plasma. In vivo fluorescence imaging system was further used to track distribution of NIPEP-IBD, and NIPEP-IBD specifically binds to impaired epithelium, co-localized with integrin beta 1 protein. The following GLP toxicity studies, ADME studies, and PK studies demonstrated that safety of NIPEP-IBD was verified as a therapeutic agent. Therefore, NIPEP-IBD is a safe and effective therapeutic peptide on IBD patients by restituting epithelial layer of colon and maintain its remission.
SELECTION OF MICROBIOME-DERIVED PEPTIDES THROUGH MULTI-TECHNOLOGY META-ANALYSIS, BINDING, AND FUNCTIONAL ASSAYS, IDENTIFIES PEPTIDES WITH THERAPEUTIC POTENTIAL THAT MODULATE IMMUNE RESPONSES AND DISEASE
Authors: Lin Michelle , Kim Eun Ok , Desnoyer Jill , Narayan Nicole , Ravichandar Jayamary , Lau Sabina , Hwang Bum-Yeol , Johnson Amy Jo , Willcoxon Michi , DeSantis Todd , Dabbagh Karim , Yamamoto Lynn 
Published: January 2022

Abstract
Microbiome-driven drug discovery holds great promise for therapeutic development. However, identification of disease-associated microbiome-host interactions are challenging, owing largely to the complexity of a diverse community and the myriad of direct and indirect interactions through which the microbiome can influence its host. Moreover, inflammatory bowel disease (IBD) is a heterogeneous disease with a complex diagnosis, and multiple etiologies, pathologies, and treatment responses. Finding robust associations between IBD and the microbiome has proven difficult. Using a systematic computational pipeline, we identified bacterially-derived peptides that were consistently increased in non-IBD samples and improved colitis in mouse models. To identify concordant changes in 15 IBD cohorts with 21 datasets, we used a novel multi-technology meta-analysis (MTMA) procedure and a curated reference database (StrainSelect). From these strains’ genomes and from metagenomic assemblies, the encoded bacterial peptides were synthesized and screened to find those which interact with the human immune system. Using phage panning, peptide libraries were assessed in a large scale screen using primary human cells to identify those that bind to our cells of interest such as T cells. Peptides that demonstrated binding were then screened in functional assays to identify bioactive peptides that influence cytokine production. Peptides with strong effects and cross-reacted to mouse cells also showed efficacy in mouse models of IBD. Identification of bioactive peptides demonstrates that a workflow in which i) a standardized computational pipeline is employed to identify peptides that are consistently decreased in IBD patients, ii) peptides are first screened by their ability to bind to cells of interest, and iii) peptides are then screened for functional activity, results in bioactive peptides with therapeutic potential.
THE SYNTHETIC GLYCAN KB295 OPTIMIZES MICROBIOME COMPOSITION AND FUNCTION IN ULCERATIVE COLITIS – RESULTS FROM A PROOF OF PRINCIPLE HUMAN STUDY
Authors: Meisner Jeffrey , Bransford Toni , Miller Kelsey , Lee Jackson , Jose Adarsh , Giuggio Michael , McComb Megan , Humphries Eric , Rosini Madeline , Wingertzahn Mark , Shanahan Fergus , van Hylckama Vlieg Johan E T , Dowling Mark 
Published: January 2022

Abstract
The pathogenesis of ulcerative colitis (UC) involves genetic susceptibility, immune-mediated tissue injury and environmental factors including disturbances of the gut microbiota. Nearly all current approved therapies modify host immunity, rather than directly targeting the microbiota. Fecal microbiota transplantation provides encouraging evidence for the therapeutic potential of gut microbiome modulation. Bacteria in the GI tract are ecologically differentiated by their ability to use specific glycans as growth substrates, making glycans a promising and safe alternative to target the microbiome. To explore this, we used an ex vivo fecal microbiota culture system to identify a synthetic glycan (KB295) with desirable microbiological activity and conducted a proof of principle study of safety and tolerability of KB295 in patients with UC.
Fecal microbial communities from healthy subjects were incubated anaerobically with and without (negative control) KB295. KB295 increased short chain fatty acid (SCFA) production across ten fecal samples to a median concentration of 47.0 mM compared to 15.2 mM with the negative control in culture supernatants, including increases in acetate, propionate, and butyrate in all cases. Metagenomic sequencing of the ex vivo fecal pellets revealed that KB295 depleted pathobionts in the family Enterobacteriaceae to a median relative abundance of 10.8% compared to 38.2% with the negative control. Pathobiont depletion was associated with enrichments of diverse genera in the phyla Bacteroidetes and Firmicutes.
Twelve patients with mild to moderate UC were enrolled in an open-label single-arm study with an 8-week intake of KB295. KB295 was well tolerated with generally mild adverse events, and only one AE resulted in discontinuation. The most frequently occurring adverse events were changes in bowel habit, flatulence, and headache. Fecal calprotectin and lactoferrin decreased by median values of 69.0% (n=11) and 86.0% (n=6), respectively, from screening to the end of the KB295 intake. Consistent with the ex vivo preclinical findings, of the subjects for whom we have data to date, the relative abundance of the fecal pathobiont family Enterobacteriaceae decreased from five participants, and the commensal genus Parabacteroides was enriched in four of five participants.
These results establish a proof of principle for the glycobiological modulation of gut microbiome composition and function and provide insight into the potential utility of this strategy in patients with ulcerative colitis. The safety, tolerability, and encouraging evidence for reduced inflammation with KB295 call for a Phase 2 study, which is planned.
INCIDENTALLY DIAGNOSED ASYMPTOMATIC CROHN’S DISEASE: LONG-TERM CLINICAL OUTCOMES OF UNTREATED PATIENTS
Authors: Grinman Ana , Ungar Bella , Lahat Adi , Kopylov Uri , Eliakim Rami , Ben-Horin Shomron 
Published: January 2022

Abstract

BACKGROUND
Crohn’s disease (CD) is occasionally diagnosed in asymptomatic patients undergoing colonoscopy for other reasons, but their clinical outcomes and optimal management remain poorly defined.

METHODS
A retrospective cohort study of asymptomatic patients with incidental diagnosis of CD. The primary outcome was defined as the occurrence of a clinical flare. Secondary outcomes included time to clinical flare, time to initiation of corticosteroids or immunomodulators/biologics, and rate of surgery.

RESULTS
Of the 2558 patients in Sheba IBD registry, 53 asymptomatic patients with incidental diagnosis of CD were identified (median age 50 (41.75-57), 52% males, 32/53 with L1, 9/53 L2, 11/53 L3,1/53 L4, 41/53 B1, 10/53 B2, 2/53 B3, 1 with perianal disease). Most patients (48/53) did not receive any treatment after diagnosis. Of these untreated patients, 43/48 (89.5%) had not experienced a flare over a median follow-up of 4.5 years (IQR 2-8, range 1-15 years). None of the patients with over 8 years follow-up (n=14) experienced a flare. When comparing the group of patients with or without immediate post-diagnosis initiation of treatment (n=5, n=48, respectively), there was no difference in survival time without flare (p=0.3). Of the 48 patients without immediate treatment, immunomodulators/biologics were initiated in 4(8.3%) during follow-up. Surgery for CD occurred in 2 patients during the follow-up. None of the parameters examined, including age, CRP, ileal versus other locations, or having a complicated phenotype (B2/B3 versus B1) was found to predict a clinical flare later on.

CONCLUSION
Many asymptomatic patients with an incidental diagnosis of Crohn’s disease can probably be followed-up without immediate treatment. Although the majority remain asymptomatic and without complications during follow-up, close monitoring for disease progression is prudent.
INFLAMMATORY BOWEL DISEASE IN APPALACHIA: AN INVESTIGATION INTO DISPARATE OUTCOMES WITHIN THE STATE OF KENTUCKY
Authors: Perry Courtney , Rhudy Christian , Flomenhoft Deborah , Talbert Jeffrey , Barrett Terrence 
Published: January 2022

Abstract

INTRODUCTION
Inflammatory Bowel Disease (IBD) affects an estimated 3.1 million US adults, with an increasing prevalence in recent years1. Of these, 1.1 million live in the CDC classified “Southern” region, which includes the state of Kentucky. The eastern portion of the state is part of the Appalachian region, a low-resourced area with a dense, vulnerable population. The majority of Kentucky’s Appalachian counties are classified as distressed (ranked bottom 10% in the US based on economic development), and suffer a higher prevalence of chronic disease2. To our knowledge, there is no published data quantifying the healthcare burden of IBD or evaluating disease outcomes in this vulnerable community.

METHODS
We utilized the hospital inpatient discharge and outpatient services databases available through the healthcare cost and utilization project (HCUP) to assess outcomes among patients with a diagnosis of either Crohn’s disease (CD) or Ulcerative Colitis (UC) in the state of Kentucky. Outcomes of interest were aggregated at the county level and included number of hospital admissions, number of total outpatient visits and visits to an emergency department, inpatient and outpatient surgeries. Data was reported as number of incident visits per 100,000 population/year, collected between the years 2009-2019.

RESULTS
We found that CD patients residing in Appalachian counties were more likely to be admitted to the hospital (42.72 vs. 29.69, p-value= 0.0001), require inpatient surgery (6.91 vs 5.35, p-value= 0.006), and be admitted for abdominal pain as a complication of their disease (3.82 vs 2.28, p-value = 0.0031) than non-Appalachians. Appalachian CD patients also had a higher number of ER visits (84.06 vs. 52.64, p-value = 0.0102), outpatient surgery visits (161.24 vs 112.35, p-value = 0.0024), and clinic visits for abdominal pain (39.8 vs 24.34, p-value=0.0002) than non-Appalachians. UC patients in Appalachian counties were more likely to require inpatient surgery (1.36 vs 0.74, p-value 0.0007) than non-Appalachians. There was no significant difference in rates of fistula, perforation, or malabsorption in either CD or UC based on Appalachian county data.

CONCLUSION
These data support the notion of disparate outcomes in IBD based on Appalachian county residence in the state of Kentucky. This was most striking when evaluating Crohn’s disease in Appalachians, as evidenced by hospital admissions, surgeries, and ER visits. Appalachian inpatients with UC had a significantly higher rate of surgical resection. These findings highlight a need for aggressive investigation into root causes of these disparate outcomes, with particular attention to identifying and subsequently alleviating barriers to IBD care. Whether these data infer treatment of Appalachian IBD patients should be managed more aggressively earlier in the disease course awaits further investigation.
PREDICTORS AND OUTCOMES OF BIOLOGIC/IMMUNOSUPPRESSIVE THERAPY FOR PSC-ASSOCIATED IBD
Authors: Sayed Amr , Silveira Marina , Assis David , Deng Yanhong , Gaidos Jill , Proctor Deborah , Al-Bawardy Badr 
Published: January 2022

Abstract

BACKGROUND
Inflammatory bowel disease (IBD) coexists in up to 80% of patients with primary sclerosing cholangitis (PSC). PSC-IBD tends to be mild and responsive to mesalamine in most patients. However, some may require immunosuppressive (IMM) or biologic therapy to treat PSC-IBD. The aims of this study are to investigate the rates, predictors, and outcomes of biologic/IMM treatment of PSC-IBD.

METHODS
This was a single center, retrospective study of patients with PSC from 1/1/2012 to 4/1/2021. Adult patients (age ≥ 18 years) with PSC-IBD were included. Primary outcomes were rates and predictors of biologic/IMM therapy to treat PSC-IBD. Secondary outcomes included rates of cholangitis, PSC-IBD clinical remission (per physician global assessment), endoscopic healing (absence of ulcers/erosions) in patients who required biologics/IMM. Patients who required biologics or IMM to treat PSC-IBD (biologic/IMM group) were compared to patients who did not require biologics/IMM. Continuous variables were compared using an unpaired Student’s t-test. Categorical variables were compared using a Chi-square or Fisher’s Exact test as appropriate.

RESULTS
A total of 106 patients with PSC were reviewed and 72 (68%) had confirmed PSC-IBD and were included in the study. The median age was 48 years (IQR 33-59.5) and 69.4% were male (Table 1). A total of 22 patients (30.6%) required biologic/small molecule therapy (infliximab in 6; ustekinumab in 6; vedolizumab in 5; adalimumab in 4; tofacitinib in 1) and 6 (8.3%) needed thiopurine monotherapy to treat PSC-IBD. Overall, 28 patients (38.9%) required biologics/IMM to treat PSC-IBD. In the biologics/IMM group, 9 patients (32.1%) had small bowel involvement compared to 2 patients (4.6%) who did not require biologic/IMM (p=0.002). In the biologic/IMM group, 7 (25%) had overlap autoimmune hepatitis (AIH) compared to 3 (6.8%) in patients who did not require biologic/IMM for PSC-IBD (p=0.04). In the biologic/IMM group, 18 (64.3%) subjects were also treated with ursodeoxycholic acid (UDCA) compared to 29 (65.9%) in the non-biologic/IMM group (p=0.89). At least 1 episode of cholangitis was noted in 12 patients (42.9%) in the biologic/IMM group compared to 14 (31.8%) in the non-biologic/IMM group (p=0.34). In the biologic/IMM group, clinical remission was achieved in 22 patients (78.6%) but endoscopic healing in only 14 (50%).

CONCLUSIONS
In our cohort, up to a third of patients with PSC-IBD required biologics/IMM. Small bowel involvement was associated with the need for biologic/IMM. The use of biologic/IMM resulted in clinical remission in over three quarters of the PSC-IBD subjects however endoscopic healing was only achieved in half. The use of biologics/IMM was not associated with a higher rate of cholangitis but larger studies are needed to investigate the effects of different biologic classes on outcomes.
CROHN’S DISEASE COMPLICATED BY ILEOSIGMOID FISTULA: ASSESSMENT AND MANAGEMENT UPDATE
Authors: Benammi Sarah , Calini Giacomo , Abdalla Solafah , Mathis Kellie 
Published: January 2022

Abstract

BACKGROUND
The preoperative evaluation of Crohn’s-related ileosigmoid fistula (ISF) is complex with multiple preoperative diagnostic modalities available. Intraoperative management is also complicated when deciding whether to repair the fistula or resect the involved sigmoid. How these choices impact outcomes is not clear. We aim to evaluate the impact of sigmoid resection versus conservative fistula repair on postoperative complications when treating ISF.

METHODS
Patients with Crohn’s disease (CD) undergoing ileocolic resection in the setting of an ISF between January 1, 2007 and December 31, 2017 were identified. A retrospective chart review was conducted to collect data on preoperative workup, intra-operative technique, and 30-day complications. Intra-abdominal sepsis was defined as the presence of an intra-abdominal abscess or anastomotic leak from the sigmoid colon postoperatively. Univariate comparisons were performed between those undergoing primary repair versus sigmoid resection with primary anastomosis.

RESULTS
61 patients (62.3% female) with a median age of 37 years (range, 18-73)were included. Computed tomography enterography (CTE) and magnetic resonance enterography (MRE) each had a sensitivity of 100% versus 42% sensitivity for colonoscopy. When accounting for pre-operative endoscopy results, patients with endoscopic sigmoidal mucosal CD more often underwent sigmoid resection than patients with a normal sigmoidal mucosa or only a solitary fistulous opening in the sigmoid colon (p&lt;0.001). When comparing primary repair vs sigmoid resection there was no difference in the occurrence of intra-abdominal septic complications (p=0.342) or anastomotic leak complication (p=0.239).

CONCLUSION
In summary, our study shows that conservative repair of the fistula is a safe option. Appropriate patient assessment and preoperative identification of the fistula is critical so that the management strategies for ISF and the potential implications can be discussed with the patient. CTE and MRE are the modalities of choice to diagnose ISF, while colonoscopy has a role in staging the burden of mucosal disease in the sigmoid colon. These tests help guide surgical decision-making with respect to resection versus primary repair of the sigmoid colon and will allow patients in whom the sigmoid colon is an innocent bystander to undergo a less extensive operation.
IBD AND THE PATIENT-PROVIDER RELATIONSHIP: DOES TRUST IMPACT TELEMEDICINE UTILIZATION?
Authors: Katta Meghna , Shao Connie , Herbey Ivan , Modi Sagar , Gleason Lauren , Marques Isabel , Duong Teressa , Lopez Elizabeth , Hair Kaycee , Chu Daniel 
Published: January 2022

Abstract

BACKGROUND
Telemedicine use has increased during the COVID-19 pandemic, but uptake among patient populations has not been equitable. Lack of access to technology or broadband connection contributes to the digital divide, but additional factors at the provider-level may contribute. We aimed to identify barriers and facilitators to inflammatory bowel disease (IBD) patient use of telemedicine with a focus on trust and the patient-provider relationship.

METHODS
Patients 18 years and older who were seen via telemedicine at a colorectal surgery clinic at a high-volume, tertiary care academic center were contacted for participation in this study. Patient demographics including age at surgery, race, sex, and diagnosis were recorded. Patient health literacy was evaluated using the BRIEF Health Literacy Screening Tool. The Wake Forest Physician Trust Scale (WFPTS) was used to measure patient trust in providers. Individual semi-structured interviews based on developed guides explored barriers and facilitators to telemedicine use. NVivo12 software was used for qualitative analysis and data organization. Coders reviewed each transcript independently, convening after initial review for discussion. Final themes were analyzed by disease process.

RESULTS
Among 29 participants, 24% of patients underwent colorectal surgery for treatment of IBD. 52% identified as female, 67% White, 30% Black, and 4% Latino, which closely mirrors the racial demographics of the study region. 33.3% of patients had limited health literacy (BRIEF score &lt; 17) with an overall mean BRIEF score of 17.6 out of 20 (SD 3.33). The WFPTS scale ranged from 44 to 50, with a mean of 48.5 (SD 2.1) in IBD patients. Among IBD patients, three major themes were identified as important with respect to trust during telemedicine visits: trust in providers, trust in the institution, and trust in the surgical process. Of these, provider-level trust appeared to most influence patient trust in telemedicine. All participants noted that surgeon confidence and reputation affected trust in telemedicine. In the majority of IBD patients, a surgery referral from a trusted provider was an important factor in a patient’s trust and utilization of telemedicine pre and post operatively. Additionally, the duration of the patient encounter, pre-operative education, and the surgeon’s ability to answer questions appeared most relevant to IBD patients.

LIMITATIONS
The generalizability of our results may be limited because all patients were seen via telemedicine at a single institution.

CONCLUSION
Provider-level trust may have an increased role in IBD patients. To improve patient trust and telemedicine engagement in the IBD patient population, providers and healthcare systems should build and integrate interventions that enhance communication and interpersonal skills.