bluuebunny/crossref_metadata_2025_split huggingface dataset:
A260 ADVANCING INFLAMMATORY BOWEL DISEASE DIAGNOSIS THROUGH STOOL PROTEOMIC SIGNATURES OBTAINED VIA DIA-MASS SPECTROMETRY AND MACHINE LEARNING
Authors: Shajari E , Gagné D , Malick M , Brunet M , Delisle M , Boisvert F , Beaulieu J 
Published: February 2024

Abstract

Background
Resembling symptoms between flare-up Inflammatory bowel disease (IBD) and other gastrointestinal diseases and conditions, make the initial diagnosis and accurate treatment of this disease challenging. Currently, the most common clinical methods used for diagnosing and monitoring IBD are colonoscopy and biopsy, which are invasive and uncomfortable procedures, and the fecal calprotectin test, which is not sufficiently accurate. Therefore, it is necessary to develop an alternative method.

Aims
In this study, our aim was to develop a robust predictive model for a noninvasive and accurate test to distinguish active IBD from non-IBD controls.

Methods
A total of 120 samples were collected, with 78 samples separated for retrospective analysis and model training, while 42 samples were set aside for prospective validation. We employed SWATH mass spectrometry for the identification and quantification of the stool proteome. The obtained data underwent multiple stages, including data preprocessing, feature selection, model training, and performance evaluation. We optimized data processing procedures through advanced bioinformatics, selecting an appropriate pipeline that included data normalization, batch effect correction, and missing value imputation. Subsequently, we assessed various machine learning algorithms to determine the most effective classifier for predicting IBD based on the selected proteins.

Results
After data preprocessing, we identified 48 differentially abundant proteins (DAPs). To eliminate redundant proteins, we employed Correlation-based Feature Selection (CFS), resulting in selecting 7 proteins. To identify the most suitable predictive model for our dataset, we assessed five popular machine learning methods: Support Vector Machines (SVM), Random Forests, Logistic Regression, k-nearest neighbors (KNN), and Naive Bayes. Among these, SVM exhibited the highest performance. Finally, we evaluated the model's performance by applying the selected algorithm to 42 prospective blind samples. The results revealed a sensitivity of 96% and a specificity of 76%, highlighting its strength and effectiveness.

Conclusions
In conclusion, this study offers a proof of concept for the application of SWATH for precise IBD diagnosis using stool proteomics and showcases the effectiveness of our data processing and machine learning approach. Additionally, it highlights the potential of this method for classifying Crohn's Disease (CD) vs. Ulcerative Colitis (UC) and distinguishing active IBD from remission.

Workflow of study

Funding Agencies
CIHRCrohn's and Colitis Canada , Studentship from CRMUS,
A272 EFFECTS OF EMPAGLIFLOZIN ON CHEMICALLY INDUCED COLITIS IN A MOUSE MODEL ARE MODULATED BY SEX AND DIETARY INTERACTIONS
Authors: Madsen K , Villaflor B , Hotte N , Thiesen A , Cheng C , Omeltchenko T 
Published: February 2024

Abstract

Background
High sugar diets have been shown to dramatically increase disease severity in mouse models of colitis. Empagliflozin (EMPA) is a highly selective sodium glucose cotransporter-2 (SGLT2) inhibitor that is used therapeutically as an antihyperglycemic agent in the management of type 2 diabetes. In human trials EMPA treatment exerts potent anti-inflammatory effects independently of glycemic control. Further, we have previously demonstrated in a genetic mouse model of colitis that EMPA treatment was highly effective in improving colonic inflammation. Based on these findings, we hypothesized that EMPA treatment may also be effective in mitigating disease severity in chemically induced colitis in mice fed a high sugar diet.

Aims
The aim of this study was to examine the effects of treatment with EMPA on chemically induced colitis in mice fed a high sugar diet

Methods
At 6-8 weeks of age, wild-type 129/SvEv mice were placed on chow (CH) or high sugar diet (HS) (50% sucrose: AIN76A) ± EMPA (10mg/kg). After two days on the diet, mice were administered dextran sodium sulfate (DSS) for 5 days in drinking water followed by water alone for 2 days (n=4-6 mice for all groups). Disease activity index (DAI) was calculated daily from animal weight change, stool consistency, and stool hemoccult. As a measurement of degree of healing, colonic tissues were evaluated at day 9 for histological changes, weight-to-length ratio, and cytokine levels by ELISA. As a measure of EMPA functionality, urinary and blood glucose levels were measured.

Results
Mice on the HS diet demonstrated increased susceptibility to colitis compared with chow fed mice with increased colonic levels of IL-1β, weight loss, and DAI. Significant interactions between sex and diet were seen in responses to EMPA treatment. EMPA treatment did not alter severity of colitis but did significantly delay healing in male mice on both the HS and chow diets as evidenced by increased DAI and increased enterocyte injury with increased levels of lamina propria neutrophils and lymphocytes. EMPA treatment did not increase disease severity in females on either diet. No differences were seen in colonic TNFα, IL-10, IL-12p70, or IL-22 between any of the groups. Urinary glucose levels were elevated in mice receiving EMPA and significantly higher in males compared with females (pampersand:003C0.05). EMPA treatment did not alter fasting blood glucose levels.

Conclusions
A high sugar diet strongly exacerbates disease severity in a sex-dependent manner in a chemically induced model of colitis. Further, contrary to our hypothesis, EMPA treatment did not improve colitis in females and worsened disease in males suggesting that the documented anti-inflammatory effects of EMPA may be condition dependent.

Funding Agencies
CCC
A273 A PILOT PROSPECITVE, MULTI-CENTRE, RANDOMIZED CONTROLLED TRIAL COMPARING FECAL MICROBIOTA TRANSPLANTATION (FMT) TO PLACEBO AT INDUCING REMISSION IN MILD TO MODERATE CROHN'S DISEASE
Authors: Wong K , Kao D , Jijon H , Franz R , Narula N , Peerani F , Turbide C , Kroeker K , Moayyedi P , Madsen K 
Published: February 2024

Abstract

Background
FMT has shown promise at inducing remission in ulcerative colitis. The effect of FMT on inducing remission in Crohn’s disease however remains unknown.

Aims
To evaluate the efficacy of FMT at inducing remission in mild-to-moderate Crohn’s disease

Methods
This double-blind, randomized, trial conducted at 3 Canadian academic centers (Edmonton, Hamilton and Calgary) randomized. Adult patients with mild-to-moderate Crohn’s disease with modified Harvey Bradshaw Index (mHBI) score of ampersand:003E5 and at least one objective measure of inflammation (CRP ≥ 8mg/L or fecal calprotectin (FCP) ≥ 250 ug/g) on stable dosing of concomitant therapy were assigned to FMT or placebo. First assigned treatment was by colonoscopy followed by 20 [DK1] capsules weekly for 7 weeks. Endoscopic severity (SES-CD) was assessed at baseline during colonoscopic delivery of assigned treatment and at week 8 by a blinded central reader using video recording. The primary endpoint was the proportion of patients in both clinical (mHBI ampersand:003C 5) and endoscopic remission (SES-CD ≤ 5) at week 8. Responders (reduction of HBI ≥ 3 or HBI ≤ 5 and reduction of CRP or FCP by ≥ 10%) in FMT group were eligible to continue with open-label FMT capsule every 2 weeks. Non-responders in the placebo group were permitted to restart the trial at week 0 with open-label FMT. Secondary outcomes included patient reported outcomes and safety outcomes.

Results
Between July 2017 to Jun 2021, 28 were randomized (16 to FMT and 12 to placebo). The study team voluntarily suspended the trial twice due to Health Canada safety warnings regarding potential transmission of multi-drug resistant organisms and SARS-CoV-2 through FMT. At week 8, 0% (0/16) of patients in the FMT group versus 8.3% (1/12) in the placebo group reached the primary endpoint of combined clinical and endoscopic remission. Of the 50% (8/16) in the FMT group who achieved a clinical response and continued on open-label FMT every 2 weeks, 12.5% (1/8) achieved the primary endpoint. Of the 7 non-responders in the placebo group who restarted the trial at week 0 and received open-label FMT, 28.6% (2/7) achieved primary endpoint at week 8 on open-label FMT. No death or hospitalization were observed. The study was terminated early at the recommendation of the Data Safety Monitoring Board.

Conclusions
FMT was not effective at inducing remission in Crohn’s disease using the FMT regimen in this study. However, this study was limited by a small sample size and recruitment barrier during the COVID pandemic. Future studies may consider other strategies to potentially enhance treatment response, including antibiotic pre-treatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet.

Funding Agencies
CIHR
A278 ACCEPTABILITY, FEASIBILITY, AND IMPACT OF THE MYGUT DIGITAL HEALTH PLATFORM IN THE MONITORING AND MANAGEMENT OF INFLAMMATORY BOWEL DISEASE
Authors: Zhen J , Simoneau M , Sharma P , Germain P , Marshall J , Afif W , Narula N 
Published: February 2024

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder that has been associated with depression, anxiety, and decreased quality of life. With new technological advancements, digital health monitoring platforms offer a promising avenue to integrate self-management strategies into the care of patients with IBD.

Aims
This study aimed to investigate patients’ acceptability to implementing the MyGut IBD health monitoring platform into their care, evaluate whether its use leads to better quality of life/improved health outcomes, and determine the feasibility of its long-term use.

Methods
We conducted a multi-centre, single-arm trial at McMaster University and McGill University, among their affiliated hospitals, from September 2020 to September 2023. Patients with IBD were recruited in gastroenterology clinics and asked to install the MyGut application onto their mobile devices. Various metrics such as willingness to use the application, patient satisfaction, symptom control/quality of life scores (measured through the short inflammatory bowel disease questionnaire (SIBDQ)), resource utilization, and feasibility statements were collected throughout the study. Patients exhibiting abnormal SIBDQ scores were identified for follow-up. After one year, patient outcome metrics were compared to baseline values.

Results
Out of the 84 patients initially enrolled, 58 patients (69%) continued until study completion at one-year. At recruitment, all 84 patients (100%) were willing to use the MyGut application after a brief tutorial and 72.6% (61/84) had already been using technology for health-related purposes. There was a significant improvement in SIBDQ scores after one year of MyGut use (median = 57.5, IQR 50.25–62) when compared to baseline (median = 54.5, IQR 47.25–58.75) (p = 0.01). However, only 42.9% of patients (21/49) were willing to continue using the application after one year, a significant decrease compared to the 71.9% (41/57) who were willing to continue after two months (p = 0.002). No differences were observed in patient satisfaction measures (p = 0.42 to 1) or number of ER visits/hospitalizations (p = 0.78) before and after one year of MyGut use.

Conclusions
Overall, IBD is a condition that often necessitates frequent medical follow-up and may benefit from proactive symptom management strategies. This study demonstrates that patients with IBD are very willing to integrate digital health monitoring platforms into their care and these may subsequently lead to improved symptom control and enhanced quality of life. Future studies should aim to investigate the subset of patients that would benefit most from these health interventions, and as illustrated, continued efforts must be made to optimize the acceptability/feasibility of its long-term use.

Funding Agencies
CCC
A300 ADVANCED HEPATIC ECHINOCOCCOSIS: A CASE REPORT
Authors: Quan S Y , Wells M 
Published: February 2024

Abstract

Background
Alveolar echinococcosis (AE) is a rare and potentially fatal disease caused by the parasite echinococcus multilocularis (EM). Humans are intermediate hosts who become infected through contact with definitive hosts (foxes, wolves, coyotes, dogs and cats) and ingestion of contaminated food and water. AE primarily affects the liver but has the potential for local or metastatic spread. It has a clinical latency time of 5-15 years and resembles a malignancy in appearance and growth, posing a challenge in diagnosis and management. Treatment includes benzimidazole therapy and surgical resection, however, removal of the entire parasitic mass is not always possible.

Aims
Present a case of hepatic AE involving the gallbladder, biliary tree, and spleen.

Methods
Case report.

Results
A 49-year-old farmer was admitted to a Saskatchewan hospital for a 2-week history of abdominal pain, jaundice, and progressive weight loss. Computed tomography (CT) of the abdomen and pelvis showed a necrotic mass in the gallbladder compromising the liver, splenic lesions and involvement of the biliary tree. The patient was given a preliminary diagnosis of metastatic cholangiocarcinoma and underwent a gallbladder biopsy which returned as echinococcus, confirmed with two liver biopsies and a positive EM nucleic acid test. He was then diagnosed with advanced hepatic AE with metastasis to the gallbladder, biliary tree, and spleen. The patient required a long-term hepatic drain and developed a hepatocutaneous fistula. While surgery is curative, his disease was too extensive for resection. He was started on Albendazole and received into our care for a liver transplant assessment 10 months later. Currently, there is limited literature on liver transplantation in advanced AE as it may not be curative. Additionally, subsequent immunosuppression may expedite residual parasite growth leading to aggressive disease recurrence. In this case, liver transplant would also require a splenectomy and excision of the hepatocutaneous fistula for complete parasite removal. Repeat CT of the abdomen and pelvis at thirteen months after the patient's initial hospitalization did not show disease progression. Given his stability on Albendazole, the added surgical complexity, and possibility of aggressive disease recurrence post liver-transplant, the multidisciplinary committee decided against liver transplant at this time. He continues to do well on Albendazole 15 months after initial presentation.

Conclusions
The reported mortality rate of AE is ampersand:003E 90% within 10-15 years of diagnosis if untreated or inadequately treated. This case highlights the complexities in management of advanced hepatic AE and the importance of early diagnosis and treatment with radical surgery. Although not curative, benzimidazole therapy is effective in slowing disease progression in unresectable cases. Further studies are needed to assess the role of liver transplantation in advanced hepatic AE.

Funding Agencies
None
A310 CANADIAN GASTROENTEROLOGY RESIDENT ATTITUDES TOWARDS TREATING PATIENTS WITH DISORDERS OF GUT BRAIN INTERACTION
Authors: Rodrigues D , Parker C H , Salim M , Liu L W 
Published: February 2024

Abstract

Background
Disorders of gut brain interaction (DGBI) are common in the Canadian population. Studies show DGBI represent 30% of new referrals to gastroenterology (GI) clinics. Despite this, evidence suggests that gastroenterologists experience challenges in providing care for these patients, with a recent study from the United States indicating that this discomfort may begin early in residency training.

Aims
Our aim was to determine Canadian GI resident attitudes towards treating patients with DGBI, with a focus on determining underlying causes and solutions for potential negative attitudes.

Methods
Gastroenterology residents participating in accredited adult GI training programs in Canada were invited to participate in an online 30-item survey. This was based on similar studies in the adjacent field of chronic pain and administered using RedCap. Recruitment occurred through email invites distributed to residency program directors and QR code links presented at national GI resident meetings over one year.

Results
In total, 42 residents participated in the survey. Most residents reported frequent exposure to DGBI. Although most residents felt confident at diagnosing DGBI, only few felt confident in managing them. The majority reported less enjoyment and personal reward at managing DGBI than other gastrointestinal diseases, finding them frustrating to treat and expressing concern regarding the uncertainty of the diagnosis and low likelihood of successful management. Residents believed that challenges in the treatment stemmed from the following: inadequate training, uncertainty regarding the severity of symptoms that were reported, co-existing psychiatric issues, a lack of clarity on therapy and inadequate time. Residents reported that senior residents and staff both expressed negative opinions about caring for those with DGBI, and felt that displeasure for managing patients with DGBI was pervasive in the GI community. Importantly, the majority of trainees believed it was important to formally learn about the physiological underpinnings of DGBI as well as their diagnosis and management. Furthermore, understanding the impact of DGBI on a patient’s quality of life was thought to be important.

Conclusions
This national survey demonstrates that Canadian GI trainees are less confident and less interested in providing care for those with DGBI due to a variety of factors including inadequate training and a potential hidden curriculum. Residents believe in the importance of education in this field. The results of this study will be used to develop educational experiences to ultimately improve the care of those with DGBI.

Funding Agencies
None
A311 EFFICACY OF PANCREATIC CANCER SCREENING IN HIGH RISK INDIVIDUALS
Authors: Harjot B , Cheng D , Buttar J , Lam E , Telford J J 
Published: February 2024

Abstract

Background
Pancreatic cancer (PC) is the 11th most prevalent cancer in Canada with about 6900 new cases in 2021. Due to late diagnosis, it is the 4th largest cause of cancer related mortality in Canada. Despite advances in diagnosis and treatment over the past decade, the 5-year survival remains ampersand:003C10%, making pancreatic cancer one of the most lethal malignancies worldwide. However, if detected early, the 5-year survival increases to 80%. The incidence of pancreatic cancer remains low. Therefore, the International Cancer of the Pancreas Screening (CAPS) consortium do not recommend screening everyone. Selective screening in high-risk individuals may be effective in early detection and treatment of pancreatic cancer.

Aims
1. To determine the characteristics of patients undergoing PC screening at a single tertiary care center in Vancouver.
2. To determine the frequency of disease progression and outcomes in patients diagnosed with high-risk lesions during screening.

Methods
Retrospective chart review was performed for patients who were screened between January 1, 2005 to June 30, 2023. As per consensus from the CAPS Consortium, patients with at least 2 close relatives with PC, and those with predisposing genetic mutations screened using endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) were included in the study. Clinical data, such as age, tobacco use, genetic risk, endoscopic findings, and outcomes, such as disease progression, were collected. Statistical analysis was performed using Rstudio and Microsoft Excel.

Results
73 patients were included, with 42 included due to pathogenic germline mutations, and 31 with familial pancreatic cancer. Most were female (52, 71.2%). Median age in the study was 54 years (range 24-74 years) at initial screening. 66 patients (90.4%) received an EUS and 7 patients (9.6%) received MRI for initial screening. At the time of initial screening. 74.6% of patients had a normal pancreas. 6 patients (8.2%) were found to have neoplastic lesions, e.g. ampulloma, neuroendocrine tumour or adenocarcinoma at initial screening and referred for surgery. In the median follow up time of 67.9 months (range 0-168.1 months), 6 patients were noted to have disease progression, 4 of which had increase in cyst size without any other worrisome features. 2 patients had progression to malignancy. 1 of those patients received chemotherapy and surgical resection and remains alive; the other patient was lost of follow up due to geographical move.

Conclusions
Pancreatic cancer screening in high risk individuals is effective in early detection and treatment. Given lower incidence of pancreatic cancer, we likely need additional patient enrolment to observe a significant improvement in patient outcomes.

Funding Agencies
None
Organizational Culture: Structure and Evolution
Authors: Gradstein Mark 
Published: February 2024

Abstract
We present a model of the formation and evolution of organizational culture and its effect on performance. The analysis reveals circumstances under which, because of cultural externalities, excessive polarization or, alternatively, homogeneity may result, indicating inter alia an important role for the performance of managing cultural diversity in organizations. The exhibited framework can be useful in dissecting how different aspects of cultural diversity and the nature of management–workers’ interactions affect organizational functioning (JEL D02, D23, M54, Z13).
Accumulation of circulating myeloid-derived suppressor cell subsets: predicting poor clinical efficacy and prognosis through T cell suppression in non-Hodgkin's lymphoma
Authors: Pu Lian-Fang , Li Man-Man , Feng Xiang-Jiang , Zhang Tun , Hu Lin-Hui , Zheng Hui-Min , Charwudzi Alice , Ding Yang-Yang , Liu Jun , Liu Ze-Lin , Xiong Shu-Dao 
Published: February 2024

Abstract
Myeloid-derived suppressor cells (MDSCs) are implicated in the regulation of immune responses closely associated with poor clinical outcomes in cancer. However, the MDSC subtypes in non-Hodgkin's lymphoma (NHL) have not been systematically investigated. So, we investigated the percentage of MDSC subsets in 78 newly diagnosed NHL patients by flow cytometry. The results showed that all MDSC subsets increased in NHL patients compared with healthy donors. Notably, MDSCs, monocytic MDSCs, and CD14 + CD66b + MDSCs significantly increased in NHL patients compared with those with lymphadenitis donors. polymorphonuclear MDSCs (PMN-MDSCs), early-stage MDSCs (e-MDSCs), and the International Prognostic Index were independent risk factors for poor clinical efficacy and were involved in constructing the nomogram for predicting clinical efficacy. Progression-free survival (PFS) was significantly shorter in patients with high level of MDSC subsets, and PMN-MDSCs emerged as an independent prognostic factor for PFS. PMN-MDSCs, e-MDSCs, and the International Prognostic Index were involved in constructing the nomogram for predicting PFS. Patients with a higher percentage of MDSCs, PMN-MDSCs, e-MDSCs, and CD14 + CD66b + MDSCs experienced a shorter overall survival compared with those with lower percentages. In addition, research on mechanisms found that T cell function was suppressed and mediated by the expansion of MDSCs via involving arginase-1 and interleukin-10 in vitro and in vivo. In conclusion, our study demonstrates that the increased circulating MDSC subsets predict poor clinical efficacy and prognosis in NHL, potentially involving T cell suppression through MDSC subset expansion. These findings indicate the potential of MDSC subsets as comprehensive diagnostic, prognostic biomarkers, and therapeutic targets for NHL.