long_output.yaml

input_text: |-
  Title: Relationship between disease activity index and sleep disorders in children with inflammatory bowel diseases.
  Abstract: The aim of the study was to assess the prevalence of sleep disturbance in pediatric IBD patients and evaluate the relationship between clinical features of IBD, disease activity, inflammatory markers and quality of sleep. A total of 99 patients who were followed-up with the diagnosis of IBD (44 Crohn's disease (CD), 55 Ulcerative colitis (UC)) between 2015-2020 and 80 healthy controls were enrolled in the study. The clinical and demographic characteristics, laboratory parameters and disease activities were obtained from medical reports retrospectively. Pittsburgh sleep quality index (PSQI) was administered to all participants. PSQI score was significantly higher in patient group than the control group (P < 0.001). The sleep time of patient group, especially patients with UC was later than the control group (P = 0.008). Sleep duration was longer in control group than the patient group (P < 0.001). A positive strong correlation was obtained in disease activity index (r = 0.886; P < 0.001) and abdominal pain (r = 0.781; P < 0.001) with PSQI scores of CD patients. Disease activity index, rectal bleeding, diarrhea and number of stool had statistically significant positive strong correlation with PSQI scores of UC patients (P < 0.001). Pediatric Crohn's disease activity index and Pediatric ulcerative colitis activity index were the only independent risk factors affecting sleep disturbances (80% sensitivity and 91.67% specificity, 93.1% sensitivity and %96.15 specificity, respectively).   Conclusion: Increased disease activity has adverse effects on sleep quality. PSQI and PCDAI were strong tests for predicting sleep disorders in pediatric patients with IBD. What is Known: • Sleep disturbances are common complaint in inflammatory bowel disease (IBD), even in clinical remission. • Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality of patients. What is New: • PSQI and Pediatric Crohn Disease Activity index (PCDAI) were strong tests for predicting sleep disorders in pediatric patients with IBD. • PSQI and PCDAI scores correlated significantly with the severity of the sleep disturbances.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
  Keywords: Children; Crohn’s disease; Inflammatory bowel disease; Pittsburgh sleep quality index; Ulcerative colitis
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: disease activity; inflammatory markers
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - disease activity
    - inflammatory markers
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Current and Emerging Targeted Therapies for Ulcerative Colitis.
  Abstract: Ulcerative colitis is one of the main entities of inflammatory bowel diseases. The clinical course of this immune-mediated disorder is marked by unpredictable exacerbations and asymptomatic remission, causing lifelong morbidity. Optimized anti-inflammatory treatment is a prerequisite to not only restore the quality of life of the affected patients but also halt progressive bowel damage and reduce the risk for colitis-associated neoplasia. Advances in understanding the underlying immunopathogenesis of ulcerative colitis have led to the advent of targeted therapies that selectively inhibit crucial molecular structures or signaling pathways that perpetuate the inflammatory reaction.We will delineate the mode of action and summarize efficacy and safety data of current and emerging targeted therapies in ulcerative colitis, which encompasses representatives of the drug classes of antibodies, small molecules, and oligonucleotides. These substances have already been approved for induction and maintenance treatment or are being tested in late-stage clinical trials in moderately-to-severely active ulcerative colitis patients. These advanced therapies have enabled us to define and achieve novel therapeutic outcomes, such as clinical and endoscopic remission, histological remission, mucosal healing, and recently, also barrier healing as an emerging outcome measure.Established and emerging targeted therapies and monitoring modalities broaden our therapeutic armamentarium and have enabled us to define novel therapeutic outcomes that have the potential to modify the individual disease course of patients with ulcerative colitis.© 2023 S. Karger AG, Basel.
  Keywords: Anti-tumor necrosis factor antibody; IL-23; Molecular resistance; Therapy; Ulcerative colitis
raw_completion_output: |-
  genes: IL-23
  exposures: Anti-tumor necrosis factor antibody
  gene_exposures_relationships: IL-23 to Anti-tumor necrosis factor antibody
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  IL-23 to Anti-tumor necrosis factor antibody

  ===

extracted_object:
  genes:
    - HGNC:15488
  exposures:
    - Anti-tumor necrosis factor antibody
  gene_exposures_relationships:
    - molecular_activity: IL-23
      gene: Anti-tumor necrosis factor antibody
named_entities:
  - id: HGNC:15488
    label: IL-23
input_text: |-
  Title: Intrahepatic cholangiocarcinoma in patients with primary sclerosing cholangitis and ulcerative colitis: Two case reports.
  Abstract: Primary sclerosing cholangitis (PSC) is an extraintestinal manifestation of ulcerative colitis (UC). PSC is a well-known risk factor for intrahepatic cholangiocarcinoma (ICC), and ICC is known to have a poor prognosis.We present two cases of ICC in patients with PSC associated with UC. In the first case, a tumor was found by magnetic resonance imaging (MRI) in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain. The second patient was asymptomatic, but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC. ICC was strongly suspected by computed tomography and MRI in both cases, and surgery was performed, but unfortunately, the first patient died of ICC recurrence 16 mo postoperatively, and the second patient died of liver failure 14 mo postoperatively.Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
  Keywords: Case report; Hepatic lobectomy; Inflammatory bowel disease; Intrahepatic cholangiocarcinoma; Primary sclerosing cholangitis; Ulcerative colitis
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: primary sclerosing cholangitis (PSC), ulcerative colitis (UC)
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - primary sclerosing cholangitis (PSC), ulcerative colitis (UC)
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Surgical management of duodenal Crohn's disease.
  Abstract: The case of Crohn's disease involving the duodenum is rare, and its surgical management requires a thorough understanding.To investigate the surgical management of duodenal Crohn's disease.We systematically reviewed patients diagnosed with duodenal Crohn's disease who underwent surgery in the Department of Geriatrics Surgery of the Second Xiangya Hospital of Central South University from January 1, 2004, to August 31, 2022. The general information, surgical procedures, prognosis, and other information of these patients were collected and summarized.A total of 16 patients were diagnosed with duodenal Crohn's disease, where 6 cases had primary duodenal Crohn's disease, and 10 had secondary duodenal Crohn's disease. Among patients with primary disease, 5 underwent duodenal bypass and gastrojejunostomy, and 1 received pancreaticoduodenectomy. Among those with a secondary disease, 6 underwent closure of duodenal defect and colectomy, 3 received duodenal lesion exclusion and right hemicolectomy, and 1 underwent duodenal lesion exclusion and double-lumen ileostomy.Crohn's disease involving the duodenum is a rare condition. Different surgical management should be applied for patients with Crohn's disease presenting with different clinical manifestations.©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
  Keywords: Crohn’s disease; Duodenum; Inflammatory bowel disease; Surgical treatment
raw_completion_output: |-
  genes: N/A
  exposures: surgical management
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - surgical management
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: Editorial: Game changers in inflammatory bowel diseases, volume II.
  Abstract: 
  Keywords: EIM; IBD; markers; systemic inflammation; tailored therapy
raw_completion_output: 'genes: Not mentioned in the text'
prompt: |+
  From the text below, extract the following entities in the following format:

  genes: <semicolon-separated list of genes>
  exposures: <a chemical or molecule whose direct or indirect effects cause one or more entities to experience biological change>
  gene_exposures_relationships: <semicolon-separated list of gene to molecular activity relationships>


  Text:
  Title: Editorial: Game changers in inflammatory bowel diseases, volume II.
  Abstract: 
  Keywords: EIM; IBD; markers; systemic inflammation; tailored therapy

  ===

extracted_object:
  genes:
    - Not mentioned in the text
input_text: |-
  Title: Administration of Bifidobacterium pseudolongum suppresses the increase of colonic serotonin and alleviates symptoms in dextran sodium sulfate-induced colitis in mice.
  Abstract: Previous studies suggested that altered gut serotonin (5-HT) signaling is implicated in the pathophysiology of inflammatory bowel disease (IBD). Indeed, 5-HT administration reportedly exacerbated the severity of murine dextran sodium sulfate (DSS)-induced colitis that mimics human IBD. Our recent study suggested that Bifidobacterium pseudolongum, one of the most predominant bifidobacterial species in various mammals, reduces the colonic 5-HT content in mice. The present study thus tested whether the administration of B. pseudolongum prevents DSS-induced colitis in mice. Colitis was induced by administering 3% DSS in drinking water in female BALB/c mice, and B. pseudolongum (109 CFU/day) or 5-aminosalicylic acid (5-ASA, 200 mg/kg body weight) was intragastrically administered once daily throughout the experimental period. B. pseudolongum administration reduced body weight loss, diarrhea, fecal bleeding, colon shortening, spleen enlargement, and colon tissue damage and increased colonic mRNA levels of cytokine genes (Il1b, Il6, Il10, and Tnf) almost to an extent similar to 5-ASA administration in DSS-treated mice. B. pseudolongum administration also reduced the increase of colonic 5-HT content, whereas it did not alter the colonic mRNA levels of genes that encode the 5-HT synthesizing enzyme, 5-HT reuptake transporter, 5-HT metabolizing enzyme, and tight junction-associated proteins. We propose that B. pseudolongum is as beneficial against murine DSS-induced colitis as the widely used anti-inflammatory agent 5-ASA. However, further studies are needed to clarify the causal relationship between the reduced colonic 5-HT content and reduced severity of DSS-induced colitis caused by B. pseudolongum administration.©2023 BMFH Press.
  Keywords: Bifidobacterium pseudolongum; dextran sodium sulfate (DSS)-induced colitis; erotonin; inflammation
raw_completion_output: |-
  genes: Il1b; Il6; Il10; Tnf
  exposures: Bifidobacterium pseudolongum; dextran sodium sulfate (DSS); 5-aminosalicylic acid (5-ASA)
  gene_exposures_relationships: Bifidobacterium pseudolongum - reduction of colonic 5-HT content; Bifidobacterium pseudolongum - prevention of DSS-induced colitis
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Bifidobacterium pseudolongum - prevention of DSS-induced colitis

  ===

extracted_object:
  genes:
    - HGNC:5992
    - HGNC:6018
    - HGNC:5962
    - HGNC:11892
  exposures:
    - Bifidobacterium pseudolongum
    - dextran sodium sulfate (DSS)
    - 5-aminosalicylic acid (5-ASA)
  gene_exposures_relationships:
    - molecular_activity: reduction
      gene: colonic 5-HT
    - molecular_activity: prevention of DSS-induced colitis
      gene: Bifidobacterium pseudolongum
named_entities:
  - id: HGNC:5992
    label: Il1b
  - id: HGNC:6018
    label: Il6
  - id: HGNC:5962
    label: Il10
  - id: HGNC:11892
    label: Tnf
input_text: |-
  Title: A Systematic Review of Self-Management Interventions for Patients with Inflammatory Bowel Disease.
  Abstract: Previous studies have reported the effectiveness of inflammatory bowel disease (IBD) self-management. However, it is unclear which types of self-management interventions are effective. We conducted a systematic literature review to clarify the status and efficacy of self-management interventions for IBD.Searches were performed in databases including Embase, Medline, and Cochrane Library. Randomized, controlled studies of interventions in adult human participants with IBD involving a self-management component published in English from 2000 to 2020 were included. Studies were stratified based on study design, baseline demographic characteristics, methodological quality, and how outcomes were measured and analyzed for statistically significant improvements in outcomes, such as psychological health, quality of life, and healthcare resource usage.Among 50 studies included, 31 considered patients with IBD and 14 and 5 focused on patients with ulcerative colitis and Crohn's disease, respectively. Improvements in an outcome were reported in 33 (66%) studies. Most of the interventions that significantly improved an outcome index were based on symptom management and many of these were also delivered in combination with provision of information. We also note that among effective interventions, many were conducted with individualized and patient-participatory activities, and multidisciplinary healthcare practitioners were responsible for delivery of the interventions.Ongoing interventions that focus on symptom management with provision of information may support self-management behavior in patients with IBD. A participatory intervention targeting individuals was suggested to be an effective intervention method.© 2023 The Author(s). Published by S. Karger AG, Basel.
  Keywords: Inflammatory bowel disease; Quality of life; Remote monitoring; Self-management; Symptom management
raw_completion_output: |-
  genes: Not mentioned
  exposures: Not mentioned
  gene_exposures_relationships: Not mentioned
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Not mentioned

  ===

extracted_object:
  genes:
    - Not mentioned
  exposures:
    - Not mentioned
  gene_exposures_relationships:
    - molecular_activity: Not mentioned
      gene: Not mentioned
input_text: |-
  Title: Construction of an Explanatory Model for Quality of Life in Outpatients with Ulcerative Colitis.
  Abstract: To date, no studies have reported explanatory models of health-related quality of life (HRQoL) in patients with ulcerative colitis. Therefore, this study aimed to examine HRQoL and its related factors in outpatients with ulcerative colitis to construct an explanatory model.We conducted a cross-sectional survey at a clinic in Japan. The HRQoL was evaluated using the 32-item Inflammatory Bowel Disease Questionnaire. We extracted explanatory variables of HRQoL from demographic, physical, psychological, and social factors reported in previous studies and created a predictive explanatory model. The relationship between explanatory variables and the questionnaire total score was examined using Spearman's rank correlation coefficient, the Mann-Whitney test, or the Kruskal-Wallis test. We conducted multiple regression and path analyses to examine the effect of explanatory variables on the total score.We included 203 patients. Variables that were associated with the total score were the partial Mayo score (r = -0.451), treatment side effects (p = 0.004), the Hospital Anxiety and Depression Scale-Anxiety score (r = -0.678), the Hospital Anxiety and Depression Scale-Depression score (r = -0.528), and the availability of an advisor during difficult times (p = 0.001). The model included the partial Mayo score, treatment side effects, the Hospital Anxiety and Depression Scale-Anxiety score, and the availability of an advisor during difficult times as explanatory variables of the total score that showed the best goodness-of-fit (adjusted R2 = 0.597). The anxiety score exerted the greatest negative effect on the questionnaire total score (β = -0.586), followed by the partial Mayo score (β = -0.373), treatment side effects (β = 0.121), and availability of an advisor during difficult times (β = -0.101).Psychological symptoms exerted the strongest direct effect on HRQoL in outpatients with ulcerative colitis and mediated the relationship between social support and HRQoL. Nurses should listen carefully to the concerns and anxieties of patients to ensure that a social support system is provided by leveraging multidisciplinary collaborations.© 2023 The Author(s). Published by S. Karger AG, Basel.
  Keywords: Psychological symptoms; Quality of life; Ulcerative colitis
raw_completion_output: |-
  genes: 

  exposures: 

  gene_exposures_relationships:
prompt: |+
  From the text below, extract the following entities in the following format:

  genes: <semicolon-separated list of genes>
  exposures: <a chemical or molecule whose direct or indirect effects cause one or more entities to experience biological change>
  gene_exposures_relationships: <semicolon-separated list of gene to molecular activity relationships>


  Text:
  Title: Construction of an Explanatory Model for Quality of Life in Outpatients with Ulcerative Colitis.
  Abstract: To date, no studies have reported explanatory models of health-related quality of life (HRQoL) in patients with ulcerative colitis. Therefore, this study aimed to examine HRQoL and its related factors in outpatients with ulcerative colitis to construct an explanatory model.We conducted a cross-sectional survey at a clinic in Japan. The HRQoL was evaluated using the 32-item Inflammatory Bowel Disease Questionnaire. We extracted explanatory variables of HRQoL from demographic, physical, psychological, and social factors reported in previous studies and created a predictive explanatory model. The relationship between explanatory variables and the questionnaire total score was examined using Spearman's rank correlation coefficient, the Mann-Whitney test, or the Kruskal-Wallis test. We conducted multiple regression and path analyses to examine the effect of explanatory variables on the total score.We included 203 patients. Variables that were associated with the total score were the partial Mayo score (r = -0.451), treatment side effects (p = 0.004), the Hospital Anxiety and Depression Scale-Anxiety score (r = -0.678), the Hospital Anxiety and Depression Scale-Depression score (r = -0.528), and the availability of an advisor during difficult times (p = 0.001). The model included the partial Mayo score, treatment side effects, the Hospital Anxiety and Depression Scale-Anxiety score, and the availability of an advisor during difficult times as explanatory variables of the total score that showed the best goodness-of-fit (adjusted R2 = 0.597). The anxiety score exerted the greatest negative effect on the questionnaire total score (β = -0.586), followed by the partial Mayo score (β = -0.373), treatment side effects (β = 0.121), and availability of an advisor during difficult times (β = -0.101).Psychological symptoms exerted the strongest direct effect on HRQoL in outpatients with ulcerative colitis and mediated the relationship between social support and HRQoL. Nurses should listen carefully to the concerns and anxieties of patients to ensure that a social support system is provided by leveraging multidisciplinary collaborations.© 2023 The Author(s). Published by S. Karger AG, Basel.
  Keywords: Psychological symptoms; Quality of life; Ulcerative colitis

  ===

extracted_object: {}
input_text: |-
  Title: Smoking Is Not an Independent Risk Factor for Surgery in Patients with Crohn's Disease on Biologic Therapy.
  Abstract: The development and course of inflammatory bowel disease appear to be influenced by environmental factors. Particularly, smoking has been shown to assume a harmful role in Crohn's disease (CD) and a protective role in ulcerative colitis. This study aims to examine the effect of smoking on need for surgery in patients with moderate to severe CD receiving biologic therapy.This was a retrospective study of adult patients with CD at a University Medical Center over a 20-year period.A total of 251 patients were included (mean age 36.0 ± 15.0; 70.1% males; current, former, and nonsmokers: 44.2%, 11.6%, and 43.8%, respectively). Mean duration on biologics was 5.0 ± 3.1 years (>2/3 received anti-TNFs, followed by ustekinumab in 25.9%) and a third of patients (29.5%) received more than one biologic. Disease-related surgeries (abdominal, perianal, or both) occurred in 97 patients (38.6%): 50 patients had surgeries prior to starting biologics only, 41 had some surgeries after, and 6 had insufficient information. There was no significant difference in surgeries between ever-smokers (current or previous) versus nonsmokers in the overall study group. On logistic regression, the odds of having any CD surgery were higher in patients with longer disease duration (OR = 1.05, 95% CI = 1.01, 1.09) and in those receiving more than one biologic (OR = 2.31, 95% CI = 1.16, 4.59). However, among patients who had surgery prior to biologic therapy, smokers were more likely to have perianal surgery compared to nonsmokers (OR = 10.6, 95% CI = 2.0, 57.4; p = 0.006).In biologic-naive CD patients requiring surgery, smoking is an independent predictor of perianal surgery. Smoking, however, is not an independent risk factor for surgery in this cohort after starting biologics. The risk of surgery in those patients is primarily associated with disease duration and the use of more than one biologic.© 2023 The Author(s). Published by S. Karger AG, Basel.
  Keywords: Abdominal surgery; Adalimumab; Anti-Tumor necrosis factor; Crohn’s disease; Fistula; Infliximab; Perianal; Tobacco; Ustekinumab; Vedolizumab
raw_completion_output: |-
  genes: None mentioned in the text.
  exposures: smoking
  gene_exposures_relationships: None mentioned in the text.
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text.

  ===

extracted_object:
  genes:
    - None mentioned in the text.
  exposures:
    - NCIT:C154329
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text.
      gene: None mentioned in the text.
named_entities:
  - id: NCIT:C154329
    label: smoking
input_text: |-
  Title: Gene-based microbiome representation enhances host phenotype classification.
  Abstract: With the concomitant advances in both the microbiome and machine learning fields, the gut microbiome has become of great interest for the potential discovery of biomarkers to be used in the classification of the host health status. Shotgun metagenomics data derived from the human microbiome is composed of a high-dimensional set of microbial features. The use of such complex data for the modeling of host-microbiome interactions remains a challenge as retaining de novo content yields a highly granular set of microbial features. In this study, we compared the prediction performances of machine learning approaches according to different types of data representations derived from shotgun metagenomics. These representations include commonly used taxonomic and functional profiles and the more granular gene cluster approach. For the five case-control datasets used in this study (Type 2 diabetes, obesity, liver cirrhosis, colorectal cancer, and inflammatory bowel disease), gene-based approaches, whether used alone or in combination with reference-based data types, allowed improved or similar classification performances as the taxonomic and functional profiles. In addition, we show that using subsets of gene families from specific functional categories of genes highlight the importance of these functions on the host phenotype. This study demonstrates that both reference-free microbiome representations and curated metagenomic annotations can provide relevant representations for machine learning based on metagenomic data. IMPORTANCE Data representation is an essential part of machine learning performance when using metagenomic data. In this work, we show that different microbiome representations provide varied host phenotype classification performance depending on the dataset. In classification tasks, untargeted microbiome gene content can provide similar or improved classification compared to taxonomical profiling. Feature selection based on biological function also improves classification performance for some pathologies. Function-based feature selection combined with interpretable machine learning algorithms can generate new hypotheses that can potentially be assayed mechanistically. This work thus proposes new approaches to represent microbiome data for machine learning that can potentiate the findings associated with metagenomic data.
  Keywords: endocannabinoidome; feature selection; gene clusters; gut-brain axis; interpretable models; machine learning; metabolic health; metagenomics; microbiome; shotgun microbiome
raw_completion_output: |-
  genes: gene-based approaches, gene families
  exposures: gut microbiome, taxonomic and functional profiles, gene cluster approach, reference-based data types, metagenomic annotations, metagenomic data
  gene_exposures_relationships: reference-based data types - gene-based approaches; gene families - specific functional categories of genes
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  gene families - specific functional categories of genes

  ===

extracted_object:
  genes:
    - gene-based approaches, gene families
  exposures:
    - gut microbiome, taxonomic and functional profiles, gene cluster approach, reference-based
      data types, metagenomic annotations, metagenomic data
  gene_exposures_relationships:
    - molecular_activity: reference-based data types
      gene: gene-based approaches
    - molecular_activity: specific functional categories of genes
      gene: gene families
input_text: |-
  Title: Development of the intestinal microbiome in cystic fibrosis in early life.
  Abstract: Cystic fibrosis (CF) is a heritable disease that causes altered physiology at mucosal sites; these changes result in chronic infections in the lung, significant gastrointestinal complications as well as dysbiosis of the gut microbiome, although the latter has been less well explored. Here, we describe the longitudinal development of the gut microbiome in a cohort of children with CF (cwCF) from birth through early childhood (0-4 years of age) using 16S rRNA gene amplicon sequencing of stool samples as a surrogate for the gut microbiota. Similar to healthy populations, alpha diversity of the gut microbiome increases significantly with age, but diversity plateaus at ~2 years of age for this CF cohort. Several taxa that have been associated with dysbiosis in CF change with age toward a more healthy-like composition; notable exceptions include Akkermansia, which decreases with age, and Blautia, which increases with age. We also examined the relative abundance and prevalence of nine taxa associated with CF lung disease, several of which persist across early life, highlighting the possibility of the lung being seeded directly from the gut early in life. Finally, we applied the Crohn's Dysbiosis Index to each sample, and found that high Crohn's-associated dysbiosis early in life (<2 years) was associated with significantly lower Bacteroides in samples collected from 2 to 4 years of age. Together, these data comprise an observational study that describes the longitudinal development of the CF-associated gut microbiota and suggest that early markers associated with inflammatory bowel disease may shape the later gut microbiota of cwCF. IMPORTANCE Cystic fibrosis is a heritable disease that disrupts ion transport at mucosal surfaces, causing a buildup of mucus and dysregulation of microbial communities in both the lungs and the intestines. Persons with CF are known to have dysbiotic gut microbial communities, but the development of these communities over time beginning at birth has not been thoroughly studied. Here, we describe an observation study following the development of the gut microbiome of cwCF throughout the first 4 years of life, during the critical window of both gut microbiome and immune development. Our findings indicate the possibility of the gut microbiota as a reservoir of airway pathogens and a surprisingly early indication of a microbiota associated with inflammatory bowel disease.
  Keywords: Crohn’s disease; cystic fibrosis; gut; microbiome
raw_completion_output: |-
  genes: N/A
  exposures: Crohn's disease; cystic fibrosis
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - Crohn's disease
    - cystic fibrosis
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: Frail Phenotype in Patients With Inflammatory Bowel Disease.
  Abstract: 
  Keywords: 
raw_completion_output: |-
  genes: 
  exposures: 
  gene_exposures_relationships:
prompt: |+
  From the text below, extract the following entities in the following format:

  genes: <semicolon-separated list of genes>
  exposures: <a chemical or molecule whose direct or indirect effects cause one or more entities to experience biological change>
  gene_exposures_relationships: <semicolon-separated list of gene to molecular activity relationships>


  Text:
  Title: Frail Phenotype in Patients With Inflammatory Bowel Disease.
  Abstract: 
  Keywords: 

  ===

extracted_object: {}
input_text: |-
  Title: Physical activity, quality of diet and bone mineral density in patients with inflammatory bowel disease.
  Abstract: The aim of this study was to find an association between moderate, vigorous and total physical activity (PA); diet quality; and bone mineral density (BMD) among patients suffering from inflammatory bowel disease (IBD).We enrolled 54 IBD patients, including those with Crohn's disease (CD) and ulcerative colitis (UC), and 24 healthy adults. All subjects completed the Questionnaire of Eating Behaviour based on which prohealthy and nonhealthy diet indexes were calculated, and the questionnaire included questions from the International Physical Activity Questionnaire. Prohealthy and nonhealthy diet indexes were divided into low-, medium- and high scores. BMD and T- and Z-scores of the lumbar spine (L1-L4) and femoral neck (FN) were assessed using dual-energy X-ray absorptiometry method.BMD, T- and Z-scores of the FN and the Z-score of L1-L4 were significantly lower among patients with CD and UC than healthy controls. We did not find any differences in the time of PA among CD, UC and control groups (CG). The prohealthy diet index was higher among healthy subjects than the CD and UC groups. The nonhealthy diet index was lower among UC patients compared with the CG or CD patients. Prohealthy diet index positively correlated with BMD and T- and Z-scores of L1-L4 and FN in IBD. The prohealthy diet index correlated negatively with C-reactive protein and positively with body mass index. The prohealthy diet index correlated only with total PA in the CD group.A well-balanced diet and proper PA may decrease the risk of osteoporosis in IBD, so education of patients referring to nutrition and PA is needed.© 2023 British Dietetic Association.
  Keywords: bone mineral density; diet quality; inflammatory bowel disease; osteoporosis; physical activity
raw_completion_output: |-
  genes: N/A
  exposures: diet quality; physical activity
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - diet quality
    - NCIT:C17708
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
named_entities:
  - id: NCIT:C17708
    label: physical activity
input_text: |-
  Title: Sweet Syndrome Associated with Active Inflammatory Bowel Disease: A Case Series of a Rare Extra-intestinal Manifestation.
  Abstract: Cutaneous extra-intestinal manifestations (EIM) occur in up to 20% of patients with IBD. Information about Sweet syndrome (SS)'s clinical course as a rare cutaneous EIM in IBD is limited to case reports. We present the largest retrospective cohort on the occurrence and management of SS in IBD.Electronic medical records and paper charts since 1980 were retrospectively reviewed at a large quaternary medical center to identify all adult IBD patients with histopathology-proven SS. Patient characteristics and clinical outcomes were evaluated.25 IBD patients with SS were identified; 3 patients were assessed to have AZA-induced SS. The majority of SS patients were female. Median age at diagnosis was 47 years (IQR 33-54 years) and SS appeared at a median of 6.4 years after IBD diagnosis. IBD patients with SS had a high rate of complicated IBD phenotypes (75% extensive colitis in UC and 73% stricturing or penetrating disease in CD, with 100% colonic involvement), as well as frequent co-occurring EIMs (60%). SS correlated with global IBD disease activity. Corticosteroids were an effective therapy for SS in IBD. Recurrence rate of SS was 36%.Contrary to previous case reports, SS was a cutaneous EIM occurring late after diagnosis of IBD in our cohort, with occurrences paralleling global IBD disease activity. Although AZA-induced and IBD-associated SS were both effectively treated with corticosteroids, distinguishing them is relevant for future IBD treatment strategies.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
  Keywords: Azathioprine; Colitis; Cutaneous manifestations; Extra-intestinal manifestation; Inflammatory bowel disease; Sweet syndrome
raw_completion_output: |-
  genes: Not mentioned in the text
  exposures: Azathioprine
  gene_exposures_relationships: Azathioprine -> Sweet syndrome
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Azathioprine -> Sweet syndrome

  ===

extracted_object:
  genes:
    - Not mentioned in the text
  exposures:
    - Azathioprine
  gene_exposures_relationships:
    - molecular_activity: Azathioprine
      gene: Sweet syndrome
input_text: |-
  Title: Decreased Risk of Preeclampsia in Women with Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy.
  Abstract: Evidence suggests that upregulation of tumor necrosis factor-alpha (TNF-α) plays a role in immune dysregulation in both preeclampsia and inflammatory bowel disease (IBD).We aimed to investigate whether anti-TNF therapy during pregnancy decreases the risk of preeclampsia in women with IBD.The study population included women with IBD and pregnancies who were followed at a tertiary care center from 2007 to 2021. Cases of preeclampsia were compared with controls with a normotensive pregnancy. Data on patient demographics, disease type and activity, pregnancy complications, and additional risk factors for preeclampsia were collected. The association between anti-TNF therapy and preeclampsia was analyzed using univariate analysis and multivariate logistic regression.Women with preeclampsia were more likely to have a preterm delivery (44% vs. 12%, p < 0.001). More women without preeclampsia were exposed to anti-TNF therapy during pregnancy than women with preeclampsia (55% vs. 30%, p = 0.029). The majority of women (32/44) on anti-TNF therapy, either adalimumab or infliximab, continued to have some degree of exposure during the third trimester. Though not significant, multivariate analysis showed a trend towards a protective effect of anti-TNF therapy against developing preeclampsia if exposed during the third trimester (OR 0.39; 95% CI 0.14-1.12, p = 0.08).In this study, anti-TNF therapy exposure was higher in IBD patients who did not develop preeclampsia than in those who did. While not significant, there was a trend towards a protective effect of anti-TNF therapy against preeclampsia if exposed during the third trimester.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
  Keywords: Anti-TNF; Crohn’s disease; Inflammatory bowel disease; Preeclampsia; Pregnancy; TNF-α; Ulcerative colitis
raw_completion_output: |-
  genes: TNF-α

  exposures: anti-TNF therapy

  gene_exposures_relationships: TNF-α to anti-TNF therapy
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  TNF-α to anti-TNF therapy

  ===

extracted_object:
  genes:
    - TNF-α
  exposures:
    - anti-TNF therapy
  gene_exposures_relationships:
    - molecular_activity: TNF-α
      gene: anti-TNF therapy
input_text: |-
  Title: Inflammatory bowel disease is not linked to a higher rate of adverse events in colonoscopy - a nationwide population-based study in Sweden.
  Abstract: Inflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide population-based Swedish study.Data from 969,532 colonoscopies, including 164,012 (17%) on inflammatory bowel disease patients, between 2003 and 2019 were retrieved from the National Patient Registers. ICD-10 codes for bleeding (T810) and perforation (T812) within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anesthesia, age, sex, endoscopic procedures and antithrombotic treatment were associated with higher odds for bleeding and perforation.Bleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding (Odds Ratio 0.66, p < 0.001) and perforation (Odds Ratio 0.79, p < 0.033) were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient inflammatory bowel disease colonoscopies compared with outpatient. The odds for bleeding but not perforation increased between 2003 to 2019. General anesthesia was associated with double the odds for perforation.Individuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, inpatient setting was associated with more adverse events, especially in inflammatory bowel disease status. General anesthesia was associated with a greater risk of perforation.© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.
  Keywords: Gastrointestinal Bleeding; Inflammatory Bowel Disease; Perforation
raw_completion_output: |-
  genes: 

  exposures: inflammatory bowel disease, general anesthesia, antithrombotic treatment

  gene_exposures_relationships: inflammatory bowel disease - bleeding, perforation; general anesthesia - perforation
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  general anesthesia - perforation

  ===

extracted_object:
  exposures:
    - inflammatory bowel disease, general anesthesia, antithrombotic treatment
  gene_exposures_relationships:
    - molecular_activity: inflammatory bowel disease
      gene: perforation
    - molecular_activity: general anesthesia
      gene: perforation
input_text: |-
  Title: Major Adverse Cardiovascular Events by Baseline Cardiovascular Risk in Patients with Ulcerative Colitis Treated with Tofacitinib: Data from the OCTAVE Clinical Programme.
  Abstract: Patients with inflammatory bowel disease have increased risk of atherosclerotic cardiovascular [CV] disease [ASCVD]. Tofacitinib is an oral small molecule Janus kinase inhibitor for treatment of ulcerative colitis [UC]. We report major adverse CV events [MACE] in the UC OCTAVE programme, stratified by baseline CV risk.Rates of MACE were analysed by baseline [first tofacitinib exposure] CV risk profile: prior ASCVD, or 10-year ASCVD risk categories [low, borderline, intermediate, high].Of 1157 patients [2814.4 patient-years' exposure; ≤7.8 years' tofacitinib treatment], 4% had prior ASCVD and 83% had no prior ASCVD and low-borderline baseline 10-year ASCVD risk. Eight patients [0.7%] developed MACE; one had prior ASCVD. Incidence rates [unique patients with events/100 patient-years of exposure; 95% confidence intervals] for MACE were: 0.95 [0.02-5.27] in patients with prior ASCVD; and 1.81 [0.05-10.07], 1.54 [0.42-3.95], 0.00 [0.00-2.85], and 0.09 [0.01-0.32] in patients without prior ASCVD and with high, intermediate, borderline, and low baseline 10year ASCVD risk, respectively. For the 5/7 patients with MACE and without prior ASCVD, 10year ASCVD risk scores were numerically higher [>1%] prior to MACE versus at baseline, primarily due to increasing age.Most patients receiving tofacitinib in the UC OCTAVE programme had low baseline 10-year ASCVD risk. MACE were more frequent in patients with prior ASCVD and higher baseline CV risk. This analysis demonstrates potential associations between baseline CV risk and MACE in patients with UC, suggesting CV risk should be assessed individually in clinical practice.© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.
  Keywords: cardiovascular risk; inflammatory bowel disease; ulcerative colitis
raw_completion_output: |-
  genes: None mentioned in the given text
  exposures: Tofacitinib
  gene_exposures_relationships: None mentioned in the given text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the given text

  ===

extracted_object:
  genes:
    - None mentioned in the given text
  exposures:
    - Tofacitinib
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the given text
      gene: None mentioned in the given text
input_text: |-
  Title: Relevance of sonographic parameters for inflammatory bowel disease in children.
  Abstract: Intestinal ultrasound (IUS) is widely used as the first exam in patients with suspected inflammatory bowel disease (IBD). This study investigated the accuracy of several IUS parameters, including increased bowel wall thickening (BWT), in detecting IBD in a paediatric population.The study included an unselected series of 113 patients aged 2-18 years (mean age 10.8 years, 65 male), referred for recurrent abdominal pain or altered bowel habits, without known organic diseases, to perform an IUS as first investigation of a diagnostic workup. Patients with full systematic IUS examination, clinical and biochemical exams, and ileocolonoscopy or an uneventful follow-up at least one year follow up were eligible.23 IBD patients (20.4%; 8 ulcerative colitis, 12 Crohn's disease and 3 indeterminate colitis) were diagnosed. We found that increased BWT > 3 mm (OR 5.4), altered IUS bowel pattern (IUS-BP, OR 9.8) and mesenteric hypertrophy (MH, OR 5.2) accurately identified IBD at the multivariate analysis. IUS-BP, MH and BWT > 3 mm had a sensitivity of 78.3%, 65.2% and 69.6% and a specificity of 93.3%, 92.2% and 96.7%, respectively. The combination of these three alterations increased the specificity up to 100%, whilst decreased sensitivity to 56.5%.Among several US parameters suggestive of IBD, the increased BWT, MH and altered echopattern are independent predictors of IBD. The ultrasonographic diagnosis of IBD could be more accurate if relied on combination of different sonographic parameters, than on the sole BWT evaluation.© 2023. The Author(s).
  Keywords: Bowel wall thickness; Children; Fecal calprotectin; Inflammatory bowel diseases; Intestinal ultrasound; Ultrasound
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: Fecal calprotectin
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - Fecal calprotectin
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Fecal acute phase proteins in cats with chronic enteropathies.
  Abstract: Chronic enteropathies (CE) are common in cats and reliable biomarkers that can distinguish different causes and predict or monitor response to treatment are currently lacking.To evaluate certain acute phase proteins in feces that could potentially be used as biomarkers in cats with CE.Twenty-eight cats with either inflammatory bowel disease (IBD; n = 13), food-responsive enteropathy (FRE; n = 3) or small cell gastrointestinal lymphoma (SCGL; n = 12) and 29 healthy control cats were prospectively enrolled.Fecal concentrations of haptoglobin, alpha-1-acid-glycoprotein (AGP), pancreatitis-associated protein-1 (PAP-1), ceruloplasmin, and C-reactive protein (CRP) were measured using Spatial Proximity Analyte Reagent Capture Luminescence (SPARCL) immunoassays before and after initiation of treatment. Cats were treated with diet and/or prednisolone (IBD cats), plus chlorambucil (SCGL cats).Compared with controls, median fecal AGP concentrations were significantly lower (25.1 vs 1.8 μg/g; P = .003) and median fecal haptoglobin (0.17 vs 0.5 μg/g), PAP-1 (0.04 vs 0.4 μg/g) and ceruloplasmin (0.15 vs 4.2 μg/g) concentrations were significantly higher (P < .001) in cats with CE. Median fecal AGP concentrations were significantly lower (P = .01) in cats with IBD and FRE (0.6 μg/g) compared with cats with SCGL (10.75 μg/g). A significant reduction was found in CE cats after treatment for median fecal ceruloplasmin concentrations (6.36 vs 1.16 μg/g; P = .04).Fecal AGP concentration shows promise to differentiate cats with SCGL from cats with IBD and FRE. Fecal ceruloplasmin concentrations may be useful to objectively monitor response to treatment in cats with CE.© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
  Keywords: AGP; PAP-1; ceruloplasmin; fecal biomarkers; haptoglobin
raw_completion_output: |-
  genes: 

  exposures: PAP-1; ceruloplasmin; haptoglobin; alpha-1-acid-glycoprotein (AGP); C-reactive protein (CRP)

  gene_exposures_relationships: PAP-1 to molecular activity; ceruloplasmin to molecular activity; haptoglobin to molecular activity; alpha-1-acid-glycoprotein (AGP) to molecular activity; C-reactive protein (CRP) to molecular activity
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  C-reactive protein (CRP) to molecular activity

  ===

extracted_object:
  exposures:
    - PAP-1
    - ceruloplasmin
    - haptoglobin
    - alpha-1-acid-glycoprotein (AGP)
    - C-reactive protein (CRP)
  gene_exposures_relationships:
    - molecular_activity: PAP-1
      gene: molecular activity
    - molecular_activity: exposure to a chemical toxin
      gene: ceruloplasmin
    - molecular_activity: molecular activity
      gene: haptoglobin
    - molecular_activity: molecular activity
      gene: HGNC:30889
    - molecular_activity: C-reactive protein (CRP)
      gene: molecular activity
named_entities:
  - id: HGNC:30889
    label: alpha-1-acid-glycoprotein (AGP)
input_text: |-
  Title: Does intestinal obstruction influence hypo-albuminemia: assessment of the physio-pathogenesis of protein-losing enteropathy with literature review.
  Abstract: Non-steroidal anti-inflammatory drug (NSAID) use may cause diaphragm-like lesions in the bowel. Although NSAID-enteropathy is among the causes of protein-losing enteropathy (PLE), intractable hypoalbuminemia is rare.Here, we discuss a case of NSAID-enteropathy with a diaphragm-like disease that presented with Protein Losing Enteropathy (PLE) rather than obstruction. The hypoalbuminemia recovered immediately after resection of the obstructive segment, despite ongoing annular ulcerations in the early postoperative period. Thus, it was not clear whether obstructive mechanisms influenced resistant hypoalbuminemia besides the ulcers. We also reviewed the English-written literature for "diaphragm-type lesion, NSAID-enteropathy, obstruction, and protein-losing enteropathy". We noted that the role of obstruction in the pathophysiology of PLE was not clear.As our case and a couple of cases reported in literature, slow-onset obstructive pathology seems to contribute to well-known factors: inflammatory response, exudation, tight-junction dysfunction, and increase in permeability in the physiopathology of NSAID-induced PLE. Factors such as distention-induced low-flow ischemia and reperfusion, cholecystectomy-related continuous bile flow, bacterial overgrowth-related bile deconjugation and concomitant inflammation are among other potential influencers. The possible role of a slow-onset obstructive pathology in the physiopathology of NSAID-induced and other PLE needs to be further elucidated.
  Keywords: 
raw_completion_output: |-
  genes: not mentioned in the text
  exposures: non-steroidal anti-inflammatory drug (NSAID)
  gene_exposures_relationships: not mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  not mentioned in the text

  ===

extracted_object:
  genes:
    - not mentioned in the text
  exposures:
    - CHEBI:35475
  gene_exposures_relationships:
    - molecular_activity: not mentioned in the text
      gene: not mentioned in the text
named_entities:
  - id: CHEBI:35475
    label: non-steroidal anti-inflammatory drug (NSAID)
input_text: |-
  Title: Comparison of infliximab with adalimumab in biologic-naïve patients with Crohn's disease: a single-center 13-year experience.
  Abstract: Long-term comparison studies between infliximab (IFX) and adalimumab (ADA) with or without immunomodulator therapy are still needed in Crohn's disease (CD). In this study, we evaluated IFX and ADA for long-term clinical effectiveness and safety in CD patients who had not previously received a biologic treatment.The data of adult CD patients were collected retrospectively between December 2007 and February 2021. We compared CD-related hospitalization, CD-related abdominal surgery, steroid use, and serious infections.Out of 224 CD patients, 101 started IFX first (median age: 38.12 years, 61.4% male), while 123 started ADA first (median age: 30.2 years, 64.2% male). The disease durations were 7.01 years and 6.91 years for IFX and ADA, respectively. There were no significant differences between the two groups with respect to age, gender, smoking, immunomodulator usage, and disease activity score at the onset of anti-TNF therapy (p>0.05). Overall, the median follow-up time was 2.36 and 1.86 years after starting anti-tumor necrosis factor-alpha (anti-TNF) therapy in the IFX and ADA groups, respectively. Steroid use (4.0% vs. 10.6%, p=0.109), hospitalization for CD (13.9% vs. 22.8%, p=0.127), abdominal surgery for CD (9.9% vs. 13.0%, p=0.608), and major infections (1.0% vs. 0.8%, p>0.999) did not differ significantly from one another. There were also no significant differences in the rates of these outcomes between concomitant immunomodulator therapy and monotherapy (p>0.05).In this study, we observed no significant differences in the long-term effectiveness and safety of IFX and ADA in biologic-naïve patients with CD.
  Keywords: 
raw_completion_output: |-
  genes: IFX, ADA, CD

  exposures: immunomodulator therapy, anti-TNF therapy

  gene_exposures_relationships: IFX - immunomodulator therapy; ADA - immunomodulator therapy; IFX - anti-TNF therapy; ADA - anti-TNF therapy
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  ADA - anti-TNF therapy

  ===

extracted_object:
  genes:
    - IFX, ADA, CD
  exposures:
    - immunomodulator therapy, anti-TNF therapy
  gene_exposures_relationships:
    - molecular_activity: immunomodulator therapy
      gene: IFX
    - molecular_activity: immunomodulator therapy
      gene: HGNC:186
    - molecular_activity: anti-TNF therapy
      gene: IFX
    - molecular_activity: anti-TNF therapy
      gene: HGNC:186
named_entities:
  - id: HGNC:186
    label: ADA
input_text: |-
  Title: Disease clearance in ulcerative colitis: Is the ultimate therapeutic target?
  Abstract: 
  Keywords: IBD; gastroenterology; inflammation; inflammatory bowel disease; ulcerative colitis
raw_completion_output: |-
  genes: none mentioned
  exposures: none mentioned
  gene_exposures_relationships: none mentioned
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  none mentioned

  ===

extracted_object:
  genes:
    - none mentioned
  exposures:
    - none mentioned
  gene_exposures_relationships:
    - molecular_activity: none mentioned
      gene: none mentioned
input_text: |-
  Title: Dissecting the effect of ileal faecal diversion on the intestine using single-cell sequencing.
  Abstract: Although ileal faecal diversion is commonly used in clinical settings, complications accompany it. Elucidating the intestinal changes caused by ileal faecal diversion will help resolve postoperative complications and elucidate the pathogenic mechanisms of associated intestinal disorders, such as Crohn's disease (CD). Therefore, our study aimed to provide new insights into the effects of ileal faecal diversion on the intestine and the potential mechanisms.Single-cell RNA sequencing was performed on proximal functional and paired distal defunctioned intestinal mucosae from three patients with ileal faecal diversion. We also performed in vitro cellular and animal experiments, tissue staining and analysed public datasets to validate our findings.We found that the epithelium in the defunctioned intestine tended to be immature, with defective mechanical and mucous barriers. However, the innate immune barrier in the defunctioned intestine was enhanced. Focusing on the changes in goblet cells, we demonstrated that mechanical stimulation promotes the differentiation and maturation of goblet cells through the TRPA1-ERK pathway, indicating that the absence of mechanical stimulation may be the main cause of defects in the goblet cells of the defunctioned intestine. Furthermore, we found obvious fibrosis with a pro-fibrotic microenvironment in the defunctioned intestine and identified that monocytes may be important targets for faecal diversion to alleviate CD.This study revealed the different transcription landscapes of various cell subsets and the potential underlying mechanisms within the defunctioned intestine, when compared to the functional intestine, based on the background of ileal faecal diversion. These findings provide novel insights for understanding the physiological and pathological roles of the faecal stream in the intestine.© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
  Keywords: Crohn's disease; TRPA1; fibrosis; ileal faecal diversion; intestinal goblet cells; single-cell RNA sequencing
raw_completion_output: |-
  genes: TRPA1
  exposures: ileal faecal diversion
  gene_exposures_relationships: TRPA1-ERK pathway; faecal diversion
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  faecal diversion

  ===

extracted_object:
  genes:
    - HGNC:497
  exposures:
    - ileal faecal diversion
  gene_exposures_relationships:
    - molecular_activity: TRPA1-ERK pathway
      gene: None
    - molecular_activity: exposure to a chemical toxin.
      gene: faecal diversion
named_entities:
  - id: HGNC:497
    label: TRPA1
input_text: |-
  Title: Diet high in linoleic acid dysregulates the intestinal endocannabinoid system and increases susceptibility to colitis in Mice.
  Abstract: Inflammatory bowel disease (IBD) is a multifactorial disease with increasing incidence in the U.S. suggesting that environmental factors, including diet, are involved. It has been suggested that excessive consumption of linoleic acid (LA, C18:2 omega-6), which must be obtained from the diet, may promote the development of IBD in humans. To demonstrate a causal link between LA and IBD, we show that a high fat diet (HFD) based on soybean oil (SO), which is comprised of ~55% LA, increases susceptibility to colitis in several models, including IBD-susceptible IL10 knockout mice. This effect was not observed with low-LA HFDs derived from genetically modified soybean oil or olive oil. The conventional SO HFD causes classical IBD symptoms including immune dysfunction, increased intestinal epithelial barrier permeability, and disruption of the balance of isoforms from the IBD susceptibility gene Hepatocyte Nuclear Factor 4α (HNF4α). The SO HFD causes gut dysbiosis, including increased abundance of an endogenous adherent invasive Escherichia coli (AIEC), which can use LA as a carbon source. Metabolomic analysis shows that in the mouse gut, even in the absence of bacteria, the presence of soybean oil increases levels of LA, oxylipins and prostaglandins. Many compounds in the endocannabinoid system, which are protective against IBD, are decreased by SO both in vivo and in vitro. These results indicate that a high LA diet increases susceptibility to colitis via microbial and host-initiated pathways involving alterations in the balance of bioactive metabolites of omega-6 and omega-3 polyunsaturated fatty acids, as well as HNF4α isoforms.
  Keywords: HNF4α; IBD; PUFAs; adherent invasive E.Coli; epithelial barrier function; gut microbiome; metabolomics; olive oil; oxylipins; soybean oil
raw_completion_output: |-
  genes: IL10, Hepatocyte Nuclear Factor 4α (HNF4α)
  exposures: linoleic acid (LA), soybean oil (SO), omega-6 and omega-3 polyunsaturated fatty acids, adherent invasive Escherichia coli (AIEC)
  gene_exposures_relationships: IL10 - linoleic acid (LA); Hepatocyte Nuclear Factor 4α (HNF4α) - linoleic acid (LA), soybean oil (SO)
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Hepatocyte Nuclear Factor 4α (HNF4α) - linoleic acid (LA), soybean oil (SO)

  ===

extracted_object:
  genes:
    - IL10, Hepatocyte Nuclear Factor 4α (HNF4α)
  exposures:
    - CHEBI:17351
  gene_exposures_relationships:
    - molecular_activity: CHEBI:17351
      gene: HGNC:5962
    - molecular_activity: exposure to a chemical toxin.
      gene: Hepatocyte Nuclear Factor 4α (HNF4α)
named_entities:
  - id: CHEBI:17351
    label: linoleic acid (LA), soybean oil (SO), omega-6 and omega-3 polyunsaturated
      fatty acids, adherent invasive Escherichia coli (AIEC)
  - id: HGNC:5962
    label: IL10
input_text: |-
  Title: A catalog of bacterial reference genomes from cultivated human oral bacteria.
  Abstract: The oral cavity harbors highly diverse communities of microorganisms. However, the number of isolated species and high-quality genomes is limited. Here we present a Cultivated Oral Bacteria Genome Reference (COGR), comprising 1089 high-quality genomes based on large-scale aerobic and anaerobic cultivation of human oral bacteria isolated from dental plaques, tongue, and saliva. COGR covers five phyla and contains 195 species-level clusters of which 95 include 315 genomes representing species with no taxonomic annotation. The oral microbiota differs markedly between individuals, with 111 clusters being person-specific. Genes encoding CAZymes are abundant in the genomes of COGR. Members of the Streptococcus genus make up the largest proportion of COGR and many of these harbor entire pathways for quorum sensing important for biofilm formation. Several clusters containing unknown bacteria are enriched in individuals with rheumatoid arthritis, emphasizing the importance of culture-based isolation for characterizing and exploiting oral bacteria.© 2023. The Author(s).
  Keywords: 
raw_completion_output: |-
  genes: Streptococcus
  exposures: quorum sensing
  gene_exposures_relationships: Streptococcus-gene expression in quorum sensing
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Streptococcus-gene expression in quorum sensing

  ===

extracted_object:
  genes:
    - Streptococcus
  exposures:
    - quorum sensing
  gene_exposures_relationships:
    - molecular_activity: quorum sensing
      gene: Streptococcus
input_text: |-
  Title: Letter to Editor in Response to: The Use of Perioperative Nutrition Score in Postoperative Pediatric Inflammatory Bowel Disease.
  Abstract: 
  Keywords: 
raw_completion_output: |-
  genes: Not mentioned in the text
  exposures: Not mentioned in the text
  gene_exposures_relationships: Not mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Not mentioned in the text

  ===

extracted_object:
  genes:
    - Not mentioned in the text
  exposures:
    - Not mentioned in the text
  gene_exposures_relationships:
    - molecular_activity: Not mentioned in the text
      gene: Not mentioned in the text
input_text: |-
  Title: Assessing Serious Infections in Children Exposed In Utero to Ustekinumab.
  Abstract: Chronic inflammatory conditions, including inflammatory bowel disease (IBD), psoriasis (PsO), and psoriatic arthritis (PsA), have a high burden among women of reproductive age. There has been significant interest in finding safe ways of controlling disease activity during pregnancy without adversely affecting the pregnancy or offspring.
  Keywords: 
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: Ustekinumab
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - Ustekinumab
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Impact of the Affordable Care Act on Providing Equitable Healthcare Access for Inflammatory Bowel Disease in the Kentucky Appalachian Region.
  Abstract: Medicaid expansion improved insurance coverage for patients with chronic conditions and low income. The effect of Medicaid expansion on patients with inflammatory bowel disease from high-poverty communities is unknown.This study aimed to evaluate the impact of Medicaid expansion in Kentucky on care for inflammatory bowel disease patients from the Eastern-Kentucky Appalachian community, a historically impoverished area.This study was a retrospective, descriptive, ecological study.This study was conducted in Kentucky using the Hospital Inpatient Discharge and Outpatient Services Database.All encounters for inflammatory bowel disease care for 2009-2020 for patients from the Eastern-Kentucky Appalachian region were included.The primary outcomes measured were proportions of inpatient and emergency encounters, total hospital charge, and hospital length of stay.825 pre-expansion and 5726 post-expansion encounters were identified. Post-expansion demonstrated decreases in the uninsured (9.2% to 1.0%, p < 0.001), inpatient encounters (42.7% to 8.1%, p < 0.001), emergency admissions (36.7% to 12.3%, p < 0.001), admission from the emergency department (8.0% to 0.2%, p < 0.001), median total hospital charge ($7080 to $3260, p < 0.001), and median total hospital length of stay (4 to 3 days, p < 0.001). Similarly, Medicaid coverage (18.8% to 27.7%, p < 0.001), outpatient encounters (57.3% to 91.9%, p < 0.001), elective admissions (46.9% to 76.2%, p < 0.001), admissions from clinic (78.4% to 90.2%, p < 0.001), and discharges to home (43.8% to 88.2%, p < 0.001) increased post-expansion.This study is subject to the limitations inherent of being retrospective and using a partially-deidentified database.This study is the first to demonstrate the changes in trends in care following Medicaid expansion for patients with inflammatory bowel disease in the Commonwealth of Kentucky, especially Appalachian Kentucky, showing significantly increased outpatient care utilization, reduced emergency department encounters, and decreased length of stays.Copyright © The ASCRS 2023.
  Keywords: 
raw_completion_output: |-
  genes: 
  exposures: Medicaid expansion
  gene_exposures_relationships: Medicaid expansion -> improved insurance coverage
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Medicaid expansion -> improved insurance coverage

  ===

extracted_object:
  exposures:
    - Medicaid expansion
  gene_exposures_relationships:
    - molecular_activity: Medicaid expansion
      gene: improved insurance coverage
input_text: |-
  Title: Prognostic role of intestinal ultrasound in Crohn's disease.
  Abstract: The majority of patients affected by Crohn's disease (CD) develop a chronic condition with persistent inflammation and relapses that may cause progressive and irreversible damage to the bowel, resulting in stricturing or penetrating complications in around 50% of patients during the natural history of the disease. Surgery is frequently needed to treat complicated disease when pharmacological therapy failes, with a high risk of repeated operations in time. Intestinal ultrasound (IUS), a non-invasive, cost-effective, radiation free and reproducible method for the diagnosis and follow-up of CD, in expert hands, allow a precise assessment of all the disease manifestations: Bowel characteristics, retrodilation, wrapping fat, fistulas and abscesses. Moreover, IUS is able to assess bowel wall thickness, bowel wall stratification (echo-pattern), vascularization and elasticity, as well as mesenteric hypertrophy, lymph-nodes and mesenteric blood flow. Its role in the disease evaluation and behaviour description is well assessed in literature, but less is known about the potential space of IUS as predictor of prognostic factors suggesting response to a medical treatment or postoperative recurrence. The availability of a low cost exam as IUS, able to recognize which patients are more likely to respond to a specific therapy and which patients are at high risk of surgery or complications, could be a very useful instrument in the hands of IBD physician. The aim of this review is to present current evidence about the prognostic role that IUS can show in predicting response to treatment, disease progression, risk of surgery and risk of post-surgical recurrence in CD.©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
  Keywords: Bowel wall thickness; Crohn’s disease; Intestinal surgery; Intestinal ultrasound; Postoperative recurrence; Remission
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: Baishideng Publishing Group Inc.
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - Baishideng Publishing Group Inc.
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Spatial cluster mapping and environmental modeling in pediatric inflammatory bowel disease.
  Abstract: Geographical (geospatial) clusters have been observed in inflammatory bowel disease (IBD) incidence and linked to environmental determinants of disease, but pediatric spatial patterns in North America are unknown. We hypothesized that we would identify geospatial clusters in the pediatric IBD (PIBD) population of British Columbia (BC), Canada and associate incidence with ethnicity and environmental exposures.To identify PIBD clusters and model how spatial patterns are associated with population ethnicity and environmental exposures.One thousand one hundred eighty-three patients were included from a BC Children's Hospital clinical registry who met the criteria of diagnosis with IBD ≤ age 16.9 from 2001-2016 with a valid postal code on file. A spatial cluster detection routine was used to identify areas with similar incidence. An ecological analysis employed Poisson rate models of IBD, Crohn's disease (CD), and ulcerative colitis (UC) cases as functions of areal population ethnicity, rurality, average family size and income, average population exposure to green space, air pollution, and vitamin-D weighted ultraviolet light from the Canadian Environmental Health Research Consortium, and pesticide applications.Hot spots (high incidence) were identified in Metro Vancouver (IBD, CD, UC), southern Okanagan regions (IBD, CD), and Vancouver Island (CD). Cold spots (low incidence) were identified in Southeastern BC (IBD, CD, UC), Northern BC (IBD, CD), and on BC's coast (UC). No high incidence hot spots were detected in the densest urban areas. Modeling results were represented as incidence rate ratios (IRR) with 95%CI. Novel risk factors for PIBD included fine particulate matter (PM2.5) pollution (IRR = 1.294, CI = 1.113-1.507, P < 0.001) and agricultural application of petroleum oil to orchards and grapes (IRR = 1.135, CI = 1.007-1.270, P = 0.033). South Asian population (IRR = 1.020, CI = 1.011-1.028, P < 0.001) was a risk factor and Indigenous population (IRR = 0.956, CI = 0.941-0.971, P < 0.001), family size (IRR = 0.467, CI = 0.268-0.816, P = 0.007), and summer ultraviolet (IBD = 0.9993, CI = 0.9990-0.9996, P < 0.001) were protective factors as previously established. Novel risk factors for CD, as for PIBD, included: PM2.5 air pollution (IRR = 1.230, CI = 1 .056-1.435, P = 0.008) and agricultural petroleum oil (IRR = 1.159, CI = 1.002-1.326, P = 0.038). Indigenous population (IRR = 0.923, CI = 0.895-0.951, P < 0.001), as previously established, was a protective factor. For UC, rural population (UC IRR = 0.990, CI = 0.983-0.996, P = 0.004) was a protective factor and South Asian population (IRR = 1.054, CI = 1.030-1.079, P < 0.001) a risk factor as previously established.PIBD spatial clusters were identified and associated with known and novel environmental determinants. The identification of agricultural pesticides and PM2.5 air pollution need
raw_completion_output: |-
  genes: IBD, CD, UC
  exposures: fine particulate matter (PM2.5) pollution, agricultural application of petroleum oil to orchards and grapes
  gene_exposures_relationships: IBD - PM2.5 pollution, IBD - agricultural application of petroleum oil to orchards and grapes
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  IBD - PM2.5 pollution, IBD - agricultural application of petroleum oil to orchards and grapes

  ===

extracted_object:
  genes:
    - IBD, CD, UC
  exposures:
    - fine particulate matter (PM2.5) pollution, agricultural application of petroleum
      oil to orchards and grapes
  gene_exposures_relationships:
    - molecular_activity: agricultural application of petroleum oil
      gene: HGNC:87
named_entities:
  - id: HGNC:87
    label: IBD
input_text: |-
  Title: Low vaccination and infection rate of Omicron in patients with inflammatory bowel disease: a comparative study of three unique cohorts.
  Abstract: The SARS-CoV-2 Omicron variant caused a large-scale outbreak of COVID-19 in Shanghai, China. Patients with inflammatory bowel disease (IBD) are at high risk of infection due to immunosuppressive interventions. We aimed to investigate the vaccination information of patients with IBD and update a vaccination guide based on a comparison of vaccination in asymptomatic carriers and healthy individuals.This retrospective study was conducted during an Omicron variant wave. We assessed the vaccination status in patients with IBD, asymptomatic carriers and healthy individuals. Factors with unvaccinated status and adverse events following vaccination were also determined in patients with IBD.The vaccination rate was 51.2% in patients with IBD, 73.2% in asymptomatic carriers, and 96.1% in healthy individuals. Female sex (p = 0.012), Crohn's disease (p = 0.026), and disease behavior of B3 (p = 0.029) were factors that indicated a lower vaccination rate. A significantly higher proportion of healthy individuals had received one booster dose (76.8%) than asymptomatic carriers (43.4%) and patients with IBD (26.2%). Patients with IBD received vaccination without an increased risk of adverse events (p = 0.768).The vaccination rate of patients with IBD remains much lower than that of asymptomatic carriers and healthy individuals. The COVID-19 vaccine has been found to be safe among all three groups and patients with IBD are not more susceptible to adverse events.Copyright © 2023 Feng, Yang, Yao, Feng, Hao, Qiao, Tong and Shen.
  Keywords: Omicron; asymptomatic; coronavirus disease-19 (COVID-19); inflammatory bowel disease (IBD); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: Omicron variant, SARS-CoV-2, COVID-19 vaccine
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - Omicron variant, SARS-CoV-2, COVID-19 vaccine
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Inappropriate Multi-Target Stool DNA Use for Colorectal Cancer Screening: Risks, Compliance, and Outcomes.
  Abstract: Background Inappropriate or "off-label" use of multi-target stool DNA (mt-sDNA) tests refers to their use in patients for whom colonoscopy or no testing at all is warranted. Examples include a positive family history of colorectal cancer, a history of inflammatory bowel disease, or medical issues necessitating diagnostic colonoscopy, among others. Current understanding of off-label mt-sDNA use for colorectal cancer screening, its associated risks, and outcomes is lacking. We examined off-label mt-sDNA prescription and compliance with testing in an outpatient setting in southeast Michigan. Aims The primary aims of the study were determining the extent of off-label mt-sDNA testing and compliance, and results of all testing, as well as demographic factors associated with off-label prescriptions. The secondary aims were to examine explanations for incomplete testing and factors contributing to successful completion. Methods Using a retrospective design, we identified mt-sDNA orders from outpatient internal medicine clinics between January 1, 2018, to July 31, 2019, to evaluate the proportion of off-label mt-sDNA, results of testing, and follow-up colonoscopies up to one year after order placement. Patients were categorized as "off-label" if any inappropriate criteria were met. Statistical analysis was performed for primary and secondary outcomes. Results From 679 mt-sDNA orders within the study period, 81 (12.1%) had at least one off-label criterion for testing. In total, 404/679 (59.5%) patients completed testing. Lack of follow-up comprised the majority of incompletions (216/275; 78.6%). Only 52 (70.3%) out of 74 positive results were followed by diagnostic colonoscopy. Retired employment status (OR = 1.87; 95%CI, 1.17-2.98; P = 0.008) and age of 76 years or older (OR = 2.28; 95%CI, 0.99-5.21; P = 0.044) were significantly associated with increased risk of off-label mt-sDNA prescription. Increasing age range was associated with higher test completion (χ2 (5) = 12.085, p = 0.034). Multinomial logistic regression revealed an increasing age range (OR = 1.29; 95% CI, 1.09-1.54; P = 0.004), predictive of a positive mt-sDNA result for both groups. There was no significant difference between off-label or on-label groups in the mean number of resected polyps or pathology scores on follow-up colonoscopy. Conclusions Off-label mt-sDNA use remains a concern in the outpatient setting. Compliance for test completion and follow-up colonoscopy for positive results require further improvement. Our findings shed new light on the factors associated with off-label testing while reiterating its burden. We also describe common reasons for incomplete tests in an attempt to augment future colorectal cancer (CRC) screening initiatives.Copyright © 2023, Lazar et al.
  Keywords: cologuard®; colon cancer prevention; colon cancer screening; colorectal canc
raw_completion_output: |-
  genes: None mentioned
  exposures: multi-target stool DNA (mt-sDNA) tests
  gene_exposures_relationships: None mentioned
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned

  ===

extracted_object:
  genes:
    - None mentioned
  exposures:
    - multi-target stool DNA (mt-sDNA) tests
  gene_exposures_relationships:
    - molecular_activity: None mentioned
      gene: None mentioned
input_text: |-
  Title: Protective effects of IRG1/itaconate on acute colitis through the inhibition of gasdermins-mediated pyroptosis and inflammation response.
  Abstract: Inflammatory bowel disease (IBD) is a chronic relapsing gastrointestinal disorder, while the treatment effect is not satisfactory. Immune responsive gene 1 (IRG1) is a highly expressed gene in macrophage in response to inflammatory response and catalyzes the production of itaconate. Studies have reported that IRG1/itaconate has a significant antioxidant effect. This study aimed to investigate the effect and mechanism of IRG1/itaconate on dextran sulfate sodium (DSS)-induced colitis in vivo and in vitro. In vivo experiments, we found IRG1/itaconate exerted protective effects against acute colitis by increasing mice weight, the length of colon, reducing disease activity index and colonic inflammation. Meanwhile, IRG1 deletion aggravated the macrophages/CD4+/CD8+ T-cell accumulation, and increased the release of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-6, the activation of nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, and gasdermin D (GSDMD) mediated pyroptosis. Four-octyl itaconate (4-OI), a derivative of itaconate, attenuated these changes, therefore relieved DSS-induced colitis. In vitro experiment, we found 4-OI inhibited the reactive oxygen species production, thereby inhibiting the activation of MAPK/NF-κB signaling pathway in RAW264.7 and murine bone-marrow-derived macrophages. Simultaneously, we found 4-OI inhibited caspase1/GSDMD-mediated pyroptosis to reduce the release of cytokines. Finally, we found anti-TNF-α agent reduced the severity of DSS-induced colitis and inhibited gasdermin E (GSDME)-mediated pyroptosis in vivo. Meanwhile, our study revealed that 4-OI inhibited caspase3/GSDME-mediated pyroptosis induced by TNF-α in vitro. Taken together, IRG1/itaconate exerted a protective role in DSS-induced colitis by inhibiting inflammatory response and GSDMD/GSDME-mediated pyroptosis, which could be a promising candidate for IBD therapy.© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
  Keywords: Colitis; Gasdermin D; Gasdermin E; IRG1; Inflammation
raw_completion_output: |-
  genes: IRG1, GSDMD, GSDME
  exposures: itaconate, DSS (dextran sulfate sodium), IL-1β, TNF-α, IL-6, NF-κB (nuclear factor-κB), MAPK (mitogen-activated protein kinase), 4-OI (four-octyl itaconate), caspase1, caspase3
  gene_exposures_relationships: IRG1/itaconate inhibits gasdermin D (GSDMD)-mediated pyroptosis; IRG1/itaconate inhibits gasdermin E (GSDME)-mediated pyroptosis; 4-OI attenuates the effects of DSS-induced colitis; 4-OI inhibits the activation of MAPK/NF-κB signaling pathway; 4-OI inhibits caspase1/GSDMD-mediated pyroptosis; 4-OI inhibits caspase3/GSDME-mediated pyroptosis; TNF-α agent reduces the severity of DSS-induced colitis; TNF-α agent inhibits gasdermin E (GSDME)-mediated pyroptosis.
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  TNF-α agent inhibits gasdermin E (GSDME)-mediated pyroptosis.

  ===

extracted_object:
  genes:
    - IRG1, GSDMD, GSDME
  exposures:
    - itaconate, DSS (dextran sulfate sodium), IL-1β, TNF-α, IL-6, NF-κB (nuclear
      factor-κB), MAPK (mitogen-activated protein kinase), 4-OI (four-octyl itaconate),
      caspase1, caspase3
  gene_exposures_relationships:
    - molecular_activity: pyroptosis
      gene: HGNC:25697
    - molecular_activity: inhibits gasdermin E (GSDME)-mediated pyroptosis
      gene: HGNC:33904
    - molecular_activity: effects
      gene: DSS-induced colitis
    - molecular_activity: activation
      gene: MAPK/NF-κB
    - molecular_activity: pyroptosis
      gene: HGNC:25697
    - molecular_activity: pyroptosis
      gene: caspase3/GSDME
    - molecular_activity: DSS-induced colitis
      gene: TNF-α agent
    - molecular_activity: inhibits
      gene: HGNC:2810
named_entities:
  - id: HGNC:25697
    label: GSDMD
  - id: HGNC:33904
    label: IRG1
  - id: HGNC:2810
    label: GSDME
input_text: |-
  Title: Autophagy in intestinal fibrosis: relevance in inflammatory bowel disease.
  Abstract: Chronic inflammation is often associated with fibrotic disorders in which an excessive deposition of extracellular matrix is a hallmark. Long-term fibrosis starts with tissue hypofunction and finally ends in organ failure. Intestinal fibrosis is not an exception, and it is a frequent complication of inflammatory bowel disease (IBD). Several studies have confirmed the link between deregulated autophagy and fibrosis and the presence of common prognostic markers; indeed, both up- and downregulation of autophagy are presumed to be implicated in the progression of fibrosis. A better knowledge of the role of autophagy in fibrosis may lead to it becoming a potential target of antifibrotic therapy. In this review we explore novel advances in the field that highlight the relevance of autophagy in fibrosis, and give special focus to fibrosis in IBD patients.Copyright © 2023 Macias-Ceja, Barrachina and Ortiz-Masià.
  Keywords: Crohn’s disease; autophagy; colitis; fibrosis; inflammatory bowel disease; intestinal fibrosis
raw_completion_output: |-
  genes: N/A
  exposures: autophagy
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - autophagy
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: Provincial variation in colorectal cancer screening adherence in Canada; evidence from the Canadian Partnership for Tomorrow's Health.
  Abstract: Although colorectal cancer (CRC) screening program is proven to reduce CRC incidence and mortality, understanding patterns and predictors of suboptimal adherence in screening program requires further investigation in Canada.We used self-reported data from five regional cohorts of the Canadian Partnership for Tomorrow's Health (CanPath), namely the BC Generations Project (BCGP), Alberta's Tomorrow Project (ATP), the Ontario Health Study (OHS), Quebec's CARTaGENE, and the Atlantic Partnership for Tomorrow's Health Study (Atlantic PATH). We stratified participants into the following four risk categories: 1) age 50-74 years, 2) family history in a first-degree relative, 3) personal history of chronic inflammatory bowel disease and/or polyps, and 4) co-existence of personal risk and family history. Multivariable logistic regression was used to identify predictors of adherence to the screening guidelines.Adherence to CRC screening varied considerably between regions, ranging from 16.6% in CARTaGENE to 47.7% in OHS. Compared to the largest cohort OHS, the likelihood of non-adherence to CRC screening was significantly higher in BCGP (OR 1.15, 95% CI 1.11-1.19), the Atlantic PATH (OR 1.90, 95% CI 1.82-1.99) and CARTaGENE (OR 5.10, 95% CI 4.85-5.36). Low physical activity, current smoking, presence of personal risk, family history of CRC significantly reduced the likelihood of adherence to screening recommendations.Compared to the national target of ≥ 60% for participation in CRC screening, adherence to regular CRC screening was suboptimal in this cohort of Canadians and varied by region. Further efforts are needed to identify the specific barriers to screening adherence in different provinces and across risk categories.Copyright © 2023 Darvishian, Moustaqim-Barrette, Awadalla, Bhatti, Broet, McDonald, Murphy, Skead, Urquhart, Vena and Dummer.
  Keywords: CanPath cohort; Canada; adherence; colorectal cancer; screening
raw_completion_output: |-
  genes: Not mentioned
  exposures: None mentioned
  gene_exposures_relationships: Not applicable
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Not applicable

  ===

extracted_object:
  genes:
    - Not mentioned
  exposures:
    - None mentioned
  gene_exposures_relationships:
    - molecular_activity: Not applicable
      gene: Not applicable
input_text: |-
  Title: 3D printed infliximab suppositories for rectal biologic delivery.
  Abstract: Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular structure, its delivery through the oral route is challenging, limiting its administration to only via the parenteral route. The rectal route offers an alternative way for administering infliximab, allowing it to be localised at the disease site and circumventing its passage across the alimentary canal and thus, maintaining its integrity and bioactivity. Three-dimensional (3D) printing is an advanced production technology that permits the creation of dose-flexible drug products from digital designs. The current study assessed the feasibility of utilising semi-solid extrusion 3D printing for the fabrication of infliximab-loaded suppositories for the local treatment of IBD. Various printing inks composed of Gelucire® (48/16 or 44/14) mixed with coconut oil and/or purified water were investigated. It was shown that following reconstitution in water, the infliximab solution can be directly incorporated into the printing ink of Gelucire® 48/16 and can withstand the extrusion process, resulting in well-defined suppositories. Since water content and temperature are critical for safeguarding infliximab's potency, the effect of changing the composition of the printing inks and printing parameters on infliximab's biologic efficiency was evaluated by measuring its binding capacity (i.e., the amount of infliximab that actively binds to its antigen to exert an effect). Despite drug loading assays showing that infliximab remains intact following printing, it was found that the incorporation of water in isolation results in only ∼65% binding capacity. However, when oil is added to the mixture, infliximab's binding capacity increases up to ∼85%. These promising results demonstrate that 3D printing has the potential to be exploited as a novel platform for fabricating dosage forms containing biopharmaceuticals, avoiding patients' compliance issues observed with injectables and addressing their unmet needs.© 2023 The Authors.
  Keywords: Biologicals and monoclonal antibodies; Digital medicine production; Extrusion-assisted additve manufacturing of a suppository formulation; Pressure-assisted syringe; Rectal drug delivery; Tumour necrosis factor-alpha (TNF-alpha) inhibitors; Ulcerative colitis (UC) and Crohn's disease (CD)
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: infliximab
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - infliximab
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Serum amyloid A and metabolic disease: evidence for a critical role in chronic inflammatory conditions.
  Abstract: Serum amyloid A (SAA) subtypes 1-3 are well-described acute phase reactants that are elevated in acute inflammatory conditions such as infection, tissue injury, and trauma, while SAA4 is constitutively expressed. SAA subtypes also have been implicated as playing roles in chronic metabolic diseases including obesity, diabetes, and cardiovascular disease, and possibly in autoimmune diseases such as systemic lupus erythematosis, rheumatoid arthritis, and inflammatory bowel disease. Distinctions between the expression kinetics of SAA in acute inflammatory responses and chronic disease states suggest the potential for differentiating SAA functions. Although circulating SAA levels can rise up to 1,000-fold during an acute inflammatory event, elevations are more modest (∼5-fold) in chronic metabolic conditions. The majority of acute-phase SAA derives from the liver, while in chronic inflammatory conditions SAA also derives from adipose tissue, the intestine, and elsewhere. In this review, roles for SAA subtypes in chronic metabolic disease states are contrasted to current knowledge about acute phase SAA. Investigations show distinct differences between SAA expression and function in human and animal models of metabolic disease, as well as sexual dimorphism of SAA subtype responses.© 2023 den Hartigh, May, Zhang, Chait and Blaser.
  Keywords: SAA; adipocytes, macrophages; cardiovascular disease; diabetes; intestine; liver; obesity
raw_completion_output: |-
  genes: SAA

  exposures: not mentioned

  gene_exposures_relationships: not mentioned
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  not mentioned

  ===

extracted_object:
  genes:
    - SAA
  exposures:
    - not mentioned
  gene_exposures_relationships:
    - molecular_activity: not mentioned
      gene: not mentioned
input_text: |-
  Title: Probiotic lactic acid bacteria alleviate pediatric IBD and remodel gut microbiota by modulating macrophage polarization and suppressing epithelial apoptosis.
  Abstract: The incidence of pediatric inflammatory bowel disease (PIBD) continues to rise. It was reported that the probiotic lactic acid bacteria Pediococcus pentosaceus (P. pentosaceus) can interfere with intestinal immunity, but it is still unknown whether it can alleviate PIBD and the concrete mechanism of immune regulation is unclear.For this study, 3-week-old juvenile mice were selected for modeling the development of PIBD. The mice treated with 2% DSS were randomly divided into two groups, which were given P. pentosaceus CECT8330 and equal amounts of solvent, respectively. The feces and intestinal tissue were collected for the mechanism exploration in vivo. THP-1 and NCM460 cells were used to investigate the effects of P. pentosaceus CECT8330 on macrophage polarization, epithelial cell apoptosis, and their crosstalk in vitro.P. pentosaceus CECT8330 obviously alleviated colitis symptoms of juvenile mice, including weight loss, colon length shortening, spleen swelling, and intestinal barrier function. Mechanistically, P. pentosaceus CECT8330 could inhibit intestinal epithelial apoptosis by suppressing the NF-κB signaling pathway. Meanwhile, it reprogramed macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, leading to a decreased secretion of IL-1β which contributes to the reduction in ROS production and epithelial apoptosis. Additionally, the 16S rRNA sequence analysis revealed that P. pentosaceus CECT8330 could recover the balance of gut microbiota, and a significantly increased content of Akkermansia muciniphila was particularly observed.P. pentosaceus CECT8330 shifts macrophage polarization toward an anti-inflammatory M2 phenotype. The decreased production of IL-1β leads to a reduction in ROS, NF-κB activation, and apoptosis in the intestinal epithelium, all of which help to repair the intestinal barrier and adjust gut microbiota in juvenile colitis mice.Copyright © 2023 Hua, Pan, Chen, Jing, Xie, Gao, Huang, Chen, Gao, Xu and Li.
  Keywords: Akkermansia muciniphila; Pediococcus pentosaceus CECT8330; intestinal epithelium apoptosis; macrophage polarization; pediatric IBD
raw_completion_output: |-
  genes: NF-κB
  exposures: Pediococcus pentosaceus CECT8330; IL-1β; ROS
  gene_exposures_relationships: NF-κB and Pediococcus pentosaceus CECT8330; IL-1β and ROS
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  IL-1β and ROS

  ===

extracted_object:
  genes:
    - NF-κB
  exposures:
    - Pediococcus pentosaceus CECT8330
    - IL-1β
    - CHEBI:26523
  gene_exposures_relationships:
    - molecular_activity: undeclared
      gene: Pediococcus pentosaceus CECT8330
    - molecular_activity: IL-1β
      gene: HGNC:1455
named_entities:
  - id: CHEBI:26523
    label: ROS
  - id: HGNC:1455
    label: ROS
input_text: |-
  Title: Comparison of the gut virus communities between patients with Crohn's disease and healthy individuals.
  Abstract: The escalating incidence of Crohn's disease (CD), a debilitating ailment that ravages individuals and their families, has become a formidable issue over recent decades.In this study, fecal samples from patients with CD and healthy individuals were investigated by means of viral metagenomics.The fecal virome was analyzed and some suspected disease-causing viruses were described. A polyomavirus named HuPyV with 5,120 base pairs (bp) was found in the disease group. In a preliminary analysis employing large T region-specific primers, it was found that HuPyV was present in 3.2% (1/31) of healthy samples and 43.2% (16/37) of disease samples. Additionally, two other viruses from the anellovirus and CRESS-DNA virus families were found in fecal samples from CD patients. The complete genome sequences of these two viruses were described respectively, and the phylogenetic trees have been built using the anticipated amino acid sequences of the viral proteins.Further research is required to elucidate the relationship between these viruses and the onset and development of Crohn's disease.Copyright © 2023 Ding, Wan, Li, Ma, Zhang and Xu.
  Keywords: CRESS-DNA virus; Crohn’s disease; anellovirus; inflammatory bowel disease; polyomavirus; viral metagenomics method
raw_completion_output: |-
  genes: HuPyV
  exposures: CRESS-DNA virus, anellovirus
  gene_exposures_relationships: HuPyV - viral metagenomics method; CRESS-DNA virus - fecal samples from CD patients; anellovirus - fecal samples from CD patients
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  anellovirus - fecal samples from CD patients

  ===

extracted_object:
  genes:
    - HuPyV
  exposures:
    - CRESS-DNA virus, anellovirus
  gene_exposures_relationships:
    - molecular_activity: viral metagenomics method
      gene: HuPyV
    - molecular_activity: CRESS-DNA virus
      gene: fecal samples from CD patients
    - molecular_activity: exposure to anellovirus
      gene: fecal samples
input_text: |-
  Title: Combination therapy is not associated with improved rates of clinical or endoscopic remission in patients with inflammatory bowel disease treated with ustekinumab or vedolizumab: a retrospective study.
  Abstract: Management of inflammatory bowel disease (IBD) involves biological agents, often in combination with thiopurines or methotrexate. The aim of our study was to compare clinical and endoscopic outcomes in IBD patients treated with vedolizumab or ustekinumab, as monotherapy or in combination with thiopurines or methotrexate.We conducted a retrospective cohort study of all patients aged ≥18 years with a diagnosis of ulcerative colitis or Crohn's disease, commenced on vedolizumab or ustekinumab between October 2015 and March 2022. Primary outcome was clinical remission or response calculated by partial Mayo score (remission: <3; response: improvement >1) for ulcerative colitis or Harvey-Bradshaw index (<5, >2 respectively) for Crohn's disease over 1 year. Secondary endpoints were treatment failure, relapse, endoscopic remission at 1 year. Statistical analysis was done using 2-sample Student's t and chi-square tests.A total of 159 IBD patients were included in the study, 85 (53%) on vedolizumab and 74 (47%) on ustekinumab. For those on vedolizumab, 61 (72%) patients had ulcerative colitis, and 24 (28%) has Crohn's disease. All patients on ustekinumab had Crohn's disease. Mean disease duration in was 9.4 and 13.5 years respectively. There was no difference in clinical response or remission for vedolizumab or ustekinumab monotherapy compared to combination therapy at 1 year. There was also no difference in treatment failure, relapse or endoscopic remission.Combining vedolizumab or ustekinumab with an immunomodulator is not superior to monotherapy in terms of clinical response or endoscopic remission up to 1 year in IBD.Copyright: © Hellenic Society of Gastroenterology.
  Keywords: Crohn’s disease; Ulcerative colitis; biologics; thiopurines
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: vedolizumab, ustekinumab, thiopurines, methotrexate
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - vedolizumab, ustekinumab, thiopurines, methotrexate
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Association of serum IgG4 and disease outcomes in patients with inflammatory bowel disease.
  Abstract: The etiology of inflammatory bowel disease (IBD) is multifactorial and thought to be influenced by inappropriate activation of the gut mucosal immune system. As the only immunoglobulin G (IgG) subclass unable to activate the classical complement cascade, the role of IgG4 in IBD pathophysiology as an immunomodulator is controversial. This study aimed to determine the association of low, normal and high IgG4 levels with the outcomes of IBD patients.This was a retrospective study of a multisite tertiary care center database evaluating patients with IBD who had an IgG4 level drawn between 2014 and 2021. Subjects were divided into low, normal, and high IgG4 level groups for evaluation of demographic and clinical indicators of IBD activity and severity.Of 284 patients with IBD, 22 had low (7.7%), 16 high (5.6%), and 246 (86.6%) normal IgG4 levels. There was no difference in IBD subtype, mean age, age at IBD diagnosis, or smoking between the 3 groups. There was no difference in number of hospitalizations (P=0.20), C-reactive protein levels, need for intestinal resection (P=0.85), or presence of primary sclerosing cholangitis (P=0.15), pancreatitis (P=0.70), or perianal disease (P=0.68) between the groups. Significantly more patients in the low IgG4 group had previous exposure to vedolizumab compared to the other groups and more patients in the low IgG4 group received vedolizumab (P=0.04), azathioprine (P=0.04) and prednisone (P=0.03) during the 5-year follow up.In this study, a low serum IgG4 level was associated with higher rates of vedolizumab, azathioprine, and steroid use.Copyright: © Hellenic Society of Gastroenterology.
  Keywords: IgG4; disease outcomes; disease severity; inflammatory bowel disease
raw_completion_output: |-
  genes: None
  exposures: IgG4, vedolizumab, azathioprine, prednisone
  gene_exposures_relationships: None
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None

  ===

extracted_object:
  genes:
    - None
  exposures:
    - IgG4, vedolizumab, azathioprine, prednisone
  gene_exposures_relationships:
    - molecular_activity: None
      gene: None
input_text: |-
  Title: Alexithymic characteristics and interoceptive abilities are associated with disease severity and levels of C-reactive protein and cytokines in patients with inflammatory bowel disease.
  Abstract: Alexithymia and atypical gut-brain signaling have been linked to the pathophysiology of inflammatory bowel disease (IBD). We herein assessed IBD patients' alexithymia levels and interoceptive abilities, and detected potential correlations with psychological distress, symptom severity and disease activity, and inflammation indices.Adult IBD outpatients and healthy controls were recruited. Alexithymia was assessed using the Toronto Alexithymia Scale, interoceptive accuracy using the Heartbeat Counting Test (cardiac interoception) and the Water Load Test-II (gastric interoception), and interoceptive sensibility using the Multidimensional Assessment of Interoceptive Awareness (MAIA).Forty-one patients with Crohn's disease (CD), 16 with ulcerative colitis (UC), and 50 healthy controls were included. In CD patients, the level of externally oriented thinking and total alexithymia score were correlated with disease activity (P=0.027 and P=0.047, respectively), while in UC patients difficulties in identifying emotions were linked to disease activity (P=0.007). In CD patients, the Noticing, Not-Worrying and Emotional Awareness MAIA subscale score were correlated with C-reactive protein levels (P=0.005, P=0.048 and P=0.005), the Noticing subscale score with interleukin (IL)-1β levels (r=-0.350, P=0.039), the Not-Distracting subscale score with IL-6 levels (r=-0.402, P=0.017), and the Emotional Awareness subscale score with IL-1β (r=-0.367, P=0.030) and IL-6 (r=-0.379, P=0.025) levels. Finally, in UC patients, the Not-Worrying subscale score was significantly associated with IL-6 levels (r=-0.532, P=0.049), while difficulties in identifying emotions were linked to IL-8 levels (r=0.604, P=0.022).Emotional and interoceptive processing is associated with IBD disease activity, suggesting a potential implication for IBD pathophysiology.Copyright: © Hellenic Society of Gastroenterology.
  Keywords: Alexithymia; cytokines; inflammatory bowel disease; interoception
raw_completion_output: |-
  genes: N/A
  exposures: cytokines
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - cytokines
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: Cutaneous Crohn's disease after proctocolectomy for medically refractory colonic Crohn's disease: a case series and review of the literature.
  Abstract: Cutaneous Crohn's disease (CCD), also known as metastatic Crohn's disease (CD), is one of the rarest and most challenging cutaneous manifestations of CD. It is characterized by non-caseating granulomatous inflammation of the skin at sites that are non-contiguous with the gastrointestinal (GI) tract. Diagnosis of CCD needs a high clinical suspicion since morphological presentation varies widely and lacks an apparent correlation to the activity of the luminal CD. The onset of CCD in patients without active GI CD is a particularly understudied phenomenon.We present a case series of a unique patient group who developed CCD while in remission from a luminal CD perspective, mainly after a proctocolectomy for Crohn's colitis. We also provide a literature review and summary of case reports of CCD after proctocolectomy.Our 4 adult patients diagnosed with CCD after proctocolectomy presented herein, were successfully treated with high-dose corticosteroids, followed by biologic therapy. Furthermore, a comprehensive review of CCD is provided regarding its pathogenesis, clinical presentation, differential diagnosis, and the evidence behind the available treatments.CCD should be considered in any CD patient presenting with skin lesions regardless of their disease activity status and history of proctocolectomy. The treatment remains challenging; biologics remain the cornerstone and a multidisciplinary approach is recommended. Larger randomized clinical trials are essential to determine the optimal treatment protocol and to improve outcomes.Copyright: © Hellenic Society of Gastroenterology.
  Keywords: Cutaneous Crohn’s disease; dermatologic manifestations; inflammatory bowel disease; metastatic Crohn’s disease; proctocolectomy
raw_completion_output: |-
  genes: None mentioned in the text.
  exposures: high-dose corticosteroids, biologic therapy, proctocolectomy.
  gene_exposures_relationships: None mentioned in the text.
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text.

  ===

extracted_object:
  genes:
    - None mentioned in the text.
  exposures:
    - high-dose corticosteroids, biologic therapy, proctocolectomy.
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text.
      gene: None mentioned in the text.
input_text: |-
  Title: Outcome of inflammatory bowel disease patients with prior malignancy.
  Abstract: Inflammatory bowel disease (IBD) treatment options, such as anti-tumor necrosis factor (TNF) agents and thiopurines, are associated with an increased risk of certain malignancies. However, the management of IBD patients with prior malignancy is not well defined and the literature is scarce. The main aim of this study was to describe the outcome of IBD patients with prior malignancy, or malignancy before first exposure to IBD-related biologic or immunosuppressive treatment.The study cohort included adult IBD patients followed in a tertiary academic center, with at least one malignancy diagnosed before IBD diagnosis or before initiation of IBD-related treatment. The main outcome of interest was a relapse of the previous malignancy or development of a second malignancy.Our database included 1112 patients with both IBD and malignancy. Of these, 86 (9%) who had their malignancy diagnosed before IBD-related treatment initiation were identified, while 10/86 patients (9%) were further diagnosed with a second primary malignancy. Twenty patients, (20/86, 23%) had recurrence of a previous malignancy, most commonly non-melanoma skin cancer (NMSC), found in 9/20 patients (45%). Treatment with infliximab was found to be significantly associated with recurrence of NMSC (P=0.003).Anti-TNF treatment may be associated with an increased risk of NMSC recurrence. This underscores the importance of rigorous dermatological follow up in IBD patients with previous NMSC treated with anti-TNFs.Copyright: © Hellenic Society of Gastroenterology.
  Keywords: Inflammatory bowel disease; malignancy; recurrent; secondary; therapy
raw_completion_output: |-
  genes: TNF
  exposures: anti-TNF agents, thiopurines, infliximab
  gene_exposures_relationships: TNF - infliximab
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  TNF - infliximab

  ===

extracted_object:
  genes:
    - HGNC:11892
  exposures:
    - anti-TNF agents, thiopurines, infliximab
  gene_exposures_relationships:
    - molecular_activity: infliximab
      gene: HGNC:11892
named_entities:
  - id: HGNC:11892
    label: TNF
input_text: |-
  Title: Knowledge mapping of COVID-19 and autoimmune diseases: a visual and bibliometric analysis.
  Abstract: Many studies have shown an association between COVID-19 and autoimmune diseases (ADs). Studies on COVID-19 and ADs have also increased significantly, but there is no bibliometric analysis to summarize the association between COVID-19 and ADs. The purpose of this study was to perform a bibliometric and visual analysis of published studies related to COVID-19 and ADs.Based on the Web of Science Core Collection SCI-Expanded database, we utilize Excel 2019 and visualization analysis tools Co-Occurrence13.2 (COOC13.2), VOSviewer, CiteSpace, and HistCite for analysis.A total of 1736 related kinds of papers were included, and the number of papers presented an overall increasing trend. The country/region with the most publications is the USA, the institution is the Harvard Medical School, the author is Yehuda Shoenfeld from Israel, and the journal is Frontiers in Immunology. Research hotspots include immune responses (such as cytokines storm), multisystem ADs (such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis), treatment modalities (such as hydroxychloroquine, rituximab), vaccination and autoimmune mechanisms (such as autoantibodies, molecular mimicry). The future research direction may be the mechanisms and treatment ideas of the association between ADs and COVID-19 (such as NF-κB, hyperinflammation, antiphospholipid antibodies, neutrophil extracellular traps, granulocyte-macrophage colony-stimulating factor), other cross-diseases of COVID-19 and ADs (such as inflammatory bowel disease, chronic mucocutaneous candidiasis, acute respiratory distress syndrome).The growth rate of publications regarding ADs and COVID-19 has risen sharply. Our research results can help researchers grasp the current status of ADs and COVID-19 research and find new research directions in the future.© 2023. The Author(s).
  Keywords: Autoimmune diseases; COVID-19; Frontiers; Hotspots; Keywords analysis
raw_completion_output: |-
  genes: NF-κB
  exposures: hydroxychloroquine, rituximab
  gene_exposures_relationships: NF-κB - hydroxychloroquine; NF-κB - rituximab
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  NF-κB - rituximab

  ===

extracted_object:
  genes:
    - NF-κB
  exposures:
    - hydroxychloroquine, rituximab
  gene_exposures_relationships:
    - molecular_activity: hydroxychloroquine
      gene: NF-κB
    - molecular_activity: NF-kB
      gene: rituximab
input_text: |-
  Title: Lymphogranuloma venereum and CMV co-infection mimicking ulcerative proctitis in a non-immunocompromised patient.
  Abstract: 
  Keywords: 
raw_completion_output: |-
  genes: N/A
  exposures: Lymphogranuloma venereum, CMV
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - Lymphogranuloma venereum, CMV
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: Mechanism by which oleracein E alleviates TNBS-induced ulcerative colitis.
  Abstract: This study aimed to investigate the effect of oleracein E (OE) in improving 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC).Lipopolysaccharide (LPS) was used to induce a UC cell model, and TNBS was used to induce a UC rat model. ELISA was performed to assess the levels of inflammatory factors (IL-1β, TNF-α, and IL-6). Moreover, the activities of catalase (CAT), myeloperoxidase (MPO), and malonaldehyde (MDA) were detected by kits. Western blotting was performed to assess related proteins of the Nrf2/HO-1 signaling pathway, tight junction protein (ZO-1, Occludin, and claudin-2) expression levels, and apoptosis-related proteins (Bcl2, Bax, and cleaved caspase 3). Flow cytometry was used to analyze ROS levels. The morphology of colon tissues and the apoptosis of cells were detected by HE and TUNEL staining, respectively.OE significantly increased the activity of CAT and decreased the activity of MPO in LPS-induced Caco-2 cells and TNBS-induced UC rats. However, the levels of IL-1β, IL-6, and TNF-α were markedly reduced both in vivo and in vitro. In addition, OE significantly increased the levels of Nrf2/HO-1 signaling pathway-related proteins and tight junction proteins and inhibited cell apoptosis. HE staining showed that OE significantly decreased the severity of acute TNBS-induced colitis in rats.OE may exert a regulatory effect on ameliorating intestinal barrier injury and reducing inflammation and oxidative stress levels by activating the Nrf2/HO-1 pathway.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
  Keywords: 
raw_completion_output: |-
  genes: Nrf2, HO-1, ZO-1, Occludin, claudin-2, Bcl2, Bax, cleaved caspase 3

  exposures: oleracein E (OE), 2,4,6-trinitrobenzene sulfonic acid (TNBS), Lipopolysaccharide (LPS)

  gene_exposures_relationships: OE to Nrf2/HO-1 pathway
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  OE to Nrf2/HO-1 pathway

  ===

extracted_object:
  genes:
    - Nrf2, HO-1, ZO-1, Occludin, claudin-2, Bcl2, Bax, cleaved caspase 3
  exposures:
    - CHEBI:48113
  gene_exposures_relationships:
    - molecular_activity: OE to Nrf2/HO-1 pathway
      gene: HGNC:4071
named_entities:
  - id: CHEBI:48113
    label: oleracein E (OE), 2,4,6-trinitrobenzene sulfonic acid (TNBS), Lipopolysaccharide
      (LPS)
  - id: HGNC:4071
    label: Nrf2
input_text: |-
  Title: Protective effect of Arum maculatum against dextran sulfate sodium induced colitis in rats.
  Abstract: Ulcerative colitis (UC) is an inflammatory disease of the large intestine that is characterized by diarrhea, bloody stools, abdominal pain and mucosal ulceration. UC is treated with nonsteroidal anti-inflammatory drugs, corticosteroids or immunosuppressants, but long-term use of these drugs can cause adverse effects. Arum maculatum is used as a traditional treatment for digestive system disorders, but its use for treatment of UC has not been investigated rigorously. We investigated the possible protective effect of a methanol extract of A. maculatum against dextran sulfate sodium (DSS) induced experimental UC in rats. Total phenolic and flavonoid contents of the extract were 32.919 ± 1.125 mg gallic acid equivalent (GAE)/g and 52.045 ± 7.902 µg rutin equivalent (RE)/mg, respectively. The half-maximal inhibitory concentration (IC50) for the extract was 105.76 µg/ml according to the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity assay. Effects of A. maculatum extract on UC induced by DSS were assessed both macroscopically and histologically. We also investigated effects of A. maculatum extract on malondialdehyde (MDA) levels and the oxidative stress index (OSI) in normal rats and rats with UC. We found that treatment with A. maculatum extract protected the colon against DSS induced UC in a dose-dependent manner.
  Keywords: Arum maculatum; inflammatory bowel disease; medicinal plant; rats; ulcerative colitis
raw_completion_output: |-
  genes: None mentioned in the text.
  exposures: dextran sulfate sodium
  gene_exposures_relationships: None mentioned in the text.
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text.

  ===

extracted_object:
  genes:
    - None mentioned in the text.
  exposures:
    - dextran sulfate sodium
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text.
      gene: None mentioned in the text.
input_text: |-
  Title: Reporting of endoscopy and histology of ulcerative colitis in routine clinical practice: How far we are!
  Abstract: 
  Keywords: clinical practice; endoscopy; histology; inflammatory bowel disease; ulcerative colitis
raw_completion_output: |-
  genes: 
  exposures: 
  gene_exposures_relationships:
prompt: |+
  From the text below, extract the following entities in the following format:

  genes: <semicolon-separated list of genes>
  exposures: <a chemical or molecule whose direct or indirect effects cause one or more entities to experience biological change>
  gene_exposures_relationships: <semicolon-separated list of gene to molecular activity relationships>


  Text:
  Title: Reporting of endoscopy and histology of ulcerative colitis in routine clinical practice: How far we are!
  Abstract: 
  Keywords: clinical practice; endoscopy; histology; inflammatory bowel disease; ulcerative colitis

  ===

extracted_object: {}
input_text: |-
  Title: Clinical features analysis of Kawasaki disease with abdominal symptoms as the first manifestation.
  Abstract: To investigate the clinical characteristics of Kawasaki disease (KD) presenting with abdominal manifestation as the first manifestation. Our findings may help improve the cognition of KD with abdominal complications, and avoid misdiagnosis and missed diagnosis. A retrospective analysis was conducted of 1490 KD patients admitted to Shengjing Hospital between January 2019 and March 2022. Clinical characteristics, related factors, and prognosis of KD with abdominal manifestation as first manifestation were analyzed. Based on the presenting symptoms, patients were divided into gastrointestinal symptom group (n = 141), liver dysfunction group (n = 55), and control group (n = 1294). In the gastrointestinal group, diarrhea [100 cases (70.9%)], vomiting [55 cases (39.0%)], and abdominal pain [34 cases (24.1%)] were the most common symptoms at onset. 8 cases (5.7%) were complicated with pseudo-intestinal obstruction, 6 cases (4.3%) with ischemic colitis, 5 cases (3.5%) with pancreatitis, 2 cases (1.4%) with appendicitis, and 1 case (0.7%) with cholecystitis. Comparied to ordinary gastroenteritis caused by infection, gastroenteritis with KD has longer fever duration before treatment, higher WBC, PLT, CRP, AST levels and lower albumin levels. All patients in the liver dysfunction group had elevated transaminases, and 19 patients (34.5%) presented with jaundice. In the gastrointestinal group, the average hospital stay was 10.3 days, and the incidence of IVIG unresponsiveness and coronary artery lesion were 18.4% and 19.9%, respectively, which were significantly higher than that in the control group. In the liver dysfunction group, the average hospital stay (11.18 days), incidence of IVIG unresponsiveness (25.5%), and incidence of coronary artery lesion (29.1%) were significantly higher than that in the control group. On multivariate logistic regression analysis, gastrointestinal involvement, fever duration, ALT, PLT, and CRP were identified as risk factors for CAL, younger age, gastrointestinal involvement and fever duration were risk factors for IVIG unresponsiveness.  Conclusion: KD with gastrointestinal involvement is associated with a higher risk of IVIG unresponsiveness and coronary artery lesion. KD should be considered in the differential diagnosis of children with acute fever, especially those with gastrointestinal involvement and liver dysfunction. What is Known: • Fever duration, PLT, and CRP were identified as risk factors for CAL. Timely diagnosis and application of IVIG treatment can avoid exploratory laparotomy for ileus, appendectomy for misdiagnosed appendicitis, colonoscopy for misdiagnosed inflammatory bowel disease, and reduce the complications of CAL and IVIG unresponsiveness. What is New: • Abdominal symptoms as the first manifestation can be an independent risk factor for CAL and IVIG unresponsiveness. KD should be conside
raw_completion_output: |-
  genes: None mentioned in the text.
  exposures: infection, pseudointestinal obstruction, ischemic colitis, pancreatitis, appendicitis, cholecystitis, gastroenteritis, IVIG treatment, fever, ALT, CRP.
  gene_exposures_relationships: None mentioned in the text.
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text.

  ===

extracted_object:
  genes:
    - None mentioned in the text.
  exposures:
    - infection, pseudointestinal obstruction, ischemic colitis, pancreatitis, appendicitis,
      cholecystitis, gastroenteritis, IVIG treatment, fever, ALT, CRP.
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text.
      gene: None mentioned in the text.
input_text: |-
  Title: Decoding the microbiome: advances in genetic manipulation for gut bacteria.
  Abstract: Studies of the gut microbiota have revealed associations between specific bacterial species or community compositions with health and disease, yet the causal mechanisms underlying microbiota gene-host interactions remain poorly understood. This is partly due to limited genetic manipulation (GM) tools for gut bacteria. Here, we review current advances and challenges in the development of GM approaches, including clustered regularly interspaced short palindromic repeats (CRISPR)-Cas and transposase-based systems in either model or non-model gut bacteria. By overcoming barriers to 'taming' the gut microbiome, GM tools allow molecular understanding of host-microbiome associations and accelerate microbiome engineering for clinical treatment of cancer and metabolic disorders. Finally, we provide perspectives on the future development of GM for gut microbiome species, where more effort should be placed on assembling a generalized GM pipeline to accelerate the application of groundbreaking GM tools in non-model gut bacteria towards both basic understanding and clinical translation.Copyright © 2023 Elsevier Ltd. All rights reserved.
  Keywords: CRISPR-Cas; genetic manipulation tools; gut microbiome; host–microbe interactions; transposon
raw_completion_output: |-
  genes: Not mentioned in the text.

  exposures: CRISPR-Cas, transposase-based systems

  gene_exposures_relationships: CRISPR-Cas to genetic manipulation tools; transposase-based systems to genetic manipulation tools
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  transposase-based systems to genetic manipulation tools

  ===

extracted_object:
  genes:
    - Not mentioned in the text.
  exposures:
    - CRISPR-Cas, transposase-based systems
  gene_exposures_relationships:
    - molecular_activity: genetic manipulation tools
      gene: CRISPR-Cas
    - molecular_activity: transposase-based systems
      gene: genetic manipulation tools
input_text: |-
  Title: Heterogeneity in protocols and outcomes to study the effect of renin-angiotensin system blockers in inflammatory bowel disease: A systematic review.
  Abstract: The renin-angiotensin system (RAS) has been associated with inflammatory bowel disease (IBD), supporting translational relevance of RAS blockers. Comparability of study design/outcomes is fundamental for data analysis/discussion.We aimed at evaluating the heterogeneity among protocols and outcomes to study the effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in IBD.This study was performed and reported in accordance with the Cochrane recommendations and PRISMA (PROSPERO-CRD42022323853). Systematic searches were performed in PubMed, Scopus and Web of Science. Studies that met the inclusion criteria were selected. Quality assessment of the studies was done with the SYRCLES's risk of bias tools for animal studies.Thirty-five pre-clinical studies and six clinical studies were included. Chemical induction of colitis was the most used model, but variable doses of the induction agent were reported. All studies reported at least a disease activity index, a macroscopic score, or a histologic assessment, but these scores were methodologically heterogeneous and reported for different characteristics. Great heterogeneity was also found in drug interventions. Inflammatory markers assessed as outcomes were different across studies.Lack of standardization of protocols and outcomes among studies threatens the evidence on how RAS blockers influence IBD outcomes.© 2023 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.
  Keywords: angiotensin-converting enzyme; colitis; heterogeneity; inflammatory bowel disease; renin-angiotensin system blockers; variability
raw_completion_output: |-
  genes: none mentioned in the text

  exposures: renin-angiotensin system blockers; angiotensin-converting enzyme inhibitors; angiotensin receptor blockers

  gene_exposures_relationships: none mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  none mentioned in the text

  ===

extracted_object:
  genes:
    - none mentioned in the text
  exposures:
    - renin-angiotensin system blockers
    - CHEBI:35457
    - angiotensin receptor blockers
  gene_exposures_relationships:
    - molecular_activity: none mentioned in the text
      gene: none mentioned in the text
named_entities:
  - id: CHEBI:35457
    label: angiotensin-converting enzyme inhibitors
input_text: |-
  Title: Antimicrobial therapies for chronic pain (part 2): the prevention and treatment of chronic pain.
  Abstract: The discovery and development of antimicrobial therapies represents one of the most significant advancements in modern medicine. Although the primary therapeutic intent of antimicrobials is to eliminate their target pathogens, several antimicrobials have been shown to provide analgesia as a secondary benefit. Antimicrobials have demonstrated analgesic effects in conditions that involve dysbiosis or potential subclinical infection (e.g ., chronic low back pain with Modic type 1 changes; chronic prostatitis/chronic pelvic pain; irritable bowel syndrome; inflammatory bowel disease; functional gastrointestinal disorders/dyspepsia; myalgic encephalomyelitis/chronic fatigue syndrome), and might even prevent the chronification of pain after acute infections that are associated with excessive systemic inflammation (e.g ., post COVID-19 condition/long Covid, rheumatic fever). Clinical studies often assess the analgesic effects of antimicrobial therapies in an observational manner, without the ability to identify causative relationships, and significant gaps in the understanding remain regarding the analgesic potential of antimicrobials. Numerous interrelated patient-specific, antimicrobial-specific, and disease-specific factors altogether contribute to the perception and experience of pain, and each of these requires further study. Given worldwide concerns regarding antimicrobial resistance, antimicrobials must continue to be used judiciously and are unlikely to be repurposed as primary analgesic medications. However, when equipoise exists among several antimicrobial treatment options, the potential analgesic benefits of certain antimicrobial agents might be a valuable aspect to consider in clinical decision-making. This article (the second in a two-part series) aims to comprehensively review the evidence on the prevention and treatment of chronic pain using antimicrobial therapies and suggest a framework for future studies on this topic.
  Keywords: Analgesia; Anti-Bacterial Agents; Anti-Infective Agents; Antiviral Agents; Central Nervous System Sensitization; Chronic Pain; Infections; Neuralgia; Nociceptive Pain; Pain Management
raw_completion_output: |-
  genes: 

  exposures: Antimicrobials, pathogens, dysbiosis, subclinical infection, excessive systemic inflammation, post COVID-19 condition/long Covid, rheumatic fever, antimicrobial resistance

  gene_exposures_relationships: Not mentioned in the text.
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Not mentioned in the text.

  ===

extracted_object:
  exposures:
    - Antimicrobials, pathogens, dysbiosis, subclinical infection, excessive systemic
      inflammation, post COVID-19 condition/long Covid, rheumatic fever, antimicrobial
      resistance
  gene_exposures_relationships:
    - molecular_activity: Not mentioned in the text.
      gene: Not mentioned in the text.
input_text: |-
  Title: Antimicrobial therapies for chronic pain (part 1): analgesic mechanisms.
  Abstract: There is increasing evidence that the relationship between chronic pain and infections is complex and intertwined. Bacterial and viral infections can cause pain through numerous mechanisms such as direct tissue damage and inflammation, the induction of excessive immunologic activity, and the development of peripheral or central sensitization. Treating infections might relieve pain by attenuating these processes, but a growing body of literature suggests that some antimicrobial therapies confer analgesic effects, including for nociceptive and neuropathic pain symptoms, and affective components of pain. The analgesic mechanisms of antimicrobials are indirect, but might be conceptualized into two broad categories: 1) the reduction of the infectious burden and associated pro-inflammatory processes; and 2) the inhibition of signaling processes (e.g., enzymatic and cytokine activity) necessary for nociception and maladaptive neuroplastic changes via off-target effects (unintended binding sites). For the former, there is evidence that symptoms of chronic low back pain (when associated with Modic type 1 changes), irritable bowel syndrome, inflammatory bowel disease, chronic pelvic pain, and functional dyspepsia might be improved after antibiotic treatment, though significant questions remain regarding specific regimens and dose, and which subpopulations are most likely to benefit. For the latter, there is evidence that several antimicrobial classes and medications exert analgesic effects independent of their reduction of infectious burden, and these include cephalosporins, ribavirin, chloroquine derivatives, rapalogues, minocycline, dapsone, and piscidin-1. This article aims to comprehensively review the existing literature for antimicrobial agents that have demonstrated analgesic efficacy in preclinical or clinical studies.
  Keywords: Analgesia; Anti-Bacterial Agents; Anti-Infective Agents; Antiviral Agents; Central Nervous System Sensitization; Chronic Pain; Infections; Neuralgia; Nociceptive Pain; Pain Management
raw_completion_output: |-
  genes: 
  exposures: antimicrobial therapies
  gene_exposures_relationships: antimicrobial therapies have analgesic effects; antimicrobial therapies reduce infectious burden and associated pro-inflammatory processes; antimicrobial therapies inhibit signaling processes necessary for nociception and maladaptive neuroplastic changes
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  antimicrobial therapies inhibit signaling processes necessary for nociception and maladaptive neuroplastic changes

  ===

extracted_object:
  exposures:
    - antimicrobial therapies
  gene_exposures_relationships:
    - molecular_activity: antimicrobial therapies
      gene: analgesic effects
    - molecular_activity: antimicrobial therapies
      gene: N/A
    - molecular_activity: inhibit signaling processes
      gene: antimicrobial therapies
input_text: |-
  Title: Spondyloarthritides.
  Abstract: The spondyloarthritides are a diverse group of distinct yet interrelated disease processes with overlapping clinical features. They are ankylosing spondylitis, reactive arthritis, inflammatory bowel disease-associated arthritis, and psoriatic arthritis. Genetically, these disease processes have been linked by the presence of HLA-B27. They manifest with axial and peripheral symptoms, such as inflammatory back pain, enthesitis, oligoarthritis, and dactylitis. The onset of symptoms can begin before the age of 45; however, because of the wide range of signs and symptoms, diagnosis can be delayed, leading to unchecked inflammation, structural damage, and later, restriction in physical mobility.Copyright © 2022 Elsevier Inc. All rights reserved.
  Keywords: Ankylosing spondylitis; Axial spondylitis; Inflammatory bowel disease–associated spondyloarthritis; Psoriatic arthritis; Reactive arthritis; Spondyloarthritides
raw_completion_output: |-
  genes: HLA-B27
  exposures: Not mentioned in the provided text.
  gene_exposures_relationships: Not applicable (N/A) as no specific gene-exposure relationships are mentioned in the text.
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Not applicable (N/A) as no specific gene-exposure relationships are mentioned in the text.

  ===

extracted_object:
  genes:
    - HLA-B27
  exposures:
    - Not mentioned in the provided text.
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: Combining ultrasound radiomics, complete blood count, and serum biochemical biomarkers for diagnosing intestinal disorders in cats using machine learning.
  Abstract: This retrospective analytical observational cohort study aimed to model and predict the classification of feline intestinal diseases from segmentations of a transverse section from small intestine ultrasound (US) image, complete blood count (CBC), and serum biochemical profile data using a variety of machine-learning approaches. In 149 cats from three institutions, images were obtained from cats with biopsy-confirmed small cell epitheliotropic lymphoma (lymphoma), inflammatory bowel disease (IBD), no pathology ("healthy"), and other conditions (warrant a biopsy for further diagnosis). CBC, blood serum chemistry, small intestinal ultrasound, and small intestinal biopsy were obtained within a 2-week interval. CBC and serum biomarkers and radiomic features were combined for modeling. Four classification schemes were investigated: (1) normal versus abnormal; (2) warranting or not warranting a biopsy; (3) lymphoma, IBD, healthy, or other conditions; and (4) lymphoma, IBD, or other conditions. Two feature selection methods were used to identify the top 3, 5, 10, and 20 features, and six machine learning models were trained. The average (95% CI) performance of models for all combinations of features, numbers of features, and types of classifiers was 0.886 (0.871-0.912) for Model 1 (normal vs. abnormal), 0.751 (0.735-0.818) for Model 2 (biopsy vs. no biopsy), 0.504 (0.450-0.556) for Model 3 (lymphoma, IBD, healthy, or other), and 0.531 (0.426-0.589), for Model 4 (lymphoma, IBD, or other). Our findings suggest model accuracies above 0.85 can be achieved in Model 1 and 2, and that including CBC and biochemistry data with US radiomics data did not significantly improve accuracy in our models.© 2023 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.
  Keywords: artificial intelligence; feline; intestine; lymphoma
raw_completion_output: |-
  genes: No genes mentioned in the text.
  exposures: No exposures mentioned in the text.
  gene_exposures_relationships: No gene-exposures relationships mentioned in the text.
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  No gene-exposures relationships mentioned in the text.

  ===

extracted_object:
  genes:
    - No genes mentioned in the text.
  exposures:
    - No exposures mentioned in the text.
  gene_exposures_relationships:
    - molecular_activity: No mention of gene-exposures relationships
      gene: No mention of gene-exposures relationships
input_text: |-
  Title: Increasing Dietary Nutrient Levels Modulates Colon Immune Adaptation and Alleviates Inflammation in the Epithelial Heterogeneous Nuclear Ribonucleoprotein I (Hnrnp I) Knockout Mice.
  Abstract: Heterogeneous nuclear ribonucleoprotein I (HNRNP I) is an RNA-binding protein essential for neonatal immune adaptation by downregulating interleukin-1 receptor-associated kinase (IRAK1) in toll-like receptor (TLR)-mediated NF-κB signaling pathways. TLR-mediated NF-κB is associated with chronic inflammation, including the development of inflammatory bowel diseases. Therefore, dietary protein intake is one of the major concerns for individuals with inflammatory bowel diseases. The present study aims to investigate the effects of a protein-enriched diet on intestinal inflammation and immune responses in a mouse model with aberrant NF-κB signaling in the colon.A transgenic mouse model with intestinal-epithelial-cell (IEC) specific Hnrnp I knocked out was used to investigate the effects of protein intake on the immune system in the colon. A control diet (CON) and a nutrient-dense modified diet (MOD) were fed to both the wild-type (WT) and the knockout (KO) male mice for 14 weeks. Inflammatory markers and colonic immune responses were examined, with gene expression and protein expression levels analyzed. IEC-specific Hnrnp I knocked out mice had significantly increased expression of the active NF-κB subunit, P65, in their colons. There was a concomitant induction of mRNA expression of Il1β, Il6, Cxcl1, and Ccl2. The number of CD4+ T cells in the distal colon was also increased in the KO mice. The results confirmed that KO mice had pro-inflammatory responses with aberrant NF-κB signaling in the colon. Importantly, increased nutrient density in their diets attenuated colon inflammation by decreasing the expression of pro-inflammatory cytokines, reducing P65 translocation, downregulating IRAK1, and limiting the number of CD4+ T cells recruited in Hnrnp I KO mice colon.A diet with increased nutrient density relieved the inflammation induced by knockout of Hnrnp I, attributable partially to the reduced expression of inflammatory and immune-modulating cytokines in the mouse distal colon.Copyright © 2023. Published by Elsevier Inc.
  Keywords: Hnrnp I; Inflammation; colon immunity; dietary protein
raw_completion_output: |-
  genes: Hnrnp I, IRAK1, Il1β, Il6, Cxcl1, Ccl2
  exposures: dietary protein, nutrient-dense modified diet
  gene_exposures_relationships: Hnrnp I - downregulates IRAK1; nutrient-dense modified diet - attenuated colon inflammation
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  nutrient-dense modified diet - attenuated colon inflammation

  ===

extracted_object:
  genes:
    - Hnrnp I, IRAK1, Il1β, Il6, Cxcl1, Ccl2
  exposures:
    - dietary protein, nutrient-dense modified diet
  gene_exposures_relationships:
    - molecular_activity: downregulates
      gene: Hnrnp I
    - molecular_activity: attenuated colon inflammation
      gene: nutrient-dense modified diet
input_text: |-
  Title: Prior Authorizations Delay Therapy, Impact Decision Making, and Lead to Adverse Events in IBD: 2022 Provider Survey.
  Abstract: 
  Keywords: Crohn’s disease; Prior authorization; biologics; inflammatory bowel disease; ulcerative colitis
raw_completion_output: |-
  genes: None given in the text
  exposures: biologics
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None given in the text
  exposures:
    - biologics
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: High Frequency of Deep Infiltrating Endometriosis in Patients with Inflammatory Bowel Disease: A Nested Case-Control Study.
  Abstract: Inflammatory bowel disease (IBD) and endometriosis are chronic inflammatory diseases occurring in young women, sharing some clinical manifestations. In a multidisciplinary approach, we aimed to investigate symptoms, type, and site of pelvic endometriosis in IBD patients versus non-IBD controls with endometriosis.In a prospective nested case-control study, all female premenopausal IBD patients showing symptoms compatible with endometriosis were enrolled. Patients were referred to dedicated gynecologists for assessing pelvic endometriosis by transvaginal sonography (TVS). Each IBD patient with endometriosis (cases) was retrospectively matched for age (±5 years) and body mass index (±1) with 4 patients with endometriosis at TVS but no-IBD (controls). Data were expressed as median [range]; the Mann-Whitney or Student t and χ2 tests were used for comparisons.Endometriosis was diagnosed in 25 (71%) out of 35 IBD patients with compatible symptoms including 12 (52.6%) Crohn's disease and 13 (47.4%) ulcerative colitis patients. Dyspareunia and dyschezia were significantly more frequent in cases versus controls (25 [73.7%] vs. 26 [45.6%]; p = 0.03). At TVS, deep infiltrating endometriosis (DIE) and posterior adenomyosis were significantly more frequently observed in cases versus controls (25 [100%] vs. 80 [80%]; p = 0.03 and 19 [76%] vs. 48 [48%]; p = 0.02).Endometriosis was detected in two-thirds of IBD patients with compatible symptoms. The frequency of DIE and posterior adenomyosis was higher in IBD than in controls. A diagnosis of endometriosis, often mimicking IBD activity, should be considered in subgroups of female patients with IBD.© 2023 S. Karger AG, Basel.
  Keywords: Deep infiltrating endometriosis; Endometriosis; Inflammatory bowel disease
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: None mentioned in the text
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - None mentioned in the text
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Manifestation of acute appendicitis as known but paradox visceral side effect of ulcerative colitis anti-inflammatory therapy with januskinase-inhibitor Tofacitinib (Xeljanz™).
  Abstract: The etiopathogenesis of accompanying inflammatory phenomena and consequences of immunomodulation constitute a challenging and innovative field in the medical treatment of patients with autoimmune diseases.Based on i) clinical management experience gained from this challenging clinical case and ii) selective references of reports published in the scientific medical literature, we present an unusual counterfactual scientific case report. A patient diagnosed with ulcerative colitis undergoing januskinase (JAK)-inhibitor therapy developed acuteappendicitis as an unusual complication or as a visceral side effect of immunosuppressive/anti-inflammatory therapy.Scientific case report.(case description): Medical history: A 52-year-old male presented with spasmodic pain in the right lower abdomen lasting for two days (no fever, no bowel movement changes (no stool irregularities), no vomiting).Steroid-resistant ulcerative colitis treated with immunosuppressive therapy (Adalimumab administered for 10 months [next generation anti-TNFα mAb], Vendolizumab for 9 months [α4β7 integrin antagonist], Tofacitinib for 6 months); fructose intolerance, no previous abdominal surgery; medication: XeljanzTM (Tofacitinib, 5 mg 2x1; JAK-inhibitor; PFIZER PHARMA GmbH, Berlin,Germany); MutaflorTM (1x1; Ardeypharm GmbH, Herdecke, Germany).Pressure pain in the right lower abdomen with local muscular defense (Mc-Burney's/Lanz's point positive), no peritonism, Psoas-muscle sign positive.Laboratory parameters: standard value of white blood cell count, CrP: 25 mg/l.-Transabdominal ultrasound revealed hypertrophic 'appendix vermiformis' with detectable target-phenomenon and surrounding fluid.Indication for laparoscopic exploration.Under perioperative single-shot antibiotic administration with UnacidTM, the patient underwent emergency laparoscopic appendectomy due to confirmed acute appendicitis with additional lavage and placement of local drainage.The postoperative phase was uneventful (sufficient analgetic therapy, removal of local drainage on the 2nd postoperative day). The patient was discharged four days after surgery. Histopathology confirmed ulcero-phlegmonous, acute purulent appendicitis with fibrinous purulent mesenteriolitis.Immunosuppressive therapy was continued.Based on the paradoxon of an acute inflammatory disease (acute appendicitis) seen in the case of a patient undergoing immunosuppressive/anti-inflammatory treatment using a JAK-Inhibitor for ulcerative colitis, we consider this case worthy of publication although this side effect has previously been described in patients with rheumatoid arthritis. This might be the manifestation of i) an immunomodulatory effect that reduced or at least altered mucosal defense, including an increased risk of opportunistic infections, presenti
raw_completion_output: |-
  genes: januskinase (JAK)
  exposures: Tofacitinib (Xeljanz™)
  gene_exposures_relationships: januskinase (JAK) - Tofacitinib (Xeljanz™)
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  januskinase (JAK) - Tofacitinib (Xeljanz™)

  ===

extracted_object:
  genes:
    - januskinase (JAK)
  exposures:
    - Tofacitinib (Xeljanz™)
  gene_exposures_relationships:
    - molecular_activity: exposure to a chemical toxin
      gene: JAK
input_text: |-
  Title: Prevention of colitis-induced liver oxidative stress and inflammation in a transgenic mouse model with increased omega-3 polyunsaturated fatty acids.
  Abstract: Inflammatory bowel disease (IBD) is an immune-mediated gut dysfunction, which might also be associated with an inflammatory phenotype in the liver. It is known that the nutritional intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) is inversely correlated to the severity and occurrence of IBD. In order to investigate whether n-3 PUFA can also reduce liver inflammation and oxidative liver damage due to colon inflammation, we explored the dextran sulfate sodium (DSS)-induced colitis model in wild-type and fat-1 mice with endogenously increased n-3 PUFA tissue content. Besides confirming previous data of alleviated DSS-induced colitis in the fat-1 mouse model, the increase of n-3 PUFA also resulted in a significant reduction of liver inflammation and oxidative damage in colitis-affected fat-1 mice as compared to wild-type littermates. This was accompanied by a remarkable increase of established inflammation-dampening n-3 PUFA oxylipins, namely docosahexaenoic acid-derived 19,20-epoxydocosapentaenoic acid and eicosapentaenoic acid-derived 15-hydroxyeicosapentaenoic acid and 17,18-epoxyeicosatetraenoic acid. Taken together, these observations demonstrate a strong inverse correlation between the anti-inflammatory lipidome derived from n-3 PUFA and the colitis-triggered inflammatory changes in the liver by reducing oxidative liver stress.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
  Keywords: Colitis; Fat-1 mice; Liver inflammation; Liver oxidative stress; n-3 PUFA
raw_completion_output: |-
  genes: No gene mentioned in the text.

  exposures: omega-3 polyunsaturated fatty acids (n-3 PUFA), dextran sulfate sodium (DSS)

  gene_exposures_relationships: No gene to molecular activity relationships mentioned in the text.
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  No gene to molecular activity relationships mentioned in the text.

  ===

extracted_object:
  genes:
    - No gene mentioned in the text.
  exposures:
    - omega-3 polyunsaturated fatty acids (n-3 PUFA), dextran sulfate sodium (DSS)
input_text: |-
  Title: Borrelia Burgdorferi, a Root Cause of Inflammatory Bowel Disease: A Case Report of Successful Treatment and Remission.
  Abstract: The Borrelia species is recognized to cause a myriad of non-specific symptoms among Lyme patients. It has also been documented in the literature to have the ability to incite autoimmune responses. Despite this, very few clinical cases have ever put together the autoimmune connection to such infections, including in Crohn's disease.A 14-year-old adolescent male with a previous diagnosis of Crohn's disease was discovered to have underlying Lyme disease caused by Borrelia burgdorferi infection. Identifying this as a potential cause of his autoimmune condition, an integrative medical approach was initiated, resulting in successful treatment and complete remission.Lyme disease should be recognized as a potential trigger of autoimmune conditions, especially Crohn's disease. This underlying cause is novel to the literature and may help many patients obtain the proper diagnosis so that curative treatment may be received.
  Keywords: 
raw_completion_output: |-
  genes: Borrelia burgdorferi

  exposures: Lyme disease, Borrelia burgdorferi

  gene_exposures_relationships: Borrelia burgdorferi -> autoimmune responses
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Borrelia burgdorferi -> autoimmune responses

  ===

extracted_object:
  genes:
    - Borrelia burgdorferi
  exposures:
    - Lyme disease, Borrelia burgdorferi
  gene_exposures_relationships:
    - molecular_activity: autoimmune responses
      gene: Borrelia burgdorferi
input_text: |-
  Title: Clinical Features and Natural History of Paediatric Patients with Ulcerative Proctitis: A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN.
  Abstract: Ulcerative proctitis (UP) is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and identify predictors of poor outcomes.Retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged<18 years diagnosed with UP between 01/01/2016-31/12/2020.We identified 196 patients with UP (median age at diagnosis 14.6 [IQR 12.5-16.0] years), with a median follow-up of 2.7 (IQR 1.7-3.8) years. The most common presenting symptoms were bloody stools (95%), abdominal pain (61%) and diarrhea )47%). At diagnosis, the median paediatric ulcerative colitis activity index (PUCAI) score was 25 (IQR 20-35), but most patients exhibited moderate-severe endoscopic inflammation. By the end-of-induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48% and 73%, respectively. The rates of treatment escalation to biologics at 1, 3 and 5 years were 10%, 22% and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and IBD-associated admission, with a score≥35 providing increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with proximal disease progression (48%) had significantly higher rates of cecal patch at diagnosis and higher PUCAI score by end-of-induction, compared to those without progression.Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.
  Keywords: children; inflammatory bowel disease; proctitis; ulcerative colitis
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: 5-aminosalicylic acid
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - 5-aminosalicylic acid
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Smoking and colorectal cancer in inflammatory bowel disease: Quantity matters?
  Abstract: 
  Keywords: 
raw_completion_output: |-
  genes: 

  exposures: smoking; 

  gene_exposures_relationships: smoking and colorectal cancer;
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  smoking and colorectal cancer

  ===

extracted_object:
  exposures:
    - NCIT:C154329
  gene_exposures_relationships:
    - molecular_activity: NCIT:C154329
      gene: colorectal cancer
named_entities:
  - id: NCIT:C154329
    label: smoking
input_text: |-
  Title: Recent developments on BMPs and their antagonists in inflammatory bowel diseases.
  Abstract: Inflammatory bowel diseases (IBDs), including ulcerative colitis, and Crohn's disease, are intestinal disorders characterized by chronic relapsing inflammation. A large proportion of patients with IBD will progress to develop colitis-associated colorectal cancer due to the chronic intestinal inflammation. Biologic agents that target tumour necrosis factor-α, integrin α4β7, and interleukin (IL)12/23p40 have been more successful than conventional therapies in treating IBD. However, drug intolerance and loss of response are serious drawbacks of current biologics, necessitating the development of novel drugs that target specific pathways in IBD pathogenesis. One promising group of candidate molecules are bone morphogenetic proteins (BMPs), members of the TGF-β family involved in regulating morphogenesis, homeostasis, stemness, and inflammatory responses in the gastrointestinal tract. Also worth examining are BMP antagonists, major regulators of these proteins. Evidence has shown that BMPs (especially BMP4/6/7) and BMP antagonists (especially Gremlin1 and follistatin-like protein 1) play essential roles in IBD pathogenesis. In this review, we provide an updated overview on the involvement of BMPs and BMP antagonists in IBD pathogenesis and in regulating the fate of intestinal stem cells. We also described the expression patterns of BMPs and BMP antagonists along the intestinal crypt-villus axis. Lastly, we synthesized available research on negative regulators of BMP signalling. This review summarizes recent developments on BMPs and BMP antagonists in IBD pathogenesis, which provides novel insights into future therapeutic strategies.© 2023. The Author(s).
  Keywords: 
raw_completion_output: |-
  genes: BMP4, BMP6, BMP7, Gremlin1, follistatin-like protein 1
  exposures: bone morphogenetic proteins (BMPs)
  gene_exposures_relationships: BMP4/6/7 are BMPs involved in IBD pathogenesis; Gremlin1 and follistatin-like protein 1 are BMP antagonists
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Gremlin1 and follistatin-like protein 1 are BMP antagonists

  ===

extracted_object:
  genes:
    - BMP4, BMP6, BMP7, Gremlin1, follistatin-like protein 1
  exposures:
    - bone morphogenetic proteins (BMPs)
  gene_exposures_relationships:
    - molecular_activity: BMPs involved in IBD pathogenesis
      gene: BMP4/6/7
    - molecular_activity: BMP antagonists
      gene: Gremlin1 and follistatin-like protein 1
input_text: |-
  Title: 7TSG6 hyaluronan matrix remodeling dampens the inflammatory response during colitis.
  Abstract: In response to tissue injury, changes in the extracellular matrix (ECM) can directly affect the inflammatory response and contribute to disease progression or resolution. During inflammation, the glycosaminoglycan hyaluronan (HA) becomes modified by tumor necrosis factor stimulated gene-6 (TSG6). TSG6 covalently transfers heavy chain (HC) proteins from inter-α-trypsin inhibitor (IαI) to HA in a transesterification reaction and is to date is the only known HC-transferase. By modifying the HA matrix, TSG6 generates HC:HA complexes that are implicated in mediating both protective and pathological responses. Inflammatory bowel disease (IBD) is a lifelong chronic disorder with well-described remodeling of the ECM and increased mononuclear leukocyte influx into the intestinal mucosa. Deposition of HC:HA matrices is an early event in inflamed gut tissue that precedes and promotes leukocyte infiltration. However, the mechanisms by which TSG6 contributes to intestinal inflammation are not well understood. The aim of our study was to understand how the TSG6 and its enzymatic activity contributes to the inflammatory response in colitis. Our findings indicate that inflamed tissues of IBD patients show an elevated level of TSG6 and increased HC deposition and that levels of HA strongly associate with TSG6 levels in patient colon tissue specimens. Additionally, we observed that mice lacking TSG6 are more vulnerable to acute colitis and exhibit an aggravated macrophage-associated mucosal immune response characterized by elevated pro-inflammatory cytokines and chemokines and diminished anti-inflammatory mediators including IL-10. Surprisingly, along with significantly increased levels of inflammation in the absence of TSG6, tissue HA levels in mice were found to be significantly reduced and disorganized, absent of typical "HA-cable" structures. Inhibition of TSG6 HC-transferase activity leads to a loss of cell surface HA and leukocyte adhesion, indicating that the enzymatic functions of TSG6 are a major contributor to stability of the HA ECM during inflammation. Finally, using biochemically generated HC:HA matrices derived by TSG6, we show that HC:HA complexes can attenuate the inflammatory response of activated monocytes. In conclusion, our data suggests that TSG6 exerts a tissue-protective, anti-inflammatory effect via the generation of HC:HA complexes that become dysregulated in IBD.Copyright © 2023. Published by Elsevier B.V.
  Keywords: Colitis; Extracellular matrix; Hyaluronan; IBD; TSG6
raw_completion_output: |-
  genes: TSG6, IL-10
  exposures: tumor necrosis factor, inter-α-trypsin inhibitor, hyaluronan
  gene_exposures_relationships: TSG6 with tumor necrosis factor, TSG6 with inter-α-trypsin inhibitor, TSG6 with hyaluronan
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  TSG6 with tumor necrosis factor, TSG6 with inter-α-trypsin inhibitor, TSG6 with hyaluronan

  ===

extracted_object:
  genes:
    - TSG6, IL-10
  exposures:
    - tumor necrosis factor, inter-α-trypsin inhibitor, hyaluronan
  gene_exposures_relationships:
    - molecular_activity: hyaluronan
      gene: HGNC:11898
named_entities:
  - id: HGNC:11898
    label: TSG6
input_text: |-
  Title: Delayed Ustekinumab Responders in Ulcerative Colitis Have Greater Inflammatory Burden but Similar Outcomes as Early Responders.
  Abstract: Differences in one-year outcomes among early compared to delayed responders to vedolizumab have been demonstrated in ulcerative colitis. However, it is unclear whether similar differences exist with ustekinumab, and what factors differentiate delayed responders from non-responders.This was a post-hoc analysis of patient-level data from the UNIFI clinical trial. Ustekinumab-treated patients with clinical response, defined as reduction in total Mayo score ≥30% and ≥3 points from baseline with reduction in rectal bleeding subscore (RBS)≥1 or RBS≤1, at week 8 were deemed early responders and their outcomes were compared with delayed responders (week 8 non-responders who subsequently responded at week 16). The primary outcome assessed was one-year clinical remission (CR), defined as total Mayo score ≤2 and no subscore >1.We included 642 ustekinumab-treated patients, including 321 (50%) early responders, 115 (17.9%) delayed responders, and 205 (32.1%) non-responders. No differences were observed for one-year CR among early vs. delayed responders [132/321 (41.1%) vs. 40/115 (34.8%), p=0.233], nor for other outcomes assessed regardless of induction dose. Compared to early responders, delayed responders had more severe baseline Mayo endoscopic disease [88/115 (76.5%) vs. 206/321 (64.2%), p=0.015] and abnormal baseline CRP >3mg/L [83/115 (72.2%) vs. 183/321 (57%), p=0.004]. Compared to non-responders, delayed responders had a significant decline in CRP (F(4, 844), p<0.0001) and fecal calprotectin (F(4, 818), p<0.0001) through week 16.Compared with early ustekinumab responders, delayed responders had greater inflammatory burden at baseline. Early and delayed responders have similar one-year outcomes. Biomarker decline observed in delayed responders can help differentiate them from non-responders.Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.
  Keywords: Endoscopic Improvement; Inflammatory Bowel Disease; Ulcerative Colitis
raw_completion_output: |-
  genes: N/A
  exposures: ustekinumab, vedolizumab
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - ustekinumab, vedolizumab
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: Eriocalyxin B ameliorated Crohn's disease-like colitis by restricting M1 macrophage polarization through JAK2/STAT1 signalling.
  Abstract: M1 polarization of macrophages in the intestine is an important maintenance factor of the inflammatory response in Crohn's disease (CD). Eriocalyxin B (EriB) is a natural medicine that antagonizes inflammation. Our study aimed to determine the effects of EriB on CD-like colitis in mice, as well as the possible mechanism.2,4,6-trinitrobenzene sulfonic acid (TNBS) mice and Il-10-/- mice were used as CD animal models, and the therapeutic effect of EriB on CD-like colitis in mice was addressed by the disease activity index (DAI) score, weight change, histological analysis and flow cytometry assay. To assess the direct role of EriB in regulating macrophage polarization, bone marrow-derived macrophages (BMDMs) were induced to M1 or M2 polarization separately. Molecular docking simulations and blocking experiments were performed to explore the potential mechanisms by which EriB regulates the macrophage polarization.EriB treatment reduced body weight loss, DAI score and histological score, demonstrating the improvement of colitis symptoms in mice. In vivo and in vitro experiments both showed that EriB decreased the M1 polarization of macrophages, and suppressed the release of proinflammatory cytokines (IL-1β, TNF-α and IL-6) in mouse colons and BMDMs. The activation of Janus kinase 2/signal transducer and activator of transcription 1 (JAK2/STAT1) signals could be inhibited by EriB, which may be related to the regulation of EriB on M1 polarization.EriB inhibits the M1 polarization of macrophages by attenuating the JAK2/STAT1 pathway, which partially explains the potential mechanism by which EriB ameliorates colitis in mice, and provides a new regimen for the clinical treatment of CD.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
  Keywords: Colitis; Crohn's disease; Eriocalyxin B; JAK2/STAT1; macrophage
raw_completion_output: |-
  genes: JAK2, STAT1
  exposures: Eriocalyxin B, 2,4,6-trinitrobenzene sulfonic acid (TNBS), IL-1β, TNF-α, IL-6
  gene_exposures_relationships: JAK2/STAT1 to Eriocalyxin B
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  JAK2/STAT1 to Eriocalyxin B

  ===

extracted_object:
  genes:
    - JAK2, STAT1
  exposures:
    - CHEBI:48113
  gene_exposures_relationships:
    - molecular_activity: JAK2/STAT1
      gene: Eriocalyxin B
named_entities:
  - id: CHEBI:48113
    label: Eriocalyxin B, 2,4,6-trinitrobenzene sulfonic acid (TNBS), IL-1β, TNF-α,
      IL-6
input_text: |-
  Title: Lack of Seroconversion Following COVID-19 Vaccination Is an Independent Risk Factor for SARS-CoV-2 Infection in Patients With Inflammatory Bowel Disease: Data from ESCAPE-IBD, an IG-IBD Study.
  Abstract: 
  Keywords: SARS-CoV-2; Seroconversion; biologics; vaccine
raw_completion_output: |-
  genes: none mentioned in the text

  exposures: SARS-CoV-2, biologics, vaccine

  gene_exposures_relationships: none mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  none mentioned in the text

  ===

extracted_object:
  genes:
    - none mentioned in the text
  exposures:
    - SARS-CoV-2, biologics, vaccine
  gene_exposures_relationships:
    - molecular_activity: none mentioned in the text
      gene: none mentioned in the text
input_text: |-
  Title: Neutrophil-only histological assessment of ulcerative colitis correlates with endoscopic activity and predicts long-term outcomes in a multicenter study.
  Abstract: Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis (UC). The PICaSSO Histological remission Index (PHRI) is a new simple index for UC based only on the detection of neutrophils. We evaluate PHRI's correlation with endoscopy and its prognostic value compared to other established indices.Consecutive patients with UC underwent colonoscopy at 2 referral centres (Birmingham, UK and Milan, Italy) and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI] and Robarts [RHI]) and endoscopy (Mayo Endoscopic Score [MES]; Ulcerative Colitis Severity Endoscopic Index of Severity [UCEIS], and PICaSSO score) was calculated as Spearman coefficients. Diagnostic performance of endoscopy was assessed with ROC curves and outcome stratification with Kaplan-meier curves.192 patients with UC were enrolled, representing all grades of endoscopic severity. Correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI. In particular, PHRI's correlation with MES, UCEIS and PICaSSO was 0.745, 0.718, and 0.694, respectively. Endoscopically-assessed remission reflected the absence of neutrophils (PHRI = 0) with areas under the ROC curve of 0.905, 0.906, and 0.877 for MES, UCEIS, and PICaSSO, respectively. The hazard ratio for disease flare between patients in histological activity/remission was statistically similar (p>0.05) across indexes (2.752, 2.706, and 2.871 for RHI, NHI, and PHRI, respectively).PHRI correlates with endoscopy and stratifies risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.
  Keywords: PHRI; PICaSSO; endoscopic remission; histological remission; inflammatory bowel diseases; neutrophils
raw_completion_output: |-
  genes: None mentioned
  exposures: PICaSSO, Nancy, Robarts, Mayo Endoscopic Score, Ulcerative Colitis Severity Endoscopic Index of Severity, PICaSSO score, RHI, NHI
  gene_exposures_relationships: PHRI correlates with MES, UCEIS, PICaSSO; RHI, NHI, and PHRI reflect histological activity/remission; endoscopically-assessed remission reflects the absence of neutrophils (PHRI = 0)
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  endoscopically-assessed remission reflects the absence of neutrophils (PHRI = 0)

  ===

extracted_object:
  genes:
    - None mentioned
  exposures:
    - PICaSSO, Nancy, Robarts, Mayo Endoscopic Score, Ulcerative Colitis Severity
      Endoscopic Index of Severity, PICaSSO score, RHI, NHI
  gene_exposures_relationships:
    - molecular_activity: PHRI
      gene: PICaSSO
    - molecular_activity: histological activity/remission
      gene: RHI
    - molecular_activity: exposure to a chemical toxin
      gene: PHRI
input_text: |-
  Title: Effect of Bariatric Surgery on Disease Outcomes in Patients with Inflammatory Bowel Disease: A US-based Propensity Matched Cohort Study.
  Abstract: A growing body of evidence suggests a negative impact of obesity on the disease activity of inflammatory bowel disease (IBD). The primary aim of the study was to evaluate disease outcomes of IBD in patients after bariatric surgery (BS).Patients with IBD and morbid obesity who underwent BS were compared with patients with IBD and morbid obesity without BS in a retrospective, propensity-score matched cohort study using TriNetX, a multi-institutional database. The primary aim was to assess the 2-year risk of a composite of disease-related complications, which included intravenous steroid use or IBD-related surgery. Risk was expressed as adjusted odds ratios (aOR) with 95% confidence intervals (CI).In all, 482 patients (3.4%) with IBD and morbid obesity underwent BS (mean age 46.9±11.2 y old, mean BMI 42.1±7.72 kg/m2, Crohn's disease 60%). After propensity-score matching, the BS cohort had a lower risk (aOR 0.31, 95% CI 0.17-0.56) of a composite of IBD-related complications compared with the control cohort. After propensity-score matching, the BS cohort with sleeve gastrectomy had a decreased risk (aOR 0.45, 95% CI 0.31-0.66) of a composite of IBD-related complications. There was no difference in the risk (aOR 0.77, 95% CI 0.45-1.31) of a composite of IBD-related complications between the BS cohort with Roux-en-Y gastric bypass (RYGB) compared with the control cohort.Sleeve gastrectomy but not Roux-en-Y gastric bypass is associated with improved disease-specific outcomes in patients with IBD and morbid obesity.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
  Keywords: 
raw_completion_output: |-
  genes: N/A
  exposures: Bariatric surgery
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - Bariatric surgery
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: The Effect of Renin-Angiotensin-Aldosterone System Blocking Agents on the Long-term Disease Course of Patients With Crohn's Disease.
  Abstract: The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn's disease (CD) taking two commonly prescribed classes of RAAS-blocking agents.Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses.Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications.Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
  Keywords: 
raw_completion_output: |-
  genes: N/A (no genes mentioned in the text)
  exposures: angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB)
  gene_exposures_relationships: N/A (no gene-molecular activity relationships mentioned in the text)
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A (no gene-molecular activity relationships mentioned in the text)

  ===

extracted_object:
  genes:
    - N/A (no genes mentioned in the text)
  exposures:
    - angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker
      (ARB)
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: The role of complex interactions between the intestinal flora and host in regulating intestinal homeostasis and inflammatory bowel disease.
  Abstract: Pharmacological treatment of inflammatory bowel disease (IBD) is inefficient and difficult to discontinue appropriately, and enterobacterial interactions are expected to provide a new target for the treatment of IBD. We collected recent studies on the enterobacterial interactions among the host, enterobacteria, and their metabolite products and discuss potential therapeutic options. Intestinal flora interactions in IBD are affected in the reduced bacterial diversity, impact the immune system and are influenced by multiple factors such as host genetics and diet. Enterobacterial metabolites such as SCFAs, bile acids, and tryptophan also play important roles in enterobacterial interactions, especially in the progression of IBD. Therapeutically, a wide range of sources of probiotics and prebiotics exhibit potential therapeutic benefit in IBD through enterobacterial interactions, and some have gained wide recognition as adjuvant drugs. Different dietary patterns and foods, especially functional foods, are novel therapeutic modalities that distinguish pro-and prebiotics from traditional medications. Combined studies with food science may significantly improve the therapeutic experience of patients with IBD. In this review, we provide a brief overview of the role of enterobacteria and their metabolites in enterobacterial interactions, discuss the advantages and disadvantages of the potential therapeutic options derived from such metabolites, and postulate directions for further research.Copyright © 2023 Li, Xu, Cheng, Chen, Yi, Xiao, Zhao, Chen, Tian, Meng, Tang, Zhou, Ruan and Wei.
  Keywords: IBD therapies; functional foods; gut metabolome; inflammatory bowel disease; intestinal flora; intestinal homeostasis; short chain fatty acids (SCFAs)
raw_completion_output: |-
  genes: N/A
  exposures: intestinal flora, enterobacteria, metabolite products, SCFAs, bile acids, tryptophan, probiotics, prebiotics, dietary patterns, functional foods, gut metabolome
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - intestinal flora, enterobacteria, metabolite products, SCFAs, bile acids, tryptophan,
      probiotics, prebiotics, dietary patterns, functional foods, gut metabolome
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: Study of the roles of caspase-3 and nuclear factor kappa B in myenteric neurons in a P2X7 receptor knockout mouse model of ulcerative colitis.
  Abstract: The literature indicates that the enteric nervous system is affected in inflammatory bowel diseases (IBDs) and that the P2X7 receptor triggers neuronal death. However, the mechanism by which enteric neurons are lost in IBDs is unknown.To study the role of the caspase-3 and nuclear factor kappa B (NF-κB) pathways in myenteric neurons in a P2X7 receptor knockout (KO) mouse model of IBDs.Forty male wild-type (WT) C57BL/6 and P2X7 receptor KO mice were euthanized 24 h or 4 d after colitis induction by 2,4,6-trinitrobenzene sulfonic acid (colitis group). Mice in the sham groups were injected with vehicle. The mice were divided into eight groups (n = 5): The WT sham 24 h and 4 d groups, the WT colitis 24 h and 4 d groups, the KO sham 24 h and 4 d groups, and the KO colitis 24 h and 4 d groups. The disease activity index (DAI) was analyzed, the distal colon was collected for immunohistochemistry analyses, and immunofluorescence was performed to identify neurons immunoreactive (ir) for calretinin, P2X7 receptor, cleaved caspase-3, total caspase-3, phospho-NF-κB, and total NF-κB. We analyzed the number of calretinin-ir and P2X7 receptor-ir neurons per ganglion, the neuronal profile area (µm²), and corrected total cell fluorescence (CTCF).Cells double labeled for calretinin and P2X7 receptor, cleaved caspase-3, total caspase-3, phospho-NF-κB, or total NF-κB were observed in the WT colitis 24 h and 4 d groups. The number of calretinin-ir neurons per ganglion was decreased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups, respectively (2.10 ± 0.13 vs 3.33 ± 0.17, P < 0.001; 2.92 ± 0.12 vs 3.70 ± 0.11, P < 0.05), but was not significantly different between the KO groups. The calretinin-ir neuronal profile area was increased in the WT colitis 24 h group compared to the WT sham 24 h group (312.60 ± 7.85 vs 278.41 ± 6.65, P < 0.05), and the nuclear profile area was decreased in the WT colitis 4 d group compared to the WT sham 4 d group (104.63 ± 2.49 vs 117.41 ± 1.14, P < 0.01). The number of P2X7 receptor-ir neurons per ganglion was decreased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups, respectively (19.49 ± 0.35 vs 22.21 ± 0.18, P < 0.001; 20.35 ± 0.14 vs 22.75 ± 0.51, P < 0.001), and no P2X7 receptor-ir neurons were observed in the KO groups. Myenteric neurons showed ultrastructural changes in the WT colitis 24 h and 4 d groups and in the KO colitis 24 h group. The cleaved caspase-3 CTCF was increased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups, respectively (485949 ± 14140 vs 371371 ± 16426, P < 0.001; 480381 ± 11336 vs 378365 ± 4053, P < 0.001), but was not significantly different between the KO groups. The total caspase-3 CTCF, phospho-NF-κB CTCF, and total NF-κB CTCF were not significantly d
raw_completion_output: |-
  genes: caspase-3, nuclear factor kappa B (NF-κB), P2X7 receptor
  exposures: 2,4,6-trinitrobenzene sulfonic acid
  gene_exposures_relationships: P2X7 receptor triggers neuronal death
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  P2X7 receptor triggers neuronal death

  ===

extracted_object:
  genes:
    - caspase-3, nuclear factor kappa B (NF-κB), P2X7 receptor
  exposures:
    - 2,4,6-trinitrobenzene sulfonic acid
  gene_exposures_relationships:
    - molecular_activity: triggers neuronal death
      gene: P2X7 receptor
input_text: |-
  Title: Crohn's disease in human immunodeficiency virus-infected patient: A case report.
  Abstract: Inflammatory bowel disease (IBD) is an autoimmune condition treated with immunosuppressive drugs. However, the need for immune system suppression becomes questionable when infection with the human immunodeficiency virus (HIV) occurs simultaneously and impacts the course of IBD. Our reported case represents the clinical course, prescribed treatment and its effect, as well as clinical challenges faced by physicians in a combination of such diseases. We also present a comprehensive literature review of similar cases.A 49-year-old woman suffering from a newly diagnosed Crohn's disease was hospitalized due to exacerbated symptoms (abdominal pain, fever, and weight loss). During her hospital stay, she tested positive for HIV. With conservative treatment, the patient improved and was discharged. In the outpatient clinic, her HIV infection was confirmed as stage C3, and antiretroviral treatment was initiated immediately. That notwithstanding, soon the patient was rehospitalized with pulmonary embolism and developed a series of complications because of the subsequent coexistence of IBD and HIV. After intensive and meticulous treatment, the patient's condition has improved and she remains in remission.The paucity of studies and data on the coexistence of HIV and IBD leaves clinicians doubting the optimal treatment options.©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
  Keywords: Case report; Crohn’s disease; Human immunodeficiency virus; Immunocompromised patient; Inflammatory bowel disease
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: immunosuppressive drugs, human immunodeficiency virus (HIV), antiretroviral treatment
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - immunosuppressive drugs, human immunodeficiency virus (HIV), antiretroviral
      treatment
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: A peculiar case of intususception in a pregnant woman: A diagnostic challenge.
  Abstract: Adult intussusception presents a diagnostic challenge given its non-specific symptoms. It is not as common as in infants and young children. Traditionally, diagnostic steps are invariably fit for normal adults, but not in pregnancy which faces certain limitations. A 40-year-old pregnant mother, gravida 9 para 8 at 34-week gestation, complained of intermittent epigastric pain for 2 days, requiring hospitalization. She soon developed minimal per rectal bleeding that was ruled out as hemorrhoid. Imaging was limited due to her pregnancy status. She later developed spontaneous delivery to a premature baby. Computed tomography (CT) revealed an ileocolic intussusception, which was confirmed via exploratory laparotomy. Histology was consistent with inflammatory fibroid polyp. Acute abdomen in pregnancy can be due to various causes, thus a high index of suspicion and early CT abdomen might help in early diagnosis and treatment. The benefit of doing CT on the mother and the risk of CT on the fetus is to be weighed as the timely diagnosis can prevent bowel ischemia and reduce maternal morbidity and mortality. Surgery remains the definite management in adult intussusception and an exact diagnosis can be made during the operation.© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.
  Keywords: Abdominal neoplasms; Cecal diseases; Ileal diseases; Intussusception; Pregnant; case report
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: None mentioned in the text
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - None mentioned in the text
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: DietaAnti-Inflamatoria or DAIN: A Crohn's disease management strategy tailored for Puerto Ricans.
  Abstract: Diet has been increasingly shown to be of therapeutic benefit for patients with inflammatory bowel diseases (IBD), especially Crohn's disease (CD). Yet dietary guidelines are nonexistent. Moreover, diets tailored to Puerto Ricans with IBD living on the island, have not been developed and tested. The rising prevalence of IBD in Puerto Rico warrants exploring the use of diet as part of the treatment strategies for these patients [1]. Here, we describe the study design of "Dieta Anti-Inflamatoria" or DAIN, a parallel two-arm randomized pilot trial aiming at testing the efficacy of IBD-Anti-inflammatory diet (IBD-AID) adapted for adults with CD living in Puerto Rico (clinical trial registration number: NCT05627128). We tailored the IBD-AID to the local cuisine preferences and food availability by creating and adapting recipes consistent with the IBD-AID principles [2,3]. In focus groups with a Community Research Advisory Panel and one-on-one consultations with implementation experts, we identified several aspects of the intervention to adapt before the implementation. The objectives of the stakeholder/expert-informed adaptation were to improve feasibility and compliance while developing the culturally tailored dietary intervention. DAIN was designed for adults living in Puerto Rico with CD and geared to be affordable, appropriate, and acceptable for patients with mild-to-moderate CD. The significance of this work is the validation of culturally appropriate nutritional guidelines to help manage CD symptoms. DAIN provides a blueprint for a comprehensive nutritional program that can be adapted to regional preferences and local food availability allowing wider implementation of diet as an adjunct treatment in diverse clinical settings.© 2023 The Authors. Published by Elsevier Inc.
  Keywords: 
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: diet, IBD-Anti-inflammatory diet (IBD-AID), local cuisine, food availability, culturally tailored dietary intervention
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - diet, IBD-Anti-inflammatory diet (IBD-AID), local cuisine, food availability,
      culturally tailored dietary intervention
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Time to incorporate pre-emptive NUDT15 testing before starting thiopurines in inflammatory bowel disease in Asia and beyond: a review.
  Abstract: Thiopurine toxicity is related to genetic polymorphism. Thiopurine methyltransferase (TPMT) variants do not explain thiopurine toxicity in more than half of patients. Asian people, despite the low prevalence of TPMT variants, are more susceptible to thiopurine toxicity. Since 2014, studies from many Asian countries have shown a strong association between nucleoside diphosphate-linked moiety X-type motif (NUDT) 15 polymorphism and thiopurine-induced myelotoxicity.An English language literature search was performed for TPMT and NUDT15 genetic variants in inflammatory bowel disease and other diseases. This article discusses the merits of preemptive NUDT15 and TPMT testing in Asian and non-Asian IBD populations.The NUDT polymorphism occurs in up to 27% of the Asian and Hispanic population. The hematological toxicity occurs in up to a third of patients with this genetic variant. Given this, preemptive testing for NUDT15 variant is worthwhile and is probably more cost-effective than TPMT testing in these groups. Prevalence of NUDT15 variants is low in non-Finnish European population but NUDT15 variants have been linked to myelotoxicity along with TPMT genetic variants. NUDT15 preemptive testing should be considered in the migrant Asian population in Europe and North America and in Caucasian populations who develop myelotoxicity.
  Keywords: Crohn’s disease; Inflammatory bowel disease; Thiopurine toxicity in asian; Ulcerative colitis; thiopurine metabolism; thiopurine toxicity; thiopurines
raw_completion_output: |-
  genes: TPMT, NUDT15 
  exposures: nucleoside diphosphate-linked moiety X-type motif (NUDT) 15 polymorphism, thiopurines 
  gene_exposures_relationships: TPMT variants and thiopurine toxicity, NUDT15 polymorphism and thiopurine-induced myelotoxicity
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  TPMT variants and thiopurine toxicity, NUDT15 polymorphism and thiopurine-induced myelotoxicity

  ===

extracted_object:
  genes:
    - TPMT, NUDT15
  exposures:
    - nucleoside diphosphate-linked moiety X-type motif (NUDT) 15 polymorphism, thiopurines
  gene_exposures_relationships:
    - molecular_activity: thiopurine-induced myelotoxicity
      gene: HGNC:23063
named_entities:
  - id: HGNC:23063
    label: NUDT15
input_text: |-
  Title: Langerhans Cell Histiocytosis Caused by Adalimumab for Crohn's Disease: A Case Report.
  Abstract: 
  Keywords: 
raw_completion_output: |-
  genes: not mentioned in the text
  exposures: Adalimumab
  gene_exposures_relationships: not mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  not mentioned in the text

  ===

extracted_object:
  genes:
    - not mentioned in the text
  exposures:
    - Adalimumab
  gene_exposures_relationships:
    - molecular_activity: not mentioned in the text
      gene: not mentioned in the text
input_text: |-
  Title: Bakdrive: identifying a minimum set of bacterial species driving interactions across multiple microbial communities.
  Abstract: Interactions among microbes within microbial communities have been shown to play crucial roles in human health. In spite of recent progress, low-level knowledge of bacteria driving microbial interactions within microbiomes remains unknown, limiting our ability to fully decipher and control microbial communities.We present a novel approach for identifying species driving interactions within microbiomes. Bakdrive infers ecological networks of given metagenomic sequencing samples and identifies minimum sets of driver species (MDS) using control theory. Bakdrive has three key innovations in this space: (i) it leverages inherent information from metagenomic sequencing samples to identify driver species, (ii) it explicitly takes host-specific variation into consideration, and (iii) it does not require a known ecological network. In extensive simulated data, we demonstrate identifying driver species identified from healthy donor samples and introducing them to the disease samples, we can restore the gut microbiome in recurrent Clostridioides difficile (rCDI) infection patients to a healthy state. We also applied Bakdrive to two real datasets, rCDI and Crohn's disease patients, uncovering driver species consistent with previous work. Bakdrive represents a novel approach for capturing microbial interactions.Bakdrive is open-source and available at: https://gitlab.com/treangenlab/bakdrive.© The Author(s) 2023. Published by Oxford University Press.
  Keywords: 
raw_completion_output: |-
  genes: Not mentioned in the text.

  exposures: Not mentioned in the text.

  gene_exposures_relationships: Not mentioned in the text.
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Not mentioned in the text.

  ===

extracted_object:
  genes:
    - Not mentioned in the text.
  exposures:
    - Not mentioned in the text.
  gene_exposures_relationships:
    - molecular_activity: Not mentioned in the text.
      gene: Not mentioned in the text.
input_text: |-
  Title: Efficacy of Crohn's disease exclusion diet in treatment -naïve children and children progressed on biological therapy: a retrospective chart review.
  Abstract: Recent trials suggested that the Crohn's disease (CD) exclusion diet (CDED) plus partial enteral nutrition (PEN) is a safe and effective strategy in remission induction of paediatric-onset CD. However, real-world evidence regarding the safety and efficacy of the CDED plus PEN approach is still lacking. The present case-series study reported our experience with the outcomes of CDED plus PEN in the paediatric-onset CD at disease onset and after the loss of response to biologics.We conducted a retrospective chart review on children who were treated with CDED plus PEN through the period from July 2019 and December 2020. Clinical and laboratory data were retrieved and compared at baseline, 6, 12, and 24 weeks of treatment. The primary endpoint of the present study was the rate of clinical remission.The present study retrieved the data from 15 patients. Of them, nine patients were treatment naïve at the time of initiation of CDED plus PEN (group A) and the remaining patients relapsed on biologics before treatment. All patients in groups A and B exhibited clinical remission in week six, which was sustained until week 12. At the end of the follow-up, the clinical remission rate was 87% and 60% in groups A and B, respectively. No side effects were observed in both groups. In group A, the faecal calprotectin (FC) and albumin improved at week six, week 12, and week 24 (p < 0.05). The erythrocyte sedimentation rate (ESR) improved significantly at week 12 (p = 0.021) and week 24 (p = 0.027). At the same time, the haemoglobin and iron levels showed significant improvement only at week 24. For group B, only FC showed numerical reductions over time that did not reach the level of statistical significance.Treatment with CDED plus PEN was well tolerated and achieved an excellent clinical remission rate in treatment-naive patients. However, the benefit of CDED plus PEN was less in patients who initiated the strategy after losing the response to biologics.© 2023. The Author(s).
  Keywords: Crohn’s disease; Crohn’s disease exclusion diet; Paediatrics; Partial enteral nutrition; Remission
raw_completion_output: |-
  genes: CD
  exposures: Crohn's disease exclusion diet (CDED), partial enteral nutrition (PEN), biologics
  gene_exposures_relationships: CD-CDED, CD-PEN, CD-biologics
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  CD-CDED, CD-PEN, CD-biologics

  ===

extracted_object:
  genes:
    - HGNC:2505
  exposures:
    - Crohn's disease exclusion diet (CDED), partial enteral nutrition (PEN), biologics
  gene_exposures_relationships:
    - molecular_activity: CD-biologics
      gene: biologics
named_entities:
  - id: HGNC:2505
    label: CD
input_text: |-
  Title: Spondyloarthritis with inflammatory bowel disease: the latest on biologic and targeted therapies.
  Abstract: Spondyloarthritis (SpA) encompasses a heterogeneous group of chronic inflammatory diseases that can affect both axial and peripheral joints, tendons and entheses. Among the extra-articular manifestations, inflammatory bowel disease (IBD) is associated with considerable morbidity and effects on quality of life. In everyday clinical practice, treatment of these conditions requires a close collaboration between gastroenterologists and rheumatologists to enable early detection of joint and intestinal manifestations during follow-up and to choose the most effective therapeutic regimen, implementing precision medicine for each patient's subtype of SpA and IBD. The biggest issue in this field is the dearth of drugs that are approved for both diseases, as only TNF inhibitors are currently approved for the treatment of full-spectrum SpA-IBD. Janus tyrosine kinase inhibitors are among the most promising drugs for the treatment of peripheral and axial SpA, as well as for intestinal manifestations. Other therapies such as inhibitors of IL-23 and IL-17, phosphodiesterase 4 inhibitor, α4β7 integrin blockers and faecal microbiota transplantation seem to only be able to control some disease domains, or require further studies. Given the growing interest in the development of novel drugs to treat both conditions, it is important to understand the current state of the art and the unmet needs in the management of SpA-IBD.© 2023. Springer Nature Limited.
  Keywords: 
raw_completion_output: |-
  genes: TNF, Janus tyrosine kinase, IL-23, IL-17, phosphodiesterase 4, α4β7 integrin
  exposures: TNF inhibitors, Janus tyrosine kinase inhibitors, inhibitors of IL-23 and IL-17, phosphodiesterase 4 inhibitor, α4β7 integrin blockers, faecal microbiota transplantation
  gene_exposures_relationships: TNF inhibitors - SpA-IBD treatment; Janus tyrosine kinase inhibitors - peripheral and axial SpA treatment and treatment of intestinal manifestations; inhibitors of IL-23 and IL-17 - control of some disease domains, potential treatment but require further studies; phosphodiesterase 4 inhibitor - potential treatment but require further studies; α4β7 integrin blockers - potential treatment but require further studies; faecal microbiota transplantation - potential treatment but require further studies
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  faecal microbiota transplantation - potential treatment but require further studies

  ===

extracted_object:
  genes:
    - TNF, Janus tyrosine kinase, IL-23, IL-17, phosphodiesterase 4, α4β7 integrin
  exposures:
    - TNF inhibitors, Janus tyrosine kinase inhibitors, inhibitors of IL-23 and IL-17,
      phosphodiesterase 4 inhibitor, α4β7 integrin blockers, faecal microbiota transplantation
  gene_exposures_relationships:
    - molecular_activity: TNF inhibitors
      gene: SpA-IBD treatment
    - molecular_activity: Janus tyrosine kinase inhibitors
      gene: not mentioned in the text
    - molecular_activity: inhibitors of IL-23 and IL-17
      gene: HGNC:5981
    - molecular_activity: phosphodiesterase 4 inhibitor
      gene: None
    - molecular_activity: α4β7 integrin blockers
      gene: N/A
named_entities:
  - id: HGNC:5981
    label: IL-17
input_text: |-
  Title: [Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn's disease].
  Abstract: Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression
raw_completion_output: |-
  genes: WNT2B, CXCL12, glycogen synthase kinase-3β
  exposures: salinomycin, SKL2001, phosphate buffer
  gene_exposures_relationships: WNT2B to macrophage activation, fibroblast transfected with WNT2B plasmid to elevated level of glycogen synthase kinase-3β phosphorylation, salinomycin to reversal of glycogen synthase kinase-3β phosphorylation change, SKL2001 to macrophage treatment, phosphate buffer as control group.
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  WNT2B to macrophage activation, fibroblast transfected with WNT2B plasmid to elevated level of glycogen synthase kinase-3β phosphorylation, salinomycin to reversal of glycogen synthase kinase-3β phosphorylation change, SKL2001 to macrophage treatment, phosphate buffer as control group.

  ===

extracted_object:
  genes:
    - WNT2B, CXCL12, glycogen synthase kinase-3β
  exposures:
    - salinomycin, SKL2001, phosphate buffer
  gene_exposures_relationships:
    - molecular_activity: macrophage treatment
      gene: SKL2001
input_text: |-
  Title: Sialylation shapes mucus architecture inhibiting bacterial invasion in the colon.
  Abstract: In the intestine, Mucin 2 (Muc2) forms a network structure and prevents bacterial invasion. Glycans are indispensable for Muc2 barrier function. Among various glycosylation patterns of Muc2, sialylation inhibits a bacteria-dependent Muc2 degradation. However, the mechanisms by which Muc2 creates the network structure and sialylation prevents the mucin degradation remain unknown. Here, by focusing on two colon-specific glycosyltransferases, St6galnac6 and B3galt5, mediating the generation of disialylated glycans, we show that sialylation forms the network structure of Muc2 by providing negative charge and hydrophilicity. The colonic mucus of mice lacking St6galnac6 and B3galt5 was less sialylated, thinner, and more permeable to microbiota, resulting in high susceptibility to intestinal inflammation. Mice with a B3galt5 mutation associated with inflammatory bowel disease (IBD) also showed the loss of disialylated glycans of mucus and the high susceptibility to intestinal inflammation, suggesting that the reduced sialylation of Muc2 is associated with the pathogenesis of IBD. In mucins of mice with reduced sialylation, negative charge was reduced, the network structure was disturbed, and many bacteria invaded. Thus, sialylation mediates the negative charging of Muc2 and facilitates crosslinking of Muc2 polymers to form the network structure, and thereby inhibits bacterial invasion in the colon to maintain gut homeostasis.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
  Keywords: 
raw_completion_output: |-
  genes: Mucin 2 (Muc2), St6galnac6, B3galt5

  exposures: sialylation

  gene_exposures_relationships: Muc2 to sialylation
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Muc2 to sialylation

  ===

extracted_object:
  genes:
    - HGNC:7512
  exposures:
    - sialylation
  gene_exposures_relationships:
    - molecular_activity: sialylation
      gene: HGNC:7512
named_entities:
  - id: HGNC:7512
    label: Mucin 2 (Muc2), St6galnac6, B3galt5
input_text: |-
  Title: Adiponectin Levels in Inflammatory Bowel Disease - A Systematic Review and Meta-analysis.
  Abstract: Adipose tissue plays an important role in the pathogenesis of inflammatory conditions. The role of adipokines in inflammatory bowel disease (IBD) has been evaluated in the current literature with conflicting results. The aim of this study was to evaluate adiponectin levels in IBD patients, including Crohn's disease (CD) and ulcerative colitis (UC), compared to controls, as well as further subgroup analyses. Hence, assessing the potential role of adiponectin as a surrogate marker.We performed a systematic electronic search on PubMed, EMBASE, Scopus and Cochrane Library, including observational or interventional studies evaluating serum or plasma adiponectin levels in IBD patients on humans. The primary summary outcome was the mean difference (MD) in serum or plasma adiponectin levels between IBD patients vs. controls. Subgroups analyses were conducted involving adiponectin levels in CD and UC compared to controls, as well as CD compared to UC.A total of 20 studies were included in our qualitative synthesis and 14 studies in our quantitative synthesis, with a total population sample of 2,085 subjects. No significant MD in serum adiponectin levels was observed between IBD patients vs. controls (-1.331 [95% CI -3.135-0.472]), UC patients vs. controls (-0.213 [95% CI -1.898-1.472]), and CD patients vs. controls (-0.851 [95% CI -2.263-0.561]). Nevertheless, a significant MD was found between UC patients vs. CD patients (0.859 [95% CI 0.097-1.622]).Serum adiponectin levels were not able to differentiate between IBD, UC and CD patients compared to controls. However, significantly higher serum adiponectin levels were observed in UC compared to CD patients.S. Karger AG, Basel.
  Keywords: 
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: adiponectin
  gene_exposures_relationships: None mentioned in the text
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - adiponectin
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text
      gene: None mentioned in the text
input_text: |-
  Title: Clinical course of new-onset Crohn's disease in children and adolescents in dependency of age, initial location, initial severity level and therapy over the period 2000-2014 based on the Saxon Pediatric IBD-Registry in Germany.
  Abstract: In Saxony, the incidence of Crohn's disease (CD) in children and adolescents increased significantly from 3.3 per 100,000 person-years in 2000 to 5.1 in 2014. The aim of this study was to describe the initial characteristics and the clinical course of CD in children and adolescents and to identify drug treatment options associated with an advantage for a mild course or remission.Clinical data were collected from patients who suffered from inflammatory bowel disease (IBD) and were recruited in the Saxon Pediatric IBD-Registry. All children newly diagnosed with CD in this registry in Saxony between 2000 and 2014 were included in this registry study. Characteristics such as age, disease location and extra-intestinal manifestations at diagnosis were accessed. The severity level of the disease at diagnosis as well as at follow-up were analysed by PCDAI index. Patients were divided into 3 groups according to length of follow-up: 1-3 years, 4-6 years and 7-9 years after diagnosis. A logistic regression model was conducted to examine which baseline parameters are associated with disease progression.There were 338 children and adolescents with CD included in this registry study. At diagnosis, the median age of patients was 12.0 (0.7-14.9), 61.5% (n = 208) of the patients were male. The most common disease location observed in pediatric CD patients was the L3 (55%, n = 176). Patients aged 10-14 years were significantly more likely to present an L2 than patients aged 0-4 years (80.3%, n = 53 vs. 19.7%, n = 13, p = 0.01). During the follow-up, data from 71.3% (n = 241) othe patients were available. Disease activity measured by PCDAI decreased in 47.7% (n = 115) of the patients, 40.7% (n = 98) of the patients were stable and increased in 11.6% (n = 28) of the patients. Patients with intermediate/severe disease at onset were more likely to have an active disease at the end of follow up, too (p = 0.00). Logistic regression analysis of the initial characteristics showed that the age at diagnosis, gender, initial location and initial extra-intestinal manifestation are not associated with the progression of the disease (p>0.05). Furthermore, drug treatment options could be identified from our data, which are associated with benefits for a milder course or remission.From 2000 to 2014, the health status of most pediatric patients with CD had improved or remained stable. Initial characteristics including age at diagnosis, initial localization and initial extra-intestinal manifestation are not associated with the progression of the disease, only the initial activity by PCDAI.Copyright: © 2023 Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestr
raw_completion_output: |-
  genes: None mentioned in the text
  exposures: drug treatment options
  gene_exposures_relationships: None relevant
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None relevant

  ===

extracted_object:
  genes:
    - None mentioned in the text
  exposures:
    - drug treatment options
  gene_exposures_relationships:
    - molecular_activity: None relevant
      gene: None relevant
input_text: |-
  Title: Nutritional aspects of inflammatory bowel disease.
  Abstract: The number of people diagnosed with inflammatory bowel disease (IBD) continues to increase in most parts of the world. Although the exact etiology of this chronic intestinal disease is not fully understood, nutritional factors appear to play key roles. Furthermore, individuals with IBD are at increased risk of adverse nutritional impacts, including micronutrient deficiencies.This review aims to summarize recent reports focusing on nutritional factors relevant to the development of IBD and to also review data on nutritional deficiencies seen in individuals with IBD.The typical Western diet, characterized by high-fat/high-sugar foods, along with food additives, appears to contribute to the etiopathogenesis of IBD. In contrast, some reports indicate that some foods are likely protective. However, there are inconsistencies in the currently available data, reflecting study design and other confounding factors. Furthermore, some of the conclusions are inferred from animal or in vitro studies. The presence of IBD can compromise the nutrition of individuals with one of these disorders: ongoing monitoring is critical. Nutrition and diet in the setting of IBD remain key areas for further and ongoing study.
  Keywords: Crohn disease; Diet; Inflammation; Inflammatory bowel disease; Nutrition; ulcerative colitis
raw_completion_output: |-
  genes: Crohn disease; ulcerative colitis
  exposures: nutritional factors; high-fat/high-sugar foods; food additives
  gene_exposures_relationships: Crohn disease - nutrition; ulcerative colitis - nutrition
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  ulcerative colitis - nutrition

  ===

extracted_object:
  genes:
    - Crohn disease
    - ulcerative colitis
  exposures:
    - nutritional factors
    - high-fat/high-sugar foods
    - CHEBI:64047
  gene_exposures_relationships:
    - molecular_activity: nutrition
      gene: Crohn disease
    - molecular_activity: nutrition
      gene: ulcerative colitis
named_entities:
  - id: CHEBI:64047
    label: food additives
input_text: |-
  Title: Incisional hernia rates between intracorporeal and extracorporeal anastomosis in minimally invasive ileocolic resection for Crohn's disease.
  Abstract: One-third of patients with Crohn's disease (CD) require multiple surgeries during their lifetime. So, reducing the incisional hernia rate is crucial. We aimed to define incisional hernia rates after minimally invasive ileocolic resection for CD, comparing intracorporeal anastomosis with Pfannenstiel incision (ICA-P) versus extracorporeal anastomosis with midline vertical incision (ECA-M).This retrospective cohort compares ICA-P versus ECA-M from a prospectively maintained database of consecutive minimally invasive ileocolic resections for CD performed between 2014 and 2021 in a referral center.Of the 249 patients included: 59 were in the ICA-P group, 190 in the ECA-M group. Both groups were similar according to baseline and preoperative characteristics. Overall, 22 (8.8%) patients developed an imaging-proven incisional hernia: seven at the port-site and 15 at the extraction-site. All 15 extraction-site incisional hernias were midline vertical incisions [7.9%; p = 0.025], and 8 patients (53%) required surgical repair. Time-to-event analysis showed a 20% rate of extraction-site incisional hernia in the ECA-M group after 48 months (p = 0.037). The length of stay was lower in the intracorporeal anastomosis with Pfannenstiel incision group [ICA-P: 3.3 ± 2.5 vs. ECA-M: 4.1 ± 2.4 days; p = 0.02] with similar 30-day postoperative complication [11(18.6) vs. 59(31.1); p = 0.064] and readmission rates [7(11.9) vs. 18(9.5); p = 0.59].Patients in the ICA-P group did not encounter any incisional hernias while having shorter hospital length of stay and similar 30-day postoperative complications or readmission compared to ECA-M. Therefore, more consideration should be given to performing intracorporeal anastomosis with Pfannenstiel incision during Ileocolic resection in patients with CD to reduce hernia risk.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
  Keywords: Anastomosis; Crohn disease; Ileocolic resection; Incisional hernia; Minimally invasive surgery
raw_completion_output: |-
  genes: N/A
  exposures: Pfannenstiel incision, midline vertical incision, intracorporeal anastomosis, extracorporeal anastomosis
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - Pfannenstiel incision, midline vertical incision, intracorporeal anastomosis,
      extracorporeal anastomosis
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
input_text: |-
  Title: The Tolerance of Gut Commensal Faecalibacterium to Oxidative Stress Is Strain Dependent and Relies on Detoxifying Enzymes.
  Abstract: Obligate anaerobic bacteria in genus Faecalibacterium are among the most dominant taxa in the colon of healthy individuals and contribute to intestinal homeostasis. A decline in the abundance of this genus is associated with the occurrence of various gastrointestinal disorders, including inflammatory bowel diseases. In the colon, these diseases are accompanied by an imbalance between the generation and elimination of reactive oxygen species (ROS), and oxidative stress is closely linked to disruptions in anaerobiosis. In this work, we explored the impact of oxidative stress on several strains of faecalibacteria. An in silico analysis of complete genomes of faecalibacteria revealed the presence of genes encoding O2- and/or ROS-detoxifying enzymes, including flavodiiron proteins, rubrerythrins, reverse rubrerythrins, superoxide reductases, and alkyl peroxidase. However, the presence and the number of these detoxification systems varied greatly among faecalibacteria. These results were confirmed by O2 stress survival tests, in which we found that strains differed widely in their sensitivity. We showed the protective role of cysteine, which limited the production of extracellular O2•- and improved the survival of Faecalibacterium longum L2-6 under high O2 tension. In the strain F. longum L2-6, we observed that the expression of genes encoding detoxifying enzymes was upregulated in the response to O2 or H2O2 stress but with different patterns of regulation. Based on these results, we propose a first model of the gene regulatory network involved in the response to oxidative stress in F. longum L2-6. IMPORTANCE Commensal bacteria in the genus Faecalibacterium have been proposed for use as next-generation probiotics, but efforts to cultivate and exploit the potential of these strains have been limited by their sensitivity to O2. More broadly, little is known about how commensal and health-associated bacterial species in the human microbiome respond to the oxidative stress that occurs as a result of inflammation in the colon. In this work, we provide insights regarding the genes that encode potential mechanisms of protection against O2 or ROS stress in faecalibacteria, which may facilitate future advances in work with these important bacteria.
  Keywords: Faecalibacterium; oxidative stress; oxygen sensitivity; transcriptional regulation
raw_completion_output: |-
  genes: flavodiiron proteins; rubrerythrins; reverse rubrerythrins; superoxide reductases; alkyl peroxidase
  exposures: oxidative stress; reactive oxygen species (ROS); cysteine; O2 tension; O2; H2O2 stress
  gene_exposures_relationships: faecalibacteria have genes encoding O2- and/or ROS-detoxifying enzymes; cysteine limits the production of extracellular O2•- and improves the survival of Faecalibacterium longum L2-6 under high O2 tension; genes encoding detoxifying enzymes are upregulated in response to O2 or H2O2 stress with different patterns of regulation; the genes encode potential mechanisms of protection against O2 or ROS stress in faecalibacteria
prompt: |+
  From the text below, extract the following entities in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  the genes encode potential mechanisms of protection against O2 or ROS stress in faecalibacteria

  ===

extracted_object:
  genes:
    - flavodiiron proteins
    - rubrerythrins
    - reverse rubrerythrins
    - superoxide reductases
    - alkyl peroxidase
  exposures:
    - oxidative stress
    - CHEBI:26523
    - CHEBI:15356
    - O2 tension
    - CHEBI:15379
    - H2O2 stress
  gene_exposures_relationships:
    - molecular_activity: exposure to high O2 tension.
      gene: Faecalibacterium longum L2-6.
    - molecular_activity: O2 or H2O2 stress
      gene: detoxifying enzymes
    - molecular_activity: O2 or ROS stress
      gene: faecalibacteria
named_entities:
  - id: CHEBI:26523
    label: reactive oxygen species (ROS)
  - id: CHEBI:15356
    label: cysteine
  - id: CHEBI:15379
    label: O2
input_text: |-
  Title: Review article: Translating STRIDE-II into clinical reality - Opportunities and challenges.
  Abstract: With the introduction of novel therapies for inflammatory bowel diseases (IBD), 'treat-to-target' strategies are increasingly discussed to improve the short- and long-term outcomes in IBD patients.To discuss opportunities and challenges of a treat-to-target approach in light of the current 'Selecting Therapeutic Targets in Inflammatory Bowel Disease' (STRIDE-II) consensus.The 2021 update of STRIDE-II encompasses 13 evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. We highlight the potential implications and limitations of these recommendations for clinical practice.STRIDE-II provides valuable guidance for personalised IBD management. It reflects scientific progress as well as increased evidence of improved outcomes when more ambitious treatment goals such as mucosal healing are achieved.Prospective studies, objective criteria for risk stratification, and better predictors of therapeutic response are needed to potentially render 'treating to target' more effective in the future.© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
  Keywords: Crohn’s disease < disease-based; biologics (IBD) < topics; inflammatory bowel disease < disease-based; ulcerative colitis < disease-based
raw_completion_output: |-
  genes: 
  exposures: novel therapies, treatments, therapeutic response
  gene_exposures_relationships: None mentioned in the text.
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None mentioned in the text.

  ===

extracted_object:
  exposures:
    - novel therapies, treatments, therapeutic response
  gene_exposures_relationships:
    - molecular_activity: None mentioned in the text.
      gene: None mentioned in the text.
input_text: |-
  Title: Real-world experience with subcutaneous infliximab: broadening treatment strategies for inflammatory bowel disease.
  Abstract: The first subcutaneous (SC) formulation of infliximab (IFX), CT‑P13 SC, has been approved in Europe and Australia, including for the treatment of inflammatory bowel disease (IBD).We provide a comprehensive overview of available clinical trial and real-world data for IFX SC treatment of IBD, focusing on potential benefits of switching from IFX intravenous (IV) to IFX SC. We evaluate emerging evidence for IFX SC treatment for difficult-to-treat IBD, use as monotherapy, and suitability for patients receiving escalated IFX IV. Therapeutic drug monitoring approaches and patient and healthcare system perspectives on IFX SC are also discussed.IFX SC represents a significant treatment innovation in the tumor necrosis factor inhibitor class after approximately 20 years of IFX IV availability. Evidence suggests that IFX SC is well tolerated and is associated with high patient acceptance and satisfaction. In addition, effectiveness is maintained in patients with stable disease following switch from IFX IV. Switching may be advisable, given the clinical benefits of IFX SC and its potential to improve healthcare service capacity. There are several areas requiring further research, including the role of IFX SC in difficult-to-treat and refractory disease, and the feasibility of IFX SC monotherapy.
  Keywords: Anti-TNF; Crohn’s disease; biologics; inflammatory bowel disease; infliximab; subcutaneous; ulcerative colitis
raw_completion_output: |-
  genes: No genes mentioned
  exposures: infliximab (IFX), CT‑P13 SC
  gene_exposures_relationships: No gene to molecular activity relationships mentioned
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  No gene to molecular activity relationships mentioned

  ===

extracted_object:
  genes:
    - No genes mentioned
  exposures:
    - infliximab (IFX), CT‑P13 SC
input_text: |-
  Title: Posttranslational modifications of NLRP3 and their regulatory roles in inflammasome activation.
  Abstract: The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is a multimolecular complex that plays a fundamental role in inflammation. Optimal activation of NLRP3 inflammasome is crucial for host defense against pathogens and the maintenance of immune homeostasis. Aberrant NLRP3 inflammasome activity has been implicated in various inflammatory diseases. Posttranslational modifications (PTMs) of NLRP3, a key inflammasome sensor, play critical roles in directing inflammasome activation and controlling the severity of inflammation and inflammatory diseases, such as arthritis, peritonitis, inflammatory bowel disease, atherosclerosis, and Parkinson's disease. Various NLRP3 PTMs, including phosphorylation, ubiquitination, and SUMOylation, could direct inflammasome activation and control inflammation severity by affecting the protein stability, ATPase activity, subcellular localization, and oligomerization of NLRP3 as well as the association between NLRP3 and other inflammasome components. Here, we provide an overview of the PTMs of NLRP3 and their roles in controlling inflammation and summarize potential anti-inflammatory drugs targeting NLRP3 PTMs.© 2023 Wiley-VCH GmbH.
  Keywords: NLRP3; inflammasome; inflammation; posttranslational modifications; ubiquitination
raw_completion_output: |-
  genes: NLRP3
  exposures: posttranslational modifications
  gene_exposures_relationships: NLRP3 to posttranslational modifications
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  NLRP3 to posttranslational modifications

  ===

extracted_object:
  genes:
    - HGNC:16400
  exposures:
    - posttranslational modifications
  gene_exposures_relationships:
    - molecular_activity: posttranslational modifications
      gene: HGNC:16400
named_entities:
  - id: HGNC:16400
    label: NLRP3
input_text: |-
  Title: Chitinase 3-Like-1 Expression Is Upregulated Under Inflammatory Conditions in Human Oral Epithelial Cells.
  Abstract: Chitinase 3-like-1 (CHI3L1), also known as YKL-40, is a partially secreted glycoprotein and is involved in inflammatory disorders, including inflammatory bowel diseases. CHI3L1 is known to play a role in biological responses such as cell proliferation, tissue remodeling, and inflammation. CHI3L1 forms an immune complex (known as a Chitosome complex) with IL-13 receptor alpha 2 (IL-13 Rα2) and transmembrane protein 219 (TMEM219) to activate the MAPK/ERK and PKB/AKT signaling pathways. The objective of this study is to investigate how the expressions of CHI3L1 and a Chitosome complex in human oral cavity epithelial cells are linked with intraoral inflammatory diseases.CHI3L1 and Chitosome complex mRNA expressions were analyzed using human oral squamous cancer cell lines, HSC3 and HSC4 cells. Signaling activation in HSC4 cells was analyzed by using the western blot technique. Immunohistological analysis was performed using surgical samples obtained from patients with benign oral cavity tumors and cysts.Increased expression of CHI3L1 was observed in both HSC3 and HSC4 cells after TNFα stimulation. The expression of Chitosome complex factors increased as CHI3L1 levels increased, resulting in the activation of a downstream signaling pathway. Among the intraoral tissues, the epithelial cells from inflammatory lesions, but not benign tumors, were found to be intensively stained with the anti-CHI3L1 antibody.It was indicated that the formation of a Chitosome complex is induced during inflammation, leading to the activation of signaling pathways.
  Keywords: chitinase 3-like-1; chitosome complex; inflammation; oral epithelial cells
raw_completion_output: |-
  genes: CHI3L1, IL-13 Rα2, TMEM219
  exposures: TNFα, Chitosome complex
  gene_exposures_relationships: CHI3L1 - TNFα stimulation; CHI3L1 - Chitosome complex; Chitosome complex - activation of signaling pathways
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  Chitosome complex - activation of signaling pathways

  ===

extracted_object:
  genes:
    - CHI3L1, IL-13 Rα2, TMEM219
  exposures:
    - TNFα, Chitosome complex
  gene_exposures_relationships:
    - molecular_activity: TNFα stimulation
      gene: HGNC:1932
    - molecular_activity: Chitosome complex
      gene: HGNC:1932
    - molecular_activity: activation of signaling pathways
      gene: Chitosome complex
named_entities:
  - id: HGNC:1932
    label: CHI3L1
input_text: |-
  Title: Drug rediscovery in gastroenterology: from off-label to on-label use of thioguanine in inflammatory bowel disease.
  Abstract: Drug rediscovery refers to the principle of using 'old' drugs outside the indications mentioned in the summary of product characteristics. In the past decades, several drugs were rediscovered in a wide variety of medical fields. One of the most recent examples is the unconditional registration of thioguanine (TG), a thiopurine derivative, in patients with inflammatory bowel disease in the Netherlands. In this paper, we aim to visualise potential hurdles that hamper drug rediscovery in general, emphasise the global need for optimal use and development of potentially useful drugs, and provide an overview of the registration process for TG in the Netherlands. With this summary, we aim to guide drug rediscovery trajectories in the near future.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
  Keywords: azathioprine; crohn's disease; drug development; drug metabolism; inflammatory bowel disease
raw_completion_output: |-
  genes: N/A
  exposures: thioguanine (TG), thiopurine derivative
  gene_exposures_relationships: N/A
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  N/A

  ===

extracted_object:
  genes:
    - N/A
  exposures:
    - CHEBI:9516
  gene_exposures_relationships:
    - molecular_activity: N/A
      gene: N/A
named_entities:
  - id: CHEBI:9516
    label: thioguanine (TG), thiopurine derivative
input_text: |-
  Title: Author's Reply: ``Use of biologics for the management of Crohn's disease''.
  Abstract: 
  Keywords: 
raw_completion_output: |-
  genes: None
  exposures: None
  gene_exposures_relationships: None
prompt: |+
  Split the following piece of text into fields in the following format:

  molecular_activity: <the name of the exposure, such as a exposure to a chemical toxin.>
  gene: <the name of the gene in the pair. This comes second in the pair.>


  Text:
  None

  ===

extracted_object:
  genes:
    - None
  exposures:
    - None
  gene_exposures_relationships:
    - molecular_activity: None
      gene: None