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  1. Artikel ; Online: The Microbiome in Celiac Disease.

    Krishnareddy, Suneeta

    Gastroenterology clinics of North America

    2018  Band 48, Heft 1, Seite(n) 115–126

    Abstract: The healthy microbiome is necessary for normal immune development in the gut. Alterations in the microbial makeup after a critical window increase the risk of autoimmunity, including celiac disease. Although this dysbiosis has been described in adult and ...

    Abstract The healthy microbiome is necessary for normal immune development in the gut. Alterations in the microbial makeup after a critical window increase the risk of autoimmunity, including celiac disease. Although this dysbiosis has been described in adult and pediatric patients, factors leading to dysbiosis are still being elucidated. Genetics has some role in determining the microbiome makeup of the host, but other factors have yet to be determined. The microbiome remains an important therapeutic target in many autoimmune conditions, including celiac disease, however studies have yet to determine the ideal replacement therapy to correct the dysbiosis.
    Mesh-Begriff(e) Celiac Disease/etiology ; Celiac Disease/immunology ; Celiac Disease/microbiology ; Celiac Disease/therapy ; Gastrointestinal Microbiome/physiology ; Homeostasis/immunology ; Humans ; Prebiotics ; Probiotics/therapeutic use
    Chemische Substanzen Prebiotics
    Sprache Englisch
    Erscheinungsdatum 2018-12-13
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 92114-2
    ISSN 1558-1942 ; 0889-8553
    ISSN (online) 1558-1942
    ISSN 0889-8553
    DOI 10.1016/j.gtc.2018.09.008
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Novel Drug Therapeutics in Celiac Disease: A Pipeline Review.

    Varma, Sanskriti / Krishnareddy, Suneeta

    Drugs

    2022  Band 82, Heft 15, Seite(n) 1515–1526

    Abstract: Celiac disease (CeD) is a chronic, autoimmune systemic disorder triggered by the ingestion of gluten, a protein found in foods such as wheat, rye, and barley. The only effective treatment for CeD is complete removal of gluten from the diet. A strict ... ...

    Abstract Celiac disease (CeD) is a chronic, autoimmune systemic disorder triggered by the ingestion of gluten, a protein found in foods such as wheat, rye, and barley. The only effective treatment for CeD is complete removal of gluten from the diet. A strict gluten-free diet (GFD) results in symptomatic, serologic, and histologic remission in most patients. However, GFD may fail to induce clinical or histologic improvement and some patients may alternatively have difficulty strictly adhering to the GFD for other reasons. Despite this, there are currently no FDA-approved drugs for the treatment of CeD. The complex pathogenic process of CeD is becoming increasingly studied and better understood, enabling the identification of various targets for future therapies. Mechanisms under evaluation include probiotics, digestion of peptides, gluten sensitization, tight junction modulation, deamidation, and immune targets. Multiple investigational drugs are in the pipeline, and several drug candidates have entered late-phase clinical trials. Indeed, current and future studies are needed to target specific etiological mechanisms and provide an alternative to GFD alone. This review provides a broad overview of the various investigative treatment approaches for CeD, summarizing the latest progress in the pipeline.
    Mesh-Begriff(e) Humans ; Celiac Disease/drug therapy ; Diet, Gluten-Free ; Glutens/adverse effects ; Peptides ; Treatment Outcome
    Chemische Substanzen Glutens (8002-80-0) ; Peptides
    Sprache Englisch
    Erscheinungsdatum 2022-10-17
    Erscheinungsland New Zealand
    Dokumenttyp Review ; Journal Article
    ZDB-ID 120316-2
    ISSN 1179-1950 ; 0012-6667
    ISSN (online) 1179-1950
    ISSN 0012-6667
    DOI 10.1007/s40265-022-01784-2
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Clinical Factors Associated With Positive Stool PCR for Gastrointestinal Pathogens in Celiac and Inflammatory Bowel Disease.

    Varma, Sanskriti / Green, Peter H / Krishnareddy, Suneeta

    Journal of clinical gastroenterology

    2022  Band 56, Heft 3, Seite(n) e196–e202

    Abstract: Goals: We aimed to identify the clinical factors of celiac disease (CeD) and inflammatory bowel disease (IBD) associated with positive stool gastrointestinal (GI) polymerase chain reaction (PCR) test.: Background: Understanding the pattern of enteric ...

    Abstract Goals: We aimed to identify the clinical factors of celiac disease (CeD) and inflammatory bowel disease (IBD) associated with positive stool gastrointestinal (GI) polymerase chain reaction (PCR) test.
    Background: Understanding the pattern of enteric infections in CeD and IBD may allow further insight into microbiome-mediated pathogeneses.
    Study: This was a retrospective study of adult patients (age 18 y or above) with CeD and IBD at a large quaternary care institution. We identified patients with CeD or IBD who underwent stool GIPCR evaluation as outpatients (office visit or at endoscopy) between March 2015 and March 2019. Patients with a negative GIPCR test within the study time frame were randomly chosen as controls (1 : 1). The independent relationship between clinical characteristics and positive GIPCR was evaluated using multivariable logistic regression.
    Results: A total of 266 patients met criteria for the study, including 92 (35%) with CeD and 174 (65%) with IBD. On multivariable analysis of factors associated with positive GIPCR test, CeD patients were more likely to have diarrheal presentation of illness [odds ratio (OR): 2.61, 95% confidence interval (CI) 1.05-6.72], experience extraintestinal manifestations (OR: 2.49, 95% CI: 1.01-6.31), and practice a gluten-free diet for at least 5 years (OR: 4.00, 95% CI: 1.36-11.67), relative to those with a negative GIPCR test. IBD patients with positive GIPCR were more likely to be on corticosteroids (OR: 2.23, 95% CI: 1.02-5.4.84), experience extraintestinal manifestations (OR: 2.60, 95% CI: 1.22-5.53), and use proton-pump inhibitors (OR: 4.07, 95% CI: 1.69-9.77).
    Conclusions: Intestinal infections in CeD and IBD are associated with important disease-specific characteristics.
    Mesh-Begriff(e) Adolescent ; Adult ; Celiac Disease/complications ; Celiac Disease/diagnosis ; Colitis ; Feces ; Humans ; Inflammatory Bowel Diseases/complications ; Inflammatory Bowel Diseases/diagnosis ; Polymerase Chain Reaction ; Retrospective Studies
    Sprache Englisch
    Erscheinungsdatum 2022-02-22
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 448460-5
    ISSN 1539-2031 ; 0192-0790
    ISSN (online) 1539-2031
    ISSN 0192-0790
    DOI 10.1097/MCG.0000000000001657
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: STAT signaling in the intestine.

    Nobel, Yael R / Stier, Kenneth / Krishnareddy, Suneeta

    International review of cell and molecular biology

    2021  Band 361, Seite(n) 1–20

    Abstract: The Janus kinase (JAK), signal transducer of activation (STAT) pathway, discovered by investigating interferon gene induction, is now recognized as an evolutionary conserved signaling pathway employed by diverse cytokines, interferons, growth factors, ... ...

    Abstract The Janus kinase (JAK), signal transducer of activation (STAT) pathway, discovered by investigating interferon gene induction, is now recognized as an evolutionary conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules. Since its discovery, this pathway has become a paradigm for membrane-to-nucleus signaling and explains how a broad range of soluble factors such as cytokines and hormones, mediate their diverse functions. The understanding of JAK-STAT signaling in the intestine has not only impacted basic science research, particularly in the understanding of intercellular communication and cell-extrinsic control of gene expression, but it has also become a prototype for transition of bench to bedside research, culminating in the clinical implementation of pathway-specific therapeutics.
    Mesh-Begriff(e) Animals ; Clinical Trials as Topic ; Humans ; Intestines/metabolism ; Intestines/pathology ; Janus Kinases/metabolism ; Neoplasms/metabolism ; Neoplasms/pathology ; STAT Transcription Factors/chemistry ; STAT Transcription Factors/metabolism ; Signal Transduction
    Chemische Substanzen STAT Transcription Factors ; Janus Kinases (EC 2.7.10.2)
    Sprache Englisch
    Erscheinungsdatum 2021-05-13
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2427220-6
    ISSN 1937-6448 ; 0074-7696
    ISSN 1937-6448 ; 0074-7696
    DOI 10.1016/bs.ircmb.2021.02.001
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Predictors of Subsequent Celiac Disease Seropositivity in Patients Diagnosed with Duodenal Villus Atrophy on Upper Endoscopy.

    Ching, Charlotte K / Lyudmer, Michael / Lewis, Suzanne / Krishnareddy, Suneeta / Green, Peter H R / Lebwohl, Benjamin

    Digestive diseases and sciences

    2023  Band 69, Heft 3, Seite(n) 876–883

    Abstract: Background: The diagnosis of celiac disease (CD) is based on positive IgA autoantibodies to tissue transglutaminase (TTG IgA) and confirmatory histopathology demonstrating duodenal villus atrophy (VA). Diagnostic challenges can occur when VA is found on ...

    Abstract Background: The diagnosis of celiac disease (CD) is based on positive IgA autoantibodies to tissue transglutaminase (TTG IgA) and confirmatory histopathology demonstrating duodenal villus atrophy (VA). Diagnostic challenges can occur when VA is found on duodenal biopsies in patients without prior CD serologies.
    Aims: To characterize the predictors of CD seropositivity in patients with VA on biopsy without prior CD serologies.
    Methods: We performed a retrospective cohort study of patients found to have duodenal VA on histopathology from 2010 to 2020 who did not have prior CD serologies measured and who had them checked after their biopsy. Patients with known or suspected CD prior to their duodenal biopsy were excluded.
    Results: Of 162 patients with VA and no prior CD serologies, 50 (31%) subsequently had an elevated TTG IgA consistent with CD. Patients with an elevated TTG IgA were more likely to be non-Hispanic (76% vs. 42%; p < 0.001), white (74% vs. 62%; p = 0.025), and younger (ages 18-39, 26% vs. 12%; p = 0.002) compared to those with a negative TTG IgA. By contrast, these patients were less likely to present in middle adulthood (ages 40-59, 6% vs. 29%; p =  0.002). The most common identified etiologies of seronegative VA were Crohn's disease (13%), seronegative CD (8.9%), H. pylori infection (6.3%), tropical sprue (5.4%), and olmesartan-related enteropathy (3.6%).
    Conclusion: Age and ethnicity may be helpful when stratifying the likelihood of CD in the absence of supporting serologies. A majority of patients (69%) diagnosed with VA without prior CD serologies have negative serologies, consistent with seronegative CD or the spectrum of non-celiac enteropathies for which further evaluation is needed.
    Mesh-Begriff(e) Humans ; Adult ; Celiac Disease/complications ; Celiac Disease/diagnosis ; Celiac Disease/epidemiology ; Retrospective Studies ; Transglutaminases ; Duodenum/pathology ; Biopsy ; Autoantibodies ; Endoscopy, Gastrointestinal ; Digestive System Abnormalities ; Immunoglobulin A ; Atrophy/pathology
    Chemische Substanzen Transglutaminases (EC 2.3.2.13) ; Autoantibodies ; Immunoglobulin A
    Sprache Englisch
    Erscheinungsdatum 2023-12-19
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 304250-9
    ISSN 1573-2568 ; 0163-2116
    ISSN (online) 1573-2568
    ISSN 0163-2116
    DOI 10.1007/s10620-023-08217-4
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: The Distribution of Gastrointestinal Pathogens on Stool PCR Prior to the Development of IBD.

    Varma, Sanskriti / Green, Peter H / Krishnareddy, Suneeta

    Journal of clinical gastroenterology

    2020  Band 56, Heft 1, Seite(n) e52–e57

    Abstract: Goals: We investigated the distribution of pathogens on stool gastrointestinal (GI) polymerase chain reaction (PCR) testing in those who subsequently developed inflammatory bowel disease (IBD).: Background: Infectious gastroenteritis has been ... ...

    Abstract Goals: We investigated the distribution of pathogens on stool gastrointestinal (GI) polymerase chain reaction (PCR) testing in those who subsequently developed inflammatory bowel disease (IBD).
    Background: Infectious gastroenteritis has been associated with later development of IBD.
    Study: This retrospective study includes patients of all ages hospitalized for diarrhea with positive GIPCR panel and subsequently a new diagnosis of IBD [confirmed by chart review and International Classification of Disease, Clinical Modification code for Crohn's disease (CD) or ulcerative colitis (UC)], between March 2015 to September 2019 at our quaternary care institution. Patients with IBD diagnosis before GIPCR were excluded. Descriptive statistics characterized the distribution of microbial pathogens in relation to later IBD diagnosis.
    Results: Fifty-four participants were eligible (UC 44%; CD 56%). Median age at time of IBD diagnosis was 35 years [interquartile range (IQR) 18 to 65]. Median time between GIPCR and IBD diagnosis was 3 months (IQR 2 to 9) for all patients. When stratified by organism class, median time to diagnosis was 6 months (IQR 2 to 10) for patients with bacteria, 3 months (IQR 1 to 8) for patients with viruses, and 1 month (IQR 0.75 to 1) for patients with parasites (log-rank P=0.001). Sixty-nine unique pathogens (83% bacteria) were identified on all tests. Escherichia coli was the most common species (71%), of which enteropathogenic E. coli was predominant (38%).
    Conclusions: The E. coli species, specifically enteropathogenic E. coli, may be implicated in the development of IBD. This is one of the first studies to evaluate the results of stool GIPCR in the link between the microbiome and IBD pathogenesis.
    Mesh-Begriff(e) Adult ; Colitis, Ulcerative/diagnosis ; Colitis, Ulcerative/epidemiology ; Escherichia coli ; Humans ; Inflammatory Bowel Diseases/diagnosis ; Inflammatory Bowel Diseases/epidemiology ; Polymerase Chain Reaction ; Retrospective Studies
    Sprache Englisch
    Erscheinungsdatum 2020-12-01
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 448460-5
    ISSN 1539-2031 ; 0192-0790
    ISSN (online) 1539-2031
    ISSN 0192-0790
    DOI 10.1097/MCG.0000000000001470
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  7. Artikel ; Online: A pan-cancer analysis implicates human

    Postler, Thomas S / Wang, Anqi / Brundu, Francesco G / Wang, Pingzhang / Wu, Zikai / Butler, Kelly E / Grinberg-Bleyer, Yenkel / Krishnareddy, Suneeta / Lagana, Stephen M / Saqi, Anjali / Oeckinghaus, Andrea / Rabadan, Raul / Ghosh, Sankar

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Band 120, Heft 46, Seite(n) e2312595120

    Abstract: The NF-κB family of transcription factors and the Ras family of small GTPases are important mediators of proproliferative signaling that drives tumorigenesis and carcinogenesis. The κB-Ras proteins were previously shown to inhibit both NF-κB and Ras ... ...

    Abstract The NF-κB family of transcription factors and the Ras family of small GTPases are important mediators of proproliferative signaling that drives tumorigenesis and carcinogenesis. The κB-Ras proteins were previously shown to inhibit both NF-κB and Ras activation through independent mechanisms, implicating them as tumor suppressors with potentially broad relevance to human cancers. In this study, we have used two mouse models to establish the relevance of the κB-Ras proteins for tumorigenesis. Additionally, we have utilized a pan-cancer bioinformatics analysis to explore the role of the κB-Ras proteins in human cancers. Surprisingly, we find that the genes encoding κB-Ras 1 (
    Mesh-Begriff(e) Animals ; Humans ; Mice ; Carcinogenesis/genetics ; Cell Transformation, Neoplastic/genetics ; Genes, ras ; NF-kappa B/metabolism ; ras Proteins/metabolism ; Genes, Tumor Suppressor ; Carrier Proteins/genetics
    Chemische Substanzen NF-kappa B ; ras Proteins (EC 3.6.5.2) ; NKIRAS1 protein, human ; Carrier Proteins
    Sprache Englisch
    Erscheinungsdatum 2023-11-06
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2312595120
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  8. Artikel ; Online: Serological Investigation of Persistent Villous Atrophy in Celiac Disease.

    Gong, Changlin / Saborit, Claudia / Long, Xin / Wang, Ao / Zheng, Beishi / Chung, Howard / Lewis, Suzanne K / Krishnareddy, Suneeta / Bhagat, Govind / Green, Peter H R / Kong, Xiao-Fei

    Clinical and translational gastroenterology

    2023  Band 14, Heft 12, Seite(n) e00639

    Abstract: Introduction: Persistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD).: Methods: We conducted a retrospective study with 122 serum samples collected from controls and patients with CeD ... ...

    Abstract Introduction: Persistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD).
    Methods: We conducted a retrospective study with 122 serum samples collected from controls and patients with CeD either at the initial diagnosis or at the follow-up during endoscopy. These samples were assigned to 3 groups: nonceliac control, non-VA CeD (Marsh score 0-2), and VA CeD (Marsh score 3a-3c). We established an in-house multiplex assay to identify potential serological biomarkers for VA. We assessed autoantibodies reported to affect the small intestine, including IgA and IgG antibodies against tissue transglutaminase (tTG), interferons, villin, actin, autoimmune enteropathy-related 75 kDa antigen (AIE-75), and tryptophan hydroxylase (TPH)-1, as well as 27 cytokines. The apolipoproteins quantified included apo A1, apo B-100, and apo A4, which were produced predominantly by the intestinal epithelium or expressed specifically in villi.
    Results: Autoantibody levels were high only for tTG antibodies, which performed well in initial CeD diagnosis, but suboptimally for VA prediction during follow-up, because 14.6% of the follow-up patients with VA had low tTG-IgA. Increasing dilution improved tTG-IgA quantification, particularly when the antibody levels were extremely high but did not significantly improve VA detection. Among those with low tTG-IgA and persistent VA, high proinflammatory cytokines were observed in 2 patients. Median low-density lipoprotein cholesterol levels were significantly lower in the VA CeD group ( P = 0.03). Apolipoprotein levels were similar in patients with and without VA but diverged between those on a GFD or not.
    Discussion: tTG-IgA as a biomarker is suboptimal for VA prediction while on a GFD. Persistent VA is associated with low low-density lipoprotein cholesterol levels and partially related to persistent high proinflammatory cytokines.
    Mesh-Begriff(e) Humans ; Celiac Disease ; Retrospective Studies ; Transglutaminases ; Biomarkers ; Autoantibodies ; Immunoglobulin A ; Atrophy ; Cytokines ; Lipoproteins, LDL ; Cholesterol
    Chemische Substanzen Transglutaminases (EC 2.3.2.13) ; Biomarkers ; Autoantibodies ; Immunoglobulin A ; Cytokines ; Lipoproteins, LDL ; Cholesterol (97C5T2UQ7J)
    Sprache Englisch
    Erscheinungsdatum 2023-12-01
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2581516-7
    ISSN 2155-384X ; 2155-384X
    ISSN (online) 2155-384X
    ISSN 2155-384X
    DOI 10.14309/ctg.0000000000000639
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Failure to thrive in a man in his late forties.

    Meyer, Benjamin J / Dale, Leigh-Anne / Kuo, Selena Z / Brandes, Steven B / Lagana, Stephen Michael / O'Toole, Kathleen M / Burt, Joseph E / Krishnareddy, Suneeta

    Journal of clinical pathology

    2021  Band 76, Heft 9, Seite(n) 578–580

    Mesh-Begriff(e) Humans ; Male ; Failure to Thrive/etiology ; Middle Aged
    Sprache Englisch
    Erscheinungsdatum 2021-12-08
    Erscheinungsland England
    Dokumenttyp Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80261-x
    ISSN 1472-4146 ; 0021-9746
    ISSN (online) 1472-4146
    ISSN 0021-9746
    DOI 10.1136/jclinpath-2020-207057
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  10. Artikel ; Online: When combination therapy isn't working: emerging therapies for the management of inflammatory bowel disease.

    Krishnareddy, Suneeta / Swaminath, Arun

    World journal of gastroenterology

    2014  Band 20, Heft 5, Seite(n) 1139–1146

    Abstract: Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and ... ...

    Abstract Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.
    Mesh-Begriff(e) Animals ; Anti-Inflammatory Agents/chemistry ; Anti-Inflammatory Agents/therapeutic use ; Drug Design ; Drug Substitution ; Drug Therapy, Combination ; Gastrointestinal Agents/chemistry ; Gastrointestinal Agents/therapeutic use ; Humans ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/immunology ; Inflammatory Bowel Diseases/metabolism ; Intestinal Mucosa/metabolism ; Intestines/drug effects ; Intestines/immunology ; Molecular Targeted Therapy ; Signal Transduction/drug effects ; Treatment Failure
    Chemische Substanzen Anti-Inflammatory Agents ; Gastrointestinal Agents
    Sprache Englisch
    Erscheinungsdatum 2014-01-19
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2185929-2
    ISSN 2219-2840 ; 1007-9327
    ISSN (online) 2219-2840
    ISSN 1007-9327
    DOI 10.3748/wjg.v20.i5.1139
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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