scholarly journals Helicobacter pylori GroEL Seropositivity Is Associated with an Increased Risk of Opisthorchis viverrini-Associated Hepatobiliary Abnormalities and Cholangiocarcinoma

2021 ◽  
Vol 59 (4) ◽  
pp. 363-368
Author(s):  
Isabelle Jala ◽  
Muhammad Luthfi Almanfaluthi ◽  
Thewarach Laha ◽  
Sakawrat Kanthawong ◽  
Sirikachorn Tangkawattana ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Logistic Regression ◽  
Early Detection ◽  
Synergistic Effect ◽  
Multinomial Logistic Regression ◽  
Opisthorchis Viverrini ◽  
Antibody Responses ◽  
Increased Risk ◽  
H Pylori

Despite the synergistic effect of Opisthorchis viverrini and Helicobacter pylori co-infection on pathogenesis of severe hepatobiliary abnormalities (HBA) including advanced periductal fibrosis and replace with cholangiocarcinoma (CCA) have been established, the immune response to H. pylori in O. viverrini infected population has never been explored. Hence, this study aimed to investigate the antibody responses to 2 immunogenic H. pylori proteins in O. viverrini-infected patients with HBA and CCA. The risk analysis by multinomial logistic regression revealed that GroEL seropositivity was associated with higher risks of hepatobiliary abnormalities and CCA with adjusted odds ratios (95% confidence intervals) of 2.11 (95% CI=1.20-3.71, P=0.008) and 2.13 (95% CI=1.21-3.75, P=0.009), respectively. These findings indicate that GroEL seropositivity might be a biomarker for early detection of O. viverrini associated HBA and CCA.

Immune responses to Helicobacter pylori colonization: mechanisms and clinical outcomes

2006 ◽  
Vol 110 (3) ◽  
pp. 305-314 ◽  
Author(s):  
Cynthia Portal-Celhay ◽  
Guillermo I. Perez-Perez
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Immune Responses ◽  
Gastric Lymphoma ◽  
Gastric Epithelium ◽  
Immune Effector ◽  
Ulcer Disease ◽  
Gastroduodenal Disease ◽  
Increased Risk ◽  
H Pylori

Helicobacter pylori colonizes the stomachs of half of the world's population and usually persists in the gastric mucosa of human hosts for decades or life. Although most H. pylori-positive people are asymptomatic, the presence of H. pylori is associated with increased risk for the development of peptic ulcer disease, gastric adenocarcinoma and gastric lymphoma. The development of a sustained gastric inflammatory and immune response to infection appears to be pivotal for the development of disease. During its long co-existence with humans, H. pylori has evolved complex strategies to maintain a mild inflammation of the gastric epithelium while limiting the extent of immune effector activity. In this review, the nature of the host immune response to H. pylori infection and the mechanism employed by the bacterium to evade them is considered. Understanding the mechanisms of colonization, persistence and virulence factors of the bacterium as well as the innate and adaptive immune responses of the host are critically important for the development of new strategies to prevent the development of H. pylori-induced gastroduodenal disease.

scholarly journals Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257060
Author(s):  
Volodymyr Dvornyk ◽  
Irina Ponomarenko ◽  
Oksana Minyaylo ◽  
Evgeny Reshetnikov ◽  
Mikhail Churnosov
Keyword(s):  
Helicobacter Pylori ◽  
Logistic Regression ◽  
Gastric Ulcer ◽  
Caucasian Population ◽  
Multiple Logistic Regression ◽  
Central Russia ◽  
Epigenetic Effects ◽  
Increased Risk ◽  
H Pylori ◽  
Mmp9 Gene

Background and purpose The study analyzed the association of functionally significant polymorphisms of matrix metalloproteinases (MMPs) genes with the development of gastric ulcer (GU) in Caucasians from Central Russia. Methods The 781 participants, including 434 patients with GU (196 Helicobacter pylori (H. pylori)-positive and 238 H. pylori-negative) and 347 controls (all H. pylori-negative) were recruited for the study. Ten SNPs of the MMP1 (rs1799750), MMP2 (rs243865), MMP3 (rs679620), MMP8 (rs1940475), and MMP9 (rs3918242, rs3918249, rs3787268, rs17576, rs17577, and rs2250889) genes were considered for association with GU using multiple logistic regression. The SNPs associated with GU and loci linked (r2≥0.8) to them were analyzed in silico for their functional assignments. Results The SNPs of the MMP9 gene were associated with H. pylori-positive GU: alleles C of rs3918249 (OR = 2.02, pperm = 0.008) and A of rs3787268 (OR = 1.60–1.82, pperm ≤ 0.016), and eight haplotypes of all studied MMP9 gene SNPs (OR = 1.85–2.04, pperm ≤ 0.016) increased risk for H. pylori-positive GU. None of the analyzed SNPs was independently associated with GU and H. pylori-negative GU. Two haplotypes of the MMP9 gene (contributed by rs3918242, rs3918249, rs17576, and rs3787268) increased risk for GU (OR = 1.62–1.65, pperm ≤ 0.006). Six loci of the MMP9 gene, which are associated with H. pylori-positive GU, and 65 SNPs linked to them manifest significant epigenetic effects, have pronounced eQTL (17 genes) and sQTL (6 genes) values. Conclusion SNPs of the MMP9 were associated with H. pylori-positive GU but not with H. pylori-negative GU in Caucasians of Central Russia.

scholarly journals Detection of Anti-VacA Antibody Responses in Serum and Gastric Juice Samples Using Type s1/m1 and s2/m2 Helicobacter pylori VacA Antigens

1999 ◽  
Vol 6 (4) ◽  
pp. 489-493 ◽  
Author(s):  
Guillermo I. Perez-Perez ◽  
Richard M. Peek ◽  
John C. Atherton ◽  
Martin J. Blaser ◽  
Timothy L. Cover
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Juice ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Ulcer Disease ◽  
Serum Igg ◽  
Increased Risk ◽  
Antigenic Properties ◽  
H Pylori

ABSTRACT Several different families of vacuolating toxin (vacA) alleles are present in Helicobacter pylori, and they encode products with differing functional activities. H. pyloristrains containing certain types of vacA alleles have been associated with an increased risk for peptic ulcer disease. In this study, we tested serum samples and gastric juice from 19 H. pylori-negative and 39 H. pylori-positive patients for enzyme-linked immunosorbent assay reactivity with two different types of VacA antigens (types s1/m1 and s2/m2), which were purified from H. pylori 60190 and 86-338, respectively. Both antigens were recognized better by serum immunoglobulin G (IgG) fromH. pylori-positive persons than by serum IgG from H. pylori-negative persons (P < 0.01). The s1/m1 VacA antigen was better recognized by sera from patients carryingvacA type s1/m1 strains than by sera from patients carryingvacA type s2/m2 or s1/m2 strains (P < 0.01). Conversely, the s2/m2 VacA antigen was better recognized by sera from patients carrying type s2/m2 or s1/m2 strains (P= 0.03). Serum IgG anti-VacA antibodies were present more frequently in patients carrying type s1/m1 strains than in other H. pylori-positive patients (P = 0.0002). In addition, the highest levels of IgA anti-VacA antibodies were detected in the gastric juice of patients carrying type s1/m1 strains. These data indicate that different VacA isoforms have distinct antigenic properties and that multiple forms of VacA elicit antibody responses inH. pylori-positive humans.

scholarly journals The Helicobacter pylori Autotransporter ImaA (HP0289) Modulates the Immune Response and Contributes to Host Colonization

2012 ◽  
Vol 80 (7) ◽  
pp. 2286-2296 ◽  
Author(s):  
William E. Sause ◽  
Andrea R. Castillo ◽  
Karen M. Ottemann
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Dependent Manner ◽  
Wild Type ◽  
Content Type ◽  
H Pylori ◽  
Murine Infections

ABSTRACTThe human pathogenHelicobacter pyloriemploys a diverse collection of outer membrane proteins to colonize, persist, and drive disease within the acidic gastric environment. In this study, we sought to elucidate the function of the host-induced geneHP0289, which encodes an uncharacterized outer membrane protein. We first generated an isogenicH. pylorimutant that lacksHP0289and found that the mutant has a colonization defect in single-strain infections and is greatly outcompeted in mouse coinfection experiments with wild-typeH. pylori. Furthermore, we used protease assays and biochemical fractionation coupled with an HP0289-targeted peptide antibody to verify that the HP0289 protein resides in the outer membrane. Our previous findings showed that theHP0289promoter is upregulated in the mouse stomach, and here we demonstrate thatHP0289expression is induced under acidic conditions in an ArsRS-dependent manner. Finally, we have shown that theHP0289mutant induces greater expression of the chemokine interleukin-8 (IL-8) and the cytokine tumor necrosis factor alpha (TNF-α) in gastric carcinoma cells (AGS). Similarly, transcription of the IL-8 homolog keratinocyte-derived chemokine (KC) is elevated in murine infections with the HP0289 mutant than in murine infections with wild-typeH. pylori. On the basis of this phenotype, we renamed HP0289 ImaA forimmunomodulatoryautotransporter protein. Our work has revealed that genes inducedin vivoplay an important role inH. pyloripathogenesis. Specifically, the outer membrane protein ImaA modulates a component of the host inflammatory response, and thus may allowH. pylorito fine tune the host immune response based on ImaA expression.

Abstract TMP50: A Polymorphism in HDAC9 was Associated with Large Vessel Stroke in the Vienna and German Stroke Studies

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
May M Luke ◽  
Carmen H Tong ◽  
Joseph J Catanese ◽  
James J Devlin ◽  
Christine Mannhalter ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Ischemic Stroke ◽  
Genome Wide Association Study ◽  
Multinomial Logistic Regression ◽  
Large Vessel ◽  
Stroke Subtype ◽  
German Study ◽  
Genome Wide ◽  
Increased Risk ◽  
Large Vessel Stroke

Introduction The International Stroke Genetics Consortium (ISGC) and the Wellcome Trust Case Control Consortium 2 (WTCCC2) performed a large genome wide association study of ischemic stroke and its subtypes (large vessel stroke (LVD), small vessel stroke (SVD), cardioembolic stroke (CE)), and identified a polymorphism in HDAC9 (rs11984041) associated with the LVD subtype of ischemic stroke. Hypothesis We assessed the hypothesis that rs11984041 is associated with LVD in two additional studies. Methods The genotype of rs11984041 was determined for participants of the Vienna Study (815 controls, 122 LVD, 165 SVD, 202 CE) and of the German Study (1040 controls, 495 LVD, 230 SVD, 462 CE). The association of rs11984041 with LVD was assessed by logistic regression. Heterogeneity of the effect of rs11984041 on LVD, CE or SVD was assessed by testing the equality of the corresponding regression coefficients from a multinomial logistic regression model. Results Carriers of the minor (T) allele of rs11984041 (23.3% of LVD cases and 17.4% of controls), compared with noncarriers, had increased risk for LVD: the odds ratios (OR) were 1.92 (95%CI 1.25-2.96) for the Vienna Study and 1.33 (95%CI 1.02-1.74) for the German Study. Adjusting for covariates including sex, age, diabetes, and hypertension did not materially change the ORs. Heterogeneity of the effects of rs11984041 on LVD vs CE was significant in the Vienna Study (p = 0.009) and in the German Study (p = 0.005). Heterogeneity of the effects of rs11984041 on LVD vs SVD trended toward significance in the Vienna Study (p = 0.088) and was significant in the German Study (p = 0.047). Adjusting for covariates did not materially change the heterogeneity test p values. Conclusions The HDAC9 polymorphism rs11984041 was associated with the LVD stroke subtype in the Vienna Study and the German Study. These results replicated the ISGC/WTCCC2 findings.

scholarly journals TIFA Signaling in Gastric Epithelial Cells Initiates the cag Type 4 Secretion System-Dependent Innate Immune Response to Helicobacter pylori Infection

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Alevtina Gall ◽  
Ryan G. Gaudet ◽  
Scott D. Gray-Owen ◽  
Nina R. Salama
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Secretion System ◽  
Innate Immune ◽  
Gastric Ulcers ◽  
Bacterial Clearance ◽  
Gastric Epithelial Cells ◽  
H Pylori

ABSTRACT Helicobacter pylori is a bacterial pathogen that colonizes the human stomach, causing inflammation which, in some cases, leads to gastric ulcers and cancer. The clinical outcome of infection depends on a complex interplay of bacterial, host genetic, and environmental factors. Although H. pylori is recognized by both the innate and adaptive immune systems, this rarely results in bacterial clearance. Gastric epithelial cells are the first line of defense against H. pylori and alert the immune system to bacterial presence. Cytosolic delivery of proinflammatory bacterial factors through the cag type 4 secretion system ( cag -T4SS) has long been appreciated as the major mechanism by which gastric epithelial cells detect H. pylori . Classically attributed to the peptidoglycan sensor NOD1, recent work has highlighted the role of NOD1-independent pathways in detecting H. pylori ; however, the bacterial and host factors involved have remained unknown. Here, we show that bacterially derived heptose-1,7-bisphosphate (HBP), a metabolic precursor in lipopolysaccharide (LPS) biosynthesis, is delivered to the host cytosol through the cag -T4SS, where it activates the host tumor necrosis factor receptor-associated factor (TRAF)-interacting protein with forkhead-associated domain (TIFA)-dependent cytosolic surveillance pathway. This response, which is independent of NOD1, drives robust NF-κB-dependent inflammation within hours of infection and precedes NOD1 activation. We also found that the CagA toxin contributes to the NF-κB-driven response subsequent to TIFA and NOD1 activation. Taken together, our results indicate that the sequential activation of TIFA, NOD1, and CagA delivery drives the initial inflammatory response in gastric epithelial cells, orchestrating the subsequent recruitment of immune cells and leading to chronic gastritis. IMPORTANCE H. pylori is a globally prevalent cause of gastric and duodenal ulcers and cancer. H. pylori antibiotic resistance is rapidly increasing, and a vaccine remains elusive. The earliest immune response to H. pylori is initiated by gastric epithelial cells and sets the stage for the subsequent immunopathogenesis. This study revealed that host TIFA and H. pylori -derived HBP are critical effectors of innate immune signaling that account for much of the inflammatory response to H. pylori in gastric epithelial cells. HBP is delivered to the host cell via the cag -T4SS at a time point that precedes activation of the previously described NOD1 and CagA inflammatory pathways. Manipulation of the TIFA-driven immune response in the host and/or targeting of ADP-heptose biosynthesis enzymes in H. pylori may therefore provide novel strategies that may be therapeutically harnessed to achieve bacterial clearance.

scholarly journals Two-Way Relationship Between Helicobacter Pylori Infection and Periodontitis: Results from A Systematic Review and Meta-Analysis

2020 ◽  
pp. 1-7
Author(s):  
Felipe Rodolfo ◽  
Silvania Conceição Furtado ◽  
Alessandro Luiz Araújo Bentes Leal ◽  
Any Carolina Cardoso Guimarães Vasconcelos ◽  
Daniel Fernando Pereira Vasconcelos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Helicobacter Pylori ◽  
Meta Analysis ◽  
Current Systematic Review ◽  
Increased Risk ◽  
Statistical Program ◽  
H Pylori ◽  
Ci Calculations ◽  
Review Manager

Aim: Helicobacter pylori (H. pylori) infection and periodontitis have considerable worldwide prevalence once they both present systemic alterations with a possible association between them. Therefore, we have performed this meta-analysis to assess the possible association between H. pylori infection and periodontitis. Material and Methods: A systematic search in the literature was performed for studies published before December 2, 2019 in diverse scientific and educational databases. The data was extracted by two investigators and the statistical analysis was performed by Review Manager statistical program with heterogeneity and Odds Ratio (OR) with 95% of Confidence Intervals (CI) calculations as well as a sensitive analysis to assess the accuracy of the results. The value of P<0.05 was considered as significant. In addition, we performed the analysis of the quality of included studies as well as the evaluation for risk of bias. Results: In overall analysis, H. pylori infection was associated with the risk of periodontitis development (OR = 1.72, CI: 1.47, 2.02, P<0.00001) and the periodontitis was considered as a risk factor for H. pylori infection (OR = 3.21, CI: 2.31, 4.47, P<0.00001). Moreover, the evaluation of dental plaque from patients with periodontitis reveled increased risk of H. pylori infection (OR = 3.46, CI: 2.39, 5.01, P<0.00001). Conclusions: This current systematic review and meta-analysis composed by 12 studies in 7,059 participants showed that H. pylori infection increased significantly the risk of the development of periodontitis and the periodontitis may be a risk for this bacterial infection.

scholarly journals Genetic Polymorphisms of CXCL8 (−251) Are Associated with the Susceptibility of Helicobacter pylori Infection Increased the Risk of Inflammation and Gastric Cancer in Thai Gastroduodenal Patients

2019 ◽  
Author(s):  
Wongwarut Boonyanugomol ◽  
Kamolchanok Rukseree ◽  
Worrarat Kongkasame ◽  
Prasit Palittapongarnpim ◽  
Seung-Chul Baik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Gene Polymorphisms ◽  
Inflammatory Responses ◽  
Increased Risk ◽  
Cxc Chemokine ◽  
H Pylori

CXC Chemokine Ligand 8 (CXCL8) plays an important role in gastric inflammation and in the progression of gastric cancer induced by Helicobacter pylori (H. pylori) infection. The association of CXCL8, CXC Chemokine Receptor 1 (CXCR1), and CXC Chemokine Receptor 2 (CXCR2) polymorphisms with H. pylori infection and gastric cancer progression needs to be investigated in a population within an enigma area consisting of multiple ethnicities, such as Thailand. To analyze the relative risk of H. pylori infection and gastric cancer among Thai gastroduodenal patients, gene polymorphisms in CXCL8 (promoter region -251) and in CXCR1 and CXCR2 (receptors for CXCL8) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR (AS-PCR). We also determined the presence of cytotoxin-associated gene A (cagA) in Thai patients with H. pylori infection. Correlation between the CXCL8 (-251) polymorphism and CXCL8 gene expression was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). We found a significant association between the T/A and A/A genotypes of CXCL8 (-251) with H. pylori infection. However, no significant correlation was found between the CXCR1 (+2607) and CXCR2 (+1208) gene polymorphisms with H. pylori infection among Thai gastroduodenal subjects. Within the H. pylori-infected group of Thai gastroduodenal patients, no significant differences in cagA were observed. In addition, the A/A genotype of CXCL8 (-251) significantly correlated with the risk of gastric cancer and correlated with higher CXCL8 gene expression levels in Thai gastroduodenal patients. These results suggest that CXCL8 (-251) polymorphisms are associated with H. pylori infection, an increased risk of stronger inflammatory responses, and gastric cancer in Thai gastroduodenal patients.  

Lactobacillus fermentum UCO-979C beneficially modulates the innate immune response triggered by Helicobacter pylori infection in vitro

2018 ◽  
Vol 9 (5) ◽  
pp. 829-841 ◽  
Author(s):  
V. Garcia-Castillo ◽  
H. Zelaya ◽  
A. Ilabaca ◽  
M. Espinoza-Monje ◽  
R. Komatsu ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Morphological Changes ◽  
Helicobacter Pylori Infection ◽  
Lactobacillus Fermentum ◽  
Gastric Tissue ◽  
Gastric Epithelial Cells ◽  
Ags Cells ◽  
H Pylori

Helicobacter pylori infection is associated with important gastric pathologies. An aggressive proinflammatory immune response is generated in the gastric tissue infected with H. pylori, resulting in gastritis and a series of morphological changes that increase the susceptibility to cancer development. Probiotics could present an alternative solution to prevent or decrease H. pylori infection. Among them, the use of immunomodulatory lactic acid bacteria represents a promising option to reduce the severity of chronic inflammatory-mediated tissue damage and to improve protective immunity against H. pylori. We previously isolated Lactobacillus fermentum UCO-979C from human gastric tissue and demonstrated its capacity to reduce adhesion of H. pylori to human gastric epithelial cells (AGS cells). In this work, the ability of L. fermentum UCO-979C to modulate immune response in AGS cells and PMA phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 (human monocytic leukaemia) macrophages in response to H. pylori infection was evaluated. We demonstrated that the UCO-979C strain is able to differentially modulate the cytokine response of gastric epithelial cells and macrophages after H. pylori infection. Of note, L. fermentum UCO-979C was able to significantly reduce the production of inflammatory cytokines and chemokines in AGS and THP-1 cells as well as increase the levels of immunoregulatory cytokines, indicating a remarkable anti-inflammatory effect. These findings strongly support the probiotic potential of L. fermentum UCO-979C and provide evidence of its beneficial effects against the inflammatory damage induced by H. pylori infection. Although our findings should be proven in appropriate experiments in vivo, in both H. pylori infection animal models and human trials, the results of the present work provide a scientific rationale for the use of L. fermentum UCO-979C to prevent or reduce H. pylori-induced gastric inflammation in humans.

scholarly journals Role of Helicobacter pylori in Upper Gastrointestinal Bleeding Among Ischemic Stroke Hospitalizations: A Nationwide Study of Outcomes

2019 ◽  
Vol 1 (3) ◽  
pp. 358-371
Author(s):  
Urvish K. Patel ◽  
Mihir Dave ◽  
Anusha Lekshminarayanan ◽  
Nidhi Patel ◽  
Abhishek Lunagariya ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Ischemic Stroke ◽  
Risk Stratification ◽  
Gastrointestinal Bleeding ◽  
Health Care Cost ◽  
Upper Gastrointestinal Bleeding ◽  
Increased Risk ◽  
H Pylori ◽  
Upper Gastrointestinal

Introduction: Helicobacter pylori (H. pylori) is a well-recognized risk factor for upper gastrointestinal bleeding (UGIB). The exposure to tissue plasminogen activator (tPA), anti-platelets, and anticoagulants increases the risk of UGIB in acute ischemic stroke (AIS) patients, the risk stratification of H. pylori infection is not known. In this retrospective cross-sectional study, we aimed to evaluate the relationship between H. pylori and GIB in patients hospitalized with AIS. Methods: In the nationwide data, hospitalization for AIS was identified by primary diagnosis using International Classification of Diseases, clinical modification (ICD-9-CM) codes. Subgroup of patients with GIB and H. pylori were identified in AIS cohort. A stepwise multivariable logistic regression model was fitted to evaluate the outcome of upper GIB and role of H. Pylori in UGIB. Results: Overall 4,224,924 AIS hospitalizations were identified, out of which 18,629 (0.44%) had UGIB and 3122 (0.07%) had H. pylori. The prevalence of H. pylori-induced UGIB among UGIB in AIS was 3.05%. The prevalence of UGIB was markedly elevated among the H. pylori infection group (18.23% vs. 0.43%; p < 0.0001) compared to the non-H. pylori group. In multivariable regression analysis, H. pylori was associated with markedly elevated odds of UGIB (aOR:27.75; 95%CI: 21.07–36.55; p < 0.0001). Conclusion: H. pylori infection had increased risk-adjusted occurrence of UGIB amongst the AIS hospitalized patients. H. pylori testing may improve risk stratification for UGIB and lower the health care cost burden in stroke hospitalization.

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