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Wanders, Alkwin
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Publications (10 of 24) Show all publications
Rönnblom, A., Holmstrom, T., Tanghoj, H., Wanders, A. & Sjoberg, D. (2015). Celiac disease, collagenous sprue and microscopic colitis in IBD. Observations from a population-based cohort of IBD (ICURE). Scandinavian Journal of Gastroenterology, 50(10), 1234-1240
Open this publication in new window or tab >>Celiac disease, collagenous sprue and microscopic colitis in IBD. Observations from a population-based cohort of IBD (ICURE)
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2015 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 10, p. 1234-1240Article in journal (Refereed) Published
Abstract [en]

Objective. Inflammatory bowel disease (IBD), microscopic colitis and celiac disease are all diseases with worldwide distribution and increased incidence has been reported from many areas. There is a shortage of studies investigating the occurrence of these diseases in the same individual and whether those affected demonstrate any particular phenotype. The aim of the study was to describe the concomitant incidence of microscopic colitis and celiac disease in a population-based IBD cohort. Methods. All 790 individuals in a prospective population-based cohort included 2005-09 from Uppsala region, Sweden, were reviewed regarding the appearance of microscopic or celiac disease before or after IBD diagnosis. Results. Fifty percent (396/790) of the patients had been examined for the possibility of celiac disease. Seventeen patients with celiac disease were found, representing 2.2% of the cohort. Patients with celiac disease were younger compared to the non-celiac patients and those with colitis had more often an extensive inflammation of the colon. Seventy-one percent (12/17) were women. The majority of the patients were diagnosed with celiac disease before IBD. Five patients with IBD had an earlier diagnosis of microscopic colitis or developed it after the IBD diagnosis. One teenager developed collagenous sprue, misinterpreted as a severe relapse of ulcerative colitis (UC) resulting in colectomy. Conclusions. The risk for celiac disease seems not to be increased in IBD, but those affected by both diseases seem to be predominantly women with extensive UC. There is a potential association between microscopic colitis and IBD.

Keyword
celiac disease, collagenous sprue, epidemiology, inflammatory bowel diseases, microscopic colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-264686 (URN)10.3109/00365521.2015.1041152 (DOI)000361324600007 ()25921772 (PubMedID)
Available from: 2015-10-16 Created: 2015-10-15 Last updated: 2017-12-01Bibliographically approved
Klar, J., Raykova, D., Gustafson, E., Tóthová, I., Ameur, A., Wanders, A. & Dahl, N. (2015). Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution. European Journal of Human Genetics, 23(12), 1679-1683
Open this publication in new window or tab >>Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution
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2015 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 23, no 12, p. 1679-1683Article in journal (Refereed) Published
Abstract [en]

Familial visceral myopathy (FVM) is a rare heritable and heterogeneous condition due to impaired smooth muscle function. We identified a family segregating 11 individuals with a spectrum of visceral symptoms involving the small intestine, colon, biliary tract, urinary tract and uterus. Whole-exome sequencing revealed a novel heterozygous tandem base substitution c.806_807delinsAA (p.(Gly269Glu)) in ACTG2, encoding smooth muscle actin γ-2, in affected family members. Variants in ACTG2 were recently identified in FVM with intestinal pseudo-obstruction as well as with the congenital megacystics-microcolon-intestinal hypoperistalsis syndrome. In our family, eight affected members presented with severe complications from the biliary and/or the urinary tracts in addition to gastrointestinal pseudo-obstructions. Furthermore, all affected mothers had a history of assisted deliveries owing to poor progress during labor and weak uterine contractions. The variable involvement of multiple smooth muscle-dependent organs in our family, including the biliary tract and the uterus, add to the phenotypic spectrum associated with ACTG2 missense variants.

National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-244419 (URN)10.1038/ejhg.2015.49 (DOI)000365129700015 ()25782675 (PubMedID)
Funder
Swedish Research Council, K2013-66X-10829-20-3
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2015-03-03 Created: 2015-02-16 Last updated: 2017-12-04Bibliographically approved
Gremel, G., Wanders, A., Cedernaes, J., Fagerberg, L., Hallström, B., Edlund, K., . . . Pontén, F. (2015). The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling.. Journal of gastroenterology, 50(1), 46-57
Open this publication in new window or tab >>The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling.
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2015 (English)In: Journal of gastroenterology, ISSN 0944-1174, E-ISSN 1435-5922, Vol. 50, no 1, p. 46-57Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The gastrointestinal tract (GIT) is subdivided into different anatomical organs with many shared functions and characteristics, but also distinct differences. We have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to describe the gene and protein expression patterns that define the human GIT.

METHODS: RNA sequencing data derived from stomach, duodenum, jejunum/ileum and colon specimens were compared to gene expression levels in 23 other normal human tissues analysed with the same method. Protein profiling based on immunohistochemistry and tissue microarrays was used to sub-localize the corresponding proteins with GIT-specific expression into sub-cellular compartments and cell types.

RESULTS: Approximately 75 % of all human protein-coding genes were expressed in at least one of the GIT tissues. Only 51 genes showed enriched expression in either one of the GIT tissues and an additional 83 genes were enriched in two or more GIT tissues. The list of GIT-enriched genes with validated protein expression patterns included various well-known but also previously uncharacterised or poorly studied genes. For instance, the colon-enriched expression of NXPE family member 1 (NXPE1) was established, while NLR family, pyrin domain-containing 6 (NLRP6) expression was primarily found in the human small intestine.

CONCLUSIONS: We have applied a genome-wide analysis based on transcriptomics and antibody-based protein profiling to identify genes that are expressed in a specific manner within the human GIT. These genes and proteins constitute important starting points for an improved understanding of the normal function and the different states of disease associated with the GIT.

National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-239503 (URN)10.1007/s00535-014-0958-7 (DOI)000348982100006 ()24789573 (PubMedID)
Available from: 2014-12-29 Created: 2014-12-29 Last updated: 2018-01-11Bibliographically approved
Sangfelt, P., Sundin, A., Wanders, A., Rasmussen, I., Karlson, B.-M., Bergquist, A. & Rorsman, F. (2014). Monitoring Dominant Strictures in Primary Sclerosing Cholangitis with Brush Cytology and FDG-PET. Journal of Hepatology, 61(6), 1352-1357
Open this publication in new window or tab >>Monitoring Dominant Strictures in Primary Sclerosing Cholangitis with Brush Cytology and FDG-PET
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2014 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 61, no 6, p. 1352-1357Article in journal (Refereed) Published
Abstract [en]

BACKGROUND/AIMS: Despite high risk of cholangiocellular adenocarcinoma (CCA) it is unclear how surveillance of patients with primary sclerosing cholangitis (PSC) should be performed.

METHOD: We evaluated a follow-up algorithm of brush cytology and positron emission tomography/computed tomography with [18F]fluorodeoxyglucose ([18F]FDG-PET/CT), measured as the maximum standardized uptake values normalized to the liver background (SUVmax/liver) at 180 minutes, in PSC patients with dominant bile duct strictures.

RESULTS: Brush cytology with high grade dysplasia (HGD) was detected in 12/70 patients (17%), yielding diagnostic sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 56%, 89%, 75% and 88%, respectively. Preemptive liver transplantations due to repeated HGD before manifest CCA were performed in six patients. Receiver operating characteristic (ROC) analysis of [18F]FDG uptake showed that a SUVmax/liver quotient of 3.3 was able to discriminate between CCA and non-malignant disease with a sensitivity, specificity, PPV and NPV for CCA of 89%, 92%, 62%, 98%, respectively. A SUVmax/liver >3.3 detected CCA in 8/9 patients whereas a quotient < 2.4 excluded CCA. Combining brush cytology and quantitative [18F]FDG-PET/CT yielded a sensitivity for HGD and/or CCA of 100% and a specificity of 88%.

CONCLUSION: Early detection of HGD before manifest CCA is feasible with repeated brush cytology and may allow for preemptive liver transplantation. [18F]FDG-PET/CT has a high sensitivity for manifest CCA and a negative scan indicates a non-malignant state of the disease. Brush cytology and [18F]FDG-PET/CT are complementary in monitoring and managing PSC patients with dominant strictures.

National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-231471 (URN)10.1016/j.jhep.2014.07.032 (DOI)000345115600023 ()25111173 (PubMedID)
Available from: 2014-09-08 Created: 2014-09-08 Last updated: 2017-12-05Bibliographically approved
Hallén, K., Sangfelt, P., Nilsson, T., Nordgren, H., Wanders, A. & Molin, D. (2014). Vanishing bile duct-like syndrome in a patient with Hodgkin lymphoma: pathological development and restitution [Letter to the editor]. Acta Oncologica, 53(9), 1271-1275
Open this publication in new window or tab >>Vanishing bile duct-like syndrome in a patient with Hodgkin lymphoma: pathological development and restitution
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2014 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 9, p. 1271-1275Article in journal, Letter (Refereed) Published
National Category
Basic Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-224045 (URN)10.3109/0284186X.2014.897001 (DOI)000342282100020 ()24697745 (PubMedID)
Available from: 2014-04-30 Created: 2014-04-30 Last updated: 2018-01-11Bibliographically approved
Dieterich, L. C., Schiller, P., Huang, H., Wawrousek, E. F., Loskog, A., Wanders, A., . . . Dimberg, A. (2013). alpha B-Crystallin regulates expansion of CD11b(+)Gr-1(+) immature myeloid cells during tumor progression. The FASEB Journal, 27(1), 151-162
Open this publication in new window or tab >>alpha B-Crystallin regulates expansion of CD11b(+)Gr-1(+) immature myeloid cells during tumor progression
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2013 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 27, no 1, p. 151-162Article in journal (Refereed) Published
Abstract [en]

The molecular chaperone αB-crystallin has emerged as a target for cancer therapy due to its expression in human tumors and its role in regulating tumor angiogenesis. αB-crystallin also reduces neuroinflammation, but its role in other inflammatory conditions has not been investigated. Here, we examined whether αB-crystallin regulates inflammation associated with tumors and ischemia. We found that CD45+ leukocyte infiltration is 3-fold increased in tumors and ischemic myocardium in αB-crystallin-deficient mice. Notably, αB-crystallin is prominently expressed in CD11b+ Gr-1+ immature myeloid cells (IMCs), known as regulators of angiogenesis and immune responses, while lymphocytes and mature granulocytes show low αB-crystallin expression. αB-Crystallin deficiency results in a 3-fold higher accumulation of CD11b+ Gr-1+ IMCs in tumors and a significant rise in CD11b+ Gr-1+ IMCs in spleen and bone marrow. Similarly, we noted a 2-fold increase in CD11b+ Gr-1+ IMCs in chronically inflamed livers in αB-crystallin-deficient mice. The effect of αB-crystallin on IMC accumulation is limited to pathological conditions, as CD11b+ Gr-1+ IMCs are not elevated in naive mice. Through ex vivo differentiation of CD11b+ Gr-1+ cells, we provide evidence that αB-crystallin regulates systemic expansion of IMCs through a cell-intrinsic mechanism. Our study suggests a key role of αB-crystallin in limiting expansion of CD11b+ Gr-1+ IMCs in diverse pathological conditions.—Dieterich, L. C., Schiller, P., Huang, H., Wawrousek, E. F., Loskog, A., Wanders, A., Moons, L., Dimberg, A. αB-Crystallin regulates expansion of CD11b+Gr-1+ immature myeloid cells during tumor progression.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-187588 (URN)10.1096/fj.12-213017 (DOI)000313103200015 ()23033322 (PubMedID)
Available from: 2012-12-07 Created: 2012-12-07 Last updated: 2018-01-12Bibliographically approved
Ramachandran, M., Yu, D., Wanders, A., Essand, M. & Eriksson, F. (2013). An infection-enhanced oncolytic adenovirus secreting H. pylori neutrophil-activating protein with therapeutic effects on neuroendocrine tumors. Molecular Therapy, 21(11), 2008-2018
Open this publication in new window or tab >>An infection-enhanced oncolytic adenovirus secreting H. pylori neutrophil-activating protein with therapeutic effects on neuroendocrine tumors
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2013 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 21, no 11, p. 2008-2018Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori Neutrophil Activating Protein (HP-NAP) is a major virulence factor involved in H. pylori infection. HP-NAP can mediate anti-tumor effects by recruiting neutrophils and inducing Th1-type differentiation in the tumor microenvironment. It therefore holds strong potential as a therapeutic gene. Here, we armed a replication-selective, infection-enhanced adenovirus with secretory HP-NAP, Ad5PTDf35-[Δ24-sNAP], and evaluated its therapeutic efficacy against neuroendocrine tumors. We observed that it could specifically infect and eradicate a wide range of tumor cells lines from different origin in vitro. Insertion of secretory HP-NAP did not affect the stability or replicative capacity of the virus and infected tumor cells could efficiently secrete HP-NAP. Intratumoral administration of the virus in nude mice xenografted with neuroendocrine tumors improved median survival. Evidence of biological HP-NAP activity was observed 24 hours after treatment with neutrophil infiltration in tumors and an increase of proinflammatory cytokines such as TNF-α and MIP2-α in the systemic circulation. Furthermore, evidence of Th1-type immune polarization was observed as a result of increase in IL-12/23 p40 cytokine concentrations 72 hours post-virus administration. Our observations suggest that HP-NAP can serve as a potent immunomodulator in promoting anti-tumor immune response in the tumor microenvironment and enhance the therapeutic effect of oncolytic adenovirus.

Keyword
Helicobacter pylori, Neutrophil Activating Protein, adenovirus, cancer therapy
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Molecular Medicine; Clinical Virology; Medical Virology; Clinical Immunology
Identifiers
urn:nbn:se:uu:diva-203649 (URN)10.1038/mt.2013.153 (DOI)000326937000007 ()23817216 (PubMedID)
Funder
Swedish Cancer Society, 10‐0105Swedish Cancer Society, 10‐0552Swedish Research Council, K2013‐55X‐22191‐01‐3
Note

De två (2) sista författarna delar sistaförfattarskapet.

Open access under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License (CC BY-NC-ND). 2013.

Supported funds:

The Swedish Children Cancer Foundation(PROJ10/027), Gunnar Nilsson’s Cancer Foundation, Marcus and Marianne Wallenberg’sFoundation

Available from: 2013-07-16 Created: 2013-07-16 Last updated: 2017-12-06Bibliographically approved
Högberg, N., Stenbäck, A., Carlsson, P.-O., Wanders, A. & Engstrand Lilja, H. (2013). Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis. Journal of Pediatric Surgery, 48(11), 2308-2312
Open this publication in new window or tab >>Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis
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2013 (English)In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 48, no 11, p. 2308-2312Article in journal (Refereed) Published
Abstract [en]

Background/purpose:

Necrotizing enterocolitis (NEC) represents one of the gravest complications in preterm infants and carries significant morbidity and mortality. Increased intestinal permeability may play an important role in the pathogenesis of NEC. In this study we investigated the genes regulating structural proteins such as tight junctions (TJ) and cell adhesion in a neonatal rat model of early NEC, as well as the expression of TJ proteins by immunohistochemistry staining.

Methods:

The studies were performed on Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment on day 1 after birth. Intestinal specimens from the ileum were obtained, mRNA was purified and the transcriptome was analyzed using microarray. Immunohistochemistry staining was performed for TJ proteins.

Results:

We found several TJ genes such as claudins 1, 8, 14, 15 and gap junction protein to be affected. Immunohistochemistry staining for TJ protein claudin-1 revealed decreased levels in experimental NEC compared to controls. Alterations in genes involved in the inflammatory response was confirmed, along with several genes regulating proteins used as biomarkers for NEC.

Conclusion:

This study indicates that tight junctions and cell adhesion may play a critical role in the pathogenesis of early experimental NEC. Better understanding of the pathogenesis of NEC may lead to novel strategies for the prevention and treatment of NEC.

National Category
Surgery Basic Medicine
Research subject
Pediatric Surgery; Pathology
Identifiers
urn:nbn:se:uu:diva-197750 (URN)10.1016/j.jpedsurg.2013.06.027 (DOI)000327140800022 ()
Note

De två sista författarna delar sistaförfattarskapet.

Available from: 2013-04-03 Created: 2013-04-03 Last updated: 2018-01-11Bibliographically approved
Nyström, N., Berg, T., Lundin, E., Skog, O., Hansson, I., Frisk, G., . . . Wanders, A. (2013). Human enterovirus species B in ileocecal Crohn's disease. Clinical and Translational Gastroenterology, 4, Article ID e38.
Open this publication in new window or tab >>Human enterovirus species B in ileocecal Crohn's disease
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2013 (English)In: Clinical and Translational Gastroenterology, ISSN 2155-384X, E-ISSN 2155-384X, Vol. 4, article id e38Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES:

Advanced ileocecal Crohn's disease (ICD) is characterized by strictures, inflammation in the enteric nervous system (myenteric plexitis), and a high frequency of NOD2 mutations. Recent findings implicate a role of NOD2 and another CD susceptibility gene, ATG16L1, in the host response against single-stranded RNA (ssRNA) viruses. However, the role of viruses in CD is unknown. We hypothesized that human enterovirus species B (HEV-B), which are ssRNA viruses with dual tropism both for the intestinal epithelium and the nervous system, could play a role in ICD.

METHODS:

We used immunohistochemistry and in situ hybridization to study the general presence of HEV-B and the presence of the two HEV-B subspecies, Coxsackie B virus (CBV) and Echovirus, in ileocecal resections from 9 children with advanced, stricturing ICD and 6 patients with volvulus, and in intestinal biopsies from 15 CD patients at the time of diagnosis.

RESULTS:

All patients with ICD had disease-associated polymorphisms in NOD2 or ATG16L1. Positive staining for HEV-B was detected both in the mucosa and in myenteric nerve ganglia in all ICD patients, but in none of the volvulus patients. Expression of the cellular receptor for CBV, CAR, was detected in nerve cell ganglia.

CONCLUSIONS:

The common presence of HEV-B in the mucosa and enteric nervous system of ICD patients in this small cohort is a novel finding that warrants further investigation to analyze whether HEV-B has a role in disease onset or progress. The presence of CAR in myenteric nerve cell ganglia provides a possible route of entry for CBV into the enteric nervous system.

National Category
Basic Medicine Gastroenterology and Hepatology
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-224046 (URN)10.1038/ctg.2013.7 (DOI)23804031 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Childhood Cancer Foundation
Note

De två sista författarna delar sistaförfattarskapet.

Available from: 2014-04-30 Created: 2014-04-30 Last updated: 2018-01-11Bibliographically approved
Urdzik, J., Bjerner, T., Wanders, A., Duraj, F., Haglund, U. & Norén, A. (2013). Magnetic resonance imaging flowmetry demonstrates portal vein dilatation subsequent to oxaliplatin therapy in patients with colorectal liver metastasis. Paper presented at This manuscript was presented at the 10th World IHPBA Congress, Paris, 1–5 July 2012.. HPB, 15(4), 265-272
Open this publication in new window or tab >>Magnetic resonance imaging flowmetry demonstrates portal vein dilatation subsequent to oxaliplatin therapy in patients with colorectal liver metastasis
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2013 (English)In: HPB, ISSN 1365-182X, E-ISSN 1477-2574, Vol. 15, no 4, p. 265-272Article in journal (Refereed) Published
Abstract [en]

Objectives: 

Sinusoidal injury (SI) after oxaliplatin-based therapies for colorectal liver metastasis (CRLM) can increase postoperative morbidity. Preoperative methods to estimate SI are lacking. The aim of this study was to identify SI by evaluating portal vein haemodynamics.

Methods: 

Magnetic resonance imaging flowmetry (MRIF) was used to estimate portal vein haemodynamics in 29 patients with CRLM before liver surgery. Sinusoidal injury was evaluated from resected non-tumorous liver parenchyma according to the combined vascular injury (CVI) score of ≥3.

Results: 

All patients with SI (six of 29) received oxaliplatin; however, a significant association could not be proven (P= 0.148). Oxaliplatin-treated patients showed portal vein dilatation in both the SI and non-SI groups compared with patients who had not received oxaliplatin (Bonferroni corrected P= 0.003 and P= 0.039, respectively). Mean portal velocity tended to be lower in patients with SI compared with oxaliplatin-treated patients without SI (Bonferroni corrected P= 0.087). A mean portal velocity of ≤14.35 cm/s together with a cross-section area of ≥1.55 cm2 was found to predict SI with sensitivity of 100% and specificity of 78%.

Conclusions: 

Oxaliplatin treatment was associated with portal vein dilatation. Patients with SI showed a tendency towards decreased mean portal flow velocity. This may indicate that SI is associated with an increased resistance to blood flow in the liver parenchyma. Portal vein haemodynamic variables estimated by MRIF can identify patients without SI non-invasively.

National Category
Medical and Health Sciences Basic Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-190126 (URN)10.1111/j.1477-2574.2012.00540.x (DOI)000315902600004 ()
Conference
This manuscript was presented at the 10th World IHPBA Congress, Paris, 1–5 July 2012.
Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2018-01-11Bibliographically approved
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