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Contribution of CARD15 variants in determining susceptibility to Crohn's disease in Sweden.

https://arctichealth.org/en/permalink/ahliterature169195
Source
Scand J Gastroenterol. 2006 Jun;41(6):700-5
Publication Type
Article
Date
Jun-2006
Author
Leif Törkvist
Colin L Noble
Mikael Lördal
Urban Sjöqvist
Ulrik Lindforss
Elaine R Nimmo
Richard K Russell
Robert Löfberg
Jack Satsangi
Author Affiliation
Department of Medical and Surgical Gastroenterology, Karolinska University Hospital, Stockholm, Sweden. leif.torkvist@ki.se
Source
Scand J Gastroenterol. 2006 Jun;41(6):700-5
Date
Jun-2006
Language
English
Publication Type
Article
Keywords
Alleles
Case-Control Studies
Crohn Disease - epidemiology - genetics
European Continental Ancestry Group
Female
Gene Frequency
Genetic Predisposition to Disease
Genetic Variation
Humans
Intracellular Signaling Peptides and Proteins - genetics
Male
Multivariate Analysis
Mutation
Nod2 Signaling Adaptor Protein
Sweden - epidemiology
Abstract
Crohn's disease (CD) is a chronic inflammatory bowel disorder caused by environmental and genetic factors. Mutations in the CARD15 gene have been associated with CD. No previous case-control CARD15 study has been performed in the Swedish population.
The study comprised of 321 individuals: 178 with CD and 143 healthy controls (HCs), all from Stockholm County. All were genotyped for the three main CD-associated CARD15 variants (R702W, G908R and 1007fs) and phenotypic associations were investigated.
The allele frequencies of the R702W variant (4.5% CD versus 0.7% HC, p=0.008, OR = 6.8) and the G908R variant (2.0% CD versus 0% HC, p=0.045) were more common in CD patients than in controls. No significant difference in1007fs variant allele frequency was found between CD patients and controls (2.0% CD versus 1.7% HC, p = 0.8, OR = 1.1). Carriage of CARD15 variants was more common in the CD patients than in controls (15.2% CD versus 4.2% HC, p = 0.001, OR = 4.1, population attributable risk (PAR) = 11.4%). Genotype-phenotype analysis demonstrated that CARD15 variants were associated with ileal disease (p=0.0006, OR = 9.3, CI = 2.2-34) and protective for colonic CD (p = 0.01, OR = 0.18). An association between CARD15 variants and ileal CD (p=0.004, OR = 6.6) was confirmed by multivariate analyses.
The CARD15 variants R702W and G908R, but not 1007fs, are associated with susceptibility to CD in Stockholm County. Genotype-phenotype analysis shows an association with ileal CD. The contribution of these CARD15 mutations in Swedish CD patients overall is low in relation to studies elsewhere in Central Europe and North America, but is consistent with emerging data from elsewhere in Scandinavia and in Northern Europe.
PubMed ID
16716969 View in PubMed
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Contribution of the IBD5 locus to Crohn's disease in the Swedish population.

https://arctichealth.org/en/permalink/ahliterature164814
Source
Scand J Gastroenterol. 2007 Feb;42(2):200-6
Publication Type
Article
Date
Feb-2007
Author
Leif Törkvist
Colin L Noble
Mikael Lördal
Urban Sjöqvist
Ulrik Lindforss
Elaine R Nimmo
Robert Löfberg
Richard K Russell
Jack Satsangi
Author Affiliation
Department of Medical & Surgical Gastroenterology, Karolinska University Hospital, Stockholm, Sweden.
Source
Scand J Gastroenterol. 2007 Feb;42(2):200-6
Date
Feb-2007
Language
English
Publication Type
Article
Keywords
Adult
Chromosomes, Human, Pair 5 - genetics
Crohn Disease - epidemiology - genetics
Female
Follow-Up Studies
Gene Frequency
Genetic Predisposition to Disease
Genetic Variation
Haplotypes
Humans
Incidence
Linkage Disequilibrium
Male
Middle Aged
Organic Cation Transport Proteins - genetics
Risk factors
Sweden - epidemiology
Abstract
Recent data have controversially suggested that variants of the organic cation transport genes SLC22A4 (OCTN1) and SLC22A5 (OCTN2) are responsible for the contribution of IBD5 to disease susceptibility in Crohn's disease (CD). The objective of this study was to assess the contribution of the SLC22A4 variant (1672T) and SLC22A5 variant (-207C) together with three IBD5 haplotype markers in the previously uninvestigated Swedish CD population.
The study comprised 178 CD patients and 143 healthy controls (HC). Genotyping for IBD5 single nucleotide polymorphisms (SNPs) IGR2096a_1, IGR2198a_1, IGR2230a_1, SLC22A4 1672T and SLC22A5 -207C was carried out using the TaqMan system. Associations with disease susceptibility and disease phenotype were investigated.
Strong linkage disequilibrium was observed between the investigated SNPs (D prime >0.92). IGR2096a_1 allelic frequency and homozygosity rates were associated with CD (44% CD versus 33.8% HC, p=0.008, OR=1.55 and 20% CD versus 12% HC, p=0.04, OR=1.93, respectively). Variant allelic frequency of SLC22A4, 1672T (44% versus 36%, p=0.03, OR=1.4) and homozygosity for the SLC22A4, SLC22A5 TC haplotype (1672T, -207C) (21.3% versus 12%, p=0.03, OR=1.78, population attributable risk (PAR)=11%) were associated with CD. There was no association between the allelic frequency of SLC22A5 and CD (46.6% CD versus 41.5% HC, p=0.82). The association of the TC haplotype with CD was not independent of the SNPs representing the extended IBD5 linkage interval.
The IBD5 locus is associated with CD in the Swedish population. The strongest association is with the marker SNP IGR2096a_1, lying p-telomeric to SLC22A4 and SLC22A5. The effect of the TC haplotype was not an independent determinant in this population.
PubMed ID
17340776 View in PubMed
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Granulocyte, monocyte/macrophage apheresis for inflammatory bowel disease: the first 100 patients treated in Scandinavia.

https://arctichealth.org/en/permalink/ahliterature164913
Source
Scand J Gastroenterol. 2007 Feb;42(2):221-7
Publication Type
Article
Date
Feb-2007
Author
Tryggve Ljung
Ole Østergaard Thomsen
Morten Vatn
Per Karlén
Lars Norman Karlsen
Curt Tysk
Stefan U Nilsson
Anders Kilander
Rolf Gillberg
Olof Grip
Stefan Lindgren
Ragnar Befrits
Robert Löfberg
Author Affiliation
Department of Gastroentereology and Hepatology, Karolinska University Hospital, Stockholm, Sweden.
Source
Scand J Gastroenterol. 2007 Feb;42(2):221-7
Date
Feb-2007
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Female
Follow-Up Studies
Granulocytes
Humans
Incidence
Inflammatory Bowel Diseases - epidemiology - therapy
Leukapheresis - methods
Macrophages
Male
Middle Aged
Monocytes
Prospective Studies
Scandinavia - epidemiology
Treatment Outcome
Abstract
Selective leukocyte apheresis is a new type of non-pharmacological treatment for patients with active ulcerative colitis and Crohn's disease. Preliminary data have indicated that this type of therapy is safe and efficacious, and large sham-controlled studies are currently in progress. In Scandinavia, a substantial number of patients with chronic inflammatory bowel disease have already received leukocyte apheresis on a compassionate use basis and the aim of this study was to report the clinical outcome and adverse events in the first patients treated.
Clinical details of the first consecutive 100 patients with inflammatory bowel disease treated with granulocyte, monocyte/macrophage (Adacolumn) apheresis in Scandinavia were prospectively registered. Median length of follow-up was 17 months, (range 5-30).
The study population comprised 52 patients with ulcerative colitis, 44 patients with Crohn's disease and 4 patients with indeterminate colitis. In 97 patients the indication for Adacolumn treatment was steroid-refractory or steroid-dependent disease. Clinical remission was attained in 48% of the patients with ulcerative colitis, and an additional 27% had a clinical response to the apheresis treatment. The corresponding figures for patients with Crohn's disease were 41% and 23%, respectively. Complete steroid withdrawal was achieved in 27 out of the 50 patients taking corticosteroids at baseline. Adverse events were reported in 15 patients and headache was most frequently reported (n=7).
Granulocyte, monocyte/macrophage apheresis treatment seems to be a valuable adjuvant therapy in selected patients with refractory inflammatory bowel disease. The risk for toxicity or severe adverse events appears to be low.
PubMed ID
17327942 View in PubMed
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Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease.

https://arctichealth.org/en/permalink/ahliterature282860
Source
J Crohns Colitis. 2016 May;10(5):556-65
Publication Type
Article
Date
May-2016
Author
Thomas Cars
Björn Wettermark
Robert Löfberg
Irene Eriksson
Johan Sundström
Mikael Lördal
Source
J Crohns Colitis. 2016 May;10(5):556-65
Date
May-2016
Language
English
Publication Type
Article
Keywords
Adult
Aged
Colitis, Ulcerative - drug therapy - epidemiology - surgery
Crohn Disease - drug therapy - epidemiology - surgery
Cross-Sectional Studies
Databases, Factual
Female
Gastrointestinal Agents - therapeutic use
Health Services - statistics & numerical data - utilization
Hospitalization - statistics & numerical data
Humans
Male
Middle Aged
Prevalence
Sweden - epidemiology
Abstract
Crohn's disease [CD] and ulcerative colitis [UC] are chronic diseases associated with a substantial utilisation of healthcare resources. We aimed to estimate the prevalence of inflammatory bowel disease [IBD], CD, and UC and to describe and compare healthcare utilisation and drug treatment in CD and UC patients.
This was a cross-sectional study of all patients with a recorded IBD diagnosis in Stockholm County, Sweden. Data on outpatient visits, hospitalisations, surgeries, and drug treatment during 2013 were analysed.
A total of 13 916 patients with IBD were identified, corresponding to an overall IBD prevalence of 0.65% [CD 0.27%, UC 0.35%, inflammatory bowel disease unclassified 0.04%]; 49% of all IBD patients were treated with IBD-related drugs. Only 3.6% of the patients received high-dose corticosteroids, whereas 32.4% were treated with aminosalicylates [CD 21.2%, UC 41.0%, p
Notes
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PubMed ID
26733406 View in PubMed
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IL23R in the Swedish, Finnish, Hungarian and Italian populations: association with IBD and psoriasis, and linkage to celiac disease.

https://arctichealth.org/en/permalink/ahliterature152922
Source
BMC Med Genet. 2009;10:8
Publication Type
Article
Date
2009
Author
Elisabet Einarsdottir
Lotta L E Koskinen
Emma Dukes
Kati Kainu
Sari Suomela
Maarit Lappalainen
Fabiana Ziberna
Ilma R Korponay-Szabo
Kalle Kurppa
Katri Kaukinen
Róza Adány
Zsuzsa Pocsai
György Széles
Martti Färkkilä
Ulla Turunen
Leena Halme
Paulina Paavola-Sakki
Tarcisio Not
Serena Vatta
Alessandro Ventura
Robert Löfberg
Leif Torkvist
Francesca Bresso
Jonas Halfvarson
Markku Mäki
Kimmo Kontula
Ulpu Saarialho-Kere
Juha Kere
Mauro D'Amato
Päivi Saavalainen
Author Affiliation
Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland. elisabet.einarsdottir@helsinki.fi
Source
BMC Med Genet. 2009;10:8
Date
2009
Language
English
Publication Type
Article
Keywords
Case-Control Studies
Celiac Disease - complications - genetics
Colitis, Ulcerative - complications - genetics
Crohn Disease - complications - genetics
Finland
Genetic markers
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Hungary
Italy
Linkage Disequilibrium
Psoriasis - complications - genetics
Receptors, Interleukin - genetics
Sweden
Abstract
Association of the interleukin-23 receptor (IL23R) with inflammatory bowel disease (IBD) has been confirmed in several populations. IL23R also associates with psoriasis, suggesting that the gene may be an important candidate for many chronic inflammatory diseases.
We studied association of single-nucleotide variants in IL23R with IBD in Swedish patients, in both Crohn's disease (CD) and ulcerative colitis (UC) subsets. The same genetic variants were also studied in Finnish patients with psoriasis or celiac disease, and in Hungarian and Italian patients with celiac disease.
Association of IL23R with IBD was replicated in our Swedish patients, and linkage and association of the IL23R region with psoriasis was found in the Finnish population. The IL23R region was also linked to celiac disease in Finnish families, but no association of IL23R variants with celiac disease was found in the Finnish, Hungarian or Italian samples.
Our study is the first to demonstrate association of IL23R with CD and UC in Swedish patients with IBD. It is also the first study to report linkage and association of the IL23R region with psoriasis in the Finnish population. Importantly, this is the first report of linkage of the IL23R region to celiac disease, a chronic inflammatory condition in which IL23R has not been previously implicated.
Notes
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PubMed ID
19175939 View in PubMed
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Inflammatory bowel disease confers a lower risk of colorectal cancer to females than to males.

https://arctichealth.org/en/permalink/ahliterature97990
Source
Gastroenterology. 2010 May;138(5):1697-703
Publication Type
Article
Date
May-2010
Author
Sverre Söderlund
Fredrik Granath
Olle Broström
Per Karlén
Robert Löfberg
Anders Ekbom
Johan Askling
Author Affiliation
Department of Medicine, Karolinska Institutet, Stockholm Söder Hospital, Stockholm, Sweden. sverresoderlund@hotmail.com
Source
Gastroenterology. 2010 May;138(5):1697-703
Date
May-2010
Language
English
Geographic Location
Sweden
Publication Type
Article
Keywords
Cohort Studies
Colorectal Neoplasms - epidemiology - etiology
Female
Humans
Incidence
Inflammatory Bowel Diseases - complications - epidemiology
Kaplan-Meiers Estimate
Male
Middle Aged
Registries
Risk assessment
Risk factors
Sex Factors
Sweden - epidemiology
Time Factors
Abstract
BACKGROUND & AIMS: Reported differences in cancer risk between male and female animals after chronic inflammation suggest that estrogen has inflammation-modifying properties. Little is known about these effects in human beings. Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC); we studied differences in inflammation-associated CRC between men and women patients with IBD. METHODS: By using a large population-based cohort (n = 7607) of individuals diagnosed with IBD from 1954 to 1989, we assessed the sex-specific incidence of CRC from 1960 to 2004. Incidence was determined within the cohort (modeled using Poisson regression) and compared with the general population (assessed as standardized incidence ratios) using data from national Swedish health and census registers. RESULTS: During 171,000 person-years of follow-up evaluation, 196 new cases of CRC were observed (123 in males, 73 in females). Males with IBD had a 60% higher risk of CRC (relative risk [RR], 1.6; 95% confidence interval [CI], 1.2-2.2) than females (cumulative incidence 40 years after IBD diagnosis, 8.3% vs 3.5%). Compared with the rate of CRC among the general population, in males with IBD the RR was 2.6 and the 95% CI was 2.2-3.1, whereas in females the RR was 1.9 and the 95% CI was 1.5-2.4. The effect of sex was limited to the period after 10 years of follow-up evaluation (RR, 0.8 before vs 2.2 after), and to patients diagnosed before age 45 (RR, 2.1 before vs 1.0 after). CONCLUSIONS: IBD confers a lower risk of CRC to females than to males.
Notes
RefSource: Gastroenterology. 2010 May;138(5):1658-60
PubMed ID
20167217 View in PubMed
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Microscopic colitis: a descriptive clinical cohort study of 795 patients with collagenous and lymphocytic colitis.

https://arctichealth.org/en/permalink/ahliterature277447
Source
Scand J Gastroenterol. 2016;51(5):556-62
Publication Type
Article
Date
2016
Author
Marie-Rose Mellander
Anders Ekbom
Rolf Hultcrantz
Robert Löfberg
Åke Öst
Jan Björk
Source
Scand J Gastroenterol. 2016;51(5):556-62
Date
2016
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Age of Onset
Aged
Aged, 80 and over
Biopsy
Chronic Disease
Colitis, Collagenous - complications - diagnosis - epidemiology
Colitis, Lymphocytic - complications - diagnosis - epidemiology
Colitis, Microscopic - complications - diagnosis - epidemiology
Colonoscopy - methods
Diagnosis, Differential
Diarrhea - diagnosis - epidemiology - etiology
Female
Follow-Up Studies
Humans
Incidence
Intestinal Mucosa - pathology
Lymphocyte Count
Male
Middle Aged
Retrospective Studies
Sweden - epidemiology
Young Adult
Abstract
Microscopic colitis is a common cause of chronic diarrhoea in the Scandinavian countries. This report comprises demographic data, clinical and endoscopic features, and occurrence of coeliac and inflammatory bowel disease (IBD) in a large urban cohort of patients with lymphocytic colitis (LC) and collagenous colitis (CC).
A total of 795 patients with microscopic colitis from two hospitals in Stockholm were included. Medical records were reviewed and clinical data, including endoscopic and histological findings, were compiled.
Forty-three percent had CC (female:male ratio 3.7:1) and 57% had LC (female:male ratio 2.7:1). The mean age at diagnosis of CC was 63 years and of LC was 59 years (p?=?0.005). Clinical features were similar in both entities, but the intensity of symptoms differed. Watery diarrhoea was reported in 55% in CC patients versus in 43% in LC patients (p?=?0.0014), and nocturnal diarrhoea in 28% versus 18% (p?=?0.002). Subtle endoscopic mucosal findings were reported in 37% of the CC patients and in 25% of the LC patients (p?=?0.0011). Colorectal adenomatous polyps were found in 5.3% of all patients. Coeliac disease occurred in 6% and IBD occurred in 2.1% of all patients.
Clinical features of LC and CC are similar but not identical. CC seems to be a more severe type of bowel inflammation and LC tends to occur earlier in life. Both forms might indeed feature endoscopic findings despite the designation 'microscopic'. Our study confirms the strong association with coeliac disease.
PubMed ID
26679722 View in PubMed
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PepT1 oligopeptide transporter (SLC15A1) gene polymorphism in inflammatory bowel disease.

https://arctichealth.org/en/permalink/ahliterature150812
Source
Inflamm Bowel Dis. 2009 Oct;15(10):1562-9
Publication Type
Article
Date
Oct-2009
Author
Marco Zucchelli
Leif Torkvist
Francesca Bresso
Jonas Halfvarson
Anna Hellquist
Francesca Anedda
Ghazaleh Assadi
Gunnar B Lindgren
Monika Svanfeldt
Martin Janson
Colin L Noble
Sven Pettersson
Maarit Lappalainen
Paulina Paavola-Sakki
Leena Halme
Martti Färkkilä
Ulla Turunen
Jack Satsangi
Kimmo Kontula
Robert Löfberg
Juha Kere
Mauro D'Amato
Author Affiliation
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Source
Inflamm Bowel Dis. 2009 Oct;15(10):1562-9
Date
Oct-2009
Language
English
Publication Type
Article
Keywords
Adult
Case-Control Studies
Cohort Studies
Colitis, Ulcerative - genetics
Crohn Disease - genetics
Female
Finland
Genotype
Humans
Male
Middle Aged
NF-kappa B - genetics - metabolism
Nod2 Signaling Adaptor Protein - genetics - metabolism
Polymorphism, Single Nucleotide - genetics
Sweden
Symporters - genetics
Abstract
Human polymorphisms affecting gut epithelial barrier and interactions with bacteria predispose to the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC). The intestinal transporter PepT1, encoded by the SLC15A1 gene, mediates intracellular uptake of bacterial products that can induce inflammation and NF-kappaB activation upon binding to NOD2, a protein often mutated in CD. Hence, we tested SLC15A1 polymorphisms for association with IBD.
Twelve SLC15A1 single nucleotide polymorphisms (SNPs) were genotyped in 1783 individuals from 2 cohorts of Swedish and Finnish IBD patients and controls. An in vitro system was set up to evaluate the potential impact of SLC15A1 polymorphism on PepT1 transporter function by quantification of NOD2-mediated activation of NF-kappaB.
The common allele (C) of a coding polymorphism (rs2297322, Ser117Asn) was associated with CD susceptibility both in Sweden and in Finland, but with genetic effects in opposite directions (risk and protection, respectively). The best evidence of association was found in both populations when the analysis was performed on individuals not carrying NOD2 common risk alleles (Sweden allelic P = 0.0007, OR 1.97, 95% confidence interval [CI] 1.34-2.92; Finland genotype P = 0.0013, OR 0.63, 95% CI 0.44-0.90). The PepT1 variant encoded by the C allele (PepT1-Ser117) was associated with reduced signaling downstream of NOD2 (P
PubMed ID
19462432 View in PubMed
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Potential role for the common cystic fibrosis DeltaF508 mutation in Crohn's disease.

https://arctichealth.org/en/permalink/ahliterature165784
Source
Inflamm Bowel Dis. 2007 May;13(5):531-6
Publication Type
Article
Date
May-2007
Author
Francesca Bresso
Johan Askling
Marco Astegiano
Brunello Demarchi
Nicoletta Sapone
Mario Rizzetto
Paolo Gionchetti
Karen M Lammers
Annalisa de Leone
Gabriele Riegler
Elaine R Nimmo
Hazel Drummond
Colin Noble
Leif Torkvist
Anders Ekbom
Marco Zucchelli
Robert Lofberg
Jack Satsangi
Sven Pettersson
Mauro D'Amato
Author Affiliation
Strategic Research Center IRIS, Karolinska Institutet, Stockholm, Sweden.
Source
Inflamm Bowel Dis. 2007 May;13(5):531-6
Date
May-2007
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Crohn Disease - genetics - pathology - physiopathology
Cystic Fibrosis Transmembrane Conductance Regulator - genetics - physiology
Female
Genetic Predisposition to Disease
Genotype
Heterozygote Detection
Humans
Italy
Male
Middle Aged
Mutation
Phenotype
Scotland
Sweden
Abstract
Inflammatory bowel disease (IBD) is an epithelial barrier disease that is thought to result from a dysregulated interaction with bacteria in the intestine of genetically predisposed individuals. The cystic fibrosis transmembrane conductance regulator (CFTR), which is mutated in the autosomal recessive disease cystic fibrosis, modulates gut permeability, mucus production, and epithelial interactions with bacteria. The cystic fibrosis DeltaF508 mutation is commonly found in the general population and has been shown to result in a reduced number of CFTR molecules at the surface of epithelial cells. Given the important biological functions of CFTR in the intestine, we tested whether this mutation is of relevance to IBD.
Using DNA heteroduplex analysis, we investigated the distribution of DeltaF508 heterozygosity in 2568 subjects from three independent cohorts of Italian, Swedish, and Scottish IBD patients and controls.
In all three cohorts an association between DeltaF508 and Crohn's disease (CD) was observed. Specifically, DeltaF508 heterozygosity was markedly underrepresented in CD patients from Italy and Sweden (P = 0.021 and 0.027 versus controls, respectively), while stratification for disease location revealed an absence of DeltaF508 carriers among Scottish CD patients with right-sided colitis (P = 0.023 versus all other locations).
DeltaF508 heterozygosity might exert a protective effect in CD.
PubMed ID
17206681 View in PubMed
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