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Faye, A. S., Axelrad, J., Sun, J., Halfvarson, J., Söderling, J., Olén, O. & Ludvigsson, J. F. (2024). Atherosclerosis as a Risk Factor of Inflammatory Bowel Disease: A Population-Based Case-Control Study. American Journal of Gastroenterology, 119(2), 313-322
Open this publication in new window or tab >>Atherosclerosis as a Risk Factor of Inflammatory Bowel Disease: A Population-Based Case-Control Study
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2024 (English)In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 119, no 2, p. 313-322Article in journal (Refereed) Published
Abstract [en]

Introduction: Data suggest atherosclerotic-related inflammation may play a role in the pathogenesis of inflammatory bowel disease (IBD), but large-scale studies are missing.

Methods: In this nationwide case-control study, we used the Swedish Patient Register and the Epidemiology Strengthened by histoPathology Reports in Sweden cohort to identify adult cases of incident IBD between 2002 and 2021, with each case matched to up to 10 general population controls. We used conditional logistic regression to calculate odds ratios (OR) for exposure to an atherosclerotic-related condition (myocardial infarction, thromboembolic stroke, or atherosclerosis itself) before being diagnosed with IBD.

Results: There were a total of 56,212 individuals with IBD and 531,014 controls. Of them, 2,334 (4.2%) cases and 18,222 (3.4%) controls had a prior diagnosis of an atherosclerotic-related condition, corresponding to an OR of 1.30 (95% confidence interval [CI] 1.24-1.37). Results were statistically significant for both Crohn's disease (OR 1.37, 95% CI 1.26-1.48) and ulcerative colitis (OR 1.27, 95% CI 1.20-1.35) and for individuals who developed IBD at 40-59 years of age and 60 years or older. In addition, associations persisted when adjusting for underlying comorbidities, including the presence of immune-mediated diseases and prior aspirin and/or statin use. The highest odds of an atherosclerotic-related condition were seen in the 6-12 months before IBD diagnosis, though odds were increased even >= 5 years before. A higher magnitude of odds was also observed when having 2 or more atherosclerotic-related conditions when compared with having only 1 condition.

Discussion: A history of an atherosclerotic-related condition is associated with increased odds of developing IBD, particularly among older adults. Future studies should investigate whether drugs targeting atherosclerotic-related inflammation may prevent IBD in higher-risk individuals.

Place, publisher, year, edition, pages
Blackwell Publishing, 2024
Keywords
inflammatory bowel disease, atherosclerosis, incidence, Crohn's disease, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-108360 (URN)10.14309/ajg.0000000000002502 (DOI)001158358100021 ()37721310 (PubMedID)2-s2.0-85184280969 (Scopus ID)
Available from: 2023-09-19 Created: 2023-09-19 Last updated: 2024-03-15Bibliographically approved
Schreiber, S., Danese, S., Dignass, A., Domènech, E., Fantini, M. C., Ferrante, M., . . . Peyrin-Biroulet, L. (2024). Defining Comprehensive Disease Control for use as a Treatment Target for Ulcerative Colitis in Clinical Practice: International Delphi Consensus Recommendations. Journal of Crohn's & Colitis, 18(1), 91-105
Open this publication in new window or tab >>Defining Comprehensive Disease Control for use as a Treatment Target for Ulcerative Colitis in Clinical Practice: International Delphi Consensus Recommendations
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2024 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 18, no 1, p. 91-105Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: Treatment of ulcerative colitis (UC) requires a patient-centric, definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process.

METHODS: The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before round 3. Consensus was met if ≥ 67% of the panel agreed. Statements without consensus in rounds 1 and 2 were revised or discarded after round 3.

RESULTS: The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials (rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use), with additional patient-reported symptoms (bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance). The panel agreed on scoring systems and thresholds for many aspects.

CONCLUSIONS: Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multi-component tool and adopt comprehensive disease control as a treatment target in clinical practice and trials.

Place, publisher, year, edition, pages
Oxford University Press, 2024
Keywords
Delphi consensus, Ulcerative colitis, patient-reported symptoms, remission
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-107662 (URN)10.1093/ecco-jcc/jjad130 (DOI)001056547700001 ()37586038 (PubMedID)2-s2.0-85173768126 (Scopus ID)
Available from: 2023-08-17 Created: 2023-08-17 Last updated: 2024-02-05Bibliographically approved
Sun, J., Yao, J., Olén, O., Halfvarson, J., Bergman, D., Ebrahimi, F., . . . Ludvigsson, J. F. (2024). Familial coaggregation of inflammatory bowel disease with cardiovascular disease: a nationwide multigenerational cohort study [Letter to the editor]. Gut, Article ID gutjnl-2023-331632.
Open this publication in new window or tab >>Familial coaggregation of inflammatory bowel disease with cardiovascular disease: a nationwide multigenerational cohort study
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2024 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, article id gutjnl-2023-331632Article in journal, Letter (Refereed) Epub ahead of print
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2024
Keywords
CARDIOVASCULAR DISEASE, EPIDEMIOLOGY, IBD
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-110624 (URN)10.1136/gutjnl-2023-331632 (DOI)001143643100001 ()38184319 (PubMedID)2-s2.0-85183352821 (Scopus ID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2016-00424
Note

This study was supported by the European Crohn's and Colitis Organization (to JS; grant number: not applicable) and FORTE (to JFL; grant number: 2016-00424).

Available from: 2024-01-09 Created: 2024-01-09 Last updated: 2024-02-05Bibliographically approved
Mårild, K., Söderling, J., Stephansson, O., Axelrad, J., Halfvarson, J., Bröms, G., . . . Ludvigsson, J. F. (2024). Histological remission in inflammatory bowel disease and female fertility: A nationwide study. Gastroenterology
Open this publication in new window or tab >>Histological remission in inflammatory bowel disease and female fertility: A nationwide study
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2024 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is linked to reduced female fertility, but it is unclear how fertility rates vary by histological disease activity.

METHODS: Nationwide IBD cohort of Swedish women aged 15-44 years. We examined fertility rates during periods with vs. without histological inflammation (n=21,046; follow-up: 1990-2016) and during periods with vs. without clinical activity (IBD-related hospitalization, surgery, or treatment escalation) (n=24,995; follow-up: 2006-2020). Accounting for socio-demographics and comorbidities, we used Poisson regression to estimate adjusted fertility rate ratios (aFRRs) for live-births conceived during 12-month-periods of histological inflammation (vs. histological remission) and 3-month-periods of clinically active IBD (vs. quiescent IBD).

RESULTS: During periods with vs. without histological inflammation, there were 6.35 (95%CI=5.98-6.73) and 7.09 (95%CI=6.48-7.70) live-births conceived per 100 person-years of follow-up, respectively, or one fewer child per fourteen women with 10 years of histological inflammation (aFRR=0.90; 95%CI=0.81-1.00). In women with histological inflammation fertility was similarly reduced in ulcerative colitis (UC, aFRR=0.89 [95%CI=0.78-1.02]) and Crohn's disease (CD, aFRR=0.86 [95%CI=0.72-1.04]). Clinical IBD activity was associated with an aFRR of 0.76 (95%CI=0.72-0.79) or one fewer child per six women with 10 years of clinical activity. Fertility was reduced in clinically active UC (aFRR=0.75 [95%CI=0.70-0.81]) and CD (aFRR=0.76 [95%CI=0.70-0.82]). Finally, also among women with clinically quiescent IBD, histological inflammation (vs. histological remission) was associated with reduced fertility (aFRR=0.85 [95%CI=0.73-0.98]).

CONCLUSIONS: An association between histological and clinical activity and reduced female fertility in CD and UC was found. Notably, histological inflammation was linked to reduced fertility also in women with clinically quiescent IBD.

Place, publisher, year, edition, pages
American Gastroenterology Association Institute, 2024
Keywords
Histology, Population-based, Remission
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-111491 (URN)10.1053/j.gastro.2024.01.018 (DOI)38331202 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF), S20-0007Swedish Research Council, 2020-01980; 2020-02002Swedish Society of Medicine, SLS-935346/935415/935418; SLS-789611Karolinska InstituteNIH (National Institutes of Health), K23DK124570Region Stockholm, 20170670
Note

Grant support: KM: ALF-funding from Region Västra Götaland, grants from the University of Gothenburg, Sweden, Birgitta och Göran Karlssons foundation, The Swedish Society for Medical Research (S20-0007), The Swedish Research Council (Dnr 2020-01980), The Swedish Society of Medicine (SLS-935346/935415/935418). JFL: Karolinska Institutet. OO: Swedish Research Council (Dnr: 2020-02002), The Swedish Society of Medicine (SLS-789611), ALF (20190638). JA: Crohn’s and Colitis Foundation, the Judith Stewart Colton Center for Autoimmunity, and the NIH NIDDK Diseases K23DK124570. GB: Stockholm Region clinical postdoctoral appointment (Dnr: 20170670).

Available from: 2024-02-09 Created: 2024-02-09 Last updated: 2024-02-09Bibliographically approved
Sun, J., Yao, J., Olén, O., Halfvarson, J., Bergman, D., Ebrahimi, F., . . . Ludvigsson, J. F. (2024). Long-term risk of myocarditis in patients with inflammatory bowel disease: a nationwide cohort study in Sweden. American Journal of Gastroenterology
Open this publication in new window or tab >>Long-term risk of myocarditis in patients with inflammatory bowel disease: a nationwide cohort study in Sweden
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2024 (English)In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVES: Despite a suggested link between inflammatory bowel disease (IBD) and myocarditis, the association has not been well-established. This study aimed to investigate the long-term risk of myocarditis in patients with IBD.

METHODS: This nationwide cohort involved all patients with biopsy-confirmed IBD in Sweden (1969-2017) (n=83,264, Crohn's disease [CD, n=24,738], ulcerative colitis [UC, n=46,409], and IBD-unclassified [IBD-U, n=12,117]), general population reference individuals (n=391,344), and IBD-free full siblings (n=96,149), and followed until 2019. Primary outcome was incident myocarditis and secondary outcome was severe myocarditis (complicated with heart failure, death, or readmission). Flexible parametric survival models were used to estimate adjusted hazard ratios (aHR) and cumulative incidence of outcomes, along with 95% confidence intervals (CIs).

RESULTS: During a median follow-up of 12 years, there were 256 myocarditis cases in IBD patients (incidence rate [IR]=22.6/100,000 person-years) and 710 in reference individuals (IR=12.9), with an aHR of 1.55 (95%CI: 1.33 to 1.81). The increased risk persisted through 20 years after IBD diagnosis, corresponding to one extra myocarditis case in 735 IBD patients until then. This increased risk was observed in CD (aHR=1.48 [1.11 to 1.97]) and UC (aHR=1.58 [1.30 to 1.93]). IBD was also associated with severe myocarditis (IR: 10.1 vs. 3.5; aHR=2.44 [1.89 to 3.15]), irrespective of IBD subtypes (CD: aHR=2.39 [1.43 to 4.01], UC: aHR=2.82 [1.99 to 4.00], and IBD-U: aHR=3.14 [1.55 to 6.33]). Sibling comparison analyses yielded similar results.

CONCLUSIONS: Patients with IBD had an increased risk of myocarditis, especially severe myocarditis, for ≥20 years after diagnosis, but absolute risks were low.

Place, publisher, year, edition, pages
Wolters Kluwer, 2024
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-111407 (URN)10.14309/ajg.0000000000002701 (DOI)38315442 (PubMedID)
Available from: 2024-02-06 Created: 2024-02-06 Last updated: 2024-02-06Bibliographically approved
Marinica Grando, L., Halfvarson, J. & van Nieuwenhoven, M. A. (2024). Rectal Sensory and Compliance Testing: A Method Comparison Study between High-Resolution Anorectal Manometry and Barostat Investigations. Diagnostics, 14(4), Article ID 351.
Open this publication in new window or tab >>Rectal Sensory and Compliance Testing: A Method Comparison Study between High-Resolution Anorectal Manometry and Barostat Investigations
2024 (English)In: Diagnostics, ISSN 2075-4418, Vol. 14, no 4, article id 351Article in journal (Refereed) Published
Abstract [en]

Abnormal visceral perception and motor function are often observed in patients with fecal incontinence, evacuation disorders and irritable bowel syndrome. The international anorectal physiology working group has proposed a standardization for anorectal function assessment, where rectal sensitivity testing is performed using an elastic balloon attached to a high-resolution anorectal manometry (HRAM) catheter. Rectal compliance, another component of rectal function evaluation, is a pressure-volume relationship that refers to the rectum's ability to stretch and expand as it receives and holds fecal matter. There are no data available regarding the possibility of compliance testing using HRAM, although this is theoretically possible by correcting for the elastic balloon's intrinsic properties. The gold standard for measurement of visceral sensitivity and compliance is the rectal barostat, according to the procedure described by the European COST action GENIEUR group. Data on the agreement between the two different procedures are scarce. Hence, we performed a comparative study of the HRAM and barostat investigations in 26 healthy individuals. We hypothesized that by inflating the balloon before the examination, rectal compliance can be measured with HRAM investigations, and we examined correlations and levels of agreement between the methods. Our results demonstrate that assessing rectal compliance with HRAM is technically possible; however, a strong correlation with the rectal barostat was only observed at the maximum tolerable volume (Spearman's rho = 0.7, p = 0.02). We only found moderate correlations (Spearman's rho = 0.562, p = 0.019) for compliance according to the barostat methodology and for rectal sensibility testing (Spearman's rho = 0.57, p = 0.03 for maximum tolerable volume). Bland-Altman plots showed poor levels of agreement between the methods. We conclude that HRAM and the rectal barostat cannot be used interchangeably for compliance or sensitivity assessments. We suggest the development of a non-elastic balloon with a fixed size and shape to assess rectal sensory function and compliance in HRAM testing.

Place, publisher, year, edition, pages
MDPI, 2024
Keywords
High-resolution anorectal manometry, rectal barostat, rectal compliance, rectal sensory function
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-111953 (URN)10.3390/diagnostics14040351 (DOI)001172324800001 ()38396390 (PubMedID)
Funder
Region Örebro County, OLL-929762; OLL-935240; OLL-978046
Note

This research was funded by the Research Committee Region Örebro County, grant numbers OLL-929762, OLL-935240 and OLL-978046, and the Research Fund of the Swedish Gastroenterological Society SLS-974222.

Available from: 2024-02-26 Created: 2024-02-26 Last updated: 2024-03-15Bibliographically approved
Mathisen, C.-W. B., Nyström, N., Bazov, I., Andersen, S., Olbjørn, C., Perminow, G., . . . Halfvarson, J. (2023). A novel diagnostic serum protein signature for paediatric Inflammatory Bowel Disease: A discovery and validation study in two independent inception cohorts. Paper presented at 8th Congress of ECCO Copenhagen, Denmark, March 1-4, 2023. Journal of Crohn's & Colitis, 17(Suppl. 1), I71-I73, Article ID DOP11.
Open this publication in new window or tab >>A novel diagnostic serum protein signature for paediatric Inflammatory Bowel Disease: A discovery and validation study in two independent inception cohorts
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2023 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no Suppl. 1, p. I71-I73, article id DOP11Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2023
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-107213 (URN)000960367600052 ()
Conference
8th Congress of ECCO Copenhagen, Denmark, March 1-4, 2023
Available from: 2023-07-31 Created: 2023-07-31 Last updated: 2023-07-31Bibliographically approved
Bazov, I., Kruse, R., Bergemalm, D., Eriksson, C., Hedin, C. R., Carlson, M., . . . Halfvarson, J. (2023). A novel serum protein signature as biomarker for Inflammatory Bowel Disease: A diagnostic performance and prediction modelling study using data from two independent inception cohorts. Paper presented at 18th Congress of ECCO Copenhagen, Denmark, March 1-4, 2023. Journal of Crohn's & Colitis, 17(Suppl. 1), I314-I315, Article ID P154.
Open this publication in new window or tab >>A novel serum protein signature as biomarker for Inflammatory Bowel Disease: A diagnostic performance and prediction modelling study using data from two independent inception cohorts
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2023 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no Suppl. 1, p. I314-I315, article id P154Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2023
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-107219 (URN)000960367600284 ()
Conference
18th Congress of ECCO Copenhagen, Denmark, March 1-4, 2023
Available from: 2023-07-31 Created: 2023-07-31 Last updated: 2024-01-02Bibliographically approved
Kalla, R., Adams, A. T., Nowak, J. K., Bergemalm, D., Vatn, S., Ventham, N. T., . . . Satsangi, J. (2023). Analysis of systemic epigenetic alterations in inflammatory bowel disease: defining geographical, genetic, and immune-inflammatory influences on the circulating methylome. Journal of Crohn's & Colitis, 17(2), 170-184
Open this publication in new window or tab >>Analysis of systemic epigenetic alterations in inflammatory bowel disease: defining geographical, genetic, and immune-inflammatory influences on the circulating methylome
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2023 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no 2, p. 170-184Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Epigenetic alterations may provide valuable insights into gene-environment interactions play in the pathogenesis of Inflammatory Bowel Disease (IBD).

METHODS: Genome-wide methylation was measured from peripheral blood using the Illumina 450k platform in a case-control study in an inception cohort (295 controls, 154 CD, 161 UC, 28 IBD-U) with covariates of age, sex, and cell counts, deconvoluted by the Houseman method. Genotyping was performed using Illumina HumanOmniExpressExome-8 BeadChips and gene expression using Ion AmpliSeq Human Gene Expression Core Panel. Treatment escalation was characterised by the need for biological agents or surgery after initial disease remission.

RESULTS: A total of 137 differentially methylated positions (DMP) were identified in IBD, including VMP1/MIR21 (p=9.11×10 -15) and RPS6KA2 (6.43×10 -13); with consistency seen across Scandinavia and UK. Dysregulated loci demonstrate strong genetic influence, notably VMP1 (p=1.53×10 -15). Age acceleration is seen in IBD (coefficient 0.94, p<2.2x10 -16). Several immuno-active genes demonstrated highly significant correlations between methylation and gene expression in IBD, in particular OSM: IBD r -0.32, p 3.64×10 -7 vs. non-IBD r -0.14, p=0.77). Multi-omic integration of methylome, genome and transcriptome also implicate specific pathways that associate with immune activation, response and regulation at disease inception. At follow up, a signature of 3 DMPs (TAP1, TESPA1, RPTOR) associated with treatment escalation to biological agents or surgery (hazard ratio of 5.19 (CI:2.14-12.56, logrank p=9.70×10 -4).

CONCLUSION: These data demonstrate consistent epigenetic alterations at diagnosis in European patients with IBD, providing insights into the pathogenetic importance and translational potential of epigenetic mapping in complex disease.

Place, publisher, year, edition, pages
Oxford University Press, 2023
Keywords
DNA methylation, epigenetic clock, gene expression, genetics, inflammatory bowel diseases (IBD), mendelian randomisation, methylation quantitative trait loci, prognosis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-100872 (URN)10.1093/ecco-jcc/jjac127 (DOI)000893054800001 ()36029471 (PubMedID)2-s2.0-85150666844 (Scopus ID)
Funder
European Commission, 2858546Wellcome trust, WT097943MA
Available from: 2022-08-29 Created: 2022-08-29 Last updated: 2023-05-11Bibliographically approved
Schreiber, S. W., Danese, S., Dignass, A., Domènech, E., Fantini, M., Ferrante, M., . . . Peyrin-Biroulet, L. (2023). Assessing comprehensive remission for Ulcerative Colitis in clinical practice: International consensus recommendations. Paper presented at 18th Congress of ECCO Copenhagen, Denmark, March 1-4, 2023. Journal of Crohn's & Colitis, 17(Suppl. 1), I311-I312, Article ID P151.
Open this publication in new window or tab >>Assessing comprehensive remission for Ulcerative Colitis in clinical practice: International consensus recommendations
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2023 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no Suppl. 1, p. I311-I312, article id P151Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2023
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-107318 (URN)10.1093/ecco-jcc/jjac190.0281 (DOI)000960367600281 ()
Conference
18th Congress of ECCO Copenhagen, Denmark, March 1-4, 2023
Available from: 2023-08-02 Created: 2023-08-02 Last updated: 2023-08-02Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-0122-7234

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