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Publications (10 of 32) Show all publications
Blöndal, V., Sundbom, F., Zhou, X., Movérare, R., Borres, M. P., Högman, M., . . . Janson, C. (2023). Allergic sensitisation and type-2 inflammation is associated with new-onset and persistent allergic disease. Clinical and Translational Allergy, 13(4), Article ID e12240.
Open this publication in new window or tab >>Allergic sensitisation and type-2 inflammation is associated with new-onset and persistent allergic disease
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2023 (English)In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 13, no 4, article id e12240Article in journal (Refereed) Published
Abstract [en]

Background: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease.

Methods: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FENO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN).

Results: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10 years, and FENO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively).

Conclusion: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2023
Keywords
asthma, ENT, epidemiology
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-501302 (URN)10.1002/clt2.12240 (DOI)000963976600001 ()37186426 (PubMedID)
Funder
Swedish Heart Lung FoundationVinnovaAgnes and Mac Rudberg FoundationVårdal FoundationSwedish Heart Lung Foundation
Available from: 2023-05-09 Created: 2023-05-09 Last updated: 2023-06-19Bibliographically approved
Färdig, M., Lie, A., Borres, M. P., Ekenkrantz, T., Granum, B., Haugen, G., . . . Nordlund, B. (2023). Eosinophil-derived neurotoxin levels in early childhood and association with preschool asthma - A prospective observational study. Clinical and Experimental Allergy, 53(11), 1198-1211
Open this publication in new window or tab >>Eosinophil-derived neurotoxin levels in early childhood and association with preschool asthma - A prospective observational study
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2023 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 53, no 11, p. 1198-1211Article in journal (Refereed) Published
Abstract [en]

Introduction: Eosinophil-derived neurotoxin (EDN) is related to childhood asthma, while normal values are lacking. We aimed to document serum EDN levels at 1 and 3 years in general and in non-atopic children, and explore if EDN levels differed by sex or were associated with preschool asthma at 3 years.

Methods: From the PreventADALL birth cohort, we included 1233 children with EDN analysed using ImmunoCAP at 1 and/or 3 years. Non-atopic children had no history of wheeze, asthma, allergic sensitization or atopic dermatitis. Preschool asthma was defined as having ≥3 episodes of bronchial obstruction between 2 and 3 years, plus doctor diagnosed asthma and/or asthma medication use by 3 years. The upper limit of normal (ULN) of EDN was defined as the 95th percentile. With Youden Index we calculated EDN cut-off levels for risk of preschool asthma.

Results: The overall median (ULN) EDN levels were 27.4 (121) μg/L at 1 year (n = 787), and 20.1 (87.8) μg/L at 3 years (n = 857). Non-atopic children had EDN levels of 24.0 (107) μg/L at 1 year (n = 147), and 17.3 (84.6) μg/L at 3 years (n = 173). EDN levels were higher in boys compared to girls; 32.0 (133) versus 24.5 (97.0) μg/L at 1 year, and 20.9 (96.3) versus 19.0 (72.4) μg/L at 3 years. Preschool asthma was observed in 109/892 (12.2%) children. Higher EDN levels at 1 (>26.7 μg/L) and 3 (≥20.5 μg/L) years were associated with preschool asthma; adjusted OR (95% CI) 2.20 (1.09, 4.41) and 4.68 (2.29, 9.55), respectively.

Conclusion and Clinical Relevance: We report EDN values in early childhood, demonstrating higher levels at 1 compared to 3 years and in boys compared to girls at both ages. Higher EDN levels at both ages were associated with preschool asthma. However, EDN cut-off levels for preschool asthma were overall lower than the ULN of non-atopic children, limiting translation into clinical practice.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
PreventADALL, asthma, child, eosinophil-derived neurotoxin, sex, type 2 inflammation, wheeze
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-520094 (URN)10.1111/cea.14409 (DOI)001080301600001 ()37795650 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2024-01-11 Created: 2024-01-11 Last updated: 2024-02-08Bibliographically approved
Thorpe, M., Movérare, R., Fischer, C., Lidholm, J., Rudengren, M. & Borres, M. P. (2023). History and Utility of Specific IgE Cutoff Levels: What is the Relevance for Allergy Diagnosis?. Journal of Allergy and Clinical Immunology: In Practice, 11(10), 3021-3029
Open this publication in new window or tab >>History and Utility of Specific IgE Cutoff Levels: What is the Relevance for Allergy Diagnosis?
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2023 (English)In: Journal of Allergy and Clinical Immunology: In Practice, ISSN 2213-2198, E-ISSN 2213-2201, Vol. 11, no 10, p. 3021-3029Article in journal (Refereed) Published
Abstract [en]

Allergy is defined clinically, by symptoms on allergen exposure. A patient is considered sensitized when allergen-specific IgE (sIgE) antibody can be detected in serum or plasma or a skin test result is positive, even if no clinical reaction has been experienced. Sensitization should be regarded as a requisite and risk factor for allergy but is not synonymous with an allergy diagnosis. To provide a correct allergy diagnosis, test results regarding allergen-sIgE must always be considered in view of the patient's case history and clinical observations. Correct assessment of a patient's sensitization to specific allergens relies on the use of accurate and quantitative methods for detection of sIgE antibodies. The evolution of sIgE immunoassays toward higher analytical performance and the use of different cutoff levels in the interpretation of test results sometimes cause confusion. Earlier versions of sIgE assays offered a limit of quantitation of 0.35 kilounits of sIgE per liter (kUA/L), which also became an established cutoff level for a positive test result in the clinical use of the assays. Current sIgE assays are capable of reliably measuring sIgE levels as low as 0.1 kUA/L and can thereby demonstrate sensitization in cases in which previous assays could not. When the outcome of sIgE test results is evaluated, it is critically important to distinguish between the analytical data as such and their clinical interpretation. Even though sIgE may be present in the absence of symptoms of allergy, available information suggests that sIgE concentrations between 0.1 kUA/L and 0.35 kUA/L may be clinically relevant in some individuals, not least among children, although this should be further evaluated for various allergies. Moreover, it is becoming widely adopted that nondichotomous interpretation of sIgE levels may offer a diagnostic benefit compared with using a predefined cutoff level.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Allergy, Specific IgE, Sensitization, Cutoff, Decision point
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-518465 (URN)10.1016/j.jaip.2023.05.022 (DOI)001088445200001 ()37245730 (PubMedID)
Available from: 2023-12-20 Created: 2023-12-20 Last updated: 2023-12-20Bibliographically approved
Movérare, R., Persson, E., Malinovschi, A. & Janson, C. (2023). Reference values of serum total IgE in Uppsala: comparison over four decades. Upsala Journal of Medical Sciences, 128, Article ID e9892.
Open this publication in new window or tab >>Reference values of serum total IgE in Uppsala: comparison over four decades
2023 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 128, article id e9892Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Total immunoglobulin E (IgE) analysis is a common tool in allergy diagnosis. Suggested reference values for IgE are divergent and sometimes based on outdated assay methods. We aimed to validate the published reference values (geometric mean [GM]: 13.2 kU/L, upper limit of normal [ULN], 114 kU/L) shown in an Uppsala cohort from 1974 using Phadebas IgE PRIST, and the suggested clinical threshold of 100 kU/L (Zetterström and Johansson 1981).

METHODS: Immunoglobulin E was measured in two Uppsala cohorts from 1997 (Blood bank) and 2011 to 2013 (the European community respiratory health survey part III [ECRHS III]) using ImmunoCAP™ Total IgE. For the reference value calculations, exclusion criteria were atopy (both cohorts), doctor's diagnosis of asthma and self-reported allergy (hay fever, rhinitis, rash) (only ECRHS III). Upper limit of normal was defined as mean + 2 standard deviations (SD) calculated using log-transformed values and back-transformation of the ULN prior to presentation. Common imputation methods for results below the assay range were evaluated.

RESULTS: The average GM was 14.2 kU/L (Blood bank, n = 63; imputation method range: 16.9-17.4 kU/L; ECRHS III, n = 113: 10.7-11.6 kU/L) and the overall mean ULN was 118 kU/L (Blood bank: 113-130 kU/L; ECRHS III: 104-128 kU/L). The clinical sensitivity and specificity of the 100 kU/L IgE threshold were 37.8 and 94.3% for atopy, 34.9 and 89.5% for doctor's diagnosis of asthma, and 24.5 and 97.3% for any self-reported allergy (ECRHS III).

CONCLUSION: The calculated ULN values were similar between the cohorts. We conclude that the total IgE reference values shown for Uppsala subjects from 1974 are still valid and suitable also for the ImmunoCAP Total IgE assay. The 100 kU/L threshold for total IgE had a low sensitivity but high specificity for atopy, asthma, and allergy.

Place, publisher, year, edition, pages
Upsala Medical Society, 2023
Keywords
Allergy, asthma, atopy, reference value, total IgE, upper limit of normal
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-520087 (URN)10.48101/ujms.v128.9892 (DOI)38084204 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Asthma and Allergy AssociationThe Swedish Heart and Lung AssociationBror Hjerpstedts stiftelse
Available from: 2024-01-11 Created: 2024-01-11 Last updated: 2024-03-14Bibliographically approved
Rydell, N., Ekoff, H., Hellström, P. M. & Movérare, R. (2022). Measurement of Serum IgG Anti-Integrin alpha v beta 6 Autoantibodies Is a Promising Tool in the Diagnosis of Ulcerative Colitis. Journal of Clinical Medicine, 11(7), Article ID 1881.
Open this publication in new window or tab >>Measurement of Serum IgG Anti-Integrin alpha v beta 6 Autoantibodies Is a Promising Tool in the Diagnosis of Ulcerative Colitis
2022 (English)In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 11, no 7, article id 1881Article in journal (Refereed) Published
Abstract [en]

IgG anti-integrin alpha v beta 6 autoantibodies (IgG anti-alpha v beta 6) have been described as highly sensitive and specific markers of ulcerative colitis (UC) in the sera of Japanese inflammatory bowel disease (IBD) patients. We aimed to evaluate the diagnostic performance of IgG anti-alpha v beta 6 as a biomarker in Swedish patients with IBD or irritable bowel syndrome (IBS). The study included adult UC (n = 59), Crohn's disease (CD, n = 38), and IBS patients (n = 100). Partial Mayo score and Harvey-Bradshaw index were used to assess disease severity for UC and CD, respectively. Serum levels of IgG anti-alpha v beta 6, reported as absorbance units (AU), were measured using an in-house ELISA where the 95th percentile of 76 healthy controls defined positivity. Faecal calprotectin (fCP) was measured using a commercial assay. The majority of the IBD patients were on medical treatment, and many were in remission (UC: 40.7%; CD: 47.4%). Seventy-one percent of the UC patients, 74.2% of CD patients, and 23.1% of the IBS patients had fCP test results >50 mg/kg. The UC group had significantly higher IgG anti-alpha v beta 6 levels (median: 1.76 AU) than the CD and IBS groups (0.34 and 0.31 AU, both p < 0.0001). The diagnostic sensitivity of IgG anti-alpha v beta 6 in UC was 76.3%, and the specificities were 79.0% (vs. CD) and 96.0% (vs. IBS). The IgG anti-alpha v beta 6 levels related to disease severity of the UC patients (p < 0.01-0.05). Our study shows that IgG anti-alpha v beta 6 is associated with UC in Swedish IBD patients and that the levels of the autoantibodies reflect disease severity. IgG anti-alpha v beta 6 could be an attractive complement to fCP in the diagnostic work up of IBD patients.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
autoantibody, diagnosis, inflammatory bowel disease, integrin alpha v beta 6, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-473188 (URN)10.3390/jcm11071881 (DOI)000780579300001 ()35407486 (PubMedID)
Available from: 2022-04-27 Created: 2022-04-27 Last updated: 2022-04-27Bibliographically approved
Rydell, N., Nagao, M., Movérare, R., Ekoff, H., Sjölander, A., Borres, M. P. & Fujisawa, T. (2022). Serum Eosinophilic Cationic Protein Is a Reliable Biomarker for Childhood Asthma. International Archives of Allergy and Immunology, 183(7), 744-752
Open this publication in new window or tab >>Serum Eosinophilic Cationic Protein Is a Reliable Biomarker for Childhood Asthma
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2022 (English)In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 183, no 7, p. 744-752Article in journal (Refereed) Published
Abstract [en]

Background: Eosinophilic cationic protein (ECP) is associated with airway inflammation and asthma. However, the clinical value of measuring ECP in childhood asthma is not fully known. We aimed to study the diagnostic performance of serum ECP and other common asthma biomarkers, individually and in combinations. Methods: In a cross-sectional study, 5-16-year-old children with current asthma (CA) (n = 37), transient asthma (TA) (n = 43), (previous history of wheezing/asthma), and healthy children (HC) (n = 86) were investigated for ECP, blood eosinophil count (B-Eos), fractional exhaled nitric oxide (FeNO), and lung function, i.e., spirometry (forced expiratory volume during the first second [FEV1]/forced vital capacity [FVC] ratio). Results: Both ECP and B-Eos were higher in CA compared to TA (p < 0.01) and HC (p < 0.0001). ECP and B-Eos were also higher in TA compared to HC (p < 0.05 and p < 0.001, respectively). FeNO was higher in CA (p < 0.0001) and TA (p < 0.01) compared to HC but similar between the asthma groups. The FEV1/FVC ratio was lower in CA compared to TA and HC (both p < 0.01) but similar between TA and HC. The best diagnostic performance regarding CA was found for ECP and B-Eos with receiver operating characteristics area under curve (AUC) of 0.801 and 0.810, respectively. The optimal cutoff for ECP (29 mu g/L) yielded a sensitivity and specificity of 70.3% and 81.4%. The corresponding AUCs for FeNO and FEV1/FVC were 0.732 and 0.670, respectively. ECP and B-Eos showed the highest AUCs (0.669 and 0.673) for differentiation between CA and TA. Combining ECP with FeNO and FEV1/FVC increased the odds ratio (OR) for having CA from OR 3.97-10.3 for the single biomarkers to OR 20.2 (95% confidence interval: 5.76-68.6). Conclusion: Our results show that serum ECP is a reliable biomarker in the diagnosis of childhood asthma, with additional value in combination with FeNO and FEV1/FVC, and that ECP can be an alternative to B-Eos.

Place, publisher, year, edition, pages
S. Karger, 2022
Keywords
Serum eosinophilic cationic protein, Blood eosinophil count, Exhaled nitric oxide, Lung function, Childhood asthma
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-484107 (URN)10.1159/000521890 (DOI)000759802500001 ()35144256 (PubMedID)
Available from: 2022-09-23 Created: 2022-09-23 Last updated: 2022-09-23Bibliographically approved
Waern, I., Molin, M., Movérare, R., Lidholm, J., Malinovschi, A., Borres, M. P. & Janson, C. (2022). Shrimp- and mite sensitization in a Swedish study: Influence on allergic disorders and lung function [Letter to the editor]. Clinical and Translational Allergy, 12(10), Article ID e12198.
Open this publication in new window or tab >>Shrimp- and mite sensitization in a Swedish study: Influence on allergic disorders and lung function
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2022 (English)In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 12, no 10, article id e12198Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2022
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-486988 (URN)10.1002/clt2.12198 (DOI)000865387400001 ()36246731 (PubMedID)
Funder
Swedish Research Council Formas, 2017-00818Swedish Heart Lung Foundation
Available from: 2022-10-24 Created: 2022-10-24 Last updated: 2022-10-24Bibliographically approved
Vitte, J., Sjölander, A., Rydell, N., Molin, M., Pejler, G., Hallgren, J., . . . Malinovschi, A. (2022). Tryptase reference values in a Swedish middle-aged general population and association with diabetes mellitus [Letter to the editor]. Clinical and Experimental Allergy, 1-4
Open this publication in new window or tab >>Tryptase reference values in a Swedish middle-aged general population and association with diabetes mellitus
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2022 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, p. 1-4Article in journal, Letter (Refereed) Epub ahead of print
Place, publisher, year, edition, pages
Wiley, 2022
National Category
Medical and Health Sciences
Research subject
Internal Medicine; Physiology
Identifiers
urn:nbn:se:uu:diva-482631 (URN)10.1111/cea.14195 (DOI)000823445100001 ()35771193 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council FormasSwedish Heart Lung FoundationVinnova
Available from: 2022-08-24 Created: 2022-08-24 Last updated: 2022-10-18Bibliographically approved
Zaigham, S., Zhou, X., Molin, M., Sjölander, A., Movérare, R., Janson, C. & Malinovschi, A. (2021). Importance of type and degree of IgE sensitisation for defining fractional exhaled nitric oxide reference values. Respiratory Medicine, 188, Article ID 106621.
Open this publication in new window or tab >>Importance of type and degree of IgE sensitisation for defining fractional exhaled nitric oxide reference values
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2021 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 188, article id 106621Article in journal (Refereed) Published
Abstract [en]

Background

Fractional exhaled nitric oxide (FENO) is a marker of type 2 airway inflammation used in clinical practice in asthma. However, reference values are needed to broaden the clinical use of FENO and this is within the scope of a newly started Global Lung Function Initiative task force. We aim to study FENO levels with special emphasis on the upper limit of normal (ULN) in relation to the type and degree of IgE sensitisation.

Methods

FENO was measured in 1855 non-smoking, respiratory healthy subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Atopic subjects (n = 424), defined as being IgE-sensitised to aeroallergens (ImmunoCAP Phadiatop™, ≥0.35 PAU/l) were compared to non-atopic subjects (<0.35 PAU/l, n = 1431). Atopic subjects were further characterised according to their grade of IgE sensitisation (IgE antibody tertiles: (T1<1.16, T2 1.16–3.72 and T3 >3.72 PAU/l) and sensitisation to perennial (cat or mite) or seasonal (birch) allergens.

Results

Subjects IgE-sensitised to cat or mite had higher FENO compared to non-atopic subjects (FENO (ppb): median 20.0 vs. 15.0, and ULN 50.4 vs. 33.0, p < 0.001). This was seen to a lesser extent for subjects IgE-sensitised to birch only (median 18.0 vs. 15.0, and ULN 38.0 vs. 33.0, p = 0.048). Atopic subjects with a high degree of IgE sensitisation (Phadiatop: >3.72 PAU/l) had the highest FENO compared to non-atopic subjects (median 20.0 vs. 15.0, and ULN 56.0 vs. 33.0, p < 0.001).

Conclusions

The type and degree of IgE sensitisation should be considered in generating FENO reference values.

Place, publisher, year, edition, pages
ElsevierElsevier BV, 2021
Keywords
IgE sensitisation, Atopy, Fractional exhaled nitric oxide, Allergy
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-458691 (URN)10.1016/j.rmed.2021.106621 (DOI)000711032600017 ()34564049 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20170673Knut and Alice Wallenberg FoundationSwedish Research CouncilVinnovaRegion Stockholm
Available from: 2021-12-01 Created: 2021-12-01 Last updated: 2024-01-15Bibliographically approved
Sato, S., Movérare, R., Ohya, Y., Ito, K., Nagao, M., Borres, M. P. & Ebisawa, M. (2019). Ana o 3-specific IgE is a predictive marker for cashew oral food challenge failure [Letter to the editor]. Journal of Allergy and Clinical Immunology: In Practice, 7(8), 2909-2911.e4
Open this publication in new window or tab >>Ana o 3-specific IgE is a predictive marker for cashew oral food challenge failure
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2019 (English)In: Journal of Allergy and Clinical Immunology: In Practice, ISSN 2213-2198, E-ISSN 2213-2201, Vol. 7, no 8, p. 2909-2911.e4Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
ELSEVIER, 2019
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-398133 (URN)10.1016/j.jaip.2019.04.049 (DOI)000495746100068 ()31108216 (PubMedID)
Available from: 2019-12-04 Created: 2019-12-04 Last updated: 2019-12-04Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-6611-5036

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