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Späth, F., Wennberg, P., Johansson, R., Weinehall, L., Norberg, M., Rosén, A., . . . van Guelpen, B. (2025). Cohort profile: the Northern Sweden health and disease study (NSHDS). International Journal of Epidemiology, 54(1), Article ID dyaf004.
Open this publication in new window or tab >>Cohort profile: the Northern Sweden health and disease study (NSHDS)
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2025 (English)In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 54, no 1, article id dyaf004Article in journal (Refereed) Published
Abstract [en]

Key features: 

  • The Northern Sweden Health and Disease Study (NSHDS) was initiated in the mid-1980s. The NSHDS is a population-based prospective longitudinal cohort comprising >140 000 participants in the two northernmost regions in Sweden, Norrbotten and Västerbotten, with >240 000 blood samples and 1.5 million person-years of follow-up.
  • The NSHDS includes three sub-cohorts: the Västerbotten Intervention Programme (VIP), the expanded Northern Sweden Monitoring of Trends and Determinants of Cardiovascular Disease (MONICA) Study, and the Mammography Screening Project (MSP). The VIP is both a community-based cardiometabolic intervention programme encouraging healthy lifestyle (targeting individuals 40, 50, and 60 years of age), and a corresponding research cohort. The MONICA is an observational study focusing on cardiovascular disease and its associated risk factors, recruiting individuals aged 25–74 years. The MSP recruited women attending mammography during 1995–2006. The NSHDS median participation age is 50 years (53% women).
  • Most participants contribute data on health, lifestyle, anthropometric measures, blood pressure, blood lipids, and glucose tolerance, along with research blood samples that are fractionated, frozen within an hour of collection, and stored at –80°C. Linkage to registries, clinical cohorts, and biological tissue archives facilitates studies of well-characterized participants (often combined with intervention studies).
  • Collaborations are encouraged. Additional information can be found at: info.brs@umu.se; https://www.umu.se/en/biobank
Place, publisher, year, edition, pages
Oxford University Press, 2025
Keywords
biobank, biomarkers, disease risk, lifestyle intervention, longitudinal cohort, NSHDS, population-based study, prospective blood samples, prospective cohort, risk factor
National Category
Epidemiology Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:umu:diva-235871 (URN)10.1093/ije/dyaf004 (DOI)001413338400001 ()39899988 (PubMedID)2-s2.0-85217499001 (Scopus ID)
Funder
Region VästerbottenNorrbotten County CouncilSwedish Research Council, 2017-00650Cancerforskningsfonden i Norrland, AMP 24-1152 FSSwedish Society of MedicineBlodcancerförbundetThe Kempe FoundationsSwedish Cancer Society, 22 2206 FKSwedish Society for Medical Research (SSMF), SG-23-0168-B
Available from: 2025-02-24 Created: 2025-02-24 Last updated: 2025-02-24Bibliographically approved
Srinivasan, S., Kryza, T., Bock, N., Tse, B. W. C., Sokolowski, K. A., Janaththani, P., . . . Batra, J. (2024). A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer. Nature Communications, 15(1), Article ID 9587.
Open this publication in new window or tab >>A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer
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2024 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 9587Article in journal (Refereed) Published
Abstract [en]

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T > C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity mediates prostate cancer pathogenesis. The ‘Thr’ PSA variant leads to small subcutaneous tumours, supporting reduced prostate cancer risk. However, ‘Thr’ PSA also displays higher metastatic potential with pronounced osteolytic activity in an experimental metastasis in-vivo model. Biochemical characterisation of this PSA variant demonstrates markedly reduced proteolytic activity that correlates with differences in in-vivo tumour burden. The SNP is associated with increased risk for aggressive disease and prostate cancer-specific mortality in three independent cohorts, highlighting its critical function in mediating metastasis. Carriers of this SNP allele have reduced serum total PSA and a higher free/total PSA ratio that could contribute to late biopsy decisions and delay in diagnosis. Our results provide a molecular explanation for the prominent 19q13.3 KLK locus, rs17632542 SNP, association with a spectrum of prostate cancer clinical outcomes.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Medical Genetics and Genomics
Identifiers
urn:nbn:se:umu:diva-232280 (URN)10.1038/s41467-024-52472-6 (DOI)39505858 (PubMedID)2-s2.0-85208688536 (Scopus ID)
Available from: 2024-11-28 Created: 2024-11-28 Last updated: 2025-02-10Bibliographically approved
Thomsen, H., Chattopadhyay, S., Weinhold, N., Vodicka, P., Vodickova, L., Hoffmann, P., . . . Försti, A. (2024). Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance. Blood Cancer Journal, 14(1), Article ID 140.
Open this publication in new window or tab >>Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance
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2024 (English)In: Blood Cancer Journal, E-ISSN 2044-5385, Vol. 14, no 1, article id 140Article in journal (Refereed) Published
Abstract [en]

Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations. We identified 23 haplotypes that were associated with the risk of MGUS at the genome-wide significance level (p < 5 × 10−8) and showed consistent results among all three populations. In 10 genomic regions, strong promoter, enhancer and regulatory element-related histone marks and their connections to target genes as well as genome segmentation data supported the importance of these regions in MGUS susceptibility. Several associated haplotypes affected pathways important for MM cell survival such as ubiquitin-proteasome system (RNF186, OTUD3), PI3K/AKT/mTOR (HINT3), innate immunity (SEC14L1, ZBP1), cell death regulation (BID) and NOTCH signaling (RBPJ). These pathways are important current therapeutic targets for MM, which may highlight the advantage of the haplotype approach homing to functional units.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Hematology Medical Genetics and Genomics
Identifiers
urn:nbn:se:umu:diva-228905 (URN)10.1038/s41408-024-01121-8 (DOI)001295007500002 ()39164264 (PubMedID)2-s2.0-85201603885 (Scopus ID)
Available from: 2024-09-02 Created: 2024-09-02 Last updated: 2025-02-10Bibliographically approved
Stefansson, H., Walters, G. B., Sveinbjornsson, G., Tragante, V., Einarsson, G., Helgason, H., . . . Stefansson, K. (2024). Homozygosity for R47H in TREM2 and the Risk of Alzheimer's Disease [Letter to the editor]. New England Journal of Medicine, 390(23), 2217-2219
Open this publication in new window or tab >>Homozygosity for R47H in TREM2 and the Risk of Alzheimer's Disease
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2024 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 390, no 23, p. 2217-2219Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Massachusetts Medical Society, 2024
National Category
Medical Genetics and Genomics
Identifiers
urn:nbn:se:umu:diva-227576 (URN)10.1056/NEJMc2314334 (DOI)001331233700015 ()38899702 (PubMedID)2-s2.0-85196684137 (Scopus ID)
Available from: 2024-07-01 Created: 2024-07-01 Last updated: 2025-04-24Bibliographically approved
Li, W., Tang, H., Xue, K., Ying, T., Wu, M., Qu, Z., . . . He, G. (2024). Personalized microbial fingerprint associated with differential glycemic effects of a whole grain rye intervention on Chinese adults. Molecular Nutrition & Food Research, 68(17), Article ID 2400274.
Open this publication in new window or tab >>Personalized microbial fingerprint associated with differential glycemic effects of a whole grain rye intervention on Chinese adults
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2024 (English)In: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 68, no 17, article id 2400274Article in journal (Refereed) Published
Abstract [en]

Scope: This study aims to identify the gut enterotypes that explain differential responses to intervention with whole grain rye by proposing an “enterotype - metabolic” model.

Methods and results: A 12-week randomized controlled trial is conducted in Chinese adults, with 79 subjects consuming whole grain products with fermented rye bran (FRB) and 77 consuming refined wheat products in this exploratory post-hoc analysis. Responders or non-responders are identified according to whether blood glucose decreased by more than 10% after rye intervention. Compared to non-responders, responders in FRB have higher baseline Bacteroides (p < 0.001), associated with reduced blood glucose (p < 0.001), increased Faecalibacterium (p = 0.020) and Erysipelotrichaceae_UCG.003 (p = 0.022), as well as deceased 7β-hydroxysteroid dehydrogenase (p = 0.033) after intervention. The differentiated gut microbiota and metabolites between responders and non-responders after intervention are enriched in aminoacyl-tRNA biosynthesis.

Conclusion: The work confirms the previously suggested importance of microbial enterotypes in differential responses to whole grain interventions and supports taking enterotypes into consideration for improved efficacy of whole grain intervention for preventing type 2 diabetes. Altered short-chain fatty acids and bile acid metabolism might be a potential mediator for the beneficial effects of whole grain rye on glucose metabolism.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
Whole grain rye, gut microbiota, bile acid, glycemic effect
National Category
Infectious Medicine Nutrition and Dietetics
Research subject
Microbiology; Nutrition
Identifiers
urn:nbn:se:umu:diva-228148 (URN)10.1002/mnfr.202400274 (DOI)001282818000001 ()39091068 (PubMedID)2-s2.0-85200138038 (Scopus ID)
Funder
Swedish Research Council, 2017‐05840Vinnova
Available from: 2024-08-03 Created: 2024-08-03 Last updated: 2025-02-11Bibliographically approved
Olsson, J., Nourmohammadi, S., Honkala, E., Johansson, A., Hallmans, G., Weidung, B., . . . Elgh, F. (2024). Time trends in herpesvirus seroepidemiology among Swedish adults. BMC Infectious Diseases, 24(1), Article ID 273.
Open this publication in new window or tab >>Time trends in herpesvirus seroepidemiology among Swedish adults
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2024 (English)In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 24, no 1, article id 273Article in journal (Refereed) Published
Abstract [en]

Background: Human herpesviruses are widespread among the human population. The infections often occurunnoticed, but severe disease as well as long-term sequelae are part of the symptom spectrum. The prevalence variesamong subpopulations and with time. The aim of this study was to describe the seroprevalence of ImmunoglobulinG against Herpes simplex 1, Herpes simplex 2, Epstein-Barr virus and Cytomegalovirus in the adult Swedish populationover a time period of several decades.

Methods: Serum samples (n = 892) from biobanks, originating from 30-year-old women, 50-year-old menand 50-year-old women sampled between 1975 and 2018, were analyzed for presence of anti-herpesvirus antibod-ies. Linear regression analysis was used to test for a correlation between birth year and seroprevalence. Multiple linearregression analysis was used to differentiate between other factors such as age and gender.

Results: Birth year correlated negatively with the prevalence of immunoglobulin G against Herpes simplex 1and Epstein-Barr virus (p = 0.004 and 0.033), and positively with Immunoglobulin G against Cytomegalovirus(p = 0.039). When participant categories were analyzed separately, birth year correlated negatively with the preva-lence of Immunoglobulin G against Herpes simplex 1 and Herpes simplex 2 (p = 0.032 and 0.028) in 30-year-old women,and with the prevalence of Immunoglobulin G against Cytomegalovirus in 50-year-old men (p = 0.011).

Conclusions: The prevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2 and Epstein-Barr virusdecreases in later birth cohorts. This indicates a trend of declining risk of getting infected with these viruses as a childand adolescen (9) (PDF) Time trends in herpesvirus seroepidemiology among Swedish adults. 

Place, publisher, year, edition, pages
Springer Nature, 2024
Keywords
Herpes, Herpes simplex, Epstein-Barr virus, Cytomegalovirus, Seroprevalence, Epidemiology, Time trends, Immunoglobulin G
National Category
Public Health, Global Health and Social Medicine Geriatrics Infectious Medicine
Research subject
Infectious Diseases; Geriatrics
Identifiers
urn:nbn:se:umu:diva-221713 (URN)10.1186/s12879-024-09155-w (DOI)001178763600001 ()38431567 (PubMedID)2-s2.0-85186556771 (Scopus ID)
Funder
Region VästerbottenUmeå UniversityThe Dementia Association - The National Association for the Rights of the DementedAlzheimerfonden
Available from: 2024-03-03 Created: 2024-03-03 Last updated: 2025-04-24Bibliographically approved
Visvanathan, K., Mondul, A. M., Zeleniuch-Jacquotte, A., Wang, M., Gail, M. H., Yaun, S.-S., . . . Ziegler, R. G. (2023). Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts. European Journal of Epidemiology, 38, 11-29
Open this publication in new window or tab >>Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts
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2023 (English)In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 38, p. 11-29Article in journal (Refereed) Published
Abstract [en]

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42–68) years at blood collection and 63 (49–75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50– < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100– < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95–1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.

Place, publisher, year, edition, pages
Springer Science+Business Media B.V., 2023
Keywords
25-Hydroxyvitamin D, Biomarker, Breast cancer, Calibration, Pooled analysis, Prospective cohort study, Vitamin D
National Category
Cancer and Oncology Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:umu:diva-202341 (URN)10.1007/s10654-022-00921-1 (DOI)000908100600003 ()2-s2.0-85145419390 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Research CouncilRegion Västerbotten
Available from: 2023-01-12 Created: 2023-01-12 Last updated: 2025-02-20Bibliographically approved
de las Fuentes, L., Schwander, K. L., Brown, M. R., Bentley, A. R., Winkler, T. W., Sung, Y. J., . . . Fornage, M. (2023). Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci. Frontiers in Genetics, 14, Article ID 1235337.
Open this publication in new window or tab >>Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci
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2023 (English)In: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 14, article id 1235337Article in journal (Refereed) Published
Abstract [en]

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes.

Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals).

Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.

Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
cholesterol, educational attainment, genome-wide association study, lipids, meta-analysis, triglycerides
National Category
Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:umu:diva-217379 (URN)10.3389/fgene.2023.1235337 (DOI)001106059400001 ()38028628 (PubMedID)2-s2.0-85177065494 (Scopus ID)
Available from: 2023-12-01 Created: 2023-12-01 Last updated: 2025-04-24Bibliographically approved
Willems, S. M., Ng, N. H. J., Fernandez, J., Fine, R. S., Wheeler, E., Wessel, J., . . . Barroso, I. (2023). Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization. Wellcome Open Research, 8, Article ID 483.
Open this publication in new window or tab >>Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization
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2023 (English)In: Wellcome Open Research, E-ISSN 2398-502X, Vol. 8, article id 483Article in journal (Refereed) Published
Abstract [en]

Background: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways.

Methods: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses.

Results: Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology.

Conclusions: Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries.

Place, publisher, year, edition, pages
F1000 Research Ltd, 2023
Keywords
effector genes, exome chip, genetic discovery, glycaemic traits, summary statistics resources
National Category
Medical Genetics and Genomics
Identifiers
urn:nbn:se:umu:diva-230493 (URN)10.12688/wellcomeopenres.18754.1 (DOI)39280063 (PubMedID)2-s2.0-85204904115 (Scopus ID)
Note

Version 1. Published: 20 Oct 2023, 8:483 https://doi.org/10.12688/wellcomeopenres.18754.1v

Available from: 2024-10-03 Created: 2024-10-03 Last updated: 2025-05-09Bibliographically approved
Nordin, E., Steffensen, S. K., Laursen, B. B., Andersson, S.-O., Johansson, J.-E., Åman, P., . . . Landberg, R. (2022). An inverse association between plasma benzoxazinoid metabolites and PSA after rye intake in men with prostate cancer revealed with a new method. Scientific Reports, 12(1), Article ID 5260.
Open this publication in new window or tab >>An inverse association between plasma benzoxazinoid metabolites and PSA after rye intake in men with prostate cancer revealed with a new method
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2022 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 5260Article in journal (Refereed) Published
Abstract [en]

Prostate cancer (PC) is a common cancer among men, and preventive strategies are warranted. Benzoxazinoids (BXs) in rye have shown potential against PC in vitro but human studies are lacking. The aim was to establish a quantitative method for analysis of BXs and investigate their plasma levels after a whole grain/bran rye vs refined wheat intervention, as well as exploring their association with PSA, in men with PC. A quantitative method for analysis of 22 BXs, including novel metabolites identified by mass spectrometry and NMR, was established, and applied to plasma samples from a randomized crossover study where patients with indolent PC (n = 17) consumed 485 g whole grain rye/rye bran or fiber supplemented refined wheat daily for 6 wk. Most BXs were significantly higher in plasma after rye (0.3–19.4 nmol/L in plasma) vs. refined wheat (0.05–2.9 nmol/L) intake. HBOA-glc, 2-HHPAA, HBOA-glcA, 2-HPAA-glcA were inversely correlated to PSA in plasma (p < 0.04). To conclude, BXs in plasma, including metabolites not previously analyzed, were quantified. BX metabolites were significantly higher after rye vs refined wheat consumption. Four BX-related metabolites were inversely associated with PSA, which merits further investigation.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022
National Category
Food Science Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-193683 (URN)10.1038/s41598-022-08856-z (DOI)000774204500041 ()35347164 (PubMedID)2-s2.0-85127262251 (Scopus ID)
Funder
Swedish Research Council, 2017-05840Academy of Finland, 321716EU, Horizon 2020
Available from: 2022-05-03 Created: 2022-05-03 Last updated: 2025-02-11Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9581-3845

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