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Article ; Online: Heterogeneity and tumor evolution reflected in liquid biopsy in metastatic breast cancer patients: a review.

Kavan, Stephanie / Kruse, Torben A / Vogsen, Marianne / Hildebrandt, Malene G / Thomassen, Mads

2022 Volume 41, Issue 2, Page(s) 433–446

Abstract: Breast cancer is a spatially and temporally dynamic disease in which differently evolving genetic clones are responsible for progression and clinical outcome. We review tumor heterogeneity and clonal evolution from studies comparing primary tumors and ... ...

Abstract	Breast cancer is a spatially and temporally dynamic disease in which differently evolving genetic clones are responsible for progression and clinical outcome. We review tumor heterogeneity and clonal evolution from studies comparing primary tumors and metastasis and discuss plasma circulating tumor DNA as a powerful real-time approach for monitoring the clonal landscape of breast cancer during treatment and recurrence. We found only a few early studies exploring clonal evolution and heterogeneity through analysis of multiregional tissue biopsies of different progression steps in comparison with circulating tumor DNA (ctDNA) from blood plasma. The model of linear progression seemed to be more often reported than the model of parallel progression. The results show complex routes to metastasis, however, and plasma most often reflected metastasis more than primary tumor. The described patterns of evolution and the polyclonal nature of breast cancer have clinical consequences and should be considered during patient diagnosis and treatment selection. Current studies focusing on the relevance of clonal evolution in the clinical setting illustrate the role of liquid biopsy as a noninvasive biomarker for monitoring clonal progression and response to treatment. In the clinical setting, circulating tumor DNA may be an ideal support for tumor biopsies to characterize the genetic landscape of the metastatic disease and to improve longitudinal monitoring of disease dynamics and treatment effectiveness through detection of residual tumor after resection, relapse, or metastasis within a particular patient.
MeSH term(s)	Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Circulating Tumor DNA/genetics ; DNA, Neoplasm/genetics ; Female ; Humans ; Liquid Biopsy ; Neoplastic Cells, Circulating/pathology
Chemical Substances	Biomarkers, Tumor ; Circulating Tumor DNA ; DNA, Neoplasm
Language	English
Publishing date	2022-03-14
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	604857-2
ISSN	1573-7233 ; 0167-7659
ISSN (online)	1573-7233
ISSN	0167-7659
DOI	10.1007/s10555-022-10023-9
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Article ; Online: Whole blood transcriptional profiling reveals highly deregulated atherosclerosis genes in Philadelphia-chromosome negative myeloproliferative neoplasms.

Skov, Vibe / Thomassen, Mads / Kjaer, Lasse / Larsen, Morten Kranker / Knudsen, Trine A / Ellervik, Christina / Kruse, Torben A / Hasselbalch, Hans Carl

European journal of haematology

2023 Volume 111, Issue 5, Page(s) 805–814

Abstract: Background: The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are associated with a huge comorbidity burden, including an increased risk of cardiovascular diseases. Recently, chronic inflammation has been suggested to be the driving ... ...

Abstract	Background: The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are associated with a huge comorbidity burden, including an increased risk of cardiovascular diseases. Recently, chronic inflammation has been suggested to be the driving force for clonal evolution and disease progression in MPN but also potentially having an impact upon the development of accelerated (premature) atherosclerosis. Objectives: Since chronic inflammation, atherosclerosis, and atherothrombosis are prevalent in MPNs and we have previously shown oxidative stress genes to be markedly upregulated in MPNs, we hypothesized that genes linked to development of atherosclerosis might be highly deregulated as well. Methods: Using whole blood gene expression profiling in patients with essential thrombocythemia (ET; n = 19), polycythemia vera (PV; n = 41), or primary myelofibrosis (PMF; n = 9), we herein for the first time report aberrant expression of several atherosclerosis genes. Results: Of 84 atherosclerosis genes, 45, 56, and 46 genes were deregulated in patients with ET, PV, or PMF, respectively. Furthermore, BCL2L1, MMP1, PDGFA, PTGS1, and THBS4 were progressively significantly upregulated and BCL2 progressively significantly downregulated from ET over PV to PMF (all FDR <0.05). Conclusions: We have for the first time shown massive deregulation of atherosclerosis genes in MPNs, likely reflecting the inflammatory state in MPNs in association with in vivo activation of leukocytes, platelets, and endothelial cells being deeply involved in the atherosclerotic process.
Language	English
Publishing date	2023-08-28
Publishing country	England
Document type	Journal Article
ZDB-ID	392482-8
ISSN	1600-0609 ; 0902-4441
ISSN (online)	1600-0609
ISSN	0902-4441
DOI	10.1111/ejh.14081
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Article ; Online: Ensemble-based classification using microRNA expression identifies a breast cancer patient subgroup with an ultralow long-term risk of metastases.

Block, Ines / Burton, Mark / Sørensen, Kristina P / Larsen, Martin J / Do, Thi T N / Bak, Martin / Cold, Søren / Thomassen, Mads / Tan, Qihua / Kruse, Torben A

Cancer medicine

2024 Volume 13, Issue 9, Page(s) e7089

Abstract: Background: Current clinical markers overestimate the recurrence risk in many lymph node negative (LNN) breast cancer (BC) patients such that a majority of these low-risk patients unnecessarily receive systemic treatments. We tested if differential ... ...

Abstract	Background: Current clinical markers overestimate the recurrence risk in many lymph node negative (LNN) breast cancer (BC) patients such that a majority of these low-risk patients unnecessarily receive systemic treatments. We tested if differential microRNA expression in primary tumors allows reliable identification of indolent LNN BC patients to provide an improved classification tool for overtreatment reduction in this patient group. Methods: We collected freshly frozen primary tumors of 80 LNN BC patients with recurrence and 80 recurrence-free patients (mean follow-up: 20.9 years). The study comprises solely systemically untreated patients to exclude that administered treatments confound the metastasis status. Samples were pairwise matched for clinical-pathological characteristics to minimize dependence of current markers. Patients were classified into risk-subgroups according to the differential microRNA expression of their tumors via classification model building with cross-validation using seven classification methods and a voting scheme. The methodology was validated using available data of two independent cohorts (n = 123, n = 339). Results: Of the 80 indolent patients (who would all likely receive systemic treatments today) our ultralow-risk classifier correctly identified 37 while keeping a sensitivity of 100% in the recurrence group. Multivariable logistic regression analysis confirmed independence of voting results from current clinical markers. Application of the method in two validation cohorts confirmed successful classification of ultralow-risk BC patients with significantly prolonged recurrence-free survival. Conclusion: Profiles of differential microRNAs expression can identify LNN BC patients who could spare systemic treatments demanded by currently applied classifications. However, further validation studies are required for clinical implementation of the applied methodology.
MeSH term(s)	Humans ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Breast Neoplasms/metabolism ; Female ; MicroRNAs/genetics ; Middle Aged ; Biomarkers, Tumor/genetics ; Aged ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/pathology ; Adult ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Risk Assessment/methods ; Neoplasm Metastasis ; Prognosis
Chemical Substances	MicroRNAs ; Biomarkers, Tumor
Language	English
Publishing date	2024-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.7089
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Article ; Online: Epithelial ovarian cancer and the use of circulating tumor DNA: A systematic review.

Thusgaard, Christine Fribert / Korsholm, Malene / Koldby, Kristina Magaard / Kruse, Torben A / Thomassen, Mads / Jochumsen, Kirsten Marie

Gynecologic oncology

2021 Volume 161, Issue 3, Page(s) 884–895

Abstract: Objective: One way to improve the survival rate of epithelial Ovarian Cancer (EOC) is by identifying effective biomarkers useful at different stages and time points of the disease. A potential biomarker is circulating tumor DNA (ctDNA) in plasma or ... ...

Abstract	Objective: One way to improve the survival rate of epithelial Ovarian Cancer (EOC) is by identifying effective biomarkers useful at different stages and time points of the disease. A potential biomarker is circulating tumor DNA (ctDNA) in plasma or serum. In this systematic review, we provide an overview of applications of ctDNA in EOC to discuss the direction of future research in this field. Methods: We performed a systematic search in Pubmed, Embase, and Scopus to identify relevant clinical studies eligible for inclusion. Furthermore, the references in the identified studies and relevant reviews were assessed to identify additional studies. The PRISMA guideline was employed to perform the systematic review, and data from the studies were extracted using piloted data extraction forms. Results: A total of 36 observational studies were included. The concordance between tumor and ctDNA was assessed in 19 studies, early diagnosis in 1, diagnosis in 23, monitoring of treatment response in 7, detection of reversion mutations in 3, prognosis in 9, but no studies assessed early detection of recurrence. Data from the studies were reported descriptively. The studies had a large variation in the methods used for ctDNA analysis and limited sample sizes of 10-126 patients. Overall, the studies show that ctDNA is a potential biomarker for EOC useful in several settings during assessment and treatment of these patients. Conclusions: Although the identified studies are limited in number and their methods for ctDNA analysis vary, it is clear that ctDNA as a biomarker for EOC is promising for several applications in diagnostics, monitoring of treatment response, and prognostics. However, more studies are needed to establish the ideal methods and settings for the clinical use of ctDNA in EOC.
MeSH term(s)	Biomarkers, Tumor/blood ; Carcinoma, Ovarian Epithelial/blood ; Carcinoma, Ovarian Epithelial/diagnosis ; Circulating Tumor DNA/blood ; Female ; Humans ; Ovarian Neoplasms/blood ; Ovarian Neoplasms/diagnosis
Chemical Substances	Biomarkers, Tumor ; Circulating Tumor DNA
Language	English
Publishing date	2021-04-21
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2021.04.020
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Article ; Online: Interferon-alpha2 treatment of patients with polycythemia vera and related neoplasms favorably impacts deregulation of oxidative stress genes and antioxidative defense mechanisms.

Skov, Vibe / Thomassen, Mads / Kjær, Lasse / Ellervik, Christina / Larsen, Morten Kranker / Knudsen, Trine Alma / Kruse, Torben A / Hasselbalch, Hans C

PloS one

2022 Volume 17, Issue 6, Page(s) e0270669

Abstract: Chronic inflammation is considered a major driving force for clonal expansion and evolution in the Philadelphia-negative myeloproliferative neoplasms, which include essential thrombocythemia, polycythemia vera and primary myelofibrosis (MPNs). One of the ...

Abstract	Chronic inflammation is considered a major driving force for clonal expansion and evolution in the Philadelphia-negative myeloproliferative neoplasms, which include essential thrombocythemia, polycythemia vera and primary myelofibrosis (MPNs). One of the key mutation drivers is the JAK2V617F mutation, which has been shown to induce the generation of reactive oxygen species (ROS). Using whole blood gene expression profiling, deregulation of several oxidative stress and anti-oxidative defense genes has been identified in MPNs, including significant downregulation of TP53, the NFE2L2 or NRF2 genes. These genes have a major role for maintaining genomic stability, regulation of the oxidative stress response and in modulating migration or retention of hematopoietic stem cells. Therefore, their deregulation might give rise to increasing genomic instability, increased chronic inflammation and disease progression with egress of hematopoietic stem cells from the bone marrow to seed in the spleen, liver and elsewhere. Interferon-alpha2 (rIFNα) is increasingly being recognized as the drug of choice for the treatment of patients with MPNs. Herein, we report the first gene expression profiling study on the impact of rIFNα upon oxidative stress and antioxidative defense genes in patients with MPNs (n = 33), showing that rIFNα downregulates several upregulated oxidative stress genes and upregulates downregulated antioxidative defense genes. Treatment with rIFNα induced upregulation of 19 genes in ET and 29 genes in PV including CXCR4 and TP53. In conclusion, this rIFNα- mediated dampening of genotoxic damage to hematopoietic cells may ultimately diminish the risk of additional mutations and accordingly clonal evolution and disease progression towards myelofibrotic and leukemic transformation.
MeSH term(s)	Antioxidants/metabolism ; Defense Mechanisms ; Disease Progression ; Genomic Instability ; Humans ; Inflammation/metabolism ; Interferons/metabolism ; Janus Kinase 2/genetics ; Janus Kinase 2/metabolism ; Mutation ; Myeloproliferative Disorders/drug therapy ; Myeloproliferative Disorders/genetics ; Neoplasms ; Oxidative Stress/genetics ; Polycythemia Vera/drug therapy ; Polycythemia Vera/genetics ; Primary Myelofibrosis/drug therapy ; Primary Myelofibrosis/genetics
Chemical Substances	Antioxidants ; Interferons (9008-11-1) ; Janus Kinase 2 (EC 2.7.10.2)
Language	English
Publishing date	2022-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0270669
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Article ; Online: Differential expression of checkpoint markers in the normoxic and hypoxic microenvironment of glioblastomas.

Petterson, Stine Asferg / Sørensen, Mia Dahl / Burton, Mark / Thomassen, Mads / Kruse, Torben A / Michaelsen, Signe Regner / Kristensen, Bjarne Winther

Brain pathology (Zurich, Switzerland)

2022 Volume 33, Issue 1, Page(s) e13111

Abstract: Glioblastoma is the most common primary malignant brain tumor in adults with an overall survival of only 14.6 months. Hypoxia is known to play a role in tumor aggressiveness but the influence of hypoxia on the immune microenvironment is not fully ... ...

Abstract	Glioblastoma is the most common primary malignant brain tumor in adults with an overall survival of only 14.6 months. Hypoxia is known to play a role in tumor aggressiveness but the influence of hypoxia on the immune microenvironment is not fully understood. The aim of this study was to investigate the expression of immune-related proteins in normoxic and hypoxic tumor areas by digital spatial profiling. Tissue samples from 10 glioblastomas were stained with a panel of 40 antibodies conjugated to photo-cleavable oligonucleotides. The free oligo-tags from normoxic and hypoxic areas were hybridized to barcodes for digital counting. Differential expression patterns were validated by Ivy Glioblastoma Atlas Project (GAP) data and an independent patient cohort. We found that CD44, Beta-catenin and B7-H3 were upregulated in hypoxia, whereas VISTA, CD56, KI-67, CD68 and CD11c were downregulated. PD-L1 and PD-1 were not affected by hypoxia. Focusing on the checkpoint-related markers CD44, B7-H3 and VISTA, our findings for CD44 and VISTA could be confirmed with Ivy GAP RNA sequencing data. Immunohistochemical staining and digital quantification of CD44, B7-H3 and VISTA in an independent cohort confirmed our findings for all three markers. Additional stainings revealed fewer T cells and high but equal amounts of tumor-associated microglia and macrophages in both hypoxic and normoxic regions. In conclusion, we found that CD44 and B7-H3 were upregulated in areas with hypoxia whereas VISTA was downregulated together with the presence of fewer T cells. This heterogeneous expression should be taken into consideration when developing novel therapeutic strategies.
MeSH term(s)	Adult ; Humans ; Glioblastoma ; Biomarkers, Tumor/genetics ; T-Lymphocytes ; Macrophages/metabolism ; Hypoxia ; Tumor Microenvironment
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2022-09-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.13111
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Article ; Online: Non-BRCA1/BRCA2 high-risk familial breast cancers are not associated with a high prevalence of BRCAness.

Andersen, Lars V B / Larsen, Martin J / Davies, Helen / Degasperi, Andrea / Nielsen, Henriette Roed / Jensen, Louise A / Kroeldrup, Lone / Gerdes, Anne-Marie / Lænkholm, Anne-Vibeke / Kruse, Torben A / Nik-Zainal, Serena / Thomassen, Mads

Breast cancer research : BCR

2023 Volume 25, Issue 1, Page(s) 69

Abstract: Background: Familial breast cancer is in most cases unexplained due to the lack of identifiable pathogenic variants in the BRCA1 and BRCA2 genes. The somatic mutational landscape and in particular the extent of BRCA-like tumour features (BRCAness) in ... ...

Abstract	Background: Familial breast cancer is in most cases unexplained due to the lack of identifiable pathogenic variants in the BRCA1 and BRCA2 genes. The somatic mutational landscape and in particular the extent of BRCA-like tumour features (BRCAness) in these familial breast cancers where germline BRCA1 or BRCA2 mutations have not been identified is to a large extent unknown. Methods: We performed whole-genome sequencing on matched tumour and normal samples from high-risk non-BRCA1/BRCA2 breast cancer families to understand the germline and somatic mutational landscape and mutational signatures. We measured BRCAness using HRDetect. As a comparator, we also analysed samples from BRCA1 and BRCA2 germline mutation carriers. Results: We noted for non-BRCA1/BRCA2 tumours, only a small proportion displayed high HRDetect scores and were characterized by concomitant promoter hypermethylation or in one case a RAD51D splice variant previously reported as having unknown significance to potentially explain their BRCAness. Another small proportion showed no features of BRCAness but had mutationally active tumours. The remaining tumours lacked features of BRCAness and were mutationally quiescent. Conclusions: A limited fraction of high-risk familial non-BRCA1/BRCA2 breast cancer patients is expected to benefit from treatment strategies against homologue repair deficient cancer cells.
MeSH term(s)	Humans ; Female ; Genes, BRCA2 ; Breast Neoplasms/epidemiology ; Breast Neoplasms/genetics ; Prevalence ; Mutation ; BRCA2 Protein/genetics
Chemical Substances	BRCA2 protein, human ; BRCA2 Protein
Language	English
Publishing date	2023-06-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-023-01655-y
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Article ; Online: Metoder til identifikation af kraeftgener.

Kruse, Torben A

Ugeskrift for laeger

2006 Volume 168, Issue 24, Page(s) 2339–2340

Abstract: Through classical genetic epidemiological studies, such as twin studies, it is possible to get an estimate of the genetic contribution to cancer risk. However, due to the high degree of complexity of the human genome, it is not an easy task to identify ... ...

Title translation	Methods for identification of cancer genes.
Abstract	Through classical genetic epidemiological studies, such as twin studies, it is possible to get an estimate of the genetic contribution to cancer risk. However, due to the high degree of complexity of the human genome, it is not an easy task to identify the genes responsible for this contribution. Linkage analysis in cancer families has allowed the localisation and subsequent identification of highly penetrant cancer genes. For the identification of weaker susceptibility genes, association studies have been and will in the coming years increasingly be used.
MeSH term(s)	Adaptor Proteins, Signal Transducing ; Carrier Proteins/genetics ; Chromosome Mapping/methods ; Genes, BRCA1 ; Genes, BRCA2 ; Genes, Neoplasm/genetics ; Genetic Predisposition to Disease/genetics ; Genetic Variation/genetics ; Humans ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein/genetics ; Neoplasms/genetics ; Nuclear Proteins/genetics
Chemical Substances	Adaptor Proteins, Signal Transducing ; Carrier Proteins ; MLH1 protein, human ; Nuclear Proteins ; MSH2 protein, human (EC 3.6.1.3) ; MutL Protein Homolog 1 (EC 3.6.1.3) ; MutS Homolog 2 Protein (EC 3.6.1.3)
Language	Danish
Publishing date	2006-06-12
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	124102-3
ISSN	1603-6824 ; 0041-5782
ISSN (online)	1603-6824
ISSN	0041-5782
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Article ; Online: Male with an apparently normal phenotype carrying a BRCA1 exon 20 duplication in trans to a BRCA1 frameshift variant.

Breast cancer research : BCR

2024 Volume 26, Issue 1, Page(s) 6

Abstract: Background: Reports of dual carriers of pathogenic BRCA1 variants in trans are extremely rare, and so far, most individuals have been associated with a Fanconi Anemia-like phenotype.: Methods: We identified two families with a BRCA1 in-frame exon 20 ... ...

Abstract	Background: Reports of dual carriers of pathogenic BRCA1 variants in trans are extremely rare, and so far, most individuals have been associated with a Fanconi Anemia-like phenotype. Methods: We identified two families with a BRCA1 in-frame exon 20 duplication (Ex20dup). In one male individual, the variant was in trans with the BRCA1 frameshift variant c.2475delC p.(Asp825Glufs21). We performed splicing analysis and used a transcription activation domain (TAD) assay to assess the functional impact of Ex20dup. We collected pedigrees and mapped the breakpoints of the duplication by long- and short-read genome sequencing. In addition, we performed a mitomycin C (MMC) assay from the dual carrier using cultured lymphoblastoid cells. Results:* Genome sequencing and RNA analysis revealed the BRCA1 exon 20 duplication to be in tandem. The duplication was expressed without skipping any one of the two exon 20 copies, resulting in a lack of wild-type transcripts from this allele. TAD assay indicated that the Ex20dup variant has a functional level similar to the well-known moderate penetrant pathogenic BRCA1 variant c.5096G > A p.(Arg1699Gln). MMC assay of the dual carrier indicated a slightly impaired chromosomal repair ability. Conclusions: This is the first reported case where two BRCA1 variants with demonstrated functional impact are identified in trans in a male patient with an apparently normal clinical phenotype and no BRCA1-associated cancer. The results pinpoint a minimum necessary BRCA1 protein activity to avoid a Fanconi Anemia-like phenotype in compound heterozygous status and yet still predispose carriers to hormone-related cancers. These findings urge caution when counseling families regarding potential Fanconi Anemia risk. Furthermore, prudence should be taken when classifying individual variants as benign based on co-occurrence in trans with well-established pathogenic variants.
MeSH term(s)	Humans ; Male ; BRCA1 Protein/genetics ; Breast Neoplasms ; Exons/genetics ; Fanconi Anemia/genetics ; Mitomycin ; Phenotype
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human ; Mitomycin (50SG953SK6)
Language	English
Publishing date	2024-01-09
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-023-01755-9
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Article ; Online: [Genomic medicine and artificial intelligence].

Kruse, Torben A / Larsen, Martin J / Tan, Qihua / Andersen, Lars / Thomassen, Mads

Ugeskrift for laeger

2019 Volume 181, Issue 7A

Abstract: In this review, we discuss the management of genomic medicine, which is based on very large data sets with up to billions of data points when analysing the whole genome. By using artificial intelligence (AI) it is possible to find patterns in such data ... ...

Abstract	In this review, we discuss the management of genomic medicine, which is based on very large data sets with up to billions of data points when analysing the whole genome. By using artificial intelligence (AI) it is possible to find patterns in such data sets and thereby identify subgroups of patients differing clinically, or to extract informative data points and construct models, which will predict disease risk, prognosis or treatment response most often in a process including training and testing (machine learning). Future clinical decision making will increasingly be based on patterns and models obtained by AI analysis of many parameters.
MeSH term(s)	Artificial Intelligence ; Genomics ; Humans ; Precision Medicine
Language	Danish
Publishing date	2019-04-04
Publishing country	Denmark
Document type	Journal Article ; Review
ZDB-ID	124102-3
ISSN	1603-6824 ; 0041-5782
ISSN (online)	1603-6824
ISSN	0041-5782
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