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Oscarsson, J. & Johansson, A. (2019). Comment from the Editor to the Special Issue: “Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation”. Journal of Clinical Medicine, 8(10), Article ID 1706.
Open this publication in new window or tab >>Comment from the Editor to the Special Issue: “Periodontitis: From Dysbiotic Microbial Immune Response to Systemic Inflammation”
2019 (English)In: Journal of Clinical Medicine, ISSN 2077-0383, Vol. 8, no 10, article id 1706Article in journal, Editorial material (Other academic) Published
Abstract [en]

The human oral cavity contains a large number of different microbial habitats. When microbes from the oral indigenous flora colonize the interspace between the tooth and the connective tissue, they induce an inflammatory response. If the microbes are in sufficient numbers, and release components that cause an imbalance in the host inflammatory response, degenerative processes in the surrounding tissues are induced, ultimately resulting in periodontal disease. The disease progress depends on bacterial load, the composition of the microbial community, and host genetic factors. The two most studied periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans express virulence factors, including proteases and exotoxins. Periodontal infections are also linked to the risk pattern of several systemic diseases. We would like to shed light on the mechanisms behind periodontitis and the associations of periodontal infections with systemic inflammation. Seven articles are included in this Special Issue and cover several pathogenic processes in the periodontal infection with capacity to cause imbalance in the host response. Highlights from each of the published papers are summarized and discussed below.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2019
Keywords
periodontitis, cardiovascular diseases, rheumatoid arthritis, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, inflammatory response
National Category
Medical Biotechnology
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-164304 (URN)10.3390/jcm8101706 (DOI)31623278 (PubMedID)
Available from: 2019-10-21 Created: 2019-10-21 Last updated: 2019-10-24Bibliographically approved
Jensen, A. B., Haubek, D., Claesson, R., Johansson, A. & Nørskov-Lauritsen, N. (2019). Comprehensive antimicrobial susceptibility testing of a large collection of clinical strains of Aggregatibacter actinomycetemcomitans does not identify resistance to amoxicillin. Journal of Clinical Periodontology, 46(8), 846-854
Open this publication in new window or tab >>Comprehensive antimicrobial susceptibility testing of a large collection of clinical strains of Aggregatibacter actinomycetemcomitans does not identify resistance to amoxicillin
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2019 (English)In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 46, no 8, p. 846-854Article in journal (Refereed) Published
Abstract [en]

AIM: The present study aims to determine the susceptibility of Aggregatibacter actinomycetemcomitans to amoxicillin by investigating a large collection of oral strains of diverse geographical origin.

METHODS: Two hundred and fifty-seven A. actinomycetemcomitans strains were serotyped using a multiplex polymerase chain reaction, and minimal inhibitory concentration (MIC) values of amoxicillin were determined using the agar dilution method (range 0.25 to 8.0 mg/L). The plates were spot-wise inoculated with approximately 104 colony-forming units, incubated in 5% CO2 at 37 C°, and visually inspected after 24 and 48 hours. A MIC ≤ 2.00 mg/L was categorised as susceptible using EUCAST interpretative criteria for Haemophilus species.

RESULTS: Amoxicillin MIC-values varied from 0.25 mg/L to 2.00 mg/L, and all tested strains, including strains previously reported as resistant, were susceptible to amoxicillin. The MIC50 was 1.00 mg/L and the MIC90 was 2.00 mg/L.

CONCLUSION: Meticulous investigation of strains including isolates previously reported as resistant could not confirm the emergence of resistance to β-lactams in A. actinomycetemcomitans. Based on the present in vitro results, amoxicillin can be considered a key oral antimicrobial agent for treatment of A. actinomycetemcomitans. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
EUCAST, Antimicrobial resistance, agar dilution method, breakpoints, β-lactams
National Category
Dentistry
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-159488 (URN)10.1111/jcpe.13148 (DOI)000476508700007 ()31124155 (PubMedID)2-s2.0-85068110794 (Scopus ID)
Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-08-12Bibliographically approved
Jensen, A. B., Lund, M., Nørskov-Lauritsen, N., Johansson, A., Claesson, R., Reinholdt, J. & Haubek, D. (2019). Differential Cell Lysis Among Periodontal Strains of JP2 and Non-JP2 Genotype of Aggregatibacter actinomycetemcomitans Serotype B Is Not Reflected in Dissimilar Expression and Production of Leukotoxin. Pathogens, 8(4), Article ID 211.
Open this publication in new window or tab >>Differential Cell Lysis Among Periodontal Strains of JP2 and Non-JP2 Genotype of Aggregatibacter actinomycetemcomitans Serotype B Is Not Reflected in Dissimilar Expression and Production of Leukotoxin
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2019 (English)In: Pathogens, ISSN 2076-0817, Vol. 8, no 4, article id 211Article in journal (Refereed) Published
Abstract [en]

Leukotoxic potential of Aggregatibacter actinomycetemcomitans strains has been studied by the use of several methods, and results differ depending on the methods used. The aim of the present study was to perform a comprehensive examination of the leukotoxic potential of a collection of A. actinomycetemcomitans strains by use of three quantitative methods, Western blotting, ELISA, and mRNA expression assay and compare these results with previous data obtained by a cell lysis assay. A higher leukotoxic potential among JP2 genotype strains compared to non-JP2 genotype strains of A. actinomycetemcomitans was found by Western blotting, ELISA and mRNA expression assay. Leukotoxicity as determined by cell lysis assay showed a variation among strains examined, not only depending on being part of JP2 genotype vs. non-JP2 genotype group of A. actinomycetemcomitans. The leukotoxicity of A. actinomycetemcomitans strains as determined by cell lysis assay did not correspond to the leukotoxic potential of A. actinomycetemcomitans strains as determined by three quantitative methods. A comparison of the results obtained by ELISA and mRNA expression assay showed a reasonable correlation between these two methods. It seems important to use more than one method to assess the LtxA-related virulence capacity of A. actinomycetemcomitans in order to obtain comprehensive understanding of the leukotoxic potential of A. actinomycetemcomitans strains.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2019
Keywords
JP2 genotype, cell lysis assay, leukotoxin, mRNA assay, quantitative ELISA
National Category
Medical Biotechnology
Research subject
Microbiology
Identifiers
urn:nbn:se:umu:diva-164810 (URN)10.3390/pathogens8040211 (DOI)31671616 (PubMedID)
Available from: 2019-11-02 Created: 2019-11-02 Last updated: 2019-11-05Bibliographically approved
Johansson, A., Claesson, R., Höglund-Åberg, C., Haubek, D., Lindholm, M., Jasim, S. & Oscarsson, J. (2019). Genetic Profiling of Aggregatibacter actinomycetemcomitans Serotype B Isolated from Periodontitis Patients Living in Sweden. Pathogens, 8(3), 1-13, Article ID 153.
Open this publication in new window or tab >>Genetic Profiling of Aggregatibacter actinomycetemcomitans Serotype B Isolated from Periodontitis Patients Living in Sweden
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2019 (English)In: Pathogens, ISSN 2076-0817, Vol. 8, no 3, p. 1-13, article id 153Article in journal (Refereed) Published
Abstract [en]

The bacterium Aggregatibacter actinomycetemcomitans is associated with aggressive forms of periodontitis and with systemic diseases, such as endocarditis. By assessing a Ghanaian longitudinal adolescent cohort, we earlier recognized the cagE gene as a possible diagnostic marker for a subgroup of JP2 and non-JP2 genotype serotype b A. actinomycetemcomitans strains, associated with high leukotoxicity as determined in a semi-quantitative cell assay. This group of A. actinomycetemcomitans is associated with the progression of attachment loss. In the present work, we used conventional polymerase chain reaction (PCR) and quantitative PCR to perform the cagE genotyping of our collection of 116 selected serotype b A. actinomycetemcomitans strains, collected over a period of 15 years from periodontitis patients living in Sweden. The A. actinomycetemcomitans strains carrying cagE (referred to as cagE+; n = 49) were compared to the cagE-negative strains (n = 67), present at larger proportions in the subgingival plaque samples, and were also much more prevalent in the young (≤35 years) compared to in the old (>35 years) group of patients. Our present results underline the potential use of cagE genotyping in the risk assessment of the development of periodontal attachment loss in Swedish adolescents.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2019
Keywords
Aggregatibacter actinomycetemcomitans; cagE; virB1; virB4; genotype; virulence
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-163485 (URN)10.3390/pathogens8030153 (DOI)000488003600042 ()31533208 (PubMedID)
Available from: 2019-09-23 Created: 2019-09-23 Last updated: 2019-10-24Bibliographically approved
Pietiäinen, M., Liljestrand, J. M., Akhi, R., Buhlin, K., Johansson, A., Paju, S., . . . Pussinen, P. J. (2019). Saliva and Serum Immune Responses in Apical Periodontitis. Journal of clinical medicine, 8(6), Article ID 889.
Open this publication in new window or tab >>Saliva and Serum Immune Responses in Apical Periodontitis
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2019 (English)In: Journal of clinical medicine, ISSN 2077-0383, Vol. 8, no 6, article id 889Article in journal (Refereed) Published
Abstract [en]

Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01-8.33) and 4.91 (2.48-9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48-2.97)), serum IgG to bacterial antigens (4.66 (1.22-10.1)), and Gram-negative subgingival species (1.98 (1.16-3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05-21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis-a putative risk factor for systemic diseases.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2019
Keywords
adaptive immunity, antibody, apical periodontitis, saliva, serum
National Category
Clinical Medicine
Research subject
Immunology
Identifiers
urn:nbn:se:umu:diva-161062 (URN)10.3390/jcm8060889 (DOI)000475349300133 ()31234349 (PubMedID)
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-08-12Bibliographically approved
Pettersson, M., Pettersson, J., Johansson, A. & Molin Thorén, M. (2019). Titanium release in peri-implantitis. Journal of Oral Rehabilitation, 46(2), 179-188
Open this publication in new window or tab >>Titanium release in peri-implantitis
2019 (English)In: Journal of Oral Rehabilitation, ISSN 0305-182X, E-ISSN 1365-2842, Vol. 46, no 2, p. 179-188Article in journal (Refereed) Published
Abstract [en]

Objectives: The aim of this study was to investigate the titanium (Ti) content of biopsies from patients with severe peri-implantitis or periodontitis and to examine whether Ti particles can be identified in samples from peri-implantitis lesions.

Background: Long-term follow-up studies show that implant usage to replace missing or lost teeth is a safe and predictable treatment. However, inflammation and loss of supporting bone around an implant (peri-implantitis) lead to patient suffering and costs. Peri-implantitis is considered to be an infectious disease, but recent studies have shown that Ti can aggravate inflammation in combination with bacterial products. The Ti content of peri-implantitis and periodontitis tissue is unknown.

Methods: Thirteen patients referred for peri-implantitis and eleven for periodontitis treatment were included in the study. Disease severity was obtained from dental records. Biopsies were taken from both groups and chemically analyzed with inductively coupled plasma mass spectrometry (ICP-MS) for Ti content. Additionally, two patients with peri-implantitis and two with periodontitis were recruited and their biopsies were analyzed microscopically with light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) with element analysis to investigate the presence of particulate Ti.

Results: All patients lost one or more implants despite undergoing peri-implant or periodontal treatment. Peri-implantitis tissue contained significantly higher concentrations of Ti than periodontitis tissue with a mean ± SDof 98.7 ± 85.6 μg/g and 1.2 ± 0.9 μg/g, respectively. Particulate metal was identified in peri-implantitis and periodontitis biopsies, but element analyses could confirm only the presence of Ti in peri-implantitis tissue. The mean size ± SDof the visible particles with LM was 10.9 ± 35.7 μm2 (mean of three repeated measurements) (95% CI, 6.5-15.3).

Conclusion: We showed that high contents of particulate and submicron Ti were present in peri-implantitis tissue. These high Ti contents in peri-implant mucosa can potentially aggravate inflammation, which might reduce the prognosis of treatment interventions.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
energy dispersive X-ray spectroscopy, inductively coupled plasma mass spectrometry, light microscopy, peri-implantitis, scanning electron microscopy, titanium
National Category
Dentistry
Research subject
Odontology
Identifiers
urn:nbn:se:umu:diva-147118 (URN)10.1111/joor.12735 (DOI)000455483300010 ()30325523 (PubMedID)
Funder
Västerbotten County Council, VLL 1147-2014
Note

Originally included in thesis in manuscript form.

Available from: 2018-04-27 Created: 2018-04-27 Last updated: 2019-02-08Bibliographically approved
Oscarsson, J., Claesson, R., Lindholm, M., Höglund-Åberg, C. & Johansson, A. (2019). Tools of Aggregatibacter actinomycetemcomitans to Evade the Host Response. Journal of Clinical Medicine, 8(7), Article ID 1079.
Open this publication in new window or tab >>Tools of Aggregatibacter actinomycetemcomitans to Evade the Host Response
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2019 (English)In: Journal of Clinical Medicine, ISSN 2077-0383, Vol. 8, no 7, article id 1079Article in journal (Refereed) Published
Abstract [en]

Periodontitis is an infection-induced inflammatory disease that affects the tooth supporting tissues, i.e., bone and connective tissues. The initiation and progression of this disease depend on dysbiotic ecological changes in the oral microbiome, thereby affecting the severity of disease through multiple immune-inflammatory responses. Aggregatibacter actinomycetemcomitans is a facultative anaerobic Gram-negative bacterium associated with such cellular and molecular mechanisms associated with the pathogenesis of periodontitis. In the present review, we outline virulence mechanisms that help the bacterium to escape the host response. These properties include invasiveness, secretion of exotoxins, serum resistance, and release of outer membrane vesicles. Virulence properties of A. actinomycetemcomitans that can contribute to treatment resistance in the infected individuals and upon translocation to the circulation, also induce pathogenic mechanisms associated with several systemic diseases.

Place, publisher, year, edition, pages
Basel: MDPI, 2019
Keywords
Aggregatibacter actinomycetemcomitans, cytolethal distending toxin, invasiveness, leukotoxin, outer membrane vesicles, serum resistance
National Category
Medical Biotechnology
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-161754 (URN)10.3390/jcm8071079 (DOI)31336649 (PubMedID)
Available from: 2019-07-25 Created: 2019-07-25 Last updated: 2019-07-29Bibliographically approved
Belibasakis, G. N., Maula, T., Bao, K., Lindholm, M., Bostanci, N., Oscarsson, J., . . . Johansson, A. (2019). Virulence and Pathogenicity Properties of Aggregatibacter actinomycetemcomitans. Pathogens, 8(4), Article ID E222.
Open this publication in new window or tab >>Virulence and Pathogenicity Properties of Aggregatibacter actinomycetemcomitans
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2019 (English)In: Pathogens, ISSN 2076-0817, Vol. 8, no 4, article id E222Article in journal (Refereed) Published
Abstract [en]

Aggregatibacter actinomycetemcomitans is a periodontal pathogen colonizing the oral cavity of a large proportion of the human population. It is equipped with several potent virulence factors that can cause cell death and induce or evade inflammation. Because of the large genetic diversity within the species, both harmless and highly virulent genotypes of the bacterium have emerged. The oral condition and age, as well as the geographic origin of the individual, influence the risk to be colonized by a virulent genotype of the bacterium. In the present review, the virulence and pathogenicity properties of A. actinomycetemcomitans will be addressed.

Place, publisher, year, edition, pages
Basel: MDPI, 2019
Keywords
Aggregatibacter actinomycetemcomitans, biofilm, cytokine binding factors, cytolethal distending toxin, horizontal gene transfer, leukotoxin, lipopolysaccharides, outer membrane vesicles, proteomic
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-165083 (URN)10.3390/pathogens8040222 (DOI)31698835 (PubMedID)2-s2.0-85074732943 (Scopus ID)
Funder
Swedish Research Council, 2017-01198Västerbotten County Council, 7003193
Available from: 2019-11-09 Created: 2019-11-09 Last updated: 2019-11-26Bibliographically approved
Perez-Cornago, A., Appleby, P. N., Boeing, H., Gil, L., Kyrø, C., Ricceri, F., . . . Travis, R. C. (2018). Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta-analysis of individual participant data from seven prospective studies including 2828 cases and 5593 controls. International Journal of Cancer, 143(11), 2677-2686
Open this publication in new window or tab >>Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta-analysis of individual participant data from seven prospective studies including 2828 cases and 5593 controls
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 11, p. 2677-2686Article in journal (Refereed) Published
Abstract [en]

Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between pre-diagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs Q1=0.61, 95% confidence interval [CI]=0.39-0.97), although there was no significant trend (OR per 75 percentile increase=0.69, 95 CI=0.46-1.05, Ptrend =0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs Q1=0.70, 0.45-1.10, and 0.71, 0.45-1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that pre-diagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
isoflavones, lignans, phytoestrogens, pooled analysis, prostate cancer risk
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-150143 (URN)10.1002/ijc.31640 (DOI)000450846900006 ()29971774 (PubMedID)2-s2.0-85054090054 (Scopus ID)
Funder
Swedish Cancer Society
Available from: 2018-07-10 Created: 2018-07-10 Last updated: 2018-12-19Bibliographically approved
Boles, U., Johansson, A., Wiklund, U., Sharif, Z., David, S., McGrory, S. & Henein, M. Y. (2018). Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis Pathogenesis. International Journal of Molecular Sciences, 19(1), Article ID 260.
Open this publication in new window or tab >>Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis Pathogenesis
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2018 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, no 1, article id 260Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Coronary artery ectasia (CAE) is a rare disorder commonly associated with additional features of atherosclerosis. In the present study, we aimed to examine the systemic immune-inflammatory response that might associate CAE.

METHODS: Plasma samples were obtained from 16 patients with coronary artery ectasia (mean age 64.9 ± 7.3 years, 6 female), 69 patients with coronary artery disease (CAD) and angiographic evidence for atherosclerosis (age 64.5 ± 8.7 years, 41 female), and 140 controls (mean age 58.6 ± 4.1 years, 40 female) with normal coronary arteries. Samples were analyzed at Umeå University Biochemistry Laboratory, Sweden, using the V-PLEX Pro-Inflammatory Panel 1 (human) Kit. Statistically significant differences (p < 0.05) between patient groups and controls were determined using Mann-Whitney U-tests.

RESULTS: The CAE patients had significantly higher plasma levels of INF-γ, TNF-α, IL-1β, and IL-8 (p = 0.007, 0.01, 0.001, and 0.002, respectively), and lower levels of IL-2 and IL-4 (p < 0.001 for both) compared to CAD patients and controls. The plasma levels of IL-10, IL-12p, and IL-13 were not different between the three groups. None of these markers could differentiate between patients with pure (n = 6) and mixed with minimal atherosclerosis (n = 10) CAE.

CONCLUSIONS: These results indicate an enhanced systemic pro-inflammatory response in CAE. The profile of this response indicates activation of macrophages through a pathway and trigger different from those of atherosclerosis immune inflammatory response.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2018
Keywords
atherosclerosis, coronary artery disease, coronary artery ectasia, cytokines, immune inflammatory response, macrophage activation
National Category
Cardiac and Cardiovascular Systems
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-144041 (URN)10.3390/ijms19010260 (DOI)000424407200254 ()29337902 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2018-01-26 Created: 2018-01-26 Last updated: 2019-09-23Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-8069-8263

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