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Article ; Online: Association of telomere length and mitochondrial DNA copy number, two biomarkers of biological aging, with the risk of venous thromboembolism.

Vostatek, Rafaela / Hohensinner, Philipp / Nopp, Stephan / Haider, Patrick / Englisch, Cornelia / Pointner, Julia / Pabinger, Ingrid / Ay, Cihan

Thrombosis research

2023 Volume 223, Page(s) 168–173

Abstract: Background: Venous thromboembolism (VTE) is the third most common cardiovascular disease and occurs in all age groups, albeit the risk increases considerably with age. Previous research indicates mitochondrial dysfunction and telomere shortening in ... ...

Abstract	Background: Venous thromboembolism (VTE) is the third most common cardiovascular disease and occurs in all age groups, albeit the risk increases considerably with age. Previous research indicates mitochondrial dysfunction and telomere shortening in cardiovascular aging. However, in the context of VTE this has not been investigated in detail. Aim: We aimed to explore biomarkers reflecting biological aging (i.e. human mitochondrial DNA copy number (mtDNA) and telomere length) and their association with VTE. Methods: mtDNA and telomere length were measured in a case-control study of 116 patients with a history of VTE and 128 age- and sex-matched healthy individuals from isolated blood using a qPCR-based assay kit. Cases had at least one unprovoked VTE event and were enrolled no earlier than 3 months after the last VTE event. Results: The mtDNA copy number was significantly lower in VTE cases compared to controls (median [IQR]: 663 per diploid cells [78.75-2204.5] vs. 2832 per diploid cells [724-4350]; p < 0.001). After adjustment for age, sex, BMI, and smoking, mtDNA copy number was independently associated with VTE risk (odds ratio per increase in 400 mtDNA per diploid cell: 0.889, 95%CI 0.834-0.947). mtDNA copy numbers were significantly different between women and men (2375 [455-3737] women vs. 893 [152-3154] men; p < 0.001). The analysis of telomere length showed no significant difference between patients and healthy controls. Conclusion: Lower mtDNA levels were found in patients with VTE compared to controls, indicating an association of biological aging with risk of VTE.
MeSH term(s)	Male ; Humans ; Female ; DNA, Mitochondrial/genetics ; Venous Thromboembolism ; DNA Copy Number Variations ; Case-Control Studies ; Telomere ; Aging/genetics ; Mitochondria ; Biomarkers
Chemical Substances	DNA, Mitochondrial ; Biomarkers
Language	English
Publishing date	2023-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2023.01.031
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Article ; Online: Role of mitochondrial DNA level in epidural-related maternal fever: a single-centre, observational, pilot study.

Hafner, Christina / Windpassinger, Marita / Tretter, Eva Verena / Rebernig, Katharina Anna / Reindl, Sophie Marie / Hochreiter, Beatrix / Dekan, Sabine / Haider, Patrick / Kiss, Herbert / Klein, Klaus Ulrich / Wohlrab, Peter

BMC pregnancy and childbirth

2024 Volume 24, Issue 1, Page(s) 341

Abstract: Introduction: Epidural analgesia has been associated with intrapartum maternal fever development. Epidural-related maternal fever (ERMF) is believed to be based on a non-infectious inflammatory reaction. Circulating cell-free mitochondrial ... ...

Abstract	Introduction: Epidural analgesia has been associated with intrapartum maternal fever development. Epidural-related maternal fever (ERMF) is believed to be based on a non-infectious inflammatory reaction. Circulating cell-free mitochondrial deoxyribonucleic acid (mtDNA) is one of the possible triggers of sterile inflammatory processes; however, a connection has not been investigated so far. Therefore, this study aimed to investigate cell-free mtDNA alterations in women in labour with ERMF in comparison with non-febrile women. Material and methods: A total of 60 women in labour were assessed for maternal temperature every 4 h and blood samples were obtained at the beginning and after delivery. Depending on the analgesia and the development of fever (axillary temperature ≥ 37.5 °C), the women were allocated either to the group of no epidural analgesia (n = 17), to epidural analgesia no fever (n = 34) or to ERMF (n = 9). Circulating cell-free mtDNA was analysed in the maternal plasma for the primary outcome whereas secondary outcomes include the evaluation of inflammatory cytokine release, as well as placental inflammatory signs. Results: Of the women with epidural analgesia, 20% (n = 9) developed ERMF and demonstrated a decrease of circulating mtDNA levels during labour (p = 0.04), but a trend towards higher free nuclear DNA. Furthermore, women with maternal pyrexia showed a 1.5 fold increased level of Interleukin-6 during labour. A correlation was found between premature rupture of membranes and ERMF. Conclusions: The pilot trial revealed an evident obstetric anaesthesia phenomenon of maternal fever due to epidural analgesia in 20% of women in labour, demonstrating counterregulated free mtDNA and nDNA. Further work is urgently required to understand the connections between the ERMF occurrence and circulating cell-free mtDNA as a potential source of sterile inflammation. Trial registration: NCT0405223 on clinicaltrials.gov (registered on 25/07/2019).
MeSH term(s)	Humans ; Female ; DNA, Mitochondrial/blood ; Pilot Projects ; Pregnancy ; Adult ; Analgesia, Epidural ; Fever/blood ; Analgesia, Obstetrical ; Labor, Obstetric/blood ; Cell-Free Nucleic Acids/blood
Chemical Substances	DNA, Mitochondrial ; Cell-Free Nucleic Acids
Language	English
Publishing date	2024-05-03
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	2059869-5
ISSN	1471-2393 ; 1471-2393
ISSN (online)	1471-2393
ISSN	1471-2393
DOI	10.1186/s12884-024-06551-7
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Article ; Online: Quantitative and Functional Assessment of the Influence of Routinely Used Cryopreservation Media on Mononuclear Leukocytes for Medical Research.

Haider, Patrick / Hoberstorfer, Timothy / Salzmann, Manuel / Fischer, Michael B / Speidl, Walter S / Wojta, Johann / Hohensinner, Philipp J

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: Quantitative and functional analysis of mononuclear leukocyte populations is an invaluable tool to understand the role of the immune system in the pathogenesis of a disease. Cryopreservation of mononuclear cells (MNCs) is routinely used to guarantee ... ...

Abstract	Quantitative and functional analysis of mononuclear leukocyte populations is an invaluable tool to understand the role of the immune system in the pathogenesis of a disease. Cryopreservation of mononuclear cells (MNCs) is routinely used to guarantee similar experimental conditions. Immune cells react differently to cryopreservation, and populations and functions of immune cells change during the process of freeze-thawing. To allow for a setup that preserves cell number and function optimally, we tested four different cryopreservation media. MNCs from 15 human individuals were analyzed. Before freezing and after thawing, the distribution of leukocytes was quantified by flow cytometry. Cultured cells were stimulated using lipopolysaccharide, and their immune response was quantified by flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). Ultimately, the performance of the cryopreservation media was ranked. Cell recovery and viability were different between the media. Cryopreservation led to changes in the relative number of monocytes, T cells, B cells, and their subsets. The inflammatory response of MNCs was altered by cryopreservation, enhancing the basal production of inflammatory cytokines. Different cryopreservation media induce biases, which needs to be considered when designing a study relying on cryopreservation. Here, we provide an overview of four different cryopreservation media for choosing the optimal medium for a specific task.
MeSH term(s)	Cell Culture Techniques/methods ; Cell Survival ; Cells, Cultured ; Cryopreservation/methods ; Female ; Flow Cytometry ; Humans ; Leukocyte Count ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Male
Language	English
Publishing date	2022-02-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031881
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Article ; Online: Reduced Monocyte and Neutrophil Infiltration and Activation by P-Selectin/CD62P Inhibition Enhances Thrombus Resolution in Mice.

Kral-Pointner, Julia B / Haider, Patrick / Szabo, Petra L / Salzmann, Manuel / Brekalo, Mira / Schneider, Karl H / Schrottmaier, Waltraud C / Kaun, Christoph / Bleichert, Sonja / Kiss, Attila / Sickha, Romana / Hengstenberg, Christian / Huber, Kurt / Brostjan, Christine / Bergmeister, Helga / Assinger, Alice / Podesser, Bruno K / Wojta, Johann / Hohensinner, Philipp

Arteriosclerosis, thrombosis, and vascular biology

2024 Volume 44, Issue 4, Page(s) 954–968

Abstract: Background: Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and ...

Abstract	Background: Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and endothelial cells. Thus, we aimed to modulate leukocyte function during thrombus resolution post-thrombus formation by blocking P-selectin/CD62P-mediated cell interactions. Methods: Thrombosis was induced by inferior vena cava stenosis through ligation in mice. After 1 day, a P-selectin-blocking antibody or isotype control was administered and thrombus composition and resolution were analyzed. Results: Localizing neutrophils and macrophages in thrombotic lesions of wild-type mice revealed that these cells enter the thrombus and vessel wall from the caudal end. Neutrophils were predominantly present 1 day and monocytes/macrophages 3 days after vessel ligation. Blocking P-selectin reduced circulating platelet-neutrophil and platelet-Ly6C Conclusions: Inhibition of P-selectin-dependent activation of monocytes and neutrophils accelerates venous thrombosis resolution due to reduced infiltration and activation of innate immune cells at the site of thrombus formation, which prevents early thrombus stabilization and facilitates fibrinolysis.
MeSH term(s)	Mice ; Humans ; Animals ; Monocytes/pathology ; P-Selectin ; Endothelial Cells ; Thromboplastin ; Neutrophil Infiltration ; Thrombosis ; Neutrophils
Chemical Substances	P-Selectin ; Thromboplastin (9035-58-9)
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.123.320016
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Book ; Online ; Thesis: Ein Modell für die Simulation und Optimierung kryogener Plattenwärmeübertrager

Haider, Patrick Verfasser] / [Klein, Harald [Akademischer Betreuer] / Harbou, Erik von Gutachter] / [Klein, Harald [Gutachter]

2022

Author's details	Patrick Haider ; Gutachter: Erik von Harbou, Harald Klein ; Betreuer: Harald Klein
Keywords	Technische Chemie ; Technical Chemistry
Subject code	sg660
Language	German
Publisher	Universitätsbibliothek der TU München
Publishing place	München
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Short-term toll-like receptor 9 inhibition leads to left ventricular wall thinning after myocardial infarction.

Lenz, Max / Kiss, Attila / Haider, Patrick / Salzmann, Manuel / Brekalo, Mira / Krychtiuk, Konstantin A / Hamza, Ouafa / Huber, Kurt / Hengstenberg, Christian / Podesser, Bruno K / Wojta, Johann / Hohensinner, Philipp J / Speidl, Walter S

ESC heart failure

2023 Volume 10, Issue 4, Page(s) 2375–2385

Abstract: Aims: Ischaemia-reperfusion injury (IRI) following myocardial infarction remains a challenging topic in acute cardiac care and consecutively arising heart failure represents a severe long-term consequence. The extent of neutrophil infiltration and ... ...

Abstract	Aims: Ischaemia-reperfusion injury (IRI) following myocardial infarction remains a challenging topic in acute cardiac care and consecutively arising heart failure represents a severe long-term consequence. The extent of neutrophil infiltration and neutrophil-mediated cellular damage are thought to be aggravating factors enhancing primary tissue injury. Toll-like receptor 9 was found to be involved in neutrophil activation as well as chemotaxis and may represent a target in modulating IRI, aspects we aimed to illuminate by pharmacological inhibition of the receptor. Methods and results: Forty-nine male adult Sprague-Dawley rats were used. IRI was induced by occlusion of the left coronary artery and subsequent snare removal after 30 min. Oligonucleotide (ODN) 2088, a toll-like receptor 9 (TLR9) antagonist, control-ODN, or DNase, were administered at the time of reperfusion and over 24 h via a mini-osmotic pump. The hearts were harvested 24 h or 4 weeks after left coronary artery occlusion and immunohistochemical staining was performed. Echocardiography was done after 1 and 4 weeks to determine ventricular function. Inhibition of TLR9 by ODN 2088 led to left ventricular wall thinning (P = 0.003) in association with drastically enhanced neutrophil infiltration (P = 0.005) and increased markers of tissue damage. Additionally, an up-regulation of the chemotactic receptor CXCR2 (P = 0.046) was found after TLR9 inhibition. No such effects were observed in control-ODN or DNase-treated animals. We did not observe changes in monocyte content or subset distribution, hinting towards neutrophils as the primary mediators of the exerted tissue injury. Conclusions: Our data indicate a TLR9-dependent, negative regulation of neutrophil infiltration. Blockage of TLR9 appears to prevent the down-regulation of CXCR2, followed by an uncontrolled migration of neutrophils towards the area of infarction and the exertion of disproportional tissue injury resulting in potential aneurysm formation. In comparison with previous studies conducted in TLR
MeSH term(s)	Rats ; Mice ; Male ; Animals ; Toll-Like Receptor 9/therapeutic use ; Rats, Sprague-Dawley ; Myocardial Infarction/drug therapy ; Heart ; Coronary Vessels
Chemical Substances	Toll-Like Receptor 9
Language	English
Publishing date	2023-05-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2814355-3
ISSN	2055-5822 ; 2055-5822
ISSN (online)	2055-5822
ISSN	2055-5822
DOI	10.1002/ehf2.14403
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Article ; Online: Neutrophil extracellular traps induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model.

Salzmann, Manuel / Gibler, Patrizia / Haider, Patrick / Brekalo, Mira / Plasenzotti, Roberto / Filip, Thomas / Nistelberger, Rebecca / Hartmann, Boris / Wojta, Johann / Hengstenberg, Christian / Podesser, Bruno K / Kral-Pointner, Julia B / Hohensinner, Philipp J

Journal of thrombosis and haemostasis : JTH

2023 Volume 22, Issue 1, Page(s) 188–198

Abstract: Background: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells, and ... ...

Abstract	Background: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells, and are highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications. However, data are sparsely available on the involvement of NETs in secondary events after virus clearance, which can lead to persistent lung damage and postacute sequelae with chronic fatigue and dyspnea. Objectives: This study focuses on late-phase events using a murine model of viral lung infection with postacute sequelae after virus resolution. Methods: C57BL/6JRj mice were infected intranasally with the betacoronavirus murine coronavirus (MCoV, strain MHV-A95), and tissue samples were collected after 2, 4, and 10 days. For NET modulation, mice were pretreated with OM-85 or GSK484 and DNase I were administered intraperitoneally between days 2 to 5 and days 4 to 7, respectively. Results: Rapid, platelet-attributed thrombus formation was followed by a second, late phase of thromboinflammation. This phase was characterized by negligible virus titers but pronounced tissue damage, apoptosis, oxidative DNA damage, and presence of NETs. Inhibition of NETs during the acute phase did not impact virus burden but decreased lung cell apoptosis by 67% and oxidative stress by 94%. Prevention of neutrophil activation by immune training before virus infection reduced damage by 75%, NETs by 31%, and pulmonary thrombi by 93%. Conclusion: NETs are detrimental inducers of tissue damage during respiratory virus infection but do not contribute to virus clearance.
MeSH term(s)	Animals ; Mice ; Extracellular Traps ; Neutrophils ; Coronavirus ; Thromboinflammation ; Disease Models, Animal ; Inflammation/complications ; Thrombosis/complications ; Mice, Inbred C57BL ; Lung ; Coronavirus Infections/complications
Language	English
Publishing date	2023-09-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.09.014
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Zs.A 5805: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 295: Show issues

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Article ; Online: Staphylococcus aureus extracellular adherence protein (Eap) reduces immune cell phenotype in developing but not in established atherosclerotic lesions.

Salzmann, Manuel / Platzer, Harald / Mussbacher, Marion / Derler, Martina / Lenz, Max / Haider, Patrick / Brekalo, Mira / Kral-Pointner, Julia B / Kastl, Stefan / Speidl, Walter S / Preissner, Klaus T / Schubert, Uwe / Bischoff, Markus / Uhrin, Pavel / Wojta, Johann / Hohensinner, Philipp J

Biochimica et biophysica acta. Molecular basis of disease

2022 Volume 1869, Issue 3, Page(s) 166616

Abstract: Atherosclerosis is a chronic, inflammatory disease of the vessel wall where triggered immune cells bind to inflamed endothelium, extravasate and sustain local inflammation. Leukocyte adhesion and extravasation are mediated by adhesion molecules expressed ...

Abstract	Atherosclerosis is a chronic, inflammatory disease of the vessel wall where triggered immune cells bind to inflamed endothelium, extravasate and sustain local inflammation. Leukocyte adhesion and extravasation are mediated by adhesion molecules expressed by activated endothelial cells, like intercellular adhesion molecule 1 (ICAM-1). Extracellular adherence protein (Eap) from Staphylococcus aureus binds to a plethora of extracellular matrix proteins, including ICAM-1 and its ligands macrophage-1 antigen (Mac-1, α
MeSH term(s)	Mice ; Animals ; Intercellular Adhesion Molecule-1/genetics ; Staphylococcus aureus/metabolism ; Endothelial Cells/metabolism ; Atherosclerosis ; Plaque, Atherosclerotic ; Lymphocyte Function-Associated Antigen-1/genetics ; Phenotype
Chemical Substances	Intercellular Adhesion Molecule-1 (126547-89-5) ; Lymphocyte Function-Associated Antigen-1
Language	English
Publishing date	2022-12-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2022.166616
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Uc I Zs.247: Show issues

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Article ; Online: MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease.

Maier, Nadine / Gatterer, Constantin / Haider, Patrick / Salzmann, Manuel / Kaun, Christoph / Speidl, Walter S / Sunder-Plassmann, Gere / Podesser, Bruno K / Wojta, Johann / Graf, Senta / Lenz, Max / Hohensinner, Philipp J

Genes

2021 Volume 12, Issue 8

Abstract: Background: Fabry disease is a hereditary genetic defect resulting in reduced activity of the enzyme α-galactosidase-A and the accumulation of globotriaosylceramide (Gb3) in body fluids and cells. Gb3 accumulation was especially reported for the ... ...

Abstract	Background: Fabry disease is a hereditary genetic defect resulting in reduced activity of the enzyme α-galactosidase-A and the accumulation of globotriaosylceramide (Gb3) in body fluids and cells. Gb3 accumulation was especially reported for the vascular endothelium in several organs. Methods: Three Fabry disease patients were screened using a micro-RNA screen. An in vitro approach in human endothelial cells was used to determine miRNA regulation by Gb3. Results: In a micro-RNA screen of three Fabry patients undergoing enzyme replacement therapy, we found that miRNAs let-7a and let-7d were significantly increased after therapy. We demonstrate in vitro in endothelial cells that Gb3 induced activation of NF-κB and activated downstream targets. In addition, NF-κB activity directly reduced let-7a and let-7d miRNA expression as inhibiting NF-kB nuclear entry abolished the Gb3 effects. Conclusion: We suggest that let-7a and let-7d are potential markers for enzyme activity and inflammation in Fabry disease patients.
MeSH term(s)	Adult ; Cells, Cultured ; Endothelial Cells/metabolism ; Enzyme Replacement Therapy ; Fabry Disease/genetics ; Fabry Disease/metabolism ; Female ; Gene Expression Regulation ; Humans ; Male ; MicroRNAs/genetics ; Middle Aged ; NF-kappa B/metabolism ; Trihexosylceramides/metabolism
Chemical Substances	MicroRNAs ; NF-kappa B ; Trihexosylceramides ; mirnlet7 microRNA, human ; globotriaosylceramide (71965-57-6)
Language	English
Publishing date	2021-07-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes12081184
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Article: Effects of Nicorandil on Inflammation, Apoptosis and Atherosclerotic Plaque Progression.

Lenz, Max / Kaun, Christoph / Krychtiuk, Konstantin A / Haider, Patrick / Brekalo, Mira / Maier, Nadine / Goederle, Laura / Binder, Christoph J / Huber, Kurt / Hengstenberg, Christian / Wojta, Johann / Hohensinner, Philipp J / Speidl, Walter S

Biomedicines

2021 Volume 9, Issue 2

Abstract: Nicorandil, a balanced vasodilator, is used in the second-line therapy of angina pectoris. In this study, we aimed to illuminate the effects of nicorandil on inflammation, apoptosis, and atherosclerotic plaque progression. Twenty-five LDL-R -/- mice were ...

Abstract	Nicorandil, a balanced vasodilator, is used in the second-line therapy of angina pectoris. In this study, we aimed to illuminate the effects of nicorandil on inflammation, apoptosis, and atherosclerotic plaque progression. Twenty-five LDL-R -/- mice were fed a high-fat diet for 14 weeks. After 6 weeks mice were randomly allocated to treatment with nicorandil (10 mg/kg/day) or tap water. Nicorandil treatment led to a more stable plaque phenotype, displaying an increased thickness of the fibrous cap (
Language	English
Publishing date	2021-01-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9020120
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