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Cieślar-Pobuda, Artur
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Publications (10 of 15) Show all publications
Sherrell, P., Cieślar-Pobuda, A., Silverå Ejneby, M., Sammalisto, L., Gelmi, A., de Muinck, E., . . . Rafat, M. (2017). Rational Design of a Conductive Collagen Heart Patch. Macromolecular Bioscience, 17(7), Article ID 1600446.
Open this publication in new window or tab >>Rational Design of a Conductive Collagen Heart Patch
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2017 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 17, no 7, article id 1600446Article in journal (Refereed) Published
Abstract [en]

Cardiovascular diseases, including myocardial infarction, are the cause of significant morbidity and mortality globally. Tissue engineering is a key emerging treatment method for supporting and repairing the cardiac scar tissue caused by myocardial infarction. Creating cell supportive scaffolds that can be directly implanted on a myocardial infarct is an attractive solution. Hydrogels made of collagen are highly biocompatible materials that can be molded into a range of shapes suitable for cardiac patch applications. The addition of mechanically reinforcing materials, carbon nanotubes, at subtoxic levels allows for the collagen hydrogels to be strengthened, up to a toughness of 30 J m-1 and a two to threefold improvement in Youngs' modulus, thus improving their viability as cardiac patch materials. The addition of carbon nanotubes is shown to be both nontoxic to stem cells, and when using single-walled carbon nanotubes, supportive of live, beating cardiac cells, providing a pathway for the further development of a cardiac patch.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2017
Keywords
Carbon nanotube, Collagen, Hydrogel, Myocardial infarction, Stem cell
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-136817 (URN)10.1002/mabi.201600446 (DOI)000405566300004 ()28322510 (PubMedID)2-s2.0-85016390421 (Scopus ID)
Note

Funding agencies: Linkoping Initiative in Life Science Technologies (LIST); Central ALF Matching Grant from Landstinget i Ostergotland [LIO-344071]; European Research Agency [304209]; GeCONiI [POIG.02.03.01-24-099/13]

Available from: 2017-04-27 Created: 2017-04-27 Last updated: 2018-04-09Bibliographically approved
Gelmi, A., Cieslar-Pobuda, A., de Muinck, E., Los, M. J., Rafat, M. & Jager, E. (2016). Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering. Advanced Healthcare Materials, 5(12), 1471-1480
Open this publication in new window or tab >>Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering
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2016 (English)In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 5, no 12, p. 1471-1480Article in journal (Refereed) Published
Abstract [en]

The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2016
Keywords
actuators; conductive polymers; scaffolds; stem cells; tissue engineering
National Category
Biophysics
Identifiers
urn:nbn:se:liu:diva-130427 (URN)10.1002/adhm.201600307 (DOI)000379550400010 ()27126086 (PubMedID)
Note

Funding Agencies|Linkoping University, Integrative Regenerative Medicine (IGEN) Center; Swedish Research Council [VR-2014-3079]; COST-Action [MP1003]; Knut och Alice Wallenberg Commemorative Fund; GeCONiI [POIG.02.03.01-24-099/13]; European Research Agency

Available from: 2016-08-07 Created: 2016-08-05 Last updated: 2019-10-08Bibliographically approved
Magnusson, K., Appelqvist, H., Cieślar-Pobuda, A., Bäck, M., Kågedal, B., Jonasson, J., . . . Nilsson, P. R. (2015). An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells. Frontiers in Chemistry, 3, Article ID 58.
Open this publication in new window or tab >>An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells
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2015 (English)In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 3, article id 58Article in journal (Refereed) Published
Abstract [en]

Molecular tools for fluorescent imaging of cells and their components are vital for understanding the function and activity of cells. Here, we report an imidazole functionalized pentameric oligothiophene, p-HTIm, that can be utilized for fluorescent imaging of cells. p-HTIm fluorescence in normal cells appeared in a peripheral punctate pattern partially co-localized with lysosomes, whereas a one-sided perinuclear Golgi associated localization of the dye was observed in malignant cells. The uptake of p-HTIm was temperature dependent and the intracellular target was reached within 1 h after staining. The ability of p-HTIm to stain cells was reduced when the imidazole side chain was chemically altered, verifying that specific imidazole side-chain functionalities are necessary for achieving the observed cellular staining. Our findings confirm that properly functionalized oligothiophenes can be utilized as fluorescent tools for vital staining of cells and that the selectivity towards distinct intracellular targets are highly dependent on the side-chain functionalities along the conjugated thiophene backbone.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2015
Keywords
Oligothiophenes, fluorescence, cells, imaging, imidazole
National Category
Clinical Medicine Chemical Sciences Medical Biotechnology
Identifiers
urn:nbn:se:liu:diva-121813 (URN)10.3389/fchem.2015.00058 (DOI)000373364600001 ()
Note

Vid tiden för disputation förelåg publikationen som manuskript

Funding agencies:  Swedish Foundation for Strategic Research; GeCONil [POIG.02.03.01-24-099/13]; ERC from the European Research Council

Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2017-12-01Bibliographically approved
Magnusson, K., Appelqvist, H., Cieslar-Pobuda, A., Wigenius, J., Karlsson, T., Los, M. J., . . . Nilsson, P. (2015). Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte. Cytometry Part A, 87(3), 262-272
Open this publication in new window or tab >>Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte
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2015 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 87, no 3, p. 262-272Article in journal (Refereed) Published
Abstract [en]

Molecular probes for imaging of live cells are of great interest for studying biological and pathological processes. The anionic luminescent conjugated polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used for vital staining of cultured fibroblasts as well as transformed cells with results indicating differential staining due to cell phenotype. Herein, we investigated the behavior of PTAA in two normal and five transformed cells lines. PTAA fluorescence in normal cells appeared in a peripheral punctated pattern whereas the probe was more concentrated in a one-sided perinuclear localization in the five transformed cell lines. In fibroblasts, PTAA fluorescence was initially associated with fibronectin and after 24 h partially localized to lysosomes. The uptake and intracellular target in malignant melanoma cells was more ambiguous and the intracellular target of PTAA in melanoma cells is still elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and microscopic analysis as well as viability assays showed no signs of negative influence on growth. Stained cells maintained their proliferation rate for at least 12 generations. Although the probe itself was nontoxic, photoinduced cellular toxicity was observed in both cell lines upon irradiation directly after staining. However, no cytotoxicity was detected when the cells were irradiated 24 h after staining, indicating that the photoinduced toxicity is dependent on the cellular location of the probe. Overall, these studies certified PTAA as a useful agent for vital staining of cells, and that PTAA can potentially be used to study cancer-related biological and pathological processes.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
Keywords
Conjugated polyelectrolyte; Fibroblast; Fluorescence; Luminescent conjugated polythiophene; Melanoma; Photoinduced toxicity
National Category
Structural Biology Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-115887 (URN)10.1002/cyto.a.22627 (DOI)000349984200009 ()25605326 (PubMedID)2-s2.0-84923259526 (Scopus ID)
Available from: 2015-03-23 Created: 2015-03-23 Last updated: 2018-09-14
Gelmi, A., Zhang, J., Cieslar-Pobuda, A., Ljunggren, M., Los, M., Rafat, M. & Jager, E. (2015). Electroactive polymer scaffolds for cardiac tissue engineering. In: Bar-Cohen (Ed.), Proc. SPIE 9430, Electroactive Polymer Actuators and Devices (EAPAD) 2015: . Paper presented at Electroactive Polymer Actuators and Devices (EAPAD) 2015 (pp. 94301T-1-94301T-7). SPIE - International Society for Optical Engineering, 9430
Open this publication in new window or tab >>Electroactive polymer scaffolds for cardiac tissue engineering
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2015 (English)In: Proc. SPIE 9430, Electroactive Polymer Actuators and Devices (EAPAD) 2015 / [ed] Bar-Cohen, SPIE - International Society for Optical Engineering, 2015, Vol. 9430, p. 94301T-1-94301T-7Conference paper, Published paper (Refereed)
Abstract [en]

By-pass surgery and heart transplantation are traditionally used to restore the heart’s functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

Place, publisher, year, edition, pages
SPIE - International Society for Optical Engineering, 2015
Series
Proceedings of SPIE, ISSN 0277-786X ; 9430
National Category
Medical Materials
Identifiers
urn:nbn:se:liu:diva-118260 (URN)10.1117/12.2084165 (DOI)000355580900052 ()
Conference
Electroactive Polymer Actuators and Devices (EAPAD) 2015
Available from: 2015-05-22 Created: 2015-05-22 Last updated: 2018-10-11Bibliographically approved
Vilas Jain, M., Jangamreddy, J., Grabarek, J., Schweizer, F., Klonisch, T., Cieslar-Pobuda, A. & Los, M. J. (2015). Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21(Waf1/Cip1) and p27(kip1). Cell Cycle, 14(13), 2109-2120
Open this publication in new window or tab >>Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21(Waf1/Cip1) and p27(kip1)
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2015 (English)In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 14, no 13, p. 2109-2120Article in journal (Refereed) Published
Abstract [en]

Cancer stem-like cells (CSCs) are a rare subpopulation of cancer cells capable of propagating the disease and causing cancer recurrence. In this study, we found that the cellular localization of PKB/Akt kinase affects the maintenance of CSCs. When Akt tagged with nuclear localization signal (Akt-NLS) was overexpressed in SKBR3 and MDA-MB468 cells, these cells showed a 10-15% increase in the number of cells with CSCs enhanced ALDH activity and demonstrated a CD44(+High)/CD24(-Low) phenotype. This effect was completely reversed in the presence of Akt-specific inhibitor, triciribine. Furthermore, cells overexpressing Akt or Akt-NLS were less likely to be in G0/G1 phase of the cell cycle by inactivating p21(Waf1/Cip1) and exhibited increased clonogenicity and proliferation as assayed by colony-forming assay (mammosphere formation). Thus, our data emphasize the importance the intracellular localization of Akt has on stemness in human breast cancer cells. It also indicates a new robust way for improving the enrichment and culture of CSCs for experimental purposes. Hence, it allows for the development of simpler protocols to study stemness, clonogenic potency, and screening of new chemotherapeutic agents that preferentially target cancer stem cells. Summary: The presented data, (i) shows new, stemness-promoting role of nuclear Akt/PKB kinase, (ii) it underlines the effects of nuclear Akt on cell cycle regulation, and finally (iii) it suggests new ways to study cancer stem-like cells.

Place, publisher, year, edition, pages
Taylor and Francis: STM, Behavioural Science and Public Health Titles, 2015
Keywords
Akt-NLS; cancer stem-like cells; mTOR; PI3K; stemness
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-120274 (URN)10.1080/15384101.2015.1041692 (DOI)000356959800021 ()26030190 (PubMedID)
Note

Funding Agencies|Linkoping University; Integrative Regenerative Medicine Center (IGEN); VR-NanoVision [K2012-99X-22325-01-5]; Cancerfonden [2013/391]; Canadian Breast Cancer Foundation (CBCF); Natural Sciences and Engineering Research Council of Canada (NSERC); [BK/265/RAU1/2014/t.10]

Available from: 2015-07-24 Created: 2015-07-24 Last updated: 2018-01-11
Bose, T., Cieślar-Pobuda, A. & Wiechec, E. (2015). Role of ion channels in regulating Ca2+ homeostasis during the interplay between immune and cancer cells.. Cell Death and Disease, 19(6), Article ID e1648.
Open this publication in new window or tab >>Role of ion channels in regulating Ca2+ homeostasis during the interplay between immune and cancer cells.
2015 (English)In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 19, no 6, article id e1648Article, review/survey (Refereed) Published
Abstract [en]

Ion channels are abundantly expressed in both excitable and non-excitable cells, thereby regulating the Ca2+ influx and downstream signaling pathways of physiological processes. The immune system is specialized in the process of cancer cell recognition and elimination, and is regulated by different ion channels. In comparison with the immune cells, ion channels behave differently in cancer cells by making the tumor cells more hyperpolarized and influence cancer cell proliferation and metastasis. Therefore, ion channels comprise an important therapeutic target in anti-cancer treatment. In this review, we discuss the implication of ion channels in regulation of Ca2+ homeostasis during the crosstalk between immune and cancer cell as well as their role in cancer progression.

Keywords
ion channels, cancer, Ca2+-influx, cytotoxic T cells, natural killer cells, anti-cancer immunity
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-115101 (URN)10.1038/cddis.2015.23 (DOI)000350575800022 ()25695601 (PubMedID)
Available from: 2015-03-08 Created: 2015-03-08 Last updated: 2017-12-04Bibliographically approved
Shakeri, R., Hosseinkhani, S., Los, M. J., Davoodi, J., Jain, M. V., Cieslar-Pobuda, A., . . . Kaboudanian Ardestani, S. (2015). Role of the salt bridge between glutamate 546 and arginine 907 in preservation of autoinhibited form of Apaf-1. International Journal of Biological Macromolecules, 81, 370-374
Open this publication in new window or tab >>Role of the salt bridge between glutamate 546 and arginine 907 in preservation of autoinhibited form of Apaf-1
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2015 (English)In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 81, p. 370-374Article in journal (Refereed) Published
Abstract [en]

Apaf-1, the key element of apoptotic mitochondrial pathway, normally exists in an auto-inhibited form inside the cytosol. WRD-domain of Apaf-1 has a critical role in the preservation of auto-inhibited form; however the underlying mechanism is unclear. It seems the salt bridges between WRD and NOD domains are involved in maintaining the inactive conformation of Apaf-1. At the present study, we have investigated the effect of E546-R907 salt bridge on the maintenance of auto-inhibited form of human Apaf-1. E546 is mutated to glutamine (Q) and arginine (R). Over-expression of wild type Apaf-1 and its E546Q and E546R variants in HEK293T cells does not induce apoptosis unlike - HL-60 cancer cell line. In vitro apoptosome formation assay showed that all variants are cytochrome c and dATP dependent to form apoptosome and activate endogenous procaspase-9 in Apaf-1-knockout MEF cell line. These results suggest that E546 is not a critical residue for preservation of auto-inhibited Apaf-1. Furthermore, the behavior of Apaf-1 variants for in vitro apoptosome formation in HEK293T cell is similar to exogenous wild type Apaf-1. Wild type and its variants can form apoptosome in HEK293T cell with different procaspase-3 processing pattern in the presence and absence of exogenous cytochrome c and dATP. (C) 2015 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2015
Keywords
Apaf-1; Apoptosome; Caspase-9
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-124522 (URN)10.1016/j.ijbiomac.2015.08.027 (DOI)000367408300045 ()26277751 (PubMedID)
Note

Funding Agencies|Research Council of University of Tehran; Tarbiat Modares University; Linkoping University; Integrative Regenerative Medicine Center (IGEN); Cancerfonden [2013/391]; VR-NanoVision [K2012-99X-22325-01-5]

Available from: 2016-02-02 Created: 2016-02-01 Last updated: 2017-11-30
Cieślar-Pobuda, A., Vilas Jain, M., Kratz, G., Rzeszowska-Wolny, J., Ghavami, S. & Wiechec, E. (2015). The expression pattern of PFKFB3 enzyme distinguishes between induced-pluripotent stem cells and cancer stem cells.. OncoTarget, 6(30), 29753--29770
Open this publication in new window or tab >>The expression pattern of PFKFB3 enzyme distinguishes between induced-pluripotent stem cells and cancer stem cells.
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2015 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 30, p. 29753--29770Article in journal (Refereed) Published
Abstract [en]

Induced pluripotent stem cells (iPS) have become crucial in medicine and biology. Several studies indicate their phenotypic similarities with cancer stem cells (CSCs) and a propensity to form tumors. Thus it is desirable to identify a trait which differentiates iPS populations and CSCs. Searching for such a feature, in this work we compare the restriction (R) point-governed regulation of cell cycle progression in different cell types (iPS, cancer, CSC and normal cells) based on the expression profile of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3) and phosphofructokinase (PFK1). Our study reveals that PFKFB3 and PFK1 expression allows discrimination between iPS and CSCs. Moreover, cancer and iPS cells, when cultured under hypoxic conditions, alter their expression level of PFKFB3 and PFK1 to resemble those in CSCs. We also observed cell type-related differences in response to inhibition of PFKFB3. This possibility to distinguish CSC from iPS cells or non-stem cancer cells by PFKB3 and PFK1 expression improves the outlook for clinical application of stem cell-based therapies and for more precise detection of CSCs.

Place, publisher, year, edition, pages
Albany, NY, USA: Impact Journals LLC, 2015
Keywords
PFKFB3; R-point; cancer stem cells; induced pluripotent stem cells
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-121349 (URN)10.18632/oncotarget.4995 (DOI)000363183200098 ()26337471 (PubMedID)
Available from: 2015-09-14 Created: 2015-09-14 Last updated: 2018-01-11Bibliographically approved
Cieslar-Pobuda, A., Bäck, M., Magnusson, K., Vilas Jain, M., Rafat, M., Ghavami, S., . . . Los, M. J. (2014). Cell Type Related Differences in Staining with Pentameric Thiophene Derivatives. Cytometry Part A, 85A(7), 628-635
Open this publication in new window or tab >>Cell Type Related Differences in Staining with Pentameric Thiophene Derivatives
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2014 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 85A, no 7, p. 628-635Article in journal (Refereed) Published
Abstract [en]

Fluorescent compounds capable of staining cells selectively without affecting their viability are gaining importance in biology and medicine. Recently, a new family of optical dyes, denoted luminescent conjugated oligothiophenes (LCOs), has emerged as an interesting class of highly emissive molecules for studying various biological phenomena. Properly functionalized LCOs have been utilized for selective identification of disease-associated protein aggregates and for selective detection of distinct cells. Herein, we present data on differential staining of various cell types, including cancer cells. The differential staining observed with newly developed pentameric LCOs is attributed to distinct side chain functionalities along the thiophene backbone. Employing flow cytometry and fluorescence microscopy we examined a library of LCOs for stainability of a variety of cell lines. Among tested dyes we found promising candidates that showed strong or moderate capability to stain cells to different extent, depending on target cells. Hence, LCOs with diverse imidazole motifs along the thiophene backbone were identified as an interesting class of agents for staining of cancer cells, whereas LCOs with other amino acid side chains along the backbone showed a complete lack of staining for the cells included in the study. Furthermore, for p-HTMI,a LCO functionalized with methylated imidazole moieties, the staining was dependent on the p53 status of the cells, indicating that the molecular target for the dye is a cellular component regulated by p53. We foresee that functionalized LCOs will serve as a new class of optical ligands for fluorescent classification of cells and expand the toolbox of reagents for fluorescent live imaging of different cells.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014
Keywords
cancer stem cells; luminescent conjugated oligothiophenes; fluorescent probes
National Category
Clinical Medicine Chemical Sciences Medical Biotechnology Computer and Information Sciences
Identifiers
urn:nbn:se:liu:diva-109171 (URN)10.1002/cyto.a.22437 (DOI)000338007700010 ()24500794 (PubMedID)
Available from: 2014-08-12 Created: 2014-08-11 Last updated: 2018-01-11Bibliographically approved
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