Vascular Cell最新文献

{"title":"Endothelial cell senescence is associated with disrupted cell-cell junctions and increased monolayer permeability.","authors":"Vincent J D Krouwer,&nbsp;Liesbeth H P Hekking,&nbsp;Miriam Langelaar-Makkinje,&nbsp;Elsa Regan-Klapisz,&nbsp;Jan Andries Post","doi":"10.1186/2045-824X-4-12","DOIUrl":"https://doi.org/10.1186/2045-824X-4-12","url":null,"abstract":"<p><strong>Unlabelled: </strong></p><p><strong>Background: </strong>Cellular senescence is associated with cellular dysfunction and has been shown to occur in vivo in age-related cardiovascular diseases such as atherosclerosis. Atherogenesis is accompanied by intimal accumulation of LDL and increased extravasation of monocytes towards accumulated and oxidized LDL, suggesting an affected barrier function of vascular endothelial cells. Our objective was to study the effect of cellular senescence on the barrier function of non-senescent endothelial cells.</p><p><strong>Methods: </strong>Human umbilical vein endothelial cells were cultured until senescence. Senescent cells were compared with non-senescent cells and with co-cultures of non-senescent and senescent cells. Adherens junctions and tight junctions were studied. To assess the barrier function of various monolayers, assays to measure permeability for Lucifer Yellow (LY) and horseradish peroxidase (PO) were performed.</p><p><strong>Results: </strong>The barrier function of monolayers comprising of senescent cells was compromised and coincided with a change in the distribution of junction proteins and a down-regulation of occludin and claudin-5 expression. Furthermore, a decreased expression of occludin and claudin-5 was observed in co-cultures of non-senescent and senescent cells, not only between senescent cells but also along the entire periphery of non-senescent cells lining a senescent cell.</p><p><strong>Conclusions: </strong>Our findings show that the presence of senescent endothelial cells in a non-senescent monolayer disrupts tight junction morphology of surrounding young cells and increases the permeability of the monolayer for LY and PO.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30863120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cooperative benefit for the combination of rapamycin and imatinib in tuberous sclerosis complex neoplasia.","authors":"Baskaran Govindarajan,&nbsp;Laura Willoughby,&nbsp;Hamid Band,&nbsp;Adam S Curatolo,&nbsp;Emir Veledar,&nbsp;Suephy Chen,&nbsp;Michael Y Bonner,&nbsp;Martin-Garrido Abel,&nbsp;Marsha A Moses,&nbsp;Jack L Arbiser","doi":"10.1186/2045-824X-4-11","DOIUrl":"https://doi.org/10.1186/2045-824X-4-11","url":null,"abstract":"<p><p> Tuberous sclerosis (TS) is a common autosomal-dominant disorder characterized by tumors of the skin, lung, brain, and kidneys. Monotherapy with rapamycin however resulted in partial regression of tumors, implying the involvement of additional pathways. We have previously implicated platelet-derived growth factor-BB in TS-related tumorigenesis, thus providing a rationale for a combination of mTOR/PDGF blockade using rapamycin and imatinib. Here, we test this combination using a well-established preclinical model of cutaneous tumorigenesis in TS, tsc2ang1 cells derived from a skin tumor from a mouse heterozygous for tsc2. Treatment of tsc2ang1 cells with a combination of rapamycin and imatinib led to an inhibition of proliferation compared with either vehicle treatment or treatment with rapamycin or imatinib monotherapy. Combination therapy also led to a decrease in Akt activation. Potent in vivo activity in animal experiments by combination therapy was noted, without toxicity to the animals. Our findings provide a rationale for the combined use of rapamycin and imatinib, both FDA approved drugs, for the treatment of TS.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30739803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The angiogenic response is dependent on ultrasound contrast agent concentration.","authors":"Chenara A Johnson,&nbsp;William D O'Brien","doi":"10.1186/2045-824X-4-10","DOIUrl":"https://doi.org/10.1186/2045-824X-4-10","url":null,"abstract":"<p><strong>Objective: </strong>Ultrasound (US) and ultrasound contrast agents (UCAs) provide a way to noninvasively induce targeted angiogenesis. However, there exists a lack of understanding regarding the mechanisms of this process that has impeded progress. This study sought to characterize the angiogenic response, by both exploring the role of UCA concentration ([UCA]) in bioeffect induction at 0 days post exposure (DPE) and assessing the bioeffect as a possible potentiator of angiogenesis at 5 DPE.</p><p><strong>Methods: </strong>A 1-MHz ultrasonic transducer was used to expose the gracilis muscles of Sprague Dawley rats for 5 min with a 10-μs pulse duration, 10-Hz pulse repetition frequency, and 0.7-MPa peak rarefactional acoustic pressure (pr). Four [UCA]s were tested: 0x (saline), 1×, 5×, and 10×, where 1× is 5% Definity by volume of solution. Evans blue dye (EBD) was used to quantify changes in acute vascular permeability (0 DPE), and VEGF expression was quantified at 5 DPE to support that angiogenesis had occurred. CD31 staining was used to assess capillary density at both time points.</p><p><strong>Results: </strong>[UCA] was a significant parameter for determining EBD leakage (permeability) and VEGF expression (p < 0.001 for both). However, [UCA] was not a significant parameter for capillary density at 0 or 5 DPE. Multiple comparisons between 0 and 5 DPE showed that only 10× [UCA] at 5 DPE was significantly different than 0 DPE, suggesting a [UCA] dependence of the angiogenic response.</p><p><strong>Conclusions: </strong>This study suggests that [UCA] was a significant parameter in the induction of an angiogenic response with US and UCAs. It also suggests that rather than damage from US and UCAs, as previously speculated, a nondestructive mechanical interaction between the UCAs and vascular endothelium induces bioeffects to potentiate the angiogenic response.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30619413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unique vascular protective properties of natural products: supplements or future main-line drugs with significant anti-atherosclerotic potential?","authors":"Mark Slevin, Nessar Ahmed, Qiuyu Wang, Garry McDowell, Lina Badimon","doi":"10.1186/2045-824X-4-9","DOIUrl":"10.1186/2045-824X-4-9","url":null,"abstract":"<p><p> Natural health products (NHP) which include minerals, vitamins and herbal remedies are not generally considered by medical practitioners as conventional medicines and as such are not frequently prescribed by health centre's as either main-line or supplemental treatments. In the field of cardiovascular medicine, studies have shown that typically, less than half of patients suffering from coronary syndromes chose to take any form of NHP supplement and these products are rarely recommended by their medical practitioner. Vascular/endothelial cell damage is a key instigator of coronary arterial plaque development which often culminates in thrombosis and myocardial infarction (MI). Current treatment for patients known to be at risk of primary or secondary (MI) includes lipid lowering statins, anti-clotting agents (e.g. tissue plasminogen activator; tPA) and drugs for stabilization of blood pressure such as beta-blockers. However, evidence has been building which suggests that components of at least several NHP (e.g. aged garlic extract (AGExt), resveratrol and green tea extracts (GTE)) may have significant vascular protective effects through reduction of oxidative stress, lowering of blood pressure, reduction in platelet aggregation, vasodilation and inhibition of abnormal angiogenesis. Therefore, in this review we will discuss in detail the potential of these substances (chosen on the basis of their potency and complimentarity) as anti-atherosclerotic agents and the justification for their consideration as main-line additional supplements or prescriptions.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40192938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiogenic efficacy of Heparin on chick chorioallantoic membrane.","authors":"Reji Bhuvanendran Rema, Karthick Rajendran, Malathi Ragunathan","doi":"10.1186/2045-824X-4-8","DOIUrl":"10.1186/2045-824X-4-8","url":null,"abstract":"<p><p> Heparin is an anticoagulant agent known to have diverse effects on angiogenesis with some reports suggesting that it can induce angiogenesis while a few have indicated of its inhibitory property. Cancer patients treated for venous thromboembolism with low molecular heparin had a better survival than the unfractionated heparin (UFH). Heparin is known to interact with various angiogenic growth factors based on its sulfation modifications within the glycosaminoglycan chains. Therefore it is important to study the mechanism of action of heparin of different molecular weight to understand its angiogenic property. In this concern, we examined the angiogenic response of higher molecular weight Heparin (15 kDa) of different concentrations using late CAM assay. Growth of blood vessels in terms of their length and size was measured and thickness of the CAM was calculated morphometrically. The observed increase in the thickness of the CAM is suggestive of the formation of capillary like structures at the treated region. Analysis of the diffusion pattern showed internalized action of heparin that could affect gene expression leading to proliferation of endothelial cells. Angiogenesis refers to formation of new blood vessels from the existing ones and occurrence of new blood vessels at the treated area strongly confirms that heparin of 15 kDa molecular weight has the ability to induce angiogenesis on CAM vascular bed in a dose dependent manner. The results demonstrate the affinity of heparin to induce angiogenesis and provide a novel mechanism by which heparin could be used in therapeutics such as in wound healing process.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30583210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notch signals in the endothelium and cancer \"stem-like\" cells: opportunities for cancer therapy.","authors":"Jian-Wei Gu,&nbsp;Paola Rizzo,&nbsp;Antonio Pannuti,&nbsp;Todd Golde,&nbsp;Barbara Osborne,&nbsp;Lucio Miele","doi":"10.1186/2045-824X-4-7","DOIUrl":"https://doi.org/10.1186/2045-824X-4-7","url":null,"abstract":"<p><p> Anti-angiogenesis agents and the identification of cancer stem-like cells (CSC) are opening new avenues for targeted cancer therapy. Recent evidence indicates that angiogenesis regulatory pathways and developmental pathways that control CSC fate are intimately connected, and that endothelial cells are a key component of the CSC niche. Numerous anti-angiogenic therapies developed so far target the VEGF pathway. However, VEGF-targeted therapy is hindered by clinical resistance and side effects, and new approaches are needed. One such approach may be direct targeting of tumor endothelial cell fate determination. Interfering with tumor endothelial cells growth and survival could inhibit not only angiogenesis but also the self-replication of CSC, which relies on signals from surrounding endothelial cells in the tumor microenvironment. The Notch pathway is central to controlling cell fate both during angiogenesis and in CSC from several tumors. A number of investigational Notch inhibitors are being developed. Understanding how Notch interacts with other factors that control endothelial cell functions and angiogenesis in cancers could pave the way to innovative therapeutic strategies that simultaneously target angiogenesis and CSC.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30562277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Co-culture of Retinal and Endothelial Cells Results in the Modulation of Genes Critical to Retinal Neovascularization.","authors":"Ravindra Kumar,&nbsp;Sandra Harris-Hooker,&nbsp;Ritesh Kumar,&nbsp;Gary Sanford","doi":"10.1186/2045-824X-4-6","DOIUrl":"https://doi.org/10.1186/2045-824X-4-6","url":null,"abstract":"","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30530589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positron emission tomography detection of human endothelial cell and fibroblast monolayers: effect of pretreament and cell density on 18FDG uptake.","authors":"Julie A Chouinard,&nbsp;Jacques A Rousseau,&nbsp;Jean-François Beaudoin,&nbsp;Patrick Vermette,&nbsp;Roger Lecomte","doi":"10.1186/2045-824X-4-5","DOIUrl":"https://doi.org/10.1186/2045-824X-4-5","url":null,"abstract":"<p><strong>Background: </strong>The non-destructive assessment and characterization of tridimensional (3D) cell and tissue constructs in bioreactors represents a challenge in tissue engineering. Medical imaging modalities, which can provide information on the structure and function of internal organs and tissues in living organisms, have the potential of allowing repetitive monitoring of these 3D cultures in vitro. Positron emission tomography (PET) is the most sensitive non-invasive imaging modality, capable of measuring picomolar amounts of radiolabeled molecules. However, since PET imaging protocols have been designed almost exclusively for in vivo investigations, suitable methods must be devised to enable imaging of cells or tissue substitutes. As a prior step to imaging 3D cultures, cell radiotracer uptake conditions must first be optimized.</p><p><strong>Methods: </strong>In this study, human umbilical vein endothelial cells (HUVEC) and human fibroblasts were cultured at different densities and PET was used to non-destructively monitor their glycolytic activity by measuring 18F-fluorodeoxyglucose (18FDG) uptake. Various cell preconditioning protocols were investigated by adjusting the following parameters to optimize 18FDG uptake: glucose starvation, insulin stimulation, glucose concentration, 18FDG incubation time, cell density and radiotracer efflux prevention.</p><p><strong>Results: </strong>The conditions yielding optimal 18FDG uptake, and hence best detection sensitivity by PET, were as follows: 2-hour cell preconditioning by glucose deprivation with 1-hour insulin stimulation, followed by 1-hour 18FDG incubation and 15-minute stabilization in standard culture medium, prior to rinsing and PET scanning.</p><p><strong>Conclusions: </strong>A step-wise dependence of 18FDG uptake on glucose concentration was found, but a linear correlation between PET signal and cell density was observed. Detection thresholds of 36 ± 7 and 21 ± 4 cells were estimated for endothelial cells and fibroblasts, respectively.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30515694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pleiotrophin expression and role in physiological angiogenesis in vivo: potential involvement of nucleolin.","authors":"Marina Koutsioumpa,&nbsp;Georgia Drosou,&nbsp;Constantinos Mikelis,&nbsp;Katerina Theochari,&nbsp;Dionussios Vourtsis,&nbsp;Panagiotis Katsoris,&nbsp;Efstathia Giannopoulou,&nbsp;Jose Courty,&nbsp;Christos Petrou,&nbsp;Vassiliki Magafa,&nbsp;Paul Cordopatis,&nbsp;Evangelia Papadimitriou","doi":"10.1186/2045-824X-4-4","DOIUrl":"https://doi.org/10.1186/2045-824X-4-4","url":null,"abstract":"<p><strong>Background: </strong>Pleiotrophin (PTN) is a heparin-binding growth factor with significant role(s) in tumour growth and angiogenesis. Although implication of endogenous PTN has been studied in several in vivo models of tumour angiogenesis, its role in physiological angiogenesis has not been addressed. In the present work, we studied expression and functional significance of endogenous PTN during angiogenesis in the chicken embryo chorioallantoic membrane (CAM).</p><p><strong>Methods: </strong>Using molecular, cellular and biochemical assays, we studied the expression pattern of PTN in CAM and human endothelial cells and its possible interaction with nucleolin (NCL). CAM cells were transfected with a pCDNA3.1 vector, empty (PC) or containing full length cDNA for PTN in antisense orientation (AS-PTN). Angiogenesis was estimated by measuring total vessel length. In vitro, human endothelial cells migration was studied by using a transwell assay, and down-regulation of NCL was performed by using a proper siRNA.</p><p><strong>Results: </strong>Endogenous PTN mRNA and protein levels, as well as protein levels of its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) were maximal at early stages, when CAM angiogenesis is active. Application of AS-PTN onto CAM at days of active angiogenesis was not toxic to the tissue and led to dose-dependent decreased expression of endogenous PTN, ERK1/2 activity and angiogenesis. Interestingly, endogenous PTN was also immunolocalized at the endothelial cell nucleus, possibly through interaction with NCL, a protein that has a significant role in the nuclear translocation of many proteins. Down-regulation of NCL by siRNA in human endothelial cells significantly decreased nuclear PTN, verifying this hypothesis. Moreover, it led to abolishment of PTN-induced endothelial cell migration, suggesting, for the first time, that PTN-NCL interaction has a functional significance.</p><p><strong>Conclusions: </strong>Expression of endogenous PTN correlates with and seems to be involved in angiogenesis of the chicken embryo CAM. Our data suggest that NCL may have a role, increasing the number of growth factors whose angiogenic/tumorigenic activities are mediated by NCL.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30506901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specific tumor-stroma interactions of EBV-positive Burkitt's lymphoma cells in the chick chorioallantoic membrane.","authors":"Jürgen Becker,&nbsp;Ana Covelo-Fernandez,&nbsp;Frederike von Bonin,&nbsp;Dieter Kube,&nbsp;Jörg Wilting","doi":"10.1186/2045-824X-4-3","DOIUrl":"https://doi.org/10.1186/2045-824X-4-3","url":null,"abstract":"<p><strong>Background: </strong>Burkitt's lymphoma (BL) is an aggressive Non-Hodgkin lymphoma. Epstein-Barr Virus (EBV) is able to transform B cells and is a causative infectious agent in BL. The precise role of EBV in lymphoma progression is still unclear. Most investigations have concentrated on cell autonomous functions of EBV in B cells. Functions of the local environment in BL progression have rarely been studied, mainly due to the lack of appropriate in vivo models. Therefore, we inoculated different human BL cell-lines onto the chorioallantoic membrane (CAM) of embryonic day 10 (ED10) chick embryos and re-incubated until ED14 and ED17.</p><p><strong>Results: </strong>All cell-lines formed solid tumors. However, we observed strong differences in the behavior of EBV+ and EBV- cell-lines. Tumor borders of EBV+ cells were very fuzzy and numerous cells migrated into the CAM. In EBV- tumors, the borders were much better defined. In contrast to EBV- cells, the EBV+ cells induced massive immigration of chick leukocytes at the tumor borders and the development of granulation tissue with large numbers of blood vessels and lymphatics, although the expression of pro- and anti-angiogenic forms of Vascular Endothelial Growth Factors/receptors was the same in all BL cell-lines tested. The EBV+ cell-lines massively disseminated via the lymphatics and completely occluded them.</p><p><strong>Conclusions: </strong>Our data suggest that the EBV+ cells attract pro-angiogenic leukocytes, which then induce secondary tumor-stroma interactions contributing to the progression of BL. We show that the CAM is a highly suitable in vivo model to study the differential behavior of BL cell-lines.</p>","PeriodicalId":23948,"journal":{"name":"Vascular Cell","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-824X-4-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40151709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}