Leela Morena MD , Isabella Ferlini Cieri MD , Daniel Marconi Mendes PhD , Sasha P. Suarez Ferreira MD , Shiv Patel BS , Samir Ghandour MD , Maria Fernanda Andrade BS , Mohit Manchella BS , Adriana A. Rodriguez MD , Henry Davies MBBS, MD, MRSC , Shruti Sharma PhD , Anahita Dua MD, MS, MBA
{"title":"The impact of platelets and antiplatelets medications on immune mediation","authors":"Leela Morena MD , Isabella Ferlini Cieri MD , Daniel Marconi Mendes PhD , Sasha P. Suarez Ferreira MD , Shiv Patel BS , Samir Ghandour MD , Maria Fernanda Andrade BS , Mohit Manchella BS , Adriana A. Rodriguez MD , Henry Davies MBBS, MD, MRSC , Shruti Sharma PhD , Anahita Dua MD, MS, MBA","doi":"10.1016/j.jvssci.2024.100278","DOIUrl":"10.1016/j.jvssci.2024.100278","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the mechanisms through which platelets and antiplatelet therapies modulate the immune response and propose directions for future research in this field, with a particular emphasis on their impact on treatment efficacy and surgical outcomes.</div></div><div><h3>Methods</h3><div>A comprehensive review of recent studies investigating the role of platelets in immune modulation, specifically highlighting their involvement in pathogen recognition, leukocyte recruitment, and lymphocyte activation. Additionally, the review evaluates the impact of antiplatelet therapies, such as aspirin, P2Y12 inhibitors, and glycoprotein IIb/IIIa inhibitors, on immune responses.</div></div><div><h3>Results</h3><div>Recent studies have emphasized the critical role of platelets in immune-driven applications, namely, atherosclerosis, cancer, viral infections, and sepsis. These studies also suggest that antiplatelet therapies may alter immune responses. However, the precise mechanisms through which platelets and antiplatelet drugs influence immune responses, as well as their effects on post-treatment and surgical outcomes, are not yet fully elucidated.</div></div><div><h3>Conclusions</h3><div>Recent studies highlight the important role of platelets in immune processes, such as in atherosclerosis, cancer, viral infections, and sepsis, and suggest that antiplatelet therapies can influence immune responses. However, the exact mechanisms by which platelets and antiplatelet drugs modulate these responses remain unclear. This area presents valuable opportunities for future research to uncover these mechanisms, which could lead to novel therapeutic strategies and better clinical outcomes for patients.</div></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100278"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul Cyréus MSc , Katarina Wadén MD , Sofie Hellberg MSc , Otto Bergman PhD , Mariette Lengquist MSc , Eva Karlöf MD, PhD , Andrew Buckler PhD , Ljubica Matic PhD , Joy Roy MD, PhD , David Marlevi PhD , Melody Chemaly PhD , Ulf Hedin MD, PhD
{"title":"Atherosclerotic plaque instability in symptomatic non-significant carotid stenoses","authors":"Paul Cyréus MSc , Katarina Wadén MD , Sofie Hellberg MSc , Otto Bergman PhD , Mariette Lengquist MSc , Eva Karlöf MD, PhD , Andrew Buckler PhD , Ljubica Matic PhD , Joy Roy MD, PhD , David Marlevi PhD , Melody Chemaly PhD , Ulf Hedin MD, PhD","doi":"10.1016/j.jvssci.2025.100280","DOIUrl":"10.1016/j.jvssci.2025.100280","url":null,"abstract":"<div><h3>Objective</h3><div>Carotid endarterectomy for symptomatic carotid stenosis is recommended for patients with >70% stenosis, but not in those with <50%. Because non-significant, low-degree stenoses may still cause strokes, refined risk stratification is necessary, which could be improved by assessing biological features of plaque instability. To challenge risk-stratification based on luminal narrowing, we compared biological features of carotid plaques from symptomatic patients with low-degree (<50%) vs high-degree (>70%) stenosis and explored potential mechanisms behind plaque instability in low-degree stenoses.</div></div><div><h3>Methods</h3><div>Endarterectomy specimens were taken from symptomatic patients with high-degree (n = 204) and low-degree (n = 34) stenosis, all part of the Biobank of Karolinska Endarterectomies. Patient demographics, image-derived plaque morphology, and gene expression analyses of extracted lesions were used for comparisons. Plaque biology was assessed by transcriptomics using dimensionality reduction, differential gene expression, and gene-set enrichment analyses. Immunohistochemistry was used to study proteins corresponding to upregulated genes.</div></div><div><h3>Results</h3><div>The demographics of the two groups were statistically similar. Calcification, lipid-rich necrotic core, intraplaque hemorrhage, plaque burden, and fibrous cap thickness were similar in both groups, whereas the sum of lipid-rich necrotic core and intraplaque hemorrhage was higher (<em>P</em> = .033) in the high-degree stenosis group. Dimensionality reduction analysis indicated poor clustering separation of plaque gene expression in low-compared with high-degree stenosis lesions, whereas differential gene expression showed upregulation of hypoxia-inducible factor 3A (log<sub>2</sub> fold change, 0.7212; <em>P</em> = .0003), and gene-set enrichment analyses identified pathways related to tissue hypoxia and angiogenesis in low-degree stenoses. Hypoxia-inducible factor 3-alpha protein was associated with smooth muscle cells in neo-vascularized plaque regions.</div></div><div><h3>Conclusions</h3><div>Plaques from symptomatic patients with non-significant low-degree carotid stenoses showed morphologic and biological features of atherosclerotic plaque instability that were comparable to plaques from patients with high-degree stenoses, emphasizing the need for improved stroke risk stratification for intervention in all patients with symptomatic carotid stenosis irrespective of luminal narrowing. An increased expression of hypoxia-inducible factor 3A in low-degree stenotic lesions suggested mechanisms of plaque instability associated with tissue hypoxia and plaque angiogenesis, but the exact role of hypoxia-inducible factor 3A in this process remains to be determined.</div></div><div><h3>Clinical relevance</h3><div>Carotid plaques from symptomatic patients with <50% stenosis show morphologic and biological features of plaque ","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"6 ","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403650","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":"Toll-Like Receptor 4, a potential therapeutic target of lower limb ischemic myopathy that raises further questions","authors":"Ali H. Hakim, Ulf Hedin","doi":"10.1016/j.jvssci.2024.100195","DOIUrl":"https://doi.org/10.1016/j.jvssci.2024.100195","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"60 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139824700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anand H. Brahmandam, Rafael Alves, Hao Liu, Luis Gonzalez, Y. Aoyagi, Yuichi Ohashi, John T. Langford, Carly Thaxton, R. Taniguchi, Weichang Zhang, Hualong Bai, B. Yatsula, Alan Dardik
{"title":"A central arteriovenous fistula reduces systemic hypertension in a mouse model","authors":"Anand H. Brahmandam, Rafael Alves, Hao Liu, Luis Gonzalez, Y. Aoyagi, Yuichi Ohashi, John T. Langford, Carly Thaxton, R. Taniguchi, Weichang Zhang, Hualong Bai, B. Yatsula, Alan Dardik","doi":"10.1016/j.jvssci.2024.100191","DOIUrl":"https://doi.org/10.1016/j.jvssci.2024.100191","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"22 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139892707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao Luo, Fattah Muhammad Tahabi, Dave M. Rollins, A. Sawchuk
{"title":"Predicting Future Occlusion or Stenosis of Lower Extremity Bypass Grafts Using Artificial Intelligence to Simultaneously Analyze All Flow Velocities Collected in Current and Previous Ultrasound Exams","authors":"Xiao Luo, Fattah Muhammad Tahabi, Dave M. Rollins, A. Sawchuk","doi":"10.1016/j.jvssci.2024.100192","DOIUrl":"https://doi.org/10.1016/j.jvssci.2024.100192","url":null,"abstract":"","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"72 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139874367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dahlia M. Kenawy MD , Jordan F. Stafford MD , Foued Amari MS , Drayson Campbell BS , Mahmoud Abdel-Rasoul MS, MPH , Jennifer Leight PhD , Youngjae Chun PhD , Bryan W. Tillman MD, PhD
{"title":"A porcine model of thoracic aortic aneurysms created with a retrievable drug infusion stent graft mirrors human aneurysm pathophysiology","authors":"Dahlia M. Kenawy MD , Jordan F. Stafford MD , Foued Amari MS , Drayson Campbell BS , Mahmoud Abdel-Rasoul MS, MPH , Jennifer Leight PhD , Youngjae Chun PhD , Bryan W. Tillman MD, PhD","doi":"10.1016/j.jvssci.2024.100212","DOIUrl":"10.1016/j.jvssci.2024.100212","url":null,"abstract":"<div><h3>Objective</h3><p>Aneurysm pathophysiology remains poorly understood, in part from the disparity of murine models with human physiology and the requirement for invasive aortic exposure to apply agents used to create aneurysm models. A retrievable drug infusion stent graft (RDIS) was developed to isolate the aortic wall intraluminally for drug exposure. We hypothesized that an RDIS could deliver aneurysm-promoting enzymes to create a porcine model of thoracic aneurysms without major surgical exposure.</p></div><div><h3>Methods</h3><p>Retrievable nitinol stent graft frames were designed with an isolated drug delivery chamber, covered with polytetrafluoroethylene, and connected to a delivery wire with a drug infusion catheter installed to the outer chamber. Institutional Animal Care and Use Committee-approved Yorkshire pigs (n = 5) underwent percutaneous access of the femoral artery, baseline aortogram and stent placement in the thoracic aorta followed by 30-minute exposure to a cocktail of elastase, collagenase, and trypsin. After aspiration of excess drug, stent retrieval, and femoral artery repair, animals were recovered, with angiograms at 1 and 4 weeks followed by explant. Histological analysis, in situ zymography, and multiplex cytokine assays were performed.</p></div><div><h3>Results</h3><p>The RDIS isolated a segment of anterior aorta angiographically, while the center lumen preserved distal perfusion during drug treatment (baseline femoral mean arterial pressure, 70 ± 14 mm Hg; after RDIS, 75 ± 12; <em>P</em> = .55). Endovascular induction of thoracic aneurysms did not require prior mechanical injury and animals revealed no evidence of toxicity. Within 1 week, significant aneurysmal growth was observed in all five animals (1.4 ± 0.1 cm baseline to 2.9 ± 0.7 cm; <em>P</em> = .002) and only within the treated region of the aorta. Aneurysms persisted out to 4 weeks. Aneurysm histology demonstrated loss of elastin and collagen that was otherwise preserved in untreated aorta. Proinflammatory cytokines and increased matrix metalloproteinase activity were increased significantly within the aneurysm.</p></div><div><h3>Conclusions</h3><p>An RDIS achieves isolated drug delivery while preserving distal perfusion to achieve an endovascular porcine model of thoracic aneurysms without major surgery. This model may have value for surgical training, device testing, and to better understand aneurysm pathogenesis. Most important, although the RDIS was used to simulate aortic pathology, this tool offers intriguing horizons for focused therapeutic drug delivery directly to aneurysms and, more broadly, focused locoregional drug delivery to vessels and vascular beds.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100212"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350324000233/pdfft?md5=081f8c71c9fcfe81f38b0cc25693ed2d&pid=1-s2.0-S2666350324000233-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141715761","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}
Anand Brahmandam MD , Joshua Huttler BA , Kirthi Bellamkonda MSc , Ocean Setia MD , Jonathan A. Cardella MD , William Stewart PhD , Raul J. Guzman MD , Cassius Iyad Ochoa Chaar MD, MS, MPH
{"title":"The radiographic relationship of the femoral head, inguinal ligament, and common femoral artery bifurcation for optimal vascular access","authors":"Anand Brahmandam MD , Joshua Huttler BA , Kirthi Bellamkonda MSc , Ocean Setia MD , Jonathan A. Cardella MD , William Stewart PhD , Raul J. Guzman MD , Cassius Iyad Ochoa Chaar MD, MS, MPH","doi":"10.1016/j.jvssci.2024.100196","DOIUrl":"10.1016/j.jvssci.2024.100196","url":null,"abstract":"<div><h3>Objective</h3><p>Common femoral artery (CFA) access is commonly used for endovascular interventions. Access site complications contribute to significant morbidity and mortality. This study characterizes the radiographic variability in the relationship of the femoral head, the inguinal ligament, and the CFA bifurcation, to identify the zone of optimal CFA access.</p></div><div><h3>Methods</h3><p>Human cadaver dissection of the inguinal ligament and CFA bifurcation was performed. The inguinal ligament and CFA bifurcation were marked with radiopaque pins and plain anteroposterior radiographs were obtained. Radiographic measurements of the femoral head length, the distance of the top of the femoral head to the inguinal ligament, and to the CFA bifurcation were obtained. Results were reported as percentage of femoral head covered by the inguinal ligament or the CFA bifurcation relative to the top of the femoral head. A heatmap was derived to determine a safe access zone between the inguinal ligament and CFA bifurcation.</p></div><div><h3>Results</h3><p>Forty-five groin dissections (male, n = 20; female, n = 25) were performed in 26 cadavers. The mean overlap of the inguinal ligament with the femoral head was 11.2 mm (range, −19.4 to 27.4 mm). There were no age (<85 vs ≥85 years) or sex-related differences. In 82.6% of cadaveric CFA exposures, there was overlap between the inguinal ligament and femoral head (mean, 27.7%; range, −85.7% to 70.1%), with 55.6% having a >25% overlap. In 11.1%, there was an overlap between the lower one-third of the femoral head and the CFA bifurcation. Cumulatively, heatmap analysis depicted a >80% likelihood of avoiding the inguinal ligament and CFA bifurcation below the midpoint of the femoral head.</p></div><div><h3>Conclusions</h3><p>Significant variability exists in the relationship between the inguinal ligament, CFA bifurcation, and the femoral head, suggesting the lack of a consistently safe access zone. The safest access zone in >80% of patients lies below the radiographic midpoint of the femoral head and the inferior aspect of the femoral head.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100196"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350324000075/pdfft?md5=74563e889c098870416176f9c73dad33&pid=1-s2.0-S2666350324000075-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140462865","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}
Mengjun Wang MD , Xiao Lu PhD , Ling Han BS , José A. Diaz MD , Seshadri Raju MD , Ghassan S. Kassab PhD
{"title":"Venous thromboembolism swine model with reflux-induced venous hypertension","authors":"Mengjun Wang MD , Xiao Lu PhD , Ling Han BS , José A. Diaz MD , Seshadri Raju MD , Ghassan S. Kassab PhD","doi":"10.1016/j.jvssci.2024.100200","DOIUrl":"10.1016/j.jvssci.2024.100200","url":null,"abstract":"<div><h3>Objective</h3><p>This study describes a novel swine model of venous thromboembolism (VTE) with reflux-induced venous hypertension.</p></div><div><h3>Methods</h3><p>Six pigs underwent disruption of the tricuspid chordae tendineae to create reflux and venous hypertension in the femoral vein. The vein was traumatized 2 to 3 weeks later by repeated withdrawal of a slightly overinflated occlusion balloon across the lumen, followed by balloon occlusion of the outflow. A small amount of thrombin was injected into the traumatized vein segment immediately after outflow occlusion. Thrombosis of the traumatized vein evolved into an organized thrombus seven weeks later. The histological features of the harvested post-thrombotic femoral vein were studied with hematoxylin and eosin and Trichrome stains.</p></div><div><h3>Results</h3><p>In all six pigs, initial disruption of the chordae tendineae was successfully performed to create tricuspid reflux and venous hypertension. After two-stage sequential procedures, a thrombus formed in the target femoral vein segment. Histology of the harvested thrombotic vein showed features of an organizing thrombus with collagen formation and fibrosis.</p></div><div><h3>Conclusions</h3><p>The novel swine VTE model may serve as a platform for developing and testing human-sized therapeutic procedures and devices in translational venous research.</p></div><div><h3>Clinical Relevance</h3><p>This study describes a swine model of VTE created by incorporating all three elements of Virchow’s triad. The model uniquely incorporates reflux-induced venous hypertension, which may be used in studying venous insufficiency and VTE in those with systemic venous hypertension. Likewise, this model may serve as a platform for development and evaluation of diagnostic imaging or therapeutic procedures and devices in subjects with systemic venous hypertension.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100200"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666350324000117/pdfft?md5=e4da82e55e93a6015beb2e6e9d227379&pid=1-s2.0-S2666350324000117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140273276","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}
Sean M. Carr PhD , Katherine Owsiany MD, PhD , Ottis Scrivner PhD , Dylan McLaughlin MD , Hanjoong Jo PhD , Luke P. Brewster , Katherine E. Hekman MD, PhD
{"title":"Hyperoxia impairs induced pluripotent stem cell-derived endothelial cells and drives an atherosclerosis-like transcriptional phenotype","authors":"Sean M. Carr PhD , Katherine Owsiany MD, PhD , Ottis Scrivner PhD , Dylan McLaughlin MD , Hanjoong Jo PhD , Luke P. Brewster , Katherine E. Hekman MD, PhD","doi":"10.1016/j.jvssci.2024.100193","DOIUrl":"10.1016/j.jvssci.2024.100193","url":null,"abstract":"<div><h3>Background</h3><p>Induced pluripotent stem cells (iPSCs) directed to endothelial identity (iPSC-ECs) are emerging as a potent tool for regenerative medicine in vascular disease. However, iPSC-ECs lose expression of key identity markers under standard in vitro conditions, limiting their clinical applications.</p></div><div><h3>Methods</h3><p>To model physiological in vivo conditions, we examined the bioenergetics, presence of key cell markers, and proliferative and angiogenic capacity in iPSC-ECs at late and early passage under hyperoxic (21%) and physiological (4%) oxygen concentrations.</p></div><div><h3>Results</h3><p>Physoxia resulted in relative preservation of mitochondrial bioenergetic activity, as well as CD144 expression in late passage iPSC-ECs, but not proliferative capacity or tube formation. Single cell RNA sequencing (scRNA-seq) revealed that late passage hyperoxic iPSC-ECs develop an endothelial-to-mesenchymal phenotype. Comparing scRNA-seq data from iPSC-ECs and from atherosclerotic ECs revealed overlap of their transcriptional phenotypes.</p></div><div><h3>Conclusions</h3><p>Taken together, our studies demonstrate that physiological 4% oxygen culture conditions were sufficient to improve mitochondrial function in high passage cells, but alone was insufficient to preserve angiogenic capacity. Furthermore, late passage cells under typical conditions take on an endothelial-to-mesenchymal phenotype with similarities to ECs found in atherosclerosis.</p></div>","PeriodicalId":74035,"journal":{"name":"JVS-vascular science","volume":"5 ","pages":"Article 100193"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266635032400004X/pdfft?md5=8e5c3056fafd9f25b14200fbd26c3111&pid=1-s2.0-S266635032400004X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140279855","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}