Biomarkers in cancer最新文献

{"title":"Circulating MicroRNAs as Biomarkers in Diffuse Large B-cell Lymphoma: A Pilot Prospective Longitudinal Clinical Study.","authors":"Céline Bouvy, Adeline Wannez, Fabienne George, Carlos Graux, Christian Chatelain, Jean-Michel Dogné","doi":"10.1177/1179299X18781095","DOIUrl":"https://doi.org/10.1177/1179299X18781095","url":null,"abstract":"Objectives: Diffuse large B-cell lymphoma (DLBCL) is highly heterogeneous in terms of phenotype and treatment response in patients. These characteristics make the prognosis difficult to establish and hinder the use of new personalized treatments in clinical practice. In this context, there is currently a need to define new biomarkers enabling a better definition of DLBCL subtypes, prognosis evaluation, and an overview of the resistance to chemotherapeutics. The aim of this study was to evaluate the use of microRNAs found in plasma from patients with DLBCL as biomarkers of tumor evolution in these patients. Method: For this purpose, a plasma biobank was created with samples from patients with DLBCL. The evolution of the level of selected microRNAs during treatment has been studied. A total of 19 patients with DLBCL were included in this pilot mono-centered study and a total of 68 samples were analyzed. Results: The first step of this study was the selection of the microRNAs to be quantified in all the samples of the biobank and that could potentially be used as biomarkers. To this end, quantification of 377 microRNAs was performed on the plasma samples of 2 selected patients with DLBCL and 1 healthy donor with no history of cancer. Among the 377 microRNAs evaluated, 7 were selected and analyzed in the entire biobank. Conclusions: This study highlighted 5 circulating microRNAs whose plasma levels would be worth further investigating for the characterization of DLBCL evolution in patients. MiR-21 and miR-197 had a significant higher plasmatic level in patients with tumors unresponsive to treatment. With a higher plasma level in patients with complete remission, miR-19b, miR-20a, and miR-451 could enable to differentiate, at the remission review, patients with residual tumor, from patients with complete remission.","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179299X18781095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36287417","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":"Vasodilator-Stimulated Phosphoprotein Biomarkers Are Associated with Invasion and Metastasis in Colorectal Cancer.","authors":"Giovanni M Pitari, Paolo Cotzia, Mehboob Ali, Ruth Birbe, Wendy Rizzo, Alessandro Bombonati, Juan Palazzo, Charalambos Solomides, Anthony P Shuber, Frank A Sinicrope, David S Zuzga","doi":"10.1177/1179299X18774551","DOIUrl":"10.1177/1179299X18774551","url":null,"abstract":"<p><strong>Background and aims: </strong>The benefit of adjuvant chemotherapy for stage II colorectal cancer (CRC) patients remains unclear, emphasizing the need for improved prognostic biomarkers to identify patients at risk of metastatic recurrence. To address this unmet clinical need, we examined the expression and phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) in CRC tumor progression. VASP, a processive actin polymerase, promotes the formation of invasive membrane structures leading to extracellular matrix remodeling and tumor invasion. Phosphorylation of VASP serine (Ser) residues 157 and 239 regulate VASP function, directing subcellular localization and inhibiting actin polymerization, respectively.</p><p><strong>Methods: </strong>The expression levels of VASP protein, pSer¹⁵⁷-VASP, and pSer²³⁹-VASP were determined by immunohistochemistry in tumors and matched normal adjacent tissue from 141 CRC patients, divided into 2 cohorts, and the association of VASP biomarker expression with clinicopathologic features and disease recurrence was examined.</p><p><strong>Results: </strong>We report that changes in VASP expression and phosphorylation were significantly associated with tumor invasion and disease recurrence. Furthermore, we disclose a novel 2-tiered methodology to maximize VASP positive and negative predictive value performance for prognostication.</p><p><strong>Conclusion: </strong>VASP biomarkers may serve as prognostic biomarkers in CRC and should be evaluated in a larger clinical study.</p>","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/3c/10.1177_1179299X18774551.PMC6419247.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37265789","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":"Clean Colorectum at Diagnostic Colonoscopy: Subsequent Detection of Extracolonic Malignancies by Plasma Protein Biomarkers?","authors":"Michael Wilhelmsen,&nbsp;Ib J Christensen,&nbsp;Lars N Jørgensen,&nbsp;Mogens R Madsen,&nbsp;Jesper Vilandt,&nbsp;Thore Hillig,&nbsp;Michael Klærke,&nbsp;Knud T Nielsen,&nbsp;Søren Laurberg,&nbsp;Susan Gawel,&nbsp;Xiaoping Yang,&nbsp;Gerard Davis,&nbsp;Anne Meike Heijboer,&nbsp;Frans Martens,&nbsp;Hans J Nielsen","doi":"10.1177/1179299X18776974","DOIUrl":"https://doi.org/10.1177/1179299X18776974","url":null,"abstract":"<p><strong>Introduction: </strong>Most of the subjects undergoing diagnostic colonoscopy do not have neoplastic bowel lesions. Potentially, some of the symptoms may therefore be caused by extracolonic malignancy, and subjects with persisting symptoms may need subsequent examinations. Blood-based, cancer-associated biomarkers may aid in directing the examinations for other specific malignant diseases.</p><p><strong>Methods: </strong>EDTA plasma samples available from a previous prospective study of subjects undergoing diagnostic colonoscopy were used for analysis of 18 protein biomarkers. The study population of 3732 subjects included 400 patients with colorectal cancer (CRC) and 177 patients with extracolonic malignancies. Univariable analysis of the association of specific biomarkers and extracolonic cancers included those with 10 or more cases. Subsequently, reduced models of 4 or 6 biomarkers, respectively, were established by choosing those with the highest likelihood; age and sex were included as well.</p><p><strong>Results: </strong>Univariable analyses showed that CyFra21-1 had an area under curve (AUC) of 0.87 for lung cancers (n = 33), CA19-9 had an AUC of 0.85 for pancreatic cancer (n = 22), CA125 had an AUC of 0.95 for ovary cancer (n = 16), B2M had an AUC of 0.81 for non-Hodgkin lymphoma (n = 12), and total prostate-specific antigen had an AUC of 0.99 for prostate cancer (n = 10). The multivariable analysis of 4 or 6 biomarkers plus age and sex as explanatory variables showed AUCs of 0.82 to 0.85 both for extracolonic cancers and CRC. The 4 biomarkers included in the model for detection of extracolonic cancers were CA125, hsCRP, CA19-9, and CyFra21-1; the 2 additional for the 6 biomarkers model were CEA and Galectin-3. Similarly, the 4 biomarkers included in the model for detection of CRC were CEA, CyFra21-1, Ferritin, and HE4; the two additional for the 6 biomarkers model were hsCRP and Pepsinogen 2.</p><p><strong>Conclusions: </strong>Results of this study indicate that it may be possible to detect subjects that have an increased risk of extracolonic cancer following a colonoscopy without findings of neoplastic lesions. Combinations of various protein biomarkers may direct subsequent examination after colonoscopy with clean colorectum. The results, although preliminary, may form the basis for additional research directed both for primary examinations of subjects with symptoms of malignancy and subsequent examinations after colonoscopy.</p>","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179299X18776974","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36196094","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":"Data Mining of Small RNA-Seq Suggests an Association Between Prostate Cancer and Altered Abundance of 5' Transfer RNA Halves in Seminal Fluid and Prostatic Tissues.","authors":"Joseph M Dhahbi,&nbsp;Hani Atamna,&nbsp;Luke A Selth","doi":"10.1177/1179299X18759545","DOIUrl":"https://doi.org/10.1177/1179299X18759545","url":null,"abstract":"<p><p>Extracellular RNAs are gaining clinical interest as biofluid-based noninvasive markers for diseases, especially cancer. In particular, derivatives of transfer RNA (tRNA) are emerging as a new class of small-noncoding RNAs with high biomarker potential. We and others previously reported alterations in serum levels of specific tRNA halves in disease states including cancer. Here, we explored seminal fluid for tRNA halves as potential markers of prostate cancer. We found that 5' tRNA halves are abundant in seminal fluid and are elevated in prostate cancer relative to noncancer patients. Importantly, most of these tRNA halves are also detectable in prostatic tissues, and a subset were increased in malignant relative to adjacent normal tissue. These findings emphasize the potential of 5' tRNA halves as noninvasive markers for prostate cancer screening and diagnosis and provide leads for future work to elucidate a putative role of the 5' tRNA halves in carcinogenesis.</p>","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179299X18759545","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35875724","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":"A Combinatorial Proteomic Biomarker Assay to Detect Ovarian Cancer in Women","authors":"Meredith C Henderson, Michael Silver, Sherri Borman, Q. Tran, Elias Letsios, R. Mulpuri, D. Reese, J. Wolf","doi":"10.1177/1179299X18756646","DOIUrl":"https://doi.org/10.1177/1179299X18756646","url":null,"abstract":"Ovarian cancer is often fatal and incidence in the general population is low, underscoring the necessity (and the challenges) for advancements in screening and early detection. The goal of this study was to design a serum-based biomarker panel and corresponding multivariate algorithm that can be used to accurately detect ovarian cancer. A combinatorial protein biomarker assay (CPBA) that uses CA125, HE4, and 3 tumor-associated autoantibodies resulted in an area under the curve of 0.98. The CPBA Ov algorithm was trained using subjects who were suspected to have gynecological cancer and were scheduled for surgery. As a surgical rule-out test, the clinical performance achieves 100% sensitivity and 83.7% specificity. Although sample size (n = 60) is a limiting factor, the CPBA Ov algorithm performed better than either CA-125 alone or the Risk of Ovarian Malignancy Algorithm.","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179299X18756646","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48567184","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}

{"title":"Integrating Circulating Immunological and Sputum Biomarkers for the Early Detection of Lung Cancer.","authors":"Jian Su,&nbsp;Qixin Leng,&nbsp;Yanli Lin,&nbsp;Jie Ma,&nbsp;Fangran Jiang,&nbsp;Cheng-Ju Lee,&nbsp;HongBin Fang,&nbsp;Feng Jiang","doi":"10.1177/1179299X18759297","DOIUrl":"https://doi.org/10.1177/1179299X18759297","url":null,"abstract":"<p><p>We have demonstrated that assessments of microRNA (miRNA) expressions in circulating peripheral blood mononucleated cell (PBMC) and sputum specimens, respectively, may help diagnose lung cancer. To assess the individual and combined analysis of the miRNAs across the different body fluids for lung cancer early detection, we analyse a panel of 3 sputum miRNAs (miRs-21, 31, and 210) and a panel of 2 PBMC miRNAs (miRs-19b-3p and 29b-3p) in a discovery cohort of 68 patients with lung cancer and 66 cancer-free smokers. We find that integrating 2 sputum miRNAs (miRs-31 and 210) and 1 PBMC miRNA (miR-19b-3p) has higher sensitivity (86.8%) and specificity (92.4%) compared with the individual panels. The synergistic value of the integrated panel of 3 biomarkers is confirmed in a validation cohort, independent of stage and histological type of lung cancer, and patients' age, sex, and ethnicity. Integrating circulating immunological and sputum biomarkers could improve the early detection of lung cancer.</p>","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179299X18759297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35851845","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":"HumanMethylation450K Array-Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer.","authors":"Mark O Kitchen,&nbsp;Richard T Bryan,&nbsp;Richard D Emes,&nbsp;Christopher J Luscombe,&nbsp;K K Cheng,&nbsp;Maurice P Zeegers,&nbsp;Nicholas D James,&nbsp;Lyndon M Gommersall,&nbsp;Anthony A Fryer","doi":"10.1177/1179299X17751920","DOIUrl":"https://doi.org/10.1177/1179299X17751920","url":null,"abstract":"<p><strong>Background: </strong>High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management.</p><p><strong>Patients and methods: </strong>A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing.</p><p><strong>Results: </strong>Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values.</p><p><strong>Conclusions: </strong>This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.</p>","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179299X17751920","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35744787","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":"miR-486-3p, miR-139-5p, and miR-21 as Biomarkers for the Detection of Oral Tongue Squamous Cell Carcinoma","authors":"Zujian Chen, Tianwei Yu, Robert J Cabay, Yi Jin, Ishrat Mahjabeen, X. Luan, Lei Huang, Yang Dai, Xiaofeng Zhou","doi":"10.1177/1179299X1700900001","DOIUrl":"https://doi.org/10.1177/1179299X1700900001","url":null,"abstract":"Oral tongue squamous cell carcinoma (TSCC) is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. The aims of the present study were to test the feasibility of performing the microRNA profiling analysis on archived TSCC specimens and to assess the potential diagnostic utility of the identified microRNA biomarkers for the detection of TSCC. TaqMan array-based microRNA profiling analysis was performed on 10 archived TSCC samples and their matching normal tissues. A panel of 12 differentially expressed microRNAs was identified. Eight of these differentially expressed microRNAs were validated in an independent sample set. A random forest (RF) classification model was built with miR-486-3p, miR-139-5p, and miR-21, and it was able to detect TSCC with a sensitivity of 100% and a specificity of 86.7% (overall error rate = 6.7%). As such, this study demonstrated the utility of the archived clinical specimens for microRNA biomarker discovery. The feasibility of using microRNA biomarkers (miR-486-3p, miR-139-5p, and miR-21) for the detection of TSCC was confirmed.","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179299X1700900001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65350049","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}

{"title":"Long Noncoding RNAs as a Key Player in Hepatocellular Carcinoma.","authors":"Mrigaya Mehra, Ranjit Chauhan","doi":"10.1177/1179299X17737301","DOIUrl":"10.1177/1179299X17737301","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a major malignancy in the liver and has emerged as one of the main cancers in the world with a high mortality rate. However, the molecular mechanisms of HCC are still poorly understood. Long noncoding RNAs (lncRNAs) have recently come to the forefront as functional non-protein-coding RNAs that are involved in a variety of cellular processes ranging from maintaining the structural integrity of chromosomes to gene expression regulation in a spatiotemporal manner. Many recent studies have reported the involvement of lncRNAs in HCC which has led to a better understanding of the underlying molecular mechanisms operating in HCC. Long noncoding RNAs have been shown to regulate development and progression of HCC, and thus, lncRNAs have both diagnostic and therapeutic potentials. In this review, we present an overview of the lncRNAs involved in different stages of HCC and their potential in clinical applications which have been studied so far.</p>","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179299X17737301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35560269","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":"More Accurate Oral Cancer Screening with Fewer Salivary Biomarkers.","authors":"James Michael Menke, Md Shahidul Ahsan, Suan Phaik Khoo","doi":"10.1177/1179299X17732007","DOIUrl":"10.1177/1179299X17732007","url":null,"abstract":"<p><p>Signal detection and Bayesian inferential tools were applied to salivary biomarkers to improve screening accuracy and efficiency in detecting oral squamous cell carcinoma (OSCC). Potential cancer biomarkers are identified by significant differences in assay concentrations, receiver operating characteristic areas under the curve (AUCs), sensitivity, and specificity. However, the end goal is to report to individual patients their risk of having disease given positive or negative test results. Likelihood ratios (LRs) and Bayes factors (BFs) estimate evidential support and compile biomarker information to optimize screening accuracy. In total, 26 of 77 biomarkers were mentioned as having been tested at least twice in 137 studies and published in 16 summary papers through 2014. Studies represented 10 212 OSCC and 25 645 healthy patients. The measure of biomarker and panel information value was number of biomarkers needed to approximate 100% positive predictive value (PPV). As few as 5 biomarkers could achieve nearly 100% PPV for a disease prevalence of 0.2% when biomarkers were ordered from highest to lowest LR. When sequentially interpreting biomarker tests, high specificity was more important than test sensitivity in achieving rapid convergence toward a high PPV. Biomarkers ranked from highest to lowest LR were more informative and easier to interpret than AUC or Youden index. The proposed method should be applied to more recently published biomarker data to test its screening value.</p>","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/94/10.1177_1179299X17732007.PMC5648090.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35559507","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}