BMC Systems Biology最新文献

{"title":"Anti-TNF- αtreatment-related pathways and biomarkers revealed by transcriptome analysis in Chinese psoriasis patients.","authors":"Lunfei Liu,&nbsp;Wenting Liu,&nbsp;Yuxin Zheng,&nbsp;Jisu Chen,&nbsp;Jiong Zhou,&nbsp;Huatuo Dai,&nbsp;Suiqing Cai,&nbsp;Jianjun Liu,&nbsp;Min Zheng,&nbsp;Yunqing Ren","doi":"10.1186/s12918-019-0698-7","DOIUrl":"https://doi.org/10.1186/s12918-019-0698-7","url":null,"abstract":"<p><strong>Background: </strong>Anti-tumor necrosis factor alpha (TNF- α) therapy has made a significant impact on treating psoriasis. Despite these agents being designed to block TNF- α activity, their mechanism of action in the remission of psoriasis is still not fully understood at the molecular level.</p><p><strong>Results: </strong>To better understand the molecular mechanisms of Anti-TNF- α therapy, we analysed the global gene expression profile (using mRNA microarray) in peripheral blood mononuclear cells (PBMCs) that were collected from 6 psoriasis patients before and 12 weeks after the treatment of etanercept. First, we identified 176 differentially expressed genes (DEGs) before and after treatment by using paired t-test. Then, we constructed the gene co-expression modules by weighted correlation network analysis (WGCNA), and 22 co-expression modules were found to be significantly correlated with treatment response. Of these 176 DEGs, 79 DEGs (M_DEGs) were the members of these 22 co-expression modules. Of the 287 GO functional processes and pathways that were enriched for these 79 M_DEGs, we identified 30 pathways whose overall gene expression activities were significantly correlated with treatment response. Of the original 176 DEGs, 19 (GO_DEGs) were found to be the members of these 30 pathways, whose expression profiles showed clear discrimination before and after treatment. As expected, of the biological processes and functionalities implicated by these 30 treatment response-related pathways, the inflammation and immune response was the top pathway in response to etanercept treatment, and some known TNF- α related pathways, such as molting cycle process, hair cycle process, skin epidermis development, regulation of hair follicle development, were implicated. Furthermore, additional novel pathways were also suggested, such as heparan sulfate proteoglycan metabolic process, vascular endothelial growth factor production, whose transcriptional regulation may mediate the response to etanercept treatment.</p><p><strong>Conclusion: </strong>Through global gene expression analysis in PBMC of psoriasis patient and subsequent co-expression module based pathway analyses, we have identified a group of functionally coherent and differentially expressed genes (DEGs) and related pathways, which has not only provided new biological insight about the molecular mechanism of anti-TNF- α treatment, but also identified several genes whose expression profiles can be used as potential biomarkers for anti-TNF- α treatment response in psoriasis.</p>","PeriodicalId":9013,"journal":{"name":"BMC Systems Biology","volume":"13 Suppl 2","pages":"29"},"PeriodicalIF":0.0,"publicationDate":"2019-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12918-019-0698-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37124661","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":"PMAMCA: prediction of microRNA-disease association utilizing a matrix completion approach.","authors":"Jihwan Ha,&nbsp;Chihyun Park,&nbsp;Sanghyun Park","doi":"10.1186/s12918-019-0700-4","DOIUrl":"https://doi.org/10.1186/s12918-019-0700-4","url":null,"abstract":"<p><strong>Background: </strong>Numerous experimental results have indicated that microRNAs (miRNAs) play a vital role in biological processes, as well as outbreaks of diseases at the molecular level. Despite their important role in biological processes, knowledge regarding specific functions of miRNAs in the development of human diseases is very limited. While attempting to solve this problem, many computational approaches have been proposed and attracted significant attention. However, most previous approaches suffer from the common problem of being inapplicable to new diseases without any known miRNA-disease associations.</p><p><strong>Results: </strong>This paper proposes a novel method for inferring disease-miRNA associations utilizing a machine learning technique called matrix factorization, which is widely used in recommendation systems. In recommendation systems, the goal is to predict rating scores that a user might assign to specific items. By replacing users with miRNAs and items with diseases, we can efficiently predict miRNA-disease associations without seed miRNAs. As a result, our proposed model, called prediction of microRNA-disease association utilizing a matrix completion approach, achieves excellent performance compared to previous approaches with a reliable AUC value of 0.882 by implementing five-fold cross validation.</p><p><strong>Conclusions: </strong>To the best of our knowledge, the proposed method applies the matrix completion technique to infer miRNA-disease associations and overcome the seed-miRNA problem negatively affects existing computational models.</p>","PeriodicalId":9013,"journal":{"name":"BMC Systems Biology","volume":"13 1","pages":"33"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12918-019-0700-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37076189","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":"Adaptive information processing of network modules to dynamic and spatial stimuli.","authors":"J Krishnan,&nbsp;Ioannis Floros","doi":"10.1186/s12918-019-0703-1","DOIUrl":"https://doi.org/10.1186/s12918-019-0703-1","url":null,"abstract":"<p><strong>Background: </strong>Adaptation and homeostasis are basic features of information processing in cells and seen in a broad range of contexts. Much of the current understanding of adaptation in network modules/motifs is based on their response to simple stimuli. Recently, there have also been studies of adaptation in dynamic stimuli. However a broader synthesis of how different circuits of adaptation function, and which circuits enable a broader adaptive behaviour in classes of more complex and spatial stimuli is largely missing.</p><p><strong>Results: </strong>We study the response of a variety of adaptive circuits to time-varying stimuli such as ramps, periodic stimuli and static and dynamic spatial stimuli. We find that a variety of responses can be seen in ramp stimuli, making this a basis for discriminating between even similar circuits. We also find that a number of circuits adapt exactly to ramp stimuli, and dissect these circuits to pinpoint what characteristics (architecture, feedback, biochemical aspects, information processing ingredients) allow for this. These circuits include incoherent feedforward motifs, inflow-outflow motifs and transcritical circuits. We find that changes in location in such circuits where a signal acts can result in non-adaptive behaviour in ramps, even though the location was associated with exact adaptation in step stimuli. We also demonstrate that certain augmentations of basic inflow-outflow motifs can alter the behaviour of the circuit from exact adaptation to non-adaptive behaviour. When subject to periodic stimuli, some circuits (inflow-outflow motifs and transcritical circuits) are able to maintain an average output independent of the characteristics of the input. We build on this to examine the response of adaptive circuits to static and dynamic spatial stimuli. We demonstrate how certain circuits can exhibit a graded response in spatial static stimuli with an exact maintenance of the spatial mean-value. Distinct features which emerge from the consideration of dynamic spatial stimuli are also discussed. Finally, we also build on these results to show how different circuits which show any combination of presence or absence of exact adaptation in ramps, exact mainenance of time average output in periodic stimuli and exact maintenance of spatial average of output in static spatial stimuli may be realized.</p><p><strong>Conclusions: </strong>By studying a range of network circuits/motifs on one hand and a range of stimuli on the other, we isolate characteristics of these circuits (structural) which enable different degrees of exact adaptive and homeostatic behaviour in such stimuli, how they may be combined, and also identify cases associated with non-homeostatic behaviour. We also reveal constraints associated with locations where signals may act to enable homeostatic behaviour and constraints associated with augmentations of circuits. This consideration of multiple experimentally/naturally releva","PeriodicalId":9013,"journal":{"name":"BMC Systems Biology","volume":"13 1","pages":"32"},"PeriodicalIF":0.0,"publicationDate":"2019-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12918-019-0703-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37052178","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":"How to schedule VEGF and PD-1 inhibitors in combination cancer therapy?","authors":"Xiulan Lai, Avner Friedman","doi":"10.1186/s12918-019-0706-y","DOIUrl":"10.1186/s12918-019-0706-y","url":null,"abstract":"<p><strong>Background: </strong>One of the questions in the design of cancer clinical trials with combination of two drugs is in which order to administer the drugs. This is an important question, especially in the case where one agent may interfere with the effectiveness of the other agent.</p><p><strong>Results: </strong>In the present paper we develop a mathematical model to address this scheduling question in a specific case where one of the drugs is anti-VEGF, which is known to affect the perfusion of other drugs. As a second drug we take anti-PD-1. Both drugs are known to increase the activation of anticancer T cells. Our simulations show that in the case where anti-VEGF reduces the perfusion, a non-overlapping schedule is significantly more effective than a simultaneous injection of the two drugs, and it is somewhat more beneficial to inject anti-PD-1 first.</p><p><strong>Conclusion: </strong>The method and results of the paper can be extended to other combinations, and they could play an important role in the design of clinical trials with combination therapy, where scheduling strategies may significantly affect the outcome.</p>","PeriodicalId":9013,"journal":{"name":"BMC Systems Biology","volume":"13 1","pages":"30"},"PeriodicalIF":0.0,"publicationDate":"2019-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37076184","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 to: Pathway crosstalk perturbation network modeling for identification of connectivity changes induced by diabetic neuropathy and pioglitazone.","authors":"Guillermo de Anda-Jáuregui,&nbsp;Kai Guo,&nbsp;Brett A McGregor,&nbsp;Eva L Feldman,&nbsp;Junguk Hur","doi":"10.1186/s12918-019-0707-x","DOIUrl":"https://doi.org/10.1186/s12918-019-0707-x","url":null,"abstract":"<p><p>.</p>","PeriodicalId":9013,"journal":{"name":"BMC Systems Biology","volume":"13 1","pages":"31"},"PeriodicalIF":0.0,"publicationDate":"2019-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12918-019-0707-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37052170","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":"Systems biology research at BGRS-2018.","authors":"Yuriy L Orlov,&nbsp;Ralf Hofestädt,&nbsp;Ancha V Baranova","doi":"10.1186/s12918-019-0685-z","DOIUrl":"https://doi.org/10.1186/s12918-019-0685-z","url":null,"abstract":"<p><p></p>","PeriodicalId":9013,"journal":{"name":"BMC Systems Biology","volume":"13 Suppl 1","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2019-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12918-019-0685-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37026906","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":"Towards embedding Caco-2 model of gut interface in a microfluidic device to enable multi-organ models for systems biology.","authors":"Dmitry Sakharov,&nbsp;Diana Maltseva,&nbsp;Evgeny Knyazev,&nbsp;Sergey Nikulin,&nbsp;Andrey Poloznikov,&nbsp;Sergey Shilin,&nbsp;Ancha Baranova,&nbsp;Irina Tsypina,&nbsp;Alexander Tonevitsky","doi":"10.1186/s12918-019-0686-y","DOIUrl":"https://doi.org/10.1186/s12918-019-0686-y","url":null,"abstract":"<p><strong>Background: </strong>A cancer cell line originating from human epithelial colorectal adenocarcinoma (Caco-2 cells) serves as a high capacity model for a preclinical screening of drugs. Recent need for incorporating barrier tissue into multi-organ chips calls for inclusion of Caco-2 cells into microperfused environment.</p><p><strong>Results: </strong>This article describes a series of systems biology insights obtained from comparing Caco-2 models cells grown as conventional 2D layer and in a microfluidic chip. When basic electrical parameters of Caco-2 monolayers were evaluated using impedance spectrometry and MTT assays, no differences were noted. On the other hand, the microarray profiling of mRNAs and miRNAs revealed that grows on a microfluidic chip leads to the change in the production of specific miRNA, which regulate a set of genes for cell adhesion molecules (CAMs), and provide for more complete differentiation of Caco-2 monolayer. Moreover, the sets of miRNAs secreted at the apical surface of Caco-2 monolayers grown in conventional 2D culture and in microfluidic device differ.</p><p><strong>Conclusions: </strong>When integrated into a multi-tissue platform, Caco-2 cells may aid in generating insights into complex pathophysiological processes, not possible to dissect in conventional cultures.</p>","PeriodicalId":9013,"journal":{"name":"BMC Systems Biology","volume":"13 Suppl 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2019-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12918-019-0686-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37026327","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":"Urine proteome changes associated with autonomic regulation of heart rate in cosmonauts.","authors":"Lyudmila H Pastushkova,&nbsp;Vasily B Rusanov,&nbsp;Anna G Goncharova,&nbsp;Alexander G Brzhozovskiy,&nbsp;Alexey S Kononikhin,&nbsp;Anna G Chernikova,&nbsp;Daria N Kashirina,&nbsp;Andrey M Nosovsky,&nbsp;Roman M Baevsky,&nbsp;Evgeny N Nikolaev,&nbsp;Irina M Larina","doi":"10.1186/s12918-019-0688-9","DOIUrl":"https://doi.org/10.1186/s12918-019-0688-9","url":null,"abstract":"<p><strong>Background: </strong>The strategy of adaptation of the human body in microgravity is largely associated with the plasticity of cardiovascular system regulatory mechanisms. During long-term space flights the changes in the stroke volume of the heart are observed, the heart rate decreases, the phase structure of cardiac cycle is readjusted The purpose of this work was to clarify urine proteome changes associated with the initial condition of the heart rate autonomic regulation mechanisms in cosmonauts who have participated in long space missions. Urine proteome of each cosmonaut was analyzed before and after space flight, depending on the initial parameters characterizing the regulatory mechanisms of the cardiovascular system.</p><p><strong>Results: </strong>The proteins cadherin-13, mucin-1, alpha-1 of collagen subunit type VI (COL6A1), hemisentin-1, semenogelin-2, SH3 domain-binding protein, transthyretin and serine proteases inhibitors realize a homeostatic role in individuals with different initial type of the cardiovascular system regulation. The role of significantly changed urine proteins in the cardiovascular homeostasis maintenance is associated with complex processes of atherogenesis, neoangiogenesis, activation of calcium channels, changes in cell adhesion and transmembrane properties, changes in extracellular matrix, participation in protection from oxidative stress and leveling the effects of hypoxia. Therefore, the concentrations of these proteins significantly differ between groups with dominant parasympathetic and sympathetic influences.</p><p><strong>Conclusion: </strong>The space flight induced urine proteome changes are significantly different in the groups identified by heart rate autonomic regulation peculiarities before space flight. All these proteins regulate the associated biological processes which affect the stiffness of the vascular wall, blood pressure level, the severity of atherosclerotic changes, the rate and degree of age-related involution of elastin and fibulin, age-related increase in collagen stiffness, genetically determined features of elastin fibers. The increased vascular rigidity (including the aorta) and of myocardium may be regarded as a universal response to various extreme factors. Significant differences in the semi-quantitative analysis of signal proteins between groups with different types of autonomic regulation are explained by a common goal: to ensure optimal adaptation regardless of age and of the genetically determined type of responses to the extreme environmental factors effects.</p>","PeriodicalId":9013,"journal":{"name":"BMC Systems Biology","volume":"13 Suppl 1","pages":"17"},"PeriodicalIF":0.0,"publicationDate":"2019-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12918-019-0688-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37026913","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":"Effects of unpaired 1 gene overexpression on the lifespan of Drosophila melanogaster.","authors":"Alexey Moskalev,&nbsp;Ekaterina Proshkina,&nbsp;Alex Zhavoronkov,&nbsp;Mikhail Shaposhnikov","doi":"10.1186/s12918-019-0687-x","DOIUrl":"https://doi.org/10.1186/s12918-019-0687-x","url":null,"abstract":"<p><strong>Background: </strong>The JAK/STAT signaling pathway is involved in many aging-related cellular functions. However, effects of overexpression of genes controlling JAK/STAT signal transduction on longevity of model organisms have not been studied. Here we evaluate the effect of overexpression of the unpaired 1 (upd1) gene, which encodes an activating ligand for JAK/STAT pathway, on the lifespan of Drosophila melanogaster.</p><p><strong>Results: </strong>Overexpression of upd1 in the intestine caused a pronounced shortening of the median lifespan by 54.1-18.9%, and the age of 90% mortality by 40.9-19.1% in males and females, respectively. In fat body and in nervous system of male flies, an induction of upd1 overexpression increased the age of 90% mortality and median lifespan, respectively. An increase in upd1 expression enhanced mRNA levels of the JAK/STAT target genes domeless and Socs36E.</p><p><strong>Conclusions: </strong>Conditional overexpression of upd1 in different tissues of Drosophila imago induces pro-aging or pro-longevity effects in tissue-dependent manner. The effects of upd1 overexpression on lifespan are accompanied by the transcription activation of genes for the components of JAK/STAT pathway.</p>","PeriodicalId":9013,"journal":{"name":"BMC Systems Biology","volume":"13 Suppl 1","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2019-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12918-019-0687-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37201451","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":"LSM-W²: laser scanning microscopy worker for wheat leaf surface morphology.","authors":"Ulyana S Zubairova,&nbsp;Pavel Yu Verman,&nbsp;Polina A Oshchepkova,&nbsp;Alina S Elsukova,&nbsp;Alexey V Doroshkov","doi":"10.1186/s12918-019-0689-8","DOIUrl":"https://doi.org/10.1186/s12918-019-0689-8","url":null,"abstract":"<p><strong>Background: </strong>Microscopic images are widely used in plant biology as an essential source of information on morphometric characteristics of the cells and the topological characteristics of cellular tissue pattern due to modern computer vision algorithms. High-resolution 3D confocal images allow extracting quantitative characteristics describing the cell structure of leaf epidermis. For some issues in the study of cereal leaves development, it is required to apply the staining techniques with fluorescent dyes and to scan rather large fragments consisting of several frames. We aimed to develop a tool for processing multi-frame multi-channel 3D images obtained from confocal laser scanning microscopy and taking into account the peculiarities of the cereal leaves staining.</p><p><strong>Results: </strong>We elaborated an ImageJ-plugin LSM-W² that allows extracting data on Leaf Surface Morphology from Laser Scanning Microscopy images. The plugin is a crucial link in a workflow for obtaining data on structural properties of leaf epidermis and morphological properties of epidermal cells. It allows converting large lsm-files (laser scanning microscopy) into segmented 2D/3D images or tables with data on cells and/or nuclei sizes. In the article, we also represent some case studies showing the plugin application for solving biological tasks. Namely the plugin is applied in the following cases: defining parameters of jigsaw-puzzle pattern for maize leaf epidermal cells, analysis of the pavement cells morphological parameters for the mature wheat leaf grown under control and water deficit conditions, initiation of cell longitudinal rows, and detection of guard mother cells emergence at the initial stages of the stomatal morphogenesis in the growth zone of a wheat leaf.</p><p><strong>Conclusion: </strong>The proposed plugin is efficient for high-throughput analysis of cellular architecture for cereal leaf epidermis. The workflow implies using inexpensive and rapid sample preparation and does not require the applying of transgenesis and reporter genetic structures expanding the range of species and varieties to study. Obtained characteristics of the cell structure and patterns further could act as a basis for the development and verification for spatial models of plant tissues formation mechanisms accounting for structural features of cereal leaves.</p><p><strong>Availability: </strong>The implementation of this workflow is available as an ImageJ plugin distributed as a part of the Fiji project (FijiisjustImageJ: https://fiji.sc/ ). The plugin is freely available at https://imagej.net/LSM_Worker , https://github.com/JmanJ/LSM_Worker and http://pixie.bionet.nsc.ru/LSM_WORKER/ .</p>","PeriodicalId":9013,"journal":{"name":"BMC Systems Biology","volume":"13 Suppl 1","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2019-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12918-019-0689-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37026905","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}