{"title":"Non-Thermal Plasma As An Innovative Anticancer Strategy On Leukemia Models","authors":"Eleonora Turrini , Augusto Stancampiano , Emanuele Simoncelli , Romolo Laurita , Elena Catanzaro , Cinzia Calcabrini , Matteo Gherardi , Vittorio Colombo , Carmela Fimognari","doi":"10.1016/j.cpme.2017.12.025","DOIUrl":"10.1016/j.cpme.2017.12.025","url":null,"abstract":"<div><p><span><span>Antitumor chemotherapy is often hampered by the low therapeutic index of most anticancer drugs and the development of chemoresistance. Furthermore, in leukemia incidence and death rates </span>in patients<span> are really close to each other, when compared to other kind of tumors; pointing out that efficacy of anticancer therapy<span><span> is suboptimal. Thus, there is a continuous need for new intervention strategies, endowed with a better pharmaco-toxicological profile. Cold atmospheric plasma (CAP) has gained interest as a promising anticancer strategy and earlier studies demonstrated the “non-aggressive” nature of CAP [1]. Several lines of evidence showed that the anticancer activity of CAP mainly depends on the increase in oxidative and nitrosative stress that leads to tumor </span>cell death [2]. However, mechanisms of CAP-cell interaction are not yet completely understood. In this context, the aim of this work is to unravel CAP anticancer effects on </span></span></span><em>in vitro</em> and <span><em>ex vivo</em></span><span><span><span> leukemia models achieved within the Italian national project “Scientific Independence for young Researchers” (SIR), that brings together a multidisciplinary team in the areas of Engineering, Pharmacology and Oncohematology. The cytotoxic impact of different CAP treatments performed by means of two plasma sources, a nanosecond pulsed </span>dielectric<span> barrier discharge (DBD) [3,4] and a microsecond pulsed DBD jet (Fig.1), on T-lymphoblastic cell lines was investigated. In particular, we analyzed apoptotic and/or necrotic events, cell-cycle progression, levels of proteins involved in the regulation of apoptosis correlated to reactive oxygen and nitrogen species (RONS) induced in culture medium by CAP treatment. Due to the key role of RONS in the biological effects of CAPs, its genotoxic potential was assessed. Furthermore, some preliminary results indicate that CAPs can induce cytotoxic effects also on leukemia cells cultivated in </span></span>hypoxia, which plays a critical role in promoting chemoresistance. Taken together, the results we obtained contribute to understand the pharmaco-toxicological potential of CAP, thus making the basis to further investigate its anticancer properties.</span><span><figure><span><img><ol><li><span>Download : <span>Download high-res image (66KB)</span></span></li><li><span>Download : <span>Download full-size image</span></span></li></ol></span></figure></span></p><p>Figure 1: Nanosecond pulsed DBD on a grounded plate (right) and microsecond pulsed DBD jet (left).</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 15-16"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91268500","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":"Immune modulatory properties of radiotherapy","authors":"Udo S. Gaipl","doi":"10.1016/j.cpme.2017.12.020","DOIUrl":"10.1016/j.cpme.2017.12.020","url":null,"abstract":"<div><p><span><span>Radiotherapy (RT) is a common treatment for cancer and about 60% of all cancer patients will receive it during their course of illness. RT primarily aims to achieve local tumor control. The induction of DNA damage by </span>reactive oxygen species<span><span> (ROS), tumor cell death and the modulation of the </span>tumor microenvironment are the main effects of ionizing irradiation to reduce tumor masses, but also to modulate the immune system. RT might thereby act as an </span></span><em>in situ</em> cancer vaccine under certain microenvironmental conditions. However, RT also fosters the upregulation of immune suppressive molecules such as immune checkpoint molecules.</p><p><span><span>The presentation will focus on how local irradiation changes the tumor cell phenotype and the tumor microenvironment and consecutively does impact on local and systemic changes in immune cell compositions. In particular the impact of ROS, danger signals and cytokines on it will be outlined. The dynamics of immune changes, the </span>radiosensitivity of distinct immune cells as well as biological basis for reasonable combination of RT with </span>immune stimulation<span> will be discussed in detail, as well as how radiation-induced immune suppression can be overcome. Based on the pre-clinical knowledge, innovative clinical study concepts of radio-immune treatments will be presented.</span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 13"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77869931","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}
Juliusz Kruszelnicki, Amanda M. Lietz, Guy Parsey, Soheila Mohades, Mark J. Kushner
{"title":"Consequences Of Environmental Factors In Plasma Treatment Of Liquids, Tissues And Materials","authors":"Juliusz Kruszelnicki, Amanda M. Lietz, Guy Parsey, Soheila Mohades, Mark J. Kushner","doi":"10.1016/j.cpme.2017.12.003","DOIUrl":"10.1016/j.cpme.2017.12.003","url":null,"abstract":"<div><p><span>The approved use of atmospheric pressure plasma sources in treatment of biological materials has as one consideration the ability to reproduce the procedure. In this context, the environment in which the plasma source is operated is a factor. Environment is used here in the most general way to refer to all components surrounding or interacting with the plasma source that may affect the </span><em>dose</em> delivered to the biological material. These components may include the physical electrical layout of the procedure (e.g., location of electrical ground planes, permittivity of the material being treated), pulse-power protocol, humidity or aerosol content of the surrounding air, alignment of the plasma source, porosity of the material being treated, or depth of the well-plate for <em>in-vitro</em><span><span> studies. In this paper, results from computational investigations will be discussed that address the consequences of environmental factors in consistency of treatment of biological materials by plasma jets and </span>dielectric barrier discharges. The computational platforms used in this investigation are </span><em>nonPDPSIM,</em><span> a 2-dimensional plasma hydrodynamics model and </span><em>Global_Kin</em>, a 0-dimensional plasma kinetics model. Emphasis will be on plasma activation of liquids, aerosols or liquid covered materials, and treatment of non-planar or porous materials, including the physical layout of <em>in-vitro</em> studies.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 2"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77908765","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":"Immunogenic Cell Death In Murine Colon-Carcinoma Cells Following Exposure To Cold Physical Plasma-Treated Saline Solution","authors":"Eric Freund , Christine Hackbarth , Lars-Ivo Partecke , Sander Bekeschus","doi":"10.1016/j.cpme.2017.12.030","DOIUrl":"10.1016/j.cpme.2017.12.030","url":null,"abstract":"<div><p>Diffuse peritoneal metastasis of gastrointestinal tumors is a life-threatening complication in end-stage tumor patients. Standard of care is hyperthermic intraperitoneal chemotherapy (HIPEC) and/or radiation therapy, both associated with significant side effects [1]. Previous studies have suggested that cold physical plasma may present a new anti-tumor tool with few to none side effects [2]. Moreover, plasma-induced reactive species can be transferred to cell culture medium where they react to more stable entities. We were able to demonstrate that phosphate-buffered saline (PBS) treated with cold physical plasma has toxic effects on mouse carcinoma cells cultured in 2D. We observed a reduced metabolic activities and apoptotic cell death. Morphological alterations, such as spiking of nuclei and changes in the shape of cytofilaments were also visible. Accordingly, treatment increased cell stiffness and reduced cell motility. Cancer cells are able to develop several mechanisms to subvert and avoid immune response. Danger associated molecular patterns (DAMPs) are linked to an immunogenic cell death (ICD) [3]. We observed an upregulation of DAMPs on the cell surface as well as increased concentrations in the cell’s liquid surroundings following incubation with plasma-treated saline. The activation of the immune system for cancer therapy is a promising approach. Animal experiments will show whether plasma-treated saline solution is effective in vivo and could be in principle considered for medical application.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 19"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78948846","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}
Philipp Jansen , Dirk Schadendorf , Sander Bekeschus , Joachim Klode , Ingo Stoffels
{"title":"Laser-Assisted Delivery Of Cold Atmospheric Plasma In Unresectable Cutaneous Metastasis In Melanoma Patients","authors":"Philipp Jansen , Dirk Schadendorf , Sander Bekeschus , Joachim Klode , Ingo Stoffels","doi":"10.1016/j.cpme.2017.12.071","DOIUrl":"10.1016/j.cpme.2017.12.071","url":null,"abstract":"<div><p>According to the World Health Organization, the incidence of melanoma<span><span> is increasing faster than that of any other major cancer in the world. Melanoma is the fifth most common cancer in the United States, posing a substantial health and economic burden. Treatment of early and multiple cutaneous unresectable </span>metastasis in melanoma patients is a major therapeutic problem.</span></p><p><span>Cold atmospheric plasma (CAP) contains electrons, charged particles, radicals, various excited molecules, UV photons, and transient electric fields. These various compositional elements have the potential either to enhance cellular activity, or to disrupt it. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell<span><span> or tumor tissue removal without influencing healthy cells. Topical application of treatment agents is a basic principle of dermatological therapy. However, the effective barrier function of the skin significantly impairs the bioavailability of most </span>topical drugs. Fractional ablative lasers represent an innovative strategy to overcome the epidermal barrier in a standardized, contact-free manner. The bioavailability of topical agents can be significantly enhanced using laser-assisted delivery. Ablative fractional laser resurfacing creates vertical channels that might assist the delivery of topically applied cold plasma into </span></span>cutaneous melanoma metastasis.</p><p>For lesions refractory to elective treatments, the laser-assisted drug delivery technique combined with cold atmospheric plasma may present a new potential option.</p><p>We report on a pilot study showing a proof of concept for enhancing topical cold atmospheric plasma permeation into depth by ablative fractional laser technique.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 46"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84584794","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}
Christina Maria Wolff, Anna Steuer, Jürgen F. Kolb, Sander Bekeschus
{"title":"Combining cold physical plasma with pulsed electrical fields for cancer treatment","authors":"Christina Maria Wolff, Anna Steuer, Jürgen F. Kolb, Sander Bekeschus","doi":"10.1016/j.cpme.2017.12.042","DOIUrl":"10.1016/j.cpme.2017.12.042","url":null,"abstract":"<div><p><span><span><span>Pallation of end-stage melanoma<span> and breast cancer patients is a challenge. Despite the generally successful use of electrochemotherapy (ECT) in these patients, response rates can still be improved. Previous studies demonstrated the anticancer potential of nano-second PEFs (nsPEFs), which are able to induce </span></span>apoptosis [1] or </span>nanopore formation when using different settings [2]. Likewise, the anticancer capacity of cold physical plasma has been demonstrated in various studies in cell lines and in </span>xenograft tumors<span><span> in mice [3-7]. The apoptotic effect of cold plasmas is mediated by a variety of reactive species being released onto the cells, where the species trigger redox signaling, and subsequent cell death in some instances [8, 9]. By contrast, PEFs act by a mechanism much less dependent on the newly generated reactive species. Our idea was to combine both </span>treatments to improve palliative cancer treatment in the future.</span></p><p><span>Malignant suspension cell lines were tested to investigate the proof of concept of additive or possible even synergistic cytotoxic effects. Plasma treatment time (kINPen) and PEF intensity as well as pulse length were varied to retrieve sublethal dosage regimens<span><span> for each treatment. The sequence of combination (first plasma, then PEF or vice versa) was also modulated. To investigate the mode of action of both therapies, a number of cellular parameters were investigated. This included oxidation at cytosolic and membrane compartments, thiol content, mitochondrial depolarization, </span>caspase activation and </span></span>phosphatidylserine<span> exposure, metabolic activity, cell membrane<span> permeabilization, cell growth and morphology, and protection by antioxidants. Furthermore, we identified a synergistic effect of plasma and PEFs using tumorigenic adherent cells in preliminary tests.</span></span></p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 26-27"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90809666","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}
Kobra Hajizadeh , Bahram Behzad , Danial Seifi , Hassan Mehdian , Mohammad Nabiouni , Kamal Haji-Sharifi , Elahe Amini
{"title":"The Effect of Plasma Activated Verbascoside on HIF-1A Expression as Valuable Metastasis and Angiogenesis factor in HT-29 Colon Cancer Cells","authors":"Kobra Hajizadeh , Bahram Behzad , Danial Seifi , Hassan Mehdian , Mohammad Nabiouni , Kamal Haji-Sharifi , Elahe Amini","doi":"10.1016/j.cpme.2017.12.056","DOIUrl":"10.1016/j.cpme.2017.12.056","url":null,"abstract":"<div><p>Colon cancer<span> is one of the most common and most prevalent Neoplasma in men; adenocarcinomas make up 95 percent of all colon cancer cases. Due to the side effects of conventional treatment methods such as chemotherapy, today, attentions have been attracted to natural compounds that have less side effects and anticancer properties.</span></p><p><span>In attempting to investigate factors which may account for cancer treatment, this study raises two interrelated questions. Firstly, what is the effect of Verbascoside<span><span> as a natural compound in inhibiting HIF-1α signaling pathway which is an effective route in the </span>metastasis<span>, angiogenesis and cell migration in the human cell line of HT-29 colon cancer; second, is it possible to enhance and raise the effect of this </span></span></span>herbal drug by cold atmospheric pressure plasma jet?</p><p>The focus of this study will be investigating the effect of Verbascoside as a natural compound in inhibiting HIF-1α signaling pathway and also examining the effect of atmospheric pressure plasma on the function of Verbascoside.</p><p><span>A the first step, 29-HT cells were treated at different concentrations of verbascoside 10, 20, 30, 40, 50, 70, 100 μg / ml for 24 hours, then MTT test was used to calculate the inhibitory concentration. The colon cancer cell migration was evaluated by scratch test and HIF-1α gene expression was evaluated by Real Time PCR. The results of the </span>MTT assay<span> showed that verboscoside dose-dependent inhibition of cancer cells<span>. The HT-29 colon is at a concentration of 50 μg/ml. Scratch repair tests showed that verboscoside reduced the migration of cells in a dose-dependent manner, and the results of Real Time PCR showed a decrease in the expression of HIF-1α gene expression. Cancer tumors undergo some changes in oxygen deficiency conditions, including increasing the expression of the HIF-1α gene, which in turn play an important role in activating and enhancing the expression of genes involved in metastasis, angiogenesis and migration.</span></span></p><p>At the second step of this study, verboscoside was primarily treated by cold atmospheric plasma jet then the same procedure has been taken for plasma activated verboscoside. In this study helium jet has been used.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 36"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89783859","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}
Dominika Sersenová , Helena Gbelcová , Adam Polakovič , Vanda Repiská , Zdenko Machala
{"title":"Effect Of Plasma Pen Treatment And Plasma Activated Medium (PAM) On Cancer And Normal Cells","authors":"Dominika Sersenová , Helena Gbelcová , Adam Polakovič , Vanda Repiská , Zdenko Machala","doi":"10.1016/j.cpme.2017.12.038","DOIUrl":"10.1016/j.cpme.2017.12.038","url":null,"abstract":"<div><p>Non-thermal atmospheric pressure plasma has recently found an ever growing use in medicine; including development of new cancer treatments. The most significant factor, produced by plasma that influence cancer cells<span> are reactive oxygen and nitrogen species (RONS). RONS react with the surrounding air, cellular aqueous media and with cells themselves; however, the exact mechanism of their interaction with the cells is not yet fully understood. Some of the studies suggest that plasma is able to induce apoptosis in cancer cells and has a potential to selectively kill cancer cells without causing a major destruction of normal cells [1]. Plasma can be applied both directly on cell or tissues or indirectly – by plasma-activated medium (PAM). It is a cellular medium, which was treated by plasma and then applied onto the cells, so the cells interact only with RONS produced in PAM [2].</span></p><p>The aim of this study was to test <em>in vitro</em><span> the effect of plasma on cancer cells A375 (human melanoma<span><span> epithelial cells) and normal cells HEK293T (human embryonic kidney cells). As a medium we used DMEM with 10% FBS. The first part focuses on direct treatment of cells by our design of air corona plasma pen [3,4]. In the second part, we evaluated the effect of PAM on the cells. We used discharges generated in atmospheric air, unlike the majority of plasma jets used for biomedical application that use </span>rare gases<span> (He, Ar). Cell viability was measured using the MTT test.</span></span></span></p><p>In the first setup, cells were treated with the corona plasma multipen. The cells were placed in 96-well plate with 100μl of medium and the corona discharge operated in between the 8 pen needles and steel wire above the medium surface. Medium temperature did not exceed 34°C. The cell viability was measured after 24-hour incubation and it was evaluated in dependence on time of plasma treatment. Viability of both types of cells decreased with the time of plasma treatment with no selectivity on cancer cells. After 5 minutes of plasma treatment almost all cells were dead (> 95 %).</p><p>In the second setup, the effect of PAM on cells was tested in various experimental setups aiming to find the most effective way of PAM production. We used transient spark or streamer corona discharges with different parameters in combination with electro-spraying of the used medium. The discharges were operated in between the high voltage needle and a grounded mesh. The cells viability was evaluated after 24- and 48-hour incubation. We investigated the cell viability dependence on time of plasma treatment, on the used discharge regime, treatment before and after FBS was added, and on the amount of PAM added to the cells.</p><p>To conclude, cold plasma has the potential to be used in cancer treatment, because it can be used on live cells and tissues. The use of direct plasma is more technically demanding and still possible mainly in surface ","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Page 24"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73527791","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":"Controlling of apoptosis and proliferation of HepG2 cancer cells by treatment of plasma jet and N-acetylcysteine combination","authors":"Zilan Xiong , Shasha Zhao","doi":"10.1016/j.cpme.2017.12.019","DOIUrl":"10.1016/j.cpme.2017.12.019","url":null,"abstract":"<div><p>It is well known that atmospheric pressure plasma could induce apoptosis of cancer cells. [1][2] However, the interaction and mechanism between plasma and cancer cells has not been fully understood yet. [3] Here, we report the controlment of apoptosis and proliferation of human hepatocellular carcinoma cell (HepG2) by combined treatment of He/O<sub>2</sub> plasma jet and N-acetylcysteine (NAC, free radical scavenger). It is found that the fate of HepG2 cells could be controlled by plasma treatment time together with NAC pretreatment. Pure plasma treatment could induce apoptosis of HepG2 cells. However, on one hand, 15s plasma with NAC pre-treatment could enhance proliferation of HepG2 cell as a function of NAC concentration. On the other hand, NAC-pretreatment could markedly compromise apoptosis effect by long time plasma treatment (e.g. >240s) without proliferation observed. The NAC and 15s plasma treatment accelerates the G1 to S phase transition of HepG2 cells causing proliferation while long time plasma treatment arrests the cell cycle at the G2/M phase inducing apoptosis.</p></div>","PeriodicalId":46325,"journal":{"name":"Clinical Plasma Medicine","volume":"9 ","pages":"Pages 12-13"},"PeriodicalIF":0.0,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cpme.2017.12.019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86863840","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}