Journal of Toxicology and Environmental Health-Part B-Critical Reviews最新文献

{"title":"Relevance of mouse lung tumors to human risk assessment.","authors":"Samuel M Cohen,&nbsp;Yan Zhongyu,&nbsp;James S Bus","doi":"10.1080/10937404.2020.1763879","DOIUrl":"https://doi.org/10.1080/10937404.2020.1763879","url":null,"abstract":"<p><p>Mouse lung is a common site for chemical tumorigenicity, but the relevance to human risk remains debated. Long-term bioassays need to be assessed for appropriateness of the dose, neither exceeding Maximum Tolerated Dose (MTD) nor Kinetically based Maximum Dose (KMD). An example of the KMD issue is 1,3-dichloropropene (1,3-D), which only produced an increased incidence of lung tumors at a dose exceeding the KMD. In addition, since mouse lung tumors are common (>1% incidence), the appropriate statistical significance is <i>p</i> < .01. Numerous differences exist for mouse lung and tumors compared to humans, including anatomy, respiratory rate, metabolism, tumor histogenesis, and metastatic frequency. The recent demonstration of the critical role of mouse lung specific Cyp2 F2 metabolism in mouse lung carcinogenicity including styrene or fluensulfone indicates that this tumor response is not qualitatively or quantitatively relevant to humans. For non-DNA reactive and non-mutagenic carcinogens, the mode of action involves direct mitogenicity such as for isoniazid, styrene, fluensulfone, permethrin or cytotoxicity with regeneration such as for naphthalene. However, the possibility of mixed mitogenic and cytotoxic modes of action cannot always be excluded. The numerous differences between mouse and human, combined with epidemiologic evidence of no increased cancer risk for several of these chemicals make the relevance of mouse lung tumors for human cancer risk dubious.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"23 5","pages":"214-241"},"PeriodicalIF":7.2,"publicationDate":"2020-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10937404.2020.1763879","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37972768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A critical review of talc and ovarian cancer.","authors":"Julie E Goodman,&nbsp;Laura E Kerper,&nbsp;Robyn L Prueitt,&nbsp;Charlotte M Marsh","doi":"10.1080/10937404.2020.1755402","DOIUrl":"https://doi.org/10.1080/10937404.2020.1755402","url":null,"abstract":"<p><p>The association between perineal talc use and ovarian cancer has been evaluated in several epidemiology studies. Some case-control studies reported weak positive associations, while other case-control and three large prospective cohort investigations found this association to be null. A weight-of-evidence evaluation was conducted of the epidemiology, toxicity, exposure, transport, <i>in vitro</i>, and mechanistic evidence to determine whether, collectively, these data support a causal association. Our review of the literature indicated that, while both case-control and cohort studies may be impacted by bias, the possibility of recall and other biases from the low participation rates and retrospective self-reporting of talc exposure cannot be ruled out for any of the case-control studies. The hypothesis that talc exposure induces ovarian cancer is only supported if one discounts the null results of the cohort studies and the fact that significant bias and/or confounding are likely reasons for the associations reported in some case-control investigations. In addition, one would need to ignore the evidence from animal experiments that show no marked association with cancer, <i>in vitro</i> and genotoxicity studies that did not indicate a carcinogenic mechanism of action for talc, and mechanistic and transport investigations that did not support the retrograde transport of talc to the ovaries. An alternative hypothesis that talc does not produce ovarian cancer, and that bias and confounding contribute the reported positive associations in case-control studies, is better supported by the evidence across all scientific disciplines. It is concluded that the evidence does not support a causal association between perineal talc use and ovarian cancer.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"23 5","pages":"183-213"},"PeriodicalIF":7.2,"publicationDate":"2020-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10937404.2020.1755402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37929307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of hepatic nanotoxicology - summation of recent findings and considerations for the next generation of study designs.","authors":"Ali Kermanizadeh,&nbsp;Leagh G Powell,&nbsp;Vicki Stone","doi":"10.1080/10937404.2020.1751756","DOIUrl":"https://doi.org/10.1080/10937404.2020.1751756","url":null,"abstract":"<p><p>The liver is one of the most important multi-functional organs in the human body. Amongst various crucial functions, it is the main detoxification center and predominantly implicated in the clearance of xenobiotics potentially including particulates that reach this organ. It is now well established that a significant quantity of injected, ingested or inhaled nanomaterials (NMs) translocate from primary exposure sites and accumulate in liver. This review aimed to summarize and discuss the progress made in the field of hepatic nanotoxicology, and crucially highlight knowledge gaps that still exist.Key considerations include <i>In vivo</i> studies clearly demonstrate that low-solubility NMs predominantly accumulate in the liver macrophages the Kupffer cells (KC), rather than hepatocytes.KCs lining the liver sinusoids are the first cell type that comes in contact with NMs <i>in vivo</i>. Further, these macrophages govern overall inflammatory responses in a healthy liver. Therefore, interaction with of NM with KCs <i>in vitro</i> appears to be very important.Many acute <i>in vivo</i> studies demonstrated signs of toxicity induced by a variety of NMs. However, acute studies may not be that meaningful due to liver's unique and unparalleled ability to regenerate. In almost all investigations where a recovery period was included, the healthy liver was able to recover from NM challenge. This organ's ability to regenerate cannot be reproduced <i>in vitro</i>. However, recommendations and evidence is offered for the design of more physiologically relevant <i>in vitro</i> models.Models of hepatic disease enhance the NM-induced hepatotoxicity.The review offers a number of important suggestions for the future of hepatic nanotoxicology study design. This is of great significance as its findings are highly relevant due to the development of more advanced <i>in vitro</i>, and <i>in silico</i> models aiming to improve physiologically relevant toxicological testing strategies and bridging the gap between <i>in vitro</i> and <i>in vivo</i> experimentation.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"23 4","pages":"137-176"},"PeriodicalIF":7.2,"publicationDate":"2020-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10937404.2020.1751756","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37862240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and cares to promote rational use of chloroquine and hydroxychloroquine in the management of coronavirus disease 2019 (COVID-19) pandemic: a timely review.","authors":"Boscolli Barbosa Pereira","doi":"10.1080/10937404.2020.1752340","DOIUrl":"https://doi.org/10.1080/10937404.2020.1752340","url":null,"abstract":"<p><p>As a result of the 2019 coronavirus disease pandemic (COVID-19), there has been an urgent worldwide demand for treatments. Due to factors such as history of prescription for other infectious diseases, availability, and relatively low cost, the use of chloroquine (CQ) and hydroxychloroquine (HCQ) has been tested <i>in vivo</i> and <i>in vitro</i> for the ability to inhibit the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, even though investigators noted the therapeutic potential of these drugs, it is important to consider the toxicological risks and necessary care for rational use of CQ and HCQ. This study provides information on the main toxicological and epidemiological aspects to be considered for prophylaxis or treatment of COVID-19 using CQ but mainly HCQ, which is a less toxic derivative than CQ, and was shown to produce better results in inhibiting proliferation of SARS-CoV-2 based upon preliminary tests.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"23 4","pages":"177-181"},"PeriodicalIF":7.2,"publicationDate":"2020-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10937404.2020.1752340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37825987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A male germ cell assay and supporting somatic cells: its application for the detection of phase specificity of genotoxins in vitro.","authors":"Khaled Habas,&nbsp;Martin H Brinkworth,&nbsp;Diana Anderson","doi":"10.1080/10937404.2020.1724577","DOIUrl":"https://doi.org/10.1080/10937404.2020.1724577","url":null,"abstract":"<p><p>Male germ stem cells are responsible for transmission of genetic information to the next generation. Some chemicals exert a negative impact on male germ cells, either directly, or indirectly affecting them through their action on somatic cells. Ultimately, these effects might inhibit fertility, and may exhibit negative consequences on future offspring. Genotoxic anticancer agents may interact with DNA in germ cells potentially leading to a heritable germline mutation. Experimental information in support of this theory has not always been reproducible and suitable <i>in vivo</i> studies remain limited. Thus, alternative male germ cell tests, which are now able to detect phase specificity of such agents, might be used by regulatory agencies to help evaluate the potential risk of mutation. However, there is an urgent need for such approaches for identification of male reproductive genotoxins since this area has until recently been dependent on <i>in vivo</i> studies. Many factors drive alternative approaches, including the (1) commitment to the principles of the 3R's (Replacement, Reduction, and Refinement), (2) time-consuming nature and high cost of animal experiments, and (3) new opportunities presented by new molecular analytical assays. There is as yet currently no apparent appropriate model of full mammalian spermatogenesis <i>in vitro</i>, under the REACH initiative, where new tests introduced to assess genotoxicity and mutagenicity need to avoid unnecessary testing on animals. Accordingly, a battery of tests used in conjunction with the high throughput STAPUT gravity sedimentation was recently developed for purification of male germ cells to investigate genotoxicity for phase specificity in germ cells. This system might be valuable for the examination of phases previously only available in mammals with large-scale studies of germ cell genotoxicity <i>in vivo</i>. The aim of this review was to focus on this alternative approach and its applications as well as on chemicals of known <i>in vivo</i> phase specificities used during this test system development.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"23 3","pages":"91-106"},"PeriodicalIF":7.2,"publicationDate":"2020-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10937404.2020.1724577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37634295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous doesn't always mean innocuous: a scoping review of iron toxicity by inhalation.","authors":"Jody Morgan,&nbsp;Robin Bell,&nbsp;Alison L Jones","doi":"10.1080/10937404.2020.1731896","DOIUrl":"https://doi.org/10.1080/10937404.2020.1731896","url":null,"abstract":"<p><p>Ambient air pollution is a leading risk factor for the global burden of disease. One possible pathway of particulate matter (PM)-induced toxicity is through iron (Fe), the most abundant metal in the atmosphere. The aim of the review was to consider the complexity of Fe-mediated toxicity following inhalation exposure focusing on the chemical and surface reactivity of Fe as a transition metal and possible pathways of toxicity via reactive oxygen species (ROS) generation as well as considerations of size, morphology, and source of PM. A broad term search of 4 databases identified 2189 journal articles and reports examining exposure to Fe via inhalation in the past 10 years. These were sequentially analyzed by title, abstract and full-text to identify 87 articles publishing results on the toxicity of Fe-containing PM by inhalation or instillation to the respiratory system. The remaining 87 papers were examined to summarize research dealing with <i>in vitro, in vivo</i> and epidemiological studies involving PM containing Fe or iron oxide following inhalation or instillation. The major findings from these investigations are summarized and tabulated. Epidemiological studies showed that exposure to Fe oxide is correlated with an increased incidence of cancer, cardiovascular diseases, and several respiratory diseases. Iron PM was found to induce inflammatory effects <i>in vitro</i> and <i>in vivo</i> and to translocate to remote locations including the brain following inhalation. A potential pathway for the PM-containing Fe-mediated toxicity by inhalation is via the generation of ROS which leads to lipid peroxidation and DNA and protein oxidation. Our recommendations include an expansion of epidemiological, <i>in vivo</i> and <i>in vitro</i> studies, integrating research improvements outlined in this review, such as the method of particle preparation, cell line type, and animal model, to enhance our understanding of the complex biological interactions of these particles.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"23 3","pages":"107-136"},"PeriodicalIF":7.2,"publicationDate":"2020-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10937404.2020.1731896","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37684524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arsenic in edible macroalgae: an integrated approach","authors":"Julieta R Camurati, Vanesa N. Salomone","doi":"10.1080/10937404.2019.1672364","DOIUrl":"https://doi.org/10.1080/10937404.2019.1672364","url":null,"abstract":"ABSTRACT Arsenic is a metalloid naturally present in marine environments. Various toxic elements including arsenic (As) are bioaccumulated by macroalgae. This metalloid is subsequently incorporated as arsenate into the organism due to similarity to phosphate. In recent decades, the use of macroalgae in food has increased as a result of their numerous benefits; however, As consumption may exert potential consequences for human health. The objective of this review was to discuss the articles published up to 2019 on As in seaweed, including key topics such as speciation, toxicity of the most common species in marine macroalgae, and their effects on human health. Further, this review will emphasize the extraction methods and analysis techniques most frequently used in seaweed and the need to develop certified reference materials (CRMs) in order to support the validation of analytical methodologies for As speciation in macroalgae. Finally, this review will discuss current legislation in relation to the risk associated with consumption. The number of articles found and the different approaches, biological, analytical and toxicological, show the growing interest there has been in this field in the last few years. In addition, this review reveals aspects of As chemistry that need further study, such as transformation of organic metalloid species during digestion and cooking, which necessitates analytical improvement and toxicological experiments. Taken together our findings may contribute to revision of current legislation on As content in edible seaweed relating to human health in a growing market.","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"12 1","pages":"1 - 12"},"PeriodicalIF":7.2,"publicationDate":"2020-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89157519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential adverse health effects of ingested micro- and nanoplastics on humans. Lessons learned from <i>in vivo</i> and <i>in vitro</i> mammalian models.","authors":"Laura Rubio,&nbsp;Ricard Marcos,&nbsp;Alba Hernández","doi":"10.1080/10937404.2019.1700598","DOIUrl":"https://doi.org/10.1080/10937404.2019.1700598","url":null,"abstract":"<p><p>In recent years, increasing global attention has focused on \"microplastics\" (MPs) and \"nanoplastics\" (NPs) resulting in many studies on the effects of these compounds on ecological and environmental aspects. These tiny particles (<5000 µm), predominantly derived from the degradation of plastics, pollute the marine and terrestrial ecosystems with the ability to enter into the food chain. In this manner, human consumption of food contaminated with MPs or NPs is unavoidable, but the related consequences remain to be determined. The aim of this review is to complement previous reviews on this topic by providing new studies related to exposure, absorption, and toxicity in mammalian <i>in vivo</i> and <i>in vitro</i> systems. With respect to novel information, gaps and limitations hindering attainment of firm conclusions as well as preparation of a reliable risk assessment are identified. Subsequently, recommendations for <i>in vivo</i> and <i>in vitro</i> testing methods are presented in order to perform further relevant and targeted research studies.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"23 2","pages":"51-68"},"PeriodicalIF":7.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10937404.2019.1700598","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37444632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The complex puzzle of dietary silver nanoparticles, mucus and microbiota in the gut.","authors":"Yuqiang Bi,&nbsp;Andrew K Marcus,&nbsp;Hervé Robert,&nbsp;Rosa Krajmalnik-Brown,&nbsp;Bruce E Rittmann,&nbsp;Paul Westerhoff,&nbsp;Marie-Hélène Ropers,&nbsp;Muriel Mercier-Bonin","doi":"10.1080/10937404.2019.1710914","DOIUrl":"https://doi.org/10.1080/10937404.2019.1710914","url":null,"abstract":"<p><p>Hundreds of consumer and commercial products containing silver nanoparticles (AgNPs) are currently used in food, personal-care products, pharmaceutical, and many other applications. Human exposure to AgNPs includes oral intake, inhalation, and dermal contact. The aim of this review was to focus on oral intake, intentional and incidental of AgNPs where well-known antimicrobial characteristics that might affect the microbiome and mucus in the gastrointestinal tract (GIT). This critical review summarizes what is known regarding the impacts of AgNPs on gut homeostasis. It is fundamental to understand the forms of AgNPs and their physicochemical characterization before and during digestion. For example, lab-synthesized AgNPs differ from \"real\" ingestable AgNPs used as food additives and dietary supplements. Similarly, the gut environment alters the chemical and physical state of Ag that is ingested as AgNPs. Emerging research on <i>in vitro</i> and <i>in vivo</i> rodent and human indicated complex multi-directional relationships among AgNPs, the intestinal microbiota, and the epithelial mucus. It may be necessary to go beyond today's descriptive approach to a modeling-based ecosystem approach that might quantitatively integrate spatio-temporal interactions among microbial groups, host factors (e.g., mucus), and environmental factors, including lifestyle-based stressors. It is suggested that future research (1) utilize more representative AgNPs, focus on microbe/mucus interactions, (2) assess the effects of environmental stressors for longer and longitudinal conditions, and (3) be integrated using quantitative modeling.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"23 2","pages":"69-89"},"PeriodicalIF":7.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10937404.2019.1710914","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37528187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic toxicity assessment using liver cell models: past, present, and future","authors":"Xiaoqing Guo, Ji‐Eun Seo, Xilin Li, N. Mei","doi":"10.1080/10937404.2019.1692744","DOIUrl":"https://doi.org/10.1080/10937404.2019.1692744","url":null,"abstract":"ABSTRACT Genotoxic compounds may be detoxified to non-genotoxic metabolites while many pro-carcinogens require metabolic activation to exert their genotoxicity in vivo. Standard genotoxicity assays were developed and utilized for risk assessment for over 40 years. Most of these assays are conducted in metabolically incompetent rodent or human cell lines. Deficient in normal metabolism and relying on exogenous metabolic activation systems, the current in vitro genotoxicity assays often have yielded high false positive rates, which trigger unnecessary and costly in vivo studies. Metabolically active cells such as hepatocytes have been recognized as a promising cell model in predicting genotoxicity of carcinogens in vivo. In recent years, significant advances in tissue culture and biological technologies provided new opportunities for using hepatocytes in genetic toxicology. This review encompasses published studies (both in vitro and in vivo) using hepatocytes for genotoxicity assessment. Findings from both standard and newly developed genotoxicity assays are summarized. Various liver cell models used for genotoxicity assessment are described, including the potential application of advanced liver cell models such as 3D spheroids, organoids, and engineered hepatocytes. An integrated strategy, that includes the use of human-based cells with enhanced biological relevance and throughput, and applying the quantitative analysis of data, may provide an approach for future genotoxicity risk assessment.","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"8 1","pages":"27 - 50"},"PeriodicalIF":7.2,"publicationDate":"2019-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75374110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}