Toxicologic Pathology最新文献_第3页

Scientific and Regulatory Policy Committee Points to Consider: Review of the United States Food and Drug Administration (FDA) Guidance on Pathology Peer Review in Nonclinical Toxicology Studies. 科学与监管政策委员会审议要点：美国食品和药物管理局 (FDA) 非临床毒理学研究病理学同行评审指南评审。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2024-02-01 Epub Date: 2024-06-06 DOI: 10.1177/01926233241248654

Kevin S McDorman, Bindu M Bennet, Karyn Colman, James D Fikes, Natalie D Keirstead, Lynda Lanning Retired, Barbara Munch, Annette Romeike, Kenneth A Schafer, Frédéric Schorsch, Michael S Thibodeau, Heath C Thomas, Sean Troth, John L Vahle, Frank J Geoly

{"title":"Scientific and Regulatory Policy Committee Points to Consider: Review of the United States Food and Drug Administration (FDA) Guidance on Pathology Peer Review in Nonclinical Toxicology Studies.","authors":"Kevin S McDorman, Bindu M Bennet, Karyn Colman, James D Fikes, Natalie D Keirstead, Lynda Lanning Retired, Barbara Munch, Annette Romeike, Kenneth A Schafer, Frédéric Schorsch, Michael S Thibodeau, Heath C Thomas, Sean Troth, John L Vahle, Frank J Geoly","doi":"10.1177/01926233241248654","DOIUrl":"10.1177/01926233241248654","url":null,"abstract":"In December 2021, the United States Food and Drug Administration (FDA) issued the final guidance for industry titled Pathology Peer Review in Nonclinical Toxicology Studies: Questions and Answers. The stated purpose of the FDA guidance is to provide information to sponsors, applicants, and nonclinical laboratory personnel regarding the management and conduct of histopathology peer review as part of nonclinical toxicology studies conducted in compliance with good laboratory practice (GLP) regulations. On behalf of and in collaboration with global societies of toxicologic pathology and the Society of Quality Assurance, the Scientific and Regulatory Policy Committee (SRPC) of the Society of Toxicologic Pathology (STP) initiated a review of this FDA guidance. The STP has previously published multiple papers related to the scientific conduct of a pathology peer review of nonclinical toxicology studies and appropriate documentation practices. The objectives of this review are to provide an in-depth analysis and summary interpretation of the FDA recommendations and share considerations for the conduct of pathology peer review in nonclinical toxicology studies that claim compliance to GLP regulations. In general, this working group is in agreement with the recommendations from the FDA guidance that has added clear expectations for pathology peer review preparation, conduct, and documentation.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thank You to Reviewers. 感谢审稿人。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-21 DOI: 10.1177/01926233241226572

引用次数: 0

Guide for Combining Primary Tumors for Statistical Analysis in Rodent Carcinogenicity Studies. 啮齿动物致癌性研究统计分析原发肿瘤组合指南》。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-03-06 DOI: 10.1177/01926233241230553

Charlotte Keenan, Muthafar Al-Haddawi, Jean-Guy Bienvenu, Alys Elizabeth Bradley, Paul Brown, Hepei Chen, Karyn Colman, Michael Elwell, Nicholas Gatto, Dawn Goodman, Binod Jacob, Lynda Lanning, LuAnn McKinney, Erin Muhlbradt, Rick Perry, Alessandro Piaia, Daniel Potenta, Karen S Regan, Benjamin Sefing, Michael Thibodeau, Erin Tibbs-Slone, Jochen Woicke, Craig M Zwickl

{"title":"Guide for Combining Primary Tumors for Statistical Analysis in Rodent Carcinogenicity Studies.","authors":"Charlotte Keenan, Muthafar Al-Haddawi, Jean-Guy Bienvenu, Alys Elizabeth Bradley, Paul Brown, Hepei Chen, Karyn Colman, Michael Elwell, Nicholas Gatto, Dawn Goodman, Binod Jacob, Lynda Lanning, LuAnn McKinney, Erin Muhlbradt, Rick Perry, Alessandro Piaia, Daniel Potenta, Karen S Regan, Benjamin Sefing, Michael Thibodeau, Erin Tibbs-Slone, Jochen Woicke, Craig M Zwickl","doi":"10.1177/01926233241230553","DOIUrl":"10.1177/01926233241230553","url":null,"abstract":"The Tumor Combination Guide was created at the request of the U. S. Food and Drug Administration (FDA) by a Working Group of biopharmaceutical experts from international societies of toxicologic pathology, the Food and Drug Administration (FDA), and members of the Standard for Exchange of Nonclinical Data (SEND) initiative, to assist pharmacology/toxicology reviewers and biostatisticians in statistical analysis of nonclinical tumor data. The guide will also be useful to study and peer review pathologists in interpreting the tumor data. This guide provides a higher-level hierarchy of tumor types or categories correlating the tumor names from the International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) publications with those available in the NEOPLASM controlled terminology (CT) code list in SEND. The version of CT used in a study should be referenced in the nonclinical study data reviewer's guide (SDRG) (section 3.1) of electronic submissions to the FDA. The tumor combination guide instructions and examples are in a tabular format to make informed decisions for combining tumor data for statistical analysis. The strategy for combining tumor types for statistical analysis is based on scientific criteria gleaned from the current scientific literature; as SEND and INHAND terminology and information evolve, this guide will be updated.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adeno-Associated Virus-Mediated Dorsal Root Ganglion Toxicity in the New Zealand White Rabbit. 腺相关病毒介导的新西兰白兔背根神经节毒性

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-02-22 DOI: 10.1177/01926233241229808

Eric Tien, Branka Grubor, Melissa Kirkland, Su Jing Chan, Nick van der Munnik, Wenlong Xu, Kate Henry, Stefan Hamann, Cong Wei, Wan-Hung Lee, Davide Gianni, Ashton Brennecke, Kalyani Nambiar, Jeron Chen, Bin Liu, Shen Shen, Claudine Tremblay, Edward D Plowey, Patrick Trapa, James Fikes, Junghae Suh, Dale Morris

{"title":"Adeno-Associated Virus-Mediated Dorsal Root Ganglion Toxicity in the New Zealand White Rabbit.","authors":"Eric Tien, Branka Grubor, Melissa Kirkland, Su Jing Chan, Nick van der Munnik, Wenlong Xu, Kate Henry, Stefan Hamann, Cong Wei, Wan-Hung Lee, Davide Gianni, Ashton Brennecke, Kalyani Nambiar, Jeron Chen, Bin Liu, Shen Shen, Claudine Tremblay, Edward D Plowey, Patrick Trapa, James Fikes, Junghae Suh, Dale Morris","doi":"10.1177/01926233241229808","DOIUrl":"10.1177/01926233241229808","url":null,"abstract":"Recombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) has been observed in non-human primates (NHPs) following intravenous (IV) and intrathecal (IT) delivery. Administration of recombinant AAV encoding a human protein transgene via a single intra-cisterna magna (ICM) injection in New Zealand white rabbits resulted in histopathology changes very similar to NHPs: mononuclear cell infiltration, degeneration/necrosis of sensory neurons, and nerve fiber degeneration of sensory tracts in the spinal cord and of multiple nerves. AAV-associated clinical signs and incidence/severity of histologic findings indicated that rabbits were equally or more sensitive than NHPs to sensory neuron damage. Another study using human and rabbit transgene constructs of the same protein demonstrated comparable changes suggesting that the effects are not an immune response to the non-self protein transgene. Rabbit has not been characterized as a species for general toxicity testing of AAV gene therapies, but these studies suggest that it may be an alternative model to investigate mechanisms of AAV-mediated neurotoxicity and test novel AAV designs mitigating these adverse effects.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139933025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep Learning-Based Spermatogenic Staging in Tissue Sections of Cynomolgus Macaque Testes. 基于深度学习的猕猴睾丸组织切片生精分期。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-03-11 DOI: 10.1177/01926233241234059

Lars Mecklenburg, C Marc Luetjens, Annette Romeike, Rohit Garg, Pranab Samanta, Amogh Mohanty, Tijo Thomas, Gerhard Weinbauer

{"title":"Deep Learning-Based Spermatogenic Staging in Tissue Sections of Cynomolgus Macaque Testes.","authors":"Lars Mecklenburg, C Marc Luetjens, Annette Romeike, Rohit Garg, Pranab Samanta, Amogh Mohanty, Tijo Thomas, Gerhard Weinbauer","doi":"10.1177/01926233241234059","DOIUrl":"10.1177/01926233241234059","url":null,"abstract":"The indirect assessment of adverse effects on fertility in cynomolgus monkeys requires that tissue sections of the testis be microscopically evaluated with awareness of the stage of spermatogenesis that a particular cross-section of a seminiferous tubule is in. This difficult and subjective task could very much benefit from automation. Using digital whole slide images (WSIs) from tissue sections of testis, we have developed a deep learning model that can annotate the stage of each tubule with high sensitivity, precision, and accuracy. The model was validated on six WSI using a six-stage spermatogenic classification system. Whole slide images contained an average number of 4938 seminiferous tubule cross-sections. On average, 78% of these tubules were staged with 29% in stage I-IV, 12% in stage V-VI, 4% in stage VII, 19% in stage VIII-IX, 18% in stage X-XI, and 17% in stage XII. The deep learning model supports pathologists in conducting a stage-aware evaluation of the testis. It also allows derivation of a stage-frequency map. The diagnostic value of this stage-frequency map is still unclear, as further data on its variability and relevance need to be generated for testes with spermatogenic disturbances.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Difference in the Mechanism of Iron Overload-Enhanced Acute Hepatotoxicity Induced by Thioacetamide and Carbon Tetrachloride in Rats. 硫代乙酰胺和四氯化碳诱导大鼠铁超载增强急性肝中毒机制的差异

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-03-25 DOI: 10.1177/01926233241235623

Yohei Inai, Takeshi Izawa, Tomomi Kamei, Sho Fujiwara, Miyuu Tanaka, Jyoji Yamate, Mitsuru Kuwamura

{"title":"Difference in the Mechanism of Iron Overload-Enhanced Acute Hepatotoxicity Induced by Thioacetamide and Carbon Tetrachloride in Rats.","authors":"Yohei Inai, Takeshi Izawa, Tomomi Kamei, Sho Fujiwara, Miyuu Tanaka, Jyoji Yamate, Mitsuru Kuwamura","doi":"10.1177/01926233241235623","DOIUrl":"10.1177/01926233241235623","url":null,"abstract":"Iron overload has been recognized as a risk factor for liver disease; however, little is known about its pathological role in the modification of liver injury. The purpose of this study is to investigate the influence of iron overload on liver injury induced by two hepatotoxicants with different pathogenesis in rats. Rats were fed a control (Cont), 0.8% high-iron (0.8% Fe), or 1% high-iron diet (1% Fe) for 4 weeks and were then administered with saline, thioacetamide (TAA), or carbon tetrachloride (CCl4). Hepatic and systemic iron overload were seen in the 0.8% and 1% Fe groups. Twenty-four hours after administration, hepatocellular necrosis induced by TAA and hepatocellular necrosis, degeneration, and vacuolation induced by CCl4, as well as serum transaminase values, were exacerbated in the 0.8% and 1% Fe groups compared to the Cont group. On the other hand, microvesicular vacuolation induced by CCl4 was decreased in 0.8% and 1% Fe groups. Hepatocellular DNA damage was increased by iron overload in both models, whereas a synergistic effect of oxidative stress by excess iron and hepatotoxicant was only present in the CCl4 model. The data showed that dietary iron overload exacerbates TAA- and CCl4-induced acute liver injury with different mechanisms.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Next-Generation Sequencing-Based Identification of Enterobacter hormaechei as Causative Agent of High Mortality Disease in NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ (NSG) Mice. 基于下一代测序的荷尔玛氏肠杆菌鉴定：NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) 小鼠高死亡率疾病的致病菌。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-03-13 DOI: 10.1177/01926233241231286

Catherine Si, Kourtney Nickerson, Taylor Simmons, Parker Denton, M Russell Nichols, Robert C Dysko, Mark Hoenerhoff, Rinosh Mani, Cheryl Woods, Kenneth S Henderson, Zachary T Freeman

{"title":"Next-Generation Sequencing-Based Identification of Enterobacter hormaechei as Causative Agent of High Mortality Disease in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) Mice.","authors":"Catherine Si, Kourtney Nickerson, Taylor Simmons, Parker Denton, M Russell Nichols, Robert C Dysko, Mark Hoenerhoff, Rinosh Mani, Cheryl Woods, Kenneth S Henderson, Zachary T Freeman","doi":"10.1177/01926233241231286","DOIUrl":"10.1177/01926233241231286","url":null,"abstract":"NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice, lacking many components of a mature immune system, are at increased risk of disease. General understanding of potential pathogens of these mice is limited. We describe a high mortality disease outbreak caused by an opportunistic bacterial infection in NSG mice. Affected animals exhibited perianal fecal staining, dehydration, and wasting. Histopathologic lesions included a primary necrotizing enterocolitis, with inflammatory and necrotizing lesions also occurring in the liver, kidneys, heart, and brain of some mice. All affected individuals tested negative for known opportunistic pathogens of immunodeficient mice. We initially identified a member of Enterobacter cloacae complex (ECC) in association with the outbreak by traditional diagnostics. ECC was cultured from extraintestinal organs, both with and without histopathologic lesions, suggesting bacteremia. Infrared spectroscopy and MALDI-TOF mass spectrometry demonstrated that isolates from the outbreak shared molecular features and likely a common origin. We subsequently hypothesized that advanced sequencing methods would identify a single species of ECC associated with clinical disease. Using a novel targeted amplicon-based next-generation sequencing assay, we identified Enterobacter hormaechei in association with this outbreak. Knowledge of this organism as a potential opportunistic pathogen in NSG mice is critical for preclinical studies to prevent loss of animals and confounding of research.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative Impact of Various Fasting Periods on the Welfare of Sprague-Dawley Rats With or Without Supplementation. 补充或不补充各种禁食期对 Sprague-Dawley 大鼠福利影响的比较

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-02-20 DOI: 10.1177/01926233241230536

Adeyemi O Adedeji, Fiona Zhong, Janice Corpuz, Fangyao Hu, Xiaofeng Zhao, Dewakar Sangaraju, Catherine F Ruff, Noel Dybdal

{"title":"Comparative Impact of Various Fasting Periods on the Welfare of Sprague-Dawley Rats With or Without Supplementation.","authors":"Adeyemi O Adedeji, Fiona Zhong, Janice Corpuz, Fangyao Hu, Xiaofeng Zhao, Dewakar Sangaraju, Catherine F Ruff, Noel Dybdal","doi":"10.1177/01926233241230536","DOIUrl":"10.1177/01926233241230536","url":null,"abstract":"In nonclinical toxicology studies, lab animals are fasted typically overnight, to reduce variability in some clinical pathology parameters. However, fasting adds undue stress, and this is particularly concerning in rodents given their fast metabolic rates. Furthermore, as rodents are nocturnal animals, an overnight fasting may cause a protracted negative metabolic state even when the fasting has technically ended, given their minimal activity and food consumption during the day. Therefore, to evaluate the impacts of different fasting durations (±DietGel supplementation) on rats' welfare, we assessed the traditional and ancillary clinical pathology parameters in Sprague-Dawley rats, along with body weight, organ weight, and histopathology. Although most endpoints were comparable between the different fasting durations (±DietGel supplementation), the long fasting times (≥8 hr) without DietGel supplementation caused significant decreases in body weight, liver weight, liver glycogen content, serum glucose, triglyceride, and creatinine concentrations-all findings suggestive of a negative energy balance that could impact animal welfare and consequently, data quality; while the short fasting time (4 hr) and DietGel supplementation were associated with higher triglycerides variability. Hence, we propose that short fasting time should be adequate for most toxicology studies in rats, and long fasting times should only be accommodated with scientific justification.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expression of Concern. 表达关切。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-03-07 DOI: 10.1177/01926233241238763

引用次数: 0

Toxicogenomics Approaches to Address Toxicity and Carcinogenicity in the Liver. 解决肝脏毒性和致癌性的毒物基因组学方法。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2024-01-30 DOI: 10.1177/01926233241227942

Arun R Pandiri, Scott S Auerbach, Jim L Stevens, Eric A G Blomme

{"title":"Toxicogenomics Approaches to Address Toxicity and Carcinogenicity in the Liver.","authors":"Arun R Pandiri, Scott S Auerbach, Jim L Stevens, Eric A G Blomme","doi":"10.1177/01926233241227942","DOIUrl":"10.1177/01926233241227942","url":null,"abstract":"Toxicogenomic technologies query the genome, transcriptome, proteome, and the epigenome in a variety of toxicological conditions. Due to practical considerations related to the dynamic range of the assays, sensitivity, cost, and technological limitations, transcriptomic approaches are predominantly used in toxicogenomics. Toxicogenomics is being used to understand the mechanisms of toxicity and carcinogenicity, evaluate the translational relevance of toxicological responses from in vivo and in vitro models, and identify predictive biomarkers of disease and exposure. In this session, a brief overview of various transcriptomic technologies and practical considerations related to experimental design was provided. The advantages of gene network analyses to define mechanisms were also discussed. An assessment of the utility of toxicogenomic technologies in the environmental and pharmaceutical space showed that these technologies are being increasingly used to gain mechanistic insights and determining the translational relevance of adverse findings. Within the environmental toxicology area, there is a broader regulatory consideration of benchmark doses derived from toxicogenomics data. In contrast, these approaches are mainly used for internal decision-making in pharmaceutical development. Finally, the development and application of toxicogenomic signatures for prediction of apical endpoints of regulatory concern continues to be area of intense research.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11014763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0