Current Research in Biotechnology最新文献

{"title":"Validation of adventitious agent safety in Yimmugo®, a novel IVIG preparation for human use","authors":"Gerhard Poelsler,&nbsp;Marcel Asper,&nbsp;Sebastian Lülf,&nbsp;Florian Zirkel","doi":"10.1016/j.crbiot.2025.100333","DOIUrl":"10.1016/j.crbiot.2025.100333","url":null,"abstract":"<div><div>Intravenous infusion of human IgG (IVIG) is of vital importance for patients suffering from primary or secondary immunodeficiency syndromes, but also has been found to be clinically beneficial in other diseases with autoimmunogenic or inflammatory background. Its clinical application and therefore its demand have been continuously rising during the last decades. Besides IgG, other human antibody classes have also entered clinical applications, therefore a novel manufacturing procedure has been conceived which allows simultaneous isolation of two immunoglobulin preparations, Yimmugo™ (an IVIG) and trimodulin (an IgM concentrate). Since the only suitable source for these antibodies is human donor plasma, from which it is isolated using a series of dedicated purification steps, there is a risk of carrying over infectious human pathogens into the final preparations. We describe here validation of the measures taken to provide Yimmugo, an IVIG product, with robust margins of biological safety, free of pathogens of microbial, viral or prion origin. To this end, we spiked manufacturing process intermediates of Yimmugo with diverse pathogens and tested the capacity of the manufacturing steps to clear these from the preparation. We show that four different purification steps of the Yimmugo procedure efficiently confer clearance of viral and prion pathogens, thereby providing a safe product even in the hypothetical case that an infectious agent in the original material were present. Consequently, the novel preparation procedure yields a provably safe product and simultaneously allows production of an additional medicine from the same plasma pool.</div></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":"10 ","pages":"Article 100333"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094595","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":"Insights from antiaging-related X discussions: A six-year #Longevity hashtag analysis study","authors":"Joanna Bensz ,&nbsp;Dariusz Sołdacki ,&nbsp;Zilin Ma ,&nbsp;Farhan Bin Matin ,&nbsp;Maima Matin ,&nbsp;Atanas G. Atanasov","doi":"10.1016/j.crbiot.2025.100280","DOIUrl":"10.1016/j.crbiot.2025.100280","url":null,"abstract":"<div><div>As social media platforms continue to play an increasingly significant role in shaping public discourse and disseminating scientific information, understanding how longevity and aging-related topics are discussed online has become crucial for researchers and healthcare professionals. This study investigates the global discourse on longevity and aging through the analysis of the hashtag #Longevity on the social media platform X (formerly Twitter) over a six-year period from August 1, 2018, to August 1, 2024. A total of 382 032 posts were shared by 109 935 users across 200 countries. The analysis focused on revealing key themes, geographical distribution, sentiment analysis, and the most frequently mentioned supplements and drugs related to longevity. The results show a high level of engagement with the hashtag, primarily driven by users from the United States, followed by the United Kingdom and Canada. Sentiment analysis revealed predominantly positive attitudes towards longevity-related topics, with a slight but statistically significant (p &lt; 0.0001) decline during and after the COVID-19 pandemic. The study identified nicotinamide mononucleotide, rapamycin, and green tea as the most frequently mentioned supplements or drugs in longevity discussions. Notably, there was a significant increase in discussions about niacin derivatives, particularly nicotinamide mononucleotide, during and after the pandemic period. This study highlights the importance of social media as a tool for gauging public interest and sentiment towards scientific topics like longevity, providing valuable insights for researchers, healthcare professionals, and policymakers to enhance science communication and public engagement.</div></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":"9 ","pages":"Article 100280"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548276","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":"Design of a thermal stress microfluidic platform to screen stability of therapeutic proteins in pharmaceutical formulations","authors":"O. Bortone ,&nbsp;S. Fiorenza ,&nbsp;M. Baldassarre ,&nbsp;N. Falco ,&nbsp;M. Amidi ,&nbsp;T. Markkula ,&nbsp;P.A. Netti ,&nbsp;E. Torino","doi":"10.1016/j.crbiot.2025.100273","DOIUrl":"10.1016/j.crbiot.2025.100273","url":null,"abstract":"<div><div>Therapeutic proteins have great potentialities for the care of a wide spectrum of diseases, for which other small synthetic drugs result ineffective. Due to challenges related to their immunogenicity, the journey of biologics into clinics still faces obstacles. Among the causes of protein immunogenicity, their natural propensity to aggregation is crucial, indeed, to study their stability, pharmaceutical formulations are generally exposed to diverse environmental physicochemical conditions. Traditional approaches to explore protein behavior are effort-demanding, lengthy and expensive, resulting in a limited knowledge of biomolecule stability. There is an urgent need to develop faster and more cost-effective technologies for biological formulation development. In this work, the conceptualization, design and implementation of a modular and automated microfluidic platform to provide thermal stress to highly concentrated and viscous pharmaceutical formulations is presented. The microfluidic platform validity in terms of reliability and comparability to a forced degradation batch-wise stimulation is demonstrated by thermally stimulating and analyzing through SE-HPLC (Size Exclusion – High Performance Liquid Chromatography) different high concentration (&gt; 100 mg/ml) therapeutic nanobody-based formulations. Remarkably, the ranking of the formulations returned by the microfluidic thermal stress platform follows the same trend obtained through well-established industrial in-batch stimulations. Furthermore, data coming from microfluidic stimulations well correlates to outcomes coming from industrial methodologies for storage and accelerated stability studies.</div></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":"9 ","pages":"Article 100273"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143136460","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":"Cultivation of the Oligo-Mouse-Microbiota OMM12 in the peristaltic mixed tubular bioreactor PETR","authors":"David Vorländer,&nbsp;Kristin Hoffmann,&nbsp;Katrin Dohnt","doi":"10.1016/j.crbiot.2025.100294","DOIUrl":"10.1016/j.crbiot.2025.100294","url":null,"abstract":"<div><div>The intestinal microbiota plays a crucial role in human health and disease, and is therefore of great interest in various research areas. However, studies with humans are limited and difficult to control, leading to a growing demand for sophisticated bioreactor systems that can mimic human intestinal conditions <em>in vitro</em>. The main objective of this study is to compare the <em>in vitro</em> growth of a defined microbiota in the recently published PEristaltic mixed Tubular bioReactor (PETR) with previously published <em>in vivo</em> data for the same microbiota. PETR simulates various colonic conditions, including peristaltic mixing, dialytic water and metabolite removal, and a temporally constant and longitudinally progressive pH gradient in a continuously operated tubular bioreactor. The Oligo-Mouse-Microbiota OMM¹² was chosen as model microbiota and consists of 12 bacteria representing the major phyla of the mouse intestine. During 10<!--> <!-->d continuous cultivation in PETR, community composition was regularly analyzed using strain-specific qPCR. The results were consistent with the formation of organic acids measured by HPLC. After approximately 6<!--> <!-->d, the optical density, concentrations of organic acids, and the microbiota composition remained relatively stable. Despite the different intestinal conditions of humans and mice, several similarities between reactor cultivation and gnotobiotic mouse model confirm PETR as a suitable system for microbiota research.</div></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":"9 ","pages":"Article 100294"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907644","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":"Exploring nutritional supplement use for countering respiratory tract infections through an X (formerly Twitter)-based survey","authors":"Rajeev K. Singla ,&nbsp;Himel Mondal ,&nbsp;Shailja Singla ,&nbsp;Ronita De ,&nbsp;Sahar Behzad ,&nbsp;Mihnea-Alexandru Găman ,&nbsp;Siva Sai Chandragiri ,&nbsp;Merisa Cenanovic ,&nbsp;Jayanta Kumar Patra ,&nbsp;Jennifer R. Depew ,&nbsp;Hemanth Kumar Boyina ,&nbsp;Abdulkadir Yusif Maigoro ,&nbsp;Soojin Lee ,&nbsp;Omar M. Atrooz ,&nbsp;Gitishree Das ,&nbsp;Fabien Schultz ,&nbsp;Emad Mohamed Abdallah ,&nbsp;Hitesh Chopra ,&nbsp;Jamil Ahmad ,&nbsp;Rupesh K. Gautam ,&nbsp;Bairong Shen","doi":"10.1016/j.crbiot.2025.100282","DOIUrl":"10.1016/j.crbiot.2025.100282","url":null,"abstract":"<div><h3>Background</h3><div>Respiratory tract infections are a common health issue, driving interest in preventive strategies like nutritional supplements, while evidence on their usage and effectiveness remains limited. In this context, social media platforms, particularly X (formerly Twitter), provide a unique opportunity to gather large-scale public health-related data.</div></div><div><h3>Objectives</h3><div>In this study, we aimed to survey participants’ uses and opinions on nutritional supplements in prevention or treatment of respiratory tract infections, by using X.</div></div><div><h3>Methods</h3><div>A survey was conducted between 1st and 15th December 2022. A single open-ended question “Which are the best dietary supplements to counteract respiratory infections?“ was asked. One week after the start of the survey, a poll was posted to get more relevant information and boost the survey’s reach. Total endorsements were calculated for each tweet posted as the total sum of replies, retweets, and likes.</div></div><div><h3>Results</h3><div>The open-ended question received a total of 118 retweets, 39 quotes, and 371 likes, while the poll received 56 retweets, 13 quotes, and 67 likes. A total of 495 replies, 2,251 retweets, 5,118 likes, and 148 quotes were received for the question and its related tweets. Vitamin D (1,607 endorsements), zinc (1,347 endorsements), vitamin C (803 endorsements), magnesium (694 endorsements), and honey (661 endorsements) were the nutritional supplements that received most endorsements.</div></div><div><h3>Conclusion</h3><div>Various foods, drinks, and natural ingredients have been suggested as potentially helpful for counteracting respiratory infections. Approximately half of respondents indicated using such supplements for themselves. The result of this study supports the idea that the X platform can be used as an effective survey tool to study global health-related behaviours and trends.</div></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":"9 ","pages":"Article 100282"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935131","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":"Biogenic silver nanoparticles produced by Trichoderma reesei inhibit SARS-CoV-2 infection, reduce lung viral load and ameliorate acute pulmonary inflammation","authors":"Marcus V.M.V. Amaral ,&nbsp;Cláudia B. Carraro ,&nbsp;Amanda C.C. Antoniêto ,&nbsp;Mariana N. Costa ,&nbsp;Thais F.C. Fraga-Silva ,&nbsp;Ualter G. Cipriano ,&nbsp;Rodrigo P.F. Abuná ,&nbsp;Tamara S. Rodrigues ,&nbsp;Ronaldo B. Martins ,&nbsp;Andreia M. Luzenti ,&nbsp;Glaucia R. Caruso ,&nbsp;Priscyla D. Marcato ,&nbsp;Vania L.D. Bonato ,&nbsp;Dario S. Zamboni ,&nbsp;Bergman M. Ribeiro ,&nbsp;Sônia N. Báo ,&nbsp;Joao S. da Silva ,&nbsp;Flávio P. Veras ,&nbsp;Roberto N. Silva","doi":"10.1016/j.crbiot.2025.100277","DOIUrl":"10.1016/j.crbiot.2025.100277","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), posed a significant global health challenge and still demands efforts to develop new therapies. In this study, we investigated the potential of biogenic silver nanoparticles (AgNPs) synthesized by the fungus <em>Trichoderma reesei</em> to combat SARS-CoV-2 infection. In silico studies showed that AgNPs, ranging from 7 nm to 50 nm, have high affinity for spike protein from different variant of SARS-CoV-2. Our findings show that AgNPs effectively do not affect cell viability in Calu-3 cells, inhibit viral infection in Vero-E6 cells and progression of infection <em>in vitro</em>. Additionally, AgNPs impair caspase-1 activation, lactate dehydrogenase release and IL-1β production by human monocytes. Moreover, our study reveals that AgNPs treatment significantly alleviated acute lung injury induced by SARS-CoV-2 infection in Syrian hamsters. This suggests that AgNPs treatment effectively impairs viral replication or propagation within lung tissue, highlighting its potential as an antiviral agent against SARS-CoV-2. Further investigations are warranted to elucidate the underlying mechanisms of action of AgNPs and to assess their safety and efficacy in clinical settings. Nonetheless, our findings offer promising insights into the development of novel therapeutic strategies for combating COVID-19 and reducing its associated morbidity and mortality.</div></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":"9 ","pages":"Article 100277"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372916","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":"Importance of substrate type and its constituents on overall performance of microbial fuel cells","authors":"Somil Thakur,&nbsp;Rajnish Kaur Calay,&nbsp;Mohamad Y. Mustafa,&nbsp;Fasil E. Eregno,&nbsp;Ravindra R. Patil","doi":"10.1016/j.crbiot.2025.100272","DOIUrl":"10.1016/j.crbiot.2025.100272","url":null,"abstract":"<div><div>Microbial Fuel Cells (MFC) have emerged as a potential wastewater treatment technology that utilizes metabolic processes of microorganisms present in the wastewater to disintegrate organic substrates and harness direct electricity. This paper reviews the potential of different wastewater types as a suitable substrate for microbial activities in MFCs. Substrate composition (carbon source, nutrient content and inhibitory compounds) directly affects the microbial growth, wastewater treatment potential, electron transfer rate and power harvested. Readily biodegradable substrates such as acetate and glucose promote microbial metabolism and electron transport, thus resulting in enhanced power generation. Substrates such as municipal or agricultural wastewater that constitute both simple and complex organic matter require longer breakdown durations but can provide MFCs with long term operational stability. On the other hand, substrates such as leachate from landfills, mining wastewater etc. are generally unsuitable for regular operations. The paper discusses the challenges such as suitability of various wastewaters, unpredictability of composition, presence of inhibitory chemicals like heavy metals or toxic organics that can subdue the microbial activity and reduce efficiency of a MFC reactor. It aims to identify the relationship between the substrate characteristics and MFC performance in order to select the substrate for achieving optimal output from MFC technology. The suitable substrates that exhibit optimal performance in terms of current and power output, coulombic efficiency, and reduction in chemical oxygen demand are identified.</div></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":"9 ","pages":"Article 100272"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143136613","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":"Peptides as a leading class therapeutic agents: future and challenges","authors":"Nikolay T. Tzvetkov,&nbsp;Atanas G. Atanasov","doi":"10.1016/j.crbiot.2025.100323","DOIUrl":"10.1016/j.crbiot.2025.100323","url":null,"abstract":"","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":"10 ","pages":"Article 100323"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879193","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":"Aptamer-based diagnostics and therapeutics in viral sepsis: current progress, application and future prospects","authors":"Noraini Abd-Aziz ,&nbsp;Fatimah Ibrahim ,&nbsp;Sun Tee Tay","doi":"10.1016/j.crbiot.2025.100318","DOIUrl":"10.1016/j.crbiot.2025.100318","url":null,"abstract":"<div><div>Sepsis is a systemic inflammatory response to microbial infection that is characterized by a spectrum of physiological and pathological disorders. Viruses have been identified with varying roles in the context of sepsis. Diagnosing viral sepsis poses a great challenge due to a lack of viral detection reagents and assays, contributing to the underreporting of prevalence. Aptamers are single-stranded nucleic acids (either DNA or RNA) that can fold into specific structures, enabling their binding with a wide array of target molecules with high affinity and selectivity. This review provides updates on advances in aptamer development for viruses implicated in sepsis, aptamer selection methodologies through Systematic Evolution of Ligands by Exponential Enrichment (SELEX), and application of aptamer-based diagnostics and therapeutics. Additionally, several critical challenges in aptamer technology are addressed, with special emphasis on its analytical sensitivity, functional complexity, and translation to clinical practice.</div></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":"10 ","pages":"Article 100318"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723517","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":"Spatial profiling technologies for research and clinical application in head and neck squamous cell cancers","authors":"Artur Nieszporek ,&nbsp;Małgorzata Wierzbicka ,&nbsp;Aadil Khan ,&nbsp;Mateusz Jeziorny ,&nbsp;Patryk Kraiński ,&nbsp;Joanna Cybinska ,&nbsp;Patrycja Gazinska","doi":"10.1016/j.crbiot.2025.100321","DOIUrl":"10.1016/j.crbiot.2025.100321","url":null,"abstract":"<div><div>The efficacy of clinical treatment in head and neck squamous cell carcinoma (HNSCC) may be influenced by interactions within the tumor microenvironment (TME), involving non-malignant cells such as tumor-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs). These cells are crucial parts of the complex and dynamic TME. High-throughput spatial profiling technologies show remarkable potential in identifying predictive biomarkers in HNSCC’s TME. Despite advancements in molecular characterization, the translation of these insights into clinical practice remains limited.</div><div>Understanding these interactions and the TME is pertinent for developing effective therapies and pinpointing biomarkers that predict treatment responses. Spatial profiling also provides comprehensive insights into the cancer multi-omics by characterizing diverse and heterogeneous cell type, cell density, location, and intercellular interactions within the TME. HNSCC continues to be a major global health issue with rising incidence and mortality rates. Although immunotherapies have been effective for some, they benefit only a subset of patients. Spatial profiling helps uncover actionable biomarkers by exposing tumor heterogeneity and immune system interactions, paving the way for more precise medicine in HNSCC. Although the clinical application of multi-omics tumor profiling is still nascent, these technologies hold promise in enhancing our understanding of HNSCC biology and immuno-oncology, guiding future precision-treatment strategies.</div><div>This review outlines the applications of high-throughput spatial profiling technologies in both research and clinical settings for HNSCC, highlighting their potential to improve therapeutic strategies through an enhanced understanding of the HNSCC microenvironment. The successful integration of spatial profiling technologies into HNSCC research and clinical practice depends on a standardized, multicenter pipeline that ensures data consistency, seamless integration, and scalability. By combining high-resolution spatial transcriptomics with clinical and genomic insights, this approach has the potential to refine biomarker discovery, enhance patient stratification, and optimize immunotherapy strategies, ultimately paving the way for more precise and effective cancer treatments.</div></div>","PeriodicalId":52676,"journal":{"name":"Current Research in Biotechnology","volume":"10 ","pages":"Article 100321"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763806","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}