\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"},{slug:"intechopen-s-chapter-awarded-the-guenther-von-pannewitz-preis-2020-20200715",title:"IntechOpen's Chapter Awarded the Günther-von-Pannewitz-Preis 2020"},{slug:"suf-and-intechopen-announce-collaboration-20200331",title:"SUF and IntechOpen Announce Collaboration"}]},book:{item:{type:"book",id:"3060",leadTitle:null,fullTitle:"Plant Breeding from Laboratories to Fields",title:"Plant Breeding from Laboratories to Fields",subtitle:null,reviewType:"peer-reviewed",abstract:"Breeding of crop plants to make them more adapted to human agricultural systems has been on-going during domestication the last 10 000 years. \r\nHowever, only recently with the invention of the Mendelian principles of genetics and the subsequent development of quantitative genetics during the twentieth century has such genetic crop improvement become based on a general theory. During the last 50 years plant breeding has entered a molecular era based on molecular tools to analyse DNA, RNA and proteins and associate such molecular results with plant phenotype. These marker trait associations develop fast to enable more efficient breeding. However, they still leave a major part of breeding to be performed through selection of phenotypes using quantitative genetic tools. The ten chapters of this book illustrate this development.",isbn:null,printIsbn:"978-953-51-1090-3",pdfIsbn:"978-953-51-5372-6",doi:"10.5772/3362",price:119,priceEur:129,priceUsd:155,slug:"plant-breeding-from-laboratories-to-fields",numberOfPages:300,isOpenForSubmission:!1,isInWos:1,hash:"5b517f307caac739435f7fbaed5326ac",bookSignature:"Sven Bode Andersen",publishedDate:"May 22nd 2013",coverURL:"https://cdn.intechopen.com/books/images_new/3060.jpg",numberOfDownloads:64011,numberOfWosCitations:92,numberOfCrossrefCitations:72,numberOfDimensionsCitations:176,hasAltmetrics:0,numberOfTotalCitations:340,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 24th 2012",dateEndSecondStepPublish:"May 15th 2012",dateEndThirdStepPublish:"August 11th 2012",dateEndFourthStepPublish:"September 10th 2012",dateEndFifthStepPublish:"October 10th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,editors:[{id:"79388",title:"Prof.",name:"Sven Bode",middleName:null,surname:"Andersen",slug:"sven-bode-andersen",fullName:"Sven Bode Andersen",profilePictureURL:"https://mts.intechopen.com/storage/users/79388/images/system/79388.jpg",biography:"Sven Bode Andersen is a Professor of Plant Breeding at the Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Denmark. He received a M.Sc. in Agronomy (Horticulture) in March 1980. In June 1983, he obtained a Ph.D. in Agronomy (Plant Breeding) with the thesis on Haploid production in plant breeding. He became the professor of Plant Breeding in May 2003. His research focuses on the following: Biotechnology for Plant Breeding, Doubled haploid systems, protoplasts, Molecular markers for Diversity analysis and genetic dissection of important traits, Quantitative trait analysis of resistance, quality and yield.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Copenhagen",institutionURL:null,country:{name:"Denmark"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"311",title:"Plant Genetics",slug:"agronomy-plant-genetics"}],chapters:[{id:"40396",title:"Genomic in situ Hybridization in Triticeae: A Methodological Approach",doi:"10.5772/52928",slug:"genomic-in-situ-hybridization-in-triticeae-a-methodological-approach",totalDownloads:4677,totalCrossrefCites:0,totalDimensionsCites:5,signatures:"Sandra Patussi Brammer, Santelmo Vasconcelos, Liane Balvedi\nPoersch, Ana Rafaela Oliveira and Ana Christina Brasileiro-Vidal",downloadPdfUrl:"/chapter/pdf-download/40396",previewPdfUrl:"/chapter/pdf-preview/40396",authors:[{id:"74308",title:"Dr.",name:"Santelmo",surname:"Vasconcelos",slug:"santelmo-vasconcelos",fullName:"Santelmo Vasconcelos"},{id:"160855",title:"Dr.",name:"Sandra",surname:"Brammer",slug:"sandra-brammer",fullName:"Sandra Brammer"},{id:"160856",title:"Dr.",name:"Ana Christina",surname:"Brasileiro-Vidal",slug:"ana-christina-brasileiro-vidal",fullName:"Ana Christina Brasileiro-Vidal"},{id:"160857",title:"BSc.",name:"Ana Rafaela",surname:"Oliveira",slug:"ana-rafaela-oliveira",fullName:"Ana Rafaela Oliveira"},{id:"160858",title:"MSc.",name:"Liane Balvedi",surname:"Poersch",slug:"liane-balvedi-poersch",fullName:"Liane Balvedi Poersch"},{id:"165999",title:"Dr.",name:"Sandra Patussi",surname:"Brammer",slug:"sandra-patussi-brammer",fullName:"Sandra Patussi Brammer"}],corrections:null},{id:"44340",title:"SRAP Molecular Marker Technology in Plant Science",doi:"10.5772/54511",slug:"srap-molecular-marker-technology-in-plant-science",totalDownloads:3748,totalCrossrefCites:4,totalDimensionsCites:11,signatures:"Genyi Li, Peter B. E. McVetty and Carlos F. Quiros",downloadPdfUrl:"/chapter/pdf-download/44340",previewPdfUrl:"/chapter/pdf-preview/44340",authors:[{id:"160577",title:"Associate Prof.",name:"Genyi",surname:"Li",slug:"genyi-li",fullName:"Genyi Li"}],corrections:null},{id:"40178",title:"Molecular Markers and Marker-Assisted Breeding in Plants",doi:"10.5772/52583",slug:"molecular-markers-and-marker-assisted-breeding-in-plants",totalDownloads:20608,totalCrossrefCites:39,totalDimensionsCites:91,signatures:"Guo-Liang Jiang",downloadPdfUrl:"/chapter/pdf-download/40178",previewPdfUrl:"/chapter/pdf-preview/40178",authors:[{id:"158810",title:"Dr.",name:"Guo-Liang",surname:"Jiang",slug:"guo-liang-jiang",fullName:"Guo-Liang Jiang"}],corrections:null},{id:"44012",title:"Genetic Dissection of Blackleg Resistance Loci in Rapeseed (Brassica napus L.)",doi:"10.5772/53611",slug:"genetic-dissection-of-blackleg-resistance-loci-in-rapeseed-brassica-napus-l-",totalDownloads:2963,totalCrossrefCites:13,totalDimensionsCites:29,signatures:"Harsh Raman, Rosy Raman and Nick Larkan",downloadPdfUrl:"/chapter/pdf-download/44012",previewPdfUrl:"/chapter/pdf-preview/44012",authors:[{id:"76347",title:"Dr.",name:"Harsh",surname:"Raman",slug:"harsh-raman",fullName:"Harsh Raman"},{id:"166451",title:"Dr.",name:"Rosy",surname:"Raman",slug:"rosy-raman",fullName:"Rosy Raman"},{id:"166452",title:"Dr.",name:"Nicholas",surname:"Larkan",slug:"nicholas-larkan",fullName:"Nicholas Larkan"}],corrections:null},{id:"44502",title:"Marker Assisted Selection for Common Bean Diseases Improvements in Tanzania: Prospects and Future Needs",doi:"10.5772/52823",slug:"marker-assisted-selection-for-common-bean-diseases-improvements-in-tanzania-prospects-and-future-nee",totalDownloads:3479,totalCrossrefCites:3,totalDimensionsCites:12,signatures:"George Muhamba Tryphone, Luseko Amos Chilagane, Deogracious\nProtas, Paul Mbogo Kusolwa and Susan Nchimbi-Msolla",downloadPdfUrl:"/chapter/pdf-download/44502",previewPdfUrl:"/chapter/pdf-preview/44502",authors:[{id:"157660",title:"M.Sc.",name:"George",surname:"Tryphone",slug:"george-tryphone",fullName:"George Tryphone"},{id:"166366",title:"Dr.",name:"Deogracious",surname:"Protas",slug:"deogracious-protas",fullName:"Deogracious Protas"},{id:"166412",title:"Dr.",name:"Luseko",surname:"Chilagane",slug:"luseko-chilagane",fullName:"Luseko Chilagane"},{id:"166413",title:"Dr.",name:"Paul",surname:"Kusolwa",slug:"paul-kusolwa",fullName:"Paul Kusolwa"},{id:"166414",title:"Dr.",name:"Susan",surname:"Nchimbi-Msolla",slug:"susan-nchimbi-msolla",fullName:"Susan Nchimbi-Msolla"}],corrections:null},{id:"44503",title:"Breeding for Drought Resistance Using Whole Plant Architecture — Conventional and Molecular Approach",doi:"10.5772/54983",slug:"breeding-for-drought-resistance-using-whole-plant-architecture-conventional-and-molecular-approach",totalDownloads:3700,totalCrossrefCites:3,totalDimensionsCites:5,signatures:"H.E. Shashidhar, Adnan Kanbar, Mahmoud Toorchi, G.M.\nRaveendra, Pavan Kundur, H.S. Vimarsha, Rakhi Soman, Naveen G.\nKumar, Berhanu Dagnaw Bekele and P. Bhavani",downloadPdfUrl:"/chapter/pdf-download/44503",previewPdfUrl:"/chapter/pdf-preview/44503",authors:[{id:"157332",title:"Dr.",name:"Halagappa",surname:"Shashidhar",slug:"halagappa-shashidhar",fullName:"Halagappa Shashidhar"}],corrections:null},{id:"44529",title:"Breeding to Improve Symbiotic Effectiveness of Legumes",doi:"10.5772/53003",slug:"breeding-to-improve-symbiotic-effectiveness-of-legumes",totalDownloads:2534,totalCrossrefCites:2,totalDimensionsCites:7,signatures:"Vladimir A. Zhukov, Oksana Y. Shtark, Alexey Y. Borisov and Igor A.\nTikhonovich",downloadPdfUrl:"/chapter/pdf-download/44529",previewPdfUrl:"/chapter/pdf-preview/44529",authors:[{id:"73360",title:"Dr.",name:"Alexey",surname:"Borisov",slug:"alexey-borisov",fullName:"Alexey Borisov"},{id:"81134",title:"Dr.",name:"Vladimir",surname:"Zhukov",slug:"vladimir-zhukov",fullName:"Vladimir Zhukov"},{id:"81139",title:"Dr.",name:"Oksana",surname:"Shtark",slug:"oksana-shtark",fullName:"Oksana Shtark"},{id:"81142",title:"Prof.",name:"Igor",surname:"Tikhonovich",slug:"igor-tikhonovich",fullName:"Igor Tikhonovich"}],corrections:null},{id:"44504",title:"Opium Poppy: Genetic Upgradation Through Intervention of Plant Breeding Techniques",doi:"10.5772/53132",slug:"opium-poppy-genetic-upgradation-through-intervention-of-plant-breeding-techniques",totalDownloads:12987,totalCrossrefCites:0,totalDimensionsCites:4,signatures:"Brij Kishore Mishra, Anu Rastogi, Ameena Siddiqui, Mrinalini\nSrivastava, Nidhi Verma, Rawli Pandey, Naresh Chandra Sharma and\nSudhir Shukla",downloadPdfUrl:"/chapter/pdf-download/44504",previewPdfUrl:"/chapter/pdf-preview/44504",authors:[{id:"156649",title:"Dr.",name:"Sudhir",surname:"Shukla",slug:"sudhir-shukla",fullName:"Sudhir Shukla"}],corrections:null},{id:"44016",title:"Castor Breeding",doi:"10.5772/56216",slug:"castor-breeding",totalDownloads:6936,totalCrossrefCites:4,totalDimensionsCites:8,signatures:"Máira Milani and Márcia Barreto de Medeiros Nóbrega",downloadPdfUrl:"/chapter/pdf-download/44016",previewPdfUrl:"/chapter/pdf-preview/44016",authors:[{id:"74313",title:"M.Sc.",name:"Maira",surname:"Milani",slug:"maira-milani",fullName:"Maira Milani"},{id:"156611",title:"Dr.",name:"Márcia",surname:"Barreto De Medeiros Nóbrega",slug:"marcia-barreto-de-medeiros-nobrega",fullName:"Márcia Barreto De Medeiros Nóbrega"}],corrections:null},{id:"41024",title:"Participatory Plant Quality Breeding: An Ancient Art Revisited by Knowledge Sharing. The Portuguese Experience",doi:"10.5772/52951",slug:"participatory-plant-quality-breeding-an-ancient-art-revisited-by-knowledge-sharing-the-portuguese-ex",totalDownloads:2380,totalCrossrefCites:4,totalDimensionsCites:4,signatures:"Maria Carlota Vaz Patto, Pedro Manuel Mendes-Moreira, Mara Lisa\nAlves, Elsa Mecha, Carla Brites, Maria do Rosário Bronze and Silas\nPego",downloadPdfUrl:"/chapter/pdf-download/41024",previewPdfUrl:"/chapter/pdf-preview/41024",authors:[{id:"70071",title:"Prof.",name:"Maria",surname:"Bronze",slug:"maria-bronze",fullName:"Maria Bronze"},{id:"160017",title:"Dr.",name:"Maria Carlota",surname:"Vaz Patto",slug:"maria-carlota-vaz-patto",fullName:"Maria Carlota Vaz Patto"},{id:"160020",title:"MSc.",name:"Pedro",surname:"Mendes-Moreira",slug:"pedro-mendes-moreira",fullName:"Pedro Mendes-Moreira"},{id:"160021",title:"Dr.",name:"Carla",surname:"Brites",slug:"carla-brites",fullName:"Carla Brites"},{id:"160022",title:"Dr.",name:"Silas",surname:"Pego",slug:"silas-pego",fullName:"Silas Pego"},{id:"166078",title:"MSc.",name:"Mara Lisa",surname:"Alves",slug:"mara-lisa-alves",fullName:"Mara Lisa Alves"},{id:"166079",title:"MSc.",name:"Elsa",surname:"Mecha",slug:"elsa-mecha",fullName:"Elsa Mecha"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"3554",title:"Rice",subtitle:"Germplasm, Genetics and Improvement",isOpenForSubmission:!1,hash:"4bd6a333920f0f208c44c2e9fbfdd215",slug:"rice-germplasm-genetics-and-improvement",bookSignature:"Wengui Yan and Jinsong Bao",coverURL:"https://cdn.intechopen.com/books/images_new/3554.jpg",editedByType:"Edited by",editors:[{id:"94348",title:"Dr.",name:"Wengui",surname:"Yan",slug:"wengui-yan",fullName:"Wengui Yan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1404",title:"Aflatoxins",subtitle:"Detection, Measurement and Control",isOpenForSubmission:!1,hash:"e3a2b9bd1c46dd47875d6a0f3d8b2a39",slug:"aflatoxins-detection-measurement-and-control",bookSignature:"Irineo Torres-Pacheco",coverURL:"https://cdn.intechopen.com/books/images_new/1404.jpg",editedByType:"Edited by",editors:[{id:"62984",title:"Dr.",name:"Irineo",surname:"Torres-Pacheco",slug:"irineo-torres-pacheco",fullName:"Irineo Torres-Pacheco"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2079",title:"Problems, Perspectives and Challenges of Agricultural Water Management",subtitle:null,isOpenForSubmission:!1,hash:"183bb777195754e887da67131255661f",slug:"problems-perspectives-and-challenges-of-agricultural-water-management",bookSignature:"Manish Kumar",coverURL:"https://cdn.intechopen.com/books/images_new/2079.jpg",editedByType:"Edited by",editors:[{id:"102967",title:"Dr.",name:"Manish",surname:"Kumar",slug:"manish-kumar",fullName:"Manish Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1782",title:"Agricultural Science",subtitle:null,isOpenForSubmission:!1,hash:"5a4e92f7ffd1fabdcfe769a0ad54d48b",slug:"agricultural-science",bookSignature:"Godwin Aflakpui",coverURL:"https://cdn.intechopen.com/books/images_new/1782.jpg",editedByType:"Edited by",editors:[{id:"93100",title:"Dr.",name:"Godwin",surname:"Aflakpui",slug:"godwin-aflakpui",fullName:"Godwin Aflakpui"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"597",title:"Crop Production Technologies",subtitle:null,isOpenForSubmission:!1,hash:"7f87c31dfd7e38f3e10cf7ec02df2201",slug:"crop-production-technologies",bookSignature:"Peeyush Sharma and Vikas Abrol",coverURL:"https://cdn.intechopen.com/books/images_new/597.jpg",editedByType:"Edited by",editors:[{id:"73200",title:"Dr.",name:"Peeyush",surname:"Sharma",slug:"peeyush-sharma",fullName:"Peeyush Sharma"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3800",title:"World Cotton Germplasm Resources",subtitle:null,isOpenForSubmission:!1,hash:"c8454ec008f1d20ebe7387b1be02b2db",slug:"world-cotton-germplasm-resources",bookSignature:"Ibrokhim Y. Abdurakhmonov",coverURL:"https://cdn.intechopen.com/books/images_new/3800.jpg",editedByType:"Edited by",editors:[{id:"213344",title:"Dr.",name:"Ibrokhim Y.",surname:"Abdurakhmonov",slug:"ibrokhim-y.-abdurakhmonov",fullName:"Ibrokhim Y. Abdurakhmonov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1248",title:"Resource Management for Sustainable Agriculture",subtitle:null,isOpenForSubmission:!1,hash:"3445faea41382312cdb15ca628229a20",slug:"resource-management-for-sustainable-agriculture",bookSignature:"Vikas Abrol and Peeyush Sharma",coverURL:"https://cdn.intechopen.com/books/images_new/1248.jpg",editedByType:"Edited by",editors:[{id:"136230",title:"Dr.",name:"Vikas",surname:"Abrol",slug:"vikas-abrol",fullName:"Vikas Abrol"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3232",title:"Organic Farming and Food Production",subtitle:null,isOpenForSubmission:!1,hash:"3610c43696a531a171044145a3a528c6",slug:"organic-farming-and-food-production",bookSignature:"Petr Konvalina",coverURL:"https://cdn.intechopen.com/books/images_new/3232.jpg",editedByType:"Edited by",editors:[{id:"77330",title:"Dr.",name:"Petr",surname:"Konvalina",slug:"petr-konvalina",fullName:"Petr Konvalina"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2030",title:"Research in Organic Farming",subtitle:null,isOpenForSubmission:!1,hash:"11136b8e73780b3196ddb1ef0ce1571e",slug:"research-in-organic-farming",bookSignature:"Raumjit Nokkoul",coverURL:"https://cdn.intechopen.com/books/images_new/2030.jpg",editedByType:"Edited by",editors:[{id:"87654",title:"Dr.",name:"Raumjit",surname:"Nokkoul",slug:"raumjit-nokkoul",fullName:"Raumjit Nokkoul"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3357",title:"Crop Production",subtitle:null,isOpenForSubmission:!1,hash:"6ed9774e3d9e1d7664640db03e659146",slug:"crop-production",bookSignature:"Aakash Goyal and Muhammad Asif",coverURL:"https://cdn.intechopen.com/books/images_new/3357.jpg",editedByType:"Edited by",editors:[{id:"97604",title:"Dr.",name:"Aakash",surname:"Goyal",slug:"aakash-goyal",fullName:"Aakash Goyal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"66301",slug:"corrigendum-to-denim-fabrics-woven-with-dual-core-spun-yarns",title:"Corrigendum to: Denim Fabrics Woven with Dual Core-Spun Yarns",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/66301.pdf",downloadPdfUrl:"/chapter/pdf-download/66301",previewPdfUrl:"/chapter/pdf-preview/66301",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/66301",risUrl:"/chapter/ris/66301",chapter:{id:"63209",slug:"denim-fabrics-woven-with-dual-core-spun-yarns",signatures:"Osman Babaarslan, Esin Sarioğlu, Halil İbrahim Çelik and Münevver\nArtek Avci",dateSubmitted:"February 5th 2018",dateReviewed:"July 12th 2018",datePrePublished:"November 5th 2018",datePublished:"February 13th 2019",book:{id:"7242",title:"Engineered Fabrics",subtitle:null,fullTitle:"Engineered Fabrics",slug:"engineered-fabrics",publishedDate:"February 13th 2019",bookSignature:"Mukesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/7242.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"36895",title:"Dr.",name:"Mukesh Kumar",middleName:null,surname:"Singh",slug:"mukesh-kumar-singh",fullName:"Mukesh Kumar Singh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",fullName:"Osman Babaarslan",slug:"osman-babaarslan",email:"teksob@cu.edu.tr",position:null,institution:{name:"Cukurova University",institutionURL:null,country:{name:"Turkey"}}},{id:"178353",title:"Dr.",name:"Halil",middleName:"İbrahim",surname:"Çelik",fullName:"Halil Çelik",slug:"halil-celik",email:"hcelik@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"216179",title:"Dr.",name:"Esin",middleName:null,surname:"Sarıoğlu",fullName:"Esin Sarıoğlu",slug:"esin-sarioglu",email:"sarioglu@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"245674",title:"Mrs.",name:"Münevver",middleName:null,surname:"Ertek Avci",fullName:"Münevver Ertek Avci",slug:"munevver-ertek-avci",email:"Munevver.ErtekAvci@calikdenim.com",position:null,institution:null}]}},chapter:{id:"63209",slug:"denim-fabrics-woven-with-dual-core-spun-yarns",signatures:"Osman Babaarslan, Esin Sarioğlu, Halil İbrahim Çelik and Münevver\nArtek Avci",dateSubmitted:"February 5th 2018",dateReviewed:"July 12th 2018",datePrePublished:"November 5th 2018",datePublished:"February 13th 2019",book:{id:"7242",title:"Engineered Fabrics",subtitle:null,fullTitle:"Engineered Fabrics",slug:"engineered-fabrics",publishedDate:"February 13th 2019",bookSignature:"Mukesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/7242.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"36895",title:"Dr.",name:"Mukesh Kumar",middleName:null,surname:"Singh",slug:"mukesh-kumar-singh",fullName:"Mukesh Kumar Singh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",fullName:"Osman Babaarslan",slug:"osman-babaarslan",email:"teksob@cu.edu.tr",position:null,institution:{name:"Cukurova University",institutionURL:null,country:{name:"Turkey"}}},{id:"178353",title:"Dr.",name:"Halil",middleName:"İbrahim",surname:"Çelik",fullName:"Halil Çelik",slug:"halil-celik",email:"hcelik@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"216179",title:"Dr.",name:"Esin",middleName:null,surname:"Sarıoğlu",fullName:"Esin Sarıoğlu",slug:"esin-sarioglu",email:"sarioglu@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"245674",title:"Mrs.",name:"Münevver",middleName:null,surname:"Ertek Avci",fullName:"Münevver Ertek Avci",slug:"munevver-ertek-avci",email:"Munevver.ErtekAvci@calikdenim.com",position:null,institution:null}]},book:{id:"7242",title:"Engineered Fabrics",subtitle:null,fullTitle:"Engineered Fabrics",slug:"engineered-fabrics",publishedDate:"February 13th 2019",bookSignature:"Mukesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/7242.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"36895",title:"Dr.",name:"Mukesh Kumar",middleName:null,surname:"Singh",slug:"mukesh-kumar-singh",fullName:"Mukesh Kumar Singh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"6679",leadTitle:null,title:"Serotonin",subtitle:null,reviewType:"peer-reviewed",abstract:"My scientific journey brought me from Lanzhou in China, Leuven in Belgium, Bethesda in the USA, all the way to San Diego. Sometimes I pick up an assortment of scattered seashells while walking along the beautiful Torrey Pines Beach in San Diego. Likewise, this book contains an assortment of discussions of different aspects of serotonin to enrich our knowledge and understanding of this neurochemical. The book contains four different chapters: 1. Introductory chapter: From Measuring Serotonin Neurotransmission to Evaluating Serotonin Post-Receptor Signaling Transduction; 2. Serotonin Reuptake Inhibitors and Their Role in Chronic Pain Management; 3. Serotonin and Emotional Decision-Making; and 4. Clinical Aspects Related to Plasma Serotonin in the Horse.",isbn:"978-1-78985-236-3",printIsbn:"978-1-78985-235-6",pdfIsbn:"978-1-83962-026-3",doi:"10.5772/intechopen.72010",price:100,priceEur:109,priceUsd:129,slug:"serotonin",numberOfPages:74,isOpenForSubmission:!1,hash:"9c833c86546ec9d3c38fb24a1072dbd0",bookSignature:"Ying Qu",publishedDate:"February 13th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/6679.jpg",keywords:null,numberOfDownloads:2038,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:4,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 20th 2017",dateEndSecondStepPublish:"December 11th 2017",dateEndThirdStepPublish:"February 9th 2018",dateEndFourthStepPublish:"April 30th 2018",dateEndFifthStepPublish:"June 29th 2018",remainingDaysToSecondStep:"3 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"94028",title:"Dr.",name:"Ying",middleName:null,surname:"Qu",slug:"ying-qu",fullName:"Ying Qu",profilePictureURL:"https://mts.intechopen.com/storage/users/94028/images/5914_n.jpg",biography:"Dr. Ying Qu is a multi-disciplinary scientist, currently working in Leulan Bioscience, USA. She received her BS and MS in Chemistry from Lanzhou University, China and her PhD in Neuroscience from the Catholic University of Leuven, Belgium. Dr. Qu has spent part of her career at the National Institutes of Health, USA, studying depression mechanisms underlying serotonin post-receptor regulated signaling transduction. She is also involved in a drug discovery program at Johnson and Johnson in the USA developing novel dual-acting antidepressants with selective serotonin reuptake inhibitors. In 2002, she received a Sevier Young Investigator Award from the Serotonin Club at the International Union of Basic and Clinical Pharmacology (IUPHAR) Satellite Meeting on Serotonin. She has published over 30 peer-reviewed papers, 40 abstracts and two book chapters in the fields of neuropsychopharmacology and bioanalysis.",institutionString:"Leulan Bioscience",position:"Senior Scientist",outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1115",title:"Neuropharmacology",slug:"neuropharmacology"}],chapters:[{id:"65286",title:"Introductory Chapter: From Measuring Serotonin Neurotransmission to Evaluating Serotonin Post-Receptor Signaling Transduction",slug:"introductory-chapter-from-measuring-serotonin-neurotransmission-to-evaluating-serotonin-post-recepto",totalDownloads:487,totalCrossrefCites:0,authors:[{id:"94028",title:"Dr.",name:"Ying",surname:"Qu",slug:"ying-qu",fullName:"Ying Qu"}]},{id:"63750",title:"Serotonin Reuptake Inhibitors and Their Role in Chronic Pain Management",slug:"serotonin-reuptake-inhibitors-and-their-role-in-chronic-pain-management",totalDownloads:647,totalCrossrefCites:0,authors:[null]},{id:"64092",title:"Serotonin and Emotional Decision-Making",slug:"serotonin-and-emotional-decision-making",totalDownloads:472,totalCrossrefCites:0,authors:[null]},{id:"61898",title:"Clinical Aspects Related to Plasma Serotonin in the Horse",slug:"clinical-aspects-related-to-plasma-serotonin-in-the-horse",totalDownloads:433,totalCrossrefCites:0,authors:[{id:"125292",title:"Dr.",name:"Katy",surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo"}]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"185543",firstName:"Maja",lastName:"Bozicevic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/185543/images/4748_n.jpeg",email:"maja.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"7256",title:"Dopamine",subtitle:"Health and Disease",isOpenForSubmission:!1,hash:"e46d08f526c35d787be15bcb17126fb8",slug:"dopamine-health-and-disease",bookSignature:"Sarat Chandra Yenisetti",coverURL:"https://cdn.intechopen.com/books/images_new/7256.jpg",editedByType:"Edited by",editors:[{id:"181774",title:"Prof.",name:"Sarat Chandra",surname:"Yenisetti",slug:"sarat-chandra-yenisetti",fullName:"Sarat Chandra Yenisetti"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6404",title:"Drug Addiction",subtitle:null,isOpenForSubmission:!1,hash:"f432d0ab93a06628d3592b4c0fea44ae",slug:"drug-addiction",bookSignature:"Fang Zhao and Meng Li",coverURL:"https://cdn.intechopen.com/books/images_new/6404.jpg",editedByType:"Edited by",editors:[{id:"207525",title:"Dr.",name:"Fang",surname:"Zhao",slug:"fang-zhao",fullName:"Fang Zhao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5894",title:"Neurotoxins",subtitle:null,isOpenForSubmission:!1,hash:"4ed24b0789b6d0bf230c24637f2f7575",slug:"neurotoxins",bookSignature:"J. Eric McDuffie",coverURL:"https://cdn.intechopen.com/books/images_new/5894.jpg",editedByType:"Edited by",editors:[{id:"161246",title:"Dr.",name:"J. Eric",surname:"McDuffie",slug:"j.-eric-mcduffie",fullName:"J. Eric McDuffie"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8166",title:"Receptors P1 and P2 as Targets for Drug Therapy in Humans",subtitle:null,isOpenForSubmission:!1,hash:"546c9abc8145b3a3ecf13557a03f7590",slug:"receptors-p1-and-p2-as-targets-for-drug-therapy-in-humans",bookSignature:"Robson Faria",coverURL:"https://cdn.intechopen.com/books/images_new/8166.jpg",editedByType:"Edited by",editors:[{id:"79615",title:"Dr.",name:"Robson",surname:"Faria",slug:"robson-faria",fullName:"Robson Faria"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7116",title:"Antidepressants",subtitle:"Preclinical, Clinical and Translational Aspects",isOpenForSubmission:!1,hash:"1bd4340dfebb60697e12fc04a461d9ac",slug:"antidepressants-preclinical-clinical-and-translational-aspects",bookSignature:"Olivier Berend",coverURL:"https://cdn.intechopen.com/books/images_new/7116.jpg",editedByType:"Edited by",editors:[{id:"71579",title:"Prof.",name:"Berend",surname:"Olivier",slug:"berend-olivier",fullName:"Berend Olivier"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"21724",title:"Phosphagen Kinase System of the Trematode Paragonimus westermani: Cloning and Expression of a Novel Chemotherapeutic Target",doi:"10.5772/24779",slug:"phosphagen-kinase-system-of-the-trematode-paragonimus-westermani-cloning-and-expression-of-a-novel-c",body:null,keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/21724.pdf",chapterXML:null,downloadPdfUrl:"/chapter/pdf-download/21724",previewPdfUrl:"/chapter/pdf-preview/21724",totalDownloads:2050,totalViews:88,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,dateSubmitted:"December 13th 2010",dateReviewed:"July 1st 2011",datePrePublished:null,datePublished:"October 12th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/21724",risUrl:"/chapter/ris/21724",book:{slug:"molecular-cloning-selected-applications-in-medicine-and-biology"},signatures:"Blanca R. Jarilla and Takeshi Agatsuma",authors:[{id:"59500",title:"Prof.",name:"Takeshi",middleName:null,surname:"Agatsuma",fullName:"Takeshi Agatsuma",slug:"takeshi-agatsuma",email:"agatsuma@kochi-u.ac.jp",position:null,institution:null},{id:"59504",title:"MSc.",name:"Blanca R.",middleName:"Rosales",surname:"Jarilla",fullName:"Blanca R. Jarilla",slug:"blanca-r.-jarilla",email:"blancajarilla@yahoo.com",position:null,institution:null}],sections:null,chapterReferences:null,footnotes:null,contributors:null,corrections:null},book:{id:"375",title:"Molecular Cloning",subtitle:"Selected Applications in Medicine and Biology",fullTitle:"Molecular Cloning - Selected Applications in Medicine and Biology",slug:"molecular-cloning-selected-applications-in-medicine-and-biology",publishedDate:"October 12th 2011",bookSignature:"Gregory G. Brown",coverURL:"https://cdn.intechopen.com/books/images_new/375.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"51165",title:"Prof.",name:"Gregory G.",middleName:null,surname:"Brown",slug:"gregory-g.-brown",fullName:"Gregory G. Brown"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"21711",title:"Screening of Bacterial Recombinants: Strategies and Preventing False Positives",slug:"screening-of-bacterial-recombinants-strategies-and-preventing-false-positives",totalDownloads:27767,totalCrossrefCites:1,signatures:"Sriram Padmanabhan, Sampali Banerjee and Naganath Mandi",authors:[{id:"46458",title:"Dr.",name:"Sriram",middleName:null,surname:"Padmanabhan",fullName:"Sriram Padmanabhan",slug:"sriram-padmanabhan"},{id:"136523",title:"Prof.",name:"Sampali",middleName:null,surname:"Banerjee",fullName:"Sampali Banerjee",slug:"sampali-banerjee"},{id:"136524",title:"Prof.",name:"Naganath",middleName:null,surname:"Mandi",fullName:"Naganath Mandi",slug:"naganath-mandi"}]},{id:"21712",title:"Non-Viral Vehicles: Principles, Applications, and Challenges in Gene Delivery",slug:"non-viral-vehicles-principles-applications-and-challenges-in-gene-delivery",totalDownloads:2636,totalCrossrefCites:0,signatures:"Abbas Padeganeh, Mohammad Khalaj-Kondori, Babak Bakhshinejad and Majid Sadeghizadeh",authors:[{id:"59270",title:"Prof.",name:"Majid",middleName:null,surname:"Sadeghizadeh",fullName:"Majid Sadeghizadeh",slug:"majid-sadeghizadeh"},{id:"60369",title:"Dr.",name:"Mohammad",middleName:null,surname:"Khalaj-Kondori",fullName:"Mohammad Khalaj-Kondori",slug:"mohammad-khalaj-kondori"},{id:"60370",title:"Dr.",name:"Abbas",middleName:null,surname:"Padeganeh",fullName:"Abbas Padeganeh",slug:"abbas-padeganeh"},{id:"96318",title:"Mr.",name:"Babak",middleName:null,surname:"Bakhshinejad",fullName:"Babak Bakhshinejad",slug:"babak-bakhshinejad"}]},{id:"21713",title:"Subcloning and Expression of Functional Human Cathepsin B and K in E. coli: Characterization and Inhibition by Flavonoids",slug:"subcloning-and-expression-of-functional-human-cathepsin-b-and-k-in-e-coli-characterization-and-inhib",totalDownloads:2183,totalCrossrefCites:1,signatures:"Lisa Wen, Soe Tha, Valerie Sutton,\nKeegan Steel, Franklin Rahman, Matthew McConnell, Jennifer Chmielowski, Kenneth Liang, Roxana Obregon, Jessica LaFollette, Laura Berryman, Ryan Keefer, Michael Bordowitz, Alice Ye, Jessica Hunter, Jenq-Kuen Huang and Rose M. McConnell",authors:[{id:"51811",title:"Prof.",name:"Lisa",middleName:null,surname:"Wen",fullName:"Lisa Wen",slug:"lisa-wen"},{id:"58392",title:"Mr",name:"Soe",middleName:null,surname:"Tha",fullName:"Soe Tha",slug:"soe-tha"},{id:"58393",title:"Ms.",name:"Valerie",middleName:null,surname:"Sutton",fullName:"Valerie Sutton",slug:"valerie-sutton"},{id:"58394",title:"Mr.",name:"Franklin",middleName:null,surname:"Rahman",fullName:"Franklin Rahman",slug:"franklin-rahman"},{id:"58395",title:"Mr",name:"Keegan",middleName:"M",surname:"Steele",fullName:"Keegan Steele",slug:"keegan-steele"},{id:"58396",title:"Mr.",name:"Matthew",middleName:null,surname:"McConnell",fullName:"Matthew McConnell",slug:"matthew-mcconnell"},{id:"58397",title:"Ms.",name:"Jennifer",middleName:null,surname:"Chmielowski",fullName:"Jennifer Chmielowski",slug:"jennifer-chmielowski"},{id:"58398",title:"Mr.",name:"Kenneth",middleName:null,surname:"Liang",fullName:"Kenneth Liang",slug:"kenneth-liang"},{id:"58399",title:"Ms",name:"Roxana",middleName:null,surname:"Obregon",fullName:"Roxana Obregon",slug:"roxana-obregon"},{id:"58400",title:"Ms.",name:"Jessica",middleName:null,surname:"LaFollette",fullName:"Jessica LaFollette",slug:"jessica-lafollette"},{id:"58401",title:"Ms",name:"Laura",middleName:"A",surname:"Berryman",fullName:"Laura Berryman",slug:"laura-berryman"},{id:"58402",title:"Mr.",name:"Ryan",middleName:null,surname:"Keefer",fullName:"Ryan Keefer",slug:"ryan-keefer"},{id:"58403",title:"Mr.",name:"Michael",middleName:null,surname:"Bordowitz",fullName:"Michael Bordowitz",slug:"michael-bordowitz"},{id:"58404",title:"Ms",name:"Alice",middleName:null,surname:"Ye",fullName:"Alice Ye",slug:"alice-ye"},{id:"58405",title:"Ms",name:"Jessica",middleName:null,surname:"Hunter",fullName:"Jessica Hunter",slug:"jessica-hunter"},{id:"58406",title:"Prof.",name:"Jenq-Kuen",middleName:null,surname:"Huang",fullName:"Jenq-Kuen Huang",slug:"jenq-kuen-huang"},{id:"58407",title:"Prof.",name:"Rose M.",middleName:null,surname:"McConnell",fullName:"Rose M. McConnell",slug:"rose-m.-mcconnell"}]},{id:"21714",title:"Molecular Cloning and Overexpression of WAP Domain of Anosmin-1 (a-WAP) in Escherichia coli",slug:"molecular-cloning-and-overexpression-of-wap-domain-of-anosmin-1-a-wap-in-escherichia-coli",totalDownloads:2426,totalCrossrefCites:0,signatures:"Srinivas Jayanthi, Beatrice Kachel, Jacqueline Morris, Igor Prudovsky and Thallapuranam K. Suresh Kumar",authors:[{id:"58708",title:"Prof.",name:"Suresh Kumar",middleName:null,surname:"Thallapuranam",fullName:"Suresh Kumar Thallapuranam",slug:"suresh-kumar-thallapuranam"},{id:"136631",title:"Dr.",name:"Srinivas",middleName:null,surname:"Jayanthi",fullName:"Srinivas Jayanthi",slug:"srinivas-jayanthi"},{id:"136632",title:"Dr.",name:"Beatrice",middleName:null,surname:"Kachel",fullName:"Beatrice Kachel",slug:"beatrice-kachel"},{id:"136633",title:"Dr.",name:"Jacqueline",middleName:null,surname:"Morris",fullName:"Jacqueline Morris",slug:"jacqueline-morris"},{id:"136635",title:"Dr.",name:"Igor",middleName:null,surname:"Prudovsky",fullName:"Igor Prudovsky",slug:"igor-prudovsky"}]},{id:"21715",title:"Effects of Two Novel Peptides from Skin of Lithobates Catesbeianus on Tumor Cell Morphology and Proliferation",slug:"effects-of-two-novel-peptides-from-skin-of-lithobates-catesbeianus-on-tumor-cell-morphology-and-prol",totalDownloads:1618,totalCrossrefCites:0,signatures:"Rui-Li ZHAO, Jun-You HAN, Wen-Yu HAN, Hong-Xuan HE and Ji-Fei MA",authors:[{id:"62519",title:"Dr.",name:"Ruili",middleName:null,surname:"Zhao",fullName:"Ruili Zhao",slug:"ruili-zhao"},{id:"110943",title:"Dr.",name:"Junyou",middleName:null,surname:"Han",fullName:"Junyou Han",slug:"junyou-han"},{id:"136636",title:"Dr.",name:"Wen-Yu",middleName:null,surname:"Han",fullName:"Wen-Yu Han",slug:"wen-yu-han"},{id:"136637",title:"Dr.",name:"Hong-Xuan",middleName:null,surname:"He",fullName:"Hong-Xuan He",slug:"hong-xuan-he"},{id:"136638",title:"Dr.",name:"Ji-Fei",middleName:null,surname:"Ma",fullName:"Ji-Fei Ma",slug:"ji-fei-ma"}]},{id:"21716",title:"Molecular Cloning of Immunoglobulin Heavy Chain Gene Translocations by Long Distance Inverse PCR",slug:"molecular-cloning-of-immunoglobulin-heavy-chain-gene-translocations-by-long-distance-inverse-pcr",totalDownloads:2211,totalCrossrefCites:0,signatures:"Takashi Sonoki",authors:[{id:"58082",title:"Dr.",name:"Takashi",middleName:null,surname:"Sonoki",fullName:"Takashi Sonoki",slug:"takashi-sonoki"}]},{id:"21717",title:"Identification of Molecules Involved in the Vulture Immune Sensing of Pathogens by Molecular Cloning",slug:"identification-of-molecules-involved-in-the-vulture-immune-sensing-of-pathogens-by-molecular-cloning",totalDownloads:1608,totalCrossrefCites:0,signatures:"Elena Crespo, José de la Fuente and José M. Pérez de la Lastra",authors:[{id:"47107",title:"Dr.",name:"Jose M.",middleName:"Manuel",surname:"Perez De La Lastra",fullName:"Jose M. Perez De La Lastra",slug:"jose-m.-perez-de-la-lastra"},{id:"59777",title:"Ms.",name:"Elena",middleName:null,surname:"Crespo",fullName:"Elena Crespo",slug:"elena-crespo"},{id:"59778",title:"Prof.",name:"José",middleName:null,surname:"De La Fuente",fullName:"José De La Fuente",slug:"jose-de-la-fuente"}]},{id:"21718",title:"Molecular Cloning, Characterization, Expression Analysis and Chromosomal Localization of the Gene Coding for the Porcine αIIb Subunit of the αIIbβ3 Integrin Platelet Receptor",slug:"molecular-cloning-characterization-expression-analysis-and-chromosomal-localization-of-the-gene-codi",totalDownloads:1512,totalCrossrefCites:0,signatures:"Gloria Esteso, Ángeles Jiménez-Marín, Gema Sanz, Juan José Garrido and Manuel Barbancho",authors:[{id:"52157",title:"Dr.",name:"Manuel",middleName:"Medina",surname:"Barbancho",fullName:"Manuel Barbancho",slug:"manuel-barbancho"},{id:"59534",title:"Dr.",name:"Gloria",middleName:null,surname:"Esteso",fullName:"Gloria Esteso",slug:"gloria-esteso"},{id:"59535",title:"Prof.",name:"Juan José",middleName:null,surname:"Garrido",fullName:"Juan José Garrido",slug:"juan-jose-garrido"},{id:"111835",title:"Dr.",name:"Ángeles",middleName:null,surname:"Jiménez-Marín",fullName:"Ángeles Jiménez-Marín",slug:"angeles-jimenez-marin"},{id:"111838",title:"Dr.",name:"Gema",middleName:null,surname:"Sanz",fullName:"Gema Sanz",slug:"gema-sanz"}]},{id:"21719",title:"Molecular Cloning, Expression, Purification and Immunological Characterization of Proteins Encoded by Regions of Difference Genes of Mycobacterium tuberculosis",slug:"molecular-cloning-expression-purification-and-immunological-characterization-of-proteins-encoded-by-",totalDownloads:2475,totalCrossrefCites:0,signatures:"Shumaila Nida Muhammad Hanif, Rajaa Al-Attiyah and Abu Salim Mustafa",authors:[{id:"52120",title:"Dr.",name:"Shumaila Nida Muhammad",middleName:null,surname:"Hanif",fullName:"Shumaila Nida Muhammad Hanif",slug:"shumaila-nida-muhammad-hanif"},{id:"54159",title:"Dr.",name:"Rajaa",middleName:null,surname:"Al-Attiyah",fullName:"Rajaa Al-Attiyah",slug:"rajaa-al-attiyah"},{id:"54160",title:"Prof.",name:"Abu Salim",middleName:null,surname:"Mustafa",fullName:"Abu Salim Mustafa",slug:"abu-salim-mustafa"}]},{id:"21720",title:"Molecular Toxinology – Cloning Toxin Genes for Addressing Functional Analysis and Disclosure Drug Leads",slug:"molecular-toxinology-cloning-toxin-genes-for-addressing-functional-analysis-and-disclosure-drug-lead",totalDownloads:1685,totalCrossrefCites:0,signatures:"Gandhi Rádis-Baptista",authors:[{id:"47894",title:"Dr.",name:"Gandhi",middleName:null,surname:"Radis-Baptista",fullName:"Gandhi Radis-Baptista",slug:"gandhi-radis-baptista"}]},{id:"21721",title:"Molecular Cloning, Expression, Function, Structure and Immunoreactivities of a Sphingomyelinase D from Loxosceles adelaida, a Brazilian Brown Spider from Karstic Areas",slug:"molecular-cloning-expression-function-structure-and-immunoreactivities-of-a-sphingomyelinase-d-from-",totalDownloads:1606,totalCrossrefCites:0,signatures:"Denise V. Tambourgi, Giselle Pidde-Queiroz, Rute M. Gonçalves-de-Andrade, Cinthya K. Okamoto, Tiago J. Sobreir, Paulo S. L. de Oliveira, Mário T. Murakami and Carmen W. van den Berg",authors:[{id:"26148",title:"Dr.",name:"Mario T.",middleName:null,surname:"Murakami",fullName:"Mario T. Murakami",slug:"mario-t.-murakami"},{id:"56841",title:"Dr.",name:"Denise V.",middleName:null,surname:"Tambourgi",fullName:"Denise V. Tambourgi",slug:"denise-v.-tambourgi"},{id:"60636",title:"Dr.",name:"Giselle",middleName:null,surname:"Pidde-Queiroz",fullName:"Giselle Pidde-Queiroz",slug:"giselle-pidde-queiroz"},{id:"60637",title:"Dr.",name:"Rute Maria",middleName:null,surname:"Gonçalves-de-Andrade",fullName:"Rute Maria Gonçalves-de-Andrade",slug:"rute-maria-goncalves-de-andrade"},{id:"60638",title:"Dr.",name:"Carmen W.",middleName:null,surname:"Van Den Berg",fullName:"Carmen W. Van Den Berg",slug:"carmen-w.-van-den-berg"},{id:"136939",title:"Dr.",name:"Cinthya K.",middleName:null,surname:"Okamoto",fullName:"Cinthya K. Okamoto",slug:"cinthya-k.-okamoto"},{id:"136940",title:"Dr.",name:"Paulo S. L.",middleName:null,surname:"de Oliveira",fullName:"Paulo S. L. de Oliveira",slug:"paulo-s.-l.-de-oliveira"},{id:"136941",title:"Dr.",name:"Tiago J.",middleName:null,surname:"Sobreir",fullName:"Tiago J. Sobreir",slug:"tiago-j.-sobreir"}]},{id:"21722",title:"Cloning the Ribokinase of Kinetoplastidae: Leishmania Major",slug:"cloning-the-ribokinase-of-kinetoplastidae-leishmania-major",totalDownloads:1646,totalCrossrefCites:0,signatures:"Patrick Ogbunude, Joy Ikekpeazu, Joseph Ugonabo, Michael Barrett and Patrick Udeogaranya",authors:[{id:"46600",title:"Prof.",name:"Patrick",middleName:null,surname:"Ogbunude",fullName:"Patrick Ogbunude",slug:"patrick-ogbunude"},{id:"94657",title:"Mrs.",name:"Joy",middleName:null,surname:"Ikekpeazu",fullName:"Joy Ikekpeazu",slug:"joy-ikekpeazu"},{id:"94658",title:"Dr.",name:"Joseph",middleName:null,surname:"Ugonabo",fullName:"Joseph Ugonabo",slug:"joseph-ugonabo"},{id:"94659",title:"Dr.",name:"Patrick",middleName:null,surname:"Udeogaranya",fullName:"Patrick Udeogaranya",slug:"patrick-udeogaranya"},{id:"108149",title:"Dr.",name:"Michael",middleName:null,surname:"Barrett",fullName:"Michael Barrett",slug:"michael-barrett"}]},{id:"21723",title:"Genome Based Vaccines Against Parasites",slug:"genome-based-vaccines-against-parasites",totalDownloads:2089,totalCrossrefCites:0,signatures:"Yasser Shahein and Amira Abouelella",authors:[{id:"56979",title:"Dr.",name:"Yasser",middleName:"Ezzat",surname:"Shahein",fullName:"Yasser Shahein",slug:"yasser-shahein"},{id:"59954",title:"Dr.",name:"Amira",middleName:null,surname:"Abouelella",fullName:"Amira Abouelella",slug:"amira-abouelella"}]},{id:"21724",title:"Phosphagen Kinase System of the Trematode Paragonimus westermani: Cloning and Expression of a Novel Chemotherapeutic Target",slug:"phosphagen-kinase-system-of-the-trematode-paragonimus-westermani-cloning-and-expression-of-a-novel-c",totalDownloads:2050,totalCrossrefCites:0,signatures:"Blanca R. Jarilla and Takeshi Agatsuma",authors:[{id:"59500",title:"Prof.",name:"Takeshi",middleName:null,surname:"Agatsuma",fullName:"Takeshi Agatsuma",slug:"takeshi-agatsuma"},{id:"59504",title:"MSc.",name:"Blanca R.",middleName:"Rosales",surname:"Jarilla",fullName:"Blanca R. Jarilla",slug:"blanca-r.-jarilla"}]},{id:"21725",title:"Molecular Cloning, Expression Pattern, and Phylogenetic Analysis of the Lysyl-tRNA Synthetase Gene from the Chinese Oak Silkworm Antheraea pernyi",slug:"molecular-cloning-expression-pattern-and-phylogenetic-analysis-of-the-lysyl-trna-synthetase-gene-fro",totalDownloads:1316,totalCrossrefCites:1,signatures:"Yan-Qun Liu and Li Qin",authors:[{id:"52410",title:"Dr.",name:"Yan-Qun",middleName:null,surname:"Liu",fullName:"Yan-Qun Liu",slug:"yan-qun-liu"},{id:"59899",title:"Dr.",name:"Li",middleName:null,surname:"Qin",fullName:"Li Qin",slug:"li-qin"}]},{id:"21726",title:"Molecular Cloning and Characterization of Fe-Superoxide Dismutase (Fe-SOD) from the Fern Ceratopteris thalictroides",slug:"molecular-cloning-and-characterization-of-fe-superoxide-dismutase-fe-sod-from-the-fern-ceratopteris-",totalDownloads:1716,totalCrossrefCites:0,signatures:"Chen Chen and Quanxi Wang",authors:[{id:"56995",title:"Prof.",name:"Quanxi",middleName:null,surname:"Wang",fullName:"Quanxi Wang",slug:"quanxi-wang"},{id:"58585",title:"Ms",name:"Chen",middleName:null,surname:"Chen",fullName:"Chen Chen",slug:"chen-chen"}]},{id:"21727",title:"Cloning and Characterization of a Candidate Gene from the Medicinal Plant Catharanthus roseus Through Transient Expression in Mesophyll Protoplasts",slug:"cloning-and-characterization-of-a-candidate-gene-from-the-medicinal-plant-catharanthus-roseus-throug",totalDownloads:2443,totalCrossrefCites:1,signatures:"Patrícia Duarte, Diana Ribeiro, Gisela Henriques, Frédérique Hilliou, Ana Sofia Rocha, Francisco Lima, Isabel Amorim and Mariana Sottomayor",authors:[{id:"51553",title:"Prof.",name:"Mariana",middleName:null,surname:"Sottomayor",fullName:"Mariana Sottomayor",slug:"mariana-sottomayor"},{id:"60022",title:"Dr.",name:"Patrícia",middleName:null,surname:"Duarte",fullName:"Patrícia Duarte",slug:"patricia-duarte"},{id:"60023",title:"MSc",name:"Diana",middleName:null,surname:"Ribeiro",fullName:"Diana Ribeiro",slug:"diana-ribeiro"},{id:"60024",title:"Prof.",name:"Isabel",middleName:null,surname:"Amorim",fullName:"Isabel Amorim",slug:"isabel-amorim"},{id:"99531",title:"MSc.",name:"Frédérique",middleName:null,surname:"Hilliou",fullName:"Frédérique Hilliou",slug:"frederique-hilliou"},{id:"99547",title:"MSc.",name:"Gisela",middleName:null,surname:"Henriques",fullName:"Gisela Henriques",slug:"gisela-henriques"},{id:"99548",title:"MSc.",name:"Ana Sofia",middleName:null,surname:"Rocha",fullName:"Ana Sofia Rocha",slug:"ana-sofia-rocha"},{id:"99549",title:"Mr.",name:"Francisco",middleName:null,surname:"Lima",fullName:"Francisco Lima",slug:"francisco-lima"}]},{id:"21728",title:"Positional Cloning in Brassica napus: Strategies for Circumventing Genome Complexity in a Polyploid Plant",slug:"positional-cloning-in-brassica-napus-strategies-for-circumventing-genome-complexity-in-a-polyploid-p",totalDownloads:1836,totalCrossrefCites:0,signatures:"Gregory G. Brown and Lydiane Gaborieau",authors:[{id:"51165",title:"Prof.",name:"Gregory G.",middleName:null,surname:"Brown",fullName:"Gregory G. Brown",slug:"gregory-g.-brown"},{id:"60393",title:"Prof.",name:"Lydiane",middleName:null,surname:"Gaborieau",fullName:"Lydiane Gaborieau",slug:"lydiane-gaborieau"}]}]},relatedBooks:[{type:"book",id:"1282",title:"DNA Repair",subtitle:null,isOpenForSubmission:!1,hash:"fd9649a587843768849e0ae8ef79cf35",slug:"dna-repair",bookSignature:"Inna Kruman",coverURL:"https://cdn.intechopen.com/books/images_new/1282.jpg",editedByType:"Edited by",editors:[{id:"40791",title:"Dr.",name:"Inna",surname:"Kruman",slug:"inna-kruman",fullName:"Inna Kruman"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"23141",title:"A Recombination Puzzle Solved: Role for New DNA Repair Systems in Helicobacter pylori Diversity/Persistence",slug:"a-recombination-puzzle-solved-role-for-new-dna-repair-systems-in-helicobacter-pylori-diversity-persi",signatures:"Ge Wang and Robert J. Maier",authors:[{id:"56034",title:"Prof.",name:"Robert",middleName:null,surname:"Maier",fullName:"Robert Maier",slug:"robert-maier"},{id:"56036",title:"Dr.",name:"Ge",middleName:null,surname:"Wang",fullName:"Ge Wang",slug:"ge-wang"}]},{id:"23142",title:"RloC: A Translation-Disabling tRNase Implicated in Phage Exclusion During Recovery from DNA Damage",slug:"rloc-a-translation-disabling-trnase-implicated-in-phage-exclusion-during-recovery-from-dna-damage",signatures:"Gabriel Kaufmann, Elena Davidov, Emmanuelle Steinfels-Kohn, Ekaterina Krutkina, Daniel Klaiman, Tamar Margalit, Michal Chai-Danino and Alexander Kotlyar",authors:[{id:"52693",title:"Prof.",name:"Gabriel",middleName:null,surname:"Kaufmann",fullName:"Gabriel Kaufmann",slug:"gabriel-kaufmann"},{id:"55747",title:"Dr.",name:"Emmanuelle",middleName:null,surname:"Steinfels-Kohn",fullName:"Emmanuelle Steinfels-Kohn",slug:"emmanuelle-steinfels-kohn"},{id:"55748",title:"Ms",name:"Elena",middleName:null,surname:"Davidov",fullName:"Elena Davidov",slug:"elena-davidov"},{id:"95750",title:"Ms.",name:"Ekaterina",middleName:null,surname:"Krutkina",fullName:"Ekaterina Krutkina",slug:"ekaterina-krutkina"},{id:"95751",title:"Dr.",name:"Daniel",middleName:null,surname:"Klaiman",fullName:"Daniel Klaiman",slug:"daniel-klaiman"},{id:"95753",title:"Prof.",name:"Alexander",middleName:null,surname:"Kotlyar",fullName:"Alexander Kotlyar",slug:"alexander-kotlyar"},{id:"95755",title:"BSc.",name:"Tamar",middleName:null,surname:"Margalit",fullName:"Tamar Margalit",slug:"tamar-margalit"},{id:"95756",title:"MSc.",name:"Michal",middleName:null,surname:"Chai-Danino",fullName:"Michal Chai-Danino",slug:"michal-chai-danino"}]},{id:"23143",title:"The Role of DDB2 in Regulating Cell Survival and Apoptosis Following DNA Damage - A Mini-Review",slug:"the-role-of-ddb2-in-regulating-cell-survival-and-apoptosis-following-dna-damage-a-mini-review",signatures:"Chuck C.-K. Chao",authors:[{id:"41415",title:"Prof.",name:"Chuck",middleName:null,surname:"Chao",fullName:"Chuck Chao",slug:"chuck-chao"}]},{id:"23144",title:"The Potential Roles of DNA-Repair Proteins in Centrosome Maintenance",slug:"the-potential-roles-of-dna-repair-proteins-in-centrosome-maintenance",signatures:"Mikio Shimada, Akihiro Kato and Junya Kobayashi",authors:[{id:"42943",title:"Dr.",name:"Mikio",middleName:null,surname:"Shimada",fullName:"Mikio Shimada",slug:"mikio-shimada"},{id:"93740",title:"Dr.",name:"Akihiro",middleName:null,surname:"Kato",fullName:"Akihiro Kato",slug:"akihiro-kato"},{id:"93741",title:"Dr.",name:"Junya",middleName:null,surname:"Kobayashi",fullName:"Junya Kobayashi",slug:"junya-kobayashi"}]},{id:"23145",title:"Shared Regulatory Motifs in Promoters of Human DNA Repair Genes",slug:"shared-regulatory-motifs-in-promoters-of-human-dna-repair-genes",signatures:"Lonnie R. Welch, Laura M. Koehly and Laura Elnitski",authors:[{id:"55045",title:"Dr.",name:"Laura",middleName:null,surname:"Elnitski",fullName:"Laura Elnitski",slug:"laura-elnitski"},{id:"58042",title:"Prof.",name:"Lonnie",middleName:"R",surname:"Welch",fullName:"Lonnie Welch",slug:"lonnie-welch"},{id:"58066",title:"Dr.",name:"Laura",middleName:"Marie",surname:"Koehly",fullName:"Laura Koehly",slug:"laura-koehly"}]},{id:"23146",title:"Mitochondrial DNA Damage: Role of Ogg1 and Aconitase",slug:"mitochondrial-dna-damage-role-of-ogg1-and-aconitase",signatures:"Gang Liu and David W. Kamp",authors:[{id:"41904",title:"Dr.",name:"David",middleName:null,surname:"Kamp",fullName:"David Kamp",slug:"david-kamp"},{id:"56879",title:"Dr.",name:"Gang",middleName:null,surname:"Liu",fullName:"Gang Liu",slug:"gang-liu"}]},{id:"23147",title:"Structure-Function Relationship of DNA Repair Proteins: Lessons from BRCA1 and RAD51 Studies",slug:"structure-function-relationship-of-dna-repair-proteins-lessons-from-brca1-and-rad51-studies",signatures:"Effrossyni Boutou, Vassiliki Pappa, Horst-Werner Stuerzbecher and Constantinos E. Vorgias",authors:[{id:"58442",title:"Prof.",name:"Constantinos",middleName:null,surname:"Vorgias",fullName:"Constantinos Vorgias",slug:"constantinos-vorgias"},{id:"58473",title:"Dr.",name:"Vassiliki",middleName:null,surname:"Pappa",fullName:"Vassiliki Pappa",slug:"vassiliki-pappa"},{id:"58579",title:"Dr.",name:"Effrossyni",middleName:null,surname:"Boutou",fullName:"Effrossyni Boutou",slug:"effrossyni-boutou"},{id:"58775",title:"Prof.",name:"Horst-Werner",middleName:null,surname:"Stuerzbecher",fullName:"Horst-Werner Stuerzbecher",slug:"horst-werner-stuerzbecher"}]},{id:"23148",title:"The Involvement of E2F1 in the Regulation of XRCC1-Dependent Base Excision DNA Repair",slug:"the-involvement-of-e2f1-in-the-regulation-of-xrcc1-dependent-base-excision-dna-repair",signatures:"Yulin Zhang and Dexi Chen",authors:[{id:"58196",title:"Prof.",name:"Dexi",middleName:null,surname:"Chen",fullName:"Dexi Chen",slug:"dexi-chen"},{id:"105721",title:"Dr.",name:"Yulin",middleName:null,surname:"Zhang",fullName:"Yulin Zhang",slug:"yulin-zhang"}]},{id:"23149",title:"Posttranslational Modifications of Rad51 Protein and Its Direct Partners: Role and Effect on Homologous Recombination – Mediated DNA Repair",slug:"posttranslational-modifications-of-rad51-protein-and-its-direct-partners-role-and-effect-on-homologo",signatures:"Milena Popova, Sébastien Henry and Fabrice Fleury",authors:[{id:"42982",title:"Prof.",name:"Fabrice",middleName:null,surname:"Fleury",fullName:"Fabrice Fleury",slug:"fabrice-fleury"},{id:"57791",title:"Dr.",name:"Milena",middleName:null,surname:"Popova",fullName:"Milena Popova",slug:"milena-popova"},{id:"57792",title:"Mr.",name:"Sébastien",middleName:null,surname:"Henry",fullName:"Sébastien Henry",slug:"sebastien-henry"}]},{id:"23150",title:"Post-Transcriptional Regulation of E2F Transcription Factors: Fine-Tuning DNA Repair, Cell Cycle Progression and Survival in Development & Disease",slug:"post-transcriptional-regulation-of-e2f-transcription-factors-fine-tuning-dna-repair-cell-cycle-progr",signatures:"Lina Dagnino, Randeep Kaur Singh and David Judah",authors:[{id:"46548",title:"Dr.",name:"Lina",middleName:null,surname:"Dagnino",fullName:"Lina Dagnino",slug:"lina-dagnino"},{id:"57591",title:"Ms.",name:"Randeep",middleName:null,surname:"Singh",fullName:"Randeep Singh",slug:"randeep-singh"},{id:"57592",title:"Mr.",name:"David",middleName:null,surname:"Judah",fullName:"David Judah",slug:"david-judah"}]},{id:"23151",title:"Eidetic Analysis of the Premature Chromosome Condensation Process",slug:"eidetic-analysis-of-the-premature-chromosome-condensation-process",signatures:"Dorota Rybaczek",authors:[{id:"40583",title:"Dr.",name:"Dorota",middleName:null,surname:"Rybaczek",fullName:"Dorota Rybaczek",slug:"dorota-rybaczek"}]},{id:"23152",title:"A DNA Repair Protein BRCA1 as a Potentially Molecular Target for the Anticancer Platinum Drug Cisplatin",slug:"a-dna-repair-protein-brca1-as-a-potentially-molecular-target-for-the-anticancer-platinum-drug-cispla",signatures:"Adisorn Ratanaphan",authors:[{id:"41290",title:"Dr.",name:"Adisorn",middleName:null,surname:"Ratanaphan",fullName:"Adisorn Ratanaphan",slug:"adisorn-ratanaphan"}]},{id:"23153",title:"Saccharomyces cerevisiae as a Model System to Study the Role of Human DDB2 in Chromatin Repair",slug:"saccharomyces-cerevisiae-as-a-model-system-to-study-the-role-of-human-ddb2-in-chromatin-repair",signatures:"Kristi L. Jones, Ling Zhang and Feng Gong",authors:[{id:"40853",title:"Prof.",name:"Feng",middleName:null,surname:"Gong",fullName:"Feng Gong",slug:"feng-gong"},{id:"40858",title:"Dr.",name:"Ling",middleName:null,surname:"Zhang",fullName:"Ling Zhang",slug:"ling-zhang"},{id:"93534",title:"Ms.",name:"Kristi",middleName:null,surname:"Jones",fullName:"Kristi Jones",slug:"kristi-jones"}]},{id:"23154",title:"Cell Cycle and DNA Damage Response in Postmitotic Neurons",slug:"cell-cycle-and-dna-damage-response-in-postmitotic-neurons",signatures:"Inna I. Kruman",authors:[{id:"40791",title:"Dr.",name:"Inna",middleName:null,surname:"Kruman",fullName:"Inna Kruman",slug:"inna-kruman"}]},{id:"23155",title:"TopBP1 in DNA Damage Response",slug:"topbp1-in-dna-damage-response",signatures:"Ewa Forma, Magdalena Brys and Wanda M. Krajewska",authors:[{id:"47014",title:"Dr.",name:"Wanda",middleName:"Małgorzata",surname:"Krajewska",fullName:"Wanda Krajewska",slug:"wanda-krajewska"},{id:"57484",title:"MSc.",name:"Ewa",middleName:null,surname:"Forma",fullName:"Ewa Forma",slug:"ewa-forma"},{id:"57485",title:"Dr.",name:"Magdalena",middleName:null,surname:"Brys",fullName:"Magdalena Brys",slug:"magdalena-brys"}]},{id:"23156",title:"Post-Meiotic DNA Damage and Response in Male Germ Cells",slug:"post-meiotic-dna-damage-and-response-in-male-germ-cells",signatures:"Frédéric Leduc, Geneviève Acteau, Marie-Chantal Grégoire, Olivier Simard, Jessica Leroux, Audrey Carrier-Leclerc, Mélina Arguin and Guylain Boissonneault",authors:[{id:"42832",title:"Dr.",name:"Guylain",middleName:null,surname:"Boissonneault",fullName:"Guylain Boissonneault",slug:"guylain-boissonneault"},{id:"93611",title:"MSc.",name:"Frédéric",middleName:null,surname:"Leduc",fullName:"Frédéric Leduc",slug:"frederic-leduc"},{id:"93613",title:"BSc.",name:"Geneviève",middleName:null,surname:"Acteau",fullName:"Geneviève Acteau",slug:"genevieve-acteau"},{id:"93614",title:"MSc",name:"Marie-Chantal",middleName:null,surname:"Grégoire",fullName:"Marie-Chantal Grégoire",slug:"marie-chantal-gregoire"},{id:"93615",title:"BSc.",name:"Olivier",middleName:null,surname:"Simard",fullName:"Olivier Simard",slug:"olivier-simard"},{id:"93616",title:"BSc.",name:"Jessica",middleName:null,surname:"Leroux",fullName:"Jessica Leroux",slug:"jessica-leroux"},{id:"93618",title:"Ms.",name:"Audrey",middleName:null,surname:"Carrier-Leclerc",fullName:"Audrey Carrier-Leclerc",slug:"audrey-carrier-leclerc"},{id:"93619",title:"MSc.",name:"Mélina",middleName:null,surname:"Arguin",fullName:"Mélina Arguin",slug:"melina-arguin"}]},{id:"23157",title:"BRCA2 Mutations and Consequences for DNA Repair",slug:"brca2-mutations-and-consequences-for-dna-repair",signatures:"Erika T. Brown",authors:[{id:"41145",title:"Dr.",name:"Erika",middleName:null,surname:"Brown",fullName:"Erika Brown",slug:"erika-brown"}]},{id:"23158",title:"Roles of MicroRNA in DNA Damage and Repair",slug:"roles-of-microrna-in-dna-damage-and-repair",signatures:"Xinrong Chen and Tao Chen",authors:[{id:"44557",title:"Dr.",name:"Tao",middleName:null,surname:"Chen",fullName:"Tao Chen",slug:"tao-chen"},{id:"44563",title:"Dr.",name:"Xinrong",middleName:null,surname:"Chen",fullName:"Xinrong Chen",slug:"xinrong-chen"}]},{id:"23159",title:"Meiosis as an Evolutionary Adaptation for DNA Repair",slug:"meiosis-as-an-evolutionary-adaptation-for-dna-repair",signatures:"Harris Bernstein, Carol Bernstein and Richard E. Michod",authors:[{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",fullName:"Carol Bernstein",slug:"carol-bernstein"},{id:"61947",title:"Prof.",name:"Rick",middleName:null,surname:"Michod",fullName:"Rick Michod",slug:"rick-michod"},{id:"62025",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",fullName:"Carol Bernstein",slug:"carol-bernstein"}]},{id:"23160",title:"From Seed to Tree: The Functioning and Evolution of DNA Repair in Plants",slug:"from-seed-to-tree-the-functioning-and-evolution-of-dna-repair-in-plants",signatures:"Jaana Vuosku, Marko Suokas, Johanna Kestilä, Tytti Sarjala and Hely Häggman",authors:[{id:"49286",title:"Dr.",name:"Jaana",middleName:null,surname:"Vuosku",fullName:"Jaana Vuosku",slug:"jaana-vuosku"},{id:"58305",title:"MSc.",name:"Marko",middleName:null,surname:"Suokas",fullName:"Marko Suokas",slug:"marko-suokas"},{id:"58306",title:"MSc.",name:"Johanna",middleName:null,surname:"Kestilä",fullName:"Johanna Kestilä",slug:"johanna-kestila"},{id:"58307",title:"Dr.",name:"Tytti",middleName:null,surname:"Sarjala",fullName:"Tytti Sarjala",slug:"tytti-sarjala"},{id:"58308",title:"Prof.",name:"Hely",middleName:null,surname:"Häggman",fullName:"Hely Häggman",slug:"hely-haggman"}]},{id:"23161",title:"The Gratuitous Repair on Undamaged DNA Misfold",slug:"the-gratuitous-repair-on-undamaged-dna-misfold",signatures:"Xuefeng Pan, Peng Xiao, Hongqun Li, Dongxu Zhao and Fei Duan",authors:[{id:"47738",title:"Prof.",name:"Xuefeng",middleName:null,surname:"Pan",fullName:"Xuefeng Pan",slug:"xuefeng-pan"}]},{id:"23162",title:"ATP-Binding Cassette Properties of Recombination Mediator Protein RecF",slug:"atp-binding-cassette-properties-of-recombination-mediator-protein-recf",signatures:"Sergey Korolev",authors:[{id:"42111",title:"Prof.",name:"Sergey",middleName:null,surname:"Korolev",fullName:"Sergey Korolev",slug:"sergey-korolev"}]},{id:"23163",title:"DNA Damage Recognition for Mammalian Global Genome Nucleotide Excision Repair",slug:"dna-damage-recognition-for-mammalian-global-genome-nucleotide-excision-repair",signatures:"Kaoru Sugasawa",authors:[{id:"51299",title:"Prof.",name:"Kaoru",middleName:null,surname:"Sugasawa",fullName:"Kaoru Sugasawa",slug:"kaoru-sugasawa"}]},{id:"23164",title:"DNA Double-Strand Break Repair Through Non-Homologous End-Joining: Recruitment and Assembly of the Players",slug:"dna-double-strand-break-repair-through-non-homologous-end-joining-recruitment-and-assembly-of-the-pl",signatures:"Radhika Pankaj Kamdar and Yoshihisa Matsumoto",authors:[{id:"42493",title:"Dr.",name:"Yoshihisa",middleName:null,surname:"Matsumoto",fullName:"Yoshihisa Matsumoto",slug:"yoshihisa-matsumoto"},{id:"57668",title:"Dr.",name:"Radhika Pankaj",middleName:null,surname:"Kamdar",fullName:"Radhika Pankaj Kamdar",slug:"radhika-pankaj-kamdar"}]},{id:"23165",title:"DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population",slug:"dna-repair-capacity-related-to-genetic-polymorphisms-of-dna-repair-genes-and-aflatoxin-b1-related-he",signatures:"Xi-Dai Long, Jin-Guang Yao, Zhi Zeng, Cen-Han Huang,\nPinhu Liao, Zan-Song Huang, Yong-Zhi Huang, Fu-Zhi Ban, Xiao-Yin Huang, Li-Min Yao, Lu-Dan Fan and Guo-Hui Fu",authors:[{id:"40527",title:"Dr.",name:"Xi-Dai",middleName:null,surname:"Long",fullName:"Xi-Dai Long",slug:"xi-dai-long"}]},{id:"23166",title:"Low Penetrance Genetic Variations in DNA Repair Genes and Cancer Susceptibility",slug:"low-penetrance-genetic-variations-in-dna-repair-genes-and-cancer-susceptibility",signatures:"Ravindran Ankathil",authors:[{id:"56743",title:"Prof.",name:"Ravindran",middleName:null,surname:"Ankathil",fullName:"Ravindran Ankathil",slug:"ravindran-ankathil"}]},{id:"23167",title:"Polymorphisms in Nucleotide Excision Repair Genes and Risk of Colorectal Cancer: A Systematic Review",slug:"polymorphisms-in-nucleotide-excision-repair-genes-and-risk-of-colorectal-cancer-a-systematic-review",signatures:"Rikke Dalgaard Hansen and Ulla Vogel",authors:[{id:"41763",title:"Prof.",name:"Ulla",middleName:null,surname:"Vogel",fullName:"Ulla Vogel",slug:"ulla-vogel"},{id:"49234",title:"Dr.",name:"Rikke Dalgaard",middleName:null,surname:"Hansen",fullName:"Rikke Dalgaard Hansen",slug:"rikke-dalgaard-hansen"}]},{id:"23168",title:"Variants and Polymorphisms of DNA Repair Genes and Neurodegenerative Diseases",slug:"variants-and-polymorphisms-of-dna-repair-genes-and-neurodegenerative-diseases",signatures:"Fabio Coppede",authors:[{id:"46639",title:"Dr.",name:"Fabio",middleName:null,surname:"Coppedè",fullName:"Fabio Coppedè",slug:"fabio-coppede"}]},{id:"23169",title:"Characterization of 5’-Flanking Regions of Various Human Telomere Maintenance Factor-Encoding Genes",slug:"characterization-of-5-flanking-regions-of-various-human-telomere-maintenance-factor-encoding-genes",signatures:"Fumiaki Uchiumi, Takahiro Oyama, Kensuke Ozaki and Sei-ichi Tanuma",authors:[{id:"47235",title:"Dr.",name:"Fumiaki",middleName:null,surname:"Uchiumi",fullName:"Fumiaki Uchiumi",slug:"fumiaki-uchiumi"},{id:"56770",title:"Mr.",name:"Takahiro",middleName:null,surname:"Oyama",fullName:"Takahiro Oyama",slug:"takahiro-oyama"},{id:"56771",title:"Dr.",name:"Sei-Ichi",middleName:null,surname:"Tanuma",fullName:"Sei-Ichi Tanuma",slug:"sei-ichi-tanuma"},{id:"91200",title:"BSc.",name:"Kensuke",middleName:null,surname:"Ozaki",fullName:"Kensuke Ozaki",slug:"kensuke-ozaki"}]},{id:"23170",title:"Roles of DNA Repair Proteins in Telomere Maintenance",slug:"roles-of-dna-repair-proteins-in-telomere-maintenance",signatures:"Masaru Ueno",authors:[{id:"41159",title:"Prof.",name:"Masaru",middleName:null,surname:"Ueno",fullName:"Masaru Ueno",slug:"masaru-ueno"}]},{id:"23171",title:"DNA Repair Measured by the Comet Assay",slug:"dna-repair-measured-by-the-comet-assay",signatures:"Amaya Azqueta, Sergey Shaposhnikov and Andrew R. Collins",authors:[{id:"47952",title:"Dr.",name:"Amaya",middleName:null,surname:"Azqueta",fullName:"Amaya Azqueta",slug:"amaya-azqueta"},{id:"57813",title:"Dr.",name:"Sergey",middleName:null,surname:"Shaposhnikov",fullName:"Sergey Shaposhnikov",slug:"sergey-shaposhnikov"},{id:"57814",title:"Prof.",name:"Andrew R",middleName:null,surname:"Collins",fullName:"Andrew R Collins",slug:"andrew-r-collins"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"74779",title:"Liquid Biopsy: A New Diagnostic Strategy and Not Only for Lung Cancer?",doi:"10.5772/intechopen.94838",slug:"liquid-biopsy-a-new-diagnostic-strategy-and-not-only-for-lung-cancer",body:'
In the era of precision medicine, the management of cancer patients has dramatically changed. An increasing number of prognostic and predictive biomarkers are being implemented in order to ensure the best treatment option for advanced stage cancer patients and pathologists have learned to refine their reports [1]. To date, the analysis epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK), and ROS 1 proto-oncogene (ROS1) rearrangements and schedules the state of death-ligand 1 (PD-L1) is capital for clinical decision making [2, 3]. In addition to these biomarkers, other activating mutations harbored by other clinically relevant genes are under investigation in clinical trials. However, despite the rapid development of this field in terms of discovered predictive biomarkers and platforms, tissue still remains an issue. To date, tissue samples represent the “gold standard” starting material to obtain nucleic acids (DNA and RNA) for molecular purposes and the only matherial available for morphological diagnosis and molecular analisys is often represented by paucicellular samples (cytological speciments or small tissue histological biopsies) [4]. However, a not negligible percentage, about 30%, of advanced stage NSCLC patients, cannot be tested because tissue sample is not adequate both for anatomo pathological revision and for molecular analysis [5]. In addition, even in high expertise centers, the percentage of inadequate molecular results, in particular when small tissue samples are adopted, may be significant [6]. In this setting, and in order to avoid to leave patients behind, liquid biopsy represents a valid option as a rapid, noninvasive and accurate clinical option. Several biosources from liquid biopsy, including free circulating DNA (cfDNA) and RNA (cfRNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs), can be isolated. While each of these modalities has the potential to provide new diagnostic information and their exploration is highly encouraged, ctDNA certainly represents the most mature example of the survey on liquid biopsy in clinical practice for lung cancer patients. Therefore, this chapter will mainly focus on the clinical value of the free circulating tumor DNA (ctDNA), a small fraction of cfDNA extracted from plasma samples and we will review the available data that suggest the role of liquid biopsy in the management of NSCLC.
To date, Food and Drug Administration (FDA) has approved the analysis of ctDNA in two different NSCLC patients settings: naïve advanced stage NSCLC (basal setting), when tissue is not available or inadequate for molecular analysis of the Epidermal Growth Factor Receptor (EGFR) in order to select patients for first or second generation EGFR tyrosine kinase inhibitor (TKI) administration; acquisition of somatic resistance mechanism after first or second EGFR TKI administration (resistance setting), in order to detect the EGFR exon 20 p.T790M resistance point mutation and select patients for third generation EGFR TKIs [7].
Here we will report the potential of liquid biopsy to help manage NSCLC throughout all stages: cancer screening, minimal residual disease detection to guide adjuvant treatment, early detection of relapse, systemic treatment initiation and monitoring of response (targeted or immune therapy), and resistance genotyping. Moreover, we will also carefully analyze each step of the pre-analytical management of liquid biopsy specimen, (sample collection, ctDNA extraction, and molecular analysis) and the advantages and disadvantages found in the use of liquid biopsy respect the adoption of gold standard tissue sample in the context of clinical practice.
The term liquid biopsy refers to the use of biological fluids as a surrogate for neoplastic tissue to obtain information useful for diagnostic, prognostic purposes or to predict the response to therapy with specific anticancer drugs. In the biological fluids (blood, urine, saliva, cerebrospinal fluid, pleural effusions, ascites or cytology specimen-derived supernatant [8, 9, 10] of tumor patients are contained cell-free DNA (cfDNA), circulating tumor DNA (ctDNA)circulating tumor cells, circulating RNA, microRNAs (miRNA), platelets and exosomes, which can be a valuable source of information about molecular assessment of cancer. Analysis of ctDNA contained in the free circulating DNA (cfDNA) that can be isolated from peripheral blood, represents to date the main liquid biopsy approach employed in clinical practice. In healthy patients, cfDNA is released in low quantity from normal cells during cellular turnover and is represented by small DNA fragments (150–200 base pairs). On the otherwise cancer patients show an increased levels of cfDNA [11, 12] with a consistent release of ctDNA generally represented, by more small fragment, with sizes ranging from 90 to 150 base pairs [13]. The amount of ctDNA is variable in cancer patients, ranging from less than 0.1% to more than 90% [11, 12]. The cf./ctDNA ratio can depends on the time of sample collection and clinical condition of the patient and is influenced by total tumor burden, location and extent of metastases, proliferation rate, apoptotic potential and genome instability [14]. ctDNA can enter the bloodstream through two different mechanisms: by a passive mechanism derived from apoptosis and necrosis or by an active mechanism derived from a spontaneous release of DNA fragment from primary tumor tissues or from circulating tumor cells or tumor-associated macrophages [15, 16].
The new College of American Pathologists (CAP), International Association for the Study of Lung Cancer (IASLC)/Association for Molecular Pathology (AMP) guideline for molecular testing of patients with NSCLC, although did not recommend the performance of molecular analysis when tissue is available, they strongly suggest liquid biopsy in those cases where tissue sample is not adequate to perform molecular analysis [17] In fact, a significant subgroup of patients cannot undergo a biopsy or rebiopsy for several reasons such as unsuitable clinical conditions or an unfavorable tumor site such as bone or central nervous system or multiple small pulmonary nodules that are not safely amenable to biopsy [18].
Let us see what are the advantages and disadvantages of using liquid biopsy.
Liquid biopsy shows several advantages over that traditional biopsy:
the procedure is not invasive, as it is a simple blood sampling and than may spare the patient an invasive procedure with the incumbent risks of major complications. Often occurs that patient need a rebiopsy due to the scant tumor tissue to obtain new tissue for further tests and to performing all the required analyses;
the ability to represent more comprehensively than tissue biopsy the molecular heterogeneity of the disease. Several studies have compared mutational profiles of different sites of metastatic disease from the same patient and have established the intratumoral heterogeneity and spatial and temporal tumor heterogeneity of solid tumors [19, 20]. While tissue only offers a snapshot of the tumor at a given time and location, may not represent the complex genetic profile of a patient’s tumor and can introduce the hypothesis of false-negative results, ctDNA that is shed into the periphery from multiple sites of disease has the potential to overcome both spatial and temporal tumor heterogeneity. Circulating markers are more effective in depicting the emergent biology in actively growing metastatic lesions which may be missed [21, 22].
can follow subclonal evolution through iterative noninvasively blood draws taking into account different clones present within all metastatic sites as a surrogate for more invasive tissue biopsies. It can be usefull to monitor molecular evolution of the disease, although there is no evidence to date that addresses a modify the therapeutic choice, in the absence of clinical progression of disease;
as a cost-effective alternative for patients considering that performing a tissue biopsy is considerably more expensive than a blood draw;
turnaround time may be shorter considering the scheduling time involved [23].
However, ctDNA suffers of several limitations that may impact on the adoption in routine predictive laboratory practice:
the amount of ctDNA in the context of cfDNA is often extremely limited, (<0.5% of the total circulating cell free DNA) [24] depending on both the volume and the localization of the disease and this can lead to misinterpret molecular results (false negatives);
ctDNA has a very low half-life (about 15 minutes) and this is a crucial limitation [24]. This aspect lead to reduce of 50% cfDNA molecules each 15 minutes from the withdrawn.
The International Association for the Study of Lung Cancer (IASLC) established in a statement paper the guideline when considering to adopt liquid biopsy samples for molecular analysis [7].
CtDNA can be extracted from various biological fluids. However, the procedures more standardized in clinical practice concern isolation of ctDNA from peripheral blood. ctDNA can be isolated from serum or plasma. Several studies compare cfDNA levels in plasma and serum samples and have shown significantly higher cfDNA concentrations in serum [25, 26] but shown that the use of plasma is preferable to serum. In the latter, in fact, the coagulation process causes the release of genomic DNA deriving from leukocytes and leads to a contamination of germline DNA that causes a ctDNA dilution.
Isolation and enrichment of ctDNA is a great challenge given the high degree of cfDNA fragmentation and its low concentration in the bloodstream to the extent of a few ng/ml, of which the ctDNA is alone a fraction [15]. Several factors affect the quality and quantity of ctDNA including: the burden of disease, the rate of release of the ctDNA in the bloodstream and the levels of DNA released by non- transformed cells. Therefore, for these reasons the pre-analytical phase must be carefully checked. to achieve superior quality results.
A first problem that can affect the quality of the sample is constituted from hemolysis that can occur during phlebotomy. It is necessary, therefore, that blood sampling is carried out by highly qualified personnel.
The sample can be collected in standard EDTA tubes or using tubes containing special fixatives, capable of stabilizing the blood and the cfDNA for several days. If the sampling is carried out using standard tubes, one important factor must be taken into account. cfDNA has a short half-life, estimated at around 2.5 hours therefore tubes can be stored before plasma isolation for a maximum of 3 hours at room temperature (Figure 1). Several studies have shown that after three hours of sampling, the wild-type cfDNA concentration could increase due to lysis of hematological cells thus reduce the relative percentage of tumor-specific ctDNA [27]. The storage of blood at a temperature of 4°C it does not prevent leukocyte lysis. Operators dealing with blood collection, handling, and eventual shipping should be cognizant of these time constraints. Blood should never be frozen before plasma extraction.
Incidence of time withdrawn in the managment of liquid biopsy specimen. The figure shows the comparison between electhropherograms performed by nanofluidic platform Tapestation 4200, (Agilent, Santa Clara, California, USA) on a sample immediately and after 1 h processed to isolate cfDNA respect time of withdrawn. In the left profile, ctDNA peak of 180–200 bp is inspected; on the right profile the peak is not detected.
There are many methods for extracting cfDNA, which include both the use of commercial kits and protocols developed by laboratories.
The extraction method must be very reliable and must generate as much possible DNA of the sample under examination. For the extraction and purification of cfDNA from plasma they are now available various commercial kits dedicated to this specific use. These kits are generally based on the use of columns equipped with silica membranes in association with a vacuum pump, or on the use of magnetic balls for the capture of nucleic acids.
Once extracted, the cfDNA must undergo quantification in order to optimize the amplification process and to know if the subsequent molecular analyzes may be possible starting from the cfDNA extract [28].
Optimal storage of cfDNA is very important as it allows its use also a time to carry out further molecular investigations, The process takes adequate equipment, including −20° C/ -80° C freezers, devices graphic temperature control, acoustic alarm systems, quality controls of the biological material stored [28].
Until recently, the available technology was not sensitive enough to detect ctDNA and use it in a meaningful way but in recent years highly sensitive blood-based assays have been developed to test cfDNA at very low concentrations for most genomic abnormalities and advances in pre-analytical processes and purification methods have enabled the capture, amplification and sequencing of ctDNA to be successful. A good molecular ctDNA test should retain an acceptable concordance to molecular testing in the tumor tissue. However, even with the increased sensitivity, a negative result from ctDNA analisys is not sufficient to exclude the potential existence of a driver alteration; therefore, in these circumstances tissue analysis should be performed.
The methods currently used to detect or measure ctDNA are numerous and can be divided into two categories: polymerase chain reaction (PCR)-based techniques and next-generation sequencing (NGS) technologies.
Within the PCR-based techniques are included real time PCR, digital PCR (dPCR), droplet digital PCR (ddPCR), peptide nucleid acid (PNA) clamp-based PCR assay (Taqman assay), beads, emulsions, amplification and magnetics (BEAMing). PCR-based approaches, can detect mutations in cfDNA at allele frequencies of 0.01% or lower. Although there are numerous platforms currently for ctDNA evaluation, the gold standards in pcr-based technologies are basically quantitative PCR (qPCR) and digital PCR.
PCR-based tests generally have faster response times and are less expensive, but can typically evaluate only one or a few specific mutations at a time. The analysis of point mutations or small insertions/deletions on ctDNA it can be often conducted through the use of Real Time technologies PCR, often modified to increase the sensitivity of the test. There are commercially available ctDNA kits based on different amplification technology (e.g. Refractory Mutation System ARMS/SCORPION) which detect mutations against EGFR exons 19, 20 and 21. These kits allow the co-amplification of one or more mutated alleles and of an endogenous control gene. The analysis with these kits allows to detect low percentages of mutated allele in the presence of high amounts of wild-type genomic DNA and can reach an even lower limit of detection (LOD) 0.5%.The main limitation related to the adoption of this approach is related to the annealing step where probes may not able to target corresponding genomic region (Figure 2).
Visual inspection of p.T790M EGFR acquired resistance mutations by using NGS system. The figure shows the manual count of aligned reads generated by Golden helix genome browse 1.1.2 (Golden helix genome browse Inc). In the red box is reported a polymorphism in the genomic region near p.T790M base change (blue box). Although the presence of this polymorphic alteration, NGS platform is able to p.T790M resistance mutation while RT-qPCR based approaches report a false negative result.
Digital PCR (dPCR) is a next-generation evolution of PCR of which there are two technological platforms: “digital droplet PCR - ddPCR” and “BEAMing dPCR” (Beam, Emulsion, Amplification, Magnetics).
Both methods, utilize emulsion technology to quantify the amount of mutant cfDNA in patient plasma and are based on the limiting dilution of DNA with a distribution of the sample in thousands of homogeneous “droplets” in an oil–water emulsion. These characteristics are of great importance in the context of the analysis of ctDNA, where it is necessary to search for and amplify rare molecules of tumor DNA in the presence of a large excess of wildtype germline DNA.
In fact, the breakdown of the sample into droplets has the function of reduce competition between mutated tumor DNA and wild-type DNA increasing the specificity and sensitivity of the analysis.
Both of these experimental approach is very useful for the identification of rare variants since only a small concentration of template is required for the analysis.
The sensibility and the specificity of the tests with ddPCR and BEAMing dPCR are, respectively 0.1% and 0.01%.
Several studies have compared multiple platforms for detecting EGFR mutations in plasma ctDNA. In one study, two non-digital platforms (cobas®EGFR mutation test and therascreen EGFR amplification refractory mutation system test) and two digital platforms (Droplet Digital PCR and BEAMing digital PCR) were compared in their ability to identify sensitizing mutations and the results support the potential use of both platforms in a clinical development program [29] .
The limit of these technologies is that of their limited ability to detect complex genomic alterations and perform multiplex testing.
In contrast to PCR-based methods, NGS is a fascinating technology able to analyze different biomarkers for different patients, simultaneously [30] and detect rare and previously uncharacterized alterations. NGS are capable of detection of mutations, indels, copy number variations and genomic rearrangements such as oncogenic fusions. Another advantage of an NGS approach is the possibility to quantify the amount of DNA that brings a particular alteration.
This technology, based on massive and parallel sequencing, ensures a high sequencing throughput, by generating from hundreds of thousands to millions of sequences (reads) [30]. To overcome the limitations of ctDNA, next generation sequencing (NGS) may be a viable option. The use of NGS for liquid biopsy requires changes to the protocols normally used for blood and tissue analysis. Operational protocols dedicated to liquid biopsy.
Different NGS platforms are commercially available and validated on liquid biopsy samples [31]. Among these, Illumina (San Diego, California) platform adopts a sequencing-by-synthesis chemistry able to identify DNA bases, while introducing them into a nucleic acid strand, by adopting a system of fluorescently labeled nucleotides; Ion Torrent (ThermoFisher Scientifics, Waltham, Massachusetts) platform adopts a sequencing-by-synthesis chemistry able to identify DNA bases, while introducing them into a nucleic acid strand, by adopting a semiconductor system useful to measure a change in pH due to the release of an H+ ion [32]. Important differences exist between these various platforms with respect to the number of genomic alterations included in a single panel, the ability to multiplex these assays, the turnaround time of the test, and its ability to detect complex genomic alterations.
Different NGS gene panels have been adopted for ctDNA analysis and numerous studies have been carried out in recent years to validate concordance to molecular testing in the tumor tissue. A higher sensitivity and specificity was obtained by Reckampet al by using a short footprint mutation enrichment NGS assay to analyze ctDNA samples extracted from plasma of NSCLC patients [8]. On the overall, taking into account the results obtained on matched tissue samples, a sensitivity of 93, 100, and 87% for EGFR exon 20 p.T790M, EGFR exon 21 p.L858R, and EGFR exon 19 deletions, was reached. The specificity, for the same mutations was 94, 100, and 96% [8]. In the experience of Paweletz et al. a high sensitivity (86% and 79%) and specificity (100% and 100%) was obtained by using a targeted NGS approach on NSCLC patients for EGFR and KRAS mutations [33]. Another valid approach is represented by the use of narrow gene panels. In the experience of the Predictive Molecular Pathology Laboratory at the University of Naples Federico II a custom, narrow NGS gene panel (named SiRe®), that cover 568 clinical relevant mutations in six genes (EGFR, KRAS, BRAF, NRAS, KIT and PDGFRA), was routinely employed for both tissue and liquid biopsy testing [34, 35]. In the validation study on different tumor types, a sensitivity of 90.5% and a specificity of 100% was reached by comparing results obtained on ctDNA extracted from serum and plasma with those obtained on matched tissue samples. In addition, this panel may be useful to detect EGFR and KRAS actionable mutations in basal setting NSCLC patients [35].
Ultra-sensitive NGS techniques dedicated to analysis have been developed of the ctDNA. The characterizing element of Cancer custom profiling deep sequencing (Capp-Seq), its is a selector that identifies different classes of somatic mutations with sensitivity and specificity greater than 90%. Similar results in terms of sensitivity and specificity were achieved with Tagged-amplicon deep sequencing (Tam-Seq) and Safe-Sequencing techniques System (Safe-SeqS).
What was once a limitation of ngs technology, the turnaround time is now acceptable for clinical management — approximately 13 days — and costs have been significantly reduced [36]. Also the difficulty of analyzing the numerous information deriving from the multigene panels has also been overcome since a variety of publically available and proprietary bioinformatics tools have been developed to assist in these calculations.
Several studies today aim to overcome the current limits of sensitivity for liquid biopsy, to support extensive research and clinics applications. Although for the evaluation of the ctDNA the gold standards are basically quantitative PCR (qPCR), digital PCR and NGS to these have been added many technologies such as whole genome sequencing (WGS) [37], Rare Ep iAlleles by Melt qPCR (DREAMing) [38] and bidirectional pyrophosphorolysis activated polymerization (bi-PAP).
Moreover, of great interest in biomedicine applied to the study of liquid biopsy are the PCR-free methods [39]. Several articles have been published dealing with PCR-free methods for the detection of point mutations [40]. These methods applied alternative isothermal-amplification methods whitch do not require thermal cycling to avoid heating and cooling steps. About the smetods include those based on nucleic acid sequences polymerization (NASBA), loop-mediated amplification (LAMP, helicase-dependent amplification (HAD), rolling - circle amplification (RCA), recombinase-polymerase amplification (RPA) and multi-displacement amplification (MDA), isothermal displacement of the circular filament polymerization (ICSPD).
Among these methods of sure interest is surface plasmon resonance imaging (SPR-I). This tecnology are able to detected Attomolar concentrations of target genomic DNA, demonstrating the ultra-sensitivity of the new method [39].
Thanks to these new ultra-sensitive technologies, several authors are pushing towards new horizons. In some studies differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for noninvasive genomic analysis of cancer. Mouliere et al. [13] argue that cfDNA fragment size analysis improved the discrimination between samples from patients with cancer and those from healthy individuals.
All these technologies are now supported by different platforms and have already been approved for clinical use [41]. However, the lack of standardization limit the clinical implementation for most of these methodologies.
There are two main scenarios in which the liquid biopsy might confer an advantage to NSCLC advanced patients:at initial molecular profiling and at progression during targeted therapy. To date, Food and Drug Administration (FDA) has approved the analysis of ctDNA extracted from plasma samples in two different patient settings: in treatment naïve advanced stage NSCLC (basal setting), when tissue is not available or inadequate for molecular purposes, for the Epidermal Growth Factor Receptor (EGFR) gene assessment in order to select patients for first or second generation EGFR tyrosine kinase inhibitor (TKI) treatments and in advanced stage NSCLC resistant to a first or second EGFR TKI (resistance setting), in order to detect the EGFR exon 20 p.T790M resistance point mutation and select patients for third generation EGFR TKIs [7].
Liquid biopsy should be taken into consideration at the time of initial diagnosis in all patients who need tumor molecular profiling, but:
tumor tissue is insufficient or unavailable;
in patients for whom invasive procedures may be risky or contraindicated;
in those cases where the biopsy scheduling time exceeds two weeks causing a serious delay in diagnosis;
in the case of bone biopsies where the decalcification processes of the sample irreversibly damage the nucleic acids and therefore invalidate any molecular investigation;
moreover, indications for choosing treatment-naive patients for ctDNA molecular testing are all patients with advanced/metastatic nonsquamous NSCLC and patients with squamous NSCLC if never smoker and/or younger age.
In clinical practice, liquid biopsy is currently mainly used for analysis of mutational status of the epidermal growth factor receptor (EGFR) in advanced NSCLC patients. Several studies and meta-analyzes [42, 43] have evaluated the diagnostic accuracy of ctDNA analysis for the identification of the most frequent activating mutations of the EGFR gene (deletions of exon 19, L858R of exon 21) in patients naïve with advanced NSCLC proving a good specificity greater than 90%. Sensitivity results instead be lower, with fluctuations between 50% and 80% depending on the technology used. On the basis of these evidences the evaluation of the mutational status of the EGFR gene on liquid biopsy is currently recommended as a possible alternative to analysis on tumor tissue.
A positive finding of an actionable mutation in ctDNA, if using a validated assay, is sufficient to initiate targeted treatment. However, a negative result it cannot be trusted and it should be followed up with a secondary test or conventional tumor testing. A negative result can be negative for several factors. The amounts of DNA into peripheral circulation of patients with indolent slow-growing tumors is often insufficient for detection and these patient may be at more risk of a false negative compared to patients with a more disseminated cancer. Therefore, it is imperative that operators are aware of the possibility of a false negative result from the liquid biopsy.
For this reason the liquid biopsy at diagnosis is far from being able to replace the traditional analysis of the tissue which therefore remains the standard goal in patient’s diagnosis.
In addition to EGFR mutations a wide range of potentially actionable alterations are of particular interest clinically and are detectable in patients with NSCLC, including ROS1, fibroblast growth factor receptor 3 (FGFR3), and neurotrophic receptor tyrosine kinase (NTRK) rearrangements and ALK, MEK, AKT, BRAF, HER2, MEK1/2, NRAS, KRAS mutations and MET receptor tyrosine kinase mutations and amplification. All of these abnormalities have been detected in ctDNA isolated from plasma and could therefore be used for screening naive patients.
As regards the study of rearrangements, which is carried out at the ctRNA level, some technical difficulties may arise due to the low stability of the circulating plasma RNA which easily undergoes degradation. The most commonly used techniques to identified ALK at the time of diagnosis, are qPCR and digital PCR or next-generation sequencing (NGS) approaches [44, 45].
The sensitivity of the techniques for studying this alteration is less high than those that can normally be used on the tissue (e.g., immunohistochemistry or Fluorescent in situ Hybridization (FISH).
Although plasma is the most widely used fluid sample for liquid biopsy, other samples are available such as urine, sputum, cerebrospinal fluid or pleural effusion as a source of ctDNA.
Sputum is an important source of nucleic acids and different studies investigated EGFR status in NSCLC patients. Wu et al. [46] identified a high concordance between sputum and tissue samples (74%). In a recent study it has been identified the potential role as a diagnostic biomarker for NSCLC of P16INK4 gene promoter methylation in both bronchoalveolar lavage (BAL) and sputum [47]. A recent study showed that sensitivity of EGFR mutation detection in the urine is comparable to that found in the plasma of the same patient [48] and concordance of mutations in the driver gene may increase when compared to plasma alone to combination of plasma, urine and sputum [49].
The ability to use ctDNA obtained from cerebrospinal fluid (CSF) to study genetic alterations and monitor response to treatment is very important as brain metastases are difficult to reach.
Resistance inevitably arises in almost all patients undergoing treatment for metastatic disease [50]. The ability to detect the presence of multiple resistance mechanisms is critical. Acquired resistance to therapy is often driven by presence of one or more tumor subclones that harbor resistance alterations [51]. These subclones drive disease progression and may reside in the same tumor lesion or in different metastatic lesions [52]. Therefore, a standard tumor biopsy of a single lesion at the time of disease progression may fail to capture resistance mechanisms present in tumor cells outside of the biopsied region [53]. This is where the liquid biopsy comes into play overcomes the limit of tumor heterogeneity.
p.T790M gatekeeper resistance identification in liquid biopsy is currently employed as a first diagnostic approach in all patients with EGFR-positive advanced NSCLC in progression after EGFR-TKI treatment. However, due to the risk of “false negatives” associated with such method, all patients in whom the mutational analysis on ctDNA results “negative” and even the initial sensitizing mutation is not detected must be subjected to test tumor tissue taken by re-biopsy, in order to define the best therapeutic strategy. However before proceeding with the tissue biopsy, it would be advisable to repeat liquid biopsy. In the absence of such a mutation, the test should be considered non-informative as the sample contains no sufficient ctDNA. In this regard, multiple studies, and a recent meta-analysis, have clearly highlighted as the site of metastases cancer significantly affects the diagnostic accuracy of the mutation analysis of the EGFR gene performed on ctDNA. The sensitivity of that method in determining both activating and p.T790M mutation can in fact vary from 80% in presence of extra-thoracic metastases at 50% in the presence of exclusively intra-thoracic localizations [28]. In order to increase the chances of success of the liquid biopsy, the test should be performed at the time of obvious progression of disease, when the probability that the tumor DNA is released into the circulation is higher.
Liquid biopsy is also utilized to detected additional coexisting resistance alterations, such as MET amplification that predicts decreased benefit from subsequent therapy with third-generation EGFR inhibitors and EGFR p.C797S mutation following therapy with the third-generation EGFR inhibitor osimertinib [52].
European Society of Pathology Task Force on Quality Assurance in Molecular Pathology and the Royal College of Pathologists published standards of molecular diagnostics reporting [54].
Reporting is an integral part of the diagnostic procedure and should contain the following information: patient identifiers, specimen type, assay methodology and the platform used including sensitivity and limit of detection, date of collection of the material used for the analysis and date of arrival of the sample in the laboratory that performs the analysis, methods of conservation of the sample investigated mutations, results of the test, data interpretation and an overall evaluation of the analysis specifying whether a detected alteration is clinically relevant.
The report must be completed on a predetermined form, dated and signed by the service manager.
Liquid biopsy is a rapidly growing field in oncology and ctDNA analysis is considered to be very promising as a biomarker for early stage detection, identification and monitoring of minimal residual disease (MRD), immuno-oncology, assessment of treatment response, and monitoring tumor evolution. Currently, several trials are ongoing in this field.
Detection of lung cancer at an earlier stage of disease, potentially susceptible of curative resection, can be critical to improve patients survival. Current screening and diagnostic tests, such as computed tomography (CT) scans and cytological/histological analyzes could be supplemented by the specificity of cfDNA [55]. The evaluation of genomic anomalies, including specific mutations, in cfDNA could offer a promising, non-invasive approach for the early diagnosis of lung cancer, considering the high specificity of these related tumors alterations. A limitation is due to the low frequency of some mutations and the fact that the mutant cfDNA can be obscured by an excess of background wild-type DNA. However, highly sensitive approaches have been developed to analyze low-level mutants cfDNA, including NGS-based options.
Many studies have focused on assessing the quantities of cfDNA. In a study carried out on smoking patients it was shown that the concentration in cfDNA, of the human telomerase reverse transcription (hTERT) gene was eight times higher in lung cancer patients than in controls and correlate with a strong risk factor for the development of lung cancer [56]. In other studies it has been shown that a greater amount of cfDNA during surgery correlates with a worse prognosis at 5 years survival, selecting a more aggressive disease [57]. Using a very sensitive quantitative test [57] it was demonstrated the possibility of discriminate between healthy subjects and NSCLC patients by measuring the quantities of cfDNA [58, 59]. cfDNA were significantly higher in NSCLC patients compared to healthy controls.
Methylation is an early and frequent epigenetic alteration that can be detected in cfDNA, including in plasma [60, 61]. Epigenetic modifications, regulate the expression of a large number of genes involved in malignant transformation and carcinogenesis. DNA alterations in methylation occur early in carcinogenesis and are remarkably more stable than other potentials diagnostic biomarkers.
Several studies have evaluated the methylation levels of single or panels of tumor suppressor genes in plasma or serum from lung cancer patients. Several genes have been found to be differentially methylated in cfDNA between patients with lung cancer and controls including MGMT, p16, RASSF1A, DAPK, RAR-β, DCLK1, SHOX2 and septin9 [62, 63]. In a recent study, a methylation panel of six genes showed a sensitivity of 72% for the detection of stage Ia NSCLC [64].
However though, methylation changes can also occur in the DNA of peritumor normal tissue which can therefore interfere with the analysis of tumor DNA generating a false positive result [65]. Considering together the fact that ctDNA is absent or very low in the early stages, the possibility to detect mutations in cfDNA derived from non tumor cells and the lack of standardized methods and large validation studies the analysis of ctDNA has not been introduced in the clinic screening yet.
Measurement of residual disease after primary tumor treatment is an area of active investigation.
Efficient methods of identifying MRD in patients treated with surgery or adjuvant chemotherapy are currently lacking. Mutation monitoring can be a significant predictor of early relapses and MRD. Several studies have focused on detecting these mutations in ctDNA as an early indicator of relapse and a potential marker of residual disease.
Monitoring of ctDNA for residual disease has been used in several studies in lung cancer. Presence of ctDNA after local treatment was highly predictive of disease recurrence in a small cohort of lung cancer patients with stage I-III lung undergoing local treatment with radiation, surgery, or both [66].
A prospective trial is ongoing to investigate the ability of ctDNA mutations and methylation monitoring to detect MRD after surgery for stage Ia–III NSCLC [67].
The limit of the use of ctDNA in detect MRD in clinical practice beyond is the lack of circulating tumor specific alterations.
CtDNA analysis could be a way to monitor cancer status in real time. Methods for monitoring treatment response and changes in tumor burden with cfDNA involve the identification of genomic alterations specific to an individual patient’s tumor and the relationship between changes in ctDNA levels, that can be monitored in real time during therapy (Figure 3).
Molecular follow up of a NSCLC patient. The figure shows the behavior of inspected molecular alterations [exon 19 deletion (blue line) and p.T790M point mutation (red line)] analyzed by serial liquid biopsy specimens in relation to the clinical outcome of a NSCLC patient.
In one study, long-term monitoring of a patient with NSCLC for analysis of EGFR mutations (p.L858R and p.T790M) using ctDNA isolated from serum and plasma a close correlation with the onset of metastasis was identified. In another study carried out with NGS technology on plasma-derived ctDNA from 168 patients with different types of cancer, the molecular alterations identified correlated to which of tissue [68].
ctDNA levels drop dramatically after one to two weeks in patients responding to treatment [69, 70]. Some authors suggested that a rise in ctDNA levels may precede radiographic progression.
Data obtained by several studies, conducted on different tumor type [71] using very sensitive new technologies involving multiplexed mutation-specific PCR and NGS suggest that the additionof ctDNA monitoring into clinical care could be a valuable tool to more accurately predict patient response and detect progression.
Cancer immunotherapy is certainly the most profound innovation recorded in recent years in the fight against cancer. The recent use of anti-programmed death receptor-1 (PD-1) /PD-1 ligand 1 immune checkpoint inhibitors (IC) in clinical trials indicates their efficacy in immune therapy against cancer.
These immune checkpoint inhibitors have been shown to have an effective therapeutic response, particularly in tumors with high tumor mutation burden (TMB) [72]. If the ctDNA can be used to guide and monitor immune therapy is just beginning to be evaluated [73].
In several studies, tumor mutation burden (TMB) can be estimated from ctDNA with good concordance with tissue results [74, 75]. Moreover, the identification of a high TMB in the ctDNA correlates closely with the two inhibitors of programmed cell death (PD)1 and its ligand (PD-L1) [74].
In a recent study it was shown that ctDNA TMB it has a closer correlation with metastatic tissue than primary tumor. Furthermore, this concordance is greater in cases with high ctDNA concentrations [76].
Another possible application of ctDNA in immunotherapy is in response monitoring. Has been proven a good correlation between ctDNA modification and clinical response. Some studies show indeed that the amount of cfDNA correlate with the response to immunotherapy and a decrease of cfDNA was an indicator of good response. Moreover, also chromosomal instability, predictive for immunotherapy response canbe evaluated by NGS in cf-DNA [77, 78].
A new interesting area is represented by the evaluation of tumor microenviroment adopting liquid biopsy specimen in the clinical administration of lung cancer patients. Cai et al. compared IC positive outcome and inflammation markers (INFγ, lymphocites ratio CD4/CD8) in relation to the conventional target biomarkers (PD-L1, CTLA4) for the selection of lung cancer patients to IC administration. They showed that a wide range of inflammatory biomarkers may integrate clinical outcome in NSCLC patients clinical administration [79].
Other applications of cfDNA are likely to emerge in the near future, in the field of immuno oncology such as the detection of minimal residual disease for adjuvant immunotherapy, and the identification of resistance mechanisms linked to the onset of new mutations such as the acquired JAK1/2 or B2M mutations [73].
However, in this context it is not yet possible to think of a complete replacement of the liquid tissue biopsy. The tumor biopsy will have more and more value, both in the evaluation of PD-L1 expression on tumor cells and in the analysis of the tumor microenvironment.
And while it is possible to identify resistance mechanisms as acquired mutations in the blood, however, acquired resistance could be linked to dynamic changes in the microenvironment, which cannot be detected by a simple blood draw.
Several pre clinical studies were performed in order to evaluate the role of cfDNA in the management of other tumor patients.
Wang et al. [80] demonstrated that ctDNA may be considered a diagnostic biomarker in head and neck squamous cell carcinoma (HNSCC) patients. 93 saliva and matching blood specimens were collected from HNSCC patients to identify somatic mutations in genes (TP53, PIK3CA, CDKN2A, HRAS, NRAS) that could play a potential clinical role in the management of this patient cohort. Results showed that ctDNA was successfully isolated from 76% and 87% of saliva and plasma samples, respectively. The authors, highlighting a percent detection rate for hot spot mutations of 100% and 76% for saliva and blood specimens respectively, defined how cfDNA extracted from saliva samples may be considered a reliable tool to identify HNSCC malignant lesions in early stage setting. Similarly, Salvi et al. [81] discussed how cfDNA may be adopted in early stage section for prostate cancer patients by elucidating an accuracy of 80% to discriminate cancer patients from benign lesions. In addition, Christensen et al. [82] showed how a digital droplet PCR approach is suitable to identify somatic alterations in urine cell free DNA (Ucf-DNA) by demonstrating how a correlation between Ucf-DNA alteration and tumor stage, size and grade, were statistically significant. In relation to this section, stool DNA also represents a promising diagnostic tool to early detect colorectal carcinoma patients in the early stage. According to this point, Imperiale et al. [83] showed that the sensitivity of novel technical approach DNA-based were characterized by higher analytical performance in the analysis of both CRC (92.3%) and advanced precancerous lesions (42.4%) respect the conventional screening test commercially available.
Is tissue still the issue?
One of the key questions facing oncologists today is whether ctDNA can replace biopsy or ribiopsy in clinical practice.
Liquid biopsy resulted improvements in the management of patients with NSCLC, offering an alternative to standard procedures in cases where tissue biopsy samples are insufficient or not feasible and providing a quick and dynamic assessment of emerging resistance mechanisms that can be used for guide treatment decisions so has been suggested to be included in clincal practice. However the fields of investigation using liquid biopsy are still restricted in routine practice. To date, FDA has approved the analysis EGFR gene assessment that is currently based on standardized and international practices recommendations and authorizes the administration of TKI. Recently, a document of the IASLC, stated that an EGFR, ALK, ROS1 or BRAF positive result of an NGS liquid biopsy analisys should be considered adequate for initiating first-line therapy in advanced NSCLC.
Although we can firmly state that liquid biopsy is a great help in NSCLC patient managing, however, in our opinion, for now it cannot replace tissue biopsy, which will remain the gold standard. Especially in the context of diagnosis where the definition of the tumor subtype can only be clarified through a cytomorphological analysis and immunohistochemical criteria. Furthermore, even the exact stage of cancer can only be obtained with tissue sampling. Moreover, in the setting of detect EGFR-sensitizing alterations in peripheral blood a negative plasma test it should be considered non-informative and will always need tissue confirmation.
Moreover, results of clinical studies have highlighted the existence of significant critical issues in the execution of a mutational test on liquid biopsy, either in the pre-analytical phase both in the analytical phase. Standardization of the various stages of the process is fundamental. It is certainly important that the analysis be performed in laboratories highly specialized, who already have experience in using highly sensitive molecular techniques in order to avoid false positives or false negatives results.
As indicated, there are numerous methods of studying circulating nucleic acids. In view of the large number of actionable targets in NSCLC, guidelines support the position that broad-based testing by NGS. The NGS technique requires workflow complex and use of multigene panels also requires the use of sophisticated software and, sometimes, the help of bioinformatics.
So it is therefore evident that the choice between the different technologies must hold account of their sustainability and the clinical use required in the context in which you operate.
In conclusion we think that ctDNA can play complementary roles in the management of patient NSCLC and act as a prognostic or predictive biomarker as a part of a thorough clinical evaluations to assess the disease, that include comparative sequence analyses of plasma DNA, and biopsies in combination with imaging studies and detailed functional studies.
The authors declare no conflict of interest.
General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed.
',metaTitle:"Horizon 2020 Compliance",metaDescription:"General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed. ",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
\\n\\nMetadata for all publications is also automatically deposited in IntechOpen's OAI repository, making them available through the Open Access Infrastructure for Research in Europe's (OpenAIRE) search interface further establishing our compliance.
\\n\\nIn other words, publishing with IntechOpen guarantees compliance.
\\n\\nRead more about Open Access in Horizon 2020 here.
\\n\\nWhich scientific publication to choose?
\\n\\nWhen choosing a publication, Horizon 2020 grant recipients are encouraged to provide open access to various types of scientific publications including monographs, edited books and conference proceedings.
\\n\\nIntechOpen publishes all of the aforementioned formats in compliance with the requirements and criteria established by the European Commission for the Horizon 2020 Program.
\\n\\nAuthors requiring additional information are welcome to send their inquiries to funders@intechopen.com
\\n"}]'},components:[{type:"htmlEditorComponent",content:'Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
\n\nMetadata for all publications is also automatically deposited in IntechOpen's OAI repository, making them available through the Open Access Infrastructure for Research in Europe's (OpenAIRE) search interface further establishing our compliance.
\n\nIn other words, publishing with IntechOpen guarantees compliance.
\n\nRead more about Open Access in Horizon 2020 here.
\n\nWhich scientific publication to choose?
\n\nWhen choosing a publication, Horizon 2020 grant recipients are encouraged to provide open access to various types of scientific publications including monographs, edited books and conference proceedings.
\n\nIntechOpen publishes all of the aforementioned formats in compliance with the requirements and criteria established by the European Commission for the Horizon 2020 Program.
\n\nAuthors requiring additional information are welcome to send their inquiries to funders@intechopen.com
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:117095},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateEndThirdStepPublish",topicId:"25"},books:[{type:"book",id:"8737",title:"Rabies Virus",subtitle:null,isOpenForSubmission:!0,hash:"49cce3f548da548c718c865feb343509",slug:null,bookSignature:"Dr. Sergey Tkachev",coverURL:"https://cdn.intechopen.com/books/images_new/8737.jpg",editedByType:null,editors:[{id:"61139",title:"Dr.",name:"Sergey",surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10830",title:"Animal Feed Science",subtitle:null,isOpenForSubmission:!0,hash:"b6091426454b1c484f4d38efc722d6dd",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10830.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10496",title:"Feed Additives in Animal Nutrition",subtitle:null,isOpenForSubmission:!0,hash:"8ffe43a82ac48b309abc3632bbf3efd0",slug:null,bookSignature:"Prof. László Babinszky",coverURL:"https://cdn.intechopen.com/books/images_new/10496.jpg",editedByType:null,editors:[{id:"53998",title:"Prof.",name:"László",surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:17},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:15},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:60},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:12,limit:12,total:3},popularBooks:{featuredBooks:[{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7796",title:"Human 4.0",subtitle:"From Biology to Cybernetic",isOpenForSubmission:!1,hash:"5ac5c052d3a593d5c4f4df66d005e5af",slug:"human-4-0-from-biology-to-cybernetic",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7796.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9711",title:"Pests, Weeds and Diseases in Agricultural Crop and Animal Husbandry Production",subtitle:null,isOpenForSubmission:!1,hash:"12cf675f1e433135dd5bf5df7cec124f",slug:"pests-weeds-and-diseases-in-agricultural-crop-and-animal-husbandry-production",bookSignature:"Dimitrios Kontogiannatos, Anna Kourti and Kassio Ferreira Mendes",coverURL:"https://cdn.intechopen.com/books/images_new/9711.jpg",editors:[{id:"196691",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Kontogiannatos",slug:"dimitrios-kontogiannatos",fullName:"Dimitrios Kontogiannatos"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10178",title:"Environmental Emissions",subtitle:null,isOpenForSubmission:!1,hash:"febf21ec717bfe20ae25a9dab9b5d438",slug:"environmental-emissions",bookSignature:"Richard Viskup",coverURL:"https://cdn.intechopen.com/books/images_new/10178.jpg",editors:[{id:"103742",title:"Dr.",name:"Richard",middleName:null,surname:"Viskup",slug:"richard-viskup",fullName:"Richard Viskup"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8511",title:"Cyberspace",subtitle:null,isOpenForSubmission:!1,hash:"8c1cdeb133dbe6cc1151367061c1bba6",slug:"cyberspace",bookSignature:"Evon Abu-Taieh, Abdelkrim El Mouatasim and Issam H. Al Hadid",coverURL:"https://cdn.intechopen.com/books/images_new/8511.jpg",editors:[{id:"223522",title:"Dr.",name:"Evon",middleName:"M.O.",surname:"Abu-Taieh",slug:"evon-abu-taieh",fullName:"Evon Abu-Taieh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9534",title:"Banking and Finance",subtitle:null,isOpenForSubmission:!1,hash:"af14229738af402c3b595d7e124dce82",slug:"banking-and-finance",bookSignature:"Razali Haron, Maizaitulaidawati Md Husin and Michael Murg",coverURL:"https://cdn.intechopen.com/books/images_new/9534.jpg",editors:[{id:"206517",title:"Prof.",name:"Razali",middleName:null,surname:"Haron",slug:"razali-haron",fullName:"Razali Haron"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"2160",title:"MATLAB",subtitle:"A Fundamental Tool for Scientific Computing and Engineering Applications - Volume 1",isOpenForSubmission:!1,hash:"dd9c658341fbd264ed4f8d9e6aa8ca29",slug:"matlab-a-fundamental-tool-for-scientific-computing-and-engineering-applications-volume-1",bookSignature:"Vasilios N. Katsikis",coverURL:"https://cdn.intechopen.com/books/images_new/2160.jpg",editors:[{id:"12289",title:"Prof.",name:"Vasilios",middleName:"N.",surname:"Katsikis",slug:"vasilios-katsikis",fullName:"Vasilios Katsikis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5126},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7796",title:"Human 4.0",subtitle:"From Biology to Cybernetic",isOpenForSubmission:!1,hash:"5ac5c052d3a593d5c4f4df66d005e5af",slug:"human-4-0-from-biology-to-cybernetic",bookSignature:"Yves Rybarczyk",coverURL:"https://cdn.intechopen.com/books/images_new/7796.jpg",editors:[{id:"72920",title:"Prof.",name:"Yves",middleName:"Philippe",surname:"Rybarczyk",slug:"yves-rybarczyk",fullName:"Yves Rybarczyk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9711",title:"Pests, Weeds and Diseases in Agricultural Crop and Animal Husbandry Production",subtitle:null,isOpenForSubmission:!1,hash:"12cf675f1e433135dd5bf5df7cec124f",slug:"pests-weeds-and-diseases-in-agricultural-crop-and-animal-husbandry-production",bookSignature:"Dimitrios Kontogiannatos, Anna Kourti and Kassio Ferreira Mendes",coverURL:"https://cdn.intechopen.com/books/images_new/9711.jpg",editors:[{id:"196691",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Kontogiannatos",slug:"dimitrios-kontogiannatos",fullName:"Dimitrios Kontogiannatos"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"10178",title:"Environmental Emissions",subtitle:null,isOpenForSubmission:!1,hash:"febf21ec717bfe20ae25a9dab9b5d438",slug:"environmental-emissions",bookSignature:"Richard Viskup",coverURL:"https://cdn.intechopen.com/books/images_new/10178.jpg",editors:[{id:"103742",title:"Dr.",name:"Richard",middleName:null,surname:"Viskup",slug:"richard-viskup",fullName:"Richard Viskup"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8511",title:"Cyberspace",subtitle:null,isOpenForSubmission:!1,hash:"8c1cdeb133dbe6cc1151367061c1bba6",slug:"cyberspace",bookSignature:"Evon Abu-Taieh, Abdelkrim El Mouatasim and Issam H. Al Hadid",coverURL:"https://cdn.intechopen.com/books/images_new/8511.jpg",editors:[{id:"223522",title:"Dr.",name:"Evon",middleName:"M.O.",surname:"Abu-Taieh",slug:"evon-abu-taieh",fullName:"Evon Abu-Taieh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editedByType:"Edited by",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editedByType:"Edited by",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Advances in Complex Valvular Disease",subtitle:null,isOpenForSubmission:!1,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:"advances-in-complex-valvular-disease",bookSignature:"Michael S. Firstenberg and Imran Khan",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10150",title:"Smart Manufacturing",subtitle:"When Artificial Intelligence Meets the Internet of Things",isOpenForSubmission:!1,hash:"87004a19de13702d042f8ff96d454698",slug:"smart-manufacturing-when-artificial-intelligence-meets-the-internet-of-things",bookSignature:"Tan Yen Kheng",coverURL:"https://cdn.intechopen.com/books/images_new/10150.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9386",title:"Direct Numerical Simulations",subtitle:"An Introduction and Applications",isOpenForSubmission:!1,hash:"158a3a0fdba295d21ff23326f5a072d5",slug:"direct-numerical-simulations-an-introduction-and-applications",bookSignature:"Srinivasa Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9386.jpg",editedByType:"Edited by",editors:[{id:"6897",title:"Dr.",name:"Srinivasa",middleName:"P",surname:"Rao",slug:"srinivasa-rao",fullName:"Srinivasa Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editedByType:"Edited by",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1182",title:"Clinical Pharmacology",slug:"clinical-pharmacology",parent:{title:"Drug Discovery",slug:"drug-discovery"},numberOfBooks:3,numberOfAuthorsAndEditors:123,numberOfWosCitations:4,numberOfCrossrefCitations:48,numberOfDimensionsCitations:100,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"clinical-pharmacology",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"8008",title:"Antioxidants",subtitle:null,isOpenForSubmission:!1,hash:"76361b4061e830906267933c1c670027",slug:"antioxidants",bookSignature:"Emad Shalaby",coverURL:"https://cdn.intechopen.com/books/images_new/8008.jpg",editedByType:"Edited by",editors:[{id:"63600",title:"Prof.",name:"Emad",middleName:null,surname:"Shalaby",slug:"emad-shalaby",fullName:"Emad Shalaby"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7258",title:"Resveratrol",subtitle:"Adding Life to Years, Not Adding Years to Life",isOpenForSubmission:!1,hash:"b02655d4c4df83b50688fa1a22661d49",slug:"resveratrol-adding-life-to-years-not-adding-years-to-life",bookSignature:"Farid A. Badria",coverURL:"https://cdn.intechopen.com/books/images_new/7258.jpg",editedByType:"Edited by",editors:[{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"716",title:"Clinical Use of Local Anesthetics",subtitle:null,isOpenForSubmission:!1,hash:"e8e4b699b914aa5fa2cf49f0ce8c42b9",slug:"clinical-use-of-local-anesthetics",bookSignature:"Asadolah Saadatniaki",coverURL:"https://cdn.intechopen.com/books/images_new/716.jpg",editedByType:"Edited by",editors:[{id:"88079",title:"Associate Prof.",name:"Asadoliah",middleName:null,surname:"Saadatniaki",slug:"asadoliah-saadatniaki",fullName:"Asadoliah Saadatniaki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:3,mostCitedChapters:[{id:"66259",doi:"10.5772/intechopen.85270",title:"Antioxidant Compounds and Their Antioxidant Mechanism",slug:"antioxidant-compounds-and-their-antioxidant-mechanism",totalDownloads:4740,totalCrossrefCites:16,totalDimensionsCites:39,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Norma Francenia Santos-Sánchez, Raúl Salas-Coronado, Claudia Villanueva-Cañongo and Beatriz Hernández-Carlos",authors:[{id:"143354",title:"Dr.",name:"Raúl",middleName:null,surname:"Salas-Coronado",slug:"raul-salas-coronado",fullName:"Raúl Salas-Coronado"},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez"},{id:"193718",title:"Dr.",name:"Beatriz",middleName:null,surname:"Hernández-Carlos",slug:"beatriz-hernandez-carlos",fullName:"Beatriz Hernández-Carlos"},{id:"278133",title:"Dr.",name:"Claudia",middleName:null,surname:"Villanueva-Cañongo",slug:"claudia-villanueva-canongo",fullName:"Claudia Villanueva-Cañongo"}]},{id:"65331",doi:"10.5772/intechopen.83731",title:"Flavonoids and Phenolic Acids as Potential Natural Antioxidants",slug:"flavonoids-and-phenolic-acids-as-potential-natural-antioxidants",totalDownloads:1743,totalCrossrefCites:14,totalDimensionsCites:25,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Biljana Kaurinovic and Djendji Vastag",authors:[{id:"142369",title:"Prof.",name:"Biljana",middleName:null,surname:"Kaurinovic",slug:"biljana-kaurinovic",fullName:"Biljana Kaurinovic"},{id:"286918",title:"Prof.",name:"Djendji",middleName:null,surname:"Vastag",slug:"djendji-vastag",fullName:"Djendji Vastag"}]},{id:"62084",doi:"10.5772/intechopen.78977",title:"Resveratrol and SIRT1 Activators for the Treatment of Aging and Age-Related Diseases",slug:"resveratrol-and-sirt1-activators-for-the-treatment-of-aging-and-age-related-diseases",totalDownloads:1569,totalCrossrefCites:2,totalDimensionsCites:5,book:{slug:"resveratrol-adding-life-to-years-not-adding-years-to-life",title:"Resveratrol",fullTitle:"Resveratrol - Adding Life to Years, Not Adding Years to Life"},signatures:"Alessandra Stacchiotti, Gaia Favero and Rita Rezzani",authors:[{id:"175171",title:"Prof.",name:"Rita",middleName:null,surname:"Rezzani",slug:"rita-rezzani",fullName:"Rita Rezzani"},{id:"238047",title:"Dr.",name:"Gaia",middleName:null,surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero"},{id:"245898",title:"Dr.",name:"Alessandra",middleName:null,surname:"Stacchiotti",slug:"alessandra-stacchiotti",fullName:"Alessandra Stacchiotti"}]}],mostDownloadedChaptersLast30Days:[{id:"66259",title:"Antioxidant Compounds and Their Antioxidant Mechanism",slug:"antioxidant-compounds-and-their-antioxidant-mechanism",totalDownloads:4740,totalCrossrefCites:16,totalDimensionsCites:39,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Norma Francenia Santos-Sánchez, Raúl Salas-Coronado, Claudia Villanueva-Cañongo and Beatriz Hernández-Carlos",authors:[{id:"143354",title:"Dr.",name:"Raúl",middleName:null,surname:"Salas-Coronado",slug:"raul-salas-coronado",fullName:"Raúl Salas-Coronado"},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez"},{id:"193718",title:"Dr.",name:"Beatriz",middleName:null,surname:"Hernández-Carlos",slug:"beatriz-hernandez-carlos",fullName:"Beatriz Hernández-Carlos"},{id:"278133",title:"Dr.",name:"Claudia",middleName:null,surname:"Villanueva-Cañongo",slug:"claudia-villanueva-canongo",fullName:"Claudia Villanueva-Cañongo"}]},{id:"65067",title:"Diseases Related to Types of Free Radicals",slug:"diseases-related-to-types-of-free-radicals",totalDownloads:872,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Narendra Maddu",authors:[{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu"}]},{id:"62579",title:"Where and How in the mTOR Pathway Inhibitors Fight Aging: Rapamycin, Resveratrol, and Metformin",slug:"where-and-how-in-the-mtor-pathway-inhibitors-fight-aging-rapamycin-resveratrol-and-metformin",totalDownloads:1603,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"resveratrol-adding-life-to-years-not-adding-years-to-life",title:"Resveratrol",fullTitle:"Resveratrol - Adding Life to Years, Not Adding Years to Life"},signatures:"Sage Arbor",authors:[{id:"245319",title:"Ph.D.",name:"Sage",middleName:null,surname:"Arbor",slug:"sage-arbor",fullName:"Sage Arbor"}]},{id:"62084",title:"Resveratrol and SIRT1 Activators for the Treatment of Aging and Age-Related Diseases",slug:"resveratrol-and-sirt1-activators-for-the-treatment-of-aging-and-age-related-diseases",totalDownloads:1569,totalCrossrefCites:2,totalDimensionsCites:5,book:{slug:"resveratrol-adding-life-to-years-not-adding-years-to-life",title:"Resveratrol",fullTitle:"Resveratrol - Adding Life to Years, Not Adding Years to Life"},signatures:"Alessandra Stacchiotti, Gaia Favero and Rita Rezzani",authors:[{id:"175171",title:"Prof.",name:"Rita",middleName:null,surname:"Rezzani",slug:"rita-rezzani",fullName:"Rita Rezzani"},{id:"238047",title:"Dr.",name:"Gaia",middleName:null,surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero"},{id:"245898",title:"Dr.",name:"Alessandra",middleName:null,surname:"Stacchiotti",slug:"alessandra-stacchiotti",fullName:"Alessandra Stacchiotti"}]},{id:"66504",title:"Antioxidants as a Double-Edged Sword in the Treatment of Cancer",slug:"antioxidants-as-a-double-edged-sword-in-the-treatment-of-cancer",totalDownloads:873,totalCrossrefCites:4,totalDimensionsCites:2,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Majid Asadi-Samani, Najmeh Kaffash Farkhad, Mohammad Reza Mahmoudian-Sani and Hedayatollah Shirzad",authors:[{id:"237542",title:"Dr.",name:"Majid",middleName:null,surname:"Asadi-Samani",slug:"majid-asadi-samani",fullName:"Majid Asadi-Samani"},{id:"275475",title:"Dr.",name:"Mohammad",middleName:null,surname:"Reza Mahmoudian-Sani",slug:"mohammad-reza-mahmoudian-sani",fullName:"Mohammad Reza Mahmoudian-Sani"},{id:"295230",title:"Dr.",name:"Najmeh",middleName:null,surname:"Kafash Farkhad",slug:"najmeh-kafash-farkhad",fullName:"Najmeh Kafash Farkhad"},{id:"295231",title:"Dr.",name:"Hedayatollah",middleName:null,surname:"Shirzad",slug:"hedayatollah-shirzad",fullName:"Hedayatollah Shirzad"}]},{id:"65331",title:"Flavonoids and Phenolic Acids as Potential Natural Antioxidants",slug:"flavonoids-and-phenolic-acids-as-potential-natural-antioxidants",totalDownloads:1743,totalCrossrefCites:14,totalDimensionsCites:25,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Biljana Kaurinovic and Djendji Vastag",authors:[{id:"142369",title:"Prof.",name:"Biljana",middleName:null,surname:"Kaurinovic",slug:"biljana-kaurinovic",fullName:"Biljana Kaurinovic"},{id:"286918",title:"Prof.",name:"Djendji",middleName:null,surname:"Vastag",slug:"djendji-vastag",fullName:"Djendji Vastag"}]},{id:"65225",title:"Antioxidant Categories and Mode of Action",slug:"antioxidant-categories-and-mode-of-action",totalDownloads:967,totalCrossrefCites:0,totalDimensionsCites:3,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Manal Azat Aziz, Abdulkareem Shehab Diab and Abeer Abdulrazak Mohammed",authors:[{id:"276717",title:"Associate Prof.",name:"Manal",middleName:null,surname:"Azat Aziz",slug:"manal-azat-aziz",fullName:"Manal Azat Aziz"},{id:"286369",title:"Dr.",name:"Abdulkareem",middleName:null,surname:"Shehab Diab",slug:"abdulkareem-shehab-diab",fullName:"Abdulkareem Shehab Diab"},{id:"312155",title:"Dr.",name:"Abeer Abdulrazak",middleName:null,surname:"Mohammed",slug:"abeer-abdulrazak-mohammed",fullName:"Abeer Abdulrazak Mohammed"}]},{id:"62439",title:"Protective Activity of Resveratrol in Cardio- and Cerebrovascular Diseases",slug:"protective-activity-of-resveratrol-in-cardio-and-cerebrovascular-diseases",totalDownloads:689,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"resveratrol-adding-life-to-years-not-adding-years-to-life",title:"Resveratrol",fullTitle:"Resveratrol - Adding Life to Years, Not Adding Years to Life"},signatures:"Albino Carrizzo, Carmine Izzo and Carmine Vecchione",authors:[{id:"209420",title:"Prof.",name:"Carmine",middleName:null,surname:"Vecchione",slug:"carmine-vecchione",fullName:"Carmine Vecchione"},{id:"210626",title:"MSc.",name:"Albino",middleName:null,surname:"Carrizzo",slug:"albino-carrizzo",fullName:"Albino Carrizzo"},{id:"219305",title:"Mr.",name:"Carmine",middleName:null,surname:"Izzo",slug:"carmine-izzo",fullName:"Carmine Izzo"}]},{id:"66809",title:"Dietary Antioxidants in the Chemoprevention of Prostate Cancer",slug:"dietary-antioxidants-in-the-chemoprevention-of-prostate-cancer",totalDownloads:465,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Dwayne Tucker, Melisa Anderson, Fabian Miller, Kurt Vaz, Lennox Anderson-Jackson and Donovan McGrowder",authors:[{id:"155804",title:"Dr.",name:"Donovan",middleName:null,surname:"McGrowder",slug:"donovan-mcgrowder",fullName:"Donovan McGrowder"},{id:"158092",title:"Mr.",name:"Lennox",middleName:null,surname:"Anderson-Jackson",slug:"lennox-anderson-jackson",fullName:"Lennox Anderson-Jackson"},{id:"280661",title:"Mr.",name:"Dwayne",middleName:null,surname:"Tucker",slug:"dwayne-tucker",fullName:"Dwayne Tucker"},{id:"280662",title:"Ms.",name:"Melisa",middleName:null,surname:"Anderson",slug:"melisa-anderson",fullName:"Melisa Anderson"},{id:"280664",title:"Mr.",name:"Fabian",middleName:null,surname:"Miller",slug:"fabian-miller",fullName:"Fabian Miller"},{id:"291987",title:"Ph.D. Student",name:"Kurt",middleName:null,surname:"Vaz",slug:"kurt-vaz",fullName:"Kurt Vaz"}]},{id:"65762",title:"Antioxidants in Date Fruits and the Extent of the Variability of the Total Phenolic Content: Review and Analysis",slug:"antioxidants-in-date-fruits-and-the-extent-of-the-variability-of-the-total-phenolic-content-review-a",totalDownloads:627,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"antioxidants",title:"Antioxidants",fullTitle:"Antioxidants"},signatures:"Abdulameer Allaith",authors:[{id:"277441",title:"Associate Prof.",name:"Abdulameer",middleName:null,surname:"Allaith",slug:"abdulameer-allaith",fullName:"Abdulameer Allaith"}]}],onlineFirstChaptersFilter:{topicSlug:"clinical-pharmacology",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"chapter.detail",path:"/books/molecular-cloning-selected-applications-in-medicine-and-biology/phosphagen-kinase-system-of-the-trematode-paragonimus-westermani-cloning-and-expression-of-a-novel-c",hash:"",query:{},params:{book:"molecular-cloning-selected-applications-in-medicine-and-biology",chapter:"phosphagen-kinase-system-of-the-trematode-paragonimus-westermani-cloning-and-expression-of-a-novel-c"},fullPath:"/books/molecular-cloning-selected-applications-in-medicine-and-biology/phosphagen-kinase-system-of-the-trematode-paragonimus-westermani-cloning-and-expression-of-a-novel-c",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()