Genes and related mitochondrial dysfunction syndromes.
\\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-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{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"}]},book:{item:{type:"book",id:"3139",leadTitle:null,fullTitle:"Wireless Ad-Hoc Networks",title:"Wireless Ad-Hoc Networks",subtitle:null,reviewType:"peer-reviewed",abstract:"A wireless ad-hoc network is a wireless network deployed without any infrastructure. This includes wireless mesh networks, mobile ad-hoc networks, and vehicular ad-hoc networks. This book focuses on the most fundamental aspects of wireless ad-hoc networks. Topics include the design of the link layer for better performance, the study on routing protocols for higher efficiency, and practical issues in its application. These topics are crucial to build a foundation in design, implementation, deployment, and analysis of a wireless ad-hoc network. Main features include: General introduction to a wireless ad-hoc network, Performance comparison and improvement of medium access protocols, New routing paradigm and algorithms, Autoconfiguration schemes and related issues and Privacy in a vehicular ad-hoc network.",isbn:null,printIsbn:"978-953-51-0896-2",pdfIsbn:"978-953-51-5721-2",doi:"10.5772/3438",price:119,priceEur:129,priceUsd:155,slug:"wireless-ad-hoc-networks",numberOfPages:174,isOpenForSubmission:!1,isInWos:1,hash:"5a8ce0920ae4a8c48e38a9bc60684aa1",bookSignature:"Hongbo Zhou",publishedDate:"December 12th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/3139.jpg",numberOfDownloads:16024,numberOfWosCitations:9,numberOfCrossrefCitations:13,numberOfDimensionsCitations:13,hasAltmetrics:1,numberOfTotalCitations:35,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 3rd 2012",dateEndSecondStepPublish:"April 24th 2012",dateEndThirdStepPublish:"August 21st 2012",dateEndFourthStepPublish:"September 20th 2012",dateEndFifthStepPublish:"October 19th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,editors:[{id:"154490",title:"Dr.",name:"Hongbo",middleName:null,surname:"Zhou",slug:"hongbo-zhou",fullName:"Hongbo Zhou",profilePictureURL:"https://mts.intechopen.com/storage/users/154490/images/system/154490.jpg",biography:"I received my Ph.D. degree in Computer Science & Enginnering from Michigan State University. My research interestes include mobile computing, network security, and applications of information technology. I received my M.E. degree in Computer Architecture & Organiztion and B.E. degree in Computer Science & Engineering in Xi'an Jiaotong University.\n\nI joined Dept. of Computer Science, Slippery Rock University in August 2005, and have been teaching courses in IT program, including Unix, HTML/CSS, JavaScript, PHP/MySQL programming, C++, system management, and computer networks. In my spare time, I am also interested in Java, Python, Shell programming, network security, database systems, DocBook, algorithms & data structures, computer graphics, electronics, etc. Other than that, I enjoy reading books, listening to relaxed music and classical music, watching documentaries, ..., and surfing the net.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Slippery Rock University",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"540",title:"Wireless Communication Network",slug:"communications-and-security-wireless-communication-network"}],chapters:[{id:"41440",title:"Comparison of the Maximal Spatial Throughput of Aloha and CSMA in Wireless Ad-Hoc Networks",doi:"10.5772/53264",slug:"comparison-of-the-maximal-spatial-throughput-of-aloha-and-csma-in-wireless-ad-hoc-networks",totalDownloads:2978,totalCrossrefCites:5,totalDimensionsCites:5,signatures:"B. Blaszczyszyn, P. Mühlethaler and S. Banaouas",downloadPdfUrl:"/chapter/pdf-download/41440",previewPdfUrl:"/chapter/pdf-preview/41440",authors:[{id:"154985",title:"Dr.",name:"Paul",surname:"Muhlethaler",slug:"paul-muhlethaler",fullName:"Paul Muhlethaler"},{id:"155011",title:"Dr.",name:"Bartlomiej",surname:"Blaszczyszyn",slug:"bartlomiej-blaszczyszyn",fullName:"Bartlomiej Blaszczyszyn"}],corrections:null},{id:"41442",title:"A Distributed Polling Service-Based Medium Access Control Protocol: Prototyping and Experimental Validation",doi:"10.5772/53772",slug:"a-distributed-polling-service-based-medium-access-control-protocol-prototyping-and-experimental-vali",totalDownloads:2182,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Yingsong Huang, Philip A. Walsh, Shiwen Mao and Yihan Li",downloadPdfUrl:"/chapter/pdf-download/41442",previewPdfUrl:"/chapter/pdf-preview/41442",authors:[{id:"156089",title:"Dr.",name:"Shiwen",surname:"Mao",slug:"shiwen-mao",fullName:"Shiwen Mao"},{id:"156126",title:"Mr.",name:"Yingsong",surname:"Huang",slug:"yingsong-huang",fullName:"Yingsong Huang"},{id:"156127",title:"Mr.",name:"Phillip",surname:"Walsh",slug:"phillip-walsh",fullName:"Phillip Walsh"},{id:"156128",title:"Dr.",name:"Yihan",surname:"Li",slug:"yihan-li",fullName:"Yihan Li"}],corrections:null},{id:"41449",title:"Graph-Based Routing, Broadcasting and Organizing Algorithms for Ad-Hoc Networks",doi:"10.5772/54146",slug:"graph-based-routing-broadcasting-and-organizing-algorithms-for-ad-hoc-networks",totalDownloads:3056,totalCrossrefCites:3,totalDimensionsCites:2,signatures:"Li Liu, Xianyue Li, Jiong Jin, Zigang Huang, Ming Liu and Marimuthu Palaniswami",downloadPdfUrl:"/chapter/pdf-download/41449",previewPdfUrl:"/chapter/pdf-preview/41449",authors:[{id:"156008",title:"Associate Prof.",name:"Li",surname:"Liu",slug:"li-liu",fullName:"Li Liu"},{id:"166197",title:"Dr.",name:"Xianyue",surname:"Li",slug:"xianyue-li",fullName:"Xianyue Li"},{id:"166198",title:"Dr.",name:"Jiong",surname:"Jin",slug:"jiong-jin",fullName:"Jiong Jin"},{id:"166199",title:"Dr.",name:"Zigang",surname:"Huang",slug:"zigang-huang",fullName:"Zigang Huang"},{id:"166200",title:"Dr.",name:"Ming",surname:"Liu",slug:"ming-liu",fullName:"Ming Liu"},{id:"166201",title:"Prof.",name:"Marimuthu",surname:"Palaniswami",slug:"marimuthu-palaniswami",fullName:"Marimuthu Palaniswami"}],corrections:null},{id:"41426",title:"Probabilistic Routing in Opportunistic Ad Hoc Networks",doi:"10.5772/53997",slug:"probabilistic-routing-in-opportunistic-ad-hoc-networks",totalDownloads:1583,totalCrossrefCites:3,totalDimensionsCites:4,signatures:"Vangelis Angelakis, Niki Gazoni and Di Yuan",downloadPdfUrl:"/chapter/pdf-download/41426",previewPdfUrl:"/chapter/pdf-preview/41426",authors:[{id:"156295",title:"Dr.",name:"Di",surname:"Yuan",slug:"di-yuan",fullName:"Di Yuan"},{id:"157141",title:"Dr.",name:"Vangelis",surname:"Angelakis",slug:"vangelis-angelakis",fullName:"Vangelis Angelakis"},{id:"157143",title:"Dr.",name:"Niki",surname:"Gazoni",slug:"niki-gazoni",fullName:"Niki Gazoni"}],corrections:null},{id:"41427",title:"Reducing Routing Loops Under Link-State Routing in Wireless Mesh Networks",doi:"10.5772/53814",slug:"reducing-routing-loops-under-link-state-routing-in-wireless-mesh-networks",totalDownloads:1931,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Takuya Yoshihiro",downloadPdfUrl:"/chapter/pdf-download/41427",previewPdfUrl:"/chapter/pdf-preview/41427",authors:[{id:"13453",title:"Dr.",name:"Takuya",surname:"Yoshihiro",slug:"takuya-yoshihiro",fullName:"Takuya Yoshihiro"}],corrections:null},{id:"41429",title:"Review of Autoconfiguration for MANETs",doi:"10.5772/52687",slug:"review-of-autoconfiguration-for-manets",totalDownloads:1866,totalCrossrefCites:2,totalDimensionsCites:2,signatures:"Hongbo Zhou and Matt W. Mutka",downloadPdfUrl:"/chapter/pdf-download/41429",previewPdfUrl:"/chapter/pdf-preview/41429",authors:[{id:"154490",title:"Dr.",name:"Hongbo",surname:"Zhou",slug:"hongbo-zhou",fullName:"Hongbo Zhou"}],corrections:null},{id:"41463",title:"Privacy-Preserving Information Gathering Using VANET",doi:"10.5772/53537",slug:"privacy-preserving-information-gathering-using-vanet",totalDownloads:2431,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"T. W. Chim, S. M. Yiu, Lucas C. K. Hui and Victor O. K. Li",downloadPdfUrl:"/chapter/pdf-download/41463",previewPdfUrl:"/chapter/pdf-preview/41463",authors:[{id:"13405",title:"Dr.",name:"Tat Wing",surname:"Chim",slug:"tat-wing-chim",fullName:"Tat Wing Chim"},{id:"13406",title:"Dr.",name:"S. M.",surname:"Yiu",slug:"s.-m.-yiu",fullName:"S. M. Yiu"},{id:"13407",title:"Dr.",name:"Lucas C. K.",surname:"Hui",slug:"lucas-c.-k.-hui",fullName:"Lucas C. K. Hui"},{id:"13408",title:"Prof.",name:"Victor O. K.",surname:"Li",slug:"victor-o.-k.-li",fullName:"Victor O. K. Li"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},relatedBooks:[{type:"book",id:"135",title:"Wireless Sensor Networks",subtitle:"Application - Centric Design",isOpenForSubmission:!1,hash:null,slug:"wireless-sensor-networks-application-centric-design",bookSignature:"Geoff V Merrett and Yen Kheng Tan",coverURL:"https://cdn.intechopen.com/books/images_new/135.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",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:"137",title:"Sustainable Wireless Sensor Networks",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"sustainable-wireless-sensor-networks",bookSignature:"Winston Seah and Yen Kheng Tan",coverURL:"https://cdn.intechopen.com/books/images_new/137.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",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:"3628",title:"Mobile and Wireless Communications",subtitle:"Network Layer and Circuit Level Design",isOpenForSubmission:!1,hash:null,slug:"mobile-and-wireless-communications-network-layer-and-circuit-level-design",bookSignature:"Salma Ait Fares and Fumiyuki Adachi",coverURL:"https://cdn.intechopen.com/books/images_new/3628.jpg",editedByType:"Edited by",editors:[{id:"3125",title:"Dr.",name:"Salma",surname:"Ait Fares",slug:"salma-ait-fares",fullName:"Salma Ait Fares"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"97",title:"Cellular Networks",subtitle:"Positioning, Performance Analysis, Reliability",isOpenForSubmission:!1,hash:"ca45ba51c623c9aef3c0d25772413039",slug:"cellular-networks-positioning-performance-analysis-reliability",bookSignature:"Agassi Melikov",coverURL:"https://cdn.intechopen.com/books/images_new/97.jpg",editedByType:"Edited by",editors:[{id:"23032",title:"Dr.",name:"Agassi",surname:"Melikov",slug:"agassi-melikov",fullName:"Agassi Melikov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"136",title:"Smart Wireless Sensor Networks",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"smart-wireless-sensor-networks",bookSignature:"Hoang Duc Chinh and Yen Kheng Tan",coverURL:"https://cdn.intechopen.com/books/images_new/136.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",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:"1938",title:"Advanced Wireless LAN",subtitle:null,isOpenForSubmission:!1,hash:"e4d4c069bc97e5c0ad97e60e023b6827",slug:"advanced-wireless-lan",bookSignature:"Song Guo",coverURL:"https://cdn.intechopen.com/books/images_new/1938.jpg",editedByType:"Edited by",editors:[{id:"15566",title:"Dr.",name:"Song",surname:"Guo",slug:"song-guo",fullName:"Song Guo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9219",title:"Recent Trends in Communication Networks",subtitle:null,isOpenForSubmission:!1,hash:"80b5339ac7ae4b7a91fd4e71b4d468e5",slug:"recent-trends-in-communication-networks",bookSignature:"Pinaki Mitra",coverURL:"https://cdn.intechopen.com/books/images_new/9219.jpg",editedByType:"Edited by",editors:[{id:"89103",title:"Prof.",name:"Pinaki",surname:"Mitra",slug:"pinaki-mitra",fullName:"Pinaki Mitra"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7322",title:"Wireless Mesh Networks",subtitle:"Security, Architectures and Protocols",isOpenForSubmission:!1,hash:"db5ab870ec11f9d4d1ebb54c7dd6e2bf",slug:"wireless-mesh-networks-security-architectures-and-protocols",bookSignature:"Mutamed Khatib and Samer Alsadi",coverURL:"https://cdn.intechopen.com/books/images_new/7322.jpg",editedByType:"Edited by",editors:[{id:"22273",title:"Dr.",name:"Mutamed",surname:"Khatib",slug:"mutamed-khatib",fullName:"Mutamed Khatib"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8662",title:"Data Service Outsourcing and Privacy Protection in Mobile Internet",subtitle:null,isOpenForSubmission:!1,hash:"697eadc7a3390023bb43d1d2406f0ebb",slug:"data-service-outsourcing-and-privacy-protection-in-mobile-internet",bookSignature:"Zhen Qin, Erqiang Zhou, Yi Ding, Yang Zhao, Fuhu Deng and Hu Xiong",coverURL:"https://cdn.intechopen.com/books/images_new/8662.jpg",editedByType:"Authored by",editors:[{id:"101193",title:"Dr.",name:"Hu",surname:"Xiong",slug:"hu-xiong",fullName:"Hu Xiong"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"3",chapterContentType:"chapter",authoredCaption:"Authored 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"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],ofsBooks:[]},correction:{item:{id:"74251",slug:"corrigendum-to-enhancing-soil-properties-and-maize-yield-through-organic-and-inorganic-nitrogen-and",title:"Corrigendum to: Enhancing Soil Properties and Maize Yield through Organic and Inorganic Nitrogen and Diazotrophic Bacteria",doi:null,correctionPDFUrl:"https://cdn.intechopen.com/pdfs/74251.pdf",downloadPdfUrl:"/chapter/pdf-download/74251",previewPdfUrl:"/chapter/pdf-preview/74251",totalDownloads:null,totalCrossrefCites:null,bibtexUrl:"/chapter/bibtex/74251",risUrl:"/chapter/ris/74251",chapter:{id:"71840",slug:"enhancing-soil-properties-and-maize-yield-through-organic-and-inorganic-nitrogen-and-diazotrophic-ba",signatures:"Arshad Jalal, Kamran Azeem, Marcelo Carvalho Minhoto Teixeira Filho and Aeysha Khan",dateSubmitted:"May 29th 2019",dateReviewed:"March 6th 2020",datePrePublished:"April 20th 2020",datePublished:"June 17th 2020",book:{id:"9345",title:"Sustainable Crop Production",subtitle:null,fullTitle:"Sustainable Crop Production",slug:"sustainable-crop-production",publishedDate:"June 17th 2020",bookSignature:"Mirza Hasanuzzaman, Marcelo Carvalho Minhoto Teixeira Filho, Masayuki Fujita and Thiago Assis Rodrigues Nogueira",coverURL:"https://cdn.intechopen.com/books/images_new/9345.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"76477",title:"Dr.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"190597",title:"Dr.",name:"Marcelo Carvalho Minhoto",middleName:null,surname:"Teixeira Filho",fullName:"Marcelo Carvalho Minhoto Teixeira Filho",slug:"marcelo-carvalho-minhoto-teixeira-filho",email:"mcm.teixeira-filho@unesp.br",position:null,institution:{name:"Sao Paulo State University",institutionURL:null,country:{name:"Brazil"}}},{id:"322298",title:"Dr.",name:"Aeysha",middleName:null,surname:"Khan",fullName:"Aeysha Khan",slug:"aeysha-khan",email:"fhw9uhfig@gmail.com",position:null,institution:null},{id:"322299",title:"Dr.",name:"Kamran",middleName:null,surname:"Azeem",fullName:"Kamran Azeem",slug:"kamran-azeem",email:"gisfgiog34sg@gmail.com",position:null,institution:null},{id:"322301",title:"Dr.",name:"Arshad",middleName:null,surname:"Jalal",fullName:"Arshad Jalal",slug:"arshad-jalal",email:"gisfgiog3465sg@gmail.com",position:null,institution:null}]}},chapter:{id:"71840",slug:"enhancing-soil-properties-and-maize-yield-through-organic-and-inorganic-nitrogen-and-diazotrophic-ba",signatures:"Arshad Jalal, Kamran Azeem, Marcelo Carvalho Minhoto Teixeira Filho and Aeysha Khan",dateSubmitted:"May 29th 2019",dateReviewed:"March 6th 2020",datePrePublished:"April 20th 2020",datePublished:"June 17th 2020",book:{id:"9345",title:"Sustainable Crop Production",subtitle:null,fullTitle:"Sustainable Crop Production",slug:"sustainable-crop-production",publishedDate:"June 17th 2020",bookSignature:"Mirza Hasanuzzaman, Marcelo Carvalho Minhoto Teixeira Filho, Masayuki Fujita and Thiago Assis Rodrigues Nogueira",coverURL:"https://cdn.intechopen.com/books/images_new/9345.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"76477",title:"Dr.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"190597",title:"Dr.",name:"Marcelo Carvalho Minhoto",middleName:null,surname:"Teixeira Filho",fullName:"Marcelo Carvalho Minhoto Teixeira Filho",slug:"marcelo-carvalho-minhoto-teixeira-filho",email:"mcm.teixeira-filho@unesp.br",position:null,institution:{name:"Sao Paulo State University",institutionURL:null,country:{name:"Brazil"}}},{id:"322298",title:"Dr.",name:"Aeysha",middleName:null,surname:"Khan",fullName:"Aeysha Khan",slug:"aeysha-khan",email:"fhw9uhfig@gmail.com",position:null,institution:null},{id:"322299",title:"Dr.",name:"Kamran",middleName:null,surname:"Azeem",fullName:"Kamran Azeem",slug:"kamran-azeem",email:"gisfgiog34sg@gmail.com",position:null,institution:null},{id:"322301",title:"Dr.",name:"Arshad",middleName:null,surname:"Jalal",fullName:"Arshad Jalal",slug:"arshad-jalal",email:"gisfgiog3465sg@gmail.com",position:null,institution:null}]},book:{id:"9345",title:"Sustainable Crop Production",subtitle:null,fullTitle:"Sustainable Crop Production",slug:"sustainable-crop-production",publishedDate:"June 17th 2020",bookSignature:"Mirza Hasanuzzaman, Marcelo Carvalho Minhoto Teixeira Filho, Masayuki Fujita and Thiago Assis Rodrigues Nogueira",coverURL:"https://cdn.intechopen.com/books/images_new/9345.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"76477",title:"Dr.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"10880",leadTitle:null,title:"Keratinocytes",subtitle:null,reviewType:"peer-reviewed",abstract:"This book will be a self-contained collection of scholarly papers targeting an audience of practicing researchers, academics, PhD students and other scientists. The contents of the book will be written by multiple authors and edited by experts in the field.",isbn:null,printIsbn:null,pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"eae9edff38d23aebd65ed631ae4c3af6",bookSignature:"",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10880.jpg",keywords:null,numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 25th 2020",dateEndSecondStepPublish:"December 16th 2020",dateEndThirdStepPublish:"February 14th 2021",dateEndFourthStepPublish:"May 5th 2021",dateEndFifthStepPublish:"July 4th 2021",remainingDaysToSecondStep:"a month",secondStepPassed:!0,currentStepOfPublishingProcess:1,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:null},relatedBooks:[{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"René Mauricio",surname:"Barría",slug:"rene-mauricio-barria",fullName:"René Mauricio Barría"}],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"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"61883",title:"Hereditary Disorders and Human Mutations of Iron-Sulfur Assembly Genes",doi:"10.5772/intechopen.78006",slug:"hereditary-disorders-and-human-mutations-of-iron-sulfur-assembly-genes",body:'\n
Mitochondria are double membrane-bound cellular organelles surrounded by outer and inner membranes [1, 2]. The organelle is considered cell’s powerhouse generating adenosine triphosphate (ATP) during cellular respiration; hence, facilitating energy conversion in eukaryotes. Uniquely, each mitochondrion has its own DNA and encodes mitochondrial genes; hence, contributing the cell’s proteome independently. The inheritance of the mitochondrial genome differs from nuclear genome since the donor of mitochondrial DNA (mtDNA) is the egg rather than sperm whose mitochondria are marked for obliteration upon entering the egg [3]. Hence, the organelle’s DNA is inherited through females known as “maternal inheritance.” Since these organelles generate energy, most biochemical reactions in the eukaryotic cells occur in the mitochondria. These reactions include pyruvate oxidation, citric acid cycle, electron transport, and oxidative phosphorylation (OXPHOS) all needed for energy production. Mitochondria also have an important role in calcium signaling, regulation of cellular metabolism, heme synthesis, steroid synthesis, apoptosis, and the biosynthesis of iron-sulfur (IS) clusters (ISC). The high number of human diseases caused by the malfunction of the mitochondrial proteins—encoded by nuclear or mtDNA—drew attention to the importance of this organelle.
\nMitochondria are genetically controlled by both nuclear DNA and the mitochondrial genome [1, 4]. A wide range of molecular defects have been identified in the human mitochondrial genome [4, 5, 6, 7, 8, 9]. Diseases due to mutations in the mitochondrial genome are clinically, genetically, and biochemically diverse [1, 2, 4, 6, 10]. Similarly, deficiencies in mitochondrial genes encoded by nuclear genome can also lead various mitochondrial disorders and a wide range of cellular perturbations such as undue reactive oxygen species and distracted apoptosis, aberrant calcium homeostasis, and deficient energy production. This in turn leads failure to meet the requirements of numerous organs, especially those with high energy needs. Hence, various pathological conditions appears due to impaired mitochondrial function in human body involving different cell types, tissues, and organs including heart and brain. Such multi-organ manifestations are all mitochondria related and these diseases varies from epilepsy to cardiac myopathies.
\nThe mitochondrial genome is a multicopy, double-stranded circular DNA molecule, which is 16.6 kb in human [11]. This genome encodes 13 essential proteins for the OXPHOS system and 24 components of the RNA machinery: 2 rRNAs and 22 tRNAs [11]. It is intronless and the only noncoding region is the displacement region (D-Loop), a region of 1.1 kb. It contains both the replication origins and the transcriptional promoters. Although mitochondria are genetically controlled by both mitochondrial and nuclear genomes, mtDNA is only maternally inherited [3]. Mitochondrial genetics differ greatly from Mendelian genetics in size, number of encoded genes, number of DNA molecules per cell, lack of introns, gene density, replication, transcription, recombination, and mode of inheritance. The 13 proteins include 7 subunits of NADH Dehydrogenase (complex I: ND1, ND2, ND3, ND4, ND4L, ND5 and ND6), Cytochrome b (subunit of complex III), 3 subunits of Cytochrome c oxidase or complex IV (COI, COII and COIII), and 2 subunits of F0F1 ATPase (ATPase 6 and ATPase 8). They are all encoded by mtDNA and synthesized in the organelle. While, complex II (Succinate Dehydrogenase) and the remaining subunits of complexes I, III, IV, and V are entirely encoded by the nuclear genome. These nuclear-encoded proteins are synthesized on cytosolic ribosomes and subsequently transported into the mitochondria.
\nISCs are evolutionarily ancient cofactors consisting of Fe (iron) and S (sulfur) associated to the cysteine sulfurs of proteins. The clusters are found in variety of organisms including archaea, protists, prokaryotes, and eukaryotes. In a eukaryotic cell, they can be found in the mitochondria, cytosol, and nucleus where they perform diverse functions [12]. ISCs play a critical role in many fundamental molecular processes and have roles in electron transfer, structural stabilization, gene regulation, enzymatic catalysis, metabolic regulation, and sensing environmental signals [13]. Almost 30 proteins in the mitochondria and the cytosol are involved in synthesizing and assembling these clusters. ISC have two most common forms [2Fe-2S] and [4Fe-4S] clusters. ISC-related proteins of the electron transport chain in the mitochondrion are mainly located in the inner membrane. Moreover, some of these proteins are also found in the mitochondrial matrix in the organelles. For the cluster assembly, two machineries are required, the mitochondrial ISC assembly machinery and the cytosolic IS protein assembly machinery [12].
\nEukaryotic IS proteins are located in mitochondria, cytosol, and nucleus, where they perform diverse functions in cellular metabolism and regulation. The mitochondrial ISC assembly machinery matures all organellar IS proteins, and additionally contributes to the biogenesis of cytosolic and nuclear IS proteins by producing an unknown sulfur-containing compound (X-S) that is exported to the cytosol and used by the cytosolic IS protein assembly machinery. Hence, mitochondria are directly responsible for the essential functions (e.g., of nuclear IS proteins involved in DNA metabolism and genome maintenance).
\nMitochondria forms iron-sulfur clusters of significant proteins such as DNA polymerase and DNA helicases, and, therefore, plays a significant role in survival. There are 17 different proteins forming iron-sulfur cluster machinery that places the clusters into the Apo proteins. The mechanism of formation of iron-sulfur clusters can be divided into three steps. First, it is synthesized on a scaffold protein. Second, it is bound to transfer protein after dislocation from scaffold protein. Third, the transfer protein, the cluster and the specific ISC targeting factor place the cluster into the Apo protein. The changes in the first two steps inhibit the maturation of extra mitochondrial Fe/S proteins and disturb the iron homeostasis [14]. Assembly of Fe-S cluster also takes place by NIF, SUF, and CIA machineries. Cysteine desulfurase is an enzyme that unites Fe-S assembly machineries. It is encoded by NFS 1 which functions to deliver sulfur to ISCU [15]. ISCU is an iron-sulfur cluster assembly enzyme; encodes component of iron-sulfur scaffold protein. The changes in this gene result in severe myopathy and lactic acidosis (“ISCU Fe-S Cluster Assembly Enzyme [Homo sapiens (Human)] - Gene - NCBI”) Complexes 1, 2, and 3 contain Fe-S clusters. They function in electron transport by transfer of one electron in redox processes [16]. The assembly of the clusters is recently studied in Yeast. In photosynthetic organisms, the iron-sulfur clusters play role in chloroplast processes and are important for plastid functioning [17].
\nYeast frataxin, Isu1, and Nfs1 (cysteine desulfurase) take part in de novo synthesis of ISC. Many genes encode ISC assembly factors such as BOLA3, NFU1, GLRX5, NUBPL, LYRM4, IBA57, ISCA1, and ISCA2. These molecules have significant role in mitochondria. They are essential cofactors in the assembly of cluster. Deficiency of these genes leads to different diseases, for instance, GLRX5 deficiency causes sideroblastic anemia, whereas NUBPL mutations lead to respiratory chain complex 1 deficiency. On the other hand, some of these deficiencies are classified under a unique category such as MMDS.
\nAs the names imply, multiple mitochondrial dysfunction syndromes are disease conditions affecting mitochondria and usually lead to reduced function of more than one stages of energy production in the organelle [18]. The genetic factors causing these disorders are associated with the biogenesis of cellular ISC and currently these are the following genes: ISCA2, NFU1, IBA57, and BOLA3. More recently, ISCA1 is also reported to lead a disease resembling MMDS and suggested to be a member of the group [19]. Interestingly, MMDS members appear to be inherited in autosomal recessive mode of inheritance (Table 1).
\nGene | \nCytoband | \nNCBI | \nGenomic location | \nMMDS-related phenotype | \nMIM PT# | \nIM | \nMIM LN | \n
---|---|---|---|---|---|---|---|
\n | \n\n | \n\n | \n\n | \nMultiple mitochondrial dysfunctions syndrome 1 | \n\n | \nAR | \n\n | \n
\n | \n\n | \n\n | \n\n | \nMultiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia | \n\n | \nAR | \n\n | \n
\n | \n\n | \n\n | \n\n | \nMultiple mitochondrial dysfunctions syndrome 3 | \n\n | \nAR | \n\n | \n
\n | \n\n | \n\n | \n\n | \nMultiple mitochondrial dysfunctions syndrome 4 | \n\n | \nAR | \n\n | \n
\n | \n\n | \n\n | \n\n | \nMultiple mitochondrial dysfunctions syndrome 5 | \n\n | \nAR | \n\n | \n
Genes and related mitochondrial dysfunction syndromes.
AR: autosomal recessive; IM: inheritance mode; LN: locus number; MIM: Mendelian inheritance in man; MMDS: mitochondrial dysfunction syndromes; PT#: phenotype number.
Iron-sulfur cluster assembly 1 (ISCA1) is one of the mitochondrial proteins required for the biogenesis and assembly of ISC [20]. This protein functions in the late stages of the ISC biogenesis and act as an iron binding molecule that may serve as a chaperone for biogenesis of Fe-S clusters [21]. It is believed that the molecule plays its pivotal role through its interaction with IOP1 (iron-only hydrogenase-like protein)/NARFL (nuclear prelamin A recognition factor-like). Knockdown of Isca1 causes reduced activity of succinate dehydrogenase, mitochondrial aconitase, and cytosolic aconitase; hence, involving in both cytosolic and mitochondrial Fe-S protein biogenesis [22].
\nAccording to GenAtlas [23, 24], the gene has four exons and produces 14 kDa protein with 129 amino acids, which is known as mitochondrial Fe-S cluster assembly 1 homolog or otherwise HESB like domain containing 2. The gene is mapped to chromosome 9q21.33, and sits on genomic coordinates: 88.879.463–88.897.490. It is 2012 base pair long, generates four transcripts (splice variants) and highly expressed heart, esophagus, bladder, uterus, and cervix. Moreover, ISCA1 is a member of consensus coding sequence (CCDS:35056.1) which are manually checked protein annotations on the reference mouse and human genomes that ensures consistent representation of the tracks of NCBI, Ensembl, and UCSC Genome Browsers. The gene has several synonyms such as hIsca, HBLD2, and ISA1, and localizes to mitochondria as well as cytoplasm.
\nEffect of depletion of ISC-related proteins on the maturation of cytosolic 4Fe-4S proteins showed that some mitochondrial Fe/S proteins such as mitochondrial aconitase, SDH, several proteins of complex I, and Rieske Fe/S protein were decreased with the deficiency of ISCA1. On the other hand, cellular heme content and mitochondrial 2Fe-2S ferrochelatase were unaffected by the depletion. This implies that ISCA1 is crucial in the maturation of mitochondrial 4Fe-4S proteins [25]. In another study, ISCA1 was found to be associated with multiple mitochondrial dysfunctions syndrome-5. A homozygous missense mutation at a conserved residue in the Fe-S biogenesis domain (c.259G>A, p.Glu87Lys) was identified in two unrelated Indian families. This mutation destabilizes the protein subsequently causing the syndrome [19].
\nISCA2 stands for iron-sulfur cluster assembly 2 protein and the gene encodes for A-type iron-sulfur cluster protein. Fe-S clusters are inorganic cofactors, mostly found in metalloproteins. The gene is located on chromosome 14 and expressed from the plus strand. According to Ensembl, this gene generates 4 different transcripts and has 96 orthologues. ISCA2 is a regulatory protein found in mitochondria as well as extra mitochondrial sites such as cytosol and nucleus. The protein takes part in assembly of Fe-S clusters in mitochondria which further take part in oxidation reduction (especially in complex 1 and 2), substrate activation, iron/sulfur storage, regulation of gene expression, and enzyme activity. Alternative name for ISCA2 is “HESB-like-domain-containing protein 1” for humans. First human mutation of ISCA2(c.229G>A; p.Glu77Ser) identified in the patients from five consanguineous families was a homozygous ancestral founder mutation that leaded to neurodegeneration, developmental, failure to thrive, quadriplegia, truncal hypotonia, optic atrophy, and leukoencephalopathy [26]. Later, additional 10 cases with the same founder mutation were also described [27]. Recently, two other patients with the same mutation were also studied with detailed functional experiments revealing complex 2 and 4 deficiencies [28]. Interestingly these patients were all Arab descent. Most recently, a second mutation, a compound heterozygous variant (a single basepair deletion causing frameshift with a premature stop codon: mutation: c.295delT; p.Phe99Leufs*18 and a missense mutation c.334A>G; p.Ser112Gly) in ISCA2 was reported in a 2-month-old girl from Italy [29]. These mutations causes disorder of energy metabolism which results in respiratory failure, severe hypotonia, nystagmus, lactic acidosis, poor neurologic development, hyperglycemia, leukodystrophy of the brainstem with longitudinally extensive spinal cord involvement, and mtDNA deficiency ultimately leading to death [26].
\nNFU1 is one of the human mitochondrial components that is involved in the assembly of the Fe-S protein cluster. It helps in the transfer of [4Fe-4S] clusters to specific protein targets and facilitates their maturation [30]. NFU1 is mapped on the 2p13-p15 chromosomal region and codes for the NFU1 protein. During Fe-S assembly, two NFU1 monomers are needed to assemble one 4Fe-4S. Complex I, II, and III of oxidative phosphorylation have multiple Fe-S clusters. Therefore, any deficiency in these clusters causes dysfunctions of respiratory chain complexes [31]. Previous studies showed that the function of the NFU1 has been associated by the fatal mitochondrial disease, multiple mitochondrial dysfunctions syndrome 1 (MMDS1) [30]. Patients with NFU1 mutations usually manifest feeding difficulty, weakness, lethargy, and decreasing responsiveness within a few days after birth and a few had epileptic seizures [31]. It has been shown that the patients with mutations in the NFU1 gene have similar biochemical features to that seen in patients with lipoic acid defects. Thus, NFU1 mutation appears to have some effect on Fe-S enzyme lipoic acid synthase (LAS). In conclusion, NFU1 is an ISC assembly protein, and there is strong evidence that LAS deficiency is important in NFU1 mutation-related disease [31].
\nIBA57 is a member of the Fe-S cluster assembly group. It is known as putative transferase CAF17 and Fe-S cluster assembly factor homolog. IBA57 is located on 1q42.13 and codes for the IBA57 protein that is located in the mitochondrion. This protein functions in the late stages of the biosynthesis of mitochondrial 4Fe-4S proteins. Any deficiency in IBA57 can cause an autosomal recessive spastic paraplegia-74 or multiple mitochondrial dysfunctions syndrome 3. In a previous study, it was found that the depletion of IBA57 in cell culture caused striking alterations in mitochondrial morphology, including a vast enlargement of the organelles and a loss of cristae membranes. It is also found that the function of IBA57 protein is conserved from bacteria to human, according to a study that provides an evidence for the requirement of bacterial and yeast relatives of human IBA57 for efficient maturation of [4Fe-4S] proteins. Moreover, potential diseases caused by mutations in these genes are expected to cause defects in mitochondrial respiration and in lipoic acid-dependent proteins [25]. Another study reported two siblings from consanguineous parents died with a condition characterized by generalized hypotonia, respiratory insufficiency, arthrogryposis, microcephaly, congenital brain malformations, and hyperglycinemia. Catalytic activities of the mitochondrial respiratory complexes I and II were deficient in skeletal muscle, a finding suggestive of an inborn error in mitochondrial biogenesis. Homozygosity mapping identified IBA57 located in the largest homozygous region on chromosome 1 as a culprit candidate gene. Their analysis of IBA57 revealed the homozygous mutation c.941A>C, p.Gln314Pro in those two patients [15].
\nBOLA3 is another essential protein in the Fe-S clusters production and involves in the normal maturation of lipoate-containing 2-oxoacid dehydrogenases. Another critical role of the molecule is to facilitate the assembly of the respiratory chain complexes. BOLA3 was identified in the year 2008 during a search for similar sequences for bacterial BolA and cloned together with BOL1 and BOL2 [32]. According to Ensembl, the gene has five different transcripts and two isoforms. The main isoform is longer and localizes to mitochondria while the shorter isoform lacking exon 2 is restrained in the cytosplasm [18, 33]. The main transcript (ENST00000327428.9) has four exons comprising 68 variations [33]. The mRNA is nearly ubiquitously expressed in human tissues. The protein has seven domains including two low complexity segments. The main BolA domain consists of a helix-turn-helix structure close to its C terminus. The gene has three published mutations (c.123dupA; p.Glu42Argfs; c.200T>A, p.Ile67Asn; c.136C>T, p.Arg46Ter) [18, 34, 35, 36] in addition to a 5 bp deletion [37] and a single basepair insertion [18]. These mutations were identified in ethnically different families. The first patients were initially described in 2001 in a mapping study [38] that included a singleton from a consanguineous family as well as three siblings from a nonconsanguineous family. Since all the patients from two different families had similar metabolic abnormalities, a mapping strategy was employed to identify the genetic interval for the causative gene. This approach located the gene on chromosome 2. Further positional cloning studies on the subjects yielded a single significant interval on p arm extending ~5 centiMorgan region and excluding the region positioned on the q arm. Interestingly, both of these families were utilized in a follow-up study that yielded deficiencies of two ISC-related genes in each family. While the larger family with three siblings were identified to harbor splice site mutation in NFU1 (c.545G>A) [18], the singleton had a single nucleotide duplication leading to a frame shift and eventually a premature stop codon (p.Glu42Argfs*13) in BOL3 [18]. Later on, a few more follow-up studies revealed additional mutations in the gene. The first follow-up study focused on two patients (male and female) with quite similar clinical course appeared with hypotonia, severe neonatal lactic acidosis, and intractable cardiomyopathy [35]. A missense mutation (c.200T>A, p.Ile67Asn) was identified in the patients’ DNA using exome sequencing. The other studies [34, 37] provided two additional missense mutations in BOLA3. Interestingly, while c.287A>G (p.His96Arg) causes a lethal infantile mitochondrial disorder [37], c.136C>T (p.Arg46*), a severe truncation mutation, leads to nonketotic hyperglycinemia [34] in the affected individuals.
\nTable 2 consists of previously published mutations in some Fe-S cluster genes.
\nGene | \nMutation type | \nMutation | \nDisease and phenotype | \nReferences | \n
---|---|---|---|---|
BOLA3 | \nMissense | \nc.200T>A; p.Ile67Asn | \nMultiple mitochondrial dysfunctions syndrome | \nHaack et al. [35] | \n
BOLA3 | \nMissense | \nc.287A>G p.His96Arg | \nLethal infantile mitochondrial disorder | \nKohda et al. [37] | \n
BOLA3 | \nNonsense | \nc.136C>T; p.Arg46* | \nNonketotic hyperglycinemia, | \nBaker et al. [34] | \n
BOLA3 | \nMicrodeletion | \nc.225_229delGAGAA; p. Lys75* | \nLethal infantile mitochondrial disorder | \nKohda et al. [37] | \n
BOLA3 | \nMicroduplication | \nc.123dupA | \nCombined respiratory chain and 2-oxoacid dehydrogenase deficiency | \nCameron et al. [18] | \n
IBA57 | \nMissense | \nc.313C>T; p.Arg105Trp | \nLeukodystrophy with acute psychomotor regression | \nTorraco et al. [39] | \n
IBA57 | \nMissense | \nc.316A>G; p.Thr106Ala | \nLeukodystrophy with acute psychomotor regression | \nTorraco et al. [39] | \n
IBA57 | \nMissense | \nc.436C>T; p.Arg146Thr | \nLeukodystrophy, fatal infantile | \nDebray et al. [40] | \n
IBA57 | \nMissense | \nc.586T>G; p.Trp196Gly | \nLeukodystrophy, developmental delay, feeding problems and recurrent vomiting | \nTorraco et al. [39] | \n
IBA57 | \nMissense | \nc.686C>T; p.Pro229Leu | \nLeukodystrophy, developmental delay, feeding problems and recurrent vomiting | \nTorraco et al. [39] | \n
IBA57 | \nMissense | \nc.706C>T; p.Pro236Ser | \nLeukodystrophy with acute psychomotor regression and feeding difficulties | \nTorraco et al. [39] | \n
IBA57 | \nMissense | \nc.757G>C; p.Val253Leu | \nLeukodystrophy with acute psychomotor regression | \nTorraco et al. [39] | \n
IBA57 | \nMissense | \nc.941A>C; p.Gln314Pro | \nMyopathy and encephalopathy | \nAjit Bolar et al. [15] | \n
IBA57 | \nSplice | \nIVS2 ds A-G-2; c.678A>G | \nSpastic paraplegia | \nLossos et al. [41] | \n
IBA57 | \nSmall insertion | \nc.87_88ins11 | \nLeukodystrophy with acute psychomotor regression | \nTorraco et al. [39] | \n
NFU1 | \nMissense | \nc.62G>C; p.Arg21Pro | \nNFU1 deficiency | \nAhting et al. [42] | \n
NFU1 | \nMissense | \nc.544C>T; p.Arg182Trp | \nNFU1 deficiency | \nAhting et al. [42] | \n
NFU1 | \nMissense | \nc.565G>A; p.Gly189Arg | \nLeukoencephalopathy with cysts and hyperglycinaemia | \nNizon et al. [43, 44, 45] | \n
NFU1 | \nMissense | \nc.568G>A; p.Gly190Arg | \nNFU1 deficiency | \nAhting et al. [42] | \n
NFU1 | \nMissense | \nc.572A>T; p.Asp191Val | \nMultiple mitochondrial dysfunctions syndrome | \nBai et al. [46] | \n
NFU1 | \nMissense | \nc.622G>T; p.Gly208Cys | \nFatal infantile encephalopathy and/or pulmonary hypertension | \nNavarro-Sastre et al. [47] | \n
NFU1 | \nMissense | \nc.629G>T; p.Cys210Phe | \nLeukoencephalopathy | \nInvernizzi et al. [44] | \n
NFU1 | \nSplice | \nc.302+3A>G; p.Val56Glyfs* | \nNFU1 deficiency | \nAhting et al. [42] | \n
NFU1 | \nSplice | \nc.545G>A; Skipping exon 6 | \nDeficiency of the 2-oxoacid dehydrogenases accompanied by respiratory chain defects | \nCameron et al. [18] | \n
NFU1 | \nSplice | \nc.545+5G>A; Skipping exon 6 | \nFatal infantile encephalopathy, pulmonary hypertension | \nNavarro-Sastre et al. [47] | \n
NFU1 | \nMicrodeletion | \nc.90delC; p. Tyr30* | \nMultiple mitochondrial dysfunctions syndrome | \nBai et al. [46] | \n
NFU1 | \nMicrodeletion | \nc.146delC; p.Pro49LeufsX8 | \nSpastic paraplegia | \nTonduti et al. [45] | \n
NFU1 | \nLarge deletion | \n55.6 kb region covering exons: 4–8 | \nNFU1 deficiency | \nAhting et al. [42] | \n
ISCA1 | \nMissense | \nc.259G>A; p. Glu87Lys | \nMultiple mitochondrial dysfunctions syndrome | \nShukla et al. [19] | \n
ISCA2 | \nMissense | \nc.229G>A; p.Glu77Ser | \nMultiple mitochondrial dysfunctions syndrome | \nAl-Hassnan et al. [26] and others [27, 28] | \n
ISCA2 | \nDeletion and Missense | \nc.295delT and c.334A>G; p.Phe99Leufs*18 and p.Ser112Gly | \nMultiple mitochondrial dysfunctions syndrome | \nToldo et al. [29] | \n
Published mutations in some Fe-S cluster genes.
Iron-sulfur clusters are indispensable inorganic cofactors for biological function and involve in numerous cellular processes such as respiration and DNA repair. The cluster’s assembly is complex and requires sophisticated protein machinery for its maturation and insertion into apoproteins. Since mitochondria is the main site for ISC biogenesis in human, any defect disturbing the biogenesis leads to a pathological outcome mostly appears as an mitochondrial entity in human. Currently, genetic alterations in several genes involving in ISC assembly and maturation have been linked to autosomal recessive mitochondrial human diseases known as multiple mitochondrial dysfunction syndromes. It is expected that more genes and alterations will appear in the literature related to ISC pathways. Moreover, there is still need to fully elucidate the phenotypic consequences of these genetic alterations and alteration of ISC pathways during the ISC related pathogenesis in human.
\nThis study was supported by King Abdulaziz City for Science and Technology grant 11-BIO2221-20 (NK) and King Salman Center for Disability Research grant: 2180 004 (NK).
\nGlaucoma is a leading cause of irreversible blindness worldwide [1]. Subjects with ocular hypertension (OHT) are known to have a higher risk of glaucoma development. OHT is defined as a mean intraocular pressure (IOP) ≥24 mmHg from two separate consecutive measurements without structural and functional evidence of glaucoma [2]. Patients with OHT are usually treated with IOP-lowering therapy based on the effectiveness of reducing the risk of glaucoma development according to the result of the Ocular Hypertension Treatment Study (OHTS) [3], which demonstrated a cumulative probability of 9.5% of developing primary open-angle glaucoma (POAG) in 5 years in the untreated OHT patients, compared with 4.4% in the treated group (patients who received IOP-lowering therapy). Hence, the incidence of POAG could be reduced by about 50% with adequate IOP reduction. In clinical practice, it is not uncommon that we adopt a treatment approach of liberally prescribing IOP-lowering medication based on the study results.
\nOn the other hand, the result of the OHTS also reflects that only <10% of the untreated OHT patients developed glaucoma in 5 years, compared to the 4.4% of the treated group. Hence, the number needed to treat to prevent one glaucoma development is 20. Indeed, it has been shown that treating all patients with OHT is not cost-effective [4, 5]. The estimated incremental cost of treating all OHT patients to prevent one subject from developing glaucoma was US$89,072 [4]. This is considered not cost-effective according to the standard of The National Institute for Health and Care Excellence (NICE), which classified a treatment as cost-effective at the level of risk when the incremental cost-effectiveness ratio (ICER) is equal to or less than US$50,000 [6]. Furthermore, long-term treatment with IOP-lowering medications can impose significant inconvenience and undesirable side effects to patients, such as ocular surface disease. For instance, a study that involved 537 OHT and POAG patients showed that side effects from medication can independently contribute to health-related quality of life scores, which could be as worse as 0.11 [7]. This is equivalent to the utility loss of patients with early to moderate stage of glaucoma [8, 9]. Therefore, selective and targeted use of medication is not merely a health economic issue; unnecessarily treating low-risk OHT patients would expose them to undesirable medication side effects without beneficial gain.
\nA more cost-effective approach is to treat OHT subjects who have higher risk of developing POAG—namely, an older age, a higher level of IOP, a thinner central corneal thickness (CCT), a larger vertical cup-to-disc ratio (VCDR) and a smaller pattern standard deviation (PSD) value on visual field (VF) test. These are risk factors of POAG development according to the joint data of the OHTS [2] and the European Glaucoma Prevention Study (EGPS) [10]. These are the two major multicentre, randomised control trials (RCTs) that involved patients with OHT. Stewart et al. suggested that it is cost-effective to treat patients with older age (≥76 years old), higher intraocular pressure (≥29 mmHg), thinner central corneal thickness (≤533 μm) and wider vertical cup-to-disc ratio (≥0.6) [4]. Kymes et al. suggested that treating OHT patients with IOP ≥24 mmHg and a ≥ 2% annual risk of glaucoma development is likely to be cost-effective [5]. Weinreb et al. suggested a risk stratification strategy: observation for patients with lower than average risk of POAG conversion (5-year risk of <5%), collaborative treatment decision between doctor and well-informed patient for those with moderate risk (5-year risk of 5–15%) and treatment for all subjects with higher than average risk (5-year risk of >15%) [11]. Based on this risk stratification strategy, it was demonstrated that nearly half (43.9%) of low-risk OHT eyes could safely have their medications reduced over 1 year, realising substantial savings [12]. In this study, only 1 out of 107 eyes (0.93%) developed a repeatable VF defect in the first year [12].
\nThe 5-year risk of POAG development can be calculated using the available risk calculator, which was developed based on a predictive model that utilised the joint data of OHTS and EGPS [13]. The calculation is based on the risk factors as mentioned—age, IOP, CCT, VCDR and PSD value of VF. It has the advantage of integrating multiple risk factors into one quantitative, estimated percentage risk of glaucoma development in OHT subjects. This can facilitate treatment decision because high-risk subjects can be identified based on simultaneous and quantitative consideration of all these available risk factors; thus, allows a more straightforward and cost-effective approach of treatment; and reduces unnecessary patient exposure to medication side effects.
\nIt is important to note that, similar to most multivariate prediction models derived from prospective studies [14], we are making several assumptions when we apply the 5-year risk calculator to guide treatment decision: [1] we assume that the baseline variables that were measured are the most predictive of the risk of glaucoma development, [2] the model also assumes that the risk of glaucoma progression is linear, and [3] patients who are being assessed have similar clinical characteristics as the participants in the OHTS and EGPS.
\nHowever, the variability of baseline risk factor measurements is a known phenomenon. IOP is well known to vary from visit to visit [15], which can be due to regression to the mean phenomenon, diurnal variation as well as order of IOP measurement [15]. This variability is also observed in the performance of VF, hence the PSD value [16]. Results of VF examination can be affected by patients’ subjectivity and the substantial test-retest variability. The PSD value is a weighted standard deviation of the differences between the measured and normal reference visual field at each test location. A higher PSD value merely suggests a more irregular ‘hill of vision’, which can contribute to variability in patients’ responses and/or areas of focal loss. Given that, by definition, OHT subjects do not have glaucomatous VF defect, the PSD value tends to be low. Therefore, a slight variability in patients’ responses can contribute to a significant change in its value. Care must be taken when interpreting PSD value as a stand-alone figure.
\nTherefore, the apparently more comprehensive risk stratification strategy that is based on the 5-year risk calculator can face several fundamental challenges. As discussed, the variability of IOP measurement and PSD value, even during baseline assessment, may add a considerable source of error to the risk calculation. Furthermore, due to the within-subject changes in risk factors’ values during follow-up, the correlation between baseline and updated values may diminish with time [17]. One study has demonstrated that risk calculation is variable over time and that longitudinal changes in baseline variables correspond with changes in the risk estimation of glaucoma development [18]. In the study, the 5-year risk of POAG development was calculated by incorporating different measurements that assume the best-case scenario (baseline age, lowest PSD, highest CCT and lowest IOP) and the worst-case scenario (final age, highest PSD, lowest CCT and highest IOP). For the VCDR, a value of ±0.2 was applied to model interobserver and intraobserver variability (i.e. -0.2 in addition to the best-case scenario and + 0.2 in addition to the worst-case scenario). It was found that, within the same individual, the mean risk of POAG conversion could increase by almost 10-fold when comparing the worst- and best-case scenarios (5.0% vs. 45.7%, P < 0.01). Hence, risk stratification is dynamic, and risk estimations should be recalculated during follow-up visits as variables can fluctuate significantly within the same individual over time.
\nIt is important to note that the VCDR data that derived the risk calculator was based on VCDR measurements on the optic disc stereophotography of the OHTS and EGPS cohorts. In the RCTs, the measurement and evaluation of the optic nerve head (ONH) were performed by highly trained, independent graders at designated optic disc centres that followed a strict protocol in a non-clinical setting [19]. In clinical practice, the assessment of ONH and the measurement of VCDR by individual ophthalmologists are susceptible to intraobserver and interobserver variability [20]. The precision and quality of the ONH evaluation is unlikely to match those in the RCTs.
\nNowadays, imaging technologies such as confocal scanning laser ophthalmoscopy by Heidelberg retinal tomography (HRT) and optical coherence tomography (OCT) provide an objective and reproducible measurement of optic disc parameters. However, different techniques of evaluating ONH (hence the VCDR measurement) may not agree with each other. For instance, there is a poor agreement in the optic disc measurements obtained from HRT and OCT [21]. A study that compared VCDR measurement obtained with OCT, HRT and stereophotography in untreated OHT patients showed that there were poor agreement and lack of interchangeability between different techniques [22]. This is due to the differences between the techniques in defining optic disc margin and optic disc cup. The assessment of ONH in HRT and stereophotography relies on the examiners to define the disc margin, which can be variable. Spectral-domain OCT demonstrated that the ‘perceived disc margin’ of HRT and stereophotography rarely correlate with the Bruch’s membrane opening (BMO) (Figure 1) [23, 24], which is considered to be the true outer border of the neural tissue because axons cannot pass through an intact Bruch’s membrane to exit the eye [25]. The BMO is also unaltered under larger change of IOP [26]. Hence, it is a more reliable landmark, especially for eyes with OHT. Spectral-domain OCT is arguably more accurate in defining the ONH because it defines the BMO at every clock hour. It can also reliably identify the cup margin by measuring the minimum distance between the BMO and the internal limiting membrane in all meridians; the built-in software can then define the maximal vertical diameter to be the vertical cup diameter. In comparison, the definition of vertical cup diameter by stereoscopic photography and HRT are likely to be less accurate. Both are based on subjective judgement of examiners in defining the cup and disc margin. In some cases of small cups that do not pass through the midline of the optic disc, HRT has difficulties in calculating the VCDR because it obtains the vertical cup diameter along the vertical axis at the midline of the disc. Hence, the value of VCDR becomes ‘0’ if the cup does not pass through the vertical midline.
\nOptic disc of a normal right eye (a) and corresponding spectral-domain optical coherence tomography (OCT, (b)) delineating the anatomical measurements of disc margin. The green dots on the fundus photo represent the Bruch’s membrane opening (BMO) identified by spectral-domain optical coherence tomography (OCT). The blue crosses represent the disc margin that was identified by an examiner with stereophotography. Hence, the green dots and blue crosses represent the potential disc margins that could be identified by different examiners (adapted from Chauhan BC and Burgoyne CF 2013 [25]).
The study that compared VCDR measured by OCT, HRT and stereophotography of the ONH in patients with untreated OHT also investigated how the degree of disagreement extended to their corresponding 5-year risk estimation when other risk factors were kept contant [22]. In the study, ONH images of 140 untreated OHT eyes (of 75 patients) were taken by fundus camera (stereoscopic images), OCT and HRT. ONH stereophotographs were evaluated with a stereo-viewer by two glaucoma specialists, and the VCDR was measured with the ImageJ software. VCDR measurements obtained with stereophotography, OCT and HRT were used to calculate the estimated 5-year risk. The study showed that there was disagreement in VCDR measurements between the three methods. This disagreement also extended to their corresponding 5-year risk estimation of POAG development [22]. When the comparison was made on the Bland–Altman plots, the range of discrepancies tended to widen with increasing mean risk, especially beyond the estimated risk of >15% (Figure 2). We should be careful when using the 5-year risk of >15% as our treatment threshold when using VCDR values that are obtained from different measurement techniques. This can dramatically alter the management approach for any OHT subjects, especially if they have a relatively high baseline estimated risk and/or larger VCDR. In the cohort of untreated OHT eyes from this study, up to 72 eyes (51.2%) would require treatment if OCT was used for assessing the VCDR, according to the ≥15% 5-year risk cut-off. On the other hand, only 54 eyes (38.6%) would require treatment if the VCDR measurements were obtained from stereophotography by one of the glaucoma specialists. Therefore, one must be cautious when applying the risk estimation obtained from the other means of measuring VCDR.
\nBland-Altman plot: comparison of 5-year risk estimations of POAG conversion that were calculated by vertical cup-to-disc ratio measured by different vertical cup-to-disc ratio measured by spectral-domain optical coherence tomography (OCT) and stereophotography performed by a glaucoma specialist. Notice that the range of discrepancies widen with increasing mean risk, especially beyond the estimated risk of >15%. OCT, optical coherence tomography; reader 1, stereophotography evaluation (adopted from Chan PP et al., 2019 [22]).
The diagnosis of glaucoma requires a confirmed glaucomatous VF defect that correlates with structural change. A glaucomatous visual field loss is defined as a cluster of ≥3 non-edged points in the PSD plot in a single hemifield with p value <5%, one of which must have a p value <1%; glaucoma hemifield test outside normal limits; and PSD with p value <5%. Any one of these criteria, if repeatable, was considered as sufficient evidence of a glaucomatous VF defect [27]. This has been considered as the gold standard of diagnosing glaucoma. OCT has gained popularity in the past decades and is now the standard for assessing structural damage of retinal nerve fibre layer (RNFL) and ONH for the detection of structural glaucomatous change. Indeed, RNFL and ONH measured by OCT were shown to be useful in differentiating normal eyes from even mild glaucoma [28]. Evidence suggests that RNFL thinning measured by OCT can detect glaucomatous damage several years before detectable functional deficits by VF testing [28, 29, 30]. The 10th World Glaucoma Association consensus meeting stated that ‘detecting progressive glaucomatous RNFL thinning and neuroretinal rim narrowing is the best currently available gold standard for glaucoma diagnosis [31]’. This emphasised the importance of detecting RNFL abnormalities in terms of the diagnosis of glaucoma. Since OCT is becoming an invaluable tool for detecting early changes of ONH and RNFL thinning, especially because of its repeatability and objectiveness, it is logical to suggest that a risk scoring system for OHT patients should include OCT measurements.
\nOn the contrary, the measurement of VCDR by stereoscopic photography or during clinical examination remains the only parameter in the risk calculator that reflects the structural status of the complex architecture of the ONH. During the slow and progressive process of glaucoma development, enlargement of VCDR could happen much later than the occurrence of RNFL thinning and other subtle structural glaucomatous damage. It is important to note that the powerful and carefully designed OHTS and EGPS were performed in the era when OCT was not widely used as an investigative tool. The two studies ruled out glaucoma patients from OHT mainly based on VF criteria and the absence of detectable structural damage on stereoscopic photography. Therefore, it might not be cavalier to suggest that a portion of these subjects might already have ‘asymptomatic disease’ (or pre-perimetric glaucoma) (Figure 3), and this damage was undetectable on stereoscopic photography, which was also suggested by Weinreb et al. [11]. The ever-evolving OCT technology and the concepts of ONH assessment can provide valuable data and new parameters for further refinement of the existing risk calculator, for instance, integrating other factors of OHN and RNFL based on OCT measurement [22]. The glaucoma risk model needs refinement that involves the advancing OCT technologies and concepts in measuring VCDR. Reliable risk estimation is important as it may guide treatment decision, which in turn has consequences on both health economics and patients’ quality of life.
\nSpectrum of disease in glaucoma. RNFL, retinal nerve fibre layer. OCT, optical coherence tomography. VF, visual field (adapted from Weinreb et al., 2004 [11]).
Evidence shows that RNFL abnormalities can often be evident without detectable VF damage [32, 33, 34, 35]. Therefore, measuring the change of RNFL is likely to be useful in detecting early disease progression. Spectral-domain OCT is now the invaluable investigation tool for glaucoma patients because it can measure RNFL thickness reliably [36] with high sensitivity and specificity to detect glaucoma [37, 38] and its progression [39]. Commercially available software event-based algorithm, such as the Guided Progression Analysis (GPA, Carl Zeiss Meditec), can detect progressive RNFL thinning using RNFL thickness maps. A study has demonstrated that GPA can detect and visualise different patterns of progressive RNFL thinning [39]. Trend-Based Progression Analysis (TPA) is another algorithm for detecting progressive RNFL thinning by measuring the rate of change in RNFL thickness for each superpixel of the RNFL thickness map (50 x 50 superpixels). A study that involved 139 POAG patients (240 eyes) followed up for ≥5 years showed that progressive RNFL thinning determined by GPA and TPA was predictive of detectable functional decline in glaucoma. The study showed that TPA outperformed GPA in detecting more eyes with progressive RNFL thinning at a similar level of specificity (84.2% vs. 81.7% for TPA and GPA, respectively) [40]. Furthermore, TPA also provides visualisation of the distribution of the rate of RNFL thinning. It was suggested that the detection of progressive RNFL loss can serve as a biomarker to reflect disease deterioration behaviour and hence guide glaucoma management [40]. However, TPA is not without its limitations. A minimum of four follow-up visits is required for the construction of the TPA, and performance can be undermined with fewer visits. In situations where there are abrupt RNFL changes or in eyes with large test-retest variability, the event-based analysis may be more useful [41]. The authors concluded that TPA enhances but may not replace GPA for topographic analysis of RNFL thinning.
\nClinical trials usually define a treatment IOP-lowering target. For instance, the OHT study aimed for an IOP lowering by 20% from baseline for patients in the treatment arm [3], whereas the Collaborative Normal Tension Glaucoma (CNTG) study targeted an IOP lowering by 30% from baseline [42]. The Laser in Glaucoma and Ocular Hypertension (LiGHT) trial is a multicentre RCT that compared eye drops versus selective laser trabeculoplasty as first-line treatment for POAG or OHT [43]. The study is unique with its well-constructed algorithm for detecting disease progression and guiding treatment escalation [44]. It has a novel approach to defining target IOP. Firstly, the target IOP is specific for each patient at baseline, based on disease severity and lifetime risk of loss of vision at recruitment (e.g. different target pressure and percentage IOP reduction according to the disease stratification suggested by Mills et al. [45]). Secondly, the IOP was adjustable based on IOP control and disease progression [44]. The disease progression (either glaucoma deterioration or conversion of OHT to POAG) was determined by a decision support software based on objective visual field and optic disc imaging criteria. Disease progression was defined as ‘strong evidence’, with the Humphrey GPA software showing ‘likely progression’ and/or HRT rim area > 1% per year (at P < 0.001), and ‘less strong evidence’ with GPA showing ‘possible progression’ and/or HRT rim area > 1% per year (at P < 0.01). ‘Likely visual field progression’ is the presence of three or more points on the GPA at <0.05 probability for change on three consecutive occasions, while ‘possible visual field progression’ is the same criterion but on only two consecutive occasions [44]. Optic disc progression was defined as the rate of neuroretinal rim loss exceeding 1% of baseline rim area/year on a minimum of five repeat HRT images, where this is equivalent to approximately twice the value of normal age-related rim area loss [22]. Following treatment escalation, there is a resetting of both the target IOP and visual field and optic disc baselines against which future assessments will be compared with.
\nAlthough the LiGHT trial is probably more complex in its target IOP setting algorithm compared with other glaucoma trials which defined treatment success based on the proportion of patients achieving a particular target percentage reduction of IOP, it resembled closer to our clinical practice. For instance, further IOP lowering beyond the ‘target IOP’ is probably required for patients with progressive disease. In some cases, patients might request to reduce medication use even when the target IOP is not achieved (e.g. OHT patients with IOP at 24 mmHg who do not want treatment and show no signs of POAG conversion). Furthermore, the LiGHT trial is also unique in that it included the evaluation of quality of life as an outcome measure. These are all novel features that might become important components for future glaucoma study design.
\nIt is more cost-effective to selectively treat OHT subjects who have a higher risk of POAG conversion. However, risk assessment can be difficult due to the variabilities in the measurement of the baseline variables of the glaucoma risk calculator. In the era of advancing OCT technology and knowledge of glaucoma, there may be a need to refine our existing risk assessment methodology.
\nAll authors have no financial/proprietary interest in the subject matters of the manuscript.
IntechOpen is the first native scientific publisher of Open Access books, with more than 116,000 authors worldwide, ranging from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery. Established in Europe with the new headquarters based in London, and with plans for international growth, IntechOpen is the leading publisher of Open Access scientific books. The values of our business are based on the same ones that any scientist applies to their research -- we have created a culture of respect, collegiality and collaboration within an atmosphere that’s relaxed, friendly and progressive.
",metaTitle:"Social Media Community Manager and Marketing Assistant",metaDescription:"We are looking to add further talent to our team in The Shard office in London with a full-time Marketing and Communications Specialist position. The candidate will bring with them a creative and enthusiastic mindset, high level problem-solving skills, the latest marketing and social media platforms skills and strong involvement in community-best practices to engage with researchers and scholars online. The ideal candidate will be a dynamic, forward thinking, approachable team player, able to communicate with all in the global, growing company, with an ability to understand and build a rapport within the research community.",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"We are looking to add further talent to our team in The Shard office in London with a full-time Social Media Community Manager and Marketing Assistant position. The candidate will bring with them a creative and enthusiastic mindset, high level problem-solving skills, the latest marketing and social media platforms skills and strong involvement in community-best practices to engage with researchers and scholars online. The ideal candidate wll be a dynamic, forward thinking, approachable team player, able to communicate with all in the global, growing company, with an ability to understand and build a rapport within the research community.
\\n\\nThe Social Media Community Manager and Marketing Assistant will report to the Senior Marketing Manager. They will work alongside the Marketing and Corporate Communications team, supporting the preparation of all marketing programs, assisting in the development of scientific marketing and communication deliverables, and creating content for social media outlets, as well as managing international social communities.
\\n\\nResponsibilities:
\\n\\nEssential Skills:
\\n\\nDesired Skills:
\\n\\nWhat makes IntechOpen a great place to work?
\\n\\nIntechOpen is a global, dynamic and fast-growing company offering excellent opportunities to develop. We are a young and vibrant company where great people do great work. We offer a creative, dedicated, committed, passionate, and above all, fun environment where you can work, travel, meet world-renowned researchers and grow your career and experience.
\\n\\nTo apply, please email a copy of your CV and covering letter to hogan@intechopen.com stating your salary expectations.
\\n\\nNote: This full-time position will have an immediate start. In your cover letter, please indicate when you might be available for a block of two hours. As part of the interview process, all candidates that make it to the second phase will participate in a writing exercise.
\\n\\n*IntechOpen is an Equal Opportunities Employer consistent with its obligations under the law and does not discriminate against any employee or applicant on the basis of disability, gender, age, colour, national origin, race, religion, sexual orientation, war veteran status, or any classification protected by state, or local law.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'We are looking to add further talent to our team in The Shard office in London with a full-time Social Media Community Manager and Marketing Assistant position. The candidate will bring with them a creative and enthusiastic mindset, high level problem-solving skills, the latest marketing and social media platforms skills and strong involvement in community-best practices to engage with researchers and scholars online. The ideal candidate wll be a dynamic, forward thinking, approachable team player, able to communicate with all in the global, growing company, with an ability to understand and build a rapport within the research community.
\n\nThe Social Media Community Manager and Marketing Assistant will report to the Senior Marketing Manager. They will work alongside the Marketing and Corporate Communications team, supporting the preparation of all marketing programs, assisting in the development of scientific marketing and communication deliverables, and creating content for social media outlets, as well as managing international social communities.
\n\nResponsibilities:
\n\nEssential Skills:
\n\nDesired Skills:
\n\nWhat makes IntechOpen a great place to work?
\n\nIntechOpen is a global, dynamic and fast-growing company offering excellent opportunities to develop. We are a young and vibrant company where great people do great work. We offer a creative, dedicated, committed, passionate, and above all, fun environment where you can work, travel, meet world-renowned researchers and grow your career and experience.
\n\nTo apply, please email a copy of your CV and covering letter to hogan@intechopen.com stating your salary expectations.
\n\nNote: This full-time position will have an immediate start. In your cover letter, please indicate when you might be available for a block of two hours. As part of the interview process, all candidates that make it to the second phase will participate in a writing exercise.
\n\n*IntechOpen is an Equal Opportunities Employer consistent with its obligations under the law and does not discriminate against any employee or applicant on the basis of disability, gender, age, colour, national origin, race, religion, sexual orientation, war veteran status, or any classification protected by state, or local law.
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"58592",title:"Dr.",name:"Arun",middleName:null,surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58592/images/1664_n.jpg",biography:"Arun K. Shanker is serving as a Principal Scientist (Plant Physiology) with the Indian Council of Agricultural Research (ICAR) at the Central Research Institute for Dryland Agriculture in Hyderabad, India. He is working with the ICAR as a full time researcher since 1993 and has since earned his Advanced degree in Crop Physiology while in service. He has been awarded the prestigious Member of the Royal Society of Chemistry (MRSC), by the Royal Society of Chemistry, London in 2015. Presently he is working on systems biology approach to study the mechanism of abiotic stress tolerance in crops. His main focus now is to unravel the mechanism of drought and heat stress response in plants to tackle climate change related threats in agriculture.",institutionString:null,institution:{name:"Indian Council of Agricultural Research",country:{name:"India"}}},{id:"4782",title:"Prof.",name:"Bishnu",middleName:"P",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4782/images/system/4782.jpg",biography:"Bishnu P. Pal is Professor of Physics at Mahindra École\nCentrale Hyderabad India since July 1st 2014 after retirement\nas Professor of Physics from IIT Delhi; Ph.D.’1975 from IIT\nDelhi; Fellow of OSA and SPIE; Senior Member IEEE;\nHonorary Foreign Member Royal Norwegian Society for\nScience and Arts; Member OSA Board of Directors (2009-\n11); Distinguished Lecturer IEEE Photonics Society (2005-\n07).",institutionString:null,institution:{name:"Indian Institute of Technology Delhi",country:{name:"India"}}},{id:"69653",title:"Dr.",name:"Chusak",middleName:null,surname:"Limsakul",slug:"chusak-limsakul",fullName:"Chusak Limsakul",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Prince of Songkla University",country:{name:"Thailand"}}},{id:"75563",title:"Dr.",name:"Farzana Khan",middleName:null,surname:"Perveen",slug:"farzana-khan-perveen",fullName:"Farzana Khan Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75563/images/system/75563.png",biography:"Dr Farzana Khan Perveen (FLS; Gold-Medallist) obtained her BSc (Hons) and MSc (Zoology: Entomology) from the University of Karachi, MAS (Monbush-Scholar; Agriculture: Agronomy) and from the Nagoya University, Japan, and PhD (Research and Course-works from the Nagoya University; Toxicology) degree from the University of Karachi. She is Founder/Chairperson of the Department of Zoology (DOZ) and Ex-Controller of Examinations at Shaheed Benazir Bhutto University (SBBU) and Ex-Founder/ Ex-Chairperson of DOZ, Hazara University and Kohat University of Science & Technology. \nShe is the author of 150 high impact research papers, 135 abstracts, 4 authored books and 8 chapters. She is the editor of 5 books and she supervised BS(4), MSc(50), MPhil(40), and Ph.D. (1) students. She has organized and participated in numerous international and national conferences and received multiple awards and fellowships. She is a member of research societies, editorial boards of Journals, and World-Commission on Protected Areas, International Union for Conservation of Nature. Her fields of interest are Entomology, Toxicology, Forensic Entomology, and Zoology.",institutionString:"Shaheed Benazir Bhutto University",institution:{name:"Shaheed Benazir Bhutto University",country:{name:"Pakistan"}}},{id:"23804",title:"Dr.",name:"Hamzah",middleName:null,surname:"Arof",slug:"hamzah-arof",fullName:"Hamzah Arof",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/23804/images/5492_n.jpg",biography:"Hamzah Arof received his BSc from Michigan State University, and PhD from the University of Wales. Both degrees were in electrical engineering. His current research interests include signal processing and photonics. Currently he is affiliated with the Department of Electrical Engineering, University of Malaya, Malaysia.",institutionString:null,institution:{name:"University of Malaya",country:{name:"Malaysia"}}},{id:"41989",title:"Prof.",name:"He",middleName:null,surname:"Tian",slug:"he-tian",fullName:"He Tian",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"East China University of Science and Technology",country:{name:"China"}}},{id:"33351",title:null,name:"Hendra",middleName:null,surname:"Hermawan",slug:"hendra-hermawan",fullName:"Hendra Hermawan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/33351/images/168_n.jpg",biography:null,institutionString:null,institution:{name:"Institut Teknologi Bandung",country:{name:"Indonesia"}}},{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Osaka University",country:{name:"Japan"}}},{id:"45747",title:"Dr.",name:"Hsin-I",middleName:null,surname:"Chang",slug:"hsin-i-chang",fullName:"Hsin-I Chang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:{name:"National Chiayi University",country:{name:"Taiwan"}}},{id:"61581",title:"Dr.",name:"Joy Rizki Pangestu",middleName:null,surname:"Djuansjah",slug:"joy-rizki-pangestu-djuansjah",fullName:"Joy Rizki Pangestu Djuansjah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61581/images/237_n.jpg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"94249",title:"Prof.",name:"Junji",middleName:null,surname:"Kido",slug:"junji-kido",fullName:"Junji Kido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Yamagata University",country:{name:"Japan"}}},{id:"12009",title:"Dr.",name:"Ki Young",middleName:null,surname:"Kim",slug:"ki-young-kim",fullName:"Ki Young Kim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12009/images/system/12009.jpg",biography:"Http://m80.knu.ac.kr/~doors",institutionString:null,institution:{name:"National Cheng Kung University",country:{name:"Taiwan"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5699},{group:"region",caption:"Middle and South America",value:2,count:5172},{group:"region",caption:"Africa",value:3,count:1689},{group:"region",caption:"Asia",value:4,count:10244},{group:"region",caption:"Australia and Oceania",value:5,count:888},{group:"region",caption:"Europe",value:6,count:15650}],offset:12,limit:12,total:10244},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateendthirdsteppublish"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:16},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:6},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:4},{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:4},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:56},{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:0,limit:12,total:null},popularBooks:{featuredBooks:[{type:"book",id:"7802",title:"Modern Slavery and Human Trafficking",subtitle:null,isOpenForSubmission:!1,hash:"587a0b7fb765f31cc98de33c6c07c2e0",slug:"modern-slavery-and-human-trafficking",bookSignature:"Jane Reeves",coverURL:"https://cdn.intechopen.com/books/images_new/7802.jpg",editors:[{id:"211328",title:"Prof.",name:"Jane",middleName:null,surname:"Reeves",slug:"jane-reeves",fullName:"Jane Reeves"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8545",title:"Animal Reproduction in Veterinary Medicine",subtitle:null,isOpenForSubmission:!1,hash:"13aaddf5fdbbc78387e77a7da2388bf6",slug:"animal-reproduction-in-veterinary-medicine",bookSignature:"Faruk Aral, Rita Payan-Carreira and Miguel Quaresma",coverURL:"https://cdn.intechopen.com/books/images_new/8545.jpg",editors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9961",title:"Data Mining",subtitle:"Methods, Applications and Systems",isOpenForSubmission:!1,hash:"ed79fb6364f2caf464079f94a0387146",slug:"data-mining-methods-applications-and-systems",bookSignature:"Derya Birant",coverURL:"https://cdn.intechopen.com/books/images_new/9961.jpg",editors:[{id:"15609",title:"Dr.",name:"Derya",middleName:null,surname:"Birant",slug:"derya-birant",fullName:"Derya Birant"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9157",title:"Neurodegenerative Diseases",subtitle:"Molecular Mechanisms and Current Therapeutic Approaches",isOpenForSubmission:!1,hash:"bc8be577966ef88735677d7e1e92ed28",slug:"neurodegenerative-diseases-molecular-mechanisms-and-current-therapeutic-approaches",bookSignature:"Nagehan Ersoy Tunalı",coverURL:"https://cdn.intechopen.com/books/images_new/9157.jpg",editors:[{id:"82778",title:"Ph.D.",name:"Nagehan",middleName:null,surname:"Ersoy Tunalı",slug:"nagehan-ersoy-tunali",fullName:"Nagehan Ersoy Tunalı"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8686",title:"Direct Torque Control Strategies of Electrical Machines",subtitle:null,isOpenForSubmission:!1,hash:"b6ad22b14db2b8450228545d3d4f6b1a",slug:"direct-torque-control-strategies-of-electrical-machines",bookSignature:"Fatma Ben Salem",coverURL:"https://cdn.intechopen.com/books/images_new/8686.jpg",editors:[{id:"295623",title:"Associate Prof.",name:"Fatma",middleName:null,surname:"Ben Salem",slug:"fatma-ben-salem",fullName:"Fatma Ben Salem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7434",title:"Molecular Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"eceede809920e1ec7ecadd4691ede2ec",slug:"molecular-biotechnology",bookSignature:"Sergey Sedykh",coverURL:"https://cdn.intechopen.com/books/images_new/7434.jpg",editors:[{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9839",title:"Outdoor Recreation",subtitle:"Physiological and Psychological Effects on Health",isOpenForSubmission:!1,hash:"5f5a0d64267e32567daffa5b0c6a6972",slug:"outdoor-recreation-physiological-and-psychological-effects-on-health",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/9839.jpg",editors:[{id:"158692",title:"Ph.D.",name:"Hilde G.",middleName:null,surname:"Nielsen",slug:"hilde-g.-nielsen",fullName:"Hilde G. Nielsen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{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",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"}},{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",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"}},{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:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],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"}}],offset:12,limit:12,total:5143},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{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",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"}},{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",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"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{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:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",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"}},{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:"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:"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:"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"}}],latestBooks:[{type:"book",id:"7434",title:"Molecular Biotechnology",subtitle:null,isOpenForSubmission:!1,hash:"eceede809920e1ec7ecadd4691ede2ec",slug:"molecular-biotechnology",bookSignature:"Sergey Sedykh",coverURL:"https://cdn.intechopen.com/books/images_new/7434.jpg",editedByType:"Edited by",editors:[{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8545",title:"Animal Reproduction in Veterinary Medicine",subtitle:null,isOpenForSubmission:!1,hash:"13aaddf5fdbbc78387e77a7da2388bf6",slug:"animal-reproduction-in-veterinary-medicine",bookSignature:"Faruk Aral, Rita Payan-Carreira and Miguel Quaresma",coverURL:"https://cdn.intechopen.com/books/images_new/8545.jpg",editedByType:"Edited by",editors:[{id:"25600",title:"Prof.",name:"Faruk",middleName:null,surname:"Aral",slug:"faruk-aral",fullName:"Faruk Aral"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9569",title:"Methods in Molecular Medicine",subtitle:null,isOpenForSubmission:!1,hash:"691d3f3c4ac25a8093414e9b270d2843",slug:"methods-in-molecular-medicine",bookSignature:"Yusuf Tutar",coverURL:"https://cdn.intechopen.com/books/images_new/9569.jpg",editedByType:"Edited by",editors:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9839",title:"Outdoor Recreation",subtitle:"Physiological and Psychological Effects on Health",isOpenForSubmission:!1,hash:"5f5a0d64267e32567daffa5b0c6a6972",slug:"outdoor-recreation-physiological-and-psychological-effects-on-health",bookSignature:"Hilde G. Nielsen",coverURL:"https://cdn.intechopen.com/books/images_new/9839.jpg",editedByType:"Edited by",editors:[{id:"158692",title:"Ph.D.",name:"Hilde G.",middleName:null,surname:"Nielsen",slug:"hilde-g.-nielsen",fullName:"Hilde G. Nielsen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7802",title:"Modern Slavery and Human Trafficking",subtitle:null,isOpenForSubmission:!1,hash:"587a0b7fb765f31cc98de33c6c07c2e0",slug:"modern-slavery-and-human-trafficking",bookSignature:"Jane Reeves",coverURL:"https://cdn.intechopen.com/books/images_new/7802.jpg",editedByType:"Edited by",editors:[{id:"211328",title:"Prof.",name:"Jane",middleName:null,surname:"Reeves",slug:"jane-reeves",fullName:"Jane Reeves"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8063",title:"Food Security in Africa",subtitle:null,isOpenForSubmission:!1,hash:"8cbf3d662b104d19db2efc9d59249efc",slug:"food-security-in-africa",bookSignature:"Barakat Mahmoud",coverURL:"https://cdn.intechopen.com/books/images_new/8063.jpg",editedByType:"Edited by",editors:[{id:"92016",title:"Dr.",name:"Barakat",middleName:null,surname:"Mahmoud",slug:"barakat-mahmoud",fullName:"Barakat Mahmoud"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10118",title:"Plant Stress Physiology",subtitle:null,isOpenForSubmission:!1,hash:"c68b09d2d2634fc719ae3b9a64a27839",slug:"plant-stress-physiology",bookSignature:"Akbar Hossain",coverURL:"https://cdn.intechopen.com/books/images_new/10118.jpg",editedByType:"Edited by",editors:[{id:"280755",title:"Dr.",name:"Akbar",middleName:null,surname:"Hossain",slug:"akbar-hossain",fullName:"Akbar Hossain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9157",title:"Neurodegenerative Diseases",subtitle:"Molecular Mechanisms and Current Therapeutic Approaches",isOpenForSubmission:!1,hash:"bc8be577966ef88735677d7e1e92ed28",slug:"neurodegenerative-diseases-molecular-mechanisms-and-current-therapeutic-approaches",bookSignature:"Nagehan Ersoy Tunalı",coverURL:"https://cdn.intechopen.com/books/images_new/9157.jpg",editedByType:"Edited by",editors:[{id:"82778",title:"Ph.D.",name:"Nagehan",middleName:null,surname:"Ersoy Tunalı",slug:"nagehan-ersoy-tunali",fullName:"Nagehan Ersoy Tunalı"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9961",title:"Data Mining",subtitle:"Methods, Applications and Systems",isOpenForSubmission:!1,hash:"ed79fb6364f2caf464079f94a0387146",slug:"data-mining-methods-applications-and-systems",bookSignature:"Derya Birant",coverURL:"https://cdn.intechopen.com/books/images_new/9961.jpg",editedByType:"Edited by",editors:[{id:"15609",title:"Dr.",name:"Derya",middleName:null,surname:"Birant",slug:"derya-birant",fullName:"Derya Birant"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8686",title:"Direct Torque Control Strategies of Electrical Machines",subtitle:null,isOpenForSubmission:!1,hash:"b6ad22b14db2b8450228545d3d4f6b1a",slug:"direct-torque-control-strategies-of-electrical-machines",bookSignature:"Fatma Ben Salem",coverURL:"https://cdn.intechopen.com/books/images_new/8686.jpg",editedByType:"Edited by",editors:[{id:"295623",title:"Associate Prof.",name:"Fatma",middleName:null,surname:"Ben Salem",slug:"fatma-ben-salem",fullName:"Fatma Ben Salem"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"183",title:"Hematology",slug:"hematology",parent:{title:"Medicine",slug:"medicine"},numberOfBooks:35,numberOfAuthorsAndEditors:565,numberOfWosCitations:209,numberOfCrossrefCitations:138,numberOfDimensionsCitations:321,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"hematology",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7845",title:"Platelets",subtitle:null,isOpenForSubmission:!1,hash:"d33b20516d6ff3a5b7446a882109ba26",slug:"platelets",bookSignature:"Steve W. Kerrigan",coverURL:"https://cdn.intechopen.com/books/images_new/7845.jpg",editedByType:"Edited by",editors:[{id:"73961",title:"Dr.",name:"Steve W.",middleName:"W.",surname:"Kerrigan",slug:"steve-w.-kerrigan",fullName:"Steve W. Kerrigan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8450",title:"Beta Thalassemia",subtitle:null,isOpenForSubmission:!1,hash:"976f72013cd8e78d8f65bfb1f51f0146",slug:"beta-thalassemia",bookSignature:"Marwa Zakaria and Tamer Hassan",coverURL:"https://cdn.intechopen.com/books/images_new/8450.jpg",editedByType:"Edited by",editors:[{id:"187545",title:"Prof.",name:"Marwa",middleName:null,surname:"Zakaria",slug:"marwa-zakaria",fullName:"Marwa Zakaria"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8316",title:"Normal and Malignant B-Cell",subtitle:null,isOpenForSubmission:!1,hash:"a12608fa8d5fdb33c956f967974a4ef1",slug:"normal-and-malignant-b-cell",bookSignature:"Mourad Aribi",coverURL:"https://cdn.intechopen.com/books/images_new/8316.jpg",editedByType:"Edited by",editors:[{id:"40046",title:"Prof.",name:"Mourad",middleName:null,surname:"Aribi",slug:"mourad-aribi",fullName:"Mourad Aribi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7181",title:"Erythrocyte",subtitle:null,isOpenForSubmission:!1,hash:"267d215004c995048557176978208b15",slug:"erythrocyte",bookSignature:"Anil Tombak",coverURL:"https://cdn.intechopen.com/books/images_new/7181.jpg",editedByType:"Edited by",editors:[{id:"202814",title:"Associate Prof.",name:"Anil",middleName:null,surname:"Tombak",slug:"anil-tombak",fullName:"Anil Tombak"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7874",title:"Germ Line Mutations Associated Leukemia",subtitle:null,isOpenForSubmission:!1,hash:"cb407bb000c66ebe6172b9dc3d6f9fb4",slug:"germ-line-mutations-associated-leukemia",bookSignature:"Zhan He Wu",coverURL:"https://cdn.intechopen.com/books/images_new/7874.jpg",editedByType:"Edited by",editors:[{id:"226446",title:"Dr.",name:"Zhan He",middleName:null,surname:"Wu",slug:"zhan-he-wu",fullName:"Zhan He Wu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6905",title:"Blood Groups",subtitle:null,isOpenForSubmission:!1,hash:"545ab2a5b402edec6332c7d632eba398",slug:"blood-groups",bookSignature:"Anil Tombak",coverURL:"https://cdn.intechopen.com/books/images_new/6905.jpg",editedByType:"Edited by",editors:[{id:"202814",title:"Associate Prof.",name:"Anil",middleName:null,surname:"Tombak",slug:"anil-tombak",fullName:"Anil Tombak"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7125",title:"Iron Deficiency Anemia",subtitle:null,isOpenForSubmission:!1,hash:"25d82a6ea6c9d80b195bb40aad06be49",slug:"iron-deficiency-anemia",bookSignature:"Luis Rodrigo",coverURL:"https://cdn.intechopen.com/books/images_new/7125.jpg",editedByType:"Edited by",editors:[{id:"73208",title:"Prof.",name:"Luis",middleName:null,surname:"Rodrigo",slug:"luis-rodrigo",fullName:"Luis Rodrigo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7086",title:"Hemophilia",subtitle:"Recent Advances",isOpenForSubmission:!1,hash:"2c281207a3bce680f1a7efbb87ff791c",slug:"hemophilia-recent-advances",bookSignature:"Pankaj Abrol",coverURL:"https://cdn.intechopen.com/books/images_new/7086.jpg",editedByType:"Edited by",editors:[{id:"90782",title:"Dr.",name:"Pankaj",middleName:null,surname:"Abrol",slug:"pankaj-abrol",fullName:"Pankaj Abrol"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7138",title:"Recent Developments in Myelodysplastic Syndromes",subtitle:null,isOpenForSubmission:!1,hash:"f25aae5d062706d31025b1b21bb1d072",slug:"recent-developments-in-myelodysplastic-syndromes",bookSignature:"Ota Fuchs",coverURL:"https://cdn.intechopen.com/books/images_new/7138.jpg",editedByType:"Edited by",editors:[{id:"36468",title:"Dr.",name:"Ota",middleName:null,surname:"Fuchs",slug:"ota-fuchs",fullName:"Ota Fuchs"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6710",title:"Update on Multiple Myeloma",subtitle:null,isOpenForSubmission:!1,hash:"229a96a2de131b3ac67f9f41b91de8f8",slug:"update-on-multiple-myeloma",bookSignature:"Khalid Ahmed Al-Anazi",coverURL:"https://cdn.intechopen.com/books/images_new/6710.jpg",editedByType:"Edited by",editors:[{id:"37255",title:"Dr.",name:"Khalid Ahmed",middleName:null,surname:"Al-Anazi",slug:"khalid-ahmed-al-anazi",fullName:"Khalid Ahmed Al-Anazi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6634",title:"Homeostasis",subtitle:"An Integrated Vision",isOpenForSubmission:!1,hash:"3731dfa513781db054545963a4394938",slug:"homeostasis-an-integrated-vision",bookSignature:"Fernanda Lasakosvitsch and Sergio Dos Anjos Garnes",coverURL:"https://cdn.intechopen.com/books/images_new/6634.jpg",editedByType:"Edited by",editors:[{id:"117630",title:"Dr.",name:"Fernanda",middleName:null,surname:"Lasakosvitsch Castanho",slug:"fernanda-lasakosvitsch-castanho",fullName:"Fernanda Lasakosvitsch Castanho"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6969",title:"Lymphocytes",subtitle:null,isOpenForSubmission:!1,hash:"1aa8ac01c934ebdeedd5d7813036beef",slug:"lymphocytes",bookSignature:"Erman Salih Istifli and Hasan Basri İla",coverURL:"https://cdn.intechopen.com/books/images_new/6969.jpg",editedByType:"Edited by",editors:[{id:"179007",title:"Dr.",name:"Erman Salih",middleName:null,surname:"Istifli",slug:"erman-salih-istifli",fullName:"Erman Salih Istifli"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:35,mostCitedChapters:[{id:"39123",doi:"10.5772/50698",title:"Measurement Techniques for Red Blood Cell Deformability: Recent Advances",slug:"measurement-techniques-for-red-blood-cell-deformability-recent-advances",totalDownloads:6215,totalCrossrefCites:18,totalDimensionsCites:53,book:{slug:"blood-cell-an-overview-of-studies-in-hematology",title:"Blood Cell",fullTitle:"Blood Cell - An Overview of Studies in Hematology"},signatures:"Youngchan Kim, Kyoohyun Kim and YongKeun Park",authors:[{id:"143622",title:"Prof.",name:"YongKeun",middleName:null,surname:"Park",slug:"yongkeun-park",fullName:"YongKeun Park"},{id:"143623",title:"Mr.",name:"Kyoohyun",middleName:null,surname:"Kim",slug:"kyoohyun-kim",fullName:"Kyoohyun Kim"},{id:"143624",title:"Mr.",name:"Sangyeon",middleName:null,surname:"Cho",slug:"sangyeon-cho",fullName:"Sangyeon Cho"}]},{id:"31178",doi:"10.5772/38961",title:"Physiological Factors in the Interpretation of Equine Hematological Profile",slug:"haematological-profile-of-the-horse-phisiological-factors-influencing-equine-haematology",totalDownloads:10362,totalCrossrefCites:12,totalDimensionsCites:30,book:{slug:"hematology-science-and-practice",title:"Hematology",fullTitle:"Hematology - Science and Practice"},signatures:"K. Satué, A. Hernández and A. Muñoz",authors:[{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo"}]},{id:"46041",doi:"10.5772/57335",title:"An Insight into the Abnormal Fibrin Clots — Its Pathophysiological Roles",slug:"an-insight-into-the-abnormal-fibrin-clots-its-pathophysiological-roles",totalDownloads:3145,totalCrossrefCites:4,totalDimensionsCites:11,book:{slug:"fibrinolysis-and-thrombolysis",title:"Fibrinolysis and Thrombolysis",fullTitle:"Fibrinolysis and Thrombolysis"},signatures:"Payel Bhattacharjee and Debasish Bhattacharyya",authors:[{id:"88185",title:"Prof.",name:"Debasish",middleName:null,surname:"Bhattacharyya",slug:"debasish-bhattacharyya",fullName:"Debasish Bhattacharyya"},{id:"170045",title:"Ms.",name:"Payel",middleName:null,surname:"Bhattacharjee",slug:"payel-bhattacharjee",fullName:"Payel Bhattacharjee"}]}],mostDownloadedChaptersLast30Days:[{id:"66374",title:"Neurocognitive Dysfunctions in Iron Deficiency Patients",slug:"neurocognitive-dysfunctions-in-iron-deficiency-patients",totalDownloads:916,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"iron-deficiency-anemia",title:"Iron Deficiency Anemia",fullTitle:"Iron Deficiency Anemia"},signatures:"Elena Zhukovskaya, Alexander Karelin and Alexander Rumyantsev",authors:null},{id:"66394",title:"Diffuse Large B-Cell Lymphoma",slug:"diffuse-large-b-cell-lymphoma",totalDownloads:1133,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"normal-and-malignant-b-cell",title:"Normal and Malignant B-Cell",fullTitle:"Normal and Malignant B-Cell"},signatures:"Patrascu Ana Maria, Ionela Rotaru, Valeriu Surlin and Stefan Patrascu",authors:[{id:"158096",title:"Associate Prof.",name:"Valeriu",middleName:null,surname:"Surlin",slug:"valeriu-surlin",fullName:"Valeriu Surlin"},{id:"194539",title:"Dr.",name:"Stefan",middleName:null,surname:"Patrascu",slug:"stefan-patrascu",fullName:"Stefan Patrascu"},{id:"290810",title:"Dr.",name:"Ana Maria",middleName:null,surname:"Patrascu",slug:"ana-maria-patrascu",fullName:"Ana Maria Patrascu"},{id:"292959",title:"Dr.",name:"Ionela",middleName:null,surname:"Rotaru",slug:"ionela-rotaru",fullName:"Ionela Rotaru"}]},{id:"51831",title:"Disorders Mimicking Myelodysplastic Syndrome and Difficulties in its Diagnosis",slug:"disorders-mimicking-myelodysplastic-syndrome-and-difficulties-in-its-diagnosis",totalDownloads:3260,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"myelodysplastic-syndromes",title:"Myelodysplastic Syndromes",fullTitle:"Myelodysplastic Syndromes"},signatures:"Lale Olcay and Sevgi Yetgin",authors:[{id:"184156",title:"Prof.",name:"Lale",middleName:null,surname:"Olcay",slug:"lale-olcay",fullName:"Lale Olcay"}]},{id:"60302",title:"Understanding the Clotting Cascade, Regulators, and Clinical Modulators of Coagulation",slug:"understanding-the-clotting-cascade-regulators-and-clinical-modulators-of-coagulation",totalDownloads:1302,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"hematology-latest-research-and-clinical-advances",title:"Hematology",fullTitle:"Hematology - Latest Research and Clinical Advances"},signatures:"Vijaya S. Pilli",authors:[{id:"217533",title:"Dr.",name:"Vijaya",middleName:null,surname:"Pilli",slug:"vijaya-pilli",fullName:"Vijaya Pilli"}]},{id:"64989",title:"Platelets: From Formation to Function",slug:"platelets-from-formation-to-function",totalDownloads:1374,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"homeostasis-an-integrated-vision",title:"Homeostasis",fullTitle:"Homeostasis - An Integrated Vision"},signatures:"Laura Twomey, Robert G. Wallace, Philip M. Cummins, Bernard\nDegryse, Sinead Sheridan, Michael Harrison, Niall Moyna,\nGerardene Meade-Murphy, Nastassia Navasiolava, Marc-Antoine\nCustaud and Ronan P. Murphy",authors:[{id:"237585",title:"Dr.",name:"Ronan",middleName:"Padraic",surname:"Murphy",slug:"ronan-murphy",fullName:"Ronan Murphy"},{id:"260576",title:"Mr.",name:"Robert",middleName:null,surname:"Wallace",slug:"robert-wallace",fullName:"Robert Wallace"},{id:"260578",title:"Dr.",name:"Michael",middleName:null,surname:"Harrison",slug:"michael-harrison",fullName:"Michael Harrison"},{id:"260579",title:"Dr.",name:"Niall",middleName:"M",surname:"Moyna",slug:"niall-moyna",fullName:"Niall Moyna"},{id:"260580",title:"Dr.",name:"Gerardene",middleName:null,surname:"Meade-Murphy",slug:"gerardene-meade-murphy",fullName:"Gerardene Meade-Murphy"},{id:"260581",title:"Dr.",name:"Bernard",middleName:null,surname:"Degryse",slug:"bernard-degryse",fullName:"Bernard Degryse"},{id:"260582",title:"Dr.",name:"Sinead",middleName:null,surname:"Sheridan",slug:"sinead-sheridan",fullName:"Sinead Sheridan"},{id:"260583",title:"Prof.",name:"Marc-Antoine",middleName:null,surname:"Custaud",slug:"marc-antoine-custaud",fullName:"Marc-Antoine Custaud"},{id:"260584",title:"Dr.",name:"Nastassia",middleName:null,surname:"Navasiolava",slug:"nastassia-navasiolava",fullName:"Nastassia Navasiolava"},{id:"260585",title:"Dr.",name:"Laura",middleName:null,surname:"Twomey",slug:"laura-twomey",fullName:"Laura Twomey"}]},{id:"65673",title:"Red Blood Cells as Redox Modulators in Hemolytic Anemia",slug:"red-blood-cells-as-redox-modulators-in-hemolytic-anemia",totalDownloads:502,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"erythrocyte",title:"Erythrocyte",fullTitle:"Erythrocyte"},signatures:"Eitan Fibach and Mutaz Dana",authors:[{id:"83134",title:"Prof.",name:"Eitan",middleName:null,surname:"Fibach",slug:"eitan-fibach",fullName:"Eitan Fibach"},{id:"280928",title:"Dr.",name:"Mutaz",middleName:null,surname:"Dana",slug:"mutaz-dana",fullName:"Mutaz Dana"}]},{id:"67667",title:"Erythrocyte Morphology and Its Disorders",slug:"erythrocyte-morphology-and-its-disorders",totalDownloads:707,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"erythrocyte",title:"Erythrocyte",fullTitle:"Erythrocyte"},signatures:"Ademola Samson Adewoyin, Oluwafemi Adeyemi, Nosimot Omolola Davies and Ann Abiola Ogbenna",authors:[{id:"281974",title:"Dr.",name:"Ademola Samson",middleName:null,surname:"Adewoyin",slug:"ademola-samson-adewoyin",fullName:"Ademola Samson Adewoyin"},{id:"304907",title:"Dr.",name:"Oluwafemi",middleName:null,surname:"Adeyemi",slug:"oluwafemi-adeyemi",fullName:"Oluwafemi Adeyemi"},{id:"304908",title:"Dr.",name:"Nosimot Omolola",middleName:null,surname:"Davies",slug:"nosimot-omolola-davies",fullName:"Nosimot Omolola Davies"},{id:"304909",title:"Dr.",name:"Ann",middleName:null,surname:"Abiola Ogbenna",slug:"ann-abiola-ogbenna",fullName:"Ann Abiola Ogbenna"}]},{id:"39118",title:"Tigers Blood: Haematological and Biochemical Studies",slug:"tigers-blood-haematological-and-biochemical-studies",totalDownloads:4685,totalCrossrefCites:3,totalDimensionsCites:4,book:{slug:"blood-cell-an-overview-of-studies-in-hematology",title:"Blood Cell",fullTitle:"Blood Cell - An Overview of Studies in Hematology"},signatures:"A.B. Shrivastav and K.P. Singh",authors:[{id:"142314",title:"Dr.",name:"K.P.",middleName:null,surname:"Singh",slug:"k.p.-singh",fullName:"K.P. Singh"}]},{id:"39114",title:"Homocysteine in Red Blood Cells Metabolism - Pharmacological Approaches",slug:"homocysteine-in-red-blood-cells-metabolism-pharmacological-approaches",totalDownloads:2949,totalCrossrefCites:1,totalDimensionsCites:3,book:{slug:"blood-cell-an-overview-of-studies-in-hematology",title:"Blood Cell",fullTitle:"Blood Cell - An Overview of Studies in Hematology"},signatures:"Filip Cristiana, Zamosteanu Nina and Albu Elena",authors:[{id:"143599",title:"Dr.",name:"Filip",middleName:null,surname:"Cristiana",slug:"filip-cristiana",fullName:"Filip Cristiana"},{id:"143791",title:"Prof.",name:"Albu",middleName:null,surname:"Elena",slug:"albu-elena",fullName:"Albu Elena"},{id:"143792",title:"Dr.",name:"Zamosteanu",middleName:null,surname:"Nina",slug:"zamosteanu-nina",fullName:"Zamosteanu Nina"}]},{id:"64548",title:"Infections in Patients with Multiple Myeloma in the Era of Novel Agents and Stem Cell Therapies",slug:"infections-in-patients-with-multiple-myeloma-in-the-era-of-novel-agents-and-stem-cell-therapies",totalDownloads:830,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"update-on-multiple-myeloma",title:"Update on Multiple Myeloma",fullTitle:"Update on Multiple Myeloma"},signatures:"Asma M. Al-Jasser and Khalid Ahmed Al-Anazi",authors:[{id:"37255",title:"Dr.",name:"Khalid Ahmed",middleName:null,surname:"Al-Anazi",slug:"khalid-ahmed-al-anazi",fullName:"Khalid Ahmed Al-Anazi"}]}],onlineFirstChaptersFilter:{topicSlug:"hematology",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:"book.detail",path:"/books/wireless-ad-hoc-networks",hash:"",query:{},params:{book:"wireless-ad-hoc-networks"},fullPath:"/books/wireless-ad-hoc-networks",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)}()