Treatment options and outcomes for older AML patients.
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6645",leadTitle:null,fullTitle:"Seabirds",title:"Seabirds",subtitle:null,reviewType:"peer-reviewed",abstract:"Changes in seabird populations are good indicators of large-scale and long-term change in marine ecosystems, and are important because of their global impacts on the marine environment. This book has six chapters that present a wide variety of global seabird-related issues, from India to Svalbard, Norway. It also gives a comprehensive history of the use and chemical content of guano and certification schemes in fisheries for seabird conservation in Argentina. With the knowledge available in this book we should know how best to protect seabirds, which need all our support to survive in changing environments and climates. We can all do our best to recycle plastic waste to reduce global plastic pollution, which has affected seabirds' physical state, food sources, and nesting areas.",isbn:"978-1-78923-657-6",printIsbn:"978-1-78923-656-9",pdfIsbn:"978-1-83881-614-8",doi:"10.5772/intechopen.71804",price:119,priceEur:129,priceUsd:155,slug:"seabirds",numberOfPages:110,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"6ce1372af411b6ada3b53e881f7b85fc",bookSignature:"Heimo Mikkola",publishedDate:"September 5th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6645.jpg",numberOfDownloads:6906,numberOfWosCitations:11,numberOfCrossrefCitations:7,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:18,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:36,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 7th 2018",dateEndSecondStepPublish:"February 28th 2018",dateEndThirdStepPublish:"April 29th 2018",dateEndFourthStepPublish:"July 18th 2018",dateEndFifthStepPublish:"September 16th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"144330",title:"Dr.",name:"Heimo",middleName:"Juhani",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola",profilePictureURL:"https://mts.intechopen.com/storage/users/144330/images/system/144330.png",biography:"Heimo Mikkola obtained a Ph.D. from the University of Kuopio (now Eastern Finland University), where he also served as an adjunct professor in Applied Zoology. From 1974 to 2007, he worked with the Food and Agriculture Organization (FAO) of the United Nations, first in Colombia and then in Africa, where he served as the organization’s resident representative. After retiring from the FAO in Uruguay, Dr. Mikkola has worked as a part-time professor at three Kazakh universities and one Kyrgyz university. His work has taken him to 137 countries, and he has written almost 700 reports and scientific papers and books, mainly on owls and other birds, fish, insects, and food. He has studied bats for many years on almost all continents as they often share night-time activity and biotopes with owls. This is the second book on bats he has edited for IntechOpen.",institutionString:"University of Eastern Finland",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"10",totalChapterViews:"0",totalEditedBooks:"9",institution:{name:"University of Eastern Finland",institutionURL:null,country:{name:"Finland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"659",title:"Aquatic Ecosystem",slug:"earth-and-planetary-sciences-marine-biology-aquatic-ecosystem"}],chapters:[{id:"61836",title:"Introductory Chapter: Seabird Occurrence in the Open Arctic Sea during the Breeding Season",doi:"10.5772/intechopen.78533",slug:"introductory-chapter-seabird-occurrence-in-the-open-arctic-sea-during-the-breeding-season",totalDownloads:862,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Heimo Mikkola",downloadPdfUrl:"/chapter/pdf-download/61836",previewPdfUrl:"/chapter/pdf-preview/61836",authors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],corrections:null},{id:"61563",title:"Feather Structure and Behavioral Patterns in Seabirds",doi:"10.5772/intechopen.77729",slug:"feather-structure-and-behavioral-patterns-in-seabirds",totalDownloads:966,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The structural details of the flight and contour feathers of seabirds closely match the requirements of their habitats and feeding habits. They serve a variety of functions ranging from intraspecific signaling to such physical qualities as thermal insulation, water repellency and resistance to impact. It comes as no surprise, therefore, that they are composed of an array of elements that confer these qualities to the optimal benefit of their avian bearer. In this chapter, the physical bases for these functions are provided in both mathematical and evolutionary terms. Some functions excel at the expense of others, and many species have evolved an optimal balance between functions in terms of both feather microstructure and behavioral patterns that suit their specific habitat and feeding habits. The effects of mechanical forces on feathers are presented in terms of the impact of diving, plunging and alighting, and the structural properties in seabird feathers identifiable as adaptations to these forces. Finally, the way oiling affects the water repellency and resistance of feathers is discussed. It is concluded that the flight and contour feathers exhibit morphological and mechanical features that are advantageous for specific habitats and feeding techniques.",signatures:"Arie M. Rijke",downloadPdfUrl:"/chapter/pdf-download/61563",previewPdfUrl:"/chapter/pdf-preview/61563",authors:[{id:"245166",title:"Prof.",name:"Arie M.",surname:"Rijke",slug:"arie-m.-rijke",fullName:"Arie M. Rijke"}],corrections:null},{id:"60398",title:"Certification Schemes in Argentine Fisheries: Opportunities and Challenges for Seabird Conservation",doi:"10.5772/intechopen.74784",slug:"certification-schemes-in-argentine-fisheries-opportunities-and-challenges-for-seabird-conservation",totalDownloads:1003,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In Argentina, one major factor playing a significant role in the implementation of better fishing practices is related to the advent of the Marine Stewardship Council (MSC) certification schemes in marine fisheries, given that one of its component addresses the impact of fishing operations on the ecosystem (e.g. effects on the environment, related species, bycatch). In recent years, several fisheries in Argentina—ranging from coastal ice trawlers targeting the Argentine anchovy Engraulis anchoita to freezer trawlers targeting the Patagonian scallop Zygochlamys patagonica and the Patagonian grenadier or Hoki Macruronus magellanicus have been certified under the MSC scheme. Although these processes are not driven by the Government certainly creates opportunities to develop better fishing practices including in the agendas of fishermen not only target species but also other management issues affecting the marine environment. In this chapter, we will review the current status of the certification schemes implemented in the latter referred fisheries regarding seabird conservation discussing challenges and opportunities from the seabird perspective.",signatures:"Juan Pablo Seco Pon, Jesica A. Paz, Rocío Mariano-Jelicich, Germán\nGarcía, Sofía Copello, María P. Berón, Gabriel Blanco, José Luis\nFlaminio and Marco Favero",downloadPdfUrl:"/chapter/pdf-download/60398",previewPdfUrl:"/chapter/pdf-preview/60398",authors:[{id:"234902",title:"Ph.D.",name:"Juan Pablo",surname:"Seco Pon",slug:"juan-pablo-seco-pon",fullName:"Juan Pablo Seco Pon"},{id:"234913",title:"Dr.",name:"Sofía",surname:"Copello",slug:"sofia-copello",fullName:"Sofía Copello"},{id:"234916",title:"Dr.",name:"Germán",surname:"García",slug:"german-garcia",fullName:"Germán García"},{id:"234917",title:"BSc.",name:"Jesica",surname:"Paz",slug:"jesica-paz",fullName:"Jesica Paz"},{id:"234918",title:"Dr.",name:"Rocío",surname:"Mariano-Jelicich",slug:"rocio-mariano-jelicich",fullName:"Rocío Mariano-Jelicich"},{id:"234920",title:"B.Sc.",name:"Gabriel",surname:"Blanco",slug:"gabriel-blanco",fullName:"Gabriel Blanco"},{id:"234922",title:"Dr.",name:"Marco",surname:"Favero",slug:"marco-favero",fullName:"Marco Favero"},{id:"241979",title:"Dr.",name:"José Luis",surname:"Flaminio",slug:"jose-luis-flaminio",fullName:"José Luis Flaminio"},{id:"241980",title:"Dr.",name:"María Paula",surname:"Berón",slug:"maria-paula-beron",fullName:"María Paula Berón"}],corrections:null},{id:"59950",title:"Seabirds as Bioindicators of Marine Ecosystems",doi:"10.5772/intechopen.75458",slug:"seabirds-as-bioindicators-of-marine-ecosystems",totalDownloads:1447,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Seabirds are those waterbirds that directly or indirectly depend on the marine environment over the waters, i.e., they foraged at sea either near shore or offshore and inhabit in coastal areas, islands, estuaries, wetlands, and ocean islands. They are mostly aerial waterbirds sailing above sea spending much of their time (weeks, months, and even years) in marine environments or floating on the water surface or diving in deep sea in search of food. Seabirds encompass of 65 genera, 222 marine, and 72 partially marine bird species. Seabirds have been used as good indicators (i.e., bioindicators) of marine ecosystems due to cause-effect association with different microclimate and habitats. They exploit broad scale of habitat, quickly respond to environmental changes, they can be detected easily (i.e., they showed their presence through vocalization), easy to identify, can be surveyed efficiently over large spatial scale, e.g., presence, abundance, and influenced by surrounding habitats as compared to other animals. Employing seabird as bioindicators is a cost-effective and informative tool (well defined matrix) to determine the effects of disturbances, contamination, i.e., effects of pollutants, organic substances, and oil-spills of the marine environment. Seabirds are top predators in the marine food chain and key component of the food web. Seabirds may indicate the status of habitat, reduction in food occurrence and abundance, rate of the predation, an effect of weather (climate change), and threats. The other reason could be that, seabirds often closely associate with inter-site more distinctly than other animals and may breed in the same site each year, easy to catch while incubating and during rearing chicks. Hence, it is crucially important to use seabirds as bioindicators within the context of ecological and spatial parameters to determine the effects of disturbances in the marine environment and for effective conservation and better management of seabirds in the future.",signatures:"Muhammad Nawaz Rajpar, Ibrahim Ozdemir, Mohamed Zakaria,\nShazia Sheryar and Abdu Rab",downloadPdfUrl:"/chapter/pdf-download/59950",previewPdfUrl:"/chapter/pdf-preview/59950",authors:[{id:"183095",title:"Dr.",name:"Muhammad Nawaz",surname:"Rajpar",slug:"muhammad-nawaz-rajpar",fullName:"Muhammad Nawaz Rajpar"},{id:"186144",title:"Prof.",name:"Mohamed",surname:"Zakaria",slug:"mohamed-zakaria",fullName:"Mohamed Zakaria"},{id:"186573",title:"Prof.",name:"Ibrahim",surname:"Ozdemir",slug:"ibrahim-ozdemir",fullName:"Ibrahim Ozdemir"},{id:"222148",title:"Mr.",name:"Abdul",surname:"Rab",slug:"abdul-rab",fullName:"Abdul Rab"},{id:"235691",title:"Ms.",name:"Shazia",surname:"Sheryar",slug:"shazia-sheryar",fullName:"Shazia Sheryar"}],corrections:null},{id:"59696",title:"Between the Land and Sea: How Yellow-Legged Gulls Have Changed Their Dependence on Marine Food in Relation to Landfill Management",doi:"10.5772/intechopen.74821",slug:"between-the-land-and-sea-how-yellow-legged-gulls-have-changed-their-dependence-on-marine-food-in-rel",totalDownloads:919,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The Basque region (Spain) is closing all its open-air landfills, which hence provides an excellent chance to account for the effects on the trophic and spatial ecology of the local yellow-legged gulls Larus michahellis, which highly depend on refuse tips to forage. The closure of several landfills across the region was mainly compensated by a higher intake of terrestrial food (mainly earthworms), though only in summer. The exploitation of terrestrial prey was marginal in winter, and seasonal trophic differences emerged, unlike findings when landfills were still open. With only one landfill now open in theory, movement and territory use analyses showed that two landfills were frequently visited. Positions at two of the target foraging habitats (landfills, pastures) summed ca. 10% of all stationary positions suggesting that, at least in these habitats, gulls seemed to invest a relatively small amount of time, which might support the idea that they were able to obtain food in a fast way and, probably, from resources that they know well and have a predictable temporal distribution.",signatures:"Juan Arizaga, Nere Zorrozua and Alexandra Egunez",downloadPdfUrl:"/chapter/pdf-download/59696",previewPdfUrl:"/chapter/pdf-preview/59696",authors:[{id:"233327",title:"Dr.",name:"Juan",surname:"Arizaga",slug:"juan-arizaga",fullName:"Juan Arizaga"}],corrections:null},{id:"62618",title:"Guano: The White Gold of the Seabirds",doi:"10.5772/intechopen.79501",slug:"guano-the-white-gold-of-the-seabirds",totalDownloads:1709,totalCrossrefCites:3,totalDimensionsCites:10,hasAltmetrics:1,abstract:"The term “Guano” applies to natural mineral deposits consisting of excrements, eggshells and carcasses of dead seabirds found in almost rainless, hot-dry climatic regions and corresponding fertilizers. Guanos are classified according to age, genesis, geographical origin and chemical composition. Main types are nitrogen- and phosphate Guanos. Phosphate Guanos require a calcareous subsoil for the development, while nitrogen Guanos are formed only under the special climatic conditions of the subtropical-edge tropical high pressure belt with coastal deserts. The most significant nitrogen Guano is the Peru-Guano, which has been used over 2000 years as agricultural fertilizer in Peru. In Europe the application of Guano as fertilizer emerged in the 1840 as “Guano boom” and lasted until the early twentieth century when Guano was replaced by industrial manufactured fertilizers. Only a small quantity is still exported to Europe as additive to organic/mineral fertilizers, more for image boosting than for effect.",signatures:"Ewald Schnug, Frank Jacobs and Kirsten Stöven",downloadPdfUrl:"/chapter/pdf-download/62618",previewPdfUrl:"/chapter/pdf-preview/62618",authors:[{id:"248076",title:"Dr.",name:"Kirsten",surname:"Stoeven",slug:"kirsten-stoeven",fullName:"Kirsten Stoeven"},{id:"248077",title:"Prof.",name:"Ewald",surname:"Schnug",slug:"ewald-schnug",fullName:"Ewald Schnug"},{id:"248087",title:"MSc.",name:"Frank",surname:"Jacobs",slug:"frank-jacobs",fullName:"Frank Jacobs"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5210",title:"Fisheries and Aquaculture in the Modern World",subtitle:null,isOpenForSubmission:!1,hash:"1c78e2a5e686279a30ed3fb640769dad",slug:"fisheries-and-aquaculture-in-the-modern-world",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/5210.jpg",editedByType:"Edited by",editors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5705",title:"Future Foods",subtitle:null,isOpenForSubmission:!1,hash:"3e0407db8b07ae39128d6454b67bc690",slug:"future-foods",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/5705.jpg",editedByType:"Edited by",editors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6478",title:"Bats",subtitle:null,isOpenForSubmission:!1,hash:"90a4ab5d70985630b12f49cb23939c02",slug:"bats",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/6478.jpg",editedByType:"Edited by",editors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8950",title:"Birds",subtitle:"Challenges and Opportunities for Business, Conservation and Research",isOpenForSubmission:!1,hash:"404a05af45e47e43871f4a0b1bedc6fd",slug:"birds-challenges-and-opportunities-for-business-conservation-and-research",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/8950.jpg",editedByType:"Edited by",editors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10248",title:"Ecosystem and Biodiversity of Amazonia",subtitle:null,isOpenForSubmission:!1,hash:"1218c819f575bd951d5de0e85f3ea006",slug:"ecosystem-and-biodiversity-of-amazonia",bookSignature:"Heimo Juhani Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/10248.jpg",editedByType:"Edited by",editors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8005",title:"Edible Insects",subtitle:null,isOpenForSubmission:!1,hash:"43f8a1ebb7293cf0d434182444e42507",slug:"edible-insects",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/8005.jpg",editedByType:"Edited by",editors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8793",title:"Owls",subtitle:null,isOpenForSubmission:!1,hash:"8df7a192b3300e2640a0e1c530f4e259",slug:"owls",bookSignature:"Heimo Mikkola",coverURL:"https://cdn.intechopen.com/books/images_new/8793.jpg",editedByType:"Edited by",editors:[{id:"144330",title:"Dr.",name:"Heimo",surname:"Mikkola",slug:"heimo-mikkola",fullName:"Heimo Mikkola"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"304",title:"Sediment Transport in Aquatic Environments",subtitle:null,isOpenForSubmission:!1,hash:"0eb11af1d03ad494253c41e1d3c998e9",slug:"sediment-transport-in-aquatic-environments",bookSignature:"Andrew J. 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\r\n\r\n\tThis book aims to have scientific chapters concerned with all aspects of nut science and particularly the biological, agricultural engineering, social and ecological knowledge application for nut crops management in the tropical and subtropical regions.
\r\n\r\n\tThis book aims to encourage the researchers to demonstrate how the field experiments contribute to the understanding of the biophysical processes related to crop development, growth, and the formation and realization of yield.
\r\n\r\n\tThe book “Nut Crops - New Insights” will provide a platform for all knowledge seekers to get the best of research that has been done around the globe relevant to plant nutrition, nut production, crop cultivation, etc. The readership of the book will include researchers and students of crop science and individuals with similar academic levels.
",isbn:"978-1-80356-633-7",printIsbn:"978-1-80356-632-0",pdfIsbn:"978-1-80356-634-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"1843d68aceace005d335966147f9b751",bookSignature:"Dr. Muhammad Akram",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11795.jpg",keywords:"Nuts, Edible Crops, Growth Regulators, Cultivar, Crop Cultivation, Micropropagation, Nut Breeding, Weed Control, Insecticides, Plant Pathogens, Nutritional Improvement, Nut Nutrition",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 17th 2022",dateEndSecondStepPublish:"June 3rd 2022",dateEndThirdStepPublish:"August 2nd 2022",dateEndFourthStepPublish:"October 21st 2022",dateEndFifthStepPublish:"December 20th 2022",remainingDaysToSecondStep:"11 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Chairperson and Associate Professor in the Department of Eastern Medicine, Government College University Faisalabad, Pakistan and ex-chairman in the Department of Eastern Medicine and Surgery, University of Poonch, Pakistan. Dr. Muhammad Akram serves as an editor and invited reviewer of several national and international journals and he has numerous publications and presentations to his credit.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"215436",title:"Dr.",name:"Muhammad",middleName:null,surname:"Akram",slug:"muhammad-akram",fullName:"Muhammad Akram",profilePictureURL:"https://mts.intechopen.com/storage/users/215436/images/system/215436.jpg",biography:"Dr. Muhammad Akram is an Associate Professor in the Department of Eastern Medicine, Government College University Faisalabad, Pakistan. He received his Ph.D. from Hamdard University Karachi-Pakistan in 2013. Dr. Akram was a chairman in the Department of Eastern Medicine and Surgery, University of Poonch, Rawalakot Azad Kashmir from 2015 to 2017. He received many honors and awards during his career. He serves as an editor and invited reviewer of several national and international journals. He has numerous publications and presentations to his credit, and he is an active member of several professional societies. Dr. Akram’s research interests include hyperuricemia, xanthine oxidase inhibition by some selected medicinal plants, enzyme inhibition, Indusyunic medicine, phytochemistry, poisonous plants, bioactivity, and phytopharmaceutical evaluation of herbal drugs and their natural products, biochemistry, and bioinformatics.",institutionString:"Government College University, Faisalabad",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited 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It is predominantly a disease of older adults, with a median age at diagnosis of 68 years [1]. Indeed, 75% of the AML patients are older than 60 years (Figure 1). Besides a higher incidence of AML at older age, AML in older adults differs biologically and clinically from AML in younger adults [2]. AML in older adults is characterised by a markedly reduced long-term survival resulting from the combination of poor chemotherapeutic tolerance and inherent chemotherapy resistance compared with younger AML patients [3]. AML in older adults has a lower frequency of favourable core-binding chromosomal abnormalities and a higher incidence of complex aberrant karyotypes [4, 5]. These differences in clinical and cellular behaviour of AML in older adults suggest activation of different target genes by oncogenic events in aged stem or progenitor cells compared with younger stem or progenitor cells. Indeed a distinct gene-expression profile noted for older compared to younger adults with AML supports a molecular basis for disparities in outcome related to age [2, 5, 6]. In addition, more frequent comorbid conditions, the decreased immune competence of older patients and psychosocial factors influence treatment outcome of AML in older adults. The effects of age on both disease- and patient-related factors result in a lower rate of disease remission, a higher incidence of early death during chemotherapy, and a reduced probability of long-term survival [2, 3]. In light of this, population based studies report a treatment percentage of only 30% in AML patients aged 65 and older [7, 8]. Indeed, regardless of treatment, outcomes for older AML patients are unsatisfactory, with median overall survival (OS) of 5–10 months and 5-year survival of about 10% [9, 10, 11]. In contrast with the progress made for younger adults with AML, the treatment in older adults has not improved significantly in recent decades, despite numerous efforts to find effective and tolerable treatments [12].
AML incidence rates by age at diagnosis (2013–2017).
The optimal treatment of older adults with AML in daily clinical practice remains challenging, and is dependent on patient characteristics (age, performance, comorbidities), disease characteristics (cytogenetic and molecular abnormalities, white blood cell count) and the preference of the patient [3]. Regular treatment options include: best supportive care (BSC), low-dose chemotherapy (e.g. low dose cytarabine (LDAC)), hypomethylating agents (HMA), and intensive chemotherapy (IC) (Table 1).
Response: CR/CRi (%) | Median OS (months) | 2-year OS (%) | 5-year OS (%) | |
---|---|---|---|---|
41–70 36–78 | 10–20 7–34 | 12–42 53 | 10–30 36 | |
18 | 4 | — | — | |
15–47 | 8–13 (25) | 20–50 | Not curative, unless consolidated with HCT | |
+ HMA [19] + LDAC [60] + IC [65] + LDAC [66] | — —66 48 30–40 78 —40 17 53–67 | — —14.7 8.4 11–13 —14.7 8.8 15 | — — — — —45.6 | — |
Treatment options and outcomes for older AML patients.
Population data from the Swedish Acute Leukaemia Registry suggest the majority of older patients should be considered candidate for antileukemic therapy [13]. However, only few prospective randomised studies in older AML patients are available to guide treatment decisions. A pivotal clinical trial, although with a limited number of patients (n = 60), showed that standard IC decreases early death rates and improves long-term survival compared with BSC [14]. Also LDAC and gemtuzumab ozogamicin (GO) have been reported to result in superior survival compared with BSC; although neither had an effect in patients with adverse cytogenetics [15, 16].
In addition to IC and LDAC, the armamentarium for the treatment of AML has been expanded in recent years with two cytosine analogues with DNA hypomethylating properties: azacitidine and decitabine. The hypomethylating agents (HMAs) azacitidine and decitabine have relatively mild side effects and are particularly feasible for the treatment of AML in older patients and patients with comorbidities. Importantly, both azacitidine and decitabine have proven efficacy in patients with adverse cytogenetic abnormalities. Although not in their primary analyses, recent phase III trials have shown the superiority of azacitidine and decitabine treatment compared with conventional care for older AML patients [17, 18].
New combinations of HMAs with targeted drugs are being explored. Recently, the results of a phase 3 study of azacitidine in combination with venetoclax versus azacitidine alone in treatment-naïve adults with AML, who were ineligible for standard induction therapy, have been reported (VIALE-A trial; NCT02993523). This study confirmed the additive value of venetoclax to azacitidine treatment by an increase in remission rate from 28–66% and an increase in median OS from 9.6 months to 14.7 months [19]. The high remission rate which was achieved by adding venetoclax to azacitidine treatment is striking. Studies are ongoing to explore the added value of IDH1 or IDH2 inhibitors (ivosidenib or enasidenib) in combination with azacitidine and azacitidine plus venetoclax, for those older AML patients with mutated
Optimal treatment selection for older patients also requires consideration of treatment tolerance and life expectancy, derived from the evaluation of comorbidities, physical function and cognition [2]. Charlson comorbidity index >1 and haematopoietic cell transplantation comorbidity index (HCT-CI) >2 have been reported to be associated with lower remission rates, increased early mortality and decreased survival in patients treated with IC [20, 21, 22]. In a study on 177 patients aged ≥65 years who received IC the early death rates were 3% if the HCT-CI score was 0, 11% if the HCT-CI score was 1 to 2, and 29% if the HCT-CI score was ≥3 [20]. In addition, performance status, scored according to ECOG or WHO guidelines, has shown to be associated with survival in several studies [10, 23, 24].
To adequately assess fitness in older patients, beyond performance status and comorbidities, geriatric assessment (GA) is attracting more attention. GA is an approach to the evaluation of multiple patient characteristics (i.e. physical function, comorbid disease(s), cognitive function, psychological state, social support, polypharmacy, nutritional status) to help characterise individual patient complexity and discriminate among fit, vulnerable and frail patients. GA in older AML patients has been associated with treatment outcomes. In a single-institution prospective study conducted with AML patients ≥60 years of age treated with IC, geriatric assessment performed at diagnosis was associated with survival. In this study (n = 74, median age 68 years), impaired physical performance (measured as short physical performance battery (SPPB) score < 9) and impaired cognition (measured as modified mini-mental state (3MS) exam score < 77) were independently associated with OS, after accounting for other disease and patient characteristics [25]. In a study of 107 non-intensively treated AML patients, the scores for independence in activities of daily living and the Karnofsky score for performance status were associated with survival in multivariate analysis [21]. Although randomised data of comprehensive assessment of older AML patients are lacking, the above mentioned studies support the use of pre-treatment performance and comorbidity assessment in the setting of AML therapy.
Various studies have been undertaken with the aim to create prediction models for treatment effectiveness and to provide support for an educated treatment choice in the setting of AML. These algorithms include patient-specific factors (e.g. performance, comorbidity, body temperature, age) and disease-specific factors (e.g. cytogenetics, white blood cell counts, blast counts, primary or secondary leukaemia, haemoglobin level, platelet count, fibrinogen level, serum concentration of lactate dehydrogenase (LDH)) [23, 24, 26, 27]. However, most prediction models have not been successfully validated in independent cohorts of older patients. In addition, the data used to create most of these algorithms come from a patient population selected to receive intensive chemotherapy and therefore likely do not reflect the real world of older patients with AML. Although prediction models might be useful in identifying patients who are ‘fit’ for intensive chemotherapy, this does not automatically imply for AML patients with specific disease characteristics (or combinations) associated with poor outcome. This includes the high-risk AML subtypes with mutant
The combination of anthracycline and cytarabine (‘3 + 7’) has been the standard of care for patients with AML for the last four decades [28]. However, the use of this regimen in older patients with AML does not yield similar results to those reported for younger patients, even in carefully selected patients. Although 50–60% of patients will attain a complete remission (CR), this does not translate into a similar survival benefit as for younger patients, with a 2-year survival of only 15–20% [3, 29]. To improve the outcome for older AML patients receiving intensive chemotherapy (IC) many studies have evaluated modifications of the traditional ‘3 + 7’ combination. Strategies have included dose attenuation [9, 30], addition of gemtuzumab ozogamicin (GO) [31, 32], addition of midostaurin [33], addition of lenalidomide [34], and other attempts (e.g. growth factors, modulation of multidrug resistance).
The HOVON43 study assessed the effect of an escalated daunorubicin dose (90 mg/m2 vs. 45 mg/m2) in older AML patients (> 60 years) receiving conventional ‘3 + 7’ chemotherapy [9]. Median age was 67 years and 24% of patients had an unfavourable or very unfavourable cytogenetic risk. Although the CR rate was higher in the escalated-treatment group (64% vs. 54% [P = 0.002]), this did not translate into a survival benefit (2-year OS 31% vs. 26% [P = 0.16]). However, an unplanned post-hoc analysis showed that patients in the escalated-treatment group who were 60 to 65 years of age had higher CR rates and increased survival compared to patients aged 60 to 65 years in the conventional dose group (CR rates 73% vs. 51% and 2-year OS 38% vs. 23%, respectively). These data suggest the survival benefit of an escalated dose of daunorubicin was limited to the younger part of older patients. The MRC-AML-14 study randomised patients four times to a higher (50 mg/m2) or lower (35 mg/m2) dose of daunorubin, a higher (400 mg/m2) or lower (200 mg/m2) dose of cytarabine, allocation to receive the multidrug resistance modulator PSC-833 or not, and to receive three or four courses of treatment [30]. The CR rate was 54% and 5-year OS 12% for all patients, and no benefits were observed in either dose escalation groups, or from a fourth course of treatment.
Several studies investigated the addition of GO to standard chemotherapy to improve outcome in older AML patients. The MRC-AML-16-I study (addition of 3 mg/m2 GO on day 1 of course 1) found 3-year relapse incidence and survival was significantly better in the GO arm (relapse 68% vs. 76%; survival 25% vs. 20%), although there was no difference in CR rate between both arms [31]. There was no difference in 30- or 60-day mortality and no major increase in toxicity with GO. The French ALFA-0701 trial investigated addition of fractionated doses of GO (3 mg/m2 on day 1, 4, and 7) to standard chemotherapy and found similar results in patients aged 50–70 years. The CR rate did not differ between both arms (81% in GO-arm vs. 75% in no GO-arm), but survival was increased in the GO-arm (median 34 vs. 19 months; 2-year OS 53.2% vs. 41.9%) [35]. However, in the EORTC-GIMEMA-AML17 trial, randomising patients to a course of GO (6 mg/m2 on day 1 and 15) followed by IC or IC alone, a trend for inferior survival in the GO-arm was observed (median OS 7.1 vs. 10 months) [32]. Patients aged ≥70 years did significantly worse with GO due to the combined effect of increased induction mortality and poorer OS among those not achieving CR. This study incorporated a higher dose of GO (6 mg/m2 vs. 3 mg/m2). GO, especially in higher doses, has been associated with increased toxicity and after initial FDA approval in 2000 was voluntarily withdrawn in 2010 after safety concerns. Since then fractionated doses have been proved safe and efficacious in a large meta-analysis of five randomised controlled trials, leading to re-approval in 2017 [36].
There is ongoing discussion whether older AML patients benefit from treatment with intensive chemotherapy. Retrospective analysis of the outcomes 446 older AML patients (≥70 years) treated with intensive chemotherapy between 1990 and 2008 showed that despite a reasonable CR rate of 45%, the median OS was only 4.6 months and 1-year survival 28% [37]. The surprisingly low median OS was due to high 4-week and 8-week mortality rates of 26% and 36%, and the authors concluded that intensive chemotherapy may not be beneficial to most older patients with AML, although some subgroups (e.g. CBF AML and good risk status) might benefit. In response to this, a Swedish group published updated outcomes of 998 unselected older AML patients, of who 55% received intensive chemotherapy between 1997 and 2006 and concluded that older patients do benefit from intensive treatment with a median OS in
For patients not eligible for intensive chemotherapy treatment a choice can be made between best supportive care (BSC), low dose chemotherapy (LDAC) or hypomethylating agents (HMAs). Several studies have shown the efficacy of the HMAs azacitidine and decitabine. In addition, HMAs are well-tolerated and have low extra-medullary toxicity. Therefore HMAs are very suitable for the treatment of older patients with AML.
Azacitidine was first studied in the context of high-risk myelodysplastic syndromes (MDS). A phase III trial conducted in intermediate-2 and high-risk MDS patients included a subset of patients with 20–30% blasts, who were reclassified to AML according to redefined WHO criteria [38, 39]. The relative efficacy and safety of azacitidine versus conventional care regimens (CCR; comprising prespecified allocation to BSC, LDAC, or IC) was thus compared in this subgroup of patients (n = 113) and showed an increased median OS (24.5 vs. 16.0 months, P = 0.005) and increased 2-year survival (50% vs. 16%, P = 0.001) for azacitidine-treated patients compared with CCR patients [40]. In addition, a phase III study on the efficacy of azacitidine versus CCR (standard IC, LDAC or BSC) in newly diagnosed AML patients with >30% blasts was conducted [17]. The median OS was longer in the azacitidine group compared to the CCR group (10.4 vs. 6.5 months), although in multivariate analysis significance was lost (HR 0.85 [95% CI 0.69–1.03], P = 0.101). However, in a pre-planned sensitivity analysis censoring for subsequent AML therapy, the median OS was 12.1 months versus 6.9 months in the azacitidine-arm and CCR-arm respectively, with a stratified HR 0.76 (95% CI 0.60–0.96, P = 0.019). Azacitidine was well tolerated as more than half of the patients received six or more treatment cycles. The difference in median OS between the two reported studies (24.5 months vs. 12.1 months) could be explained by the lower blast count in the first study and thereby selection of more indolent disease. Unfortunately both studies were not powered to detect direct differences between azacitidine treatment and intensive chemotherapy.
Decitabine is another hypomethylating agent registered for treatment of AML. Two decitabine schedules are currently in use in clinical practice: the 5-day schedule and the 10-day schedule. A randomised phase III trial compared the efficacy and safety of 5-day decitabine (20 mg/m2) (n = 242) with treatment choice of BSC (n = 28) or LDAC (n = 215) in older patients(≥ 65 years) with newly diagnosed AML and poor- or intermediate-risk cytogenetics [18]. The CR rate in the decitabine group was 15.7%. Although the planned primary analysis after 396 deaths did not show a significant improvement of OS with decitabine versus treatment choice (median OS 7.7 months vs. 5.0 months), an unplanned analysis after 446 deaths showed a significant benefit for decitabine (HR 0.82 [95% CI 0.68–0.99], P = 0.037). A small but pivotal phase II trial in 53 patients evaluated the effect of a longer 10-day decitabine schedule and found an increased CR rate of 47% and overall response of 64% with a median OS of 13 months [41]. The beneficial effects of the 10-day decitabine schedule were confirmed in two large single-centre retrospective studies that found response rates and median OS of 40% and 11 months, and 35% and 11 months, respectively [42, 43]. Recently, the result of a phase II trial directly comparing 5-day versus 10-day decitabine treatment was reported. The researchers concluded both schedules have similar efficacy (CR rates 29% vs. 30% [P = 0.88], median OS 5.5 vs. 6.0 months [P = 0.47]), although there was an uncorrected imbalance in disease characteristics favouring the 5-day schedule and the randomisation allocation was skewed towards the 10-day schedule [44]. Therefore caution has to be taken when interpreting the results. However, these data show that decitabine, both in 5-day and 10-day schedules, is efficient and suggest that decitabine as a single agent might provide a framework upon which to build future combination studies to improve outcomes for older AML patients.
Guadecitabine is a next generation HMA given subcutaneously which provides prolonged in vivo exposure to its active metabolite decitabine, thus offering potential clinical advantages over current HMAs. In a large randomised trial 815 untreated AML patients not eligible for IC were randomised to either guadecitabine (5 days 60 mg/m2 every 4 weeks) or a preselected treatment of azacitidine, decitabine, or LDAC (ASTRAL-1 trial, NCT02920008). Although this trial showed that guadecitabine is an effective drug, the trial did not achieve its primary endpoints of statistically significant superiority of guadecitabine vs. preselected treatment for CR or OS [45].
ASTX727 is a next generation HMA with a unique fixed-dose combination of the hypomethylating agent decitabine and the novel cytidine deaminase inhibitor, E7727 (cedazuridine). ASTX727 was designed to deliver decitabine by oral administration. By inhibiting cytidine deaminase, cedazuridine inhibits the major mechanism by which decitabine is degraded in the gastrointestinal tract and liver, and the combination therefore permits the efficient delivery of decitabine orally. It has shown promising effects in a phase II trial conducted in intermediate- and high-risk myelodysplastic syndromes and chronic myelomonocytic leukaemia patients [46]. This trial is now expanding to include AML patients (NCT04093570).
An important question is whether intensive chemotherapy is superior to hypomethylating agents in older AML patients. The results of the above reported clinical trials cannot be directly compared due to differences in patient population studied. The MD Anderson Cancer Center reported the results of a retrospective cohort study of 671 patients, including 114 patients treated with HMAs (either azacitidine or decitabine) and 557 patients treated with IC [47]. Both groups were balanced according to cytogenetics and performance status and were older than 65 years. Patients who had received IC had a higher CR rate compared to patients who had received HMAs (42% vs. 28% [P = 0.001], respectively). However, the median OS was comparable in the 2 groups (6.7 vs. 6.5 months, P = 0.41). Multivariate analysis confirmed that type of AML therapy (IC or HMAs) was not an independent prognostic factor for survival. Interestingly, this study revealed that decitabine was associated with improved median OS compared with azacitidine (8.8 vs. 5.5 months, respectively, P = .03), also in multivariate analysis. No published prospective randomised trials have compared the efficacy of azacitidine with decitabine nor the efficacy of intensive chemotherapy (‘3 + 7’) with hypomethylating agents. The results of the EORTC-1301 phase III trial, comparing upfront treatment with intensive chemotherapy or decitabine, are eagerly awaited (NCT02172872).
Low-dose cytarabine (LDAC) (20 mg twice daily for 10 days) has been used in the treatment of AML for several years. Treatment with LDAC has low toxicity and a higher CR rate than best supportive care (18% vs. 1%) [15]. Although the OS for the LDAC-treated group has been demonstrated to be statistically significantly better, it is worth noting that in absolute terms, the therapeutic advantage is marginal, with a prolongation of OS of only a few months. Additionally, the benefit is restricted to the small fraction of patients who achieve a response (median survival 19 months vs. 2 months in responders vs. non-responders respectively) [15]. Patients with adverse cytogenetics do not seem to benefit from LDAC. Combinations of LDAC with other agents have been tested in clinical trials and although some additions resulted in higher CR rates survival was not improved [48, 49, 50, 51, 52, 53]. Thus, the OS in patients receiving LDAC is still highly unsatisfactory (median 5 months) [3]. Recently, the results of the VIALE-C trial have been reported, demonstrating an increased efficacy by adding venetoclax to LDAC (see 7.1).
Since 2017 the FDA has approved 8 new drugs for the treatment of AML [54]. New developments to treat AML, especially in older patients, include 1) drugs targeting specific signalling pathways (like the hedgehog pathway or apoptosis); 2) drugs specifically targeting mutations in AML (e.g. targeting the epigenetic modifiers IDH1/IDH2 and mutated cytokine receptor FLT3) and 3) an alternative formulation of classic chemotherapeutic drugs (CPX-315).
Venetoclax (ABT-199/GDC-0199), an orally available inhibitor of the anti-apoptotic molecule Bcl-2, has shown great efficacy in chronic lymphocytic leukaemia [55, 56, 57]. After observing single-agent activity in AML cell lines [58], venetoclax has been tested as monotherapy in relapsed and refractory AML patients showing activity with a CR/CRi rate of 19% [59]. Promising results have been reported for combinatorial studies with venetoclax in AML. In the randomised phase 3 trial VIALE-C (LDAC +/− venetoclax) 211 patients were randomised 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus LDAC on days 1 to 10 [60]. The primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs. LDAC alone, although not statistically significant (hazard ratio [HR], 0.75; P = .11), and a median OS of 7.2 vs. 4.1 months, respectively. An unplanned analysis with additional 6-month follow-up did demonstrate a significant benefit with a median OS of 8.4 months for venetoclax added to LDAC (HR, 0.70; P = .04).
In addition, the results of a phase 3 study of venetoclax in combination with azacitidine versus azacitidine alone in treatment-naïve older AML patients, who were ineligible for standard induction therapy, have recently been reported (VIALE-A trial; NCT02993523). This study confirms the additive value of venetoclax to azacitidine by a significant increase in CR/CRi rate from 28–66% and an increase in median OS from 9.6 months to 14.7 months [19]. The high remission rate which can be achieved by adding venetoclax to azacitidine treatment is striking. The impressive results of this study will likely make the combination of an hypomethylating agent with venetoclax the new standard for the treatment of older unfit AML patients.
The
Glasdegib is small molecule inhibitor of the hedgehog receptor smoothened. The hedgehog pathway is important during embryogenesis but repressed after birth. However, aberrant hedgehog signalling has been identified in AML, particularly in leukaemic stem cells, and has been associated with chemoresistance [64]. Inhibition of hedgehog signalling with glasdegib has shown promising results. A phase II study evaluating the combination of glasdegib and intensive chemotherapy in patients over 55 years of age with newly diagnosed AML reported a CR rate of 40% and median OS of 14.7 months [65]. Glasdegib was also evaluated in combination with LDAC in older patients unfit for intensive chemotherapy. Patients receiving glasdegib + LDAC had increased CR rates, 17.0% vs. 2.3%, and improved median OS 8.8 vs. 4.9 months, compared to patients receiving LDAC alone [66]. Based on these results, the FDA has approved glasdegib in combination with LDAC for AML patients ≥75 years or patients ineligible for intensive chemotherapy. In addition, glasdegib is being evaluated in combination with hypomethylating agents and a phase III trial of glasdegib in combination with intensive chemotherapy is ongoing (BRIGHT AML1019, NCT03416179).
CPX-315 is a liposomal formulation that delivers a 5:1 fixed-molar ratio of cytarabine and daunorubicine. With the liposomal encapsulation both drugs can be delivered in a fixed ratio with the highest proportion of synergy to enhance treatment efficacy [67]. CPX-351 preferentially targets leukaemic cells to a greater degree than non-leukaemic cells in the bone marrow, leading to decreased cytotoxicity against normal haematopoietic cells [68]. A small study of CPX-351 as first-line therapy in 30 newly-diagnosed AML patients ≥65 years showed a promising remission rate of 53.2% with a median OS 14.5 months [68]. In a randomised phase II trial in older adults with untreated AML comparing CPX-351 and conventional ‘3 + 7’ treatment a trend towards increased response rates was observed in the CPX-351 group, 66.7% vs. 51.2%. Survival was comparable between both treatment groups (14.7 vs. 12.9 for the CPX-351 and ‘3 + 7’ group respectively). However, CPX-351 treatment was superior in the subset of secondary AML patients with a median OS of 12.1 months vs. 6.1 months in the ‘3 + 7’ group [67]. Superiority of CPX-351 to conventional ‘3 + 7’ chemotherapy in secondary AML, also including AML with MDS related changes, was confirmed in a phase III trial including 309 older AML patients. The observed remission rates were 47.7% vs. 33.3% and median OS was 9.6 vs. 6.0 months in favour of CPX-351 [69]. The safety profile of CPX-351 was similar to that of conventional chemotherapy.
Allogeneic haematopoietic cell transplantation (HCT), as post-remission treatment, offers the highest potential for long-term survival and cure for patients with AML. For younger patients, the choice for consolidation with an allogeneic transplant is nuanced, as particular younger patients with high-risk disease, entailing high-risk mutations and presence of measurable residual disease after treatment, benefit post-remission treatment with an allogeneic HCT. As older patients generally have low chance for long-term survival, also if they have “good-risk” cytogenetic abnormalities, allogeneic HCT should be considered in older (fit) AML patients [10, 70, 71]. Nevertheless, only a minority of older patients actually receives an allogeneic HCT [72, 73]. Allogeneic HCT in older patients is limited by concerns related to treatment-related mortality (TRM) (e.g. TRM is >40% in patients with a HCT-comorbidity score ≥ 3) [74]. However, the development of less toxic conditioning regimens (reduced intensity conditioning (RIC) and non-myeloablative (NMA)), has been an important conceptual change that has created the opportunity for older patients with AML to receive an allogeneic HCT. These conditioning regimen are less dependent on cytotoxic effects of the conditioning regimen and more dependent on the graft-versus-leukaemia effect.
Several studies evaluating allogeneic HCT after RIC in older AML patients have shown promising results. A phase II study of 114 older patients receiving an allogeneic HCT after RIC with fludarabine and busalfan reported a 2-year OS of 48% with a non-relapse mortality (NRM) of 15%. However, cumulative incidence of relapse was 44% at 2 years [75]. A large retrospective study analysing the outcomes of 1080 AML patients who underwent allogeneic HCT after RIC found a 2-year OS of 36% in patients age ≥ 65 years, a NRM of 34%, and 2-year relapse probability of 33% [76]. This analysis included several age groups ranging from 40 to above 65 years and found no significant impact of age on NRM, relapse, disease-free survival, or OS. In addition, studies comparing allogeneic HCT after RIC to conventional post-remission treatments have reported favourable outcomes with allogeneic HCT after RIC. A study comparing allogeneic HCT after RIC (n = 97), chemotherapy (n = 44), autologous transplantation (n = 23), and no further treatment (n = 336) as post-remission therapy reported a 5-year OS of 35% for patients receiving allogeneic HCT after RIC compared to 26% and 21% for chemotherapy/autologous transplantation and no treatment, respectively [77]. Multivariate analysis confirmed the beneficial effect allogeneic HCT after RIC on 5-year survival. A comparison between allogeneic HCT after RIC and chemotherapy in patients age 60–70 years showed that allogeneic HCT after RIC was associated with a lower risk of relapse at 3 years (32 vs. 81%) although NRM was increased (36% vs. 4%), leading to an OS of 37% vs. 25% at 3 years [78]. These studies underscore the delicate balance between sufficient antileukemic effect and treatment toxicity, which is challenging in post-remission treatment of older AML patients.
The efficacy and safety of NMA conditioning consisting of low-dose total body irradiation alone or combine with fludarabine (90 mg/m2) in older patients was evaluated in a prospective cohort of 372 patients aged 60 to 75 years. The OS at 5 years post-transplantation was 35% with an NRM of 27%. Relapse rate was 41% at 5 years indicating the need for further improvement [73]. Nevertheless, these data compare very favourably with historical data on long-term survival of about 10% after treatment of older AML patients with intensive chemotherapy without post-remission treatment with allogeneic HCT.
Treatment of relapsed or refractory (R/R) AML, in general, has presented challenges for haematologists for decades. Despite numerous clinical studies, outcomes are consistently disappointing with 5-year OS rates of ∼10%. Allogeneic HCT at the time of second complete remission remains the only reliable option with curative potential. For older patients, treatment of R/R AML is even more difficult and outcomes poorer. However, the availability of new drugs, like venetoclax, gilteritinib, ivosidenib and enasidenib offer reasonable chances of temporally disease control with acceptable side effects. This implies the importance of detailed molecular analysis, also in the R/R setting, as the R/R disease might contain different (targetable) mutations. Phase 1 studies are generally an option for those patients with a strong wish to receive treatment. Finally, only best supportive care with antibiotics and transfusions can be a preferable option.
Hemorrhage is the cause of 12.0–18.0% of deaths during pregnancy [1, 2, 3]. Severe postpartum hemorrhage (PPH) is a major cause of maternal mortality and morbidity [4, 5] and is increasing in incidence worldwide [6, 7], especially in low resource countries [8]. Emergency hysterectomy is increasingly performed to treat uncontrollable PPH [1, 2, 3]. It was performed at the time of, or within 24 h of, a vaginal or abdominal delivery for the treatment of hemorrhage that was unresponsive to unservative approaches [9]. Variability in the incidence of PPH-related hysterectomy is different in various countries and even among institutions [9, 10, 11, 12, 13].
According to recent reports, 0.20–5.09 of every 1000 postnatal women across the globe have undergone an emergency hysterectomy [14]. Hysterectomy is considered to be a safe, low-risk surgery. It is, by nature, unplanned and performed expeditiously in the case of severe PPH. It may not be the best option for all women, especially those who still want to have children. Some people may have an adverse reaction to the anesthetic, heavy bleeding, and infection around the incision site [15].
The guidelines of the World Health Organization (WHO) aim to prevent and manage PPH by active management of the third stage of labor (AMTSL) [16]. Thai government policy to prevent PPH in 2013 was involved in the project—Every Woman Every Child (EWEC) to decrease maternal mortality and child mortality by 16 million cases in 2015 [17, 18]. However, the incidence of PPH was increased from 2.30 to 2.65% from 2009 to 2015 [19]. In low-resource city with various ethnic groups, surrounded by mountains and forests as in Chiang Rai province and Sakon Nakhon province [20, 21]. The incidence of PPH is increasing in Chiang Rai from 1.12 to 2.07%, but maternal death from PPH decreased from 3.05 to 1.23% during 2012-2015 [20]. In the fiscal year 2014–2015, PPH-related hysterectomy decreased in number from 2 cases to 1 case [20]. In Sakon Nakhon, during 2015–2018 the incidence of PPH is about 1.13–1.39%. The maternal deaths were decreased from 33.83 to 27.84 per 100,000 infant live births. However, it was higher than the standard criterion of 17.0 per 100,000 infant live births [21].
A tool developed from significantly high-risk factors [22, 23, 24] associated with PPH was performed in western societies and Thailand [25, 26, 27, 28, 29]. These tools can detect PPH earlier and can reduce the number of maternal deaths and PPH-related hysterectomies in Thailand [20, 21].
This study aimed to synthesize knowledge about the early management of PPH, summarize the appropriate risk score tool for the prediction of PPH, and reduce the number of maternal deaths and PPH-related hysterectomy cases in two lower resource cities in the north and northeast of Thailand.
The objective of this study was to synthesize knowledge about the early management of PPH and an appropriate risk score tool to reduce PPH-related hysterectomy cases in two lower resource cities in the north and northeast of Thailand.
The study reviewed the results of the author’s research in four steps as follows:
The research review was approved by the Ethics Committee for Human Research at Khon Kaen University, Thailand [HE 601234, HE 611093], the Chiang Rai Regional Hospital Ethics Committee on July 21st, 2017, and the Ethics committee of Sakon Nakhon Hospital (SKHREC 422562). Most of the research was based on secondary data. Those who volunteered had signed a consent form.
There are four steps to this research result as follows:
Risk factors | Subgroup | Statistical procedures | ||
---|---|---|---|---|
Heterogeneity Test I2 | Estimate size (fixed effect) | |||
OR (95% CI) | ||||
I. Eight of high-risk factors (odds ratio > 2.0) | ||||
1. Antepartum hemoglobin level | >10 g/dL | 95.71 | 4.80 (4.00–5.76) | <0.001 |
2. Coagulopathy | 35.18 | 11.96 (2.64–54.10) | 0.004 | |
3. History of prior pregnancy and delivery | Prior PPH | 40.89 | 4.01 (2.32–6.93) | <0.001 |
4. Complication of current pregnancy, 1st stage of labor, received procedure of 1st stage of labor | Fibroid | 89.97 | 0.73 (0.70–0.75) | <0.001 |
5. Complication of current pregnancy, 1st stage of labor, received procedure of 1st stage of labor | Multiple pregnancy | 51.23 | 2.69 (2.32–3.11) | <0.001 |
6. Complication of current pregnancy, 1st stage of labor, received procedure of 1st stage of labor | Gestational hypertensive disorder | 69.13 | 2.07 (1.72–2.50) | <0.001 |
7. Placenta factors | Placenta previa | 28.44 | 5.01 (3.61–6.97) | <0.001 |
8. Placenta Factors | Placenta accrete | 0.00 | 3.55 (1.84–6.86) | <0.001 |
II. Six moderate risk factors (odds ratio > 1.5–2.0) | ||||
1. Obstetric factors parity | Nulliparous | 72.62 | 1.93 (1.53–2.43) | <0.001 |
2. Gestational age (large gestational age) | >40 weeks | 47.19 | 1.35 (1.28–1.42) | <0.001 |
3. Placenta factors | Placenta abruption | 39.13 | 1.70 (1.06–2.73) | 0.029 |
4. Complication of current pregnancy, 1st stage of labor, received procedure of 1st stage of labor | Chorioamnionitis | 0.00 | 1.85 (1.45–2.98) | 0.012 |
5. Complication of current pregnancy, 1st stage of labor, received procedure of 1st stage of labor | Induction of labor | 69.33 | 1.77 (1.57–2.00) | <0.001 |
6. Complication of current pregnancy, 1st stage of labor, received procedure of 1st stage of labor | Augmentation of Labor | 69.66 | 1.57 (1.35–5.87) | <0.001 |
III. Seven of low-risk factors (odds ratio > 1.0–1.5) | ||||
1. Individual factors maternal age | <20 years old | 31.40 | 1.36 (1.26–1.46) | <0.001 |
2. Individual factors maternal age | >35 years old | 17.37 | 1.32 (1.29–1.35) | <0.001 |
3. 1 Body mass index (BMI) level | <30 kg/m2 | 0.00 | 1.17 (1.05–1.31) | 0.050 |
3. 2 Body mass index (BMI) level | >30 kg/m2 | 0.00 | 1.18 (1.01–1.38) | 0.027 |
4. Obstetric Factors parity | Primiparous | 97.64 | 1.29 (1.18–1.41) | <0.001 |
5. Gestational age | >42 weeks | 47.19 | 1.35 (1.28–1.42) | <0.001 |
6. Complication of current pregnancy, 1st stage of labor, received procedure of 1st stage of labor | Gestational diabetes mellitus | 0.00 | 1.35 (1.22–1.45) | <0.001 |
7. Complication of current pregnancy and 1st stage of labor receive procedure | Received analgesic drugs | 10.03 | 1.38 (1.27–1.49) | <0.001 |
Med calc version 18.6 was used to analyze risk factors for PPH during vaginal deliveries.
Source: approved by I-Tuporn, et al. [29].
This study was analyzed and identified risk factors for PPH via vaginal deliveries from 20 articles from 2005 to 2017 in Thailand and globally, using MedCalc version 18.2.1 and version 18.6 [30].
The results showed that 21 factors, including eight high-risk factors for PPH (odds ratio > 2.0) include antepartum hemoglobin ≤10 g/dL, coagulopathy, prior PPH, fibroid, placenta previa, placenta accrete, multiple pregnancy, and gestational hypertensive disorder. Six moderate risk factors for PPH (odds ratio > 1.5–2.0) include nulliparous status, large gestational age, placenta abruption, chorioamnionitis, induction, and augmentation of labor. Seven low-risk factors for PPH (odds ratio > 1.0–1.5) include maternal age < 20 years old and ≥ 35 years old, BMI level, primiparous, gestational age ≥ 42 weeks, gestational diabetes mellitus, and having received analgesic drugs.
Form for recording risk scores to predict postpartum hemorrhage (PPH) of blood loss over 300 ml after vaginal delivery. Source: approved by I-Tuporn, et al. [
The results showed that the eight predictors of I-Tuporn et al. [31] (Figure 1) from the cause of PPH (4 T’s and 7 steps of the clinical prediction model of Steyerberg) [32, 33] and by comparison with the standard monogram of Biguzzi [34], Sittipan [28], and Suta [27] could predict postpartum blood loss over 300 ml at Chiang Rai Regional Hospital with a sensitivity of 80.7%, a specificity of 60.8%, and the ROC curve equal to 0.71 at the optional cut-off score of four marks or above (see Figure 1) [31].
Level of blood loss | ROC curve | Sensitivity (%) | Specificity (%) | Accuracy (%) | Positive predictive value (%) | Negative predictive value (%) | 95% CI | P-Value |
---|---|---|---|---|---|---|---|---|
>250 ml | 0.627 | 57.33 | 61.95 | 59.84 | 58.01 | 61.48 | 0.592–0.662 | <0.001 |
>275 ml | 0.608 | 15.69 | 92.92 | 56.04 | 66.96 | 54.66 | 0.554–0.662 | <0.001 |
>300 ml | 0.606 | 15.48 | 92.92 | 55.94 | 66.66 | 54.60 | 0.552–0.661 | <0.001 |
>500 ml | 0.653 | 5.02 | 98.66 | 53.94 | 77.41 | 53.19 | 0.563–0.744 | 0.004 |
Review of risk score at the different levels of blood loss from 250 ml. to 500 ml. in 1001 cases who underwent vaginal delivery at Sakhon Nakhon hospital, Thailand, during June 2018 to December 2019.
Source: Approved by Nutravong et al. [35], on An Appropriate Assessment of PPH by using a Risk Score Tool for prediction at Sakon Nakhon, Hospital, Thailand oral presentation in the International Webinar on Primary Healthcare and Medicare held during November 08–09, 2021/Vienna Austria.
It found that the eight predictors of I-Tuporn et al. [31] (Figure 1) can be used to predict early PPH in Sakon Nakhon Hospital since blood loss is 250 ml and over with a sensitivity of 57.33%, a specificity of 61.95%, and a ROC curve equal to 0.62 (Table 2 and Figure 2).
The ROC curve’s performance at different levels of blood loss at over (a) 250 mL, (b) 275 mL, (c) 300 mL, and (d) 500 mL of a risk score for PPH prediction from 1001 cases after delivery at Sakon Nakhon hospital, Thailand from July 2018 to December 2019.
The results of one-year follow-up showed the incidence of Chiang Rai Regional Hospital.
The number of cases of PPH-related hysterectomy decreased from 4.61% to 3.81% from 2019 to 2020 report of. It had no cases of PPH-related hysterectomy but had reported no maternal death per 100,000 infant live births, 36.60 and 37.36 respectively.
In Sakon Nakhon province, the incidence of PPH decreased from 1.39 to 1.10%, but there was no report of PPH-related hysterectomy. The maternal death rate decreased from 27.84 to 15.12 per 100,000 live births, from 2018 to 2019 (Table 3).
Setting | Pregnancy Problems | Fiscal years | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
2009 | 2010 | 2011 | 2012 | 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | 2019 | 2020 | |||
Thailand* | Incidence of PPH | 2.30% | 2.37% | 2.44% | 2.40% | 2.39% | 2.54% | 2.65% | NA | NA | NA | NA | NA | |
Chiang Rai** Province | Incidence of PPH | NA | NA | NA | 1.12% | 1.15% | 1.34% | 2.07% | NA | NA | NA | NA | NA | |
PPH related Hysterectomy | NA | NA | NA | NA | NA | 2 | 1 case | NA | NA | NA | NA | NA | ||
Maternal death/100,000 infant live birth | NA | NA | NA | 3.05 | 4.58 | 1.82 | 1.23 | NA | NA | NA | NA | NA | ||
Chiang Rai** Regional Hospital | Incidence of PPH | NA | NA | NA | NA | 9.0% | 1.98% | 2.64% | 2.58% | 2.61% | 3.85% | 4.61% | 3.81% | |
PPH related Hysterectomy | NA | NA | NA | NA | 1 case | NA | NA | NA | NA | NA | NA | NA | ||
Maternal death/ 100,000 infant live birth | NA | NA | NA | NA | NA | 36.14 | 18.09 | NA | NA | 17.45 | 36.60 | 37.36 | ||
Sakon Nakhon*** Province | Incidence of PPH | NA | NA | NA | NA | NA | NA | 1.13% | 0.93% | 1.00% | 1.39% | 1.10% | NA | |
PPH related Hysterectomy | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | ||
Maternal death/100,000 infant live birth | NA | NA | NA | NA | NA | NA | 33.83 | 17.68 | 26.88 | 27.84 | 15.12 | NA |
Statistics on PPH, PPH-related hysterectomy, and maternal deaths were collected in Thailand’s Chiang Rai Province. Chiang Rai regional hospital, Sakon Nakhon Province.
Medical Department, Ministry of Public Health document 2013 [17].
Ajalapung, 2015 [20].
Statistic Report for NE Thailand, 2019 [21].
Remarks: The standard Criterion of maternal deaths was 17 per 100,000 infant live birth.
The postpartum hemorrhage (PPH) in I-Tuporn et al. [31] study, which was conducted in the Chiang Rai Regional Hospital in 2017, was 2.61%. It was lower than the study in Chonburi Hospital (4.95%) [28] and Maharat Nakorn Ratchasima Hospital (6.67%) [26], but it was related to the report of Bhumibol Adulyadej Hospital (1.98%) [25] and the report of Calvert et al. [36] that presented Asia’s regional PPH rate of 1.90% [36].
Emergency hysterectomy for the treatment of severe hemorrhage from vaginal delivery was not reported widely in Chiang Rai Regional Hospital or Sakon Nakhon province. It was presented only some years ago and reported only a few cases. However, the maternal death rate in Sakon Nakhon province from 2015 to 2018 was higher than the standard criterion of 17 per 100,000 infant live births. It was decreased in the year 2019 to 15.12 per 100,000 infant live births after this hospital used a risk score tool with 8 predictors by I-Tuporn et al. [31] to detect earlier PPH and early treatment as blood loss over 250 mL from the collector bag.
The risk score tool for the prediction of PPH in Thailand had five studies [25, 26, 27, 28, 29]. They were developed in different settings. They had some similar risk factors for the detection of PPH. The study of I-Tuporn et al. [31] developed the risk score tool with 8 predictors, covering the cause of PPH (4 T’s and 7 steps of the clinical prediction model of Steyerberg [32, 33] and by comparison with the standard monogram of Biguzzi [34], Sittipan [28], and Suta et al. [27]) I-Tuporn et al. [31] risk score tool could be used in low-resource cities with various ethnic groups, as in Chiang Rai and Sakon Nakhon province, which are in the north and northeast of Thailand, respectively.
The results of the Chiang Rai and Sakon Nakhon provinces study after 1 year of follow-up showed that the maternal death rate in Sakon Nakhon province had decreased to normal criterion, and there were no reports of PPH-related hysterectomy cases in these two provinces.
In conclusion, the problems of PPH concerned the Thai government. Many projects were carried out in accordance with World Health Organization’s (WHO) [16] guidelines to reduce PPH, PPH-related hysterectomy, and maternal death.
Due to some settings in Thailand, the government’s policy is not suitable for some women because of their low resources and distance from the cities. Some of the settings are surrounded by mountains and forests, and it is very hard to refer a pregnant woman with PPH to the provincial hospital. Most of them belong to different ethnic groups and cannot communicate with other people. Therefore, some of them die before seeing a doctor.
There should be a policy of early detection of PPH in those lower resource settings by using an appropriate risk score tool to predict the PPH risk for a pregnant woman’s life.
The authors would like to thank all of the respondents for their valuable contributions to this study and extend their special gratitude to the Department of Obstetrics and Gynecology in Chiang Rai Regional Hospital and Sakon Nakhon Hospital for the data support, and the Thai Society of Maternal and Fetal Medicine for funding support.
All authors declare that they have no conflicts of interest.
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Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"47",title:"Cell Biology",slug:"biochemistry-genetics-and-molecular-biology-cell-biology",parent:{id:"6",title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"},numberOfBooks:14,numberOfSeries:0,numberOfAuthorsAndEditors:323,numberOfWosCitations:116,numberOfCrossrefCitations:154,numberOfDimensionsCitations:332,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"47",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10541",title:"Regulation and Dysfunction of Apoptosis",subtitle:null,isOpenForSubmission:!1,hash:"1d45e84353c25037adb996a7a46c1af1",slug:"regulation-and-dysfunction-of-apoptosis",bookSignature:"Yusuf Tutar",coverURL:"https://cdn.intechopen.com/books/images_new/10541.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:"7999",title:"Free Radical Medicine and Biology",subtitle:null,isOpenForSubmission:!1,hash:"083e5d427097d368a3f8a02bd6c76bf8",slug:"free-radical-medicine-and-biology",bookSignature:"Kusal Das, Swastika Das, Mallanagouda Shivanagouda Biradar, Varaprasad Bobbarala and S. 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Buchholz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6683",title:"Ion Channels in Health and Sickness",subtitle:null,isOpenForSubmission:!1,hash:"8b02f45497488912833ba5b8e7cdaae8",slug:"ion-channels-in-health-and-sickness",bookSignature:"Kaneez Fatima Shad",coverURL:"https://cdn.intechopen.com/books/images_new/6683.jpg",editedByType:"Edited by",editors:[{id:"31988",title:"Prof.",name:"Kaneez",middleName:null,surname:"Fatima Shad",slug:"kaneez-fatima-shad",fullName:"Kaneez Fatima Shad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:14,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"64565",doi:"10.5772/intechopen.81552",title:"Two-Dimensional (2D) and Three-Dimensional (3D) Cell Culturing in Drug Discovery",slug:"two-dimensional-2d-and-three-dimensional-3d-cell-culturing-in-drug-discovery",totalDownloads:3283,totalCrossrefCites:11,totalDimensionsCites:40,abstract:"Cell culture is an indispensable in vitro tool used to improve our perception and understanding of cell biology, the development of tissue engineering, tissue morphology, mechanisms of diseases and drug action. Efficient cell culturing techniques both in vitro and in vivo allow researchers to design and develop new drugs in preclinical studies. Two-dimensional (2D) cell cultures have been used since 1900s and are still a dominant method in many biological studies. However, 2D cell cultures poorly imitate the conditions in vivo. Recently three-dimensional (3D) cell cultures have received remarkable attention in studies such as drug discovery and development. Optimization of cell culture conditions is very critical in ensuring powerful experimental reproducibility, which may help to find new therapies for cancer and other diseases. In this chapter, we discuss the 2D and 3D cell culture technologies and their role in drug discovery.",book:{id:"6964",slug:"cell-culture",title:"Cell Culture",fullTitle:"Cell Culture"},signatures:"Jitcy Saji Joseph, Sibusiso Tebogo Malindisa and Monde Ntwasa",authors:null},{id:"68141",doi:"10.5772/intechopen.87778",title:"Nonenzymatic Exogenous and Endogenous Antioxidants",slug:"nonenzymatic-exogenous-and-endogenous-antioxidants",totalDownloads:1888,totalCrossrefCites:16,totalDimensionsCites:29,abstract:"Nonenzymatic exogenous and endogenous antioxidants play an important role in human health and act as preservatives for cosmetics, pharmaceuticals, and food products. This chapter will discuss the chemical structure and mechanism of action of the most important nonenzymatic small exogenous and endogenous organic molecules that act as antioxidants. The chapter will focus on the structural features, functional groups, properties, biosynthetic origin, and mechanism of action of such antioxidants. It also covers damages that free radicals create and the mechanisms by which they are neutralized by the various antioxidants. The scope of this chapter will be limited to nonenzymatic exogenous and endogenous antioxidants since enzymatic antioxidants have been discussed extensively in several reviews.",book:{id:"7999",slug:"free-radical-medicine-and-biology",title:"Free Radical Medicine and Biology",fullTitle:"Free Radical Medicine and Biology"},signatures:"Ziad Moussa, Zaher M.A. Judeh and Saleh A. Ahmed",authors:[{id:"300774",title:"Dr.",name:"Ziad",middleName:null,surname:"Moussa",slug:"ziad-moussa",fullName:"Ziad Moussa"},{id:"306324",title:"Dr.",name:"Zaher",middleName:null,surname:"M. A. Judeh",slug:"zaher-m.-a.-judeh",fullName:"Zaher M. A. Judeh"},{id:"306325",title:"Prof.",name:"Saleh",middleName:null,surname:"A. Ahmed",slug:"saleh-a.-ahmed",fullName:"Saleh A. Ahmed"}]},{id:"62562",doi:"10.5772/intechopen.79502",title:"Keratin Waste: The Biodegradable Polymers",slug:"keratin-waste-the-biodegradable-polymers",totalDownloads:2265,totalCrossrefCites:9,totalDimensionsCites:15,abstract:"Keratins are everywhere, from being the major components of household dust to common contaminants of laboratory protein analysis. Keratin is the major structural fibrous protein belonging to the large family of structural proteins to form hair, wool, feathers, nails, and horns of many kinds of animals and has a high concentration of cysteine, 7–20% of the total amino acid residues, that form inter- and intramolecular disulfide bonds. Keratin wastes are considered as the environmental pollutants and produced mostly from the poultry farms, slaughterhouses, and leather industries. Keratin wastes are dumped, buried, used for landfilling, or incinerated and all these actions increase the threats of environmental hazards, pollution, negatively influence the public health, and increase greenhouse gases concentration. Nature has provided planet Earth with a variety of beneficial organisms. Soil is considered as a well-known source for the growth of keratinophilic microflora (fungi and bacteria), which have the capability to degrade the keratin waste. The keratin-degradation ability of keratinophilic microflora has been credited with the production of the microbial keratinase enzyme and biodegradation takes place (enzymatic degradation). So, the keratin wastes are the biodegradable polymers. Keratinase is the industrially significant enzyme that offers bioconversion of keratin waste, utilization as animal feed supplements, and dehairing agents in tannery industries and textile industries.",book:{id:"6820",slug:"keratin",title:"Keratin",fullTitle:"Keratin"},signatures:"Tarun Kumar Kumawat, Anima Sharma, Vishnu Sharma and\nSubhash Chandra",authors:[{id:"250905",title:"Dr.",name:"Anima",middleName:null,surname:"Sharma",slug:"anima-sharma",fullName:"Anima Sharma"},{id:"257932",title:"Dr.",name:"Tarun Kumar",middleName:null,surname:"Kumawat",slug:"tarun-kumar-kumawat",fullName:"Tarun Kumar Kumawat"},{id:"257942",title:"Dr.",name:"Vishnu",middleName:null,surname:"Sharma",slug:"vishnu-sharma",fullName:"Vishnu Sharma"},{id:"257944",title:"Prof.",name:"Subhash",middleName:null,surname:"Chandra",slug:"subhash-chandra",fullName:"Subhash Chandra"}]},{id:"62159",doi:"10.5772/intechopen.79050",title:"Keratins in Skin Epidermal Development and Diseases",slug:"keratins-in-skin-epidermal-development-and-diseases",totalDownloads:2402,totalCrossrefCites:5,totalDimensionsCites:13,abstract:"Epidermal keratinocyte (KC), the major cell type in the skin epidermis, plays critical roles in forming a permeability barrier to separate internal organs from external stimuli. Keratins, constituting about 30–80% of the total protein in KCs, form the major intermediate filament cytoskeleton of KC. Keratins consist of 54 unique genes in humans and they are expressed in cell-, differentiation- and development-dependent manner. While keratin pairs K5-K14 and K1-K10 are normally associated with KCs at different cell differentiation stages, other keratin pairs such as K6-K16/K17 and K8–K18 and are usually not expressed in normal skin interfollicular epidermis, but are elevated during wounding, inflammatory skin diseases such as psoriasis or malignant conversion of KC. The expression and function of keratins are tightly regulated at both transcriptional and post-transcriptional levels. Inherited or spontaneous mutations in keratins or abnormal keratin regulations or modifications can cause KC and cutaneous tissue fragility, skin hypertrophic and inflammatory conditions or malignant transformation of KC, therefore accounting for a large number of disorders in human skin. Here we review the recent literature on how keratins are normally expressed during skin development and how mutations or misregulations of these keratins are involved in the pathogenesis of skin diseases.",book:{id:"6820",slug:"keratin",title:"Keratin",fullTitle:"Keratin"},signatures:"Ling-juan Zhang",authors:[{id:"241614",title:"Dr.",name:"Lingjuan",middleName:null,surname:"Zhang",slug:"lingjuan-zhang",fullName:"Lingjuan Zhang"}]},{id:"67488",doi:"10.5772/intechopen.85416",title:"Milk Exosomes: Isolation, Biochemistry, Morphology, and Perspectives of Use",slug:"milk-exosomes-isolation-biochemistry-morphology-and-perspectives-of-use",totalDownloads:1988,totalCrossrefCites:1,totalDimensionsCites:10,abstract:"Cells of the multicellular organisms communicate with each other in many different ways, among which extracellular vesicles play a unique role. Almost all cell types secrete vesicles into the extracellular space and deliver their contents to recipient cells. Today, one of the groups of extracellular vesicles that is of particular interest for studying is exosomes—membrane vesicles with a diameter of 40–100 nm. Exosomes are secreted by cells and found in various biological fluids—blood, tears, saliva, urine, cerebrospinal fluid, and milk. Exosomes provide not only targeted delivery of molecular signals to recipient cells but also carry unique markers, which makes them a promising substrate in diagnostic studies, primarily due to their small RNA and protein contents. The milk of cows, horses, humans, and other mammals is a unique source of exosomes since these organisms can produce liters of milk per day, which is much higher than the volume of exosomes produced in cell culture fluid or blood plasma. Unfortunately, milk exosomes are currently much less studied than exosomes of blood or culture fluid. This review examines the methods of the isolation, biochemical analysis (composition of proteins, lipids, and nucleic acids), morphology, and prospects for the use of milk exosomes.",book:{id:"8498",slug:"extracellular-vesicles-and-their-importance-in-human-health",title:"Extracellular Vesicles and Their Importance in Human Health",fullTitle:"Extracellular Vesicles and Their Importance in Human Health"},signatures:"Sergey E. Sedykh, Evgeniya E. Burkova, Lada V. Purvinsh, Daria A. Klemeshova, Elena I. Ryabchikova and Georgy A. Nevinsky",authors:[{id:"47119",title:"Dr.",name:"Georgy",middleName:null,surname:"Nevinsky",slug:"georgy-nevinsky",fullName:"Georgy Nevinsky"},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh"},{id:"291659",title:"Prof.",name:"Elena",middleName:null,surname:"Ryabchikova",slug:"elena-ryabchikova",fullName:"Elena Ryabchikova"},{id:"291660",title:"MSc.",name:"Evgeniya",middleName:null,surname:"Burkova",slug:"evgeniya-burkova",fullName:"Evgeniya Burkova"},{id:"291662",title:"MSc.",name:"Lada",middleName:null,surname:"Purvinsh",slug:"lada-purvinsh",fullName:"Lada Purvinsh"},{id:"291663",title:"MSc.",name:"Daria",middleName:null,surname:"Klemeshova",slug:"daria-klemeshova",fullName:"Daria Klemeshova"}]}],mostDownloadedChaptersLast30Days:[{id:"67793",title:"Kinetic Studies on Cell Growth",slug:"kinetic-studies-on-cell-growth",totalDownloads:3729,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"The kinetic model of cell growth is substantially capable to predict product formation. Mathematical models provide a strategy for solving problems encountered in fermentation process. A biochemical engineering approach to address this problem could be to develop a mathematical model which not only helps in the understanding of the system but also predicts various cultivation strategies to facilitate the optimization of a fermentation process, saving much of the time and cost for performing experiments. The presented overview indicates that many of the environmentally relevant aspects in growth kinetics are still waiting to be discovered, established, and exploited. A kinetic model that describes microbial growth, product formation and substrate consumption and the experimental data were fitted with modified logistic equation.",book:{id:"7121",slug:"cell-growth",title:"Cell Growth",fullTitle:"Cell Growth"},signatures:"Punniavan Sakthiselvan, Setti Sudharsan Meenambiga and Ramasamy Madhumathi",authors:[{id:"268626",title:"Dr.",name:"Punniavan",middleName:null,surname:"Sakthiselvan",slug:"punniavan-sakthiselvan",fullName:"Punniavan Sakthiselvan"},{id:"269591",title:"Dr.",name:"Madhumathi",middleName:null,surname:"Ramasamy",slug:"madhumathi-ramasamy",fullName:"Madhumathi Ramasamy"},{id:"279920",title:"Dr.",name:"S S",middleName:null,surname:"Meenambiga",slug:"s-s-meenambiga",fullName:"S S Meenambiga"}]},{id:"69690",title:"Ion Homeostasis Response to Nutrient-Deficiency Stress in Plants",slug:"ion-homeostasis-response-to-nutrient-deficiency-stress-in-plants",totalDownloads:2436,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"A crucial feature of plant performance is its strong dependence on the availability of essential mineral nutrients, affecting multiple vital functions. Indeed, mineral-nutrient deficiency is one of the major stress factors affecting plant growth and development. Thereby, nitrogen and potassium represent the most abundant mineral contributors, critical for plant survival. While studying plant responses to nutrient deficiency, one should keep in mind that mineral nutrients, along with their specific metabolic roles, are directly involved in maintaining cell ion homeostasis, which relies on a finely tuned equilibrium between cytosolic and vacuolar ion pools. Therefore, in this chapter we briefly summarize the role of the ion homeostasis system in cell responses to environmental deficiency of nitrate and potassium ions. Special attention is paid to the implementation of plant responses via NO3− and K+ root transport and regulation of ion distribution in cell compartments. These responses are strongly dependent on plant species, as well as severity and duration of nutrient deficiency.",book:{id:"7121",slug:"cell-growth",title:"Cell Growth",fullTitle:"Cell Growth"},signatures:"Natalia Osmolovskaya, Julia Shumilina, Ksenia Bureiko, Veronika Chantseva, Tatiana Bilova, Ludmila Kuchaeva, Nikolai Laman, Ludger A. Wessjohann and Andrej Frolov",authors:[{id:"177609",title:"Dr.",name:"Natalia",middleName:null,surname:"Osmolovskaya",slug:"natalia-osmolovskaya",fullName:"Natalia Osmolovskaya"},{id:"309520",title:"Ms.",name:"Julia",middleName:null,surname:"Shumilina",slug:"julia-shumilina",fullName:"Julia Shumilina"},{id:"309521",title:"Ms.",name:"Ksenia",middleName:null,surname:"Bureiko",slug:"ksenia-bureiko",fullName:"Ksenia Bureiko"},{id:"309522",title:"Ms.",name:"Veronika",middleName:null,surname:"Chantseva",slug:"veronika-chantseva",fullName:"Veronika Chantseva"},{id:"309523",title:"Dr.",name:"Tatiana",middleName:null,surname:"Bilova",slug:"tatiana-bilova",fullName:"Tatiana Bilova"},{id:"309524",title:"Mrs.",name:"Ludmila",middleName:null,surname:"Kuchaeva",slug:"ludmila-kuchaeva",fullName:"Ludmila Kuchaeva"},{id:"309525",title:"Prof.",name:"Ludger A.",middleName:null,surname:"Wessjohann",slug:"ludger-a.-wessjohann",fullName:"Ludger A. Wessjohann"},{id:"309526",title:"Dr.",name:"Andrej",middleName:null,surname:"Frolov",slug:"andrej-frolov",fullName:"Andrej Frolov"}]},{id:"62159",title:"Keratins in Skin Epidermal Development and Diseases",slug:"keratins-in-skin-epidermal-development-and-diseases",totalDownloads:2396,totalCrossrefCites:5,totalDimensionsCites:12,abstract:"Epidermal keratinocyte (KC), the major cell type in the skin epidermis, plays critical roles in forming a permeability barrier to separate internal organs from external stimuli. Keratins, constituting about 30–80% of the total protein in KCs, form the major intermediate filament cytoskeleton of KC. Keratins consist of 54 unique genes in humans and they are expressed in cell-, differentiation- and development-dependent manner. While keratin pairs K5-K14 and K1-K10 are normally associated with KCs at different cell differentiation stages, other keratin pairs such as K6-K16/K17 and K8–K18 and are usually not expressed in normal skin interfollicular epidermis, but are elevated during wounding, inflammatory skin diseases such as psoriasis or malignant conversion of KC. The expression and function of keratins are tightly regulated at both transcriptional and post-transcriptional levels. Inherited or spontaneous mutations in keratins or abnormal keratin regulations or modifications can cause KC and cutaneous tissue fragility, skin hypertrophic and inflammatory conditions or malignant transformation of KC, therefore accounting for a large number of disorders in human skin. Here we review the recent literature on how keratins are normally expressed during skin development and how mutations or misregulations of these keratins are involved in the pathogenesis of skin diseases.",book:{id:"6820",slug:"keratin",title:"Keratin",fullTitle:"Keratin"},signatures:"Ling-juan Zhang",authors:[{id:"241614",title:"Dr.",name:"Lingjuan",middleName:null,surname:"Zhang",slug:"lingjuan-zhang",fullName:"Lingjuan Zhang"}]},{id:"62187",title:"Calcium and Cell Response to Heavy Metals: Can Yeast Provide an Answer?",slug:"calcium-and-cell-response-to-heavy-metals-can-yeast-provide-an-answer-",totalDownloads:1239,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Despite constant efforts to maintain a clean environment, heavy metal pollution continues to raise challenges to the industrialized world. Exposure to heavy metals is detrimental to living organisms, and it is of utmost importance that cells find rapid and efficient ways to respond to and eventually adapt to surplus metals for survival under severe stress. This chapter focuses on the attempts done so far to elucidate the calcium-mediated response to heavy metal stress using the model organism Saccharomyces cerevisiae. The possibilities to record the transient elevations of calcium within yeast cells concomitantly with the heavy metal exposure are presented, and the limitations imposed by interference between calcium and heavy metals are discussed.",book:{id:"7264",slug:"calcium-and-signal-transduction",title:"Calcium and Signal Transduction",fullTitle:"Calcium and Signal Transduction"},signatures:"Ileana Cornelia Farcasanu, Claudia Valentina Popa and Lavinia\nLiliana Ruta",authors:[{id:"203734",title:"Dr.",name:"Ileana",middleName:"Cornelia",surname:"Farcasanu",slug:"ileana-farcasanu",fullName:"Ileana Farcasanu"},{id:"203865",title:"Dr.",name:"Lavinia",middleName:null,surname:"Ruta",slug:"lavinia-ruta",fullName:"Lavinia Ruta"},{id:"255728",title:"Dr.",name:"Claudia Valentina",middleName:null,surname:"Popa",slug:"claudia-valentina-popa",fullName:"Claudia Valentina Popa"}]},{id:"61953",title:"L-Type Calcium Channels: Structure and Functions",slug:"l-type-calcium-channels-structure-and-functions",totalDownloads:2723,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"Voltage-gated calcium channels (VGCCs) manage the electrical signaling of cells by allowing the selective-diffusion of calcium ions in response to the changes in the cellular membrane potential. Among the different VGCCs, the long-lasting or the L-type calcium channels (LTCCs) are prevalently expressed in a variety of cells, such as skeletal muscle, ventricular myocytes, smooth muscles and dendritic cells and forms the largest family of the VGCCs. Their wide expression pattern and significant role in diverse cellular events, including neurotransmission, cell cycle, muscular contraction, cardiac action potential and gene expression, has made these channels the major targets for drug development. In this book chapter, we aim to provide a comprehensive overview of the different VGCCs and focus on the sequence-structure–function properties of the LTCCs. Our chapter will summarize and review the various experimental and computational analyses performed on the structures of the LTCCs and their implications in drug discovery applications.",book:{id:"6683",slug:"ion-channels-in-health-and-sickness",title:"Ion Channels in Health and Sickness",fullTitle:"Ion Channels in Health and Sickness"},signatures:"Tianhua Feng, Subha Kalyaanamoorthy and Khaled Barakat",authors:[{id:"57391",title:"Dr.",name:"Khaled",middleName:"Hasaan",surname:"Barakat",slug:"khaled-barakat",fullName:"Khaled Barakat"},{id:"236912",title:"B.Sc.",name:"Tianhua",middleName:null,surname:"Feng",slug:"tianhua-feng",fullName:"Tianhua Feng"},{id:"236999",title:"Dr.",name:"Subha",middleName:null,surname:"Kalyaanamoorthy",slug:"subha-kalyaanamoorthy",fullName:"Subha Kalyaanamoorthy"}]}],onlineFirstChaptersFilter:{topicId:"47",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"80484",title:"The Use of Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) to Study Ivermectin-Mediated Molecular Pathway Changes in Human Ovarian Cancer Cells",slug:"the-use-of-stable-isotope-labeling-with-amino-acids-in-cell-culture-silac-to-study-ivermectin-mediat",totalDownloads:80,totalDimensionsCites:0,doi:"10.5772/intechopen.102092",abstract:"Stable isotope labeling with amino acids in cell culture (SILAC) was to use isotopic essential amino acids to replace the original amino acids for cell culture and passage for 8–10 generations, followed by mass spectrometry to identify proteins and the isotopic abundance difference to quantify proteins. SILAC can be used to characterize proteomic changes, and analyze protein turnover, protein interactions, and dynamic changes with quantitative accuracy, and high reproducibility. For this study, SILAC “light” (L-Lysine-2HCl [12C6, 14N2], L-Arginine-HCl [12C6, 14N4])- or “heavy” (L-Lysine-2HCl [13C6, 15N2], L-Arginine-HCl [13C6, 15N4])-labeling RPMI 1640 medium was used to culture human ovarian cancer TOV-21G cells for 10 passages, followed by the treatment of 0.1% dimethylsulfoxide for 24 h and 20 µM ivermectin for 24 h, respectively. The light- and heavy-isotope-labeled proteins were equally mixed (1:1) for digestion with trypsin. The tryptic peptide mixture was fractionated with liquid chromatography and analyzed with tandem mass spectrometry. In total, 4,447 proteins were identified in ivermectin-treated TOV-21G cells in relation to controls. Those proteins were enriched in 89 statistically significant signaling pathways and 62 statistically significant biological processes. These findings clearly demonstrated that SILAC quantitative proteomics was a useful and reliable method to study ivermectin-related proteomic changes in cancer cells, which in combination with molecular pathway networks and biological processes enrichments provided more comprehensive insights into molecular mechanisms of ivermectin in inhibiting TOV-21G cells.",book:{id:"10797",title:"Cell Culture - Advanced Technology and Applications in Medical and Life Sciences",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg"},signatures:"Na Li and Xianquan Zhan"},{id:"79031",title:"Isolation and Expansion of Mesenchymal Stem/Stromal Cells, Functional Assays and Long-Term Culture Associated Alterations of Cellular Properties",slug:"isolation-and-expansion-of-mesenchymal-stem-stromal-cells-functional-assays-and-long-term-culture-as",totalDownloads:78,totalDimensionsCites:0,doi:"10.5772/intechopen.100286",abstract:"Mesenchymal stem cell/stromal cells (MSCs) can differentiate into a variety of cell types, including osteocytes, adipocytes and chondrocytes. MSCs are present in the multiple types of adult tissue, such as bone marrow, adipose tissue, and various neonatal birth-associated tissues. Given their self-renewal and differentiation potential, immunomodulatory and paracrine properties, and lacking major histocompatibility complex (MHC) class II molecules, MSCs have attracted much attention for stem cell-based translational medicine research. Due to a very low frequency in different types of tissue, MSCs can be isolated and expanded in vitro to derive sufficient cell numbers prior to the clinical applications. In this chapter, the methodology to obtain primary bone marrow-derived MSCs as well as their in vitro culture expansion will be described. To assess the functional properties, differentiation assays, including osteogenesis, chondrogenesis and adipogenesis, 3-D culture of MSCs and co-culture of MSCs and tumor cells are also provided. Finally, the long-term culture associated alterations of MSCs, such as replicative senescence and spontaneous transformation, will be discussed for better understanding of the use of MSCs at the early stages for safe and effective cell-based therapy.",book:{id:"10797",title:"Cell Culture - Advanced Technology and Applications in Medical and Life Sciences",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg"},signatures:"Chenghai Li"},{id:"78960",title:"Two-Dimensional and Three-Dimensional Cell Culture and Their Applications",slug:"two-dimensional-and-three-dimensional-cell-culture-and-their-applications",totalDownloads:250,totalDimensionsCites:0,doi:"10.5772/intechopen.100382",abstract:"Cell culture is one of the most important and commonly used in vitro tools to comprehend various aspects of cells or tissues of a living body such as cell biology, tissue morphology, mechanism of diseases, cell signaling, drug action, cancer research and also finds its great importance in preclinical trials of various drugs. There are two major types of cell cultures that are most commonly used- two-dimensional (2D) and three-dimensional culture (3D). The former has been used since the 1900s, owing to its simplicity and low-cost maintenance as it forms a monolayer, while the latter being the advanced version and currently most worked upon. This chapter intends to provide the true meaning and significance to both cultures. It starts by making a clear distinction between the two and proceeds further to discuss their different applications in vitro. The significance of 2D culture is projected through different assays and therapeutic treatment to understand cell motility and treatment of diseases, whereas 3D culture includes different models and spheroid structures consisting of multiple layers of cells, and puts a light on its use in drug discovery and development. The chapter is concluded with a detailed account of the production of therapeutic proteins by the use of cells.",book:{id:"10797",title:"Cell Culture - Advanced Technology and Applications in Medical and Life Sciences",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg"},signatures:"Sangeeta Ballav, Ankita Jaywant Deshmukh, Shafina Siddiqui, Jyotirmoi Aich and Soumya Basu"},{id:"78812",title:"Nanotechnology Application and Intellectual Property Right Prospects of Mammalian Cell Culture",slug:"nanotechnology-application-and-intellectual-property-right-prospects-of-mammalian-cell-culture",totalDownloads:121,totalDimensionsCites:1,doi:"10.5772/intechopen.99146",abstract:"The significant challenges faced by modern-day medicine include designing a target-specific drug delivery system with a controlled release mechanism, having the potential to avoid opsonization and reduce bio-toxicity. Nanoparticles are materials with nanoscale dimensions and maybe natural and synthetic in origin. Engineered nano-sized materials are playing an indispensable role in the field of nanomedicine and nanobiotechnology. Besides, engineered nano-sized particles impart therapeutic applications with enhanced specificity because of their unique bespoke properties. Moreover, such application-customized nanoparticles offer an enormous possibility for their compatibility with different biological molecules like proteins, genetic materials, cell membranes, and organelles at the nano-bio frame. Besides, surface functionalization with targeting moieties such as small molecule ligands, monoclonal antibodies, aptamers, cell-penetrating peptides, and proteins facilitate nanoparticle-based specific tissue targeting. This review summarizes some of the advances in nanoparticle-based therapeutics and theranostics. A better understanding of idealistic preparation methods, physicochemical attributes, surface functionalization, biocompatibility can empower the potential translation of nanomaterials from the ‘bench-to-bedside’. In modern-day medicine, engineered nanoparticles have a wide range of demands ranging from bio-imaging, theranostics, tissue engineering, sensors, drug and nucleic acid delivery, and other pharmaceuticals applications. 2D and 3D mammalian cell-based assays are widely used to model diseases, screening of drugs, drug discovery, and toxicity analyses. Recent advances in cell culture technology and associated progress in nanotechnology have enabled researchers to study a wide variety of physiologically relevant questions. This chapter explores the properties of nanoparticles, different targeted delivery methods, biological analysis, and theranostics. Moreover, this chapter also emphasizes biosafety and bioethics associated with mammalian cell culture and discusses the significance of intellectual property rights from an industrial and academic perspective.",book:{id:"10797",title:"Cell Culture - Advanced Technology and Applications in Medical and Life Sciences",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg"},signatures:"Harikrishnareddy Rachamalla, Anubhab Mukherjee and Manash K. Paul"},{id:"78274",title:"A Brief Concept of Cell Culture: Challenges, Prospects and Applications",slug:"a-brief-concept-of-cell-culture-challenges-prospects-and-applications",totalDownloads:175,totalDimensionsCites:0,doi:"10.5772/intechopen.99387",abstract:"Cell culture is an in vitro technique in which cells, tissues, or organs (animal origin) are artificially grown with the support of an artificial environment that encompasses culture medium, CO2 level, pH indicator, temperature keeping tissues alive and growing appropriately. Organ culture, Primary explant culture, and Cell culture among them cell culture widely used for the understanding of cell growth, normal functions, identification of growth factors, viral vaccine development, recombinant DNA (rDNA) technology, and immunobiological research. Due to high feasibility, cell culture practices highly demandable in the pharmaceutical industry. As well as animal cell culture used in laboratory research to study the cytotoxicity of new drug metabolic studies, aging, therapeutic proteins, the effects of drugs and toxic compounds on the cells and mutagenesis and carcinogenesis. There are a lot of issues in cell culture, Mycoplasma is one of the major. During cell culture, a single antibiotic often cannot kill the mycoplasma. Besides, culture media, pH indicator, incubation, cryopreservation, thawing, passaging of cells, and trypsinization have a great impact on cell culture. This chapter will help the reader to understand the whole process of cell culture and its applications, which will take them one step forward in their virology and cell culture research along with inspiration. This chapter also aids in the concept of cell count, cell suspension, CCF measurement, MOI (Multiplicity of Infection), and cell infection. Eventually, the reader will get a crystal clear concept of cell culture.",book:{id:"10797",title:"Cell Culture - Advanced Technology and Applications in Medical and Life Sciences",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg"},signatures:"Md. Salauddin"}],onlineFirstChaptersTotal:5},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:10,editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",institutionString:null,institution:{name:"Universidade Paulista",institutionURL:null,country:{name:"Brazil"}}},{id:"191123",title:"Dr.",name:"Juan José",middleName:null,surname:"Valdez-Alarcón",slug:"juan-jose-valdez-alarcon",fullName:"Juan José Valdez-Alarcón",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBfcQAG/Profile_Picture_1631354558068",institutionString:"Universidad Michoacana de San Nicolás de Hidalgo",institution:{name:"Universidad Michoacana de San Nicolás de Hidalgo",institutionURL:null,country:{name:"Mexico"}}},{id:"161556",title:"Dr.",name:"Maria Dos Anjos",middleName:null,surname:"Pires",slug:"maria-dos-anjos-pires",fullName:"Maria Dos Anjos Pires",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS8q2QAC/Profile_Picture_1633432838418",institutionString:null,institution:{name:"University of Trás-os-Montes and Alto Douro",institutionURL:null,country:{name:"Portugal"}}},{id:"209839",title:"Dr.",name:"Marina",middleName:null,surname:"Spinu",slug:"marina-spinu",fullName:"Marina Spinu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLXpQAO/Profile_Picture_1630044895475",institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}},{id:"92185",title:"Dr.",name:"Sara",middleName:null,surname:"Savic",slug:"sara-savic",fullName:"Sara Savic",profilePictureURL:"https://mts.intechopen.com/storage/users/92185/images/system/92185.jfif",institutionString:'Scientific Veterinary Institute "Novi Sad"',institution:{name:'Scientific Veterinary Institute "Novi Sad"',institutionURL:null,country:{name:"Serbia"}}}]},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. 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Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}},{id:"351158",title:"Prof.",name:"David W.",middleName:null,surname:"Anderson",slug:"david-w.-anderson",fullName:"David W. Anderson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Calgary",country:{name:"Canada"}}}]}},subseries:{item:{id:"92",type:"subseries",title:"Health and Wellbeing",keywords:"Ecology, Ecological, Nature, Health, Wellbeing, Health production",scope:"\r\n\tSustainable approaches to health and wellbeing in our COVID 19 recovery needs to focus on ecological approaches that prioritize our relationships with each other, and include engagement with nature, the arts and our heritage. This will ensure that we discover ways to live in our world that allows us and other beings to flourish. We can no longer rely on medicalized approaches to health that wait for people to become ill before attempting to treat them. We need to live in harmony with nature and rediscover the beauty and balance in our everyday lives and surroundings, which contribute to our well-being and that of all other creatures on the planet. This topic will provide insights and knowledge into how to achieve this change in health care that is based on ecologically sustainable practices.
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