Table shows disorders characterized in AA and the mechanism of action of MSCs in AA pathology.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"9560",leadTitle:null,fullTitle:"Creativity - A Force to Innovation",title:"Creativity",subtitle:"A Force to Innovation",reviewType:"peer-reviewed",abstract:"Creativity and innovation go hand in hand. This book presents a plethora of creative interventions in education, culture, expressions, communications, and other areas. Each chapter brings forth a core idea well attested on the scales of creative interventions. It is a collaborative effort to bring forth multidisciplinary creativity in the ever-evolving world of design, communication, and possibilities. There is really no logical order to the book. You do not necessarily have to start at the beginning, just find a chapter that interests you and read. I hope that you find the book stimulating as well as informative.",isbn:"978-1-83881-041-2",printIsbn:"978-1-83881-040-5",pdfIsbn:"978-1-83881-042-9",doi:"10.5772/intechopen.87355",price:119,priceEur:129,priceUsd:155,slug:"creativity-a-force-to-innovation",numberOfPages:188,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"58f740bc17807d5d88d647c525857b11",bookSignature:"Pooja Jain",publishedDate:"March 3rd 2021",coverURL:"https://cdn.intechopen.com/books/images_new/9560.jpg",numberOfDownloads:5713,numberOfWosCitations:0,numberOfCrossrefCitations:3,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:4,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:7,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 25th 2020",dateEndSecondStepPublish:"June 15th 2020",dateEndThirdStepPublish:"August 14th 2020",dateEndFourthStepPublish:"November 2nd 2020",dateEndFifthStepPublish:"January 1st 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"316765",title:"Dr.",name:"Pooja",middleName:null,surname:"Jain",slug:"pooja-jain",fullName:"Pooja Jain",profilePictureURL:"https://mts.intechopen.com/storage/users/316765/images/system/316765.jpg",biography:"Pooja Jain, Ph.D., is an academician in graphic design and visual communication. She holds a Ph.D. in Advertising from Delhi University, India, and is an avid researcher with several publications in international peer-reviewed journals and paper presentations in national and international conferences. Currently, she is actively working on multiple startups and corporate projects as a freelance design practitioner. Dr. Jain is professionally associated with many eminent Indian institutions of art and design, serving in multiple roles including external examiner, paper setter, Ph.D. advisor, career counselor, advisory board member, and others. At present, Dr. Jain is working as an academic coordinator and faculty member in the Department of Visual Communication at Srishti Institute of Art Design & Technology, Bengaluru, India.",institutionString:"Srishti Institute of Art Design and Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Srishti Institute of Art Design and Technology",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"265",title:"Education",slug:"social-sciences-education"}],chapters:[{id:"73497",title:"Peace Education in Times of Covid-19: Rethinking Other Kind of Logic from the Imagination, Fantasy, Creativity and Utopia",doi:"10.5772/intechopen.93895",slug:"peace-education-in-times-of-covid-19-rethinking-other-kind-of-logic-from-the-imagination-fantasy-cre",totalDownloads:419,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This article aims to reflect on the challenges of peace education in times of Covid-19 global pandemic from a positive perspective, understood as a new opportunity for education to consider the teaching of how to make peace from our daily experiences; and in this way, humanity can forge a more peaceful future. In this task, the use of imagination, fantasy and creativity as educational resources will be revalued. Likewise, utopia is proposed as that unknown horizon, still to come, that will show us, in the face of so many doubts and uncertainties, those possible scenarios which will motivate us to continue working for cultures of peace. This reflection starts from the Reconstructive-Empowering Peace Education approach that I have been proposing in my research as a member of the Interuniversity Institute of Social Development and Peace.",signatures:"Sofia Herrero Rico",downloadPdfUrl:"/chapter/pdf-download/73497",previewPdfUrl:"/chapter/pdf-preview/73497",authors:[{id:"322093",title:"Dr.",name:"Sofia",surname:"Herrero Rico",slug:"sofia-herrero-rico",fullName:"Sofia Herrero Rico"}],corrections:null},{id:"73321",title:"Dare to be Disruptive! The Social Stigma toward Creativity in Higher Education and a Proposed Antidote",doi:"10.5772/intechopen.93663",slug:"dare-to-be-disruptive-the-social-stigma-toward-creativity-in-higher-education-and-a-proposed-antidot",totalDownloads:607,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Despite the fact that creativity has been named one of the top-10 skills necessary for success in the twenty-first century, the current educational system in the developed world stifles creativity through its focus on convergent thinking and standardized testing. We propose that a stigma toward creativity exists among educators, which prevents successful implementation of creative teaching and fostering creativity within the classroom. The proposed root cause of the stigma toward creativity in education – that creativity is perceived as disruptive – is examined through the lens of the Adaptor-Innovator theory of creativity and the implicit and explicit theories of creativity, as well as the psychological factors inherent to the social construction of stigma. Seminal and current research in the fields of creativity studies and communication studies offer insight into this phenomenon. The chapter concludes by proposing an antidote to address and fight this stigma as seen through the lens of Fishbein and Ajzen’s Theory of Reasoned Action.",signatures:"Amanda Lohiser and Gerard J. Puccio",downloadPdfUrl:"/chapter/pdf-download/73321",previewPdfUrl:"/chapter/pdf-preview/73321",authors:[{id:"323876",title:"Prof.",name:"Gerard",surname:"Puccio",slug:"gerard-puccio",fullName:"Gerard Puccio"},{id:"327541",title:"Dr.",name:"Amanda",surname:"Lohiser",slug:"amanda-lohiser",fullName:"Amanda Lohiser"}],corrections:null},{id:"73781",title:"The Light Penetrates Silence: Kolok Dance Study in Bengkala Village, Buleleng, Bali",doi:"10.5772/intechopen.94397",slug:"the-light-penetrates-silence-em-kolok-em-dance-study-in-bengkala-village-buleleng-bali",totalDownloads:358,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Art is an expression of the pure soul of humans that is not limited by physical. Therefore, everyone can express their art in various forms of art acts such as dancing, singing, painting, and others. This occurs to the Kolok (mute) community in Bengkala village where they express their artistic spirit by dancing. The Kolok community in this village dances Janger Kolok Dance, Baris Bebek Bingar Bengkala (Bebila) Dance or Baris Bebila Dance, and Jalak Anguci Starling Dance. This dance illustrates the joy and excitement of the mute people in Bengkala village who are able to surpass their limitations into an opportunity to fill themselves up. The creation of this dance is motivated by esthetic, economic and religious reasons. Structurally, all Kolok dances in Bengkala follow the same pattern of general dance but there are adjustments to the conditions of the dancers. This dance has the meaning of struggle, discipline, hard work, cooperation, entertainment based on excitement through the limitations of those who are deaf Kolok.",signatures:"Ida Ayu Trisnawati",downloadPdfUrl:"/chapter/pdf-download/73781",previewPdfUrl:"/chapter/pdf-preview/73781",authors:[{id:"322558",title:"Dr.",name:"Ida Ayu",surname:"Trisnawati",slug:"ida-ayu-trisnawati",fullName:"Ida Ayu Trisnawati"}],corrections:null},{id:"73320",title:"Creativity in Public Relations: The Case from Croatia – How to Make the History of the Insurance Company “Cool”",doi:"10.5772/intechopen.93689",slug:"creativity-in-public-relations-the-case-from-croatia-how-to-make-the-history-of-the-insurance-compan",totalDownloads:400,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The chapter deals with the role of creativity in public relations. Creativity is usually associated with marketing and design, while public relations is associated with information and communication management, respectively, as the information and educational component, but often as persuasion. However, in modern conditions in which there is a kind of inflation of content transmitted by public relations experts to the media and the public, it is very difficult to fight for media attention and public attention. Therefore, the public relations professional is forced to bring creativity to the way of communicating, presenting key messages, and achieving communication goals. For that reason, creativity is becoming an essential strategic and tactical tool for public relations professionals to shift the task to a higher level. The authors present a case study of the leading Croatian insurance company—Croatia osiguranje, which had the challenging task of using the anniversary to communicate its own identity and values, strengthen its image, and attract new clients. The project “Croatia je Hrvatska” has received a number of national and international awards and can serve as an excellent example of synergy between communication management and creativity in achieving communication and business goals.",signatures:"Bozo Skoko and Dejan Gluvacevic",downloadPdfUrl:"/chapter/pdf-download/73320",previewPdfUrl:"/chapter/pdf-preview/73320",authors:[{id:"322984",title:"Prof.",name:"Bozo",surname:"Skoko",slug:"bozo-skoko",fullName:"Bozo Skoko"},{id:"323694",title:"Dr.",name:"Dejan",surname:"Gluvacevic",slug:"dejan-gluvacevic",fullName:"Dejan Gluvacevic"}],corrections:null},{id:"73747",title:"Assessing Creativity and Innovation in Islam",doi:"10.5772/intechopen.94110",slug:"assessing-creativity-and-innovation-in-islam",totalDownloads:736,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"The purpose of this study is to understand how Islam assesses creativity—specifically, to determine if an Islamic framework for assessing creativity can be identified. Islam does not provide a framework for assessing creativity, but Islamic scholars continue to assess creativity in the absence of this framework. This study was conducted with the assistance of seven informants from seven leading Islamic traditions based in the UK. Each informant provided a unique insight into their understanding and interpretations of Islamic scriptures and texts in relation to creativity and to determine how creativity in Islam is assessed.",signatures:"Cameron Iqbal",downloadPdfUrl:"/chapter/pdf-download/73747",previewPdfUrl:"/chapter/pdf-preview/73747",authors:[{id:"322647",title:"Dr.",name:"Cameron",surname:"Iqbal",slug:"cameron-iqbal",fullName:"Cameron Iqbal"}],corrections:null},{id:"73601",title:"A Design Thinking Approach for Museum Institutions",doi:"10.5772/intechopen.93950",slug:"a-design-thinking-approach-for-museum-institutions",totalDownloads:666,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In these recent years, museum institutions are facing challenges such as deepening diversity among audiences and within the workforce, shifting authority and keeping pace with the creation of a digital offering to be provided in the new shared economy. Additionally, museums cannot just deliver knowledge as information anymore. They are forced to seek to be relevant and meaningful for the audiences and the society. Thus, a visitor-centered approach needs to be developed. The design thinking framework can help museum professionals to face the challenges they handle in today’s world. Indeed, this approach is focused on people and not on a specific product or service. The goal is to understand the needs of customers, their wishes and, based on this information, find the best solution to respond to the type of problem identified or the strategy to be developed. For this reason, the ratio of this discipline provides that people are stimulated to find alternative, creative, and innovative solutions designed and built on the reality of the facts and not dictated by instinct. The aim of this chapter is to investigate the characteristics of the design thinking approach and to analyze how this framework can be implemented in museum institutions.",signatures:"Luigi Nasta and Luca Pirolo",downloadPdfUrl:"/chapter/pdf-download/73601",previewPdfUrl:"/chapter/pdf-preview/73601",authors:[{id:"168999",title:"Dr.",name:"Luca",surname:"Pirolo",slug:"luca-pirolo",fullName:"Luca Pirolo"},{id:"262571",title:"Ph.D.",name:"Luigi",surname:"Nasta",slug:"luigi-nasta",fullName:"Luigi Nasta"}],corrections:null},{id:"73301",title:"A Framework for Assessing the Creativity Manifested in the Emergent Outcomes of Open-Ended Tasks Based on a “Puzzle”",doi:"10.5772/intechopen.93688",slug:"a-framework-for-assessing-the-creativity-manifested-in-the-emergent-outcomes-of-open-ended-tasks-bas",totalDownloads:391,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In creative disciplines, “basic design” is offered as a foundation course to foster diverse thinking skills and creativity. The tasks are generally framed based on the principles such as “progressive transformation,” “borrowing,” and “deconstruction.” The emergent outcomes of such tasks are unique and very challenging to evaluate. In this context, this chapter aims to discuss a framework for assessing the creativity manifested in the emergent outcomes of generative tasks based on a puzzle. Three tasks based on “TANGRAM,” a dissection puzzle with slight variations, were formulated. The task was introduced as a practicum at a faculty development program conducted at the AMS School of Architecture in association with the Council of Architecture, India. Besides, the framed tasks were introduced as an assignment for a theory course and also as a basic design task at the Department of architecture, Sathyabama Institute of Science and Technology, India. The emergent outcomes are explored, decoded, and analyzed. The findings are triangulated and a framework is developed that can be suitably modified so as to investigate the degrees of creativity manifested in the emergent outcomes of an open-ended task.",signatures:"Arulmalar Ramaraj and Jothilakshmy Nagammal",downloadPdfUrl:"/chapter/pdf-download/73301",previewPdfUrl:"/chapter/pdf-preview/73301",authors:[{id:"321996",title:"Mrs.",name:"Arulmalar",surname:"Ramaraj",slug:"arulmalar-ramaraj",fullName:"Arulmalar Ramaraj"},{id:"328627",title:"Dr.",name:"Jothilakshmy",surname:"Nagammal",slug:"jothilakshmy-nagammal",fullName:"Jothilakshmy Nagammal"}],corrections:null},{id:"73433",title:"Assessment of Creativity: Theories and Methods",doi:"10.5772/intechopen.93971",slug:"assessment-of-creativity-theories-and-methods",totalDownloads:1042,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The history of creativity assessment is as old as the concept itself. Researchers from various cultures and disciplines attempted to define the concept of creativity and offer a valid way to assess it. Creativity is generally defined as the ability to produce work that is novel and appropriate. Researchers in the field attempted to measure creativity from different perspectives and tried to answer the question like “What are the mental processes involved in creative thought?, Which personality traits are associated with creativity?, How can a product can be judged to be creative? and, What are the external forces that affect creativity?”. The answers of these questions constitute the most commonly used creativity assessment instruments. This chapter presents a brief overview on assessment of creativity through the eyes of the psychometric perspective and discusses the strengths and weaknesses of various instruments used in the field.",signatures:"Esra Kanlı",downloadPdfUrl:"/chapter/pdf-download/73433",previewPdfUrl:"/chapter/pdf-preview/73433",authors:[{id:"323220",title:"Dr.",name:"Esra",surname:"Kanli",slug:"esra-kanli",fullName:"Esra Kanli"}],corrections:null},{id:"74760",title:"Using Ideation Grids to Power Collaborative Creativity in Face-to-Face and Remote Innovation Sessions",doi:"10.5772/intechopen.93850",slug:"using-ideation-grids-to-power-collaborative-creativity-in-face-to-face-and-remote-innovation-session",totalDownloads:590,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"This chapter outlines a design-led approach to ideation. Ideation is a structured way to develop innovative ideas via collaborative workshops. The chapter starts by contextualising ideation within an overview of the ways in which design supports innovation both as a definable mindset as well as via a standardised methodology. People, behavioural approaches and methods for design innovation are described in section three. Design Thinking is positioned from this analysis as a practical asset in the innovators’ toolkit and also as a natural inheritor and embodiment of applied creativity. The chapter concludes by detailing how ideation works in practice and describes an evolved set of techniques, principles and methods for maximising the value of the approach through ideation grids that can be used in face-to-face and remote innovation work.",signatures:"John Knight, Elliot Ross and Dan Fitton",downloadPdfUrl:"/chapter/pdf-download/74760",previewPdfUrl:"/chapter/pdf-preview/74760",authors:[{id:"321992",title:"Dr.",name:"John",surname:"Knight",slug:"john-knight",fullName:"John Knight"},{id:"322330",title:"Dr.",name:"Dan",surname:"Fitton",slug:"dan-fitton",fullName:"Dan Fitton"},{id:"322331",title:"Mr.",name:"Elliot",surname:"Ross",slug:"elliot-ross",fullName:"Elliot Ross"}],corrections:null},{id:"73199",title:"Examining the Structures and Textures of Gender-Based Japanese Advertisements",doi:"10.5772/intechopen.93475",slug:"examining-the-structures-and-textures-of-gender-based-japanese-advertisements",totalDownloads:509,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"For the non-Japanese native speakers, including foreigner Japanese learners, watching a Japanese advertisement commercial (CM) can be entertaining due to their unique language and visual presentation. There are some Japanese commercials based on display, for example, the 2D advertisements in magazines or posters and the 3D video-based advertisements accompanied by side comments that can always be seen on YouTube videos. This research is based on Japanese commercials (CMs), in the form of YouTube videos, with the same product types but showing gender differences for men and women. Thus, the main research objective is to examine the structure and texture of Japanese commercials (CMs) in terms of how they market the same product type for both men and women. This research has find that most of the Japanese advertisements for men’s products use a more straightforward style of speaking with an opening and closing commercial structure, and there is a short description of the commercial content. Advertisements for women’s products, meanwhile, are more varied in their opening, closing, and content, as well as in the product introduction and narration. The tenses used in men’s products usually contain present tenses and imperative sentences, which are also prominent. While some advertisers typically use the present tenses for women’s products as well as men’s products, they also use past tenses and different Japanese dictionary formats. Proper sentences also used in the advertisements for women’s products. As for lexicon, or word choice, used for men’s products, only zo and ore are used. The lexicon in women’s products, meanwhile, is more varied with kashira, wa, wayo, wane, no, noyo, none, koto, and kotoyo that being used. For advertisements with high selling power, the structure comprises just an opening and closing, and they are more straightforward and less wordy.",signatures:"Sri Aju Indrowaty, Djatmika, Dwi Purnanto and Tatang Hariri",downloadPdfUrl:"/chapter/pdf-download/73199",previewPdfUrl:"/chapter/pdf-preview/73199",authors:[{id:"322178",title:"Ph.D. Student",name:"Sri Aju",surname:"Indrowaty",slug:"sri-aju-indrowaty",fullName:"Sri Aju Indrowaty"},{id:"322609",title:"Prof.",name:"Djatmika",surname:null,slug:"djatmika",fullName:"Djatmika null"},{id:"322610",title:"Dr.",name:"Dwi",surname:"Purnanto",slug:"dwi-purnanto",fullName:"Dwi Purnanto"},{id:"322611",title:"Dr.",name:"Tatang",surname:"Hariri",slug:"tatang-hariri",fullName:"Tatang Hariri"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6674",title:"Contemporary Pedagogies in Teacher Education and 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\r\n\tNowadays, high-performance carbon fibers and their advanced composites have been increasingly utilized in many cutting-edge fields and play an irreplaceable role in all aspects of modern society. It is very necessary to summarize a professional book involving the latest developments and research status of carbon fibers comprehensively and systematically. Undoubtedly, how to further improve the comprehensive performance of polyacrylonitrile-based carbon fibers at a price competitive becomes a challenge, and accelerating progress in the practical applications of carbon fibers in the broad field of advanced composites is overwhelming. Currently, the low-cost production, recycling, and reuse of carbon fibers have drawn widespread attention. Pitch-based carbon fibers and lignin-based carbon fibers have received much attention due to their low-cost superiority, tunable structure-property, and promising applications. In particular, mesophase pitch-based carbon fibers with superhigh Young’s modulus and thermal conductivity become the research hotspots and frontiers and show an absolute advantage in the thermal management field. Recently, versatile carbon nanofibers made by electrospinning technique and activated carbon fibers with the tailorable porous structure for energy and environment inspired intense research interest. Therefore, this book will mainly focus on recent advances in the preparation, characterization, and applications of carbon fibers with high performance and multifunction and provide a useful reference for the readers.
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He won the prize for the Excellent Doctoral Dissertation of Hubei Province in 2013. He has been an academic visitor in the Department of Chemical Engineering at Imperial College London during 2019.02-2020.02. Now he works as a professor at School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology. \nSince 2002, he has been engaged in the research, development and application of new carbon materials. Recently his research mainly focuses on the development of carbonaceous mesophase, the preparation of pitch-based carbon fibers and their high-performance composites, the applications of carbon-based high-conductive materials for thermal management and carbon-based high-efficient catalysts for hydrogen-production and hydrogenation. Up to now, the research work has received many funded research projects from the government and enterprise. As a principal investigator, he has chaired one National Natural Science Foundation of China (No. 52072275) and executively completed five ones (Nos. 50672070, 50972110, 91016003, 51372177, U1960106). 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The autoimmunity process in AA occurs due to the activation of the oligoclonal cytotoxic T cells that will lead the hematopoietic cells to apoptosis. Its triggering occurs by the imbalance between CD8 +, CD4 +, T-Helper (Th), Th type 1 (Th1), Th type 2 (Th2), Th17 type (Th17), Natural Killer (NK) and T-regulatory cells (Treg). Besides, there is also an abnormal production of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and transformed growth factor (TGF) [3, 4, 5, 6, 7].
\nBenefits of MSCs paracrine effect (immunomodulatory) on immune cells imbalance. MSCs secrete many soluble mediators, including anti-inflammatory cytokines stimulation that regulates APCs functions capable to decrease proliferation of DCs and regulate macrophage activity by polarizing proinflammatory phenotype (M1) to anti-inflammatory phenotype (M2). Therefore, they are responsible for humoral response regulation by the decrease of B cells proliferation and antibodies production. The APCs are also capable to regulate the T cell activities as well as inhibit cytotoxic T cell proliferation and upregulation and increase of Treg cells. MSCs may also promote the decrease of proinflammatory cytokines secretion. And act on the homing regulation of HSCs mechanism on stages of adhesion, expansion, and migration through chemokine and other factors secretion.
AA disorders x MSC benefits | \n|
---|---|
Aberrant secretion of pro-inflammatory cytokines ↑IFN-γ ↑TNF-α ↑IL-17 ↑IL-2; | \nImmunomodulatory effect: Decreased secretion of proinflammatory cytokines, ↓IFN-γ ↓TNF-α ↓IL-17 ↓IL-2; | \n
Imbalance between CD8+ and CD4+ T cells; ↑ Cytotoxic T cell ↓Treg | \nRegulation of T cell activity and Treg cell proliferation ↓ Cytotoxic T cell ↑Treg | \n
Apoptosis of HSC and progenitor cells ↑ Apoptosis | \nProtect BM by antiapoptotic properties ↓ Apoptosis | \n
BM hypoplasia | \nRecovery of BM ↑ Hematopoiesis improvements ↑ CXCL12 ↑FLT3LG ↑TPO ↑IL-6 | \n
Abnormal APC activation ↑ DCs ↑ Macrophage | \nRegulate APCs functions ↓ DCs maturation and proliferation and ↓ Macrophages M1 activation ↑ Macrophages M2 activation | \n
Abnormal humoral response ↑ B cells ↑ Antibodies production | \nRegulate humoral response ↓ B cells ↓ Antibodies production | \n
Irregular activity of NK cells ↑ Cytotoxicity of NK cells | \n↓ Cytotoxicity of NK cells | \n
Table shows disorders characterized in AA and the mechanism of action of MSCs in AA pathology.
MSC can decrease secretion of pro-inflammatory cytokines such as TGF, IFN-γ TNF-α, IL-17, regulate T cell activity, inhibit proliferation of cytotoxic T cells and stimulate Treg activity. MSC has anti-apoptotic properties, protects BM environment and recovery BM through cytoprotective effect and stimulates macrophages M2 activation and hematopoiesis improvements. MSCs may also regulate APCs functions, humoral response, and cytotoxicity of NK cells.
For severe cases, immunosuppressive therapy is accepted as the first-line treatment option and the allogeneic transplantation of BM and hematopoietic stem cells (HSCs). However, 30–40% of patients with severe aplastic anemia (SAA) remain pancytopenia following the treatment. The transplant option still has a restricted number of compatibility between suitable donors. Additionally, patients aged >50 years are not eligible for transplant [8].
\nA new viable alternative for the treatment of AA has been sought and the use of mesenchymal stem (MSCs) therapy may be a promising therapeutic candidate mainly because of their hypoimmunogenicity and the lack of rejection after transplants and immunomodulatory effects, which may promote decreasing the symptoms of the disease [9, 10]. These benefits are attributed to the paracrine effects, above all by its ability to regulate the immune system [11].
\nActually, is known that MSCs have wide therapeutically potential attributed by paracrine effects and the past decades have seen explosion research directed to understand better these MSCs mechanism and function [12]. One of the main and most important features of MSCs is the low expression of human leukocyte antigen (HLA) class I, with no expression of HLA class II. This feature allows the cell to be characterized as hypoimmunogenic, since it does not stimulate the patient’s immune system and can be used safely in transplants [13]. More recently, the studies showed that the main cause of AA is autoimmunity. Through the secretion of bioactive molecules, MSCs have the capacity of regulating immune responses. The mechanism of MSCs may decrease secretion of proinflammatory cytokines such as transforming growth factor (TGF), IFN-γ TNF-α, interleukin (IL)-17 and increase secretion of many soluble mediators, including anti-inflammatory cytokines stimulation that inhibit antigen-presenting cells (APCs) functions, which are capable to decrease proliferation of dendritic cells (DCs) and regulate macrophage activity by polarizing proinflammatory phenotype (M1) to anti-inflammatory phenotype (M2) [14, 15]. Therefore, the decrease of B cells proliferation and antibodies production and adjustment of T cells activities as well as inhibit the proliferation of cytotoxic T cells and stimulate Treg activity [16].
\nMSCs therapy has gained space due to its vast therapeutic potentials such as immunomodulation mechanisms and main safety as bioproduct. Thus, this chapter will discuss the challenges of allogeneic MSCs as an alternative for an efficient therapeutic in AA immune-mediated treatment.
\nAA is a disorder characterized by BM hypocellularity, and peripheral blood pancytopenia due to a deficit of HSCs. It affects mostly children, young adults, and adults, over 60 years of age [17]. This condition can be similar to other hematologic disorders, however, in most cases, the AA is caused by reduced HSCs function, an increase in HSCs apoptosis level, consequently, the decreased of HSCs and hematopoietic progenitors and lastly, microenvironment fat replacement [18, 19].
\nFollowing the patient diagnosis, AA can be considered as moderate or severe. The patients with pancytopenia may present symptoms of anemia purpura or skin hemorrhage, and in most of the cases there is an infection association, that may worsen the symptoms [20]. Three main criteria are used for the diagnostic: neutrophil count lower than 0.5 × 109 cells/L, reticulocyte count lower than 1% and platelet count lower than 20 × 109 cells/L [21]. To confirm acquired AA, the clinical case must be differentiated from other hematological diseases, as well as from the signs of malignant cell transformation or myelodysplasia [22].
\nNormally the first AA etiology is uncertain and for this reason, the disorder is considered heterogeneous in origin and characterized as idiopathic [23]. AA is associated with exposures to chemical agents (pesticides and benzene), cytotoxic drugs (antineoplastics, antibiotics, non-steroidal anti-inflammatory drugs), active viral infections exposure (Epstein Barr, hepatitis virus, human immunodeficiency virus parvovirus) and radiation exposure [18, 24, 25]. However, these causes considered secondary etiologies, since the studies are directed to the primary etiology of AA to autoimmunity [26, 27]. AA pathogenesis involves an immunity dysfunction, initially provoked by the activated T cells [23], which leads to an abnormal hematopoietic microenvironment, destruction of hematopoietic stem/progenitor cell and differentiation deficiency. These findings suggest that the immune system plays an important role in the pathogenesis of AA.
\nCurrently, the studies of AA etiology are focused on the immune mechanism of hematopoietic cells destruction. Many researchers [28, 29, 30, 31] have demonstrated that the dysfunction of T cells might be a key factor in recent characterization as an autoimmune disease [28]. Most of the acquired AA is the result of an immune-mediated process as an imbalance between CD8+ and CD4+ T cells, including Th1, Th2, Treg and Th17 cells, NK, and natural killer T cells (NK T) that leads to apoptosis of BM cells triggered by cytotoxic T cells activation [6, 17].
\nThe abnormal immunoregulatory cell functions observed in AA can be attributable to abnormal antigen stimulation and some inappropriate T cells activation [28]. Studies demonstrated that patients with AA have a significantly increased proportion of Th1 cells, and showed a reduced fraction of natural killer T cells and regulatory T cells, together with an increased level of TNF-α, a consequent elevation of IL-6, IL-8, and IL17 productions [18]. Additionally, there is also an abnormal production of proinflammatory cytokines including IFN-γ and TGF [4, 5, 28, 32]. The new T cells subset was characterized as Th17 and currently is known that both Th17 cells and the cytokine IL-17, which is secreted by Th17 cells, also is in an association with AA pathogenesis [31]. Studies showed that AA patients who presented an increase in the frequency of Th17 cells had a positive correlation with an increase in the IFN- γ and IL-17 expression. Autoimmunity promotes inflammatory Th17 immune responses that contributed to disease pathophysiology [29].
\nOtherwise, AA is attributed to inappropriate antigen stimulation and abnormal APCs activation [28], resulting in the priming of T cells specific for hematopoietic cells [33, 34]. APCs exhibit a significant increase in the expression of major histocompatibility class 2 (MHCII), increasing the recognition of CD4+ T cells. In AA, T cells are also stimulated by unknown antigens or abnormal APC activation as DCs and macrophages, which trigger a series of immune responses. Studies have shown that immunoregulatory cell dysfunction leads to a corresponding immune tolerance disorder and renders the body unable to recognize autologous hematopoietic cells [28].
\nAlthough the definitive mechanism has not been identified, some genetic factors are the targets of ongoing research, such as the molecular basis of the aberrant immune response and hematopoietic cell deficiency, telomere repair gene mutations in the target cells and unregulated T cell activation pathways and cytokine genes polymorphisms [9, 26, 28]. These changes in the nucleotide sequence and gene regulation are associated with an increased immune response and suggest a genetic basis for aberrant T cells activation in BM failure [35].
\nThe treatment depends on the severity of the disease, once for moderate cases are based on red blood cell (RBC) transfusions, on platelet transfusions to prevent bleeding, and on supportive care in association with antibiotic aiming to reestablish blood cell volume and prevent secondary infections [17]. However, the pancytopenia of many moderate cases may progress to severe [21]. For severe cases, immunosuppressive therapy is accepted as a first-line treatment option. However, 30–40% of patients with SAA remain pancytopenia following the treatment. Patients with SAA, which are refractory or have a relapse after immunosuppressive treatment, may undergo allogeneic hematopoietic stem cells transplantation (HSCT). However, about one-third of patients do not have a suitable donor for HSCT. Additionally, patients aged >50 years are not eligible for transplant [8].
\nFurthermore, the immunosuppressive drug treatment has several side effects on patients. On the other hand, the patients often do not respond adequately to the therapies and are not suitable for life treatment (refractory patients) [24]. Therefore, immunosuppressive drugs are considered supporting AA treatment, once it does not promote the cure [20].
\nGenerally, patients are treated with allogeneic HSCs or whole BM transplantations, which replace since HSCs, hematopoietic precursors, until differentiated bloodstream cells and immune system cells. However, in all types of transplants, the treatment involves a combination of immunosuppressive agents or radiation therapy to prevent and to eliminate residual host BM [24]. The transplantation success varies according to risk factors, such as age and mainly histocompatibility allogeneic HLA-matched sibling donors, which are rare for the majority of patients. Despite being well established for many years, the transplanted patients can trigger late complications, such as the development of graft versus host disease (GVHD) and infections, especially in patients who have received hematopoietic grafts from HLA antigen matched donor [36, 37]. Studies show that the incidence of GVHD after unrelated donor transplantation can achieve ∼14%, and overall survival index was 57% for all 8 HLA-loci matched transplants and 39% for 1-loci mismatched transplant [38]. Thus, for BM and HSCT, the immediate challenge is the extension of stem cell therapies to all patients, regardless of age, with a histocompatible sibling [24].
\nSince then a new viable alternative for the treatment of AA has been sought and the use of MSCs transplantation becomes of choice. The MSCs therapy may be a promising therapeutic candidate mainly because of their hypoimmunogenicity, the lack of rejection after transplants and immunomodulatory effects, which may promote decreasing the symptoms of the disease [39]. These benefits are attributed to MSCs paracrine effects, above all to their ability to regulate the immune system. MSCs may help for AA treatment, especially for autoimmune type [11].
\nMSCs are multipotent progenitors, which were first isolated from an adult organism by Friedenstein and colleagues in 1968, and described years later by Caplan and colleagues [40, 41]. These cells include firstly an inherent autocrine effect, as self-renewal and differentiation potential for a variety of cell types, as main adipocytes, osteoclasts, and chondrocytes [42], depending on the surrounding microenvironment conditions [43]. Currently, such cells have shown to be isolated from many postnatal and adult tissues, such as adipose tissue, umbilical cord, placenta, dental pulp, and others [44, 45].
\nInitially, the mechanism therapeutic potential of the MSCs was based only on the potential for regeneration through cellular self-renewal and its plasticity. Further studies have shown low engraft of MSCs in injured areas that questioned the hypothesis that MSCs repair tissue damage by replacing cell loss with newly differentiated cells [46, 47].
\nIt is known that MSCs have wide therapeutically potential attributed to paracrine effects and the past decades explosion research was directed to understand better these MSCs mechanism and function [12]. Although the therapeutic mechanisms of MSCs are not yet well characterized, it is possible to say that their paracrine effects consist in the secretion of bioactive molecules such as a variety of cytokines and growth factors as like anti-inflammatory, anti-apoptotic and angiogenic [46, 47, 48, 49, 50, 51].
\nMSCs can to migrate to the lesion site through signals from specific chemokines. This process called homing consists of the steps of activating adhesion molecules, rolling to the endothelium, adhesion, and migration to the tissue that is the source of chemokine inflammation production [52, 53]. The current hypothesis is that paracrine factors secreted by MSCs promote protective microenvironment and repair by local tissue-resident progenitor populations, favoring the hypothesis of detecting favorable effects even in the absence of the cells at lesion sites [54].
\nOne of the main and most important features of MSC is the low expression of HLA class I, with no expression of HLA class II. Also, MSCs do not appear to express the co-stimulatory molecules CD80 or CD86 required for effector T cell induction [55]. The absence of co-stimulatory molecules implies that any residual engagement of the T cell receptor on Th cells would result in absence of the normal immune response to a particular antigen and contribute to tolerance rather than allogeneic responses. This feature allows the cell to be characterized as hypoimmunogenic, since it does not stimulate the patient’s immune system and can be used safely in transplants [113]. As well, MSCs have properties attributed to immune functions, indicating their ability to immunomodulatory activity. Studies indicated that MSCs can regulate immune responses during chronic inflammation through the innate and adaptive immune system, regulating the recruitment and their function [56, 57].
\nThe paracrine effects of MSCs may have great importance in the treatment of autoimmune diseases. Through the secretion of bioactive molecules, MSCs have the capacity of regulating immune responses. These cells can regulate adaptive immune responses through multiple redundant pathways, interacting with various immune cells and secreting soluble mediators such as IL-6, IL-10, prostaglandin E2 (PGE2), nitric oxide (NO), transforming growth factor-β1 (TGF-β1), and hepatocyte growth factor (HGF), indoleamine-pyrrole 2, 3-dioxygenase (IDO) [58, 59]. They can regulate APCs activity, decreasing maturation and proliferation of DCs [14]. MSC also may regulate macrophage activity by polarizing its pro-inflammatory phenotype (M1) to its anti-inflammatory phenotype (M2) [15]. Therefore, suppress T cell proliferation and activation and regulate the differentiation of Th cells and act on the humoral response by inhibiting of B cell activation and antibody production [60]. MSCs may also reduce pro-inflammatory cytokines proliferation, such TNF-α, which has an important role of the pathogenesis of autoimmune diseases and chronic inflammation (Figure 1) [14, 16, 61].
\nThe first paracrine effect, showed for MSCs, was the capacity to support HSCs growth
At BM microenvironment, MSCs niche supports hematopoietic cells and produce factors recruiting HSCs and supporting hematopoiesis [64]. This mechanism occurs through chemokine secretion of C-X-C motif chemokine ligand 12 (CXCL12), which acts on the homing regulation of HSCs, regulating the stages of adhesion, expansion and migration [65, 66]. The secretion of other factors is also important in the proliferation of HSCs mechanisms such as Flt-3 ligand (FLT3LG) [67], thrombopoietin (TPO) [68] and IL-6 [17]. That despite being a proinflammatory cytokine in general, when IL-6 is secreted in BM microenvironment, is capable to stimulate hematopoiesis [69, 70].
\nMore recently, the studies showed that the main cause of AA is autoimmunity. This process occurs in the result of an imbalance between CD8 + and CD4 + T cells, including Th1, Th2, Th17, NK, leading to the death of hematopoietic cells and their precursors [28]. Many studies have hypothesized that the onset of the immune imbalance in AA begins by stimulating APCs through an unknown antigen resulting in the T cells activation [71]. Another important mechanism of MSCs is the immunomodulation mechanism. MSCs can act directly on AA imbalance by T cells suppression, inhibiting activation and proliferation of T cells [72]. MSCs also inhibit the secretion of two important cytokines present in the pathology of AA, the INF-γ and TNF-α and stimulate the proliferation of Treg, promoting the production of the anti-inflammatory cytokine IL-10 Table 1 [73, 74]. In addition, some studies also show that MSCs also acts through its anti-apoptotic effects [75].
\nIn the last years, several studies have been exploring intravenous administrations (IV) due to being safe and do not present morbidity risk for patients. However, still lack the data about the biodistribution mechanism of MSCs and about how these cells engraftment on the target organ, which is essential for the success of clinical studies. It is known that the biodistribution is influenced in vivo and in vitro conditions. Stromal cell-derived factor 1 (SDF-1) (also known as CXCL12) is upregulated at sites of injury and acts as a chemoattractant to recruit circulating or residing MSCs expressing its cognate receptor CXC chemokine receptor 4 (CXCR4). It has been demonstrated that the CXCR4-SDF-1 axis is critical for BM homing [76]. Diverse studies demonstrate that some in vitro conditions may influence the expression of adhesion molecules [77, 78]. For instance, long expansion periods [79] and cells culturing at high density may reduce CXCR4 cell expression; the cells cultured at higher confluence secrete more metalloproteinase inhibitor 3, which decreases migration of MSCs when compared to those cultured at the low confluence [80]. Hypoxia condition may increase CXCR4 expression; on the other hand, hypoxia may decrease matrix metalloproteinase-2 secretion and an increase in membrane-type 1 matrix metalloproteinase [81].
\nIn vivo engraftment is influenced by interactions of MSCs with different types of immune cells that depend on their ability to respond to signals from the immune system. On the other hands, the MSCs biodistribution and homing depend on the host niche. Interesting the MSCs migration and homing to target tissue can be influenced positively by irradiation. It has been demonstrated an increased absolute number of human MSCs in the brain, heart, bone marrow, and muscles after total body irradiation and MSCs IV administrations in mice, when compared to the untreated control [82].
\nSome animal studies evidence that MSCs can engraftment in BM after systemic administration [83]. Studies in patients showed MSCs engraftment into BM 30 days after the second MSCs IV administration. Although, after MSCs infusion was observed no recovery of hematopoietic tissue, interstitial hemorrhage, edema, and all adipocytic necrosis disappeared in BM [84]. Other studies indicate the engraftment due to myeloid and plated recovery after HSCs and MSCs transplantation [85, 86].
\nMSCs have been implicated in immunomodulatory therapy, in particular, in GVHD treatment and as an adjunct to hematopoietic stem cell transplantation (HSCT) to help enhance engraftment [87, 88]. The first major clinical trial of MSCs (Prochymal) was for the treatment of steroid-refractory of GVHD (NCT00366145) [89, 90]. The primary endpoint of the study was complete remission at day 28 after allogeneic BM-MSCs infusion but was not significantly increased compared to placebo [89, 91]. In 2012, MSCs have bens conditional approval to treat children GVHD in Canada, based on subset analysis that suggested children with GVHD were responsive to MSCs [89, 92, 93]. Many new studies have been developed in recent years; however, a few of them have attempted to look at biological correlates of response to therapy. Isolated studies reported serum biomarkers of GVHD severity including IL-2,
Cotransplantation of HSCs with (umbilical cord) UC-MSCs has been performed to study whether the last will be able to support hematopoiesis, enhance the engraftment of HSCs, and reduce the incidence of GVHD following HSCT [98, 99, 100]. These studies include adult and children in AA patients [101, 102]. Stem cells application was mainly intravenous. In some of the studies multiple (five) infusions were used. All clinical protocols have been developed in the presence of traditional immunosuppressive protocol to prevent GVHD manifestation [98, 99, 100, 101, 102].
\nOne pioneer study, where the conditioning of patients was myeloablative or reduced, followed BM-MSCs treatment together with allogeneic HSCT. This study showed that co-transplantation of MSCs resulted in fast engraftment of absolute neutrophil count and platelets and 100% donor chimerism [87]. In turn, Yamei and co-workers (2014) demonstrate prolonged survival (follow up of 78 months) in 80.9% patients after cotransplantation of the culture-expanded third party donor-derived UC-MSCs in 21 young people with SAA undergoing haplo-HSCT [103]. Even so, the patients did not show infusion toxicity. This study showed that MSCs support
Nowadays there a few clinical studies using only MSCs single to treat AA. All studies used MSCs isolated from BM s and adult patients with severe or non-severe AA and refractory. The via of MSCs administration used was IV and the number of administrations was 2 until 5 depending on study in combination with conventional immunosuppressive therapy.
\nThe study development by Pang et al. showed, six of 18 patients (33.3%) achieved a complete response or a partial response to MSCs treatment [107]. In six patients, two achieved a complete response including recovery of three hematopoietic cell lines after MSCs therapy. Similar results was achieved by Cle et al. 2015 using MSCs being 22% of all patients (18 patients) presents hematologic response at 6 months after MSCs transplantation [108]. One clinical trial phase II conducted in China evaluated the MSC overall response rate and safety using a significant number of refractory AA younger patients (n = 72). The study performed full quality control of BM-MSCs production, which includes counts, viability, morphology, endotoxin, aseptic culture, immunophenotype. It was the first clinical study that showed significant results in BM functional recovery. The rate response of patients was 28.4% being that 6.8% complete response and 21.6% partial response after MSCs transplantation. Among patients with hematologic response, ten patients had normalization of cellularity BM followed for more than 1 year MSCs transplantation. Seven patients got adverse events such as fever and headaches. No other adverse events were observed in the study. At the follow-up endpoint, nine patients died. One patient with RAEB-II died of disease progression, two patients died of intracranial hemorrhages, and six patients died of serious infection [107]. In other two studies were reported adverse events such as, fever, hypoxemia, mild dyspnea and diarrhea during MSCs administration or some hours after MSCs injection, this phenomenon occurs in 2 of 16 patients [107] and 7 of the 18 patients [108]. None major adverse effects were reported in all studies during months of follow-up of each respective study. Fuillard et al., 2003 reported one death due to fungal infection and Cle et al. 2015 four patients died in consequence result of heart failure and bacterial or invasive fungal infections and none of the deaths in both studies were directly attributable to MSCs infusions [84, 108].
\nThese preliminary studies support the concept that MSCs replacement can improve BM stroma and may alleviate symptoms severe and non-severe AA patients. However, larger studies with a significant number of patients are needed to evaluate the utility of MSCs further.
\nThe progress in dissecting the underlying and complex pathophysiology of AA has been gain space over the past years in the hematology research community [26]. In addition to that, the need for an optimal alternative of a targeted treatment for this disorder. It is too soon to place the conventional AA treatment methods, but MSCs have gained space for demonstrating positive results in several AA clinical studies and other hematological diseases. The hypoimmunogenicity advantages, ensuring the absence of rejection in patients due to no expression of MHC class II, prevention and treatment of GVHD traditional transplants, and mainly immunomodulatory action presented [109]. Essential in the environment imbalance provoked by own immune system in people committed by the AA disorder. The MSCs are able in a modulating way to relieve the BM self-attack [110].
\nContemporary, personalized therapies are famous in the whole scientific world. The MSCs may fit into this class due to their paracrine effects. These cells can assist in diverse situations such as: migration, injury recovery, stimulates cells renewal, death cell prevention, anti-inflammatory and modulation of the immune system to control the autoimmune environment [111]. Thus, MSCs have the heterogeneous capacity in varied therapies field. And the patient may have alternative use according to their needs.
\nIn that event, the current way is providing the MSCs safety and acceptance by regulatory agencies as new biological product [112], which has already been proven to be more efficient than synthetic industries products [113]. And finally, implement the MSCs as ideal allogeneic transplant model, even for adequacy periods used as support for other established therapies.
\nThanks to everyone on the Cellavita team who helped us so much. Special thanks to the company Cellavita Ltda., for financial and professional supporting. And to Butantan Institute, to providing us space and the research opportunity.
\nThe authors declare no conflict of interest.
The benzimidazole nucleus is fairly unique among heterocyclic ring systems because of its outstanding structural similarity with various naturally occurring nucleotides [1]. In 1872, Hoebrecker synthesized the first benzimidazole molecule by the reduction of 2-nitro-4-methylacetanilide [2]. The biological significance is because its structure is similar to purines, and the importance of the applications depends on their abundance in most of the biologically active molecules. The discovery of the structure of vitamin B12 with 5, 6-dimethylbenzimidazole moiety in it, also elicited the search for benzimidazole - similar motifs for various pharmacological applications [3, 4, 5]. Following this, various research groups have outlined the synthesis and applications of benzimidazole [6, 7]. Benzene when fused with imidazole results in the formation of benzimidazole (
Benzimidazole (compound
The greater reactivity of the 2nd position towards various electrophiles and nucleophiles is the outcome of tautomerization. Many drugs contain the benzimidazole nucleus as a core unit and have a widespread application in the pharmaceutical field [8, 9, 10, 11, 12, 13, 14]. The presence of benzimidazole pharmacophore in the various branches of medical science is inexplicable. The therapeutic uses of benzimidazole include anticancer [15, 16, 17, 18, 19, 20], antimicrobial [21, 22, 23, 24], antiparasitic [25, 26], anti-inflammatory and analgesics [27, 28, 29], antiviral [30, 31, 32], and antiulcerative [33] activities and in fields like ophthalmology, neurology, endocrinology, etc. The first example of a benzimidazole that was clinically available was thiabendazole (
Drugs (compound
In this chapter, a plethora of benzimidazole analogs with different pharmacological properties such as anticancer, antibacterial, antifungal, antiviral, anticoagulant, anti-inflammatory, antiparasitic, anthelmintic activity, etc. has been discussed.
Benzimidazoles were initially used as a plant fungicide and veterinary anthelminthic. After the discovery and use of thiabendazole (
Various substituted derivatives of (
Cytotoxicity of benzimidazole derivatives is well known and, recently Noha et al. reported compounds of benzimidazole which are
Benzimidazole derivatives (compound
The role of benzimidazole analogs as potential metal-based DNA-sensor is unanimous. Fluorogenic differential/sequential Schiff base chemosensors which solely consists of benzimidazole derivatives (
Drug repurposing of benzimidazole compounds is generally considered for the reason that, it has antitumor activities. Florio and coworkers screened anthelmintics which are derivatives of benzimidazole [37]. Certain drugs like albendazole (
Synthesis of
The stabilization of proteins in the cell is being coordinated by heat shock proteins (HSPs). HSP90 plays a major role in it. This can be reflected in cancer therapy. Neverdauskas et al. synthesized benzimidazole derivatives with resorcinol (
Benzimidazole derivatives (compound
Benzimidazole is considered a privileged molecule in the medicinal world. Hernández-Romero et al. in 2021 synthesized first-row transition metal compounds which contain benzimidazole moieties (
Benzimidazole derivatives (compound
Bistrović et al. synthesized monocationic benzimidazoles (
Benzimidazole derivatives (compound
The 1, 3-disubstituted benzimidazoles (
Synthesis of imidazo[1,2-
Benzimidazole derivatives (compound
Srour et al. in 2020 reported the formation of a novel class of 2-thiazol linked benzimidazoles (
Benzimidazole-tethered pyrazoles (
Mn(I) and benzimidazole co-ligands (
Derivatives of benzimidazole (compound
Prosser et al. synthesized a Cu(II) complex of benzimidazole (
Research works concentrating on the effective therapeutic agent possessing antiproliferative activity for human gastric cancer paved the way to the discovery of yet another benzimidazole derivative (
Aromatase inhibitors (AIs) are compounds that control estrogen-related diseases and hence breast cancer, as its concentration was found to be higher in such cases. Çevik et al. in 2020 synthesized some novel benzimidazole- triazolothiadiazine libraries and examined its aromatase inhibition activities [49]. Initial screening of these compounds towards anticancer properties against breast cancer cell line (MCF-7) in humans, resulted in getting good results. Upon further subjecting it to
among them was found to be almost equal in activity when compared with a reference drug letrozole (Figure 10).
Benzimidazole derivatives (compound
The role of benzimidazole compounds in the treatment of breast cancer is exemplary. Gangrade et al. demonstrated the use of benzimidazole derivatives in the inhibition of Wnt/β-catenin signaling [50]. The upregulation of Wnt/β-catenin signaling in triple-negative breast cancer (TNBC), when compared to normal and other breast cancer subtypes, is inevitable. Benzimidazole compounds like SRI33576 (
Cheong and co-workers designed and synthesized benzimidazole methylcarbamate analogue (
Liang and co-workers synthesized selenium-containing benzimidazole derivatives through condensation of peptide coupling reagents and irradiation of microwaves [52]. These selenediazole derivatives were recognized as potent anticancer agents against MDA-MB-231 and MCF-7 breast cancer cell lines. Compounds (
Husain et al. prepared various derivatives of furanone appended benzimidazoles, which effectively contribute to cancer therapy [53]. Compound (
Benzimidazole analogs (compound
Compounds (
Molinspiration software and they possess high bioactivity scores. It was also found that they obey Lipinski’s rule and could be emerged as a lead anticancer drug (Figure 11).
Shinde and co-workers used D-glucose as the precursor for the synthesis of ribofuranosyl nucleosides (
Sireesha et al. designed and synthesized benzimidazole/benzoxazole-linked
Benzimidazole derivatives (
Synthesis of organoruthenium(II) complexes of benzimidazoles (
Organoruthenium benzimidazole derivatives (compound
Heterocyclic appended benzimidazoles were synthesized and their antibacterial and antifungal activities were tested [59]. The mechanism of action of these molecules was also examined by using docking studies with bacterial proteins such as DNA gyrase subunit B (DNAG) and penicillin-binding protein 1a (PBP1a). The compounds with thiazole and thiadiazole moieties (
Benzimidazole derivatives (compound
Ajani et al. synthesized various
Benzene-1,2- diamine undergoes condensation reactions with anthranilic acid, 3, 5-dinitrophenylbenzoic acid, and phenylacetic acid, catalyzed by NH4Cl yielded the precursor molecules, which on reaction with electrophile-releasing agents produced the corresponding
1-aryl-substituted 1, 2, 3-triazole appended amidinobenzimidazoles linked
Benzimidazole derivatives (compound
A microwave-assisted, Ni(II) catalyzed novel preparation of 2,6-disubstituted and 1,2,6-trisubstituted benzimidazoles were achieved by Patel and his group (Figure 15) [62]. The
Benzimidazole derivatives (compound
A comparative antimycobacterial activity study of 2,5-disubstituted and 1,2,5-trisubstituted benzimidazoles was reported in 2020 [63]. The
A library of mono and disubstituted benzimidazoles were synthesized by applying different methodologies, i.e., by using the microwave, ultrasound (US), infrared (IR), simultaneous application of US and IR, and by conventional heating [64]. The antimicrobial and antifungal activities of these benzimidazole derivatives were then evaluated. It was found that some compounds such as (
Potential benzimidazole-derived antibiotics (compound
Very recently, Khan et al. designed and synthesized pyrimidine-benzimidazole hybrids (
Zha et al. demonstrated benzimidazole derivatives (
Claisen-Schmidt condensation of 2-acetylbenzimidazole and aldehydes followed by a series of steps resulted in the synthesis of benzimidazole derivative (
Benzimidazole derivatives (compound
Karaburun et al. described the multi-step synthesis of a series of benzimidazole-1,3,4-oxadiazole derivatives (
Recently, Aroso and co-workers computationally designed benzimidazole derivatives through palladium-catalyzed reactions [69]. The reaction between 4-bromo-1,2-diaminobenzene and 2-nitrobenzaldehyde, followed by a couple of palladium-catalyzed Suzuki–Miyaura and Buchwald-Hartwig amination cross-coupling reactions resulted in the formation of (
Chen et al. designed flavonoid analogs (
Derivatives of benzimidazoles (compound
Compound (
Synthesis of benzimidazole derivatives like triazinane (
Wang et al. reported the synthesis of a series of benzimidazole moieties (
Quinolone analogs of benzimidazole (compound
A novel, one-pot synthesis of 2-substituted benzimidazoles and Mannich bases (
Qualitative and quantitative antimicrobial bioassay of these benzimidazole derivatives showed activity against a broad spectrum of gram-positive and negative bacterial strains both in planktonic and adherent states. The presence of nucleophilic groups like -OH or -CH3 accounts for the microbicidal activity (Figure 20).
Potent antimicrobial derivatives of benzimidazole (compound
Benzimidazoles moieties linked with
Antoci and co-workers synthesized
Benzimidazole derivatives (compound
The synthesis of naphthyl-substituted benzimidazole derivatives (
Sirim et al. designed and synthesized benzimidazole-acrylonitrile hybrid derivatives from benzene-1, 2-phenyleneamine and ethyl cyanoacetate followed by reaction with piperazines [78]. All the derived compounds exhibited anti-mycobacterial activity against
Taman et al. evaluated the antischistosomal activity of newly synthesized benzimidazole-related compounds like NBTP-OH (
Benzimidazole derivatives (compound
Synthesis of 1, 3-disubstituted benzimidazol-2-ones (
Molecular docking studies and quantitative structure–activity relationship (QSAR) delivered that benzimidazole derivatives (
Benzimidazole derivatives (compound
Tonelli et al. designed and synthesized benzimidazole derivatives from benzene-1, 2-diamine and various acids followed by suitable functionalization and used it as a potent antileishmanial agent [82]. Benzimidazole derivatives were tested against
Compounds
Exploration of the inhibitory activity of certain benzimidazole compounds like albendazole (
Compound (
Potential antiviral derivatives of benzimidazole (compound
Ibba et al. demonstrated the role of benzimidazole derivatives (
Research for the inhibitory action of
Imran et al. in 2021 [87]. The derivatives lowered the neurodegeneration and inflammation of neurons by down-regulating inflammatory cascades caused by oxidative stress (Figure 27).
Benzimidazole derivatives (compound
The prominence of benzimidazole in the field of medicine is exceptional. Etazene (
Tantray and co-workers studied psychiatric disorders like depression and acknowledged the fact that glycogen synthase kinase-3
Hussain et al. synthesized certain benzimidazole analogs (
Dabigatran is an effective drug having a benzimidazole core as the activity center and is used for the treatment of cardiovascular diseases because of its antithrombin as well as anticoagulant activities. Zhang et al. in 2020 enhanced the activity and bioavailability of dabigatran by adding methyl and methoxy groups into the benzene ring [91]. By studying the anticoagulant action and thrombin inhibition properties of compounds (
To sum up, benzimidazole is a chemical compound that belongs to the family of heterocyclic aromatic organic compounds. It is a potent biologically important molecule with a noticeable therapeutic activity. Applications of benzimidazole extend to medicinal chemistry. Several advanced research in this area also found out that the aforementioned compound has significant antimicrobial activities especially against many strains of viruses, fungus, bacteria, etc. It is also widely used in medicinal chemistry as an accepted drug against parasites and their allied infections. Benzimidazole is also used as an analgesic and anti-inflammatory agent. Recent studies have also created a lot of attention for the compound since it has an anti-carcinogenic activity like cytotoxicity and hence may become a viable cure for cancer in the future. The applications of benzimidazole cannot be marginalized. It has got a whole spectrum of medicinal agents. Benzimidazole has gained popularity in material science.
Apart from this, the multi-target capability of benzimidazole scaffolds has not been explored extensively. Being a versatile motif, benzimidazole could provide a plethora of novel multi-target ligands against various debilitated pathological conditions. The lack of comprehensive compilation about the SAR of many compounds and the various research reports stemmed the reason for less number of active benzimidazole compounds reaching the market. The existing design of benzimidazole derivatives can be further revised to accommodate potential multitargeting agents, thus enhancing and treating multifactorial disorders. This can be a breakthrough establishment in benzimidazole history.
In short, the importance of this imidazoline compound has been proved by the number of research papers getting published in a short period. This chapter is trying to narrate the formulation as well as execution of benzimidazoles in different fields of medicinal chemistry.
The authors would like to acknowledge the support given by the Department of Chemistry, Amrita Vishwa Vidyapeetham, Amritapuri campus for providing the necessary facilities to carry out research work.
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",metaTitle:"Waiver Policy",metaDescription:"We feel that financial barriers should never prevent researchers from publishing their research. With the need to make scientific research more publically available and support the benefits of Open Access, more institutions and funders have dedicated funds to assist their faculty members and researchers cover the APCs associated with publishing in Open Access. Below we have outlined several options available to secure financing for your Open Access publication.",metaKeywords:null,canonicalURL:"/page/waiver-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"At IntechOpen, the majority of OAPFs are paid by an Author’s institution or funding agency - Institutions (73%) vs. Authors (23%).
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\n\nThe first step in obtaining funds for your Open Access publication begins with your institution or library. IntechOpen’s publishing standards align with most institutional funding programs. Our advice is to petition your institution for help in financing your Open Access publication.
\n\nHowever, as Open Access becomes a more commonly used publishing option for the dissemination of scientific and scholarly content, in addition to institutions, there are a growing number of funders who allow the use of grants for covering OA publication costs, or have established separate funds for the same purpose.
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\n\nOur mission is to support Authors in publishing their research and making an impact within the scientific community. Currently, 14% of Authors receive full waivers and 6% receive partial waivers.
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She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"117248",title:"Dr.",name:"Andrew",middleName:null,surname:"Macnab",slug:"andrew-macnab",fullName:"Andrew Macnab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}}]}},subseries:{item:{id:"24",type:"subseries",title:"Computer Vision",keywords:"Image Analysis, Scene Understanding, Biometrics, Deep Learning, Software Implementation, Hardware Implementation, Natural Images, Medical Images, Robotics, VR/AR",scope:"The scope of this topic is to disseminate the recent advances in the rapidly growing field of computer vision from both the theoretical and practical points of view. Novel computational algorithms for image analysis, scene understanding, biometrics, deep learning and their software or hardware implementations for natural and medical images, robotics, VR/AR, applications are some research directions relevant to this topic.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11420,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). 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