Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\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:"9158",leadTitle:null,fullTitle:"Sports Science and Human Health - Different Approaches",title:"Sports Science and Human Health",subtitle:"Different Approaches",reviewType:"peer-reviewed",abstract:"In this era of sedentary lifestyles and disruption, sports science can propose solutions to human health matters. There is no doubt about the positive impact of sports on the physical as well as mental health of an individual, by extrapolation to the society at large. But with the advent of the latest technologies in the sports domain, the body of knowledge about sports science and human health is reaching new heights. The “Sports Science and Human Health - Different Approaches” book aims to expose worldwide research and development works in an explicit manner. Readers will appreciate the diversity of the topics, ranging from the use of machine learning in sports science to the psychological impact of sports and sports for peace initiatives. A large section is dedicated to wearable devices like biomechanical devices to gauge motor skills, and other smart devices to assess player performance. Beyond awareness, the multidisciplinary nature of this book is a source of inspiration for the scientific community.",isbn:"978-1-83880-392-6",printIsbn:"978-1-83880-391-9",pdfIsbn:"978-1-83962-509-1",doi:"10.5772/intechopen.83154",price:119,priceEur:129,priceUsd:155,slug:"sports-science-and-human-health-different-approaches",numberOfPages:140,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"2e9d3cc22773ce656e50633f8f1721f4",bookSignature:"Daniel Almeida Marinho, Henrique P. Neiva, Christopher P. Johnson and Nawaz Mohamudally",publishedDate:"December 23rd 2020",coverURL:"https://cdn.intechopen.com/books/images_new/9158.jpg",numberOfDownloads:5450,numberOfWosCitations:2,numberOfCrossrefCitations:14,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:19,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:35,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 16th 2019",dateEndSecondStepPublish:"June 12th 2019",dateEndThirdStepPublish:"August 11th 2019",dateEndFourthStepPublish:"October 30th 2019",dateEndFifthStepPublish:"December 29th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"177359",title:null,name:"Daniel A.",middleName:"Almeida",surname:"Marinho",slug:"daniel-a.-marinho",fullName:"Daniel A. Marinho",profilePictureURL:"https://mts.intechopen.com/storage/users/177359/images/system/177359.jpeg",biography:"Daniel Almeida Marinho received his Habilitation in Sport Sciences – Biomechanics (2013) from the University of Beira Interior, Portugal, where he became an Associate Professor at the Department of Sport Sciences in December 2014. He holds a Ph.D. degree in Biomechanics (2009) from the University of Trás-os-Montes and Alto Douro, Portugal. He received his BSc in Sports and Physical Education from the Faculty of Sports of the University of Porto in 2004. His main research interests are biomechanics, performance, training, and swimming. He is an Editorial Member of several international journals and Vice-Director of the Research Centre in Sports, Health and Human Development (CIDESD, Portugal). He has published more than 75 journal peer-reviewed papers, more than 50 conference proceedings, and 5 books.",institutionString:null,position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Beira Interior",institutionURL:null,country:{name:"Portugal"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"213786",title:"Dr.",name:"Henrique P.",middleName:null,surname:"Neiva",slug:"henrique-p.-neiva",fullName:"Henrique P. Neiva",profilePictureURL:"https://mts.intechopen.com/storage/users/213786/images/system/213786.png",biography:"Henrique Pereira Neiva holds a Ph.D. in Sport Sciences from the University of Beira Interior, Portugal, in 2015. He received his BSc in Sports and Physical Education from the Faculty of Sports of the University of Porto (Portugal) in 2008. Recently he became a member of the Research Center of Sports Sciences, Health Sciences and Human Development (CIDESD). His main areas of research are training, performance, strength, sports physiology and biomechanics and recently he has been developing post-doctoral studies on wearable devices and technology in the sport context. He is the author of more than 50 documents, including books, book chapters, papers in peer-reviewed journals, and conference proceedings.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Beira Interior",institutionURL:null,country:{name:"Portugal"}}},coeditorTwo:{id:"289721",title:"Dr.",name:"Christopher P.",middleName:null,surname:"Johnson",slug:"christopher-p.-johnson",fullName:"Christopher P. Johnson",profilePictureURL:"https://mts.intechopen.com/storage/users/289721/images/system/289721.jpg",biography:"Christopher Paul Johnson received his Doctor of Education in Sports Management – Sports Leadership/Sports, Fitness, & Health (2018) from the United States Sports Academy. He received his M.S. in Management/Marketing and his B.S. Sports Science/Business from Lasell University where he lectures in their School of Business. Chris is the co-owner of Boston Strength and Conditioning where he coaches athletes around the world from a range of sports. He is also a consultant for start-ups in the fields of medical technology, technology, health & fitness. His main research interests are human performance, leadership, and gamification. He is the co-editor chief of the Journal of Marketing Communications for Higher Education and a Medical Services Officer in the U.S. Army National Guard.",institutionString:null,position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:{id:"119486",title:"Dr.",name:"Nawaz",middleName:null,surname:"Mohamudally",slug:"nawaz-mohamudally",fullName:"Nawaz Mohamudally",profilePictureURL:"https://mts.intechopen.com/storage/users/119486/images/system/119486.jpeg",biography:"Dr. Nawaz Mohamudally graduated in telecommunications from the University of Science and Technology of Lille I in France. He is presently an Associate Professor at the University of Technology, Mauritius, where he has occupied the posts of Head of School of Business Informatics and Software Engineering and recently the Chairman of the Research Degrees Committee. He was formerly the Chairman of the Internet Management Committee at the national level and a member of the Mauritius Academy of Science and Technology. He is an academic researcher and practitioner in the fields of pervasive computing and data science. His latest ongoing research and development work with the industry is on customers behaviors insights. He is the recipient of the Outstanding Contribution in Education award from Stars of The Industry-Indo-African Forum and Best Professor in Industrial Systems Engineering from Africa Leadership Awards.",institutionString:"University of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"University of Technology, Mauritius",institutionURL:null,country:{name:"Mauritius"}}},coeditorFour:null,coeditorFive:null,topics:[{id:"1015",title:"Healthcare Informatics",slug:"healthcare-informatics"}],chapters:[{id:"74013",title:"Introductory Chapter: Rising Interests in Sports Sciences",doi:"10.5772/intechopen.94837",slug:"introductory-chapter-rising-interests-in-sports-sciences",totalDownloads:321,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Daniel Almeida Marinho and Henrique Pereira Neiva",downloadPdfUrl:"/chapter/pdf-download/74013",previewPdfUrl:"/chapter/pdf-preview/74013",authors:[{id:"177359",title:null,name:"Daniel A.",surname:"Marinho",slug:"daniel-a.-marinho",fullName:"Daniel A. Marinho"},{id:"213786",title:"Dr.",name:"Henrique P.",surname:"Neiva",slug:"henrique-p.-neiva",fullName:"Henrique P. Neiva"}],corrections:null},{id:"71234",title:"Sports as a Mechanism for Reaching Your Potential: The Relationship between Positive Psychology and Sports",doi:"10.5772/intechopen.91417",slug:"sports-as-a-mechanism-for-reaching-your-potential-the-relationship-between-positive-psychology-and-s",totalDownloads:718,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"People have been searching for the good life or personal well-being since the ancient Greeks. During this same period, people have been expressing themselves through sport, participating in games of athleticism as a means of discovering who they are and reaching their potential. This chapter examines the relationship between sports and a flourishing life. By examining sports as a mechanism of achieving specific traits of positive psychology associated with flourishing, the researcher is able to determine that sports are a matrix in which human potential can be nourished.",signatures:"Christopher Johnson",downloadPdfUrl:"/chapter/pdf-download/71234",previewPdfUrl:"/chapter/pdf-preview/71234",authors:[{id:"289721",title:"Dr.",name:"Christopher P.",surname:"Johnson",slug:"christopher-p.-johnson",fullName:"Christopher P. Johnson"}],corrections:null},{id:"69149",title:"Sport for Development and Peace: Current Perspectives of Research",doi:"10.5772/intechopen.89192",slug:"sport-for-development-and-peace-current-perspectives-of-research",totalDownloads:1223,totalCrossrefCites:4,totalDimensionsCites:5,hasAltmetrics:1,abstract:"Sport for Development and Peace (SDP) is an international movement that began in the 2000s with the Millennium Development Goals (2000–2015) and is currently continuing around the United Nations’ Sustainable Development Goals 2015–2030, driven by international organizations such as UNESCO. Often located in an international development context, organizations and associations use sport as a vehicle to reach several social and humanitarian missions (e.g., education, social cohesion, health, reintegration, diplomacy, and peace). This chapter presents the origins and objectives of the SDP, but it also looks at current research in the field. Since 2010, studies have significantly increased in the field around four main areas (macrosociological, field explorations, program management and evaluation, and literature reviews). This chapter also provides illustrations of SDP research projects, axis of tensions between practice and theory, and perspectives for future research in the field.",signatures:"Tegwen Gadais",downloadPdfUrl:"/chapter/pdf-download/69149",previewPdfUrl:"/chapter/pdf-preview/69149",authors:[{id:"308043",title:"Prof.",name:"Tegwen",surname:"Gadais",slug:"tegwen-gadais",fullName:"Tegwen Gadais"}],corrections:null},{id:"71225",title:"Challenges and Future of Wearable Technology in Human Motor-Skill Learning and Optimization",doi:"10.5772/intechopen.91356",slug:"challenges-and-future-of-wearable-technology-in-human-motor-skill-learning-and-optimization",totalDownloads:702,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Learning how to move is a challenging task. Even the most basic motor skill of walking requires years to develop and can quickly deteriorate due to aging and sedentary lifestyles. More specialized skills such as ballet and acrobatic kicks in soccer require “talent” and years of extensive practice to fully master. These practices can easily cause injuries if conducted improperly. 3D motion capture technologies are currently the best way to acquire human motor skill in biomechanical feedback training. Owing to their tremendous promise for a plethora of applications, wearable technologies have garnered great interest in biofeedback training. Using wearable technology, some physical activity parameters can be tracked in real time and a noninvasive way to indicate the physical progress of a trainee. Yet, the application of biomechanical wearables in human motor-skill learning, training, and optimization is still in its infant phase due to the absence of a reliable method. This chapter elaborates challenges faced by developing wearable biomechanical feedback devices and forecasts potential breakthroughs in this area. The overarching goal is to foster interdisciplinary studies on wearable technology to improve how we move.",signatures:"Gongbing Shan",downloadPdfUrl:"/chapter/pdf-download/71225",previewPdfUrl:"/chapter/pdf-preview/71225",authors:[{id:"70691",title:"Prof.",name:"Gongbing",surname:"Shan",slug:"gongbing-shan",fullName:"Gongbing Shan"}],corrections:null},{id:"69421",title:"Smart Wearables for Tennis Game Performance Analysis",doi:"10.5772/intechopen.89544",slug:"smart-wearables-for-tennis-game-performance-analysis",totalDownloads:758,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"For monitoring the progress of athletes in various sports and disciplines, several different approaches are nowadays available. Recently, miniature wearables have gained popularity for this task due to being lightweight and typically cheaper than other approaches. They can be positioned on the athlete’s body, or in some cases, the devices are incorporated into sports requisites, like tennis racquet handles, balls, baseball bats, gloves, etc. Their purpose is to monitor the performance of an athlete by gathering essential information during match or training. In this chapter, the focus will be on the different possibilities of tennis game monitoring analysis. A miniature wearable device, which is worn on a player’s wrist during the activity, is going to be presented and described. The smart wearable device monitors athletes’ arm movements with sampling the output of the 6 DOF IMU. Parallel to that, it also gathers biometric information like pulse rate and skin temperature. All the collected information is stored locally on the device during the sports activity. Later, it can be downloaded to a PC and transferred to a cloud-based service, where visualization of the recorded data and more detailed game/training statistics can be performed.",signatures:"Marko Kos and Iztok Kramberger",downloadPdfUrl:"/chapter/pdf-download/69421",previewPdfUrl:"/chapter/pdf-preview/69421",authors:[{id:"306398",title:"Dr.",name:"Marko",surname:"Kos",slug:"marko-kos",fullName:"Marko Kos"},{id:"309519",title:"Dr.",name:"Iztok",surname:"Kramberger",slug:"iztok-kramberger",fullName:"Iztok Kramberger"}],corrections:null},{id:"72859",title:"Machine Learning in Wearable Biomedical Systems",doi:"10.5772/intechopen.93228",slug:"machine-learning-in-wearable-biomedical-systems",totalDownloads:735,totalCrossrefCites:6,totalDimensionsCites:10,hasAltmetrics:0,abstract:"Wearable technology has added a whole new dimension in the healthcare system by real-time continuous monitoring of human body physiology. They are used in daily activities and fitness monitoring and have even penetrated in monitoring the health condition of patients suffering from chronic illnesses. There are a lot of research and development activities being pursued to develop more innovative and reliable wearable. This chapter will cover discussions on the design and implementation of wearable devices for different applications such as real-time detection of heart attack, abnormal heart sound, blood pressure monitoring, gait analysis for diabetic foot monitoring. This chapter will also cover how the signals acquired from these prototypes can be used for training machine learning (ML) algorithm to diagnose the condition of the person wearing the device. This chapter discusses the steps involved in (i) hardware design including sensors selection, characterization, signal acquisition, and communication to decision-making subsystem and (ii) the ML algorithm design including feature extraction, feature reduction, training, and testing. This chapter will use the case study of the design of smart insole for diabetic foot monitoring, wearable real-time heart attack detection, and smart-digital stethoscope system to show the steps involved in the development of wearable biomedical systems.",signatures:"Muhammad E.H. Chowdhury, Amith Khandakar, Yazan Qiblawey, Mamun Bin Ibne Reaz, Mohammad Tariqul Islam and Farid Touati",downloadPdfUrl:"/chapter/pdf-download/72859",previewPdfUrl:"/chapter/pdf-preview/72859",authors:[{id:"129681",title:"Dr.",name:"Mamun Bin Ibne",surname:"Reaz",slug:"mamun-bin-ibne-reaz",fullName:"Mamun Bin Ibne Reaz"},{id:"244639",title:"Dr.",name:"Muhammad E.H.",surname:"Chowdhury",slug:"muhammad-e.h.-chowdhury",fullName:"Muhammad E.H. Chowdhury"},{id:"245398",title:"MSc.",name:"Amith M. A.",surname:"Khandakar",slug:"amith-m.-a.-khandakar",fullName:"Amith M. A. Khandakar"},{id:"279345",title:"Prof.",name:"Mohammad Tariqul",surname:"Islam",slug:"mohammad-tariqul-islam",fullName:"Mohammad Tariqul Islam"},{id:"312319",title:"Prof.",name:"Farid",surname:"Touati",slug:"farid-touati",fullName:"Farid Touati"},{id:"321692",title:"M.Sc.",name:"Yazan",surname:"Qiblawey",slug:"yazan-qiblawey",fullName:"Yazan Qiblawey"}],corrections:null},{id:"74086",title:"Application of Basketball Game Models through Sports Technology",doi:"10.5772/intechopen.88432",slug:"application-of-basketball-game-models-through-sports-technology",totalDownloads:430,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The purpose of this chapter is to present the application of basketball game models through sports technology. The chapter contains introduction, terminology, sports technology practices, basketball models through technology, compilation of basketball models in sports technology, and references. In this chapter, there will be other sub-chapters that will be considered in case of depth exploration of the chapter, writing, processing, and modification of data from other authors. We will present realistically the most renowned thinkers and theorists of the field of models and sports technology from which to draw the most practical model of evolution of basketball.",signatures:"Artan R. Kryeziu",downloadPdfUrl:"/chapter/pdf-download/74086",previewPdfUrl:"/chapter/pdf-preview/74086",authors:[{id:"297734",title:"Dr.",name:"Artan",surname:"Kryeziu",slug:"artan-kryeziu",fullName:"Artan Kryeziu"}],corrections:null},{id:"69168",title:"Sports and Health as Cornerstones of Tourism Development: Case Study of Montenegro",doi:"10.5772/intechopen.89386",slug:"sports-and-health-as-cornerstones-of-tourism-development-case-study-of-montenegro",totalDownloads:563,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The modern phenomenon of tourism is more focused on specific forms of tourism in which sports and health tourism play a very important role. That fact is not surprising having in mind that they represent interconnected activities that complement each other and give each other completely new dimension. On one side, sports and health represent very important content of tourist offer because of the fact they enable tourists to become active participants in various activities, and on the other side, they represent important driving force for visiting particular destination. The idea of this chapter is to provide a theoretical and practical framework of this issue with a special focus on case study of Montenegro. According to the results of the research that was carried out, the general conclusion is that Montenegro has extremely valuable natural resources and potentials for the development of sports and health tourism, but there are still a lot of challenges that should be faced in the future in order to improve the quality of tourist offer and the level of tourists’ satisfaction as well as to create completely new image of the destination and position it as high-quality sports and health tourist destination on international market.",signatures:"Anđela Jakšić-Stojanović and Neven Šerić",downloadPdfUrl:"/chapter/pdf-download/69168",previewPdfUrl:"/chapter/pdf-preview/69168",authors:[{id:"306003",title:"Prof.",name:"Andjela",surname:"Jaksic-Stojanovic",slug:"andjela-jaksic-stojanovic",fullName:"Andjela Jaksic-Stojanovic"},{id:"310367",title:"Prof.",name:"Neven",surname:"Šerić",slug:"neven-seric",fullName:"Neven Šerić"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6826",title:"The Use of Technology in Sport",subtitle:"Emerging Challenges",isOpenForSubmission:!1,hash:"f17a3f9401ebfd1c9957c1b8f21c245b",slug:"the-use-of-technology-in-sport-emerging-challenges",bookSignature:"Daniel Almeida Marinho and Henrique Pereira Neiva",coverURL:"https://cdn.intechopen.com/books/images_new/6826.jpg",editedByType:"Edited by",editors:[{id:"177359",title:null,name:"Daniel A.",surname:"Marinho",slug:"daniel-a.-marinho",fullName:"Daniel A. 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It can also be classified into before, during, and after event activities. A flood risk assessment is an assessment of the risk of flooding from all flooding mechanisms and consists of three components: (1) hazard identification, (2) vulnerability analysis, and (3) exposure assessment. Mathematically, it can be expressed:
\nAccording to UN-ISDR [1], hazard can be defined as a dangerous phenomenon, substance, human activity, or condition that may cause loss of life, injury or other health impacts, property damage, loss of livelihoods and services, social and economic disruption, or environmental damage. It can be quantified by a probability of occurrence within a specified period of time and within a given area and given intensity. The term exposure is used to indicate elements subject to potential damage due to a hazard. Elements here may be referred to population, houses, facilities, or physical and life infrastructure essential to the functioning of a society or community such as water supply system.
\nThere are many aspects of vulnerability, related to physical, social, economic, and environmental conditions (see, for example, Birkmann [2]). Therefore, vulnerability can be defined in a number of different ways from as simple a notion as the degree of damage to an object exposed to a given hazard, to a more sophisticated one such as the characteristics and circumstances of a community, system, or asset that make it susceptible to the damaging effects of a hazard. Thus, the choice of definition may depend on its suitability for a particular vulnerability study and its interpretation for policy or action. The fact that it can be approached in manifold ways offers both flexibility and difficulty to use and interpret.
\nVillagran de Leon proposed a different framework of risk, which consists of hazard, vulnerability, and deficiencies in preparedness [3]. Exposure was treated as a component of the hazard. The term “deficiencies in preparedness” was used to emphasize the lack of coping capacities of a society at risk. The pressure and release model [4] considers disaster as a product of two major forces: natural hazard and vulnerability. It was intended to stress the importance of vulnerability assessment.
\nNo matter what framework one employs to deal with vulnerability and risk, the assessment should go beyond the identification of vulnerability and risk. It should probe into underlying driving forces and root causes in order to reduce or minimize them.
\nThe objective of the present study is to highlight a number of shortcomings in conventional frameworks for flood risk management. A focal point is the framework for vulnerability.
\nFlood hazard is conventionally described by its probability of occurrence and severity (magnitude, duration, and extent of flooding). However, evidence has been mounting that the timing of a flood really matters. On July 7, 2018, Mabi town in Okayama Prefecture, Japan, near the confluence of the Takahashi River and the Odagawa River, was inundated due to levee breaches in the two rivers. As shown in Figure 1, the highest water level in the Takahashi River near the river junction occurred at 3:00 AM and exceeded the historical records. In this disaster, more than 50 people perished with 90% of the victims aged from 66 to 91. These elders lived either alone or with a senior spouse. For elders, evacuation during the night is difficult both physically and mentally. Besides, there were media reports and our own interviews heard the same story from people who suffered from inundation in various places in recent years that flood waters entering their homes rose so quickly that they had difficulty to escape. Therefore, inundation is not just a matter of depth but also the rate of rising. The rate of inundation depth increase may depend on many factors such as local topography, the presence of structures, and urban drainage systems as well. So far, there is little information on the variation patterns of inundation depth with time during flood disasters. How fast the inundation depth would increase should be given serious consideration in flood risk management plans.
\nHydrograph of the Takahashi River, Japan, on July 7, 2018, that peaked at 3:00 AM.
Figure 2 shows the comparison of rising limb of hydrography at the Sakazu hydrological station between the largest-ever flood of the Takahashi River occurred in 2018, the second largest flood in 2011, and a small flood in 2015. It is clearly seen that the rate of water level increase depended on the intensity of a flood. The larger the intensity, the fast the water level increased. The current flood warning system in Japan is based on four water levels: (1) stand-by level, (2) flood watch level, (3) flood alert level, and (4) flood danger level. Such a warning system is essential for emergency evacuation. However, a problem with this system is that information on how fast the water level may rise from one level to another in an unprecedented flood is not available because it is intensity dependent as shown in Figure 2. How to provide real-time forecast on water level rising speed and incorporate it into the warning system is a technical issue to be explored. Besides, a related question is: is there a link between the rate of water level increase in channel and the temporal variation pattern of inundation depth in flooded area? It is also question deserving in-depth study.
\nIntensity dependency of flood water level rising rate.
On July 30 2011, the Ikarashi River in Niigata Prefecture, Japan, breached around 5:00 AM. In addition to the timing of inundation, other characteristics of this flood can be described as having two consecutive floods or a two-peak hydrological event. For the first peak, a dam in the upstream of the river regulated the peak, but for the even larger second peak, the dam failed to function since it was already at capacity.
\nThese pieces of evidence serve to demonstrate that hazard identification should include flood peak timing and the possibility of multipeaks in addition to probability and magnitude. However, methodology to consider these factors has not been developed.
\nVulnerability can be defined as follows:
\nHowever, if the framework for risk (1) is used, the definition of vulnerability should simply be inability to cope with hazard since exposure is treated separately. Füssel [5] reviewed the range of definitions of vulnerability and argued that continued plurality would become a hindrance in interdisciplinary research. A common definition of vulnerability is much needed to advance the understanding of vulnerability, yet reaching consensus is challenging. As a matter of fact, some scholars have argued that previous attempts to develop a shared vulnerability framework were superficial [6, 7].
\nO’Brien et al. [8] presented two dominant interpretations of vulnerability, which they refer to as outcome vulnerability and contextual vulnerability. Outcome vulnerability is considered as the residual exposure to impacts of climatic changes after adaptation responses have been factored in. Studies following this interpretation often take a sectoral view, looking at which/where is likely to be worst affected. Contextual vulnerability deals dynamically with the institutional, biophysical, socioeconomic, and technological conditions that affect the extent of exposure to climate changes and the ways in which those exposed can respond. Studies following this interpretation often take a more multidimensional view in a local setting, looking at how and why groups are affected differently in the context of other changes happening simultaneously. It is, therefore, more suitable to interdisciplinary and transdisciplinary studies. The present study attempts to combine outcome vulnerability and context vulnerability for the purpose of developing a more comprehensive and structured framework.
\nIt is a two-layer structure consisting of system vulnerability (contextual vulnerability) and component vulnerability (outcome vulnerability) as shown in Figure 3. Factors affecting system vulnerability can be classified into four categories. (1) The social-economic-demographic category includes factors such as general risk perception, disaster insurance, medical care, GDP, and population distribution. (2) The institutional category includes planning capability, legal system and management capability, such as evacuation operations. (3) The biophysical category includes landform and land use, river basin scale, and river dynamics. Steep river channels often generate flash floods that are difficult to predict. On the other hand, mild waterways may generate much larger floods that could be more destructive if overflow occurred. (4) The engineering category includes flood defense and warning systems.
\nA two-layer framework for vulnerability.
System vulnerability can be regulated by various structural measures such as levee and retarding basin construction and nonstructural measures such as flood hazard mapping and land use regulation. The interaction of various factors results in residual system vulnerability that is then passed on to component vulnerability (or outcome vulnerability). Component vulnerability is determined by awareness, self-preparedness, community strength, and even local culture. For example, a type of old Japanese house-Mizuka as shown in Figure 4 is a measure of self-defense. It is a two-house compound, in which one is for everyday living and another is used as shelter in case of emergency. Living in such a house reduced component vulnerability. Nevertheless, the number of such houses in Japan has been largely reduced due to various reasons, especially changes in life style and a lowering of risk awareness.
\nA self-prepared traditional house in Japan-Mizuka.
System vulnerability acts at city, regional, or river basin scale, while component vulnerability acts at individual or community scale. The degree of passage from system to component vulnerability is termed as vulnerability conductivity hereafter. It depends upon risk communication and public participation. Risk communication is the exchange of information and opinions, and establishment of an effective dialog, among those responsible for assessing, minimizing, and regulating risks and those who may be affected by the outcomes of those risks. This is the first attempt to incorporate risk communication into a vulnerability framework and to place one of its roles in the linkage between contextual and outcomes vulnerability.
\nFlood disasters may cause extensive loss of life and property damage, which is essentially an anthropogenic phenomenon with social roots. However, the dimension of loss and damage has been less focused on vulnerability framing so far. A conventional framework to address loss and damage is the C × L framework as below:
\nwhere (i) likelihood is the probability of occurrence of an impact that affects the environment and (ii) consequence is the social and environmental impact if an event occurs.
\nThis framework combines the scores from the qualitative or semiquantitative ratings of consequence and the likelihood that a specific consequence will occur to generate a risk score and risk rating. Although this risk framework takes into consideration the consequence of an event, it is not suitable for conducting integrated risk and vulnerability analyses. To incorporate loss and damage into the framework (1), vulnerability should be redefined as:
\nThe logic to include loss and damage in vulnerability is justifiable. If the level of impact upon an individual or community is low, then this individual or community is not truly vulnerable although they may not able to prevent certain consequences from happening. Accordingly, the two-layer framework includes loss and damage as already depicted in Figure 2.
\nFollowing this vulnerability framework, a policy that is different from the conventional can be proposed as below.
\nConventional flood countermeasures have focused on preventing flood waters from reaching populated areas such that blocking may be considered a keyword to describe the concept of conventional flood countermeasures. However, such a zero-risk approach has been shown to be in vain, especially in urban areas. In urban areas, in addition to the problems of asset concentration and surface imperviousness, complex urban structures may affect the behavior of flood waters in the case of inundation. Either intentionally or by chance, roads, railroads, and buildings may function as barriers to keep flood waters from spreading to a wider area [9]. Consequently, urban flooding may be characterized as being confined and deep. It is well documented that the degree of fatality and direct economic cost of flooding is proportional to inundation depth [10]. Therefore, redesigning urban form to transform confined and deep flooding to wide and shallow flooding is a way to reduce vulnerability if the prevention of inundation is not totally avoidable. The concept can be rephrased as “managing flood waters up to your knees”. Policy supporting such a concept can be termed flood sharing. How it can be implemented is a question to be answered.
\nAn important driver of vulnerability reduction is better planning. Poorly planned and managed urbanization leads to growing flood hazard due to unsuitable land use change and increasing flood vulnerability due to development in flood-prone areas and overpopulation of such areas. As shown in Figure 5, river flood management planning in Japan starts with setting up a planning scale, which is the level of safety against flood disasters to be provided in the area of concern. The next step is to select a number of target rainfalls for the planning site based on rainfall and historical flood records. Then, by performing rainfall-runoff simulations, a flood hydrograph can be determined as the management target, which is termed as either design flood without regulation or maximum probable flood. Once the maximum probable flood is estimated, allocation of flood water by dam, retarding basin, and river channel will be determined to safely convey flood water to its destination. In this planning procedure, however, the increase of maximum probable flood due to future urbanization is not directly considered. The increase in the total volume of the direct runoff is also not taken into consideration in dam and retarding basin planning. In addition, urban development planners often neglect, or are not aware of, the possibility that development may partially invalidate the river flood management design in operation in the absence of sound development planning. The fact that the maximum probable flood would vary with significant changes in land use, resulting in an increase in peak flow in a river channel, has been given less attention by urban planners in planning development of housing projects along waterways. What is often observed is that countermeasures were being taken to reduce urbanization-induced flood risk years or decades after large-scale urban development, especially after experiencing serious flood disasters. Wording differently, approaches so far have often been reactive, not proactive. Therefore, a key principle of Low Impact Development or of a Sponge City should be that no significant increase in maximum probable flood results from the process of urban development. In Japan, the Act on Countermeasures against Flood Damage of Specified Rivers Running across Cities was put into effect in 2005. According to this law, any urban development with an area larger than 1000 m2 should not cause any increase in surface runoff. If any increase is likely, permission from the competent authority is required. This law was first applied to the Tsurumi River basin since 2006 and currently implemented in seven river basins across Japan. However, monitoring studies on change of surface runoff in the seven targeted river basins are limited. The overall effectiveness of this regulation has not been validated. Figure 6 shows where waterlogging occurred during the period of 2008–2017 in Kawasaki City, which is part of the Tsurumi River basin. Figure 7 shows where waterlogging occurred during the period of 2006–2010 in Machida City, which is also part of the Tsurumi River basin. Although 3300 storage facilities have been installed in the river basin, inundation is still a frequent visitor to the region. Besides, the waterlogging locations in Kawasaki City are more or less uniformly distributed, while the waterlogging in Machida City mainly occurred along its administrative boundary on the west side. Such a difference in distribution of vulnerable locations may be viewed as one aspect of system vulnerability.
\nProcedure of flood management planning in Japan and a proposed modification (marked with red color and underline).
Locations of waterlogging (red dot) occurred in Kawasaki City during the period of 2008–2017 (source: Kawasaki City).
Locations of waterlogging (blue dot) occurred in Machida City during the period of 2006–2010 (source: Machida City).
A fundamental issue in implementing this law is that it has not been directly linked to the river flood management planning procedure. To strike a good balance between flood risk reduction and economic development, the present study proposes a new planning scheme as shown in Figure 5 with red color and underline. For new or redevelopment, the possibility of increasing maximum probable flood should be examined. If it is not possible to deal with the increase in maximum probable flood, the Act on Countermeasures against Flood Damage of Specified Rivers Running across Cities must be strictly implemented. If additional amounts of flood waters can be handled through reallocation such as constructing new or expanding the capacities of existing storage facilities, or by in-channel engineering works such as excavation, then the law can be executed to control the total amount of increase of surface runoff while having a priority setting to give permissions to economically important development projects.
\nIn cities like Tokyo, flood waters stay on streets for a few hours or a few days at most if inundation occurs. In other places such as Bangkok, however, flood waters may stay on streets for more than 2 months due to the city’s topography and insufficient drainage capacity. In Thailand, the flood damage to Bangkok and five adjoining provinces in 1983 was estimated by the National Statistical Office to be billions of Bath with the bulk of the damage shouldered by the private sector. A study by Tang et al. indicated that flood depth and flood duration were significant factors explaining flood damage in the residential and industrial areas [11].
\nIn view of such a difference in flood water residence time, the duration of inundation should be factored into exposure component, the longer the duration, the higher the level of exposure. Adding such a temporal factor to vulnerability framework will certainly lead to better planning for vulnerability reduction and smooth emergency response. It is also related to disaster insurance. To protect buildings that are constructed in flood-prone hazard areas from damage caused by flood forces, the National Flood Insurance Program (NFIP) in the United States requires that all construction below the base flood elevation must consist of flood damage-resistant building materials [12, 13]. What constitutes flood damage-resistant building materials is indeed duration dependent. The impact of duration is a much less explored research area and is envisioned to gain more attention in the near future.
\nEcosystem-based disaster risk reduction (Eco-DRR) is a relatively new concept to reduce the risk of being exposed to natural hazards by avoiding development in disaster-prone areas or by using natural systems as a way to buffer the worst impacts of natural hazards, maintain the resilience of natural ecosystems and their ecosystem services, and help people and communities adapt to changing conditions [14, 15]. The core thinking of Eco-DRR is based on the realization that disasters cause massive damage to the environment, while degraded environments exacerbate disaster impacts and responding to disasters often leads to additional environmental impacts. Well-managed ecosystems, such as wetlands, forests, and coastal systems, act as natural infrastructure, reducing physical exposure to many hazards and increasing socioeconomic resilience of people. For example, mangroves and seagrass beds can dissipate the destructive energy of storm surge and Tsunami and prevent coastal erosion while supporting fishing and tourism activities and storing high amounts of carbon. Therefore, Eco-DRR is also aimed at reducing the vulnerability of society and establishing disaster-resilient communities.
\nJapan has a tradition of using ecosystems for disaster mitigation such as maintaining forests to prevent soil erosion, planting trees along its coast to reduce wind-related disasters, and utilizing paddy fields to store flood waters temporarily. Since 2012, Eco-DRR has been incorporated into national policies and planning of the Japanese government. The Basic Act for National resilience, enacted in 2013, is aimed at taking advantage of regional ecosystem-based functions to prevent and reduce disasters. Following this Act, Fundamental Plan for National Resilience was established to promote the use of ecosystem-based disaster reduction approaches and assessment of functions of Eco-DRR initiatives provided during nondisaster times. The National Spatial Strategy and the National Land Use Plan, approved in 2015, also called for the promotion of disaster management using natural ecosystems. Furthermore, Japan’s Forest Law requires that Disaster Risk Management (DRM) forests should be planted along the coast to prevent damages from blown sand and salt, high tides, and tsunamis. Under such strong policy drivers, a question is “does it work?”
\nOn March 11, 2011, the Great East Japan Earthquake occurred and trigged a major Tsunami. Consequently, the Tohoku area of Japan was so badly hit Tsunami. In total, this disaster caused more than 15,000 deaths, 2800 missing, and approximately 300,000 people being evacuated [16]. Among the disaster-stricken areas, Miyagi Prefecture suffered the most in terms of fatalities and infrastructure damage. Before the disaster, there were 200- to 400-m-wide pine forests along the Sendai Plains of Miyagi Prefecture having protected the area for the past four centuries. Nevertheless, the forest failed to stop the intrusion of the Tsunami. The coastline of Rikuzentakata City, Iwate Prefecture, was also very famous for its 2-km-long and 200-m-wide pine trees as shown in Figure 8. Again, the forest was completely destroyed except for one tree after the 3/11 Tsunami. There is no doubt that the forest along the coast of Tohoku region did reduce the energy of Tsunami. Although the forest was destroyed during the disaster, without it, fatalities and property damage would undoubtedly have been much greater. The question is how to quantify its effectiveness in relation to Tsunami height. It is not difficult to imagine that a coastal forest is effective to a Tsunami with low wave height. The information needed is the threshold of wave height above which a coast forest may fail to dissipate the energy of Tsunamis significantly. Koshimizu [17] pointed out that coastal forests could be rendered useless by liquefaction, but no countermeasures had been discussed. Besides, it should not be forgotten that a fallen tree being moved by a Tsunami can kill people and damage houses.
\nCoast forest before and after the Tsunami disaster on March 11, 2011.
An interesting phenomenon was observed in Ishinomaki City, Iwate Prefecture. Along a portion of the Watanoha coast, the levee was lightly damaged, but the residential area behind was devastated as can be clearly seen in Figure 9. The levee height before the disaster was 4 m, and the Tsunami height in Ishinomaki was more than 8.6 m according to Japan Meteorology Agency. This implies that the Tsunami overtopped the levee without much energy dissipation. Otherwise, the levee would have been badly damaged. The same phenomenon may also apply to coastal forests if the height of a Tsunami is much higher than the height of the forest. After the disaster, the Japanese Government decided to invest ¥59 billion to restore 3660 hectares of trees in Tohoku, which were destroyed by the Tsunami [18]. However, as can be seen from Google Earth, the restoration of coastal forests has not produced any visible progress. Instead of costal forest, concrete levee is expanding along the coast as shown in Figure 10. This was also confirmed by author’s field survey conducted in July 2018. Despite legislative development with regard to Eco-DRR in Japan, the implementation appears not straightforward. A multilayered defense system combining Eco-DRR measures with conventional concrete-based measures may deserve serious discussion or even debate.
\nDevastated residential area behind a coastal levee.
Current situation of defense construction along the Tsunami-hit coast.
Another case, which has been advocated as an example of Eco-DRR, is the Kabukuri-numa wetland in Osaki City, Miyagi Prefecture, Japan. In the 1970s, it was merely used as a flood-retarding basin. Large-scale dredging of the wetland was planned to increase its flood regulation capacity in 1996. However, in response to environmental concerns, the dredging plan was withdrawn. Instead, the area of the Kabukuri-numa wetland was expanded by transforming surrounding fallow farmland to wetland to meet the flood regulation demand. Furthermore, water was retained in surrounding paddies during the winter so as to function as seminatural, but still important, habitat for wetland-dependent wildlife. In 2005, the Kabukuri-numa wetland and surrounding paddy fields were registered together as a Ramsar wetland site [19, 20]. As a result of this wetland expansion, a large number of waterfowls overwinter in Kabukuri-numa, eating fallen grain and weeds in the flooded paddy fields. The bird droppings, which are rich in phosphate, function as high-quality natural fertilizers for rice and enrich the soil. Rice cultivated under such an environment is branded as such and can be sold at a higher-than-average price. In addition, the large number of overwintering birds attracts a large number of tourists every winter. Although the ecosystem services of the Kabukuri-numa wetland during nondisaster times have been well demonstrated, its flood regulation capability has not been tested since there have been no large-scale floods in recent decades. In addition, there are concerns over the water quality of the wetland due to the large number and high concentration of birds. Bird droppings entering paddy fields may contribute to rice production but may also impact the water quality of adjacent wetlands if entering into its water body. As a matter of fact, water quality testing in the Kabukuri-numa wetland by the author of this chapter indicated that the water body is already eutrophic. How to make this Eco-DRR initiative sustainable is a question to be answered.
\nThe present work highlights a number of subjects in the arena of flood risk management that deserve further in-depth research, as summarized below.
\nIn terms of flood hazard identification, flood peak timing and multipeak hydrographs should be given more attention.
\nDue to the existence of various definitions and interpretations of vulnerability, there is a need to combine or group some of the notions, if the integration of all is impossible, for the sake of a better and deeper understanding of what really constitutes vulnerability. Following this line of thinking, a new two-layer framework of vulnerability is proposed, integrating existing concepts to a certain extent. This new framework may help develop new approaches to vulnerability reduction, with new concepts such as flood sharing.
\nThis new framework also suggests that inundation duration should be included in the analysis of exposure.
\nEco-DRR is an emerging approach to achieving both flood risk management and environmental conservation and may contribute to local economies as well. However, more cases of Eco-DRR across the world should be collected and analyzed from various angles in order to quantify its effectiveness and promote best practice. In Japan, Eco-DRR is advanced in terms of the legal framework supporting it, but there is great uncertainty in terms of its performance. Innovation is indispensable in reaching a new stage of flood risk management.
\nThis work was supported by Sophia Research Branding Project 2016.
\nThe authors declare no conflict of interest.
Chronic myeloproliferative disorders are a group of clonal diseases of the stem cell. It is a group of several diseases with some common features. They derive from a multipotential hematopoietic stem cell. A clone of neoplastic cells in all these neoplams is characterized by a lower proliferative activity than that of acute myeloproliferative diseases. In each of these diseases, leukocytosis, thrombocythemia, and polyglobulia may appear at some stage, depending on the diagnosis [1, 2].
The research on interferon has been going on since the 1950s [3]. Then, the attention was paid to its influence on the immune system. It has been noted that it can exert an antiproliferative effect by stimulating cells of the immune system [4]. In 1987, a publication by Ludwig et al. was published, which reported the effectiveness of interferon alpha in the treatment of chronic myeloproliferative disorders [5].
More and more new studies have been showing the effectiveness of interferon alpha in reducing the number of platelets, reducing the need for phlebotomies in patients with polycythemia vera and also in reducing the number of leukocytes. Moreover, interferon reduced the symptoms of myeloproliferative disorders such as redness and itching of the skin. Additionally, it turned out to be effective in reducing the size of the spleen.
Further studies on the assessment of remission using molecular-level response assessments indicate that the interferon action in chronic myeloproliferation diseases targets cells from the mutant clone with no effect on normal bone marrow cells [6].
Over the years, interferon alpha-2a and interferon alpha-2b have been introduced into the treatment of chronic myeloproliferation, followed by their pegylated forms. The introduction of pegylated forms allowed for a reduction in the number of side effects and less frequent administration of the drug to patients. In recent years, monopegylated interferon alpha-2b has been used to further increase the interval between drug administrations while maintaining its antiproliferative efficacy.
The exact mechanism of action of interferon alpha in the treatment of chronic myeloproliferative disease is still not fully understood, but it has an impact on JAK2 (Janus Kinase) signal transducers and activates the STAT signal pathway (Janus Kinase/SignalTransducer and Activator of Transcription).
Interferon alpha binds to IFNAR1 and IFNAR2c, which are type I interferon receptors. Interferon alpha has an impact on JAK2(Janus Kinase) signal transducers and activates the STAT signal pathway. The disturbances in this signaling pathway are observed in chronic myeloproliferative disorders [7].
Interferon inhibits the JAK-STAT signaling pathway by directly inhibiting the action of thrombopoietin in this pathway [8].
So far, three driver mutations have been described in the course of chronic myeloproliferative diseases that affect the functioning of the JAK-STAT pathway.
JAK2 kinase and JAK1, JAK3, and TYK2 kinases belong to the family of non-receptor tyrosine kinases. They are involved in the intracellular signal transduction of the JAK-STAT pathway. It is a system of intracellular proteins used by growth factors and cytokines to express genes that regulate cell activation, proliferation, and differentiation. The mechanism of JAK activation is based on the autophosphorylation of tyrosine residues that occurs after ligand binds to the receptor. JAK2 kinase transmits signals from the hematopoietic cytokine receptors of the myeloid lineage (erythropoietin, granulocyte-colony stimulating factor thrombopoietin, and lymphoid lineage [9].
A somatic G/T point mutation in exon 14 of the JAK2 kinase gene converts valine to phenylalanine at position 617 (V617F) in the JAK2 pseudokinase domain, which allows constitutive, ligand-independent activation of the receptor to trigger a proliferative signal [10].
Mutation of the MPL gene, which encodes the receptor for thrombopoietin, increases the sensitivity of magekaryocytes to the action of thrombopoietin, which stimulates their proliferation [11].
Malfunction of calreticulin as a result of mutation of the CARL gene leads to the activation of the MPL-JAK/STAT signaling pathway, which is independent of the ligand, as calreticulin is responsible, for the proper formation of the MPL receptor. Consequently, there is a clonal proliferation of hematopoietic stem cells [12].
Below, we provide an overview of some clinical studies on the efficacy of interferon in chronic myeloproliferative disorders.
Polycythemia vera (PV) is characterized by an increase in the number of erythrocytes in the peripheral blood.
Polycythemia vera is caused by a clonal mutation in the multipotential hematopoietic stem cell of the bone marrow. The mutation leads to an uncontrolled proliferation of the mutated cell clone, independent of erythropoietin and other regulatory factors. As the mutation takes place at an early stage of hematopoiesis, an increase of the number of erythrocytes as well as of leukocytes and platelets is observed in the peripheral blood. The cause of proliferation in PV independent from external factors is a mutation in the Janus 2 (JAK2) tyrosine kinase gene. The V617F point mutation in the JAK2 gene is responsible for about 96% mutation, and in the remaining cases the mutation arises in exon 12. Both mutations lead to constitutive activation of the JAK-STAT signaling pathway [13].
As a result of the uncontrolled proliferation, blood viscosity increases, which generates symptoms such as headaches and dizziness, visual disturbances, or erythromelalgia. As the number of all hematopoietic cells, including the granulocytes ones, increases, the difficult to control symptoms of their hyperdegranulation may appear, among which gastric ulcer or skin itching is often observed. During the disease progression, the spleen and liver become enlarged.
The most common complication of the disease is episodes of thrombosis, especially arterial one. During the course of the disease, it can also evolve into myelofibrosis or acute myeloid leukemia.
The treatment of PV is aimed at preventing thromboembolic complications, relieving the general symptoms, the appearance of hepatosplenomegaly as well as preventing its progression.
Each patient should receive an antiplatelet drug chronically, and usually acetylsalicylic acid is the choice. Most often, the treatment is started with phlebotomy in order to rapidly lower the hematocrit level. If cytoreductive therapy is necessary, the drugs of first choice are hydroxycarbamide and interferon [2].
However, the research on the mechanism of the action of interferons is still ongoing. In vitro studies with CD34+ cells from peripheral blood of patients diagnosed with polycythemia vera showed that interferon inhibits clonal changed cells selectively. It was found that interferon alpha-2b and pegylated interferon alpha-2a reduce the percentage of cells with JAK2 V617F mutation by about 40%. Pegylated interferon alpha-2a works by activating mitogen-activated protein kinase P38. It affects CD34+ cells of patients with polycythemia vera by increasing the rate of their apoptosis [6].
A case of a patient with PV with a confirmed chromosomal translocation t(6;8) treated with interferon alpha-2b, which resulted in a reduction of the clone with translocation by 50% from the baseline value, was also described [14].
In 2019, the results of a phase II multicenter study were published, which aimed at assessing the effectiveness of recombinant pegylated interferon alpha-2a in cases of refractory to previously hydroxycarbamide therapy. The study included 65 patients with essential thrombocythemia (ET) and 50 patients with polycythemia vera. All patients had previously been treated with hydroxycarbamide and showed resistance to this drug or its intolerance.
The assessment of the response was performed after 12 months of treatment. Overall response rate to interferon was higher in patients diagnosed with ET than in patients with polycythemia vera. In essential thrombocythemia, the percentage of achieved complete remissions was 43 and 26% of partial remissions. The remission rate in ET patients was higher if calreticulin CALR gene mutation was present. Patients with polycythemia vera achieved complete remission in 22% of cases and partial remission in 38% of cases.
Treatment-related side effects that follow to discontinuation of treatment were reported in almost 14% of patients [15].
The duration of response to treatment with pegylated interferon alpha-2a and the assessment of its safety in long-term use in patients with chronic myeloproliferative disorders was the goal of a phase II of the single-center study. Forty-three adult patients with polycythemia vera and 40 patients with essential thrombocythemia were enrolled in the study. The complete hematological response was defined as a decrease in hemoglobin concentration below 15.0 g/l, without phlebotomies, a resolution of splenomegaly, and no thrombotic episodes in the case of PV, and for essential thrombocythemia—a decrease platelet count below 440,000/μl and two other conditions as above. The assessment of the hematological response was performed every 3–6 months. The median follow-up was 83 months.
The hematological response was obtained in 80% of cases for the entire group. In patients with polycythemia vera, 77% of patients achieved a complete response (CR) while 7% a partial response (PR). The duration of response averaged 65 months for CR and 35 months for PR. In the group of patients diagnosed with essential thrombocythemia, CR was achieved in 73% and PR in 3%. The durance of CR was 58 months and PR was 25 months.
The molecular response for the entire group was achieved in 63% of cases.
The overall analysis showed that the duration of hematological remission and its achievement with pegylated interferon alpha-2a treatment is not affected neither by baseline disease characteristics nor JAK2 allele burden and disease molecular status. There was also no effect on age, sex, or the presence of splenomegaly.
During the course of the study, 22% of patients discontinued the treatment, because of toxicity. Toxicity was the greatest at the beginning of treatment. The starting dose was 450 μg per week and was gradually tapered off.
Thus, on the basis of the above observations, the researchers established that pegylated interferon alpha-2a may give long-term hematological and molecular remissions [16].
The assessment of pegylated interferon alpha-2a in group of patients diagnosed with polycythemia vera only was performed. The evaluation was carried out on a group of 27 patients. Interferon decreased the JAK2 V617F allele burden in 89% of cases. In three patients who were JAK2 homozygous at baseline, after the interferon alpha-2a treatment wild-type of JAK2 reappeared. The reduction of the JAK2 allele burden was estimated from 49% to an average 27%, and additional in one patient the mutant JAK2 allele was not detectable after treatment. It can therefore be postulated that the action of pegylated interferon alpha-2a is directed to cells of the polycythemia vera clone [17].
In 2005, the results of treatment by pegylated interferon alpha-2b of 21 patients diagnosed with polycythemia vera and 21 patients diagnosed with essential thrombocythemia were published. In the case of polycythemia vera in 14 patients, PRV-1 gene mutation was initially detected. In 36% of cases, PRV-1 expression normalized after treatment with pegylated interferon alpha-2b. For the entire group of 42 patients, the remission assessment showed that complete remission was achieved in 69% cases after 6 months of treatment. However, only in 19 patients remission was still maintained 2 years after the start of the study. Pegylated interferon alpha-2b was equally effective in patients with PV and ET. The use and the type of prior therapy did not affect the achievement of remission [18].
Another study with enrolled only PV patients included 136 patients. They were divided into two arms. One group received interferon alpha-2b and the other group received hydroxycarbamide. Interferon dosage was administered in 3 million units three times a week for 2 years and then 5 million units two times a week. Hydroxycarbamide was administered at a dose between 15 and 20 mg/kg/day.
In the group of patients treated with interferon, a significantly lower percentage of patients developed erythromelalgia (9.4%) and distal parasthesia (14%) compared with the group treated with hydroxycarbamide, for whom these percentages were respectively: 29 and 37.5%. Interferon alpha-2b was found to be more effective in inducing a molecular response, which was achieved in 54.7% of cases, in comparison with hydroxycarbamide—19.4% of cases, despite the fact that the percentage of achieved general hematological responses did not differ between the groups and amounted about 70%. The 5-year progression free period in the interferon group was achieved in a higher percentage (66%) than in the hydroxycarbamide group (46.7%) [19].
The most recent form of interferon approved by the
Thanks to these changes to the structure of the molecule, it was possible to achieve a significant increase in its half-life. Ropeginterferon can be administered subcutaneously to patients every 14 days. The clinical trials conducted so far have assessed the ropeginterferon dose from 50 micrograms to a maximum dose of 500 microgams administered as standard every 2 weeks. The possible dose change in case of side effects includes not only the reduction of the drug dose itself, but also the extension of the interval between doses. The extension of the dosing interval up to 4 weeks was assessed.
Ropeginterforn was approved in 2019 by the EMA for the use in patients diagnosed with polycythemia vera without splenomegaly, as monotherapy.
Ropeginterferon, like the previous forms of interferons used in treatment, is contraindicated in patients with severe mental disorders, such as severe depression. It is also a contraindication in patients with noncompensatory standard treatment of disorders of the thyroid gland as well as severe forms of autoimmune diseases. The safety profile of ropeginterferon is similar to that of other forms of alpha interferons. The most common side effects are flu-like symptoms [20].
Ropeginterferon has been shown to exhibit in vitro activity against JAK2-mutant cells. The activity of ropeginterferon against JAK2-positive cells is similar to that of other forms of interferons used actually for standard therapy. Ropeginterferon has an inhibitory effect on erythroid progenitor cells with a mutant JAK2 gene. At the same time, it has almost no effect on progenitor cells without the mutated allele (JAK2-wile-type) and normal CD34+ cells. A gradual decrease of JAK2-positive cells was observed in patients with PV during ropeginterferon treatment. The examination was performed after 6 and 12 months of treatment. In comparison, the reduction in the percentage of JAK2 positive cells in patients treated with hydroxycarbamide was significantly lower.
These results may suggest that ropeginterferon may cause elimination of the mutant clone, but further prospective clinical trials are needed to confirm this theory. The evaluation was performed on a group of patients enrolled in the PROUD-PV study who were treated in France [21].
In 2017, a multicenter study was opened in Italy. The study was of the second phase. In total, 127 patients with polycythemia vera were included in the study. All patients enrolled on the study had low-risk PV. The clinical trial consisted of two arms. Patients received phlebotomies and low-dose aspirin in one arm and ropeginterferon in the other arm. The aim of the study was to achieve a hematocrit of 45% or lower without any evidence of disease progression. Ropeginterferon was administered every 2 weeks at a constant dose of 100 μg.
The response to the treatment was assessed after 12 months. The reduction of hematocrit to the assumed level was achieved in significantly higher percentage of patients in the ropeginterferon group than of patients who received only phlebotomies and aspirin. In addition, none of the patients treated with ropeginterferon experienced disease progression during the course of the study, while among those treated with phlebotomies, 8% of patients progressed.
Grade 4 or 5 adverse events were not observed in patients treated with ropeginterferon, and the incidence of remaining adverse event (AE) was small and comparable in both arms. The most common side effects in the ropeginterferon group were flu-like symptoms and neutropenia; however, the third-grade neutropenia was the most common (8% of cases) [22].
One of the most important clinical studies on the use of ropeginterferon was the PROUD-PV study and its continuation: the CONTINUATION-PV study. These were three-phase, multicenter studies. The aim of the study was to compare the effectiveness of ropeginterferon in relation to hydroxycarbamide. The study included adult patients diagnosed with polycythemia vera treated with hydroxycarbamide for less than 3 years and no cytoreductive treatment at all. In total, 257 patients received this treatment. The patients were divided into two groups: those receiving ropeginterferon or the other being given hydroxycarbamide.
During the PROUD-study, drug doses were increased until the hematocrit was achieved below 45% without the use of phlebotomies, and the normalization of the number of leukocytes and platelets was reached.
The PROUD-PV study lasted 12 months. After this time, the patients continued the treatment under the CONTINUATION-PV study for further 36 months. After the final analysis performed in the 12th month at the end of PROUD study, it was found that the hematological response rates did not differ between the ropeginterferon and hydroxycarbamide treatment groups. These were consecutively 43% in the ropeginterferon arm and 46% in the control arm.
However, after analyzing the CONTINUATION- PV study, it turned out that after 36 months of treatment, the rates of hematological responses begin to prevail in the group of patients receiving ropeginterferon, 53% versus 38% in the control group. Thus, from the above data, it can be seen that the response rate to ropeginterferon increases with the duration of treatment [23].
Another analysis of patients participating in the PROUD and CONTINUATION studies was based on the assessment of treatment results after 24 months, dividing patients into two groups according to age (under and over 60 years).
The initial comparison of both groups of patients showed that older patients had a more aggressive course of the disease. Patients over 60 years of age had a higher percentage of cells with a mutant JAK2 allele. They experienced both general symptoms and some complications, such as thrombosis, more frequently. Both patients under 60 years of age and over 60 years of age in the ropeginterferon arm had a higher rate of molecular response, namely 77.1 and 58.7% compared with the HU remission: 33.3 and 36.1%, respectively. Significantly higher reductions in the JAK2 allele were observed in both groups of patients after ropeginterferon treatment: it was 54.8% for younger patients and 35.1% for elderly patients. For comparison, this difference in the group of patients treated with HU was 4.5 and 18.4%, respectively.
What is more, the age did not affect the frequency of ropeginterferon side effects. In addition, the incidence of adverse ropeginterferon disorders was similar to that observed in the hydroxycarbamide group [24].
Essential thrombocythemia is a clonal growth of multipotential stem cells in the bone marrow. The consequence of this is increased proliferation of megakaryocytes in the bone marrow and an increase in the number of platelets in the peripheral blood. The level of platelets above 450,000/μl is considered a diagnostic criterion.
Essential thrombocythemia may progress over time to a more aggressive form of myeloproliferation, i.e., myelofibrosis. The disease can also evolve into acute myeloid leukemia or myelodysplastic syndrome, both with very poor prognosis. Thromboembolic complications are serious, and they concern over 20% of patients. Thrombosis occurs in the artery and venous area. Moreover, in patients with a very high platelet count, above 1,000,000/μl, bleeding may occur as a result of secondary von Willebrand syndrome [1, 2].
The treatment of ET is primarily aimed to prevent thrombotic complications.
In low-risk patients, only acetylsalicylic acid is used. In cases of high-risk patients, hydroxycarbamide is the first-line drug for most patients. Anagrelide and interferon are commonly used as second-line drugs.
Due to the possible effects of hydroxycarbamide of cytogenetic changes in the bone marrow cells after long-lasting usage, some experts recommend the use of interferon in younger patients in the first line. Interferon is also used as the drug of choice in patients planning a pregnancy [25].
The efficacy of pegylated interferon alpha-2a was assessed on the basis of the group of 39 patients with essential thrombocythemia and 40 patients with polycythemia vera.
Of the overall group, 81% of patients were previously treated prior to the study entry. The patients received pegylated interferon alpha-2a in a dose of 90 μg once a week. The dose of 450 μg was associated with a high percentage of intolerance.
In patients with essential thrombocythemia, the complete remission was achieved in 76%, while the overall hematological response rate brought 81%. Moreover, the molecular remission was achieved in 38%, in 14% of cases, JAK2 transcript became not detectable.
Patients diagnosed with polycythemia vera achieved 70% complete hematological remission and 80% general hematological response to treatment. JAK2 transcript was undetectable in 6% of patients. Molecular remission was achieved in 54% of cases.
Pegylated interferon alpha-2a at the dose of 90 μg per week was very well tolerated. In total, 20% of patients experienced a grade of 3 or 4 of adverse reaction, which was neutropenia. In addition, an increase in liver function tests was observed. Grade 4 of AE was not observed among patients who started the treatment with 90 μg/week while grade 3 neutropenia was an adverse event in only 7% of cases [26].
The effect of interferon alpha-2b treatment in patients with ET and PV was investigated. The study was prospective. Some of the results concerning the group of patients with polycythemia vera are presented in the subsection on polycythemia vera. In total, 123 patients with diagnosed essential thrombocythemia participated in the study. All of them received interferon alpha-2b. The patients were divided into two groups depending on the presence of the JAK2 V617F mutation. The enrolled patients were between 18 and 65 years of age. The treatment they received was, sequentially, interferon alpha-2b in the dose of 3 million units three times a week for the first 2 years, after which time the dose was changed into a maintenance dose, which amounted to 5 million units two times a week.
The analysis showed that the patients with the JAK2 V617F mutation present in a higher percentage achieved an overall hematological response as well as a complete hematological response. The overall hematological response was achieved in 83% of patients with JAK2 mutation, and the complete hematological remission was achieved in 23 cases. In the group of ET patients without the JAK2 V617F mutation, overall hematological response was achieved in 61.4%, while the complete hematological remission was achieved in 12 patients. The 5-year progression-free survival was obtained in 75.9% in the JAKV617F group and only in 47.6% without the mutation.
A significant proportion of patients experienced mild side effects. Grade 3 and 4 of adverse events were severe, most of them being a fever. The isolated cases of elevated liver tests and nausea have also been reported [19].
Pegylated interferon alpha-2b in patients with essential thrombocythemia who were previously treated with hydroxycarbamide, anagrelide, and other forms of interferon alpha, however, due to the lack of efficacy or toxicity, the patients required a change of treatment, was assessed. Pegylated interferon alpha-2b turned out to be effective in these cases. It led to the complete hematological remission in 91% of patients after 2 months of therapy, and in 100% of patients after 4 months. However, merely 11 patients participated in the study. Also only two patients required treatment discontinuation due to the side effects such as depression and general fatigue grade 3 [27].
In case of pregnant patients, interferon is currently considered the only safe cytoreductive drug. Over the years, several analyses of the results of interferon treatment during pregnancy have been carried out.
The assessment of 34 pregnancies in 23 women diagnosed with ET was performed retrospectively. All the pregnancies included in the analysis were of high risk. This high risk was associated with a high platelet count above 1,500,000/μl, a history of thrombotic episode, severe microcirculation disorders, or a history of major hemorrhage.
It turned out that the use of interferon allowed the birth of an alive child in 73.5% of cases. There was no difference in efficacy between the basic and pegylated forms of interferon alpha. In pregnancies without interferon treatment, the percentage of live births was only 60%. Moreover, it was not found if the presence of the JAK2 V617F mutation had any influence on the course of pregnancy [28].
An analysis of the course of pregnancy in patients with ET was assessed in Italy. Data from 17 centers were taken into account. Data from 122 pregnancies were collected from 92 women. In patients diagnosed with essential thrombocythemia, the risk of the spontaneous loss of pregnancy is about 2.5 times higher than among the general population. In the contrary to the study quoted above, it was found that the presence of the JAK2 mutation increases the risk of pregnancy loss. The proportion of live births in patients exposed to interferon during pregnancy was 95%, compared with 71.6% in the group of patients not treated with interferon.
The multivariate analysis also showed that the use of acetylsalicylic acid during pregnancy had no effect on the live birth rate of patients with ET [29].
Whatever its form, interferon is the drug of first choice in pregnancy. Hydroxycarbamide and anagrelide should be withdrawn for about 6 months, and at least for 3 months, before the planned conception. Experts recommend the use of interferon in high-risk pregnancies [30]. A Japanese analysis of 10 consecutive pregnancies in ET patients showed 100% live births in patients who received interferon [31].
In myelofibrosis (MF), monoclonal megakaryocytes produce cytokines that stimulate the proliferation of normal, non-neoplastic fibroblasts and stimulate angiogenesis. The consequence of this is the gradual fibrosis of the bone marrow, impaired hematopoiesis in the bone marrow, and the formation of extramedullary location mainly in the sites of fetal hematopoiesis, i.e., in the spleen and the liver.
The production of various cytokines by neoplastic megakaryocytes leads to the proliferation of normal, noncancerous fibroblasts as well as to increased angiogenesis.
Progressive bone marrow fibrosis leads to worsening anemia and thrombocytopenia. On the other hand, the production of proinflammatory cytokines by megakaryoblasts leads to the general symptoms such as weight loss, fever, joint pain, night sweats, and consequently, progressive worsening of general condition.
The prognosis for myelofibrosis is poor. In about 20% of patients, myelofibrosis evolves into acute myeloid leukemia with poor prognosis.
Currently, the only effective method of treatment that gives a chance to prolong the life is allogeneic bone marrow transplantation. However, this method is only available to younger patients.
The goal of treatment of patients who have not been qualified for allotranspalntation is to reduce the symptoms and to improve the patient’s quality of life. In case of leukocytosis cytoreducing drugs, such as hydroxycarbamide, melphalan, or cladribine can be used. They cause a reduction in the number of leukocytes and may, to some extent, inhibit splenomegaly. Interferon alpha has been used successfully for the treatment of myelofibrosis for many years. The results of its effectiveness will be presented below [2].
Currently, the JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis with enlarged spleen in intermediate and high-risk patients. Ruxolitinib reduces the size of the spleen, reduces general symptoms, and improves the quality of life; however, it does not prolong the overall survival of patients [32].
In 2015, the results of a retrospective study were published to compare the histological parameters of the bone marrow before and after interferon treatment. Twelve patients diagnosed with primary myelofibrosis as well as post-PV MF and post-ET MF were enrolled in the study. Patients were treated with pegylated recombinant interferon alpha-2a or recombinant interferon alpha-2b in standard doses. The time of treatment was from 1 to 10 years. Some patients had previously been treated with hydroxycarbamide or anagrelide. In all cases, karyotype was normal. The prognostic factor of Dynamic International Prognostic Scoring System (DIPSS) was assessed at the beginning as well as during the treatment.
Bone marrow cellularity decreased in cases with increased bone marrow cellularity before the treatment. After the interferon treatment, a reduction in the degree of bone marrow fibrosis was found. The parameters, such as the density of naked nuclei and the density of megakaryocytes in the bone marrow, also improved.
It proves that if the JAK2 V617F mutation had been present, DIPSS was decreased after interferon treatment. This relationship was not observed in patients without the JAK2 V617F mutation. The improvement in peripheral blood morphological parameters and the overall clinical improvement correlated with the improvement in the assessed histological parameters of the bone marrow.
Before the initiation of interferon, seven patients had splenomegaly. During the treatment with interferon, the complete resolution of splenomegaly was achieved in 17% of patients (two cases), and its size decreased in 25% (three cases). A good clinical response was achieved in 83% during interferon therapy. There was no significant difference in response between the two types of interferon used [33].
A prospective study was also conducted in patients with low and intermediate-1 risk group myelofibrosis. Seventeen patients were enrolled. Patients received interferon alpha-2b (0.5–3 milion units/three times a week) or pegylated interferon alpha-2a (45–90 μg/week). The duration of therapy was on average 3.3 years.
Most of the patients responded to the treatment. Partial remission was found in seven patients and complete remission in two patients. Moreover, in four cases, the disease was stabilized and in one case the clinical improvement was achieved. Three patients did not respond to treatment at all and progressed to myelofibrosis. Additionally, the assessment in reducing spleen size was performed. At baseline, 15 patients have splenomegaly, nine of them achieved the compete regression of spleen size [34].
However, the efficacy of interferon in the treatment of myelofibrosis appears to be limited only to a less advanced form, when the bone marrow still has an adequate percentage of normal hemopoiesis and the marrow stroma is not significantly fibrotic. In more advanced stages, interferon was not shown to have any significant effect on the regression of the fibrosis process [35].
In 2020, the results of the COMBI study were published. That was a two-phase, multicenter, single-arm study that investigated the efficacy and safety of the combination of ruxolitinib and pegylated interferon alpha. Thirty-two patients with PV and 18 patients with primary and secondary myelofibrosis participated in the study. The patients were at age 18 and older. Remission was achieved in 44% of myelofibrosis cases, including 28% (5 patients) of complete remission. In patients with PV, the results were slightly worse: 31% of remissions, including 9% of complete remissions. Patients received pegylated interferon alpha-2a (45 μg/week) or pegylated interferon alpha-2b (35 μg/week) in low doses and ruxolitinib in doses of 5–20 mg twice a day.
For the entire group of patients (with PV and MF), the initial JAK2 allele burden was 47% at baseline, and after 2 years of treatment with interferon and ruxolitinib, it decreased to 12%.
The treatment toxicity was low. The highest incidence of side effects occurred at initiation of therapy. It was mostly anemia and thrombocytopenia.
The observations from the COMBI study show that, for the combination of interferon in lower doses with ruxolitinib, it may be effective and well tolerated even in the group of patients who had intolerance to interferon used as the only drug in higher doses. The combined treatment improved the bone marrow in terms of fibrosis and its cellularity. It also allowed to improve the value of peripheral blood counts [36].
It is currently known that some of the additional mutations are associated with a worse prognosis in patients with myelorpoliferation, including patients with myelofibrosis. Some of these mutations have been identified as high-risk molecular mutations. These are ASXL1, EZH2, IDH1/2, or SRSF2. Earlier studies have shown their association with a more aggressive course of the disease, worse prognosis, and shorter survival of patients, as well as a poorer response to treatment. Due to their importance, they have been included in the diagnostic criteria of myelofibrosis [37].
It is also known that the presence of driver mutations, i.e., JAK2, CALR, and MPL or triple negativity, may affect the course of myeloproliferation, including the incidence of thromboembolic complications.
The assessment of the influence of driver mutations and a panel of selected additional mutations on the effectiveness of interferon treatment in patients with myelofibrosis was performed on a group of 30 patients. Only the patients with low- and intermediate-1-risk were enrolled in the study. The treatment with pegylated interferon alpha-2a or interferon alpha-2b resulted in a complete remission in two patients and partial remission in nine patients. The disease progressed in three cases. One patient relapsed and four died. The remaining patients achieved a clinical improvement or disease stabilization. In the studied group, it was not found if the effectiveness of interferon treatment was influenced by the lack of driver mutations. Among the group of four patients with additional mutations, two died and one had disease progression. It was a mutation of ASXL1 and SRSF2. The treatment with interferon in patients without additional molecular mutations in the early stages of the disease may prevent further progression of the disease [38].
The side effects of interferon in the group of patients with myelofibrosis are similar to those occurring after the treatment of other chronic myeloproliferative diseases. The most frequently described are hematological toxicity- anemia and thrombocytopenia, less often is the appearance of leukopenia. Hematological toxicity usually resolves with dose reduction or extension of the dose interval. The most frequently nonhematological toxicity was fatigue, muscle pain, weakness, and depression symptoms. All symptoms are usually mild and do not exceed grade 2 [38].
However, the use of interferon in the treatment of myelofibrosis has not been recommended as a standard therapy. Interferon is still being evaluated in clinical trials, or it is used in selected patients as a nonstandard therapy in this diagnosis.
Mastocytosis is characterized by an excessive proliferation of abnormal mast cells and their accumulation in various organs.
The basis for the development of mastocytosis is ligand-independent activation of the KIT receptor, resulting from mutations in the KIT proto-oncogene. The KIT receptor is a trans membrane receptor with tyrosine kinase’s activity. Its activation stimulates the proliferation of mast cells. That excessive numbers of mast cells infiltrate tissues and organs and release mediators such as histamine, interleukine-6, tryptase, heparin, and others, which are responsible for the appearance of symptoms typical of mastocytosis. In addition, the infiltration of tissues for mast cells itself causes damage to the affected organs.
The prognosis of mastocytosis depends on the type of the disease. In the case of cutaneous mastocytosis (CM), in the majority of cases prognosis is good and the disease does not shorten the patient’s life, but in aggressive systemic mastocytosis (ASM), the average follow-up is about 40 months. Mast cell leukemia has a poor prognosis with a median follow-up of approximately 1 year.
Systemic mastocytosis usually requires the implementation of cytoreductive therapy. The first line of therapy is interferon alone or its combination with corticosteroids. In aggressive systemic mastocytosis, the first line in addition to interferon 2-CdA can be used. An effective drug turned out to be midostaurin in the case of the present KIT mutation. In patients without the KIT D816V mutation, treatment with imatinib may be effective. In the case of mast cell leukemia, multidrug chemotherapy is most often required, as in acute leukemias, followed by bone marrow transplantation [39].
Systemic mastocytosis requiring treatment is a rare disease, this is why the studies available in the literature evaluating various therapies concern mostly small groups of patients.
In 2002, the French authors presented their experiences on the use of interferon in patients with systemic mastocytosis. They included 20 patients. The patients received interferon alpha-2b in gradually increased doses.
The patients were assessed after 6 months. In cases in which bone marrow was infiltrated for mast cells at baseline, it still remained infiltrated after 6 months of treatment.
However, the responses were obtained in terms of symptoms related to mast cell degranulation. Partial remission was achieved in 35% of patients and minor remission in 30%. It concerns mainly skin lesions and vascular congestion. Moreover, the assessment of the histamine level in the plasma revealed a decrease of it in patients who previously presented symptoms related to the degranulation of mast cells, such as gastrointestinal disorders and flushing.
A high percentage of side effects were found during treatment. They concerned 35% of patients. Depression and cytopenia were most frequent ones [40].
Another analysis was a report of five patients with systemic mastocytosis treated with interferon and prednisolone. All patients received interferon alpha-2b in a dose of 3 million units three times a week and four patients additionally received prednisolone. Four patients responded to interferon treatment at varying degrees. One patient, who at baseline had bone marrow involvement by mast cells in above 10%, progressed to mast cell leukemia. In two patients, the symptoms C resolved completely and in one of them they partially disappeared. In one case, stabilizing disease was achieved [41].
In 2009, a retrospective analysis of patients treated with cytoreductive therapy due to mastocytosis was published. The authors collected data from 108 patients treated at the Mayo Clinic. This analysis allowed for the comparison of the efficacy of four drugs used in systemic mastocytosis. There were interferon alpha alone or in the combination with prednisone—among 40 patients, hydroxycarbamide—among 26 ones, imatinib—among 22 persons, and 2-chlorodeoxyadenosine (2-CdA)—among 22 patients.
After dividing the patients into three additional groups on the basis of the type of mastocytosis—indolent systemic mastocytosis, aggressive systemic mastocytosis, and systemic mastocytosis associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD)—the effectiveness of each of type of therapy was assessed.
The highest response rates in indolent and aggressive mastocytosis were achieved with interferon treatment. They were 60% of the responses in both groups, and in the SM-AHNMD group of patients, the percentage was also one of the highest and amounted to 45%. The second most effective drug was 2-CdA. The response rates were 56% for indolent MS, 50% for aggressive MS, and 55% for SM-AHNMD. The patients treated with imatinib achieved response in 14, 50, and 9% by following groups, respectively. In contrast, patients with indolent and aggressive systemic mastocytosis did not respond to hydroxycarbamide treatment at all. The response rate in both groups was 0%. However, patients with MS associated with another clonal hematological nonmast cell lineage disease achieved 21% response to hydroxycarbamide. Additionally, it was found that only interferon relieved symptoms caused by the release of inflammatory mediators by mast cells.
The additional analysis showed no influence of the TET 2 mutation on the response to treatment [42].
In the literature, there are also single cases of mastocytosis presenting trials of nonstandard treatment. That is description of a patient with systemic mastocytosis with mast cell bone marrow involvement. Mutation of c-kit Asp816Val was present. Patient progressed despite treatment with dasatinib and 2-chlorodeoxyadenosine. The patient developed symptoms related to the degranulation of mast cells and increased ascites.
The patient was treated with pranlukast, which is an anti-leukotriene receptor antagonist due to an asthma episode. The rate of ascites growth decreased significantly after one administration. The patient required paracentesis every 10 days and not every 3 days, as before starting to take the drug. After 15 days of treatment with pranlukast, the patient received interferon alpha, which resulted in complete regression of ascites, resolution of pancytopenia, and complete disappearance of the c-kit mutation clone. The infiltration of mast cells in the bone marrow significantly decreased [43].
Interferon alpha was also effective in a patient with systemic mastocytosis associated with myelodysplastic syndrome with the c-kit D816V mutation, which was refractory to imatinib treatment [44].
Interferon alpha also proved to be effective in the treatment of osteoporotic lesions appearing in the course of mastocytosis.
The series of 10 cases with resolved mastocytosis and osteoporosis-related fractures was presented in 2011. The patients received interferon alpha in a dose of 1.5 million units three times a week as well as pamindronic acid. The patients were treated for an average of 60 months. For the first 2 years, pamindronate was given at a dose of 1 mg/kg every month, and then every 3 months.
During the course of the study, no patient had a new-bone fracture. The level of alkaline phosphatase decreased by 25% in relation to the value before treatment and tryptase by 34%. Bone density increased during treated with interferon and pamindronate. The increase was on average 12% in the spine bones and 1.9% in the hip bones. At the same time, there was no increase in the density of the hip bone and a minimal increase in the density of the spine in patients treated with pamindronate alone.
The results of this observation suggest that it is beneficial to add low doses of interferon alpha to pamindronate treatment in terms of bone density increase [45].
That experiences show that interferon used in systemic mastocytosis significantly improves the quality of life of patients by inhibiting the symptoms caused by degranulation of mast cells. They prevent bone fractures and, in some patients, they cause remission of bone marrow infiltration by mast cells.
Chronic neutrophilic leukemia (CNL) is a very rare disease. It is characterized by the clonal proliferation of mature neutrophils.
The diagnostic criteria proposed by the World Health Organization (WHO) comprise leukocyte counts above 25,000/μl (including more than 80% of rod and segmented
Physical examination often shows enlargement of the liver and spleen, moreover, patients complain on weight loss and weakness [1].
The prognosis varies. The average survival time for patients with CNL is less than 2 years.
Only few descriptions of chronic neutrophilic leukemia are available in the literature, and these are mostly single case reports.
Because it is an extremely rare disease, there are no established and generally accepted treatment standards. In most cases, patients are given hydroxycarbamide or interferon. Patients who are eligible for a bone marrow transplant may benefit from this treatment. Bone marrow allotransplantation remains the only method that gives a chance for a significant extension of life.
The German authors presented a series of 14 cases of chronic neutrophilic leukemia. The group of patients consisted of eight women and six men. The average age was 64.7 years. From the entire group of patients, longer survival was achieved only in three cases. One of these patients was treated with interferon alpha and achieved hematological remission, the other underwent bone marrow allotransplantation from a family donor, and the third one was treated with hydroxycarbamide and transfusions as needed. The follow-up period of the patient after allogeneic matched related donor transplantation (allo-MRD) was 73 months, and for the patient after interferon treatment it was 41 months.
The remaining patients died within 2 years of diagnosis. Six patients, the largest group, died due to intracranial bleeding, three patients died because of leukemia cell tissue infiltration, one patient because of the disease transformation into leukemia, and one patient because of pneumonia [46].
It can be seen from these experiences that treatment with interferon alpha can significantly extend the survival time of patients.
The case of a 40-year-old woman diagnosed with chronic neutrophilic leukemia is presented by Yassin and coauthors. Initially, the patient had almost 41,000 leukocytes in the peripheral blood. In a physical examination, splenomegaly and hepatomegaly were not present. Patient received pegylated interferon alpha-2a. The initially dose was 50 μg once a week for the first 2 weeks, then the dose was increased to 135 μg weekly for 6 weeks, and then the dose interval was extended to another 2 weeks. As a result of the treatment, the general condition of the patient improved and the parameters of peripheral blood counts were normalized [47].
Another case report presented in the literature describes a 41-year-old woman diagnosed with CNL accompanied by focal segmental glomerulosclerosis (FSGS). The patient had increasing leukocytosis for several months. On the admission to the hospital, leukocytosis was 94,000/μl. Moreover, the number of platelets in the morphology exceeded 1,000,000/μl. More than a year earlier, the patient had splenectomy due to splenomegaly and spleen infraction.
Additionally, JAK2 V617F mutation was found. Some authors suggest that the presence of JAK2 mutation may be associated with longer survival in CNL.
The patient received hydroxycarbamide for 3 months and reduction in the number of leukocytes was achieved. After this time, interferon alpha-2b was added to hydroxycarbamide. As a result, focal segmental glomerulosclerosis disappeared and the renal tests improved [48].
Another case of chronic neutrophilic leukemia with a JAK2 gene mutation concerns a 53-year-old man. The patient’s baseline leukocytosis was 33,500/μl, including the neutrophil count of 29,700/μl. The patient also had splenomegaly.
The treatment with interferon alpha-2b at a dose of 3 million units every other day was started. After a month of treatment, the number of leukocytes was reduced to less than 10,000/μl. Then the patient was treated chronically with interferon alpha-2b in doses of 3 million units every 2 weeks. As a result of the therapy, the number of leukocytes remains between 8 and 10,000/μl. The patient remains in general good condition [49].
A series of two CNL cases are also shown. The first patient was a 70-year-old woman with stable leukocytosis of about 35,000/μl and the remaining morphology parameters in normal range. The patient was only observed for 5 years until hepasplenomegaly progressed rapidly. Then, interferon alpha-2b was included. Due to the treatment, the rapid regression of hepatosplenomegaly was achieved.
The second case is a 68-year-old woman with baseline leukocytosis of almost 14,000/μl. In this case, the treatment with hydroxycarbamide was started immediately. However, no improvement was achieved. After 6 weeks of HU treatment, interferon alpha-2b 3 million units 3 times a week was implemented and leukocytosis decreased. Due to the interferon treatment, the disease stabilized for a long time. Because the patient experienced an adverse reaction, a severe flu-like syndrome, interferon was discontinued. After interferon withdrawal, the disease progressed gradually and the treatment attempts by busulfan and 6-mercaptopurine were unsuccessful. Therefore, interferon was readministered and the disease went into remission. Interferon treatment was continued at a reduced dose. The disease regression was achieved again.
Additionally, the patient showed an improvement in the function of granulocytes in terms of phagocytosis and an improvement in neutral killer (NK) cell function after treatment with interferon [50].
The above examples show that interferon alpha is effective in the treatment of chronic neutrophilic leukemia. The side effects are rare and can be managed with dose reductions. Moreover, in these cases, interferon is also effective in a reduced dose. Disease remission or regression can be achieved without typical of CNL complications, such as intracranial bleeding.
Interferon has been used in the past to treat chronic myeloid leukemia. The treatment with tyrosine kinase inhibitors is now a standard practice. However, in a small number of patients, they are ineffective or exhibit unmanageable toxicity. Therefore, the attempts are underway to use interferon in combination with TKI in lower doses, which is to ensure the enhancement of the antiproliferative effect while reducing the toxicity.
There are ongoing attempts to use ropeginterferon in patients diagnosed with chronic myeloid leukemia, in whom treatment with imatinib alone has not led to deep molecular response (DMR). The first phase study was conducted in a small group of patients with chronic myeloid leukemia. The patients in first chronic phase treated with imatinib who did not achieve DMR, but in complete hematologic remission and complete cytogenetic remission, were included in the study. Patients have been treated with imatinib for at least 18 months. Twelve patients were enrolled in the study, and they completed the study according to the protocol. These patients received additional ropeginterferon to imatinib and four achieved DMR. Low toxicity was observed during the treatment. Among the hematological toxicities, neutropenia was the most common. There was no nonhematological toxicity with a degree higher than 1/2 during the treatment. Moreover, it has been found that better effects and fewer side effects are obtained when ropeginterferon is administered for a longer time, but in lower doses. The comparison of the effectiveness of interferon in chronic myeloproliferative disorders based on selected articles is presented in Table 1 [51].
Source | Type of trial | Interferon | Diagnosis | No. | Prior treatment status | Response rate |
---|---|---|---|---|---|---|
Yacoubet al. [15] | Phase II, multicenter | Pegylated IFN alfa-2a | PV | 50 | Resistance to HU or HU intolerance | CR:22% PR:38% |
ET | 65 | CR:43% PR:26% | ||||
Masarova et al. [16] | Phase II, single-center | Pegylated IFN alfa-2a | PV | 43 | Untreated or previously treated with cytoreductive therapy | CR:77% PR:7% |
ET | 40 | CR:73% PR:3% | ||||
Samuelsson et al. [18] | Phase II | Pegylated IFN alfa-2b | PV | 21 | Untreated or previously treated with cytoreductive therapy | CR: 69% for the entire group |
ET | 21 | |||||
Huang BT et al. [19] | Open label, multicenter | IFN alfa-2b | PV | 136 | Untreated or previously treated with cytoreductive therapy | OHR:70% Molecular response:54.7% |
ET | 123 | OHR (JAK2+ patients):83% CHR:23 cases OHR (JAK2-patients): 61.4% CHR:12 cases | ||||
Gisslinger et al. [23] | phase III, multicenter | Ropeginterferon | PV | 257 | Previously treated | OHR:53% |
Quintás-Cardama et al. [26] | phase II | Pegylated IFN alfa-2a | PV | 40 | Untreated or previously treated with cytoreductive therapy | OHR:80% CR:70% Molecular remission:54% |
ET | 39 | OHR:81% CR:76% Molecular remission:38% | ||||
Sørensen et al. [36] | Phase III, multicenter, COMBI | Pegylated IFN alfa-2a with ruxolitinib or Pegylated IFN alfa-2b with ruxolitinib | PV | 32 | Untreated or previously treated with cytoreductive therapy | OHR:44% CR:28% |
MF | 18 | OHR:31% CR:9% | ||||
Casassus et al. [40] | Open label, multicenter | IFN alpha-2b | Mastocytosis | 20 | Untreated and previously treated | PR:35% Minor remission: 30% |
Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
PV: polycythemia vera; ET: essential thrombocythemia; MF: myelofibrosis; HU: hydroxycarbamide/hydroxyurea; CR: complete remission; PR: partial remission; and OHR: overall hematological response.
Interferon alpha appears to be an effective and safe drug in the most type of chronic myeloproliferative disorders. Nowadays, all forms of its using have similar effectiveness. Interferon alpha can be effective even in cases of resistance for first-line treatment. Trial research is currently underway to combine it with some new drugs, such as ruxolitinib, and to add it to the already well-established therapy, it is a promising option for patients with refractory disease.
From time to time, new forms of interferon, such as ropeginterferon, are introduced, which gives hope for better effectiveness, better safety profile, and greater comfort in its use for patients who have to be treated for many years. In the case of the use of interferons alpha in the treatment of chronic myeloproliferative diseases, there are still opportunities to extend its use and to study its combination with newly introduced drugs.
Our journals are currently in their launching issue. They will be applied to all relevant indexes as soon as they are eligible. These include (but are not limited to): Web of Science, Scopus, PubMed, MEDLINE, Database of Open Access Journals (DOAJ), Google Scholar and Inspec.
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The chapter describes the design, implementation and integration of a ground penetrating radar (GPR) using a software defined radio (SDR) platform into the aerial drone. The chapter?s goal is first to tackle in detail the development of a custom-designed lightweight GPR by approaching interplay between hardware and software radio on an SDR platform. The SDR-based GPR system results on a much lighter sensing device compared against the conventional GPR systems found in the literature and with the capability of re-configuration in real-time for different landmines and terrains, with the capability of detecting landmines under terrains with different dielectric characteristics. Secondly, the chapter introduce the integration of the SDR-based GPR into an autonomous drone by describing the mechanical integration, communication system, the graphical user interface (GUI) together with the landmine detection and geo-mapping. This chapter approach completely the hardware and software implementation topics of the on-board GPR system given first a comprehensive background of the software-defined radar technology and second presenting the main features of the Tx and Rx modules. Additional details are presented related with the mechanical and functional integration of the GPR into the UAV system.",book:{id:"5905",slug:"robots-operating-in-hazardous-environments",title:"Robots Operating in Hazardous Environments",fullTitle:"Robots Operating in Hazardous Environments"},signatures:"Manuel Ricardo Pérez Cerquera, Julian David Colorado Montaño\nand Iván Mondragón",authors:[{id:"177422",title:"Dr.",name:"Julian",middleName:null,surname:"Colorado",slug:"julian-colorado",fullName:"Julian Colorado"},{id:"197884",title:"Prof.",name:"Ivan",middleName:null,surname:"Mondragon",slug:"ivan-mondragon",fullName:"Ivan Mondragon"},{id:"199958",title:"Prof.",name:"Manuel",middleName:null,surname:"Perez",slug:"manuel-perez",fullName:"Manuel Perez"}]},{id:"15855",title:"Kinematics of AdeptThree Robot Arm",slug:"kinematics-of-adeptthree-robot-arm",totalDownloads:14668,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"152",slug:"robot-arms",title:"Robot Arms",fullTitle:"Robot Arms"},signatures:"Adelhard Beni Rehiara",authors:[{id:"29287",title:"Dr.",name:"Adelhard",middleName:"Beni",surname:"Rehiara",slug:"adelhard-rehiara",fullName:"Adelhard Rehiara"}]},{id:"62978",title:"Intelligent Robotic Perception Systems",slug:"intelligent-robotic-perception-systems",totalDownloads:2443,totalCrossrefCites:5,totalDimensionsCites:11,abstract:"Robotic perception is related to many applications in robotics where sensory data and artificial intelligence/machine learning (AI/ML) techniques are involved. Examples of such applications are object detection, environment representation, scene understanding, human/pedestrian detection, activity recognition, semantic place classification, object modeling, among others. Robotic perception, in the scope of this chapter, encompasses the ML algorithms and techniques that empower robots to learn from sensory data and, based on learned models, to react and take decisions accordingly. The recent developments in machine learning, namely deep-learning approaches, are evident and, consequently, robotic perception systems are evolving in a way that new applications and tasks are becoming a reality. Recent advances in human-robot interaction, complex robotic tasks, intelligent reasoning, and decision-making are, at some extent, the results of the notorious evolution and success of ML algorithms. This chapter will cover recent and emerging topics and use-cases related to intelligent perception systems in robotics.",book:{id:"7227",slug:"applications-of-mobile-robots",title:"Applications of Mobile Robots",fullTitle:"Applications of Mobile Robots"},signatures:"Cristiano Premebida, Rares Ambrus and Zoltan-Csaba Marton",authors:[{id:"203409",title:"Ph.D.",name:"Cristiano",middleName:null,surname:"Premebida",slug:"cristiano-premebida",fullName:"Cristiano Premebida"},{id:"254880",title:"Dr.",name:"Rares",middleName:null,surname:"Ambrus",slug:"rares-ambrus",fullName:"Rares Ambrus"},{id:"254881",title:"Dr.",name:"Zoltan-Csaba",middleName:null,surname:"Marton",slug:"zoltan-csaba-marton",fullName:"Zoltan-Csaba Marton"}]},{id:"67705",title:"Advanced UAVs Nonlinear Control Systems and Applications",slug:"advanced-uavs-nonlinear-control-systems-and-applications",totalDownloads:1971,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Recent development of different control systems for UAVs has caught the attention of academic and industry, due to the wide range of their applications such as in surveillance, delivery, work assistant, and photography. In addition, arms, grippers, or tethers could be installed to UAVs so that they can assist in constructing, transporting, and carrying payloads. In this book chapter, the control laws of the attitude and position of a quadcopter UAV have been derived basically utilizing three methods including backstepping, sliding mode control, and feedback linearization incorporated with LQI optimal controller. The main contribution of this book chapter would be concluded in the strategy of deriving the control laws of the translational positions of a quadcopter UAV. The control laws for trajectory tracking using the proposed strategies have been validated by simulation using MATLAB®/Simulink and experimental results obtained from a quadcopter test bench. Simulation results show a comparison between the performances of each of the proposed techniques depending on the nonlinear model of the quadcopter system under investigation; the trajectory tracking has been achieved properly for different types of trajectories, i.e., spiral trajectory, in the presence of unknown disturbances. Moreover, the practical results coincided with the results of the simulation results.",book:{id:"7792",slug:"unmanned-robotic-systems-and-applications",title:"Unmanned Robotic Systems and Applications",fullTitle:"Unmanned Robotic Systems and Applications"},signatures:"Abdulkader Joukhadar, Mohammad Alchehabi and Adnan Jejeh",authors:null}],onlineFirstChaptersFilter:{topicId:"22",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82223",title:"Biomechanical Design Principles Underpinning Anthropomorphic Manipulators",slug:"biomechanical-design-principles-underpinning-anthropomorphic-manipulators",totalDownloads:12,totalDimensionsCites:0,doi:"10.5772/intechopen.105434",abstract:"The biomechanical design of an artificial anthropomorphic manipulator is the focus of many researchers in diverse fields. Current electromechanical artificial hands are either in the research stage, expensive, have patents, lack severely in function, and/or are driven by robotic/mechanical principles, which tend to ignore the biological requirements of such designs. In response to the challenges addressed above this chapter discusses the potential of current technology and methods used in design to bridge the chasm that exists between robot manipulators and the human hand. This chapter elucidates artificial anthropomorphic manipulator design by outlining biomechanical concepts that contribute to the function, esthetics and performance of artificial manipulators. This chapter addresses joint stabilization, tendon structures and tendon excursion in artificial anthropomorphic manipulators.",book:{id:"11455",title:"Recent Advances in Robot Manipulators",coverURL:"https://cdn.intechopen.com/books/images_new/11455.jpg"},signatures:"Mahonri William Owen and Chikit Au"},{id:"82056",title:"Learning Robotic Ultrasound Skills from Human Demonstrations",slug:"learning-robotic-ultrasound-skills-from-human-demonstrations",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.105069",abstract:"Robotic ultrasound system plays a vital role in assisting or even replacing sonographers in some cases. However, modeling and learning ultrasound skills from professional sonographers are still challenging tasks that hinder the development of ultrasound systems’ autonomy. To solve these problems, we propose a learning-based framework to acquire ultrasound scanning skills from human demonstrations1. First, ultrasound scanning skills are encapsulated into a high-dimensional multi-modal model, which takes ultrasound images, probe pose, and contact force into account. The model’s parameters can be learned from clinical ultrasound data demonstrated by professional sonographers. Second, the target function of autonomous ultrasound examinations is proposed, which can be solved roughly by the sampling-based strategy. The sonographers’ ultrasound skills can be represented by approximating the limit of the target function. Finally, the robustness of the proposed framework is validated with the experiments on ground-true data from sonographers.",book:{id:"10823",title:"Cognitive Robotics",coverURL:"https://cdn.intechopen.com/books/images_new/10823.jpg"},signatures:"Miao Li and Xutian Deng"},{id:"82057",title:"An Episodic-Procedural Semantic Memory Model for Continuous Topological Sensorimotor Map Building",slug:"an-episodic-procedural-semantic-memory-model-for-continuous-topological-sensorimotor-map-building",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.104818",abstract:"For humans to understand the world around them, learning and memory are two cognitive processes of the human brain that are deeply connected. Memory allows information to retain and forms an experiences reservoir. Computational models replicating those memory attributes can lead to the practical use of robots in everyday human living environments. However, constantly acquiring environmental information in real-world, dynamic environments has remained a challenge for many years. This article proposes an episodic-procedure semantic memory model to continuously generate topological sensorimotor maps for robot navigation. The proposed model consists of two memory networks: i) episodic-procedural memory network (EPMN) and ii) semantic memory network (SMN). The EPMN comprises an Incremental Recurrent Kernel Machines (I-RKM) that clusters incoming input vectors as nodes and learns the activation patterns of the nodes for spatiotemporal encoding. The SMN then takes neuronal activity trajectories from the EPMN and task-relevant signals to update the SMN and produce more compact representations of episodic experience. Thus, both memory networks prevent catastrophic forgetting by constantly generating nodes when the network meets new inputs or updating node weights when the incoming input is similar to previously learned knowledge. In addition, idle or outlier nodes will be removed to preserve memory space.",book:{id:"10823",title:"Cognitive Robotics",coverURL:"https://cdn.intechopen.com/books/images_new/10823.jpg"},signatures:"Wei Hong Chin, Naoyuki Kubota and Chu Kiong Loo"},{id:"81922",title:"Skill Acquisition for Resource-Constrained Mobile Robots through Continuous Exploration",slug:"skill-acquisition-for-resource-constrained-mobile-robots-through-continuous-exploration",totalDownloads:18,totalDimensionsCites:0,doi:"10.5772/intechopen.104996",abstract:"We present a cognitive mobile robot that acquires knowledge, and autonomously learns higher-level abstract capabilities based on play instincts, inspired by human behavior. To this end, we (i) model skills, (ii) model the robot’s sensor and actuator space based on elementary physical properties, and (iii) propose algorithms inspired by humans’ play instincts that allow the robot to autonomously learn the skills based on its sensor and actuator capabilities. We model general knowledge in the form of competencies (skills) of the mobile robot based on kinematic properties using physical quantities. Thus, by design, our approach has the potential to cover very generic application domains. To connect desired skills to the primitive capabilities of the robot’s sensors and actuators, it playfully explores the effects of its actions on its sensory input, thus autonomously learning relations and dependencies and eventually the desired skill. KnowRob is used for knowledge representation and reasoning, and the robot’s operation is based on ROS. In the experiments, we use a millirobot, sized 2 cm2, equipped with two wheels, motion, and distance sensors. We show that our cognitive mobile robot can successfully and autonomously learn elementary motion skills based on a playful exploration of its wheels and sensors.",book:{id:"10823",title:"Cognitive Robotics",coverURL:"https://cdn.intechopen.com/books/images_new/10823.jpg"},signatures:"Markus D. Kobelrausch and Axel Jantsch"},{id:"81693",title:"The Neo-Mechanistic Model of Human Cognitive Computation and Its Major Challenges",slug:"the-neo-mechanistic-model-of-human-cognitive-computation-and-its-major-challenges",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104995",abstract:"The neo-mechanistic theory of human cognition is currently one of the most accepted major theories in fields, such as cognitive science and cognitive neuroscience. This proposal offers an account of human cognitive computation, and it has been considered by its proponents as revolutionary and capable of integrating research concerning human cognition with new evidence provided by fields of biology and neuroscience. However, some complex cognitive capacities still present a challenge for explanations constructed by using this theoretical structure. In this chapter, I make a presentation of some of the central tenets of this framework and show in what dimensions it helps our understanding of human cognition concerning aspects of capacities, such as visual perception and memory consolidation. My central goal, however, is to show that to understand and explain some particular human cognitive capacities, such as self-consciousness and some conscious informal reasoning and decision making, the framework shows substantial limitations. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. 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He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. 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She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. 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