Somatic mutations (TCGA findings).
\\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:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"9878",leadTitle:null,fullTitle:"Electromagnetic Wave Propagation for Industry and Biomedical Applications",title:"Electromagnetic Wave Propagation for Industry and Biomedical Applications",subtitle:null,reviewType:"peer-reviewed",abstract:"This book highlights original research and high-quality technical briefs on electromagnetic wave propagation, radiation, and scattering, and their applications in industry and biomedical engineering. It also presents recent research achievements in the theoretical, computational, and experimental aspects of electromagnetic wave propagation, radiation, and scattering. The book is divided into three sections. Section 1 consists of chapters with general mathematical methods and approaches to the forward and inverse problems of wave propagation. Section 2 presents the problems of wave propagation in superconducting materials and porous media. Finally, Section 3 discusses various industry and biomedical applications of electromagnetic wave propagation, radiation, and scattering.",isbn:"978-1-83968-582-8",printIsbn:"978-1-83968-581-1",pdfIsbn:"978-1-83968-583-5",doi:"10.5772/intechopen.87687",price:119,priceEur:129,priceUsd:155,slug:"electromagnetic-wave-propagation-for-industry-and-biomedical-applications",numberOfPages:196,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"e57ef4b5bada0d966637cd303d76278f",bookSignature:"Lulu Wang",publishedDate:"March 16th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/9878.jpg",numberOfDownloads:1739,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:0,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 26th 2020",dateEndSecondStepPublish:"November 3rd 2020",dateEndThirdStepPublish:"January 2nd 2021",dateEndFourthStepPublish:"March 23rd 2021",dateEndFifthStepPublish:"May 22nd 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",slug:"lulu-wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",biography:"Lulu Wang is a Distinguished Professor of Biomedical Engineering, Shenzhen Technology University, China. Dr. Wang is a member of the American Society of Mechanical Engineers (ASME), Institute of Electrical and Electronics Engineers (IEEE), American Association for the Advancement of Science (AAAS), Physiological Society of New Zealand (PSNZ), and Institution of Professional Engineers New Zealand (IPENZ). Her research interests include medical devices, electromagnetic sensing and imaging, and computational mechanics. Over the past five years, Dr. Wang has authored more than seventy peer-reviewed publications, two ASME books, seven book chapters, and ten issued patents. She is an active reviewer of numerous journals, books, and conferences. She has edited four books and three special issues of international journals. She has received multiple national and international awards from various professional societies and organizations. She is an active organizer of several international conferences, including the ASME International Mechanical Engineering Congress & Exposition and the International Conference on Computational & Experimental Engineering Sciences. She has been selected as the World’s Top 2% Scientists 2021 (by Stanford University).",institutionString:"Shenzhen Technology University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"737",title:"Electromagnetism",slug:"electrical-and-electronic-engineering-electromagnetism"}],chapters:[{id:"76338",title:"Dyadic Green’s Function for Multilayered Planar, Cylindrical, and Spherical Structures with Impedance Boundary Condition",doi:"10.5772/intechopen.95834",slug:"dyadic-green-s-function-for-multilayered-planar-cylindrical-and-spherical-structures-with-impedance-",totalDownloads:139,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The integral equation (IE) method is one of the efficient approaches for solving electromagnetic problems, where dyadic Green’s function (DGF) plays an important role as the Kernel of the integrals. In general, a layered medium with planar, cylindrical, or spherical geometry can be used to model different biomedical media such as human skin, body, or head. Therefore, in this chapter, different approaches for the derivation of Green’s function for these structures will be introduced. Due to the recent great interest in two-dimensional (2D) materials, the chapter will also discuss the generalization of the technique to the same structures with interfaces made of isotropic and anisotropic surface impedances. To this end, general formulas for the dyadic Green’s function of the aforementioned structures are extracted based on the scattering superposition method by considering field and source points in the arbitrary locations. Apparently, by setting the surface conductivity of the interfaces equal to zero, the formulations will turn into the associated problem with dielectric boundaries. This section will also aid in the design of various biomedical devices such as sensors, cloaks, and spectrometers, with improved functionality. Finally, the Purcell factor of a dipole emitter in the presence of the layered structures will be discussed as another biomedical application of the formulation.",signatures:"Shiva Hayati Raad and Zahra Atlasbaf",downloadPdfUrl:"/chapter/pdf-download/76338",previewPdfUrl:"/chapter/pdf-preview/76338",authors:[{id:"18749",title:"Dr.",name:"zahra",surname:"atlasbaf",slug:"zahra-atlasbaf",fullName:"zahra atlasbaf"},{id:"313000",title:"Ph.D.",name:"Shiva",surname:"Hayati Raad",slug:"shiva-hayati-raad",fullName:"Shiva Hayati Raad"}],corrections:null},{id:"76596",title:"A TLM Formulation Based on Fractional Derivatives for Dispersive Cole-Cole Media",doi:"10.5772/intechopen.96378",slug:"a-tlm-formulation-based-on-fractional-derivatives-for-dispersive-cole-cole-media",totalDownloads:158,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"An auxiliary differential equation (ADE) transmission line method (TLM) is proposed for broadband modeling of electromagnetic (EM) wave propagation in biological tissues with the Cole-Cole dispersion Model. The fractional derivative problem is surmounted by assuming a linear behavior of the polarization current when the time discretization is short enough. The polarization current density is approached using Lagrange extrapolation polynomial and the fractional derivation is obtained according to Riemann definition of a fractional α-order derivative. Reflection coefficients at an air/muscle and air/fat tissues interfaces simulated in a 1-D domain are found to be in good agreement with those obtained from the analytic model over a broad frequency range, demonstrating the validity of the proposed approach.",signatures:"Mohammed Kanjaa, Otman El Mrabet and Mohsine Khalladi",downloadPdfUrl:"/chapter/pdf-download/76596",previewPdfUrl:"/chapter/pdf-preview/76596",authors:[{id:"335735",title:"Dr.",name:"Mohammed",surname:"Kanjaa",slug:"mohammed-kanjaa",fullName:"Mohammed Kanjaa"},{id:"451607",title:"Dr.",name:"Otman El Mrabet",surname:"El Mrabet",slug:"otman-el-mrabet-el-mrabet",fullName:"Otman El Mrabet El Mrabet"},{id:"451608",title:"Dr.",name:"Mohsine",surname:"Khalladi",slug:"mohsine-khalladi",fullName:"Mohsine Khalladi"}],corrections:null},{id:"74643",title:"Averaged No-Regret Control for an Electromagnetic Wave Equation Depending upon a Parameter with Incomplete Initial Conditions",doi:"10.5772/intechopen.95447",slug:"averaged-no-regret-control-for-an-electromagnetic-wave-equation-depending-upon-a-parameter-with-inco",totalDownloads:173,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter concerns the optimal control problem for an electromagnetic wave equation with a potential term depending on a real parameter and with missing initial conditions. By using both the average control notion introduced recently by E. Zuazua to control parameter depending systems and the no-regret method introduced for the optimal control of systems with missing data. The relaxation of averaged no-regret control by the averaged low-regret control sequence transforms the problem into a standard optimal control problem. We prove that the problem of average optimal control admits a unique averaged no-regret control that we characterize by means of optimality systems.",signatures:"Abdelhak Hafdallah and Mouna Abdelli",downloadPdfUrl:"/chapter/pdf-download/74643",previewPdfUrl:"/chapter/pdf-preview/74643",authors:[{id:"330025",title:"Dr.",name:"Abdelhak",surname:"Hafdallah",slug:"abdelhak-hafdallah",fullName:"Abdelhak Hafdallah"},{id:"339881",title:"Dr.",name:"Mouna",surname:"Abdelli",slug:"mouna-abdelli",fullName:"Mouna Abdelli"}],corrections:null},{id:"76123",title:"Using Electromagnetic Properties to Identify and Design Superconducting Materials",doi:"10.5772/intechopen.97327",slug:"using-electromagnetic-properties-to-identify-and-design-superconducting-materials",totalDownloads:130,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Superconductors have a wide array of applications, such as medical imaging, supercomputing, and electric power transmission, but superconducting materials only operate at very cold temperatures. Thus, the quest to engineer room temperature superconductors is currently a hot topic of research. To accomplish this mission, it is important to have a complete understanding of the material properties that are being used to create these superconductors. Understanding the atomic and electromagnetic properties of the prospective materials will provide tremendous insight into the best choice for the materials. Therefore, a theoretical model that incorporates electromagnetic field theory and quantum mechanics principles is utilized to explain the electrical and magnetic characteristics of superconductors. This model can be used to describe the electrical resistance response and why it vanishes at the material’s critical temperature. The model can also explain the behavior of magnetic fields and why some superconducting materials completely exclude magnetic fields while other superconductors partially exclude these fields. Thus, this theoretical analysis produces a model that describes the behavior of both type I and type II superconductors. Since there are subtle differences between superconductors and perfect conductors, this model also accounts for this distinction and explains why superconductors behave differently than perfect conductors. Therefore, this theory addresses the major properties associated with superconducting materials and thus will aid researchers in the pursuit of designing room temperature superconductors.",signatures:"Fred Lacy",downloadPdfUrl:"/chapter/pdf-download/76123",previewPdfUrl:"/chapter/pdf-preview/76123",authors:[{id:"62715",title:"Dr.",name:"Fred",surname:"Lacy",slug:"fred-lacy",fullName:"Fred Lacy"}],corrections:null},{id:"78176",title:"Physics of Absorption and Generation of Electromagnetic Radiation",doi:"10.5772/intechopen.99037",slug:"physics-of-absorption-and-generation-of-electromagnetic-radiation",totalDownloads:270,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The chapter is divided into two parts. In the first part, the chapter discusses the theory of propagation of electromagnetic waves in different media with the help of Maxwell’s equations of electromagnetic fields. The electromagnetic waves with low frequency are suitable for the communication in sea water and are illustrated with numerical examples. The underwater communication have been used for the oil (gas) field monitoring, underwater vehicles, coastline protection, oceanographic data collection, etc. The mathematical expression of penetration depth of electromagnetic waves is derived. The significance of penetration depth (skin depth) and loss angle are clarified with numerical examples. The interaction of electromagnetic waves with human tissue is also discussed. When an electric field is applied to a dielectric, the material takes a finite amount of time to polarize. The imaginary part of the permittivity is corresponds to the absorption length of radiation inside biological tissue. In the second part of the chapter, it has been shown that a high frequency wave can be generated through plasma under the presence of electron beam. The electron beam affects the oscillations of plasma and triggers the instability called as electron beam instability. In this section, we use magnetohydrodynamics theory to obtain the modified dispersion relation under the presence of electron beam with the help of the Poisson’s equation. The high frequency instability in plasma grow with the magnetic field, wave length, collision frequency and the beam density. The growth rate linearly increases with collision frequency of electrons but it is decreases with the drift velocity of electrons. The real frequency of the instability increases with magnetic field, azimuthal wave number and beam density. The real frequency is almost independent with the collision frequency of the electrons.",signatures:"Sukhmander Singh, Ashish Tyagi and Bhavna Vidhani",downloadPdfUrl:"/chapter/pdf-download/78176",previewPdfUrl:"/chapter/pdf-preview/78176",authors:[{id:"282807",title:"Dr.",name:"Sukhmander",surname:"Singh",slug:"sukhmander-singh",fullName:"Sukhmander Singh"},{id:"421908",title:"Mr.",name:"Ashish",surname:"Tyagi",slug:"ashish-tyagi",fullName:"Ashish Tyagi"},{id:"421909",title:"Mrs.",name:"Bhavna",surname:"Vidhani",slug:"bhavna-vidhani",fullName:"Bhavna Vidhani"}],corrections:null},{id:"76372",title:"Electromagnetism of Microwave Heating",doi:"10.5772/intechopen.97288",slug:"electromagnetism-of-microwave-heating",totalDownloads:41,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Detailed electrodynamic descriptions of the fundamental workings of microwave heating devices are presented. We stress that all results come from Maxwell equations and the boundary conditions (BC). We analyze one by one the principal components of a microwave heater; the cooking chamber, the waveguide, and the microwave sources, either klystron or magnetron. The boundary conditions at the walls of the resonant cavity and at the interface air/surface of the food are given and show how relevant the BC are to understand how the microwaves penetrate the nonconducting, electric polarizable specimen. We mention the application of microwaving waste plastics to obtain a good H2 quantity that could be used as a clean energy source for other machines. We obtained trapped stationary microwaves in the resonant cavity and traveling waves in the waveguides. We show 3D plots of the mathematical solutions and agree quite well with experimental measurements of hot/cold patterns. Simulations for cylindrical cavities are shown. The radiation processes in klystrons and magnetrons are described with some detail in terms of the accelerated electrons and their trajectories. These fields are sent to the waveguides and feed the cooking chamber. Whence, we understand how a meal or waste plastic, or an industrial sample is microwave heated.",signatures:"Rafael Zamorano Ulloa",downloadPdfUrl:"/chapter/pdf-download/76372",previewPdfUrl:"/chapter/pdf-preview/76372",authors:[{id:"176210",title:"Dr.",name:"Rafael",surname:"Zamorano Ulloa",slug:"rafael-zamorano-ulloa",fullName:"Rafael Zamorano Ulloa"}],corrections:null},{id:"76524",title:"High-Frequency Electromagnetic Interference Diagnostics",doi:"10.5772/intechopen.97613",slug:"high-frequency-electromagnetic-interference-diagnostics",totalDownloads:238,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Electromagnetic interference (EMI) is becoming more troublesome in modern electronic systems due to the continuous increase of communication data rates. This chapter reviews some new methodologies for high-frequency EMI diagnostics in recent researches. Optical modules, as a typical type of gigahertz radiator, are studied in this chapter. First, the dominant radiation modules and EMI coupling paths in an explicit optical module are analyzed using simulation and measurement techniques. Correspondingly, practical mitigation approaches are proposed to suppress the radiation in real product applications. Moreover, an emission source microscopy (ESM) method, which can rapidly localize far-field radiators, is applied to diagnose multiple optical modules and identify the dominant sources. Finally, when numerous optical modules work simultaneously in a large network router, a formula based on statistical analysis can estimate the maximum far-field emission and the probability of passing electromagnetic compatibility (EMC) regulations. This chapter reviews a systematic procedure for EMI diagnostics at high frequencies, including EMI coupling path analysis and mitigation, emission source localization, and radiation estimation using statistical analysis.",signatures:"Ling Zhang, Yuru Feng, Jun Fan and Er-Ping Li",downloadPdfUrl:"/chapter/pdf-download/76524",previewPdfUrl:"/chapter/pdf-preview/76524",authors:[{id:"331035",title:"Dr.",name:"Ling",surname:"Zhang",slug:"ling-zhang",fullName:"Ling Zhang"},{id:"355320",title:"Prof.",name:"Er-Ping",surname:"Li",slug:"er-ping-li",fullName:"Er-Ping Li"},{id:"356452",title:"Dr.",name:"Yuru",surname:"Feng",slug:"yuru-feng",fullName:"Yuru Feng"},{id:"356453",title:"Dr.",name:"Jun",surname:"Fan",slug:"jun-fan",fullName:"Jun Fan"}],corrections:null},{id:"74935",title:"UHF RFID in a Metallic Harsh Environment",doi:"10.5772/intechopen.95611",slug:"uhf-rfid-in-a-metallic-harsh-environment",totalDownloads:244,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The use of the UHF RFID system in a warehouse that contains steel coils is a challenge for the technology itself since there are countless reflections of the radio frequency waves in the environment causing the multipath effect, which represents one of the most complex problems for wireless communication. Thus, this effect must be managed with the hardware, such as the antenna radiation diagram, and with the software, in the middleware, the software developed for the application. In this chapter, an application of RFID in metallic items will be discussed, tracking them since the product’s hot rolling, controlling the receiving process, shipping, and inventory, working together with equipment such as overhead crane.",signatures:"Renata Rampim and Ivan de Pieri Baladei",downloadPdfUrl:"/chapter/pdf-download/74935",previewPdfUrl:"/chapter/pdf-preview/74935",authors:[{id:"343131",title:"Dr.",name:"Renata",surname:"Rampim",slug:"renata-rampim",fullName:"Renata Rampim"},{id:"345072",title:"Dr.",name:"Ivan",surname:"de Pieri Baladei",slug:"ivan-de-pieri-baladei",fullName:"Ivan de Pieri Baladei"}],corrections:null},{id:"74858",title:"RFID Applications in Retail",doi:"10.5772/intechopen.95787",slug:"rfid-applications-in-retail",totalDownloads:347,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Radio Frequency Identification (RFID) technology is one of the latest product tracking technologies being utilized by retailers. Operations management improvements were among the first recognized applications of this technology earlier in the century. RFID applications in managing retail operations, such as inventory management and control, lead to significant benefits. However, RFID applications are not limited to operations management and go beyond the operations side to offer improvements in other areas in retail such as marketing and managing customers’ shopping experiences. In this research, we review the applications of RFID technology in retail since its introduction and how those applications have evolved over the last two decades to help retailers provide omnichannel services to their customers in the current market. We will demonstrate what strategic and tactical factors have helped retailers implement this technology and what factors have slowed down the process of adoption. 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Head neck squamous cell carcinomas (HNSCC) include cancers arising in the mucosa of oral cavity, pharynx, larynx, hypopharynx. According to GLOBOCAN 2020 report, worldwide head neck cancer statistics indicate that there are 1,518,133 cases of head neck cancers per year, resulting in approximately 510,771 deaths per year. In Asia there are 944,946 cases of head neck cancers per year, resulting in approximately 347,870 deaths per year. High incidence rates have been reported from developing countries including India, Pakistan, Bangladesh, Taiwan, and Sri Lanka [1].
Treatment of HNSCC is guided uniformly by anatomic location, tumor size, presence or absence of nodal and distant metastases. Oral cavity cancers are primary treated with surgery followed by adjuvant radiation or chemo-radiation based on pathological features. Cancers in the oropharynx, larynx and hypopharynx are primary treated with chemo-radiation with function preservation as the main goal of therapy. Neo-adjuvant chemotherapy is used in locally advanced tumors to improve resectability. EGFR targeting drugs afatinib, Cetuximab and immune check point inhibitors pembrolizumab, nivolumab are the only FDA approved biological treatments today.
Clinicians managing HNSCC face number of challenges today. Some of these include.
High mortality in spite of optimal use of currently existing therapeutics.
Lack of clinically meaningful biological classifier of HNSCC other than HPV status.
Continued emergence of treatment resistance.
Great variability in clinical outcome despite uniformity in approach.
Continued reliance on anatomical factors (TNM) to guide treatment.
High morbidity and poor quality of life after conventional treatments
Lack of robust biomarkers to select EGFR targeted therapy which seems to be the only existing targeted therapy for HNSCC.
Lack of effective systemic adjuvant systemic therapies in high-risk patients.
Lack of genomically directed therapies similar to other oncogene addicted cancers.
Lack of effective later lines of therapies
Low response rates to currently approved immune check point inhibitors
Lack of robust biomarkers to predict nodal, distant metastases and recurrence
And even lack of predictive biomarkers for selection of conventional treatments, not to mention lack of robust biomarkers for prognosis.
Considerable work has been done on deciphering HNSCC at genomic level. Major alterations in tumor suppressor genes and oncogenes in HNSCC have been identified. Multi-omics studies have shed considerable light on how genomic alterations shape HNSCC biology and clinical behavior. Number of studies are addressing how knowledge about HNSCC genomics/multi-omics can leveraged to address some of the challenges faced by clinicians managing HNSCC. The need to break the ground in HNSCC prevention and therapy has never been so urgent.
This chapter attempts to review key alterations in tumor suppressor genes and oncogenes in HPV negative HNSCC and the potential clinical implications of these alterations. Key insights gained from multi-omics studies will also be highlighted. This review also quotes some of the novel targeting therapies and novel strategies. Specifically, insights gained in EGFR targeting and immune therapies will also be discussed in the context of genomics. Since the amount of literature being published is so large, it is beyond the scope of this review to provide exhaustive coverage on each aspect of head neck cancer genomics. Hence few indicative studies are quoted to elaborate each point to give the reader a basic orientation. This review will focus on HPV- HNSCC.
The Cancer Genome Atlas (TCGA) provided landscape of somatic genomic alterations by profiling 279 head neck squamous cell carcinomas. Tobacco related head neck squamous cell cancers showed loss of function mutations of TP53, CDKN2A inactivation, Copy number alterations of 3q26/28, 11q13/22. Few subgroups showed alterations in NSD1, WNT pathway genes AJUBA and FAT1, NFE2L2 [2]. HPV positive cases showed mutations of PIK3CA, loss of TRAF3 and amplification of cell cycle gene E2F1.Whole exome sequencing and microarray data showed unstable HNSCC genome showing high copy number alterations including copy number loss and copy number gains. Co amplifications of CCND1, FADD and CTTN and BIRC2 and YAP1 were found. Focal deletions were found in NSD1 and tumor suppressor genes including FAT1, NOTCH1, SMAD4, CDKN2A. Focal amplifications were found in receptor tyrosine kinases (RTKs) like EGFR, ERBB2, FGFR1. There was a small subset of oral cavity cancer characterized by activating mutations in HRAS, inactivating mutations in CASP8 and wild type TP53. This subset has been labeled as ‘M’ class which is driven by mutations rather than copy number alterations with tumorigenesis involving RAS, cell death pathway and NFkB. Fusion oncogenes like ALK, ROS or RET were not observed. MET exon 14 skipping mutation was uncommon. Loss of tumor suppressor function was more common than protein coding fusion events.
TCGA identified genes which can be grouped into (1) genes responsible for cell survival and proliferation (TP53, HRAS, EGFR, PIK3CA), (2) cell cycle control genes (CDKN2A AND CCND1), (3) cellular differentiation (NOTCH1) and (4) adhesion and invasion signaling (FAT1). Out of the most commonly mutated genes, TP53, CDKN2A, CASP8 AND NSD1 are differentially mutated across anatomic sites in the head neck region.
Frequency wise the common mutations in HNSCC are listed in Table 1.
More than 70% of HNSCC harbor mutations in the tumor suppressor p53 (TP53). TP53 mutations have been characterized in several ways. These mutations could be somatic or missense mutations, functional, partially functional or non-functional, and based on the alteration of DNA binding, as disruptive and non-disruptive.
TP53 mutations influence cell cycle, genomic integrity causing aberrant proliferation, disrupted apoptosis and defective DNA repair. TP53 mutation is probably the main actor in HNSCC pathogenesis and occur early in carcinoma. These mutations are also very high in metastatic HNSCC. Mutation rates of TP53 vary across different subsites in head neck. Larynx and hypopharynx have the highest TP53 mutation rate (83.5%), oral cavity and tongue 75.6%. oropharynx including tonsils and base of tongue have the lowest mutation rate 28.6% [3].
CDKN2A is the second most commonly altered gene in HNSCC CDKN2A encodes a CDK4/CDK6 kinase inhibitor which constrains cells from progressing through G1 restriction point. CDKN2A mutations are rare in HPV+ HNSCC [3]. Mutations involving NOTCH gene are third most common in HNSCC [3, 4]. NOTCH family members are transmembrane proteins (NOTCH 1-4) and two family of ligands the Jagged and the Delta-like proteins, involved in cell to cell communication and regulations of squamous differentiation.
CCND1 encodes cyclin D1 and regulates G1-to-S phase transition by formation of complexes with cyclin dependent kinases like CDK4 and CDK6. CCND1 is amplified in 30-40% of HNSCC with cyclin D1 overexpression [3]. AJUBA regulates cell division, vertebrate ciliogenesis and left–right axis determination. NSD1 is a tumor suppressor gene. Mutations in KMT2D and HLA-A contribute to a defective immunosurveillance. EGFR is commonly overexpressed in HNSCC and has been explored as a therapeutic target. PIK3CA alterations are common in HNSCC especially in HPV+ cancers. PIK3CA are seen in patients with advanced HNSCC harboring multiple PI3K pathway mutations [3]. MET is a Hepatocyte Growth Factor (HGF) receptor which regulates cancer cell plasticity through reversible programming of epithelia-mesenchymal transition (EMT) [3]. MET overexpression leads to MET/HGF pathway activation and corelates with worse outcome.
Epigenetic changes such as DNA methylation, histone acetylation and expression of small non coding RNAs affect gene expression. There is some evidence of importance of epigenetic changes in HNSCC. Global hypomethylation has been linked to poor prognosis. Epigenetic changes is one major method for tumor resistance. Many tumor suppressor genes like CDKN2A, CDH1, MGME, RASSF1A show promoter hypermethylation [5].
In terms of key driver oncogenic events in HNSCC can be summarized as follows; (Table 2).
Mutations | Percentage |
---|---|
TP53 | 72 |
CDKN2A | 22 |
FAT1 | 23 |
NOTCH1 | 19 |
PIK3CA | 21 |
KMT2D | 18 |
NSD1 | 10 |
CASP8 | 9 |
NFE2L2 | 6 |
FBXW7 | 5 |
TGFBR2 | 4 |
HRAS | 4 |
CUL3 | 4 |
RB1 | 3 |
HLA-A | 3 |
PTEN | 2 |
TRAF3 | 1 |
Somatic mutations (TCGA findings).
Function | Gene | Event |
---|---|---|
Tumor Suppressor | TP53 | Loss of function mutation |
Tumor suppressor | CDKN2A | Mutation, homozygous deletion, protein down regulation |
Tumor suppressor | NF1 | Mutation, amplification |
PI(3)K | PIK3CA | Amplification, mutation |
PI(3)K | PTEN | Mutation, protein downregulation |
PI(3)K | PIK3R1 | mutation |
Oncogenes | CCND1 | amplification |
Oncogenes | MYC | Amplification |
Oncogenes | HRAS | Mutation |
Receptor Tyrosine Kinases (RTKs) | EGFR | Amplification, mutation, protein up regulation |
RTKs | FGFR1 | Mostly amplification, rarely mutation |
RTKs | ERBB2 | Amplification, protein up regulation, mutation |
RTKs | IGF1R | Amplification, mutation |
RTKs | EPHA2 | Mutation |
RTKs | DDR2 | Amplification, mutation |
RTKs | FGFR2 | Amplification, mutation |
RTKs | FGFR3 | Amplification, mutation |
RTKs | MET | Amplification, exon 14 skipping mutation |
Oncogenic events in HNSCC.
In the TCGA dataset, most of the tumors that were sequenced were from early-stage surgical samples. The genomic profile of recurrent/metastatic HNSCC could be different. The American Association for Cancer Research has undertaken a project Genomic Evidence Neoplasia Information Exchange (GENIE) which is an international data sharing project allowing multiple international institutions to share their data of cancer sequencing. This combined dataset includes 700 patients with HNSCC, 40% representing patients with metastases. The frequency of common mutations in HNSCC in the three datasets TCGA, AACR GENIE and COSMIC are found comparable and has paved the way for developing targeted therapies [6].
In addition to HPV status as one important biological differential, different subsites of HNSCC seem to harbor differences at genomic level. TP53 mutations are most frequent in Laryngeal/hypopharyngeal sites followed by oral cavity followed by oropharynx [3]. David Vossena et al. did DNA sequencing on 111 HPV negative HNSCC, 55 oral and 56 laryngeal/pharyngeal cancers and identified somatic point mutations and copy number alterations. They also included sample data from TCGA to expand analysis. Mutational profiles of oral and laryngeal pharyngeal squamous cell carcinoma showed many similarities. However, oral squamous cell carcinoma was significantly enriched for CASP8 and HRAS mutations. Laryngeal/pharyngeal squamous cell cancers were enriched in LAMA and NSD1. Overall, oral squamous cell carcinoma had fewer somatic point mutations and copy number alterations. Laryngeal/pharyngeal squamous cancer scored higher on mutational and genomic scar signatures associated with homologous recombination DNA repair defects explaining differential response to chemoradiation [7].
Recurrent and metastatic HNSCC do share driver mutations with their primaries in addition to accumulating new mutations. High rates of TERT promoter mutations are found in recurrent or metastatic HPV- HNSCC. HPV+ HNSCC may also start exhibiting mutational landscape of HPV- negative tumors after recurrence and metastases. Recurrent HPV+ positive tumors may get enriched in TP53 mutations and lack PIK3CA mutations as compared to primary HPV+ primary tumors [8].
As noted earlier, head neck mucosal squamous cell carcinoma occurs at several subsites. Clinical behavior heterogeneity in terms of response to therapy, metastatic rate is commonly observed. Clinical heterogeneity is observed even within a single subsite. Tumor cells are known to accumulate genetic alterations over time. Some of these are driver mutations and some are passenger mutations. Heterogenic cell clones undergo selection leading to development of aggressive clones with growth advantage. This is one main reason for development of resistance to chemotherapy and radiation therapy. High degree of intratumor heterogeneity leads to tumor progression, inferior treatment outcome and reduced survival. Whole genome analysis of 74 cases of HNSCC used to calculate Mutant Allele Tumor Heterogeneity (MATH) can be a genetic biomarker of high-risk disease. High MATH has been found to have shorter overall survival [9, 10]. Targeted monotherapies are unlikely to be major breakthrough in HNSCC. Rational combination of two or several therapies or effective co-targeting seems to be the way forward.
Chung et al. and Walter et al. described four distinct molecular classes in HNSCC based on gene expression patterns: basal, mesenchymal, atypical, and classical (Table 3) [11, 12]. The basal subtype is characterized by over-expression of genes functioning in cell adhesion including COL17A1, and growth factor and receptor TGFA and EGFR, high expression of transcription factor TP63. The mesenchymal subtype shows over expression of genes involved in immune response and genes associated with epithelial to mesenchymal transition including vimentin, desmin, TWIST1, and HGF. The classical subtype is shows over-expression of genes related to oxidative stress response and xenobiotic metabolism. The atypical subtype shows elevated expression of CDKN2A, LIG1, and RPA2, low expression of EGFR.
Molecular subtype | Key features |
---|---|
Classical | TP53 mutation CDKN2A loss 3q amplification Alterations in oxidative stress genes like KEAP1, NFE2L2, CUL3, Smoking history Laryngeal subsite |
Basal | NOTCH1 inactivation Decreased SOX2 expression HRAS-CASP8 co-mutation Co-amplified 11q13/q22 |
Atypical | Lack of chromosome 7 amplification Activating exon 9 mutations (PIK3CA domain) |
Mesenchymal | Alterations in innate immunity genes, High expression of CD56 Low frequency of HLA class I mutations |
Molecular subtypes of HNSCC and key features.
Huang et al. did proteogenomic study on 108 HPV negative HNSCCs in order to gain biological insights and novel treatment strategies [13]. They found correlation between 263 proteins, 173 phosphoproteins and overall survival. Poor prognosis associated proteins/phosphoproteins were enriched in pathways for somatic copy number alteration drivers, DNA replication, cell cycle and RNA processing. They also found poor prognosis associated with FAT1 truncation or 11q13.3 amplification. Analysis of Rb pathway showed interesting observations. CDKN2A and CCND1 alterations do not always result in increased CCND1 protein and CDK4/6 activity. Rb status was found more effective indicator of CDK4/6 dependent cell cycle activity than genomic or transcriptomic markers.
Similarly, novel insight was obtained in EGFR pathway. EGFR amplification activates EGFR in a ligand independent manner. The EGFR monoclonal antibody works by binding to the extracellular domain of EGFR to prevent ligand induced activity. Therefore, EGFR ligand abundance is more important to activity of anti EGFR moAbs than EGFR amplification or overexpression.
Immune-proteogenomic analysis revealed immunosuppressive somatic copy number alterations. Higher immune cell infiltration was linked to low clinical stage, less smoking and better prognosis. Immune hot tumors showed both cytotoxic immune enzymes and immunosuppressive proteins. This explains why the response to immune check point inhibitors in PD L1 positive HNSCC patients is modest. In immune cold tumors, the low immune infiltration was not driven by lack of tumor antigen sources but deficient Antigen Presentation Machinery (APM) pathway.
Further Huang et al. divided HNSCC tumors into three clusters using multi-omics data. Cluster I was associated with laryngeal site, strong smoking and high chromosome instability (CIN). Proteomic data suggested linkage between aberrant epigenetic activity, smoking and high CIN. This cluster had the worst prognosis. Cluster II showed elevation of several basal factors and high translational activity. Cluster III showed tumors with weak smoking history, higher immune scores and higher stromal scores. So, cluster I, II and III were CIN, Basal and Immune subtypes respectively. In terms of treatment selection, CIN subtype was associated with frequent aberrations of CCND1, CDKN2A and Rb hyperphosphorylation indicating potential for CDK 4/6 inhibitors. Basal subtype was associated with high EGFR ligand activity suggesting a potential role for anti-EGFR mAbs. The immune subtype could be appropriate for immune checkpoint blockade. Frequency of high level of biomarkers were 32% in CIN tumors, 62% in Basal tumors and 83% in Immune tumors emphasizing the tremendous potential to select appropriate therapy.
New targets for therapy were also identified including KIT, ECER1G, PLAU, SERPINE1, TOP2A, MMPs, several cell cycle and DNA damage related kinases. Multiple C/T and neoantigens were also found in their analysis which could be potential immunotherapy targets.
Thorsson et al. and Tamborero et al. did extensive immunogenomic analysis of many tumors and came out with six molecular immune subtypes: wound healing (C1), IFN gamma dominant (C2), inflammatory (C3), lymphocyte depleted (C4), immunologically quiet (C5) and TGF-beta dominant (C6) [14, 15]. In the TCGA HNSCC cohort, most tumors were C1 with elevated expression of angiogenic genes, high proliferation rate and a Th2 cell bias to the adaptive immune infiltrate or C2 with the highest M1/M2 macrophage polarization, a strong CD8 signal and prominent TCR diversity.
Genomic and neoantigen evolution from primary to first metastases was studied by Charles Schutt et al. between 23 paired primary and recurrent HNSCC tumors [16]. They found 6 genes which predicted neoantigens in 4 or more patients. Neoantigens in shared genes had increased CD3+ and CD8+ T cell infiltration and duration of survival with disease.
Yao Yao et al. in a study involving 5 HNSCC tumors and normal tissue found four immune related genes, PVR, TNFRSF12A, IL21R, SOCS1 to be significantly associated with overall survival [17]. They tried to integrate these four genes with pathological N stage to better predict overall survival. High expression of PVR AND TNFRSF12A indicated poor overall survival whereas high expression of IL21R and SOCS1 indicated better overall survival.
Chen et al. characterized the immune landscape of HNSC by their tumor and stromal compartments to identify novel immune molecular subgroups [18]. In their study, a training cohort of 522 HNSC samples from the Cancer Genome Atlas profiled by RNA sequencing was analyzed. Gene patterns from tumor, stromal, and immune cell genes were separated. Correlations were studied between the expression patterns with a set of immune-related gene signatures, potential immune biomarkers, and clinicopathological features. Validation was done with six independent datasets containing 838 HNSC samples.
Approximately 40% of HNSCs were labeled as immune class based on enriched inflammatory response, enhanced cytolytic activity, and active interferon-c signaling. Within this, some samples had markers of exhausted immune response and some had markers of active immune response. The Exhausted Immune Class was characterized by enrichment of activated stroma and anti-inflammatory M2 macrophage signatures, WNT/transforming growth factor-b signaling pathway activation and poor survival. Active immune class showed enriched proinflammatory M1 macrophage signature, enhanced cytolytic activity, abundant tumor-infiltrating lymphocytes, high human papillomavirus (HPV) infection, and favorable prognosis. Such a subgrouping might help in tailoring immune therapies to appropriate subsets of patients.
Several genomic features may influence response to immune check point inhibitors [19]. High tumor mutational burden is associated with neoepitope presentation and immune hot phenotype leading to enhanced benefit with immune check point inhibitors. NSD1 inactivating mutations, global DNA hypomethylation, aneuploidy, may lead to impaired chemokine signaling and immune effector response leading to an immune cold phenotype and low benefit from immune checkpoint inhibitors. Groups led by Many HNSCC specific studies tried to subtype patients as immune molecular subtypes. Considerable work is also being done to understand immune events occurring in the areas of field cancerization around an oral premalignant lesion raising the hope for using immunotherapy as immunoprevention. Integrated omics studies are also being pursued to understand occurrence of immune related adverse events and development of immune resistance.
TP53 mutation which is common in HNSCC has predictive value for disease free and overall survival. There is a correlation between TP53 mutations and resistance to chemotherapy drugs like cisplatin, doxorubicin, paclitaxel also leading to lower rates of pathological complete responses to neoadjuvant chemotherapy. Absence of TP53 mutated DNA in the surgical margins has been found to improve local recurrence free survival. Patients with no TP53 mutated DNA in the surgical margins may be spared post-operative radiation therapy. Disruptive TP53 mutations predict locoregional recurrence.
Mutant TP53 could be targeted in several ways; (1) introduction of wild type TP53 inside the cancer cells, (2) reactivation of some function of wild type TP53 in mutant cancer cells, (3) degradation of mutant TP53, or (4) targeting coexisting genetic alterations such as CDKN2A deletions or PIK3CA activation to induce synthetic lethality.
CDKN2A It is associated with worse survival in recurrent metastatic HNSCC. Frequent alterations of PI3K-AKT- m TOR pathway has raised the hope for therapeutic targets. However, the results with PI3K/AKT/m TOR pathway targeting have been inconsistent.
There could be a scope for combination of PI3K inhibition with chemotherapy and/or radiation. Currently there are trials underway combining buparlisib, copanlisib and alpelisib in combination with radiation, cisplatin and/or cetuximab. mTOR inhibitors sirolimus, everolimus and temsirolimus have limited efficacy in HNSCC. Further work is needed in this area to develop effective strategies. Activated PI3K/Akt also confers resistance to MET inhibition. Therefore, combining MET/PI3K inhibition might be a good strategy. CCND1 amplification has been associated with recurrence and metastases. It may also confer resistance to cisplatin and EGFR inhibitors. CDK4/6 inhibitors abemaciclib and palbocilib are being tested in combination with cetuximab and IMRT in locally advanced HNSCC. Oral squamous cell carcinoma patients with NOTCH pathway mutations are three times more likely to die with recurrent disease. NOTCH1 mutation may sever as biomarker for identification of HNSCC with higher sensitivity to radiotherapy and chemotherapy. Activated NOTCH1 also contributes to resistance of PI3K inhibitors. NOTCH1 inhibition may enhance efficacy of conventional chemotherapeutic agents by targeting head neck cancer stem cells. Exposure to chemotherapeutic agents may lead to selection of recurrent tumors enriched in cancer stem cells. NOTCH1 inhibition may attenuate such an effect [4].
EGFR is commonly overexpressed in HNSCC [20]. It is associated with resistance to radiation therapy and chemotherapy and worse locoregional and disease-free survival. Two agents Cetuximab a monoclonal antibody binding to the extracellular domain of EGFR and Afatinib a small anti molecule tyrosine kinase inhibitor have been approved by FDA [21, 22]. However, currently there is no biomarker to select patients for these drugs. Considerable work has been done to understand resistance mechanisms to anti-EGFR monoclonal antibodies and -EGFR tyrosine kinase inhibitors. These include (1) Metabolic pathways, (2) cross talk with other signaling pathways, (3) dysregulation of EGFR pathway, (4) epithelial mesenchymal transition and nuclear translocation of EGFR. This understanding will help in overcoming EGFR resistance.
There could be several ways to augment EGFR targeting such as (1) combination of EGFR Mab and EGFR TKi, (2) Horizontal targeting multiple HER receptors, (3) Vertical targeting with inhibition of EGFR and other RTKs involved in nuclear translocation of EGFR.
MET alterations are low but important in terms of serving as a target for therapy. Several drugs are available such as tivantinib, cabozantinib, crizotinib to target MET. MET mutations are also associated with EGFR inhibitor resistance and reduced sensitivity to VEGFR TKIs. Dual VEGFR/c-MET inhibition or dual blockade of MET/EGFR could enhance efficacy.
We know that progression from normal epithelium to fully developed squamous cell cancer occurs through a multistep process often involving a stage of pre-malignant lesions. It has been found that these stages of normal epithelium, pre-malignant lesions and malignant lesions are not only different histologically, but are different in terms of genomics. Some earlier studies using Affymetrix Gene Chips found that progression from normal epithelium to pre-malignant lesions are associated with more transcriptional alterations than progression from pre-malignant lesions to malignant lesions. Moreover, the normal, pre-malignant and malignant lesions cluster differently. Based on this, there could be potential to classify pre-malignant lesions into low risk and high risk with appropriate treatment approach of aggressive treatment of high- risk lesions to prevent occurrence of HNSCC [23].
Currently, presence or absence of neck nodal metastases is the only robust predictor of recurrence and metastases. Therefore, in most cases clinical N0 necks are addressed with surgical neck dissection. This often means treating a great majority of patients with unnecessary surgery. Currently, there is no single gene mutation or genomic profile which can predict recurrence and metastases as effectively as neck nodal status. This could be due to the fact that occurrence of metastases involves multiple genetic, molecular and metabolic pathways in addition to influence of host immune system. Genomic changes necessary for metastases may exist in majority of primary tumor at diagnosis paving the way to develop a robust metastatic gene signature.
Cromer et al. studied patients with hypopharyngeal squamous cell cancers using gene expression and found metastatic prediction accuracy of 92% using 168 gene targets [24].
Roepman et al. studied expression profiles of 82 primary oral cavity and oropharynx squamous cell cancers using 102 genes as predictors and observed predictive accuracy of 86% in comparison to clinical staging accuracy of 68% [25].
In view of the different lymphatic drainage patterns of different anatomical subsites, probably each anatomic subsite will need different genetic signature to predict nodal metastases.
Karpothiou et al. studied 18 HNSCC and corresponding node metastases and non-neoplastic tissue for RT-qPCR for EGFR, VEGF, Claudin7, Maspin, Survivin and SCCA [26]. They found differential gene expression levels in node metastases compared to the primary tumor and some correlation with prognosis.
Zevallos et al. did a retrospective study applying four molecular subtypes of HNSCC namely Basal (BA), Mesenchymal (MS), Atypical (AT) and Classical (CL) to oral cavity and laryngeal squamous cell cancers [27]. They found that early-stage oral cavity cancer with MS subtype was associated with high risk of nodal metastases. In laryngeal cancer, CL subtype was associated with worse overall survival. Oral cavity squamous cell cancers were predominantly BA and MS whereas laryngeal cancers were predominantly CL and AT subtype.
Ribeiro et al. used array comparative genomic hybridization data from HNSCC patients to develop a model to predict HNSCC recurrence/metastasis [28]. In their study of 104 HNSCC patients, this predictive model showed a good accuracy (>80%). Validation was done in an independent population from TCGA data portal. The genomic model included chromosomal regions from 5p, 6p, 8p, 9p, 11q, 12q, 15q and 17p, containing many upstream and downstream signaling pathways associated with cell proliferation and invasion. This model will need further large-scale study and has the potential to individualize clinical management and also identify potential therapeutic targets.
There is considerable heterogeneity in the outcome of HNSCC patients with similar TNM stage. Number of studies are addressing this question. Investigators from China came out with a six gene signature (PEX11A, NLRP2, SERPINE1, UPK, CTTN, D2HGDH) using bioinformatics analysis of TCGA dataset, as a new prognostic marker for predicting survival of HNSCC patients [29]. They also did Gene Set Enrichment Analysis and found some pathways significantly enriched between high risk and low risk groups. Clinical trials testing such signature will be helpful.
Reddy et al. in a meta-analysis approach identified respective differentials (tongue: 3508, laryngopharynx: 4893, oropharynx: 2386) [30]; validation in TCGA revealed markers with high incidence (altered in >10% of patients) in tongue (n = 331), laryngopharynx (n = 701) and oropharynx (n = 404). Assessment of these genes in clinical sub-cohorts of TCGA indicated that early stage tongue (MTFR1, C8ORF33, OTUD6B) and laryngeal cancers (TWISTNB, KLHL13 and UBE2Q1) were defined by distinct prognosticators. Similarly, correlation with perineural/angio-lymphatic invasion, identified discrete marker panels with survival impact (tongue: NUDCD1, PRKC1; laryngopharynx: SLC4A1AP, PIK3CA, AP2M1). Alterations in ANO1, NUDCD1, PIK3CA defined survival in tongue cancer patients with nodal metastasis (node+ ECS-), while EPS8 is a significant differential in node+ ECS- laryngopharyngeal cancers.
Goal of head neck cancer surgery includes wide resection of the primary tumor, neck dissection in clinically selected patients with the goal of obtaining adequate negative margins and acceptable functional outcome. Adjuvant therapy depends upon presence or absence of certain histopathological findings like positive margins, angiolymphatic space invasion, perineural invasion, nodal metastases, nodal metastatic burden, extracapsular extension in the involved nodes. How can HNSCC genomics help in precision surgery [31]?
Refining indications for surgery: There is often a dilemma in early - stage oral cavity cancers that are clinically N0, whether to do elective neck node dissection. Here genomic characterization of the primary tumor might help in prediction of nodal metastases and help in selection of patients for neck dissection [32]. Similarly, negative predictive value of transcriptomic signature in early - stage oral cavity cancer might help in avoiding unnecessary neck dissection [33].
Surgery for pre-malignant lesions.
Some premalignant lesions progress to malignant lesions. Molecular genomic studies might help to identify such lesions so that they can be resected immediately [34].
Some patients with oligometastatic cancer with indolent behavior might be surgical candidates. Genomic studies on tumor dormancy might help identify such patients who could benefit by metastasectomy [35].
Genomic prediction of radiosensitivity (discussed below) might help avoid surgery in such patients.
Markers of aggressiveness: Genomics might predict for occurrence of extracapsular spread in involved and hence help allocate patients for adjuvant chemoradiation [36].
Perineural invasion is a known pathological marker of aggressiveness. Genomic expression profile of perineural invasion indicating aggressiveness might help triage patients for appropriate adjuvant therapies after surgery [37].
Genomic analysis of surgical margins.
In-spite of clear surgical margins about 15% patients do recur after surgery. Molecular analysis of the surgical margins might identify such patients and improve surgical resectability [38, 39, 40, 41].
Many oral cavity cancers involve mandible. Mandibular resections add considerable morbidity and impair quality of life. Genomic studies might help in deciding extent of mandibular resections based on tumor tropism to involve bone [42].
Neoadjuvant immunotherapy is being increasing pursued in clinical trials with it’s potential to real down stage the tumor and prevent metastases. This might redefine approach to surgery in near future [43, 44, 45, 46].
Follow up of patients after cancer surgery: Functional genomics might help in optimizing follow of patients after curative surgical resection by identifying markers of aggressiveness. Genomic profile identification of perineural invasion might help in enhanced surveillance of such patients [47]. Patients with intratumor heterogeneity might be at risk of recurrence. Such patients can be identified prospectively [48]. Genomics may also help in prediction of loco-regional relapse. Group led by Davide Gissi analyzed DNA methylation for the following genes: ZAP70, ITGA4, KIF1A, PARP15, EPHX3, NTM, LRRTM1, FLI1, MIR193, LINC00599, MIR296, TERT, and GP1BB in the brushings from the tumor area at diagnosis and from the regenerating area 6 months after surgery in 49 consecutive patients [49]. As per a predefined cut-off value, sample was labeled as positive or negative. At diagnosis 47 out of 49 specimens were found positive. 16 out of 49 patients had positive scores at six months after resection. 7 patients relapsed and out of these 6 patients had a positive score in the regenerative area after surgery. The presence of a positive score after oral cancer treatment was the most powerful variable related to the appearance of locoregional relapse. The authors concluded that 13-gene DNA methylation analysis by oral brushing may have a clinical application as a prognostic non-invasive tool in the follow-up of patients surgically treated for oral cavity squamous cancers.
Radiation therapy is mainstay of therapy in majority of HNSCC either as an adjuvant after surgery in oral cavity cancers, as principal treatment with or without chemotherapy in non-oral cavity cancers, as palliative or salvage therapy. Currently, radiation therapy strategies are same across anatomic sites based purely on TNM stage. There are no robust biomarkers of prediction of response, resistance and outcome in HPV- HNSCC.
Genomics have the potential to guide radiation response/resistance and predict toxicities. SF2, survival fraction at 2Gy in cell lines was published by Torres-Roca et al [50].
Pramana et al. also found potential to use gene expression profiling to predict outcome after chemo-radiation in head neck cancer [51].
Radiosensitivity index has been shown to predict clinical outcome in HNSCC patients treated with chemo-radiation in clinical trials, with 2 year survival of 86% in radiation sensitive signature versus 61% in resistant signature [52].
Concept of GARD (Genomic adjusted radiation dose) was developed by Jacob Scott et al., using a gene expression-based radiation-sensitivity index and linear quadratic model to derive GARD. GARD based clinical module potentially can allow individualization of radiation therapy and guide new design for genomically guided clinical trials [53].
Tumor hypoxia is known to lead to radiation resistance. Work has been to develop genomic signature to predict tumor hypoxia so that appropriate intervention strategies targeting tumor hypoxia can be developed [54].
Along the same lines immunogenomics might be used to predict outcome of radiation and immune therapies given in different combinations. Biology based radiation adaptation trials are already going in HPV positive HNSCC.
Gene alterations can also predict radiation induced toxicity and identify patients who are super sensitive to radiation therapy. Whitney Sumner et al. analyzed 37 HNSCC patients and found that genetic alterations in BRCA2, ERBB3, NOTCH1, and CCND1 were associated with higher mean grad radiation toxicity [55]. Alterations in TNFAIP3, HNF1A, SPTA1 and CASP8 were found in radiation supersensitive patients. Such an approach will help in improving therapeutic index of radiation therapy in HNSCC.
Overexpression of FOXC2, MDR1, MRP2, ERCC1. PDGF-C, NRG1, survivin are linked to treatment resistance. Amongst the miRNAs, overexpression of miR-371a-p, miR- 34c-50, miR-1323 and downregulation of miR-324-3p, miR-93-3p, miR-4501 has been linked to radio-resistance in nasopharyngeal carcinoma [56].
Cisplatin remains the most common chemotherapy drug used in HNSCC. However, resistance to cisplatin is common. Number of genomic correlates of cisplatin response/resistance have been identified. Sanne et al. employed an array of 21,121 pools of siRNAs targeting unique human genes in the NCBI RefSeq database and performed in vitro genome-wide functional genetic screen to identify genes that influence the response to cisplatin in HNSCC cells [57]. By siRNA-mediated knockdown, Fanconi anemia/BRCA pathway emerged as the predominant pathway for cisplatin response in HNSCC cells. Goretti Duran et al. investigated thirty-six selected single nucleotide polymorphisms (SNPs) in 29 genes in 110 patients treated with cisplatin-based chemoradiotherapy and found that genetic polymorphisms with activity in intracellular detoxification (GSTP1), DNA repair (ERCC1, ERCC4, ERCC5, RAD51), and multidrug resistance-associated protein (ABCB1, ABCC1, ABCC2) affect drug toxicity in patients with head and neck who received platinum-based CRT [58]. Gene variants and haplotypes of ERCC1 were associated with the risk of developing hematologic toxicity.
Hiroyuki Shimomura et al. examined Non-SMC Condensin I Complex Subunit H (NCAPH) expression in OSCC and performed a functional analysis of human Oral Squamous Carcinoma Cells (OSCC) and found that resistance to cisplatin, carboplatin, and nedaplatin was enhanced by NCAPH in OSCC cells. NCAPH silencing combined with platinum decreased multidrug resistance [59]. There was no association between NCAPH and resistance to paclitaxel, docetaxel, and 5-fluorouracil.
Lot of studies are looking at potential of using circulating tumor cells and circulating tumor DNA to monitor for recurrence and evolution of treatment resistance.
Immunotherapy is a promising approach and seems to have added a new paradigm to several cancers including HNSCC. However, with currently available immune checkpoint inhibitors, the response rate is low, very few patients derive benefit, many patients fail to respond, some patients develop hyper-progressive disease and patients may develop immune related adverse events in an unpredicted fashion.
In 2016, FDA approved anti PD1 antibodies pembrolizumab and nivolumab [60, 61]. With establishment of nivolumab and pembrolizumab in the treatment of recurrent metastatic HNSCC, there are several studies looking at different ways to combine them with established treatments like surgery, radiation therapy and chemotherapy including cetuximab. These molecules are being tested in the neoadjuvant, concurrent and adjuvant therapeutic spaces in HNSCC. Ipilimumab an anti-CTLA-4 antibody which works well has been shown to reverse resistance to treatment in HNSCC. Ipilimumab given after cetuximab has been shown to reverse resistance to cetuximab. It has been observed that there is increased infiltration with Treg cells following exposure to cetuximab. Ipilimumab eliminates these Treg cells. Several trials are underway looking at combinations of ipilimumab, radiation and nivolumab.
Several genomic features may influence response to immune check point inhibitors [19]. High tumor mutational burden is associated with neoepitope presentation and immune hot phenotype leading to enhanced benefit with immune check point inhibitors. NSD1 inactivating mutations, global DNA hypomethylation, aneuploidy, may lead to impaired chemokine signaling and immune effector response leading to an immune cold phenotype and low benefit from immune checkpoint inhibitors.
Several studies have found association of drug resistance and genomic alterations listed below. This knowledge might help in selecting appropriate patients for chemotherapy/drugs including targeted drugs and avoiding un-necessary treatment in those who may not benefit from it [3].
Genomic marker | Therapy resistance |
---|---|
TP53 | Cisplatin resistance |
EGFR | Radiation resistance |
CCND1 | Gefitinib resistance |
NOTCH1 | PI3K inhibitor |
MET | Resistance to Cetuximab, Erlotinib |
PIK3CA | Bio-radiation with cetuximab, PI3K inhibitors MET inhibitors |
Imaging including contrast enhanced CT scan, MRI scans and recently PET scans are commonly used to accurately stage the patient at diagnosis and also to monitor response and recurrence. Radiomics based on image texture analysis has the potential to provide valuable real time information about tumor biology and response/resistance to treatment. Studies are looking at correlation between radiomics and genomics. Group led by Kerstin Zwirner at Eberhard Karls university in Germany looked at genetic tumor profiles and radiomic features in 20 HNSCC patients treated with primary radio-chemotherapy [62]. They did NGS of the tumor and corresponding normal tissue and analyzed 327 genes. TP53, FAT1 and KMT2D were the most frequently mutated driver genes in their cohort. They found good correlation between reduced radiomic intra-tumor heterogeneity and somatic mutations in FAT1 with small tumor volumes. Radiomic features of heterogeneity did not corelate with somatic mutations in TP53 or KMT2D. Radiomics and genomics remain work under progress.
In addition to focusing on common mutations, there are rare mutations with druggable targets worth exploring [6].
Rearrangement of Neutrotrophic Tropomyosin Receptor Kinase (NTRK) gene. NTRK 1,2 and 3 fusions are found in 3%, 1.6% and 3% of HNSCC in the AACR GENIE data set. Pan TRK inhibitor Larotrectinib is being tested in these patients.
HRAS
HRAS is a farnesyl transferase substrate depending exclusively on farnesylation. HRAS mutations have been found in 4% of HNSCC patients in the GENIE data set. Tipifarnib which is highly selective inhibitor of farnesyl transferase is being tested in HRAS mutated HNSCC.
Antibody Drug Conjugate (ADC) are monoclonal antibodies conjugated to cytotoxic agents. Antibody targets a particular cell surface protein and the drug payload is delivered inside the cell. Several ADCs are being tested in HNSCC including ABBV-221, AVID100 which target EGFR, BAY1129980 targeting C4.4a, IMMU-132 which targets TROP-2 antigen and tisotumab vedotin targeting human tissue factor.
DNA damage repair. DNA damage response (DDR) pathway is a druggable target. The most glaring example is PARP inhibitors in BRCA1/2 mutated cancers. About 8% of HNSCC cases have alterations in the DDR related genes. There are several DDR pathway inhibitors targeting DNA damage signaling proteins like ATM, ATR, DNA-PK, WEE1, CHK1 and 2.
Tumor Mutational Burden (TMB). High tumor mutational burden is associated with increased expression of tumor specific antigens on the cancer cell surface making the cancer more immunogenic. About 25% HNSCC patients have high TMB having >20 mutations per mega-base of DNA making them susceptible to immunotherapy.
Dynamic Monitoring of tumor using ctDNA. As the cancer clinically evolves, it’s genomic and molecular landscape changes. ctDNA are short fragments of double stranded DNA shed in the blood by the tumor undergoing necrosis and apoptosis. ctDNA may have mutational profile not seen in the normal cells and could represent the changing genomic landscape of tumor in vivo. Serial monitoring of ctDNA could help in detecting early relapse and help appropriately matched therapies to be delivered in real time.
FGFR2 and FGFR3 fusion occurs in 1-3% of HNSCC. These patients might benefit by FGFR inhibitors.
Several targeted drugs are being tested in clinical trials. Exhaustive review of these are beyond the scope of this chapter.
HNSCC are genetically highly heterogenous. Monotherapies with targeted therapies yield modest benefit with eventual development of resistance. So, combining two or more molecularly targeted agents might emerge as effective therapy.
There could be several ways to do this; (1) targeting molecules within convergent signaling pathways, (2) targeting molecules with non-overlapping mechanisms of action, (3) targeting anti-tumorigenic molecules working synergistically with conventional chemotherapy or radiation therapy. Several clinical trials evaluating this strategy are listed below (Table 4) [5].
Clinical trial | Intervention |
---|---|
NCT02124850 | Cetuximab + motolimod + Nivolumab |
NCT01218048 | cetuximab + surgical resection + adjuvant cisplatin, carboplatin, radiation |
NCT02277197 | ficlatuzumab + Cetuximab |
NCT 0957853 | Cetuximab + anti IgG1 antibody + surgical resection |
NCT 3153982 | Ruxolitinib + Surgical resection |
NCT02035527 | Raf inhibitor + Doectaxel + cisplatin |
NCT01051791 | Everolimus |
NCT01588431 | Bevacizumab + Cetuximab + Docetaxel + Cisplatin followed by radiation/surgical resection |
NCT02769520 | Pembrolizumab |
NCT01316757 | Erlotinib + Cetuximab + paclitaxel + carboplatin |
NCT01016769 | Temsirolimus + Paclitaxel + Carboplatin |
NCT02741570 | nivolumab + ipilimumab + cetuximab + cisplatin + carboplatin +5fluracil |
NCT02952586 | Avelumab + cisplatin + radiation |
NCT02499120 | Cetuximab + Palbociclib |
Clinical trials evaluating molecular co-targeting strategies.
Most HNSCC will have complex genomes making it difficult to select therapy. This might not be corelating with traditional risk factors. There could be multiple driver mutations in a case or part of a tumor. E. g. a patient might be NOTCH1/PIK3CA double mutant. The question could be should this patient receive a WNT pathway inhibitor or PIK3CA inhibitor or both? The treating Head neck cancer clinician will have to document the genomic data, use of targeted drugs and record longitudinal follow up of each case to further develop use of NGS data in the clinic.
Multidisciplinary involvement of head neck surgeons, geneticists, medical oncologists, radiation oncologists, translational biologists will be integral to formulate personalized treatment approaches in head neck cancers.
European Society for Medical Oncology (ESMO) has a designed a scale (ESCAT) to guide the clinician to select a novel targeted drug with highest potential of efficacy in an HNSCC patient. The most Accordingly, compelling actionable molecular alterations in HNSCC included HRAS activating mutations (tipifarnib, farnesyl transferase inhibitor), MSI, high TMB (for immune check point inhibitors), NTRK fusions (TRK tyrosine kinase inhibitors), CDKN2A inactivating alterations (CDK 4/6 inhibitors) and EGFR amplification (afatinib) [63].
Big data approach is being explored in head neck oncology integrating data generated from genomic studies, radiomic data generated from CT, MRI and PET scans, data generated from clinical evaluation and optical imaging, data generated from radiation therapy response and toxicity and integration of all other non- genetic data such as epidemiology, diet, habits, stress, socioeconomic factors etc. There is a multicentric study BD2Decide (Big Data Models for personalized head neck cancer decision support) going on to explore Big Data approach. Three main goals for Big Data in HNSCC will be 1) support and augment clinical decisions, 2) generate new knowledge, 3) develop guidelines for HNSCC prevention and management [64].
HNSCC is genomically unstable. TCGA has identified key alterations in tumor suppressor genes and oncogenes in HNSCC. TP53 alteration is a key player in HNSCC tumorigenesis and biology. Principally loss of tumor suppressor drives tumorigenesis than oncogene addiction in HNSCC, however, a small subset of oral cavity cancer may be driven by mutations rather than loss of tumor suppressor gene function. Tumor heterogeneity is prominent in HNSCC and is a major challenge in developing effective therapies. Biologic classifier of HNSCC remains to be implemented in the clinic. Clustering of HNSCC according to multi-omics studies may be more clinically meaningful. Immune therapy is a major treatment paradigm in oncology in general including HNSCC. Corelative genomics and immune contexture will help realize the full potential of this approach. Sufficient indication exists linking major genomic alterations in HNSCC and clinical behavior including performance of conventional treatments. Opportunity exists to leverage this knowledge to fine tune currently existing surgical, radiation and chemotherapeutic approaches. EGFR targeting remains important in HNSCC in spite of lack of predictive biomarker and eventual treatment resistance. Mutli-omics studies have shed light on resistance to EGFR targeting and novel ways to target EGFR axis. Several studies are addressing genomically targeted monotherapies, molecular co targeting strategies and ways to escalate and deescalate treatment intensity based on biology. Time has come to implement molecular tumor boards in HNSCC regularly. BIG data approach will certainly help design multi-pronged approach to control HNSCC globally. Tissue repositories, participation in clinical trials and multi-institutional collaboration remains critical to further progress.
None.
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MRI is commonly used once treating brain, prostate cancers, ankle and foot. The Magnetic Resonance Imaging (MRI) images are usually liable to suffer from noises such as Gaussian noise, salt and pepper noise and speckle noise. So getting of brain image with accuracy is very extremely task. An accurate brain image is very necessary for further diagnosis process. During this chapter, a median filter algorithm will be modified. Gaussian noise and Salt and pepper noise will be added to MRI image. A proposed Median filter (MF), Adaptive Median filter (AMF) and Adaptive Wiener filter (AWF) will be implemented. The filters will be used to remove the additive noises present in the MRI images. The noise density will be added gradually to MRI image to compare performance of the filters evaluation. The performance of these filters will be compared exploitation the applied mathematics parameter Peak Signal-to-Noise Ratio (PSNR).",book:{id:"6144",slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Hanafy M. Ali",authors:[{id:"213318",title:"Dr.",name:"Hanafy",middleName:"M.",surname:"Ali",slug:"hanafy-ali",fullName:"Hanafy Ali"}]},{id:"41589",doi:"10.5772/50323",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:9671,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"2599",slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. Watt",authors:[{id:"145620",title:"Dr.",name:"Gina",middleName:null,surname:"Forster",slug:"gina-forster",fullName:"Gina Forster"},{id:"146553",title:"BSc.",name:"Andrew",middleName:null,surname:"Novick",slug:"andrew-novick",fullName:"Andrew Novick"},{id:"146554",title:"MSc.",name:"Jamie",middleName:null,surname:"Scholl",slug:"jamie-scholl",fullName:"Jamie Scholl"},{id:"146555",title:"Dr.",name:"Michael",middleName:null,surname:"Watt",slug:"michael-watt",fullName:"Michael Watt"}]},{id:"26258",doi:"10.5772/28300",title:"Excitotoxicity and Oxidative Stress in Acute Ischemic Stroke",slug:"excitotoxicity-and-oxidative-stress-in-acute-ischemic-stroke",totalDownloads:7157,totalCrossrefCites:6,totalDimensionsCites:25,abstract:null,book:{id:"931",slug:"acute-ischemic-stroke",title:"Acute Ischemic Stroke",fullTitle:"Acute Ischemic Stroke"},signatures:"Ramón Rama Bretón and Julio César García Rodríguez",authors:[{id:"73430",title:"Prof.",name:"Ramon",middleName:null,surname:"Rama",slug:"ramon-rama",fullName:"Ramon Rama"},{id:"124643",title:"Prof.",name:"Julio Cesar",middleName:null,surname:"García",slug:"julio-cesar-garcia",fullName:"Julio Cesar García"}]},{id:"62072",doi:"10.5772/intechopen.78695",title:"Brain-Computer Interface and Motor Imagery Training: The Role of Visual Feedback and Embodiment",slug:"brain-computer-interface-and-motor-imagery-training-the-role-of-visual-feedback-and-embodiment",totalDownloads:1439,totalCrossrefCites:13,totalDimensionsCites:23,abstract:"Controlling a brain-computer interface (BCI) is a difficult task that requires extensive training. Particularly in the case of motor imagery BCIs, users may need several training sessions before they learn how to generate desired brain activity and reach an acceptable performance. A typical training protocol for such BCIs includes execution of a motor imagery task by the user, followed by presentation of an extending bar or a moving object on a computer screen. In this chapter, we discuss the importance of a visual feedback that resembles human actions, the effect of human factors such as confidence and motivation, and the role of embodiment in the learning process of a motor imagery task. Our results from a series of experiments in which users BCI-operated a humanlike android robot confirm that realistic visual feedback can induce a sense of embodiment, which promotes a significant learning of the motor imagery task in a short amount of time. We review the impact of humanlike visual feedback in optimized modulation of brain activity by the BCI users.",book:{id:"6610",slug:"evolving-bci-therapy-engaging-brain-state-dynamics",title:"Evolving BCI Therapy",fullTitle:"Evolving BCI Therapy - Engaging Brain State Dynamics"},signatures:"Maryam Alimardani, Shuichi Nishio and Hiroshi Ishiguro",authors:[{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro"},{id:"231131",title:"Dr.",name:"Maryam",middleName:null,surname:"Alimardani",slug:"maryam-alimardani",fullName:"Maryam Alimardani"},{id:"231134",title:"Dr.",name:"Shuichi",middleName:null,surname:"Nishio",slug:"shuichi-nishio",fullName:"Shuichi Nishio"}]}],mostDownloadedChaptersLast30Days:[{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192666,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. Vaccaro",authors:[{id:"91165",title:"Prof.",name:"Vafa",middleName:null,surname:"Rahimi-Movaghar",slug:"vafa-rahimi-movaghar",fullName:"Vafa Rahimi-Movaghar"}]},{id:"63258",title:"Anatomy and Function of the Hypothalamus",slug:"anatomy-and-function-of-the-hypothalamus",totalDownloads:4558,totalCrossrefCites:6,totalDimensionsCites:12,abstract:"The hypothalamus is a small but important area of the brain formed by various nucleus and nervous fibers. Through its neuronal connections, it is involved in many complex functions of the organism such as vegetative system control, homeostasis of the organism, thermoregulation, and also in adjusting the emotional behavior. The hypothalamus is involved in different daily activities like eating or drinking, in the control of the body’s temperature and energy maintenance, and in the process of memorizing. It also modulates the endocrine system through its connections with the pituitary gland. Precise anatomical description along with a correct characterization of the component structures is essential for understanding its functions.",book:{id:"6331",slug:"hypothalamus-in-health-and-diseases",title:"Hypothalamus in Health and Diseases",fullTitle:"Hypothalamus in Health and Diseases"},signatures:"Miana Gabriela Pop, Carmen Crivii and Iulian Opincariu",authors:null},{id:"57103",title:"GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets",slug:"gaba-and-glutamate-their-transmitter-role-in-the-cns-and-pancreatic-islets",totalDownloads:3478,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"Glutamate and gamma-aminobutyric acid (GABA) are the major neurotransmitters in the mammalian brain. Inhibitory GABA and excitatory glutamate work together to control many processes, including the brain’s overall level of excitation. The contributions of GABA and glutamate in extra-neuronal signaling are by far less widely recognized. In this chapter, we first discuss the role of both neurotransmitters during development, emphasizing the importance of the shift from excitatory to inhibitory GABAergic neurotransmission. The second part summarizes the biosynthesis and role of GABA and glutamate in neurotransmission in the mature brain, and major neurological disorders associated with glutamate and GABA receptors and GABA release mechanisms. The final part focuses on extra-neuronal glutamatergic and GABAergic signaling in pancreatic islets of Langerhans, and possible associations with type 1 diabetes mellitus.",book:{id:"6237",slug:"gaba-and-glutamate-new-developments-in-neurotransmission-research",title:"GABA And Glutamate",fullTitle:"GABA And Glutamate - New Developments In Neurotransmission Research"},signatures:"Christiane S. Hampe, Hiroshi Mitoma and Mario Manto",authors:[{id:"210220",title:"Prof.",name:"Christiane",middleName:null,surname:"Hampe",slug:"christiane-hampe",fullName:"Christiane Hampe"},{id:"210485",title:"Prof.",name:"Mario",middleName:null,surname:"Manto",slug:"mario-manto",fullName:"Mario Manto"},{id:"210486",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Mitoma",slug:"hiroshi-mitoma",fullName:"Hiroshi Mitoma"}]},{id:"35802",title:"Cross-Cultural/Linguistic Differences in the Prevalence of Developmental Dyslexia and the Hypothesis of Granularity and Transparency",slug:"cross-cultural-linguistic-differences-in-the-prevalence-of-developmental-dyslexia-and-the-hypothesis",totalDownloads:3601,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"673",slug:"dyslexia-a-comprehensive-and-international-approach",title:"Dyslexia",fullTitle:"Dyslexia - A Comprehensive and International Approach"},signatures:"Taeko N. Wydell",authors:[{id:"87489",title:"Prof.",name:"Taeko",middleName:"N.",surname:"Wydell",slug:"taeko-wydell",fullName:"Taeko Wydell"}]},{id:"58597",title:"Testosterone and Erectile Function: A Review of Evidence from Basic Research",slug:"testosterone-and-erectile-function-a-review-of-evidence-from-basic-research",totalDownloads:1331,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Androgens are essential for male physical activity and normal erectile function. Hence, age-related testosterone deficiency, known as late-onset hypogonadism (LOH), is considered a risk factor for erectile dysfunction (ED). This chapter summarizes relevant basic research reports examining the effects of testosterone on erectile function. Testosterone affects several organs and is especially active on the erectile tissue. The mechanism of testosterone deficiency effects on erectile function and the results of testosterone replacement therapy (TRT) have been well studied. Testosterone affects nitric oxide (NO) production and phosphodiesterase type 5 (PDE-5) expression in the corpus cavernosum through molecular pathways, preserves smooth muscle contractility by regulating both contraction and relaxation, and maintains the structure of the corpus cavernosum. Interestingly, testosterone deficiency has relationship to neurological diseases, which leads to ED. Testosterone replacement therapy is widely used to treat patients with testosterone deficiency; however, this treatment might also induce some problems. Basic research suggests that PDE-5 inhibitors, L-citrulline, and/or resveratrol therapy might be effective therapeutic options for testosterone deficiency-induced ED. Future research should confirm these findings through more specific experiments using molecular tools and may shed more light on endocrine-related ED and its possible treatments.",book:{id:"5994",slug:"sex-hormones-in-neurodegenerative-processes-and-diseases",title:"Sex Hormones in Neurodegenerative Processes and Diseases",fullTitle:"Sex Hormones in Neurodegenerative Processes and Diseases"},signatures:"Tomoya Kataoka and Kazunori Kimura",authors:[{id:"219042",title:"Ph.D.",name:"Tomoya",middleName:null,surname:"Kataoka",slug:"tomoya-kataoka",fullName:"Tomoya Kataoka"},{id:"229066",title:"Prof.",name:"Kazunori",middleName:null,surname:"Kimura",slug:"kazunori-kimura",fullName:"Kazunori Kimura"}]}],onlineFirstChaptersFilter:{topicId:"18",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81998",title:"Understanding the Neuropathophysiology of Psychiatry Disorder Using Transcranial Magnetic Stimulation",slug:"understanding-the-neuropathophysiology-of-psychiatry-disorder-using-transcranial-magnetic-stimulatio",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.103748",abstract:"Transcranial magnetic stimulation (TMS) is a safe and non-invasive tool that allows researchers to probe and modulate intracortical circuits. The most important aspect of TMS is its ability to directly stimulate the cortical neurons, generating action potentials, without much effect on intervening tissue. This property can be leveraged to provide insight into the pathophysiology of various neuropsychiatric disorders. Using multiple patterns of stimulations (single, paired, or repetitive), different neurophysiological parameters can be elicited. Various TMS protocol helps in understanding the neurobiological basis of disorder and specific behaviors by allowing direct probing of the cortical areas and their interconnected networks. While single-pulse TMS can provide insight into the excitability and integrity of the corticospinal tract, paired-pulse TMS (ppTMS) can provide further insight into cortico-cortical connections and repetitive TMS (rTMS) into cortical mapping and modulating plasticity.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Jitender Jakhar, Manish Sarkar and Nand Kumar"},{id:"81646",title:"Cortical Plasticity under Ketamine: From Synapse to Map",slug:"cortical-plasticity-under-ketamine-from-synapse-to-map",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.104787",abstract:"Sensory systems need to process signals in a highly dynamic way to efficiently respond to variations in the animal’s environment. For instance, several studies showed that the visual system is subject to neuroplasticity since the neurons’ firing changes according to stimulus properties. This dynamic information processing might be supported by a network reorganization. Since antidepressants influence neurotransmission, they can be used to explore synaptic plasticity sustaining cortical map reorganization. To this goal, we investigated in the primary visual cortex (V1 of mouse and cat), the impact of ketamine on neuroplasticity through changes in neuronal orientation selectivity and the functional connectivity between V1 cells, using cross correlation analyses. We found that ketamine affects cortical orientation selectivity and alters the functional connectivity within an assembly. These data clearly highlight the role of the antidepressant drugs in inducing or modeling short-term plasticity in V1 which suggests that cortical processing is optimized and adapted to the properties of the stimulus.",book:{id:"11374",title:"Sensory Nervous System - Computational Neuroimaging Investigations of Topographical Organization in Human Sensory Cortex",coverURL:"https://cdn.intechopen.com/books/images_new/11374.jpg"},signatures:"Ouelhazi Afef, Rudy Lussiez and Molotchnikoff Stephane"},{id:"81582",title:"The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline and Dementia",slug:"the-role-of-cognitive-reserve-in-executive-functioning-and-its-relationship-to-cognitive-decline-and",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.104646",abstract:"In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Gabriela Álvares-Pereira, Carolina Maruta and Maria Vânia Silva-Nunes"},{id:"81488",title:"Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT1A and 5-HT1B Receptors",slug:"aggression-and-sexual-behavior-overlapping-or-distinct-roles-of-5-ht1a-and-5-ht1b-receptors",totalDownloads:20,totalDimensionsCites:0,doi:"10.5772/intechopen.104872",abstract:"Distinct brain mechanisms for male aggressive and sexual behavior are present in mammalian species, including man. However, recent evidence suggests a strong connection and even overlap in the central nervous system (CNS) circuitry involved in aggressive and sexual behavior. The serotonergic system in the CNS is strongly involved in male aggressive and sexual behavior. In particular, 5-HT1A and 5-HT1B receptors seem to play a critical role in the modulation of these behaviors. The present chapter focuses on the effects of 5-HT1A- and 5-HT1B-receptor ligands in male rodent aggression and sexual behavior. Results indicate that 5-HT1B-heteroreceptors play a critical role in the modulation of male offensive behavior, although a definite role of 5-HT1A-auto- or heteroreceptors cannot be ruled out. 5-HT1A receptors are clearly involved in male sexual behavior, although it has to be yet unraveled whether 5-HT1A-auto- or heteroreceptors are important. Although several key nodes in the complex circuitry of aggression and sexual behavior are known, in particular in the medial hypothalamus, a clear link or connection to these critical structures and the serotonergic key receptors is yet to be determined. This information is urgently needed to detect and develop new selective anti-aggressive (serenic) and pro-sexual drugs for human applications.",book:{id:"10195",title:"Serotonin and the CNS - New Developments in Pharmacology and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/10195.jpg"},signatures:"Berend Olivier and Jocelien D.A. Olivier"},{id:"81093",title:"Prehospital and Emergency Room Airway Management in Traumatic Brain Injury",slug:"prehospital-and-emergency-room-airway-management-in-traumatic-brain-injury",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.104173",abstract:"Airway management in trauma is critical and may impact patient outcomes. Particularly in traumatic brain injury (TBI), depressed level of consciousness may be associated with compromised protective airway reflexes or apnea, which can increase the risk of aspiration or result in hypoxemia and worsen the secondary brain damage. Therefore, patients with TBI and Glasgow Coma Scale (GCS) ≤ 8 have been traditionally managed by prehospital or emergency room (ER) endotracheal intubation. However, recent evidence challenged this practice and even suggested that routine intubation may be harmful. This chapter will address the indications and optimal method of securing the airway, prehospital and in the ER, in patients with traumatic brain injury.",book:{id:"11367",title:"Traumatic Brain Injury",coverURL:"https://cdn.intechopen.com/books/images_new/11367.jpg"},signatures:"Dominik A. Jakob, Jean-Cyrille Pitteloud and Demetrios Demetriades"},{id:"81011",title:"Amino Acids as Neurotransmitters. The Balance between Excitation and Inhibition as a Background for Future Clinical Applications",slug:"amino-acids-as-neurotransmitters-the-balance-between-excitation-and-inhibition-as-a-background-for-f",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.103760",abstract:"For more than 30 years, amino acids have been well-known (and essential) participants in neurotransmission. They act as both neuromediators and metabolites in nervous tissue. Glycine and glutamic acid (glutamate) are prominent examples. These amino acids are agonists of inhibitory and excitatory membrane receptors, respectively. Moreover, they play essential roles in metabolic pathways and energy transformation in neurons and astrocytes. Despite their obvious effects on the brain, their potential role in therapeutic methods remains uncertain in clinical practice. In the current chapter, a comparison of the crosstalk between these two systems, which are responsible for excitation and inhibition in neurons, is presented. The interactions are discussed at the metabolic, receptor, and transport levels. Reaction-diffusion and a convectional flow into the interstitial fluid create a balanced distribution of glycine and glutamate. Indeed, the neurons’ final physiological state is a result of a balance between the excitatory and inhibitory influences. However, changes to the glycine and/or glutamate pools under pathological conditions can alter the state of nervous tissue. Thus, new therapies for various diseases may be developed on the basis of amino acid medication.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Yaroslav R. Nartsissov"}],onlineFirstChaptersTotal:18},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:290,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:1,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:7,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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This includes, but is not limited to: single-neuron modeling, sensory processing, motor control, memory, and synaptic plasticity, attention, identification, categorization, discrimination, learning, development, axonal patterning, guidance, neural architecture, behaviors, and dynamics of networks, cognition and the neuroscientific basis of consciousness. Particularly interesting are models of various types of more compound functions and abilities, various and more general fundamental principles (e.g., regarding architecture, organization, learning, development, etc.) found at various spatial and temporal levels.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",keywords:"Single-Neuron Modeling, Sensory Processing, Motor Control, Memory and Synaptic Pasticity, Attention, Identification, Categorization, Discrimination, Learning, Development, Axonal Patterning and Guidance, Neural Architecture, Behaviours and Dynamics of Networks, Cognition and the Neuroscientific Basis of Consciousness"},{id:"24",title:"Computer Vision",scope:"The scope of this topic is to disseminate the recent advances in the rapidly growing field of computer vision from both the theoretical and practical points of view. Novel computational algorithms for image analysis, scene understanding, biometrics, deep learning and their software or hardware implementations for natural and medical images, robotics, VR/AR, applications are some research directions relevant to this topic.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",keywords:"Image Analysis, Scene Understanding, Biometrics, Deep Learning, Software Implementation, Hardware Implementation, Natural Images, Medical Images, Robotics, VR/AR"},{id:"25",title:"Evolutionary Computation",scope:"Evolutionary computing is a paradigm that has grown dramatically in recent years. This group of bio-inspired metaheuristics solves multiple optimization problems by applying the metaphor of natural selection. It so far has solved problems such as resource allocation, routing, schedule planning, and engineering design. Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. For example, some of the issues of interest could be the following: Advances in evolutionary computation (Genetic algorithms, Genetic programming, Bio-inspired metaheuristics, Hybrid metaheuristics, Parallel ECs); Applications of evolutionary algorithms (Machine learning and Data Mining with EAs, Search-Based Software Engineering, Scheduling, and Planning Applications, Smart Transport Applications, Applications to Games, Image Analysis, Signal Processing and Pattern Recognition, Applications to Sustainability).",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization"},{id:"26",title:"Machine Learning and Data Mining",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence"},{id:"27",title:"Multi-Agent Systems",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems.
\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
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",annualVolume:11967,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},{id:"40",title:"Ecosystems and Biodiversity",keywords:"Ecosystems, Biodiversity, Fauna, Taxonomy, Invasive species, Destruction of habitats, Overexploitation of natural resources, Pollution, Global warming, Conservation of natural spaces, Bioremediation",scope:"