Analysis of two webpages in order to identify signs-as-agents.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"6595",leadTitle:null,fullTitle:"Ballistics",title:"Ballistics",subtitle:null,reviewType:"peer-reviewed",abstract:"The edited volume Ballistics is a collection of reviewed and relevant research chapters, offering a comprehensive overview of recent developments in the field of engineered mechanics. The book comprises single chapters authored by various researchers and edited by an expert from the respective research area. Each chapter is complete in itself but united under a common research study topic. This publication aims to provide a thorough overview of the latest research efforts by international authors on engineered mechanics and opens new possible research paths for further novel developments.",isbn:"978-1-83880-656-9",printIsbn:"978-1-83880-655-2",pdfIsbn:"978-1-83880-715-3",doi:"10.5772/intechopen.71462",price:119,priceEur:129,priceUsd:155,slug:"ballistics",numberOfPages:112,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"3e7fa96253ce890c092b37a8678e4d03",bookSignature:"Charles Osheku",publishedDate:"June 5th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/6595.jpg",numberOfDownloads:7274,numberOfWosCitations:2,numberOfCrossrefCitations:3,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:5,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:10,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 12th 2017",dateEndSecondStepPublish:"November 2nd 2017",dateEndThirdStepPublish:"January 5th 2018",dateEndFourthStepPublish:"March 22nd 2018",dateEndFifthStepPublish:"May 21st 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"148660",title:"Dr.",name:"Charles",middleName:"Attah",surname:"Osheku",slug:"charles-osheku",fullName:"Charles Osheku",profilePictureURL:"https://mts.intechopen.com/storage/users/148660/images/6109_n.png",biography:"Dr. Charles Attah Osheku was the Director of the Centre for Space Transport and Propulsion, Epe, Lagos, an activity Centre of the National Space Research and Development Agency (NASRDA), Nigeria. He obtained BSc in Mechanical Engineering from the Obafemi Awolowo University; MSc and PhD in Mechanical Engineering (Engineering Mechanics) from the University of Lagos, Nigeria. He was the incumbent Chairman of the Lagos Branch of Nigeria Society of Engineers\\\\\\' (NSE) Space Engineering Division and a Board Member of the Division. Dr Osheku was a Research Expert in Rockets and Missiles Solid Fuel Physics, Solid Rocket Engines Design, Structural, Flow and Combustion-induced Vibrations, Aircraft and Jet Noise Modelling and Dissipation and Vibration of Laminated Structures. Dr Osheku has 63 scientific papers to his credit, published in reputable International Journals, ASME International Offshore Mechanics Conferences. He is a COREN (Nigeria) - registered Engineer and a professional member of ASME and AIAA.\r\n\r\nNote from the publisher:\r\n\r\nIt is with great sadness and regret that we inform the contributing authors and future readers of this book that the Editor, Dr. Charles Attah Osheku passed away during the publishing process of the book and before having a chance to see its publication. Dr. Osheku was IntechOpen\\'s long term collaborator and edited his first book with us in 2018 (\\'\\'Lamination\\'\\'). The book \\'\\'Ballistics\\'\\' was his secont edited volume and contains his third published chapter with us. The fruitful collaboration continued until his final days. We would like to acknowledge Dr. Osheku\\'s contribution to scientific publishing, which he made during years of dedicated work and express our gratitude for his pleasant cooperation with us.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"813",title:"Engineering Mechanics",slug:"mechanical-engineering-engineering-mechanics"}],chapters:[{id:"59098",title:"Adaptive Navigation, Guidance and Control Techniques Applied to Ballistic Projectiles and Rockets",doi:"10.5772/intechopen.73511",slug:"adaptive-navigation-guidance-and-control-techniques-applied-to-ballistic-projectiles-and-rockets",totalDownloads:1251,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Accuracy and precision are the cornerstone for ballistic projectiles from the earliest days of this discipline. In the beginnings, impact point precision in artillery devices deteriorated when range were extended, particularly for non-propelled artillery rockets and shells. Later, inertial navigation and guidance systems are introduced and precision was unlinked from range increases. In the last 30 years, hybridization between inertial systems and GNSS devices has improved precision enormously. Unfortunately, during the last stages of flight, inertial and GNSS methods (hybridized or not) feature big errors on attitude and position determination. Low cost devices, which are precise on terminal guidance and do not feature accumulative error, such as quadrant photo-detector, seem to be appropriate to be included on the guidance systems. Hybrid algorithms, which combine GNSSs, IMUs and photodetectors, and a novel technic of attitude determination, which avoids the use of gyroscopes, are presented in this chapter. Hybridized measurements are implemented on modified proportional navigation law and a rotatory force control method. A realistic non-linear flight dynamics model has been developed to perform simulations to prove the accuracy of the presented algorithms.",signatures:"Raúl de Celis and Luis Cadarso",downloadPdfUrl:"/chapter/pdf-download/59098",previewPdfUrl:"/chapter/pdf-preview/59098",authors:[{id:"210535",title:"Associate Prof.",name:"Luis",surname:"Cadarso",slug:"luis-cadarso",fullName:"Luis Cadarso"},{id:"210536",title:"Mr.",name:"Raúl",surname:"De Celis",slug:"raul-de-celis",fullName:"Raúl De Celis"}],corrections:null},{id:"64567",title:"State-Space Modeling of a Rocket for Optimal Control System Design",doi:"10.5772/intechopen.82292",slug:"state-space-modeling-of-a-rocket-for-optimal-control-system-design",totalDownloads:2050,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This chapter is the first of two others that will follow (a three-chapter series). Here we present the derivation of the mathematical model for a rocket’s autopilots in state space. The basic equations defining the airframe dynamics of a typical six degrees of freedom (6DoFs) are nonlinear and coupled. Separation of these nonlinear coupled dynamics is presented in this chapter to isolate the lateral dynamics from the longitudinal dynamics. Also, the need to determine aerodynamic coefficients and their derivative components is brought to light here. This is the crux of the equation. Methods of obtaining such coefficients and their derivatives in a sequential form are also put forward. After the aerodynamic coefficients and their derivatives are obtained, the next step is to trim and linearize the decoupled nonlinear 6DoFs. In a novel way, we presented the linearization of the decoupled 6DoF equations in a generalized form. This should provide a lucid and easy way to implement trim and linearization in a computer program. The longitudinal model of a rocket presented in this chapter will serve as the main mathematical model in two other chapters that follow in this book.",signatures:"Aliyu Bhar Kisabo and Aliyu Funmilayo Adebimpe",downloadPdfUrl:"/chapter/pdf-download/64567",previewPdfUrl:"/chapter/pdf-preview/64567",authors:[{id:"200807",title:"M.Sc.",name:"Bhar",surname:"Aliyu",slug:"bhar-aliyu",fullName:"Bhar Aliyu"}],corrections:null},{id:"61821",title:"Discrete Element Modeling of a Projectile Impacting and Penetrating into Granular Systems",doi:"10.5772/intechopen.75550",slug:"discrete-element-modeling-of-a-projectile-impacting-and-penetrating-into-granular-systems",totalDownloads:1133,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"From theoretical standpoint, it is difficult to analytically build a general theory and physical principles that critically describe the mechanical behaviour of granular systems. There are many substantial gaps in understanding the mechanical principles that govern these particulate systems. In this chapter, based on a two-dimensional soft particle discrete element method (DEM), a numerical approach is developed to investigate the vertical penetration of a non-rotating and rotating projectile into a granular system. The model outcomes reveal that there is a linear proportion between the projectile’s impact velocity and its penetration downward displacement. Moreover, depending on the rotation direction, there is a significant deviation of the x-coordinate of the final stopping point of a rotating projectile from that of its original impact point. For negative angular velocities, a deviation to the right occurs while a left deviation has been recorded for positive angular velocities.",signatures:"Waseem Ghazi Alshanti",downloadPdfUrl:"/chapter/pdf-download/61821",previewPdfUrl:"/chapter/pdf-preview/61821",authors:[{id:"227098",title:"Dr.",name:"Waseem",surname:"Alshanti",slug:"waseem-alshanti",fullName:"Waseem Alshanti"}],corrections:null},{id:"66819",title:"Analytical Prediction for Grain Burn Time and Burning Area Kinematics in a Solid Rocket Combustion Chamber",doi:"10.5772/intechopen.82822",slug:"analytical-prediction-for-grain-burn-time-and-burning-area-kinematics-in-a-solid-rocket-combustion-c",totalDownloads:1197,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter proposes the application of Newtonian particle mechanics for the derivation of predictive equations for burn time, burning and unburnt area propagation for the case of a core propellant grain. The grain is considered to be inhibited in a solid rocket combustion chamber subject to the assumption that the flame propagation speed is constant for the particular solid fuel formulation and formation chemistry in any direction. Here, intricacies surrounding reaction chemistry and kinetic mechanisms are not of interest at the moment. Meanwhile, the physics derives from the assumption of a regressive solid fuel pyrolysis in a cylindrical combustion chamber subject to any theoretical or empirical burn rate characterization law. Essential parametric variables are expressed in terms of the propellant geometrical configuration at any instantaneous time. Profiles from simulation studies revealed the effect of modulating variables on the burning propagation arising from the kinematics and ordinary differential equations models. In the meantime, this mathematical exercise explored the tendency for a tie between essential kernels and matching polynomial approximations. In the limiting cases, closed form expressions are couched in terms of the propellant grain geometrical parameters. Notably, for the fuel burn time, a good agreement is observed for the theoretical and experimental results.",signatures:"Charles A. Osheku, Oluleke O. Babayomi and Oluwaseyi T. Olawole",downloadPdfUrl:"/chapter/pdf-download/66819",previewPdfUrl:"/chapter/pdf-preview/66819",authors:[{id:"148660",title:"Dr.",name:"Charles",surname:"Osheku",slug:"charles-osheku",fullName:"Charles Osheku"},{id:"287885",title:"Dr.",name:"Oluleke",surname:"Babayomi",slug:"oluleke-babayomi",fullName:"Oluleke Babayomi"}],corrections:null},{id:"62018",title:"Ballistic Testing of Armor Panels Based on Aramid",doi:"10.5772/intechopen.78315",slug:"ballistic-testing-of-armor-panels-based-on-aramid",totalDownloads:1643,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Industry and market of ballistic protection materials and systems are characterized by a dynamic and competing succession of inventions for projectiles and protective systems. The requirements for the ballistic panels are many and complex, varying depending on the threat type, the required mobility in the tactical theater, and protection level. The safety degree, the price, and the dynamics of research in the field are also taken into account. This chapter underlines the necessity of testing ballistic protection panels made of LFT SB1 plus (multidirectional fiber fabrics, supplied by Teijin) against a certain threat in order to assess their resistance to this specific threat and the investigation of failure mechanisms in order to improve their behavior at ballistic impact. The models for ballistic impact are useful when they are particularly formulated for resembling the actual system projectile, target, and can be validated through laboratory experiments. Tests made on panels made of LFT SB1plus, according to NIJ Standard-0101.06-2008 gave good results for the panels made of 12 layers of this fabric, and the backface signature (BFS) was measured. The BFS upper tolerance limit of 24,441 mm recommends this system for protection level IIA, according to the abovementioned standard.",signatures:"Catalin Pirvu and Lorena Deleanu",downloadPdfUrl:"/chapter/pdf-download/62018",previewPdfUrl:"/chapter/pdf-preview/62018",authors:[{id:"229928",title:"Dr.",name:"Catalin",surname:"Pirvu",slug:"catalin-pirvu",fullName:"Catalin Pirvu"},{id:"230862",title:"Prof.",name:"Lorena",surname:"Deleanu",slug:"lorena-deleanu",fullName:"Lorena Deleanu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5759",title:"Lamination",subtitle:"Theory and Application",isOpenForSubmission:!1,hash:"9a4f81291f9d75ed83b1f4f5e0b56f36",slug:"lamination-theory-and-application",bookSignature:"Charles A. 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These lesions represent a symptom and a sign that denotes the presence of a disease pathology. The current book publication will discuss the classifications, the etiopathogenic factors, forms and clinical presentations, updates on the diagnosis and advancing management strategies of purpura in clinical settings.
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I do this by focusing on the development of a theoretical and analytical framework for identifying signs-as-agents that was shown to be applicable to other educational tools and scenarios. In themselves, the proposals may not be very novel, since they include or build on well-established traditions in various fields, though perhaps less so in the field of Education. However, I wish to suggest that a Semiotic Technologies approach, focused on signs-as-agents, applied to educational scenarios, can unite a number of well-established perspectives on digital tool use. Such an approach can also be very relevant for researchers and practitioners working with STEAM and STEM.
Through the presentation of three examples, from various educational, digital scenarios, I will show how the theoretical and analytical framework, involving the identification of initiation and response turns, understood as a multimodal exchange structure, can be used to identify screen-based signs-as-agents. In addition, I show how through the establishment of such multimodal exchange structures, signs can be understood as being agentalised. Throughout this process, I highlight how theoretical and contributions from research in Human-Computer Interaction [1]; [2, 3, 4], Social Cognition Theory [5], Critical digital literacy [6, 7, 8], Distributed Cognition Theory [9] as well as theoretical and methodological contributions from a Semiotic Technologies perspective [10, 11], can support a more holistic and critical understanding of agency and agents – both ‘human’ and ‘digital’ – in educational scenarios. The central contribution of this chapter is a typology of signs-as-agents that has been conceived in order to expand the Critical Digital Literacies teaching and research agenda specific to pedagogy. It is aimed at supporting critiques of how digital tools can shape how teachers and learners
The term Semiotic Technologies refers to “the whole array of technologies people use in order to make meaning as part of specific social practices, such as writing and drawing on a blackboard with chalk in mathematic lessons in schools, photographing beaches and mountains for image bank stock photos, or taking a selfie and uploading it on Instagram for sharing with friends and acquaintances” (p. 596) [12]. A Social Semiotic Technologies perspective is a growing subfield of social semiotics [12]. An analytic model for analysing semiotic technologies has been developed within this perspective [10, 11], that according to Djonov and Van Leeuwen [13] involves an analysis of the semiotic practices and artefacts (e.g., a written text or illustration) that warrant critical attention, as well as an analysis of the technologies that support them. Such a critical multimodal study of software, that includes the evaluation of software design, its use, and its relationship to broader semiotic and cultural practices would conceivably offer a holistic analytical approach [13] to digital technologies and their use in educational scenarios.
While a small number of studies have focused on digital tools in education from a social semiotic perspective (e.g., [14, 15, 16, 17]) the model for analytic separation of artefact and practices developed by (Zhao et al. [10] and Zhao and Van Leeuwen [11], has only more recently been applied to other digital tools in education (e.g., [10, 11, 18]). This approach to the study of the relationship between semiotic technology and social practices is highly relevant and applicable for the study of technologies in digital-based teaching and learning practices because teachers may not be the only actors (or agents) participating in what appears on the interface pages that students face [18].
I will argue that this approach is fruitful for understanding agency in digital scenarios because, following the emphasis on analytical separation, it conceivably allows us to look at how agency and agents may present themselves in relation to the digital tool itself, as well as in the social practices by teachers and/or learners with the tool. Another relevant contribution to the study of agents from a Semiotic Technologies perspective is the notion of “exchange structures” that can be realised multimodally through “user-user interactions” and “system-user interactions” and must at least contain an initiating move and a response [19]. Such an analytical focus conceivably would give insight into the intentions of human or digital agents as exchanges take place between the teacher or learner and system as well and may also give insight into how these exchanges can shape their semiotic work.
My arguments for a Social Semiotic Technologies approach are based on a critique of three premises that often underly much discourse in studies surrounding digital tool use in educational scenarios. The first premise is that digital tools should be evaluated and researched for their ‘affordances’ [20] as potential uses for supporting human intentions. While countless studies within the field of Education attest to this premise, it is important to highlight that a digital tool with a screen does not typically have a singular design intention, unlike a chair (which the notion of ‘affordance’ was initially applied to). But rather, digital tools are increasingly more complex, and are increasingly seen as having unlimited potentials, including new roles like instructing or advising humans (e.g., service bots with Artificial Intelligence) [18]. An interface that learners may face, for example, may have been designed by multiple people including interface designers and teachers and may have also passed through the hands of translation or legal teams for final touches with logos or orthographic corrections. Furthermore, a screen might present the user with many digital tools at once, so that grammar checkers, for example, can be installed ‘within’ other tools so that the affordances across multiple tools can be customised to each user. Designers may be multiple and the final product or digital tool(s), often incorporating a screen, may be the result of many months or years of design input by each one: each with their own intentions imbued in the presence of their signs.
The second premise is that digital tool use is favourable in supporting individual learner empowerment. Many studies in the field of Education also attest to this. Within a university environment, for example, e-Learning tools can create ‘leaner-centric’ and ‘collaborative-learning environments’ where learners are empowered to self-control their learning processes [21]. However, this perspective, which can be understood as part of the ‘empowerment paradigm’ [22] is often typically focused on learners and their agency rather than the potential agency that digital resources on the screen may ‘enact’ through learners’ use of them. This enactment of ‘digital’ agency, or agency enacted through digital means, can be traced back to studies in Human-Computer Interaction from the 1980’s with the creation and the identification of pedagogical agents as ‘passive’ or ‘active’ [1, 4]. A passive agent waits until it receives a request to act, while an active agent takes action on its own when it sees an opportunity to do so. These studies have highlighted the technological intentions to communicate and/or shape human action, that originate in the design of human others. More recent studies in Social Semiotics (e.g., [10, 11]) and linguistics (e.g., [23]) highlight the ability of digital technologies to shape and influence human semiotic work. This shaping potential does not refer to the shaping potential of ideas or ideology communicated typically through text and image, but rather its shaping potential is carried out through ‘exchange structures’. ‘Exchange structures’ is a notion that was originally drawn from conversational analysis and functional linguistics. Following this understanding of exchange structures, exchanges must at least contain an initiating move and a response, which can be realised multimodally. Jovanovic and Van Leeuwen [19] also mapped out the ways that digitally-mediated interactions occur across various forms of social media, including “user-user interactions” and “system-user interactions”, in what the authors describe as “a multimodal realisation of an exchange structure”. This notion has also been reflected in educational research as ‘semiotic initiations or responses’ [24] that can be understood as part of ‘multimodal turn-taking’ [25]. An example of this is a pop-up that ‘requests’ a user to accept cookies and then the user clicks the screen-based icon as the ‘acceptance’. These exchange structures have attributes of design, intention and enactment that can be assigned to constructs of agency. Therefore, the learner as a user may be only one social agent that is being empowered when digital tool use is being enacted: the social interests of each screen-based resource and how they may be empowered through turn-taking with them, should conceivably also be considered when learners carry out their semiotic work. This is especially the case in educational scenarios because, as Djonov and Van Leeuwen [26] propose, there are social interests that permeate the design and use of software.
The third premise is that a screen is solely for learners as ‘end’ users. However, unlike a page, whatever is communicated by the user through the screen, is connected to a network. The information that is passed through a screen, either entered by humans through typed text or through navigation and touch, is at least a two-way information flow. Therefore, resources on a screen can conceivably be considered more than just signs on an interface in which meaning is communicated to the user. Indeed, it could be argued that there is a relationship between humans and the screen, not only in terms of content (e.g., ideas communicated through text that is read or watched by users) but also in terms of a relationship made up of a human-digital system that is carried out through “exchange structures” [19]. With this altered conceptualisation, the screen is not just for the human users at the ‘end’ but also for digital and human ‘users’ at the other ‘end’ of the exchange which teachers and/or learners do not see. The screen is the point at which, however, potentially part of the exchange structures between the human and digital ‘system’ can be made visible to teachers and/or learners.
The three premises that I have briefly described above can be critiqued within a Social Semiotic Technologies perspective. I propose that it is therefore a potentially valuable perspective in advancing the development of Critical Digital Literacies [6, 7, 8] within educational scenarios which Pangrazio [27] has proposed is in need of expanding. Such an expansion could involve a focus on identifying signs-as-agents. While many definitions of Critical Digital Literacies exist, Luke [28] refers to it as processes of “naming and renaming the world, seeing its patterns, designs and complexities, and developing the capacity to redesign and reshape it” [28] (p. 29).
Such a critique, broadly focusing on ‘patterns’, ‘designs’ and ‘shaping’ [28] signals a number of shifts in how educationalists might (re)conceptualise digital tools and their use through a critical lens.
Firstly, this reconceptualisation is a shift in emphasis from the notion of a digital tool with a singular design intention, to a tool with multiple design intentions and designers and designs with various signs that may change meaning, patterns of use and use for different purposes over time. Secondly, while many studies in the field of Education attest to digital tool-use as being linked with learners’ individual and/or social empowerment, if learners’ creations can be shaped in the process of tool use, students’ digital semiotic work might be conceivably re-conceptualised more accurately as a
Thirdly, because a Social Semiotic Technologies methodological approach involves analysis of digital tool use and the tool itself, including design intentions of the tool, this approach conceivably also supports an analytical as well as a theoretical shift. This shift may be from tool-use and its affordances towards tool-use for different social practices. I propose that this approach can facilitate a space for identifying and analysing the various ‘voices’ of the designers and/or creators that may be ‘at play’ at any point in its use/re-use.
In the next section (Section 2), I will focus on the theoretical and analytical framework for identifying signs-as-agents, how this can be applied to other educational tools and scenarios and finish with some conclusions.
Section 2 focuses on the theoretical framework for identifying signs-as-agents. It highlights the framework’s compatibility with theoretical contributions from Human Computer Interaction [1, 2, 3, 4], Social Semiotics [29, 30, 31], Social Cognition Theory [5], Critical digital literacy [6, 7, 8] and Distributed Cognition Theory (see Hutchins [9]).
Section 3, illustrates how signs (or screen-based resources) can be identified and agentalised through use, thus becoming agents. For this, an exploratory study of ‘hidden’ digital agents in an online language scenario with a digital App called Tandem [18] is summarised in order to highlight key findings and demonstrates how an analytical tool for identifying signs-as-agents emerged.
Sections 4 and 5 focus on how the theoretical and analytical insights from the exploratory study, outlined in Section 3, can be applied to other digital tools and social practices that are commonly used in educational contexts: namely two webpages for Webquests and two ‘Google for Education’ tools for communication purposes between teachers and students.
Finally, I will conclude with some arguments as to why it is necessary for educationalists involved in educational, digital scenarios such as STEM and STEAM to critically rethink the three premises of ‘affordance’, ‘agency’ and ‘user’ and how this might be carried out.
Sign is a key concept in traditional semiotics. “Signs are elements in which the signified (‘meaning’) and signifier (‘form’) have been brought together. Social semiotics holds that the process of sign-making is subject to the interest of sign-makers, their availability of semiotic resources and the aptness of those resources to the meanings which they wish to realise” (p.3) [31]. That is to say, the relation between ‘form’ and ‘meaning’ is not arbitrary but motivated [29]. While the notion of ‘sign’ emphasised available resources as part of a system, the notion of ‘semiotic resource’ that also evolved from social semiotics, focused on how the context of communication and the sign maker shaped signs and meaning. It was focused on people’s situated choice of resources rather than a system (p. 3) [31]. This is relevant to our understanding of digital tools and their use because whereas the screen may offer learners signs, that in the designers’ intentions have a ‘logic’ which connects the signs through layout and colour for example, learners can also bring other resources from their own environment. Such resources can include the choice of language that they use while using the tool or their decision about what to include in the background if they are making a video call. Van Leeuwen [30] describes semiotic resource as follows:
Semiotic resources are the actions, materials and artefacts we use for communicative purposes, whether produced physiologically – for example, with our vocal apparatus, the muscles we use to make facial expressions and gestures – or technologically – for example, with pen and ink, or computer hardware and software – together with the ways in which these resources can be organised [30]. Van Leeuwen [30] also noted that the notion of ‘resource’ began to replace the notion of ‘sign’.
The distinction between ‘sign’ and ‘resource’ is important in understanding a digital tool in use because it allows teachers and researchers to choose whose perspective we are looking at a screen-based resource from, at any given time. That is to say, the intentions of the pre-embedded signs on the screen by an interface designer for example, or alternatively, the intentions of the learner while using the signs on the screen, or indeed, the incorporation of their own semiotic resources made available through the screen. A Semiotic Technologies approach allows for both perspectives and analysis of intentions because it attends to a) the materiality of the digital tool and also b) how that tool is used in a social practice. Intentions are an important aspect of the construct of agency because human goals, whether related to expression of identity or carrying out and completing a task, are not achieved without intentionality.
To understand ‘signs’ as potential agents that can take part in exchanges with humans, we can draw from studies in Human Computer Interaction (henceforth HCI). Knight, Dooly and Barberà [18] highlighted how the screen-based signs, were considered as pedagogical agents in HCI studies in the following way:
Pedagogical (non-human agents have been classified into two different categories: animated pedagogical agents [3] and reactive pedagogical agents [2]. Animated agents simulate human behaviour, such as facial expression, body movement and gesture whereas “reactive agents” respond to events in the environment, for instance displaying messages when certain threshold values have been reached. According to Jondahl and Mørch [4], reactive agents can be further classified as passive or active: a passive agent waits until it receives a request to act; an active agent takes action on its own when it sees an opportunity for doing so.
From the field of psychology, Social Cognition Theory, developed from Social Learning Theory (SLT) by Albert Bandura in the 1960s, also contributed significantly to theory on human agency. There are two notions that are relevant to researching signs-as-agents from Social Cognition Theory. The first is Bandura’s notion of “proxy agent” [5] and the second is a systems-based understanding of agency, all be it human systems.
The role of a “proxy-agent” [5] is where a (human) agent can be enacted or represented by others (e.g., a parent completing a task on behalf of a child). To extend this notion, signs on a screen can be understood as proxy agents that act on behalf of their designers in that they are designed to communicate an idea or act on the designer’s/designers’ behalf.
Bandura’s [5] human, systems-based understanding of human agency highlights the motor, sensory and cognitive systems in carrying out of intentional actions. This notion connects with important notions from the field of Social Semiotics, namely ‘signs’, that can be made up of ‘modes’, such as image, text and speech. The motor and sensory systems of humans are conceivably co-reliant on such modes in order to be put to use by humans to carry out their intentional actions. If humans initiate or respond to signs on the screen through their sensory or motor systems, the interaction conceivably becomes a shared human-computer one. This interaction can be characterised as “user-user interactions” and “system-user interactions” [19]: the screen facilitates oral/visual interaction between humans and users are faced by a number of signs on the screen to which they can respond to in various ways in what Jovanovic and Van Leeuwen describe as “a multimodal realisation of an exchange structure” [19]. In addition to this, a “user-system” initiated exchange [18] can also be considered a structure, given that users can initiate ‘turns’ with the digital system, through touch for navigation or voice activation for example. This human computer exchange foregrounds the notion of a systems-based notion of agency: a recognition of human systems to carry out intentional actions and also of digital systems to establish or carry out intentional actions. This understanding of agency recognises digital tools and established human experience as forming “unified ecologies, with agency distributed throughout the system [as] artefacts, context, and humans together create particular morphologies of action” (p. 9) [32]. This notion stems from Distributed Cognition Theory, a theoretical framework that was originally introduced by Edwin Hutchins and his colleagues in the mid-1980s (see Hutchins [9] for the principles of Distributed Cognition).
Following on from the theoretical framework, Section 3 illustrates how signs (or screen-based resources) were identified and agentalised through use, which led to the key concept presented in this section (Section 2) of ‘signs-as-agents’. Section 3 revisits the data from an exploratory study, spanning over 5 years, that focused initially on learner agency in an online language learning scenario to develop speaking skills [23, 25, 33] and evolved into a focus on ‘hidden’ digital agents from a more critical perspective [18].
In order to illustrate how educationalists and researchers might research and identify signs-as-agents, rather than just affordances of digital tools, it is pertinent to revisit the first data set from an exploratory study and its relevant findings. The signs-as-agents in the Tandem tool were initially identified in a study by Knight, Dooly and Barbera [18] but the term ‘signs-as-agents’ has not been used in relation to the exploratory study until this section.
The following screenshots and analysis relate to a language learning App called Tandem which is an audioconferencing tool that facilitates oral interaction between students in a synchronous mode. Students cannot see each other. Instead, they are faced with various textual instructions, navigation buttons and texts in order to support the student interaction.
As in keeping with a Semiotic Technology approach, the materiality of the tool, in this case the screen-based resources or signs, were analysed separately from their use. However, also in keeping within a Semiotic Technology approach, the tool in-use by students was also analysed in the form of the audio recordings of what students were saying during the process of interacting with the screen as well as each other. This gave insight into intentions and actions taking place during the learning process from the student perspective.
Pop-ups (Figures 1 and 2) appeared on the screen at different moments, “inviting” students to “respond” by clicking on the screen ‘button’ provided, namely ‘Start’ (Figure 1) and ‘Close’ (Figure 2). These were identified and later labelled as ‘active agents’ according to the classification of Pedagogical agents from studies in HCI, shown in Figure 3.
Pop-up on Interface page before students start conversing orally.
Pop-up on Interface page (when time is up for task 1).
Classification of pedagogical agents in HCI studies (cf. Fischer et al., 1985; Müller, 1998; Johnson et al., 2000; Jondahl and Mørch, 2002).
Navigation resources such as ‘Next Task’ (Figure 4) and ‘See solution’ (Figure 5), were identified and later labelled as ‘passive agents’. Passive agents were available on the screen and when students wanted to use them to move forward (or back) through the task sequence, they clicked on them.
Navigational button on Interface page for students to navigate to the ‘next task’.
Navigational button on Interface page for students to check their answers ‘see solution’.
This identification highlighted the ‘semiotic initiation and responses’ [24] or ‘multimodal turn-taking’ [25] that was carried out between student and the screen, also while students were interacting orally. Consequently, these screen-based resources or signs were considered to be “direct discourse agents” [18] because they could carry out turns with humans as ‘agentive turn takers’ [23]. When initiations, either human or digital, met with a response (e.g., from the screen ‘moving on’ to another page or from the learner, clicking) the signs were considered to be “agentalised”, a notion from Van Leuwen [34]. This “multimodal experience revealed how peer-to-peer talk can occasionally resemble a multi-party encounter whereby some resources can act as or be oriented towards as participants in the interaction” [23].
This dual-focused analysis, particularly in the analysis of learners’ oral turns from the audio-recordings, also revealed another type of human-computer ‘relationship’ in the form of screen-based resources that acted as “shaping agents” [18]. The resources that acted as “shaping agents” were invoked or made relevant in the context of learners’ oral turns, thereby they became part of the oral messages in the human, user-user, oral interaction. Specifically, the screen-based resources became: 1) embedded or modified in oral turns (as in Figure 6); 2) resources to initiate and support oral turns (also in Figure 6) or 3) diverse topics of talk (as in Figure 7).
Transcript of student-student oral interaction whereby screen-based resources became embedded or modified in oral turns or resources to initiate and support oral turns.
The screen-based resources become topics of talk.
Regarding shaping agents, The ‘?’ sign, with suggested answers next to it (Figure 6), was used by learners as a resource to initiate and support oral turns. Also in Figure 6, a textual lexical item on the screen, ‘Where do you live?’ becomes embedded in learners’ oral turns.
In Figure 7, the visual textual signs are used as topics of talk, namely about whether the students are going to ‘close’ the pop-up or not, a word that also appears on the pop-up.
Signs were also considered turn-takers in the interaction, as shown in Figure 7 where the pop-ups initiates an action and the students refer to the pop-up as “the computer” or “it” (Figure 7).
These examples and results from the exploratory study on learner agency in an online language scenario contributed theoretically as a first step towards a typology of signs-as-agents: Signs can shape human (oral) turns [23] and can be understood as ‘shaping agents’ [18]. In addition, signs that can establish an exchange structure with humans (either ‘system-user’ [19] or ‘user-system’ [18]) can be understood as either ‘active’ or ‘passive’ ‘direct discourse agents’ [18]. This emerging typology is illustrated in Figure 8. It reflects the classification of agents from HCI studies but also expands on how the concept of agents relates to the notion of signs from the field of Social Semiotics. The notion of “shaping agents” is not in Figure 3 of the classification of pedagogical agents in HCI studies because social practices, or use of the digital tool or signs was not explicitly considered in such HCI studies. However, I incorporate it into the typology of signs-as agents now in Figure 8. Figure 8 also includes the notion related to “shaping agents”, that signs are agentalised when the screen-based signs shape the human (oral) turn in some way.
Emerging typology: Version A.
The following sections, Sections 4 and 5, illustrate how this emerging typology can be applied to two other educational scenarios, involving digital tools, and can be developed even further.
A WebQuest is an inquiry-oriented lesson format in which most or all the information that learners work with comes from one or more websites [35]. The following screenshots are from webpages that were incorporated into pre-service teachers’ designs for WebQuests. Webquests typically involve teachers creating questions and choosing internet-based links so that students can follow the links and collect specific information on a topic.
The following examples illustrate how the typology for signs-as-agents, developed in the first analysis from the Tandem tool, can be applied to websites incorporated into WebQuests. WebQuests are particularly interesting to analyse, because depending on the WebQuest designer, the web sites included in the quest may include a wide range of internet pages with diverse modes (e.g., static, moving images, videos), functionalities (e.g., ability to ‘like’, ‘dislike’, leave textual comments on the site) as well as ‘housing’ different intentions which may be designed for educational purposes or not.
The following screenshots (Figures 9–12) were taken from a screencast video recording of a pre-service teacher trying out various webpages as part of WebQuests designed by other pre-service teachers. It is a common educational (social) practice for teachers to try out teaching and learning activities to check whether they are appropriate for the students that they are going to teach. They need to check whether the activities will develop the particular competences that they are trying to develop in their students. Additional screenshots (Figures 13–16) of the webpages were also taken by the researcher, while navigating to and within the web pages. The two websites in the analysis pertain to ‘Cool Kids Facts on Photosynthesis’ and ‘Kids Britannica’ focused on the topic of ‘culture’.
A screenshot of a screencast video recording of a pre-service teacher trying out the ‘Cool Kids Facts’ webpage.
A screenshot of a screencast video recording of a pre-service teacher trying out the ‘Cool Kids Facts’ webpage.
Pop-up translation tool offering a translation of the English website to ‘Espanyol’ (Spanish). Offered by Google translate.
A Britannica kids banner with ‘7 day free trial’ in another colour.
Animated advertisement for furniture company ‘Rochebobois’ (right) and hyperlink for a ‘quiz’ (bottom).
Animated advertisement for an technology company ‘IBM’ (right) and animated advertisement for furniture compant ‘Rochebobois’ (bottom).
Pop-up with ‘subscribe today’ (bottom) and an invite to know about cookies (top).
Tabs with different options – ‘Fundamentals’, ‘kids’, ‘students’, ‘scholars’ that can be clicked (top) and 6 square images representing ‘articles and videos’.
As in keeping with a Semiotic Technology approach, the signs on the screen, captured from a pre-service teacher’s video of her/him “checking out” different webpages that form part of other pre-service teachers’ WebQuests, were analysed separately from their use. During the researcher’s follow up navigation, the researcher used the opportunity to check if the signs, were ‘passive’ or ‘active’ by clicking various signs, as the pre-service teacher did not do this because he/she had his/her own navigational path and intentions. The screenshots were chosen, to illustrate how the developing typology, outlined in Section 3, might be applied to different educational, digital resources and scenarios apart from the Tandem App.
Table 1 illustrates how the typology was used to analyse web pages in order to identify signs-as agents. While the analysis is not systematic1 in the sense that not every sign was analysed in relation to the different semiotic modes (e.g., layout, texture, colour, sound, etc.), which is a common feature of studies from a Social Semiotics perspective, there is enough visual, textual and navigational information from the two web pages (Cool Kids Facts Photosynthesis and Kids Britannica) to tentatively apply the typology for the purposes of this chapter.
Webpage | Signs-as-agents | ||
---|---|---|---|
Active (REACTIVE) | Passive (REACTIVE) | Animated | |
Cool Kids Facts Photosythesis | Pop-up about consent for using Data and Cookies. Requiring to be clicked by the user (Figure 9) | The word ‘quiz’ is a hyperlink, that when clicked leads to a ‘Photosythesis Facts Quiz’ (Figure 13) | Adverts on the left change and are animated with moving arrows or the start of a video which then stops (Figures 13 and 14) |
Advert banners at the bottom whereby the companies change (Roche Bobois/Just Eat/Western Union) and some of the text in the banner changes as well (Figure 14) | |||
Kids Britannica | Pop-up translation tool offering a translation of the English website to ‘Espanyol’ (Spanish) offered by Google Translate. It can be removed by clicking the ‘x’ (Figure 11) | Banner at the top of the page giving information about Cookies with an ‘x’ that symbolises ability to close this banner (Figure 15) | None |
A Britannica Kids Banner with ‘7 Day Free Trial’ in another colour (Top of Figure 12) | |||
A ‘Subscribe Today’ text in a coloured box (Figure 15) | |||
Tabs with different options – ‘Fundamentals’, ‘Kids’, ‘Students’, ‘Scholars’ that can be clicked (Figure 16) | |||
6 Square images representing ‘Articles and videos’ |
Analysis of two webpages in order to identify signs-as-agents.
The pop-ups that appeared when navigating to both webpages, ‘Cool Kids Facts’, and the ‘Kids Britannica’, can be conceptualised as signs as potential agents because they “invite” the user to click on them. The pop-up consent for using Data and Cookies in Figure 9 requires the user to “Aceptar” (Accept) or “Cambiar Las Preferencias” (Change the preferences). When the user clicks in response, the exchange structure can be considered to be established and the sign is ‘agentalised’.
Similarly, when navigating to the Kids Britannica webpage, a pop-up in the top right corner occurs before the webpage fully appears (Figure 11). The text on the pop-up says “Traducir siempre de Ingles” (Always tanslate from English) which can be considered to be an invite to change the language preferences when navigating to a page in another language. The pop-up requires the user to click “Espanyol” (Spanish) to translate to or close the pop-up indicated by an ‘x’. In this case, the pop-up was closed. This pop-up was not generated by the webpage Kids Britannica but rather “Google Translate” (Figure 11). Importantly, this highlights a need to recognise distributed agents and agency across the “layers” [36] “of message, interface, communication flow, organisation of information, the platform” [36] in order to unveil power relationships more fully. Designers (or signmakers) can be involved not only in webpage design but also navigation design between pages, namely browser design, in this case from Google.
Both websites had what can be considered to be ‘passive agents’ on the pages. These were in the form of hypertext, indicated by a different colour than the body copy (Figures 12 and 13) and visual icons that could be made up of colour, text and shape such as the ‘Free 7 day Trial’ (Figure 12) and ‘Subscribe Today’ icon (Figure 15). These could be clicked, or “initiated”, at any moment by the user, depending on user intentions. The “response” of the system would be to move the user on to another page. Therefore, they are considered to be passive signs as potential agents that can be “agentalised” when clicked. Similarly, visual/textual icons including ‘tabs’ (4 Tabs in Figure 16) and visual icons including images could also be clicked (6 square images in Figure 16).
During the analysis, another type of agent was present that did not emerge in the results of the exploratory study with the Tandem tool, namely ‘Animated agents’. Animated agents simulate human behaviour, such as facial expression, body movement and gesture. In the case of webpages for example, certain signs flickered on and off and people in embedded videos moved, all of which humans could click through navigation. Such animated movement can be understood as mirroring human behaviour.
Finally, with respect to animated signs, only the Cool Kids Facts webpage housed these. These were located on the right hand side of the page (Figures 13 and 14), taking up a third of the page space. In addition, an animated sign banner was also present at the bottom of the screen saying ‘Nueva Tienda’ (New shop) for the furniture company Roche Borbois (Figure 14). This banner changed adverstisements from different companies including the companies ‘Just Eat’ and ‘Western Union’ while the researcher was observing. Clicking on this banner led the user to the various company web pages.
The key point to highlight before applying the typology to another digital tool, is to note the presence of animated signs that were highlighted in the HCI classification of agents (Figure 3. Classification of pedagogical agents in HCI studies), as well as passive and active signs/agents. These are signs/agents that can be agentalised through the completion of either a computer generated or human initiation and response. These turns are multimodal in nature and through analysing the webpage, as well as its use, agents can be identified.
The analysis of the webpages for WebQuests shows how the typology outlined in Section 3, can be applied to another digital tool and practice within Education. Unlike the Tandem tool, where the social interests were pedagogical in nature, the webpages house social interests that are not purely educational in nature, but rather, have legal and commercial interests. Legal interests are present in the Cookies ‘agreement’ as the pop-up seeks acceptance to use users’ data. Commercial interests can be seen in the ‘7 Day Free Trial’ for access to Britannia Kids Encyclopedia, which requires later payment. Although this commercial aspect does relate to the area of education, commercial interests that are unrelated to education are also present. Notably, these interests can take up approximately half of the screen space, underscoring how the co-existence of different social interests can be embued in the diferent design intentions of signs on one ‘educational’ webpage. While these signs/agents can be considered as ‘direct discourse agents’ because users can click on them as a response or initiation, they can also be understood as attempts to shape users’ tool use. The adverts (Figures 13 and 14) have the potential to shape a user’s attention, and therefore the user’s interests, away from the educational content on the webpage on ‘photosynthesis’, towards commercial interests. Similarly, the navigation choices on the Cookies pop-up are limited to ‘accept’ and continue, to change preferences or to click away from the site to another. The use of a solid block of colour used to highlight ‘accept’ can be understood as an attempt to shape the user’s navigation pattern towards ‘accepting’ a legal interest before the continuation to the educational content for the user is made navigationally possible.
The final example in this study relates to two tools within the ‘Google Workspace for Education’ suite of tools for educators. Google Workspace for Education is used by many educational institutions including universities and schools. It is a cloud-based tool that according to Google, provides “a free suite of easy-to-use tools that provide a flexible and secure foundation for learning, collaboration, and communication” (Google, 2020 https://edu.google.com/products/workspace-for-education/education-fundamentals/). The range of tools include Gmail (email tool), Calendar, Meet (videoconferencing tool), Docs, Sheets, Slides, Forms, Classroom, Assignments, Sites, Groups, Drive, and the Administrator Dashboard. The suite of tools can be shared with other users so that they can collaborate synchronously or asynchronously.
Screenshots of the tools in use were taken by the researcher. The screenshots are from my own social practice, in my role as a teacher who has to manage a wide variety of social actions related to teaching and learning. These roles include contacting students and communicating with colleagues by email (Gmail) as well as creating educational resources by ‘writing’ on a document in Google Drive.
Figure 17 is a screenshot of an email from an (anonymized) student to me. In the email, the student has sent me work, attached as a document. At the bottom of the screenshot there are three phrases: ‘Great’, Thanks for letting me know’, ‘Great!’ and ‘Great. Thanks!’. One of the affordances of these phrases for the user is being able to click these phrases for intentional use as a response to the sender, that may save time writing. It is also useful for making sure that the phrases used by the writer of the email are grammatically and orthographically correct. This is conceivably important if English is not your first language. However, using the typology in Figure 8 of signs-as-agents, I propose that these phrases, that can be clicked on by users as “off the shelf” pre-made responses, can be understood as passive agents. The design intention of the signs (‘Great. Thanks for letting me know.’, ‘Great!’ and ‘Great. Thanks!’) is presented to the user in order for the user to initiate (click) instead of making a human typed response. In this action, the initiation serves to
Screenshot of an email from an (anonymized) student to me.
At this point it is useful to compare this finding with the findings from the Tandem tool, specifically how learners’ oral turns can be shaped in different ways. Whereas Knight, Dooly and Barberà [23] highlighted how screen-based resources could shape oral turns by lexical/visual items becoming embedded or becoming topics of talk, results of the analysis in this study illustrates how screen-based resources can shape written (typed) turns of humans in a different way. This is illustrated in Figure 17 whereby if the user intentionally clicks on a sign/screen-based resource, the chosen sign can then replace the user’s (typed) turn completely. We can understand these signs as other potential shaping agents.
In Figure 18, I turn to another tool in the Google Suite, namely a Google Document in Google Drive. The affordance of using Google documents is that they can be shared across time, space and also be used by a number of users, synchronously or unsynchronously.
Screenshot of a Google Document that is being used for planning and educational course.
In the Google Document, in my role as a teacher, I have started to use the document for course planning purposes within an educational setting. As I am typing, the system ‘suggests’ how I might finish the word that I have started to type (‘said’) as well as suggesting complete words that I might type next (‘and done’): acting as a predictor. To ‘accept’ the suggestion, I can press the right-arrow key. To ‘reject’ the suggestion, I can keep typing. Following the emerging typology, we can understand this predictive text to be a shaping agent that is passive and that can become embedded in my typed turn (understood as the completion of the word). Also following the typolgy, I can agentalise it by ‘accepting’ using the right-arrow key. This choice of ‘accepting’ and ‘rejecting’ can be understood as my response turn. Furthermore, this process conceivably resembles a negotiating process with the digital tool, rather than a purely creative one, as I negotiate my responses through touch, with the screen-based resources.
Before concluding, a second version of the typology is presented in Figure 19, encompassing all the signs-as-agents identified across the three examples analysed.
Emerging typology: Version B.
This study aimed to highlight how educationalists might (re)conceptualise digital tools and their use through a critical lens. It achieved this by specifically focusing on the development of a theoretical and analytical framework that formed the basis for a typology for identifying signs-as-agents. This typology was shown to be applicable to other educational tools and scenarios. It can be expanded further, taking into account different digital technologies in use and different social practices it is being applied to. The study has highlighted, through analysis with examples, why educationalists should rethink the concepts of ‘affordances’ of tools and ‘agency’ because digital agents are also present as human users/agents carry out their semiotic work. This focus highlights a shift in emphasis from a human centric, individual agency towards a systems-based understanding of agency in which the human systems (e.g., motor system) together with the digital system, form a part. Furthermore, the focus highlighted why the notion of ‘designers’ and ‘design intentions’, rather than end ‘user’ is perhaps a more relevant concept for a more holistic and critical understanding of how semiotic work is produced/created in educational social practices. Importantly, the study has shown how and why this process is a negotiated process with other designers’ intentions, not a purely productive or creative endeavour of a human user.
This paper, as a critique, broadly focused on ‘patterns’, ‘designs’ and ‘shaping’ [28] which are key notions in Critical Digital Literacies. The patterns under focus were exchange structures (or interactional patterns), understood as turn-taking. This focus included an analysis of the ‘designs’ of potentially many designers and users of others’ designs across time and with different social interests or intentions. This highlighted the social interests that permeate the designs and use of digital tools [26]. Furthermore, signs-as-agents can be understood as an extension of their human designers (as agents) highlighting the role of signs as ‘proxy agents’ [5] for designers. Signs understood as extensions of their designers also underscores the notion of designers’ interests or intentions being ‘distributed’, echoing Distributed Cognition Theory [9]. Furthermore, the ability of signs-as-agents to
In addition, the results highlighted how the ‘shaping’ of both learners’ and teachers’ semiotic work can occur, as well as the use of/shaping of pre-designed digital tools and their accompanying signs-as-agents. The ways of ‘shaping’ human semiotic work were shown to be extremely diverse, understood through an analysis of human oral and typed turns.
The chapter sought to add to pre-existing theoretical and analytical tools for educationalists to understand and approach digital tool use from a more critical stance. In doing so, the author proposes that the process of identifying and uncovering signs-as-agents, can contribute to the development of Critical Digital Literacies for Education. This could include looking beyond notions of creation and empowerment to notions that are centred on awareness, design intentions and teachers’ and learners’ abilities to identify and negotiate with those intentions.
Finally, the central contribution of this chapter is a typology of signs-as-agents. Specifically, it has emerged and been developed in order to critique how digital tools shape how we
Regarding future research, the typology could be applied in order to support a much wider analysis of digital tools by teachers and researchers. In doing so, the typology can be added to and developed further. Furthermore, while this chapter has focused on tools and scenarios that involve human responses to signs-as agents while speaking, reading and/or typing as social practices, greater attention could be made to human initiations. For example, the use of QR codes in Mobile Assisted Learning as well as the use of human voice activation with digital tools which would encompass more modes and signs than exist in the current version of the typology.
I would like to thank Leo van Lier, who is no longer with us, but through his chapter ‘From Input to Affordance’ (2000), helped to inspire this paper.
Chronic myeloproliferative disorders are a group of clonal diseases of the stem cell. It is a group of several diseases with some common features. They derive from a multipotential hematopoietic stem cell. A clone of neoplastic cells in all these neoplams is characterized by a lower proliferative activity than that of acute myeloproliferative diseases. In each of these diseases, leukocytosis, thrombocythemia, and polyglobulia may appear at some stage, depending on the diagnosis [1, 2].
The research on interferon has been going on since the 1950s [3]. Then, the attention was paid to its influence on the immune system. It has been noted that it can exert an antiproliferative effect by stimulating cells of the immune system [4]. In 1987, a publication by Ludwig et al. was published, which reported the effectiveness of interferon alpha in the treatment of chronic myeloproliferative disorders [5].
More and more new studies have been showing the effectiveness of interferon alpha in reducing the number of platelets, reducing the need for phlebotomies in patients with polycythemia vera and also in reducing the number of leukocytes. Moreover, interferon reduced the symptoms of myeloproliferative disorders such as redness and itching of the skin. Additionally, it turned out to be effective in reducing the size of the spleen.
Further studies on the assessment of remission using molecular-level response assessments indicate that the interferon action in chronic myeloproliferation diseases targets cells from the mutant clone with no effect on normal bone marrow cells [6].
Over the years, interferon alpha-2a and interferon alpha-2b have been introduced into the treatment of chronic myeloproliferation, followed by their pegylated forms. The introduction of pegylated forms allowed for a reduction in the number of side effects and less frequent administration of the drug to patients. In recent years, monopegylated interferon alpha-2b has been used to further increase the interval between drug administrations while maintaining its antiproliferative efficacy.
The exact mechanism of action of interferon alpha in the treatment of chronic myeloproliferative disease is still not fully understood, but it has an impact on JAK2 (Janus Kinase) signal transducers and activates the STAT signal pathway (Janus Kinase/SignalTransducer and Activator of Transcription).
Interferon alpha binds to IFNAR1 and IFNAR2c, which are type I interferon receptors. Interferon alpha has an impact on JAK2(Janus Kinase) signal transducers and activates the STAT signal pathway. The disturbances in this signaling pathway are observed in chronic myeloproliferative disorders [7].
Interferon inhibits the JAK-STAT signaling pathway by directly inhibiting the action of thrombopoietin in this pathway [8].
So far, three driver mutations have been described in the course of chronic myeloproliferative diseases that affect the functioning of the JAK-STAT pathway.
JAK2 kinase and JAK1, JAK3, and TYK2 kinases belong to the family of non-receptor tyrosine kinases. They are involved in the intracellular signal transduction of the JAK-STAT pathway. It is a system of intracellular proteins used by growth factors and cytokines to express genes that regulate cell activation, proliferation, and differentiation. The mechanism of JAK activation is based on the autophosphorylation of tyrosine residues that occurs after ligand binds to the receptor. JAK2 kinase transmits signals from the hematopoietic cytokine receptors of the myeloid lineage (erythropoietin, granulocyte-colony stimulating factor thrombopoietin, and lymphoid lineage [9].
A somatic G/T point mutation in exon 14 of the JAK2 kinase gene converts valine to phenylalanine at position 617 (V617F) in the JAK2 pseudokinase domain, which allows constitutive, ligand-independent activation of the receptor to trigger a proliferative signal [10].
Mutation of the MPL gene, which encodes the receptor for thrombopoietin, increases the sensitivity of magekaryocytes to the action of thrombopoietin, which stimulates their proliferation [11].
Malfunction of calreticulin as a result of mutation of the CARL gene leads to the activation of the MPL-JAK/STAT signaling pathway, which is independent of the ligand, as calreticulin is responsible, for the proper formation of the MPL receptor. Consequently, there is a clonal proliferation of hematopoietic stem cells [12].
Below, we provide an overview of some clinical studies on the efficacy of interferon in chronic myeloproliferative disorders.
Polycythemia vera (PV) is characterized by an increase in the number of erythrocytes in the peripheral blood.
Polycythemia vera is caused by a clonal mutation in the multipotential hematopoietic stem cell of the bone marrow. The mutation leads to an uncontrolled proliferation of the mutated cell clone, independent of erythropoietin and other regulatory factors. As the mutation takes place at an early stage of hematopoiesis, an increase of the number of erythrocytes as well as of leukocytes and platelets is observed in the peripheral blood. The cause of proliferation in PV independent from external factors is a mutation in the Janus 2 (JAK2) tyrosine kinase gene. The V617F point mutation in the JAK2 gene is responsible for about 96% mutation, and in the remaining cases the mutation arises in exon 12. Both mutations lead to constitutive activation of the JAK-STAT signaling pathway [13].
As a result of the uncontrolled proliferation, blood viscosity increases, which generates symptoms such as headaches and dizziness, visual disturbances, or erythromelalgia. As the number of all hematopoietic cells, including the granulocytes ones, increases, the difficult to control symptoms of their hyperdegranulation may appear, among which gastric ulcer or skin itching is often observed. During the disease progression, the spleen and liver become enlarged.
The most common complication of the disease is episodes of thrombosis, especially arterial one. During the course of the disease, it can also evolve into myelofibrosis or acute myeloid leukemia.
The treatment of PV is aimed at preventing thromboembolic complications, relieving the general symptoms, the appearance of hepatosplenomegaly as well as preventing its progression.
Each patient should receive an antiplatelet drug chronically, and usually acetylsalicylic acid is the choice. Most often, the treatment is started with phlebotomy in order to rapidly lower the hematocrit level. If cytoreductive therapy is necessary, the drugs of first choice are hydroxycarbamide and interferon [2].
However, the research on the mechanism of the action of interferons is still ongoing. In vitro studies with CD34+ cells from peripheral blood of patients diagnosed with polycythemia vera showed that interferon inhibits clonal changed cells selectively. It was found that interferon alpha-2b and pegylated interferon alpha-2a reduce the percentage of cells with JAK2 V617F mutation by about 40%. Pegylated interferon alpha-2a works by activating mitogen-activated protein kinase P38. It affects CD34+ cells of patients with polycythemia vera by increasing the rate of their apoptosis [6].
A case of a patient with PV with a confirmed chromosomal translocation t(6;8) treated with interferon alpha-2b, which resulted in a reduction of the clone with translocation by 50% from the baseline value, was also described [14].
In 2019, the results of a phase II multicenter study were published, which aimed at assessing the effectiveness of recombinant pegylated interferon alpha-2a in cases of refractory to previously hydroxycarbamide therapy. The study included 65 patients with essential thrombocythemia (ET) and 50 patients with polycythemia vera. All patients had previously been treated with hydroxycarbamide and showed resistance to this drug or its intolerance.
The assessment of the response was performed after 12 months of treatment. Overall response rate to interferon was higher in patients diagnosed with ET than in patients with polycythemia vera. In essential thrombocythemia, the percentage of achieved complete remissions was 43 and 26% of partial remissions. The remission rate in ET patients was higher if calreticulin CALR gene mutation was present. Patients with polycythemia vera achieved complete remission in 22% of cases and partial remission in 38% of cases.
Treatment-related side effects that follow to discontinuation of treatment were reported in almost 14% of patients [15].
The duration of response to treatment with pegylated interferon alpha-2a and the assessment of its safety in long-term use in patients with chronic myeloproliferative disorders was the goal of a phase II of the single-center study. Forty-three adult patients with polycythemia vera and 40 patients with essential thrombocythemia were enrolled in the study. The complete hematological response was defined as a decrease in hemoglobin concentration below 15.0 g/l, without phlebotomies, a resolution of splenomegaly, and no thrombotic episodes in the case of PV, and for essential thrombocythemia—a decrease platelet count below 440,000/μl and two other conditions as above. The assessment of the hematological response was performed every 3–6 months. The median follow-up was 83 months.
The hematological response was obtained in 80% of cases for the entire group. In patients with polycythemia vera, 77% of patients achieved a complete response (CR) while 7% a partial response (PR). The duration of response averaged 65 months for CR and 35 months for PR. In the group of patients diagnosed with essential thrombocythemia, CR was achieved in 73% and PR in 3%. The durance of CR was 58 months and PR was 25 months.
The molecular response for the entire group was achieved in 63% of cases.
The overall analysis showed that the duration of hematological remission and its achievement with pegylated interferon alpha-2a treatment is not affected neither by baseline disease characteristics nor JAK2 allele burden and disease molecular status. There was also no effect on age, sex, or the presence of splenomegaly.
During the course of the study, 22% of patients discontinued the treatment, because of toxicity. Toxicity was the greatest at the beginning of treatment. The starting dose was 450 μg per week and was gradually tapered off.
Thus, on the basis of the above observations, the researchers established that pegylated interferon alpha-2a may give long-term hematological and molecular remissions [16].
The assessment of pegylated interferon alpha-2a in group of patients diagnosed with polycythemia vera only was performed. The evaluation was carried out on a group of 27 patients. Interferon decreased the JAK2 V617F allele burden in 89% of cases. In three patients who were JAK2 homozygous at baseline, after the interferon alpha-2a treatment wild-type of JAK2 reappeared. The reduction of the JAK2 allele burden was estimated from 49% to an average 27%, and additional in one patient the mutant JAK2 allele was not detectable after treatment. It can therefore be postulated that the action of pegylated interferon alpha-2a is directed to cells of the polycythemia vera clone [17].
In 2005, the results of treatment by pegylated interferon alpha-2b of 21 patients diagnosed with polycythemia vera and 21 patients diagnosed with essential thrombocythemia were published. In the case of polycythemia vera in 14 patients, PRV-1 gene mutation was initially detected. In 36% of cases, PRV-1 expression normalized after treatment with pegylated interferon alpha-2b. For the entire group of 42 patients, the remission assessment showed that complete remission was achieved in 69% cases after 6 months of treatment. However, only in 19 patients remission was still maintained 2 years after the start of the study. Pegylated interferon alpha-2b was equally effective in patients with PV and ET. The use and the type of prior therapy did not affect the achievement of remission [18].
Another study with enrolled only PV patients included 136 patients. They were divided into two arms. One group received interferon alpha-2b and the other group received hydroxycarbamide. Interferon dosage was administered in 3 million units three times a week for 2 years and then 5 million units two times a week. Hydroxycarbamide was administered at a dose between 15 and 20 mg/kg/day.
In the group of patients treated with interferon, a significantly lower percentage of patients developed erythromelalgia (9.4%) and distal parasthesia (14%) compared with the group treated with hydroxycarbamide, for whom these percentages were respectively: 29 and 37.5%. Interferon alpha-2b was found to be more effective in inducing a molecular response, which was achieved in 54.7% of cases, in comparison with hydroxycarbamide—19.4% of cases, despite the fact that the percentage of achieved general hematological responses did not differ between the groups and amounted about 70%. The 5-year progression free period in the interferon group was achieved in a higher percentage (66%) than in the hydroxycarbamide group (46.7%) [19].
The most recent form of interferon approved by the
Thanks to these changes to the structure of the molecule, it was possible to achieve a significant increase in its half-life. Ropeginterferon can be administered subcutaneously to patients every 14 days. The clinical trials conducted so far have assessed the ropeginterferon dose from 50 micrograms to a maximum dose of 500 microgams administered as standard every 2 weeks. The possible dose change in case of side effects includes not only the reduction of the drug dose itself, but also the extension of the interval between doses. The extension of the dosing interval up to 4 weeks was assessed.
Ropeginterforn was approved in 2019 by the EMA for the use in patients diagnosed with polycythemia vera without splenomegaly, as monotherapy.
Ropeginterferon, like the previous forms of interferons used in treatment, is contraindicated in patients with severe mental disorders, such as severe depression. It is also a contraindication in patients with noncompensatory standard treatment of disorders of the thyroid gland as well as severe forms of autoimmune diseases. The safety profile of ropeginterferon is similar to that of other forms of alpha interferons. The most common side effects are flu-like symptoms [20].
Ropeginterferon has been shown to exhibit in vitro activity against JAK2-mutant cells. The activity of ropeginterferon against JAK2-positive cells is similar to that of other forms of interferons used actually for standard therapy. Ropeginterferon has an inhibitory effect on erythroid progenitor cells with a mutant JAK2 gene. At the same time, it has almost no effect on progenitor cells without the mutated allele (JAK2-wile-type) and normal CD34+ cells. A gradual decrease of JAK2-positive cells was observed in patients with PV during ropeginterferon treatment. The examination was performed after 6 and 12 months of treatment. In comparison, the reduction in the percentage of JAK2 positive cells in patients treated with hydroxycarbamide was significantly lower.
These results may suggest that ropeginterferon may cause elimination of the mutant clone, but further prospective clinical trials are needed to confirm this theory. The evaluation was performed on a group of patients enrolled in the PROUD-PV study who were treated in France [21].
In 2017, a multicenter study was opened in Italy. The study was of the second phase. In total, 127 patients with polycythemia vera were included in the study. All patients enrolled on the study had low-risk PV. The clinical trial consisted of two arms. Patients received phlebotomies and low-dose aspirin in one arm and ropeginterferon in the other arm. The aim of the study was to achieve a hematocrit of 45% or lower without any evidence of disease progression. Ropeginterferon was administered every 2 weeks at a constant dose of 100 μg.
The response to the treatment was assessed after 12 months. The reduction of hematocrit to the assumed level was achieved in significantly higher percentage of patients in the ropeginterferon group than of patients who received only phlebotomies and aspirin. In addition, none of the patients treated with ropeginterferon experienced disease progression during the course of the study, while among those treated with phlebotomies, 8% of patients progressed.
Grade 4 or 5 adverse events were not observed in patients treated with ropeginterferon, and the incidence of remaining adverse event (AE) was small and comparable in both arms. The most common side effects in the ropeginterferon group were flu-like symptoms and neutropenia; however, the third-grade neutropenia was the most common (8% of cases) [22].
One of the most important clinical studies on the use of ropeginterferon was the PROUD-PV study and its continuation: the CONTINUATION-PV study. These were three-phase, multicenter studies. The aim of the study was to compare the effectiveness of ropeginterferon in relation to hydroxycarbamide. The study included adult patients diagnosed with polycythemia vera treated with hydroxycarbamide for less than 3 years and no cytoreductive treatment at all. In total, 257 patients received this treatment. The patients were divided into two groups: those receiving ropeginterferon or the other being given hydroxycarbamide.
During the PROUD-study, drug doses were increased until the hematocrit was achieved below 45% without the use of phlebotomies, and the normalization of the number of leukocytes and platelets was reached.
The PROUD-PV study lasted 12 months. After this time, the patients continued the treatment under the CONTINUATION-PV study for further 36 months. After the final analysis performed in the 12th month at the end of PROUD study, it was found that the hematological response rates did not differ between the ropeginterferon and hydroxycarbamide treatment groups. These were consecutively 43% in the ropeginterferon arm and 46% in the control arm.
However, after analyzing the CONTINUATION- PV study, it turned out that after 36 months of treatment, the rates of hematological responses begin to prevail in the group of patients receiving ropeginterferon, 53% versus 38% in the control group. Thus, from the above data, it can be seen that the response rate to ropeginterferon increases with the duration of treatment [23].
Another analysis of patients participating in the PROUD and CONTINUATION studies was based on the assessment of treatment results after 24 months, dividing patients into two groups according to age (under and over 60 years).
The initial comparison of both groups of patients showed that older patients had a more aggressive course of the disease. Patients over 60 years of age had a higher percentage of cells with a mutant JAK2 allele. They experienced both general symptoms and some complications, such as thrombosis, more frequently. Both patients under 60 years of age and over 60 years of age in the ropeginterferon arm had a higher rate of molecular response, namely 77.1 and 58.7% compared with the HU remission: 33.3 and 36.1%, respectively. Significantly higher reductions in the JAK2 allele were observed in both groups of patients after ropeginterferon treatment: it was 54.8% for younger patients and 35.1% for elderly patients. For comparison, this difference in the group of patients treated with HU was 4.5 and 18.4%, respectively.
What is more, the age did not affect the frequency of ropeginterferon side effects. In addition, the incidence of adverse ropeginterferon disorders was similar to that observed in the hydroxycarbamide group [24].
Essential thrombocythemia is a clonal growth of multipotential stem cells in the bone marrow. The consequence of this is increased proliferation of megakaryocytes in the bone marrow and an increase in the number of platelets in the peripheral blood. The level of platelets above 450,000/μl is considered a diagnostic criterion.
Essential thrombocythemia may progress over time to a more aggressive form of myeloproliferation, i.e., myelofibrosis. The disease can also evolve into acute myeloid leukemia or myelodysplastic syndrome, both with very poor prognosis. Thromboembolic complications are serious, and they concern over 20% of patients. Thrombosis occurs in the artery and venous area. Moreover, in patients with a very high platelet count, above 1,000,000/μl, bleeding may occur as a result of secondary von Willebrand syndrome [1, 2].
The treatment of ET is primarily aimed to prevent thrombotic complications.
In low-risk patients, only acetylsalicylic acid is used. In cases of high-risk patients, hydroxycarbamide is the first-line drug for most patients. Anagrelide and interferon are commonly used as second-line drugs.
Due to the possible effects of hydroxycarbamide of cytogenetic changes in the bone marrow cells after long-lasting usage, some experts recommend the use of interferon in younger patients in the first line. Interferon is also used as the drug of choice in patients planning a pregnancy [25].
The efficacy of pegylated interferon alpha-2a was assessed on the basis of the group of 39 patients with essential thrombocythemia and 40 patients with polycythemia vera.
Of the overall group, 81% of patients were previously treated prior to the study entry. The patients received pegylated interferon alpha-2a in a dose of 90 μg once a week. The dose of 450 μg was associated with a high percentage of intolerance.
In patients with essential thrombocythemia, the complete remission was achieved in 76%, while the overall hematological response rate brought 81%. Moreover, the molecular remission was achieved in 38%, in 14% of cases, JAK2 transcript became not detectable.
Patients diagnosed with polycythemia vera achieved 70% complete hematological remission and 80% general hematological response to treatment. JAK2 transcript was undetectable in 6% of patients. Molecular remission was achieved in 54% of cases.
Pegylated interferon alpha-2a at the dose of 90 μg per week was very well tolerated. In total, 20% of patients experienced a grade of 3 or 4 of adverse reaction, which was neutropenia. In addition, an increase in liver function tests was observed. Grade 4 of AE was not observed among patients who started the treatment with 90 μg/week while grade 3 neutropenia was an adverse event in only 7% of cases [26].
The effect of interferon alpha-2b treatment in patients with ET and PV was investigated. The study was prospective. Some of the results concerning the group of patients with polycythemia vera are presented in the subsection on polycythemia vera. In total, 123 patients with diagnosed essential thrombocythemia participated in the study. All of them received interferon alpha-2b. The patients were divided into two groups depending on the presence of the JAK2 V617F mutation. The enrolled patients were between 18 and 65 years of age. The treatment they received was, sequentially, interferon alpha-2b in the dose of 3 million units three times a week for the first 2 years, after which time the dose was changed into a maintenance dose, which amounted to 5 million units two times a week.
The analysis showed that the patients with the JAK2 V617F mutation present in a higher percentage achieved an overall hematological response as well as a complete hematological response. The overall hematological response was achieved in 83% of patients with JAK2 mutation, and the complete hematological remission was achieved in 23 cases. In the group of ET patients without the JAK2 V617F mutation, overall hematological response was achieved in 61.4%, while the complete hematological remission was achieved in 12 patients. The 5-year progression-free survival was obtained in 75.9% in the JAKV617F group and only in 47.6% without the mutation.
A significant proportion of patients experienced mild side effects. Grade 3 and 4 of adverse events were severe, most of them being a fever. The isolated cases of elevated liver tests and nausea have also been reported [19].
Pegylated interferon alpha-2b in patients with essential thrombocythemia who were previously treated with hydroxycarbamide, anagrelide, and other forms of interferon alpha, however, due to the lack of efficacy or toxicity, the patients required a change of treatment, was assessed. Pegylated interferon alpha-2b turned out to be effective in these cases. It led to the complete hematological remission in 91% of patients after 2 months of therapy, and in 100% of patients after 4 months. However, merely 11 patients participated in the study. Also only two patients required treatment discontinuation due to the side effects such as depression and general fatigue grade 3 [27].
In case of pregnant patients, interferon is currently considered the only safe cytoreductive drug. Over the years, several analyses of the results of interferon treatment during pregnancy have been carried out.
The assessment of 34 pregnancies in 23 women diagnosed with ET was performed retrospectively. All the pregnancies included in the analysis were of high risk. This high risk was associated with a high platelet count above 1,500,000/μl, a history of thrombotic episode, severe microcirculation disorders, or a history of major hemorrhage.
It turned out that the use of interferon allowed the birth of an alive child in 73.5% of cases. There was no difference in efficacy between the basic and pegylated forms of interferon alpha. In pregnancies without interferon treatment, the percentage of live births was only 60%. Moreover, it was not found if the presence of the JAK2 V617F mutation had any influence on the course of pregnancy [28].
An analysis of the course of pregnancy in patients with ET was assessed in Italy. Data from 17 centers were taken into account. Data from 122 pregnancies were collected from 92 women. In patients diagnosed with essential thrombocythemia, the risk of the spontaneous loss of pregnancy is about 2.5 times higher than among the general population. In the contrary to the study quoted above, it was found that the presence of the JAK2 mutation increases the risk of pregnancy loss. The proportion of live births in patients exposed to interferon during pregnancy was 95%, compared with 71.6% in the group of patients not treated with interferon.
The multivariate analysis also showed that the use of acetylsalicylic acid during pregnancy had no effect on the live birth rate of patients with ET [29].
Whatever its form, interferon is the drug of first choice in pregnancy. Hydroxycarbamide and anagrelide should be withdrawn for about 6 months, and at least for 3 months, before the planned conception. Experts recommend the use of interferon in high-risk pregnancies [30]. A Japanese analysis of 10 consecutive pregnancies in ET patients showed 100% live births in patients who received interferon [31].
In myelofibrosis (MF), monoclonal megakaryocytes produce cytokines that stimulate the proliferation of normal, non-neoplastic fibroblasts and stimulate angiogenesis. The consequence of this is the gradual fibrosis of the bone marrow, impaired hematopoiesis in the bone marrow, and the formation of extramedullary location mainly in the sites of fetal hematopoiesis, i.e., in the spleen and the liver.
The production of various cytokines by neoplastic megakaryocytes leads to the proliferation of normal, noncancerous fibroblasts as well as to increased angiogenesis.
Progressive bone marrow fibrosis leads to worsening anemia and thrombocytopenia. On the other hand, the production of proinflammatory cytokines by megakaryoblasts leads to the general symptoms such as weight loss, fever, joint pain, night sweats, and consequently, progressive worsening of general condition.
The prognosis for myelofibrosis is poor. In about 20% of patients, myelofibrosis evolves into acute myeloid leukemia with poor prognosis.
Currently, the only effective method of treatment that gives a chance to prolong the life is allogeneic bone marrow transplantation. However, this method is only available to younger patients.
The goal of treatment of patients who have not been qualified for allotranspalntation is to reduce the symptoms and to improve the patient’s quality of life. In case of leukocytosis cytoreducing drugs, such as hydroxycarbamide, melphalan, or cladribine can be used. They cause a reduction in the number of leukocytes and may, to some extent, inhibit splenomegaly. Interferon alpha has been used successfully for the treatment of myelofibrosis for many years. The results of its effectiveness will be presented below [2].
Currently, the JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis with enlarged spleen in intermediate and high-risk patients. Ruxolitinib reduces the size of the spleen, reduces general symptoms, and improves the quality of life; however, it does not prolong the overall survival of patients [32].
In 2015, the results of a retrospective study were published to compare the histological parameters of the bone marrow before and after interferon treatment. Twelve patients diagnosed with primary myelofibrosis as well as post-PV MF and post-ET MF were enrolled in the study. Patients were treated with pegylated recombinant interferon alpha-2a or recombinant interferon alpha-2b in standard doses. The time of treatment was from 1 to 10 years. Some patients had previously been treated with hydroxycarbamide or anagrelide. In all cases, karyotype was normal. The prognostic factor of Dynamic International Prognostic Scoring System (DIPSS) was assessed at the beginning as well as during the treatment.
Bone marrow cellularity decreased in cases with increased bone marrow cellularity before the treatment. After the interferon treatment, a reduction in the degree of bone marrow fibrosis was found. The parameters, such as the density of naked nuclei and the density of megakaryocytes in the bone marrow, also improved.
It proves that if the JAK2 V617F mutation had been present, DIPSS was decreased after interferon treatment. This relationship was not observed in patients without the JAK2 V617F mutation. The improvement in peripheral blood morphological parameters and the overall clinical improvement correlated with the improvement in the assessed histological parameters of the bone marrow.
Before the initiation of interferon, seven patients had splenomegaly. During the treatment with interferon, the complete resolution of splenomegaly was achieved in 17% of patients (two cases), and its size decreased in 25% (three cases). A good clinical response was achieved in 83% during interferon therapy. There was no significant difference in response between the two types of interferon used [33].
A prospective study was also conducted in patients with low and intermediate-1 risk group myelofibrosis. Seventeen patients were enrolled. Patients received interferon alpha-2b (0.5–3 milion units/three times a week) or pegylated interferon alpha-2a (45–90 μg/week). The duration of therapy was on average 3.3 years.
Most of the patients responded to the treatment. Partial remission was found in seven patients and complete remission in two patients. Moreover, in four cases, the disease was stabilized and in one case the clinical improvement was achieved. Three patients did not respond to treatment at all and progressed to myelofibrosis. Additionally, the assessment in reducing spleen size was performed. At baseline, 15 patients have splenomegaly, nine of them achieved the compete regression of spleen size [34].
However, the efficacy of interferon in the treatment of myelofibrosis appears to be limited only to a less advanced form, when the bone marrow still has an adequate percentage of normal hemopoiesis and the marrow stroma is not significantly fibrotic. In more advanced stages, interferon was not shown to have any significant effect on the regression of the fibrosis process [35].
In 2020, the results of the COMBI study were published. That was a two-phase, multicenter, single-arm study that investigated the efficacy and safety of the combination of ruxolitinib and pegylated interferon alpha. Thirty-two patients with PV and 18 patients with primary and secondary myelofibrosis participated in the study. The patients were at age 18 and older. Remission was achieved in 44% of myelofibrosis cases, including 28% (5 patients) of complete remission. In patients with PV, the results were slightly worse: 31% of remissions, including 9% of complete remissions. Patients received pegylated interferon alpha-2a (45 μg/week) or pegylated interferon alpha-2b (35 μg/week) in low doses and ruxolitinib in doses of 5–20 mg twice a day.
For the entire group of patients (with PV and MF), the initial JAK2 allele burden was 47% at baseline, and after 2 years of treatment with interferon and ruxolitinib, it decreased to 12%.
The treatment toxicity was low. The highest incidence of side effects occurred at initiation of therapy. It was mostly anemia and thrombocytopenia.
The observations from the COMBI study show that, for the combination of interferon in lower doses with ruxolitinib, it may be effective and well tolerated even in the group of patients who had intolerance to interferon used as the only drug in higher doses. The combined treatment improved the bone marrow in terms of fibrosis and its cellularity. It also allowed to improve the value of peripheral blood counts [36].
It is currently known that some of the additional mutations are associated with a worse prognosis in patients with myelorpoliferation, including patients with myelofibrosis. Some of these mutations have been identified as high-risk molecular mutations. These are ASXL1, EZH2, IDH1/2, or SRSF2. Earlier studies have shown their association with a more aggressive course of the disease, worse prognosis, and shorter survival of patients, as well as a poorer response to treatment. Due to their importance, they have been included in the diagnostic criteria of myelofibrosis [37].
It is also known that the presence of driver mutations, i.e., JAK2, CALR, and MPL or triple negativity, may affect the course of myeloproliferation, including the incidence of thromboembolic complications.
The assessment of the influence of driver mutations and a panel of selected additional mutations on the effectiveness of interferon treatment in patients with myelofibrosis was performed on a group of 30 patients. Only the patients with low- and intermediate-1-risk were enrolled in the study. The treatment with pegylated interferon alpha-2a or interferon alpha-2b resulted in a complete remission in two patients and partial remission in nine patients. The disease progressed in three cases. One patient relapsed and four died. The remaining patients achieved a clinical improvement or disease stabilization. In the studied group, it was not found if the effectiveness of interferon treatment was influenced by the lack of driver mutations. Among the group of four patients with additional mutations, two died and one had disease progression. It was a mutation of ASXL1 and SRSF2. The treatment with interferon in patients without additional molecular mutations in the early stages of the disease may prevent further progression of the disease [38].
The side effects of interferon in the group of patients with myelofibrosis are similar to those occurring after the treatment of other chronic myeloproliferative diseases. The most frequently described are hematological toxicity- anemia and thrombocytopenia, less often is the appearance of leukopenia. Hematological toxicity usually resolves with dose reduction or extension of the dose interval. The most frequently nonhematological toxicity was fatigue, muscle pain, weakness, and depression symptoms. All symptoms are usually mild and do not exceed grade 2 [38].
However, the use of interferon in the treatment of myelofibrosis has not been recommended as a standard therapy. Interferon is still being evaluated in clinical trials, or it is used in selected patients as a nonstandard therapy in this diagnosis.
Mastocytosis is characterized by an excessive proliferation of abnormal mast cells and their accumulation in various organs.
The basis for the development of mastocytosis is ligand-independent activation of the KIT receptor, resulting from mutations in the KIT proto-oncogene. The KIT receptor is a trans membrane receptor with tyrosine kinase’s activity. Its activation stimulates the proliferation of mast cells. That excessive numbers of mast cells infiltrate tissues and organs and release mediators such as histamine, interleukine-6, tryptase, heparin, and others, which are responsible for the appearance of symptoms typical of mastocytosis. In addition, the infiltration of tissues for mast cells itself causes damage to the affected organs.
The prognosis of mastocytosis depends on the type of the disease. In the case of cutaneous mastocytosis (CM), in the majority of cases prognosis is good and the disease does not shorten the patient’s life, but in aggressive systemic mastocytosis (ASM), the average follow-up is about 40 months. Mast cell leukemia has a poor prognosis with a median follow-up of approximately 1 year.
Systemic mastocytosis usually requires the implementation of cytoreductive therapy. The first line of therapy is interferon alone or its combination with corticosteroids. In aggressive systemic mastocytosis, the first line in addition to interferon 2-CdA can be used. An effective drug turned out to be midostaurin in the case of the present KIT mutation. In patients without the KIT D816V mutation, treatment with imatinib may be effective. In the case of mast cell leukemia, multidrug chemotherapy is most often required, as in acute leukemias, followed by bone marrow transplantation [39].
Systemic mastocytosis requiring treatment is a rare disease, this is why the studies available in the literature evaluating various therapies concern mostly small groups of patients.
In 2002, the French authors presented their experiences on the use of interferon in patients with systemic mastocytosis. They included 20 patients. The patients received interferon alpha-2b in gradually increased doses.
The patients were assessed after 6 months. In cases in which bone marrow was infiltrated for mast cells at baseline, it still remained infiltrated after 6 months of treatment.
However, the responses were obtained in terms of symptoms related to mast cell degranulation. Partial remission was achieved in 35% of patients and minor remission in 30%. It concerns mainly skin lesions and vascular congestion. Moreover, the assessment of the histamine level in the plasma revealed a decrease of it in patients who previously presented symptoms related to the degranulation of mast cells, such as gastrointestinal disorders and flushing.
A high percentage of side effects were found during treatment. They concerned 35% of patients. Depression and cytopenia were most frequent ones [40].
Another analysis was a report of five patients with systemic mastocytosis treated with interferon and prednisolone. All patients received interferon alpha-2b in a dose of 3 million units three times a week and four patients additionally received prednisolone. Four patients responded to interferon treatment at varying degrees. One patient, who at baseline had bone marrow involvement by mast cells in above 10%, progressed to mast cell leukemia. In two patients, the symptoms C resolved completely and in one of them they partially disappeared. In one case, stabilizing disease was achieved [41].
In 2009, a retrospective analysis of patients treated with cytoreductive therapy due to mastocytosis was published. The authors collected data from 108 patients treated at the Mayo Clinic. This analysis allowed for the comparison of the efficacy of four drugs used in systemic mastocytosis. There were interferon alpha alone or in the combination with prednisone—among 40 patients, hydroxycarbamide—among 26 ones, imatinib—among 22 persons, and 2-chlorodeoxyadenosine (2-CdA)—among 22 patients.
After dividing the patients into three additional groups on the basis of the type of mastocytosis—indolent systemic mastocytosis, aggressive systemic mastocytosis, and systemic mastocytosis associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD)—the effectiveness of each of type of therapy was assessed.
The highest response rates in indolent and aggressive mastocytosis were achieved with interferon treatment. They were 60% of the responses in both groups, and in the SM-AHNMD group of patients, the percentage was also one of the highest and amounted to 45%. The second most effective drug was 2-CdA. The response rates were 56% for indolent MS, 50% for aggressive MS, and 55% for SM-AHNMD. The patients treated with imatinib achieved response in 14, 50, and 9% by following groups, respectively. In contrast, patients with indolent and aggressive systemic mastocytosis did not respond to hydroxycarbamide treatment at all. The response rate in both groups was 0%. However, patients with MS associated with another clonal hematological nonmast cell lineage disease achieved 21% response to hydroxycarbamide. Additionally, it was found that only interferon relieved symptoms caused by the release of inflammatory mediators by mast cells.
The additional analysis showed no influence of the TET 2 mutation on the response to treatment [42].
In the literature, there are also single cases of mastocytosis presenting trials of nonstandard treatment. That is description of a patient with systemic mastocytosis with mast cell bone marrow involvement. Mutation of c-kit Asp816Val was present. Patient progressed despite treatment with dasatinib and 2-chlorodeoxyadenosine. The patient developed symptoms related to the degranulation of mast cells and increased ascites.
The patient was treated with pranlukast, which is an anti-leukotriene receptor antagonist due to an asthma episode. The rate of ascites growth decreased significantly after one administration. The patient required paracentesis every 10 days and not every 3 days, as before starting to take the drug. After 15 days of treatment with pranlukast, the patient received interferon alpha, which resulted in complete regression of ascites, resolution of pancytopenia, and complete disappearance of the c-kit mutation clone. The infiltration of mast cells in the bone marrow significantly decreased [43].
Interferon alpha was also effective in a patient with systemic mastocytosis associated with myelodysplastic syndrome with the c-kit D816V mutation, which was refractory to imatinib treatment [44].
Interferon alpha also proved to be effective in the treatment of osteoporotic lesions appearing in the course of mastocytosis.
The series of 10 cases with resolved mastocytosis and osteoporosis-related fractures was presented in 2011. The patients received interferon alpha in a dose of 1.5 million units three times a week as well as pamindronic acid. The patients were treated for an average of 60 months. For the first 2 years, pamindronate was given at a dose of 1 mg/kg every month, and then every 3 months.
During the course of the study, no patient had a new-bone fracture. The level of alkaline phosphatase decreased by 25% in relation to the value before treatment and tryptase by 34%. Bone density increased during treated with interferon and pamindronate. The increase was on average 12% in the spine bones and 1.9% in the hip bones. At the same time, there was no increase in the density of the hip bone and a minimal increase in the density of the spine in patients treated with pamindronate alone.
The results of this observation suggest that it is beneficial to add low doses of interferon alpha to pamindronate treatment in terms of bone density increase [45].
That experiences show that interferon used in systemic mastocytosis significantly improves the quality of life of patients by inhibiting the symptoms caused by degranulation of mast cells. They prevent bone fractures and, in some patients, they cause remission of bone marrow infiltration by mast cells.
Chronic neutrophilic leukemia (CNL) is a very rare disease. It is characterized by the clonal proliferation of mature neutrophils.
The diagnostic criteria proposed by the World Health Organization (WHO) comprise leukocyte counts above 25,000/μl (including more than 80% of rod and segmented
Physical examination often shows enlargement of the liver and spleen, moreover, patients complain on weight loss and weakness [1].
The prognosis varies. The average survival time for patients with CNL is less than 2 years.
Only few descriptions of chronic neutrophilic leukemia are available in the literature, and these are mostly single case reports.
Because it is an extremely rare disease, there are no established and generally accepted treatment standards. In most cases, patients are given hydroxycarbamide or interferon. Patients who are eligible for a bone marrow transplant may benefit from this treatment. Bone marrow allotransplantation remains the only method that gives a chance for a significant extension of life.
The German authors presented a series of 14 cases of chronic neutrophilic leukemia. The group of patients consisted of eight women and six men. The average age was 64.7 years. From the entire group of patients, longer survival was achieved only in three cases. One of these patients was treated with interferon alpha and achieved hematological remission, the other underwent bone marrow allotransplantation from a family donor, and the third one was treated with hydroxycarbamide and transfusions as needed. The follow-up period of the patient after allogeneic matched related donor transplantation (allo-MRD) was 73 months, and for the patient after interferon treatment it was 41 months.
The remaining patients died within 2 years of diagnosis. Six patients, the largest group, died due to intracranial bleeding, three patients died because of leukemia cell tissue infiltration, one patient because of the disease transformation into leukemia, and one patient because of pneumonia [46].
It can be seen from these experiences that treatment with interferon alpha can significantly extend the survival time of patients.
The case of a 40-year-old woman diagnosed with chronic neutrophilic leukemia is presented by Yassin and coauthors. Initially, the patient had almost 41,000 leukocytes in the peripheral blood. In a physical examination, splenomegaly and hepatomegaly were not present. Patient received pegylated interferon alpha-2a. The initially dose was 50 μg once a week for the first 2 weeks, then the dose was increased to 135 μg weekly for 6 weeks, and then the dose interval was extended to another 2 weeks. As a result of the treatment, the general condition of the patient improved and the parameters of peripheral blood counts were normalized [47].
Another case report presented in the literature describes a 41-year-old woman diagnosed with CNL accompanied by focal segmental glomerulosclerosis (FSGS). The patient had increasing leukocytosis for several months. On the admission to the hospital, leukocytosis was 94,000/μl. Moreover, the number of platelets in the morphology exceeded 1,000,000/μl. More than a year earlier, the patient had splenectomy due to splenomegaly and spleen infraction.
Additionally, JAK2 V617F mutation was found. Some authors suggest that the presence of JAK2 mutation may be associated with longer survival in CNL.
The patient received hydroxycarbamide for 3 months and reduction in the number of leukocytes was achieved. After this time, interferon alpha-2b was added to hydroxycarbamide. As a result, focal segmental glomerulosclerosis disappeared and the renal tests improved [48].
Another case of chronic neutrophilic leukemia with a JAK2 gene mutation concerns a 53-year-old man. The patient’s baseline leukocytosis was 33,500/μl, including the neutrophil count of 29,700/μl. The patient also had splenomegaly.
The treatment with interferon alpha-2b at a dose of 3 million units every other day was started. After a month of treatment, the number of leukocytes was reduced to less than 10,000/μl. Then the patient was treated chronically with interferon alpha-2b in doses of 3 million units every 2 weeks. As a result of the therapy, the number of leukocytes remains between 8 and 10,000/μl. The patient remains in general good condition [49].
A series of two CNL cases are also shown. The first patient was a 70-year-old woman with stable leukocytosis of about 35,000/μl and the remaining morphology parameters in normal range. The patient was only observed for 5 years until hepasplenomegaly progressed rapidly. Then, interferon alpha-2b was included. Due to the treatment, the rapid regression of hepatosplenomegaly was achieved.
The second case is a 68-year-old woman with baseline leukocytosis of almost 14,000/μl. In this case, the treatment with hydroxycarbamide was started immediately. However, no improvement was achieved. After 6 weeks of HU treatment, interferon alpha-2b 3 million units 3 times a week was implemented and leukocytosis decreased. Due to the interferon treatment, the disease stabilized for a long time. Because the patient experienced an adverse reaction, a severe flu-like syndrome, interferon was discontinued. After interferon withdrawal, the disease progressed gradually and the treatment attempts by busulfan and 6-mercaptopurine were unsuccessful. Therefore, interferon was readministered and the disease went into remission. Interferon treatment was continued at a reduced dose. The disease regression was achieved again.
Additionally, the patient showed an improvement in the function of granulocytes in terms of phagocytosis and an improvement in neutral killer (NK) cell function after treatment with interferon [50].
The above examples show that interferon alpha is effective in the treatment of chronic neutrophilic leukemia. The side effects are rare and can be managed with dose reductions. Moreover, in these cases, interferon is also effective in a reduced dose. Disease remission or regression can be achieved without typical of CNL complications, such as intracranial bleeding.
Interferon has been used in the past to treat chronic myeloid leukemia. The treatment with tyrosine kinase inhibitors is now a standard practice. However, in a small number of patients, they are ineffective or exhibit unmanageable toxicity. Therefore, the attempts are underway to use interferon in combination with TKI in lower doses, which is to ensure the enhancement of the antiproliferative effect while reducing the toxicity.
There are ongoing attempts to use ropeginterferon in patients diagnosed with chronic myeloid leukemia, in whom treatment with imatinib alone has not led to deep molecular response (DMR). The first phase study was conducted in a small group of patients with chronic myeloid leukemia. The patients in first chronic phase treated with imatinib who did not achieve DMR, but in complete hematologic remission and complete cytogenetic remission, were included in the study. Patients have been treated with imatinib for at least 18 months. Twelve patients were enrolled in the study, and they completed the study according to the protocol. These patients received additional ropeginterferon to imatinib and four achieved DMR. Low toxicity was observed during the treatment. Among the hematological toxicities, neutropenia was the most common. There was no nonhematological toxicity with a degree higher than 1/2 during the treatment. Moreover, it has been found that better effects and fewer side effects are obtained when ropeginterferon is administered for a longer time, but in lower doses. The comparison of the effectiveness of interferon in chronic myeloproliferative disorders based on selected articles is presented in Table 1 [51].
Source | Type of trial | Interferon | Diagnosis | No. | Prior treatment status | Response rate |
---|---|---|---|---|---|---|
Yacoubet al. [15] | Phase II, multicenter | Pegylated IFN alfa-2a | PV | 50 | Resistance to HU or HU intolerance | CR:22% PR:38% |
ET | 65 | CR:43% PR:26% | ||||
Masarova et al. [16] | Phase II, single-center | Pegylated IFN alfa-2a | PV | 43 | Untreated or previously treated with cytoreductive therapy | CR:77% PR:7% |
ET | 40 | CR:73% PR:3% | ||||
Samuelsson et al. [18] | Phase II | Pegylated IFN alfa-2b | PV | 21 | Untreated or previously treated with cytoreductive therapy | CR: 69% for the entire group |
ET | 21 | |||||
Huang BT et al. [19] | Open label, multicenter | IFN alfa-2b | PV | 136 | Untreated or previously treated with cytoreductive therapy | OHR:70% Molecular response:54.7% |
ET | 123 | OHR (JAK2+ patients):83% CHR:23 cases OHR (JAK2-patients): 61.4% CHR:12 cases | ||||
Gisslinger et al. [23] | phase III, multicenter | Ropeginterferon | PV | 257 | Previously treated | OHR:53% |
Quintás-Cardama et al. [26] | phase II | Pegylated IFN alfa-2a | PV | 40 | Untreated or previously treated with cytoreductive therapy | OHR:80% CR:70% Molecular remission:54% |
ET | 39 | OHR:81% CR:76% Molecular remission:38% | ||||
Sørensen et al. [36] | Phase III, multicenter, COMBI | Pegylated IFN alfa-2a with ruxolitinib or Pegylated IFN alfa-2b with ruxolitinib | PV | 32 | Untreated or previously treated with cytoreductive therapy | OHR:44% CR:28% |
MF | 18 | OHR:31% CR:9% | ||||
Casassus et al. [40] | Open label, multicenter | IFN alpha-2b | Mastocytosis | 20 | Untreated and previously treated | PR:35% Minor remission: 30% |
Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
PV: polycythemia vera; ET: essential thrombocythemia; MF: myelofibrosis; HU: hydroxycarbamide/hydroxyurea; CR: complete remission; PR: partial remission; and OHR: overall hematological response.
Interferon alpha appears to be an effective and safe drug in the most type of chronic myeloproliferative disorders. Nowadays, all forms of its using have similar effectiveness. Interferon alpha can be effective even in cases of resistance for first-line treatment. Trial research is currently underway to combine it with some new drugs, such as ruxolitinib, and to add it to the already well-established therapy, it is a promising option for patients with refractory disease.
From time to time, new forms of interferon, such as ropeginterferon, are introduced, which gives hope for better effectiveness, better safety profile, and greater comfort in its use for patients who have to be treated for many years. In the case of the use of interferons alpha in the treatment of chronic myeloproliferative diseases, there are still opportunities to extend its use and to study its combination with newly introduced drugs.
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Cows",slug:"inflammatory-response-and-acute-phase-proteins-in-the-transition-period-of-high-yielding-dairy-cows",totalDownloads:3188,totalCrossrefCites:11,totalDimensionsCites:39,abstract:null,book:{id:"534",slug:"acute-phase-proteins-as-early-non-specific-biomarkers-of-human-and-veterinary-diseases",title:"Acute Phase Proteins as Early Non-Specific Biomarkers of Human and Veterinary Diseases",fullTitle:"Acute Phase Proteins as Early Non-Specific Biomarkers of Human and Veterinary Diseases"},signatures:"Erminio Trevisi, Massimo Amadori, Ivonne Archetti, Nicola Lacetera and Giuseppe Bertoni",authors:[{id:"40371",title:"Dr.",name:"Massimo",middleName:null,surname:"Amadori",slug:"massimo-amadori",fullName:"Massimo Amadori"},{id:"47776",title:"Prof.",name:"Erminio",middleName:null,surname:"Trevisi",slug:"erminio-trevisi",fullName:"Erminio Trevisi"},{id:"47777",title:"Dr.",name:"Ivonne",middleName:null,surname:"Archetti",slug:"ivonne-archetti",fullName:"Ivonne Archetti"},{id:"47778",title:"Prof.",name:"Nicola",middleName:null,surname:"Lacetera",slug:"nicola-lacetera",fullName:"Nicola Lacetera"},{id:"47779",title:"Prof.",name:"Giuseppe",middleName:null,surname:"Bertoni",slug:"giuseppe-bertoni",fullName:"Giuseppe Bertoni"}]},{id:"21680",doi:"10.5772/19492",title:"Application of Acute Phase Proteins for Monitoring Inflammatory States in Cattle",slug:"application-of-acute-phase-proteins-for-monitoring-inflammatory-states-in-cattle",totalDownloads:3311,totalCrossrefCites:2,totalDimensionsCites:21,abstract:null,book:{id:"534",slug:"acute-phase-proteins-as-early-non-specific-biomarkers-of-human-and-veterinary-diseases",title:"Acute Phase Proteins as Early Non-Specific Biomarkers of Human and Veterinary Diseases",fullTitle:"Acute Phase Proteins as Early Non-Specific Biomarkers of Human and Veterinary Diseases"},signatures:"Burim N. Ametaj, Afshin Hosseini, John F. Odhiambo, Summera Iqbal, Sumeet Sharma, Qilan Deng, Tran H. Lam, Umar Farooq, Qendrim Zebeli and Suzanna M. Dunn",authors:[{id:"35129",title:"Prof.",name:"Burim",middleName:null,surname:"Ametaj",slug:"burim-ametaj",fullName:"Burim Ametaj"},{id:"49239",title:"Prof.",name:"Qendrim",middleName:null,surname:"Zebeli",slug:"qendrim-zebeli",fullName:"Qendrim Zebeli"},{id:"49242",title:"MSc",name:"Sarah",middleName:null,surname:"Terrill",slug:"sarah-terrill",fullName:"Sarah Terrill"}]},{id:"21456",doi:"10.5772/18241",title:"Haptoglobin and Hemopexin in Heme Detoxification and Iron Recycling",slug:"haptoglobin-and-hemopexin-in-heme-detoxification-and-iron-recycling",totalDownloads:4138,totalCrossrefCites:5,totalDimensionsCites:20,abstract:null,book:{id:"234",slug:"acute-phase-proteins-regulation-and-functions-of-acute-phase-proteins",title:"Acute Phase Proteins",fullTitle:"Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins"},signatures:"Deborah Chiabrando, Francesca Vinchi, Veronica Fiorito and Emanuela Tolosano",authors:[{id:"30837",title:"Prof.",name:"Emanuela",middleName:null,surname:"Tolosano",slug:"emanuela-tolosano",fullName:"Emanuela Tolosano"},{id:"48270",title:"Dr.",name:"Deborah",middleName:null,surname:"Chiabrando",slug:"deborah-chiabrando",fullName:"Deborah Chiabrando"},{id:"48271",title:"Dr.",name:"Francesca",middleName:null,surname:"Vinchi",slug:"francesca-vinchi",fullName:"Francesca Vinchi"},{id:"48272",title:"Dr.",name:"Veronica",middleName:null,surname:"Fiorito",slug:"veronica-fiorito",fullName:"Veronica Fiorito"}]},{id:"45299",doi:"10.5772/56101",title:"Molecular Aspects of Human Alpha-1 Acid Glycoprotein — Structure and Function",slug:"molecular-aspects-of-human-alpha-1-acid-glycoprotein-structure-and-function",totalDownloads:3383,totalCrossrefCites:6,totalDimensionsCites:20,abstract:null,book:{id:"3318",slug:"acute-phase-proteins",title:"Acute Phase Proteins",fullTitle:"Acute Phase Proteins"},signatures:"Kazuaki Taguchi, Koji Nishi, Victor Tuan Giam Chuang, Toru\nMaruyama and Masaki Otagiri",authors:[{id:"158116",title:"Prof.",name:"Masaki",middleName:null,surname:"Otagiri",slug:"masaki-otagiri",fullName:"Masaki Otagiri"},{id:"158238",title:"Dr.",name:"Kazuaki",middleName:null,surname:"Taguchi",slug:"kazuaki-taguchi",fullName:"Kazuaki Taguchi"},{id:"165882",title:"Dr.",name:"Koji",middleName:null,surname:"Nishi",slug:"koji-nishi",fullName:"Koji Nishi"},{id:"165883",title:"Dr.",name:"Victor Tuan Giam",middleName:null,surname:"Chuang",slug:"victor-tuan-giam-chuang",fullName:"Victor Tuan Giam Chuang"},{id:"165884",title:"Prof.",name:"Toru",middleName:null,surname:"Maruyama",slug:"toru-maruyama",fullName:"Toru Maruyama"}]},{id:"46263",doi:"10.5772/57507",title:"HLA-E, HLA-F and HLA-G — The Non-Classical Side of the MHC Cluster",slug:"hla-e-hla-f-and-hla-g-the-non-classical-side-of-the-mhc-cluster",totalDownloads:2508,totalCrossrefCites:10,totalDimensionsCites:16,abstract:null,book:{id:"3824",slug:"hla-and-associated-important-diseases",title:"HLA and Associated Important Diseases",fullTitle:"HLA and Associated Important Diseases"},signatures:"Iris Foroni, Ana Rita Couto, Bruno Filipe Bettencourt, Margarida\nSantos, Manuela Lima and Jácome Bruges-Armas",authors:[{id:"70522",title:"Dr.",name:"Jacome",middleName:null,surname:"Bruges Armas",slug:"jacome-bruges-armas",fullName:"Jacome Bruges Armas"},{id:"81144",title:"Dr.",name:"Ana Rita",middleName:null,surname:"Couto Rendeiro",slug:"ana-rita-couto-rendeiro",fullName:"Ana Rita Couto Rendeiro"},{id:"81147",title:"Prof.",name:"Manuela",middleName:null,surname:"Lima",slug:"manuela-lima",fullName:"Manuela Lima"},{id:"82501",title:"Ph.D.",name:"Bruno Filipe",middleName:null,surname:"Bettencourt",slug:"bruno-filipe-bettencourt",fullName:"Bruno Filipe Bettencourt"},{id:"170238",title:"Dr.",name:"Iris",middleName:null,surname:"Foroni",slug:"iris-foroni",fullName:"Iris Foroni"},{id:"170824",title:"Dr.",name:"Margarida",middleName:null,surname:"Santos",slug:"margarida-santos",fullName:"Margarida Santos"}]}],mostDownloadedChaptersLast30Days:[{id:"65210",title:"Introductory Chapter: Concept of Human Leukocyte Antigen (HLA)",slug:"introductory-chapter-concept-of-human-leukocyte-antigen-hla-",totalDownloads:2788,totalCrossrefCites:2,totalDimensionsCites:5,abstract:null,book:{id:"7140",slug:"human-leukocyte-antigen-hla-",title:"Human Leukocyte Antigen (HLA)",fullTitle:"Human Leukocyte Antigen (HLA)"},signatures:"Batool Mutar Mahdi",authors:[{id:"77656",title:"Dr.",name:"Batool Mutar",middleName:null,surname:"Mahdi",slug:"batool-mutar-mahdi",fullName:"Batool Mutar Mahdi"}]},{id:"21456",title:"Haptoglobin and Hemopexin in Heme Detoxification and Iron Recycling",slug:"haptoglobin-and-hemopexin-in-heme-detoxification-and-iron-recycling",totalDownloads:4138,totalCrossrefCites:5,totalDimensionsCites:20,abstract:null,book:{id:"234",slug:"acute-phase-proteins-regulation-and-functions-of-acute-phase-proteins",title:"Acute Phase Proteins",fullTitle:"Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins"},signatures:"Deborah Chiabrando, Francesca Vinchi, Veronica Fiorito and Emanuela Tolosano",authors:[{id:"30837",title:"Prof.",name:"Emanuela",middleName:null,surname:"Tolosano",slug:"emanuela-tolosano",fullName:"Emanuela Tolosano"},{id:"48270",title:"Dr.",name:"Deborah",middleName:null,surname:"Chiabrando",slug:"deborah-chiabrando",fullName:"Deborah Chiabrando"},{id:"48271",title:"Dr.",name:"Francesca",middleName:null,surname:"Vinchi",slug:"francesca-vinchi",fullName:"Francesca Vinchi"},{id:"48272",title:"Dr.",name:"Veronica",middleName:null,surname:"Fiorito",slug:"veronica-fiorito",fullName:"Veronica Fiorito"}]},{id:"46315",title:"In Phase HLA Genotyping by Next Generation Sequencing — A Comparison Between Two Massively Parallel Sequencing Bench-Top Systems, the Roche GS Junior and Ion Torrent PGM",slug:"in-phase-hla-genotyping-by-next-generation-sequencing-a-comparison-between-two-massively-parallel-se",totalDownloads:4541,totalCrossrefCites:1,totalDimensionsCites:7,abstract:null,book:{id:"3824",slug:"hla-and-associated-important-diseases",title:"HLA and Associated Important Diseases",fullTitle:"HLA and Associated Important Diseases"},signatures:"Jerzy K. Kulski, Shingo Suzuki, Yuki Ozaki, Shigeki Mitsunaga,\nHidetoshi Inoko and Takashi Shiina",authors:[{id:"169295",title:"Dr.",name:"Jerzy",middleName:"Kazimierz",surname:"Kulski",slug:"jerzy-kulski",fullName:"Jerzy Kulski"},{id:"170241",title:"Dr.",name:"Shingo",middleName:null,surname:"Suzuki",slug:"shingo-suzuki",fullName:"Shingo Suzuki"},{id:"170242",title:"Dr.",name:"Yuki",middleName:null,surname:"Ozaki",slug:"yuki-ozaki",fullName:"Yuki Ozaki"},{id:"170243",title:"Dr.",name:"Shigeki",middleName:null,surname:"Mitsunaga",slug:"shigeki-mitsunaga",fullName:"Shigeki Mitsunaga"},{id:"170244",title:"Prof.",name:"Hidetoshi",middleName:null,surname:"Inoko",slug:"hidetoshi-inoko",fullName:"Hidetoshi Inoko"},{id:"170245",title:"Prof.",name:"Takashi",middleName:null,surname:"Shiina",slug:"takashi-shiina",fullName:"Takashi Shiina"}]},{id:"66411",title:"TNFR2 and Regulatory T Cells: Potential Immune Checkpoint Target in Cancer Immunotherapy",slug:"tnfr2-and-regulatory-t-cells-potential-immune-checkpoint-target-in-cancer-immunotherapy",totalDownloads:1003,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"TNF has both proinflammatory and antiinflammatory effects. It binds to two structurally related but functionally distinct receptors TNFR1 and TNFR2. Unlike TNFR1 that is ubiquitously expressed, TNFR2 expression is more limited to myeloid and lymphoid cell lineages including a fraction of regulatory T cells (Treg). In general, TNFR1 is responsible for TNF-mediated cell apoptosis and death, and mostly induces proinflammatory reactions. However, TNFR2 mainly leads to functions related to cell survival and immune suppression. Treg play an indispensable role in maintaining immunological self-tolerance and restraining excessive immune reactions deleterious to the host. Impaired Treg-mediated immune regulation has been observed in various autoimmune diseases as well as in cancers. Therefore, Treg might provide an ideal therapeutic target for diseases where the immune balance is impaired and could benefit from the regulation of Treg properties. TNFR2 is highly expressed on Treg in mice and in humans, and TNFR2+ Treg reveal the most potent suppressive capacity. TNF-TNFR2 ligation benefits Treg proliferation, although the effect on Treg suppressive function remains controversial. Here, we will describe in detail the TNF-mediated regulation of Treg and the potential clinical applications in cancer immunotherapy as well as in autoimmune diseases, with the focus on human Treg subsets.",book:{id:"7853",slug:"cytokines",title:"Cytokines",fullTitle:"Cytokines"},signatures:"Xuehui He and Xinhui Wang",authors:[{id:"284559",title:"Dr.",name:"Xuehui",middleName:null,surname:"He",slug:"xuehui-he",fullName:"Xuehui He"},{id:"296531",title:"Dr.",name:"Xinhui",middleName:null,surname:"Wang",slug:"xinhui-wang",fullName:"Xinhui Wang"}]},{id:"46259",title:"HLA in Gastrointestinal Inflammatory Disorders",slug:"hla-in-gastrointestinal-inflammatory-disorders",totalDownloads:2075,totalCrossrefCites:2,totalDimensionsCites:2,abstract:null,book:{id:"3824",slug:"hla-and-associated-important-diseases",title:"HLA and Associated Important Diseases",fullTitle:"HLA and Associated Important Diseases"},signatures:"M.I. Torres, T. Palomeque and P. Lorite",authors:[{id:"34102",title:"Dr.",name:"Isabel",middleName:null,surname:"Torres",slug:"isabel-torres",fullName:"Isabel Torres"},{id:"213607",title:"Dr.",name:"Pedro",middleName:null,surname:"Lorite",slug:"pedro-lorite",fullName:"Pedro Lorite"},{id:"213610",title:"Prof.",name:"Palomeque",middleName:null,surname:"T",slug:"palomeque-t",fullName:"Palomeque T"}]}],onlineFirstChaptersFilter:{topicId:"1040",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{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"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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