Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"9239",leadTitle:null,fullTitle:"Digital Imaging",title:"Digital Imaging",subtitle:null,reviewType:"peer-reviewed",abstract:"Digital imaging is used widely in various real-life applications today. There are a number of potential digital imaging applications that include different areas such as television, photography, robotics, remote sensing, medical diagnosis, reconnaissance, architectural and engineering design, art, crime prevention, geographical information systems, communication, intellectual property, retail catalogs, nudity detection, face finding, industrial, and others. This book is specifically dedicated to digital imaging research, applications, techniques, tools, and algorithms that originate from different fields such as image processing, computer vision, pattern recognition, signal processing, artificial intelligence, intelligent systems, and soft computing. In general, this comprehensive book contains state-of-the-art chapters focusing on the latest developments using theories, methods, approaches, algorithms, analyses, display of images, visual information, and videos.",isbn:"978-1-78985-600-2",printIsbn:"978-1-78985-599-9",pdfIsbn:"978-1-83880-389-6",doi:"10.5772/intechopen.83239",price:119,priceEur:129,priceUsd:155,slug:"digital-imaging",numberOfPages:104,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"656ebe9652b39a1f5dc33d004170a1c4",bookSignature:"Muhammad Sarfraz",publishedDate:"May 13th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/9239.jpg",numberOfDownloads:4407,numberOfWosCitations:1,numberOfCrossrefCitations:3,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:6,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:10,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 6th 2019",dateEndSecondStepPublish:"April 3rd 2019",dateEndThirdStepPublish:"June 2nd 2019",dateEndFourthStepPublish:"August 21st 2019",dateEndFifthStepPublish:"October 20th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Kuwait University",institutionURL:null,country:{name:"Kuwait"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"601",title:"Digital Image Processing",slug:"numerical-analysis-and-scientific-computing-digital-image-processing"}],chapters:[{id:"71817",title:"Introductory Chapter: On Digital Image Processing",doi:"10.5772/intechopen.92060",slug:"introductory-chapter-on-digital-image-processing",totalDownloads:1110,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:null,signatures:"Muhammad Sarfraz",downloadPdfUrl:"/chapter/pdf-download/71817",previewPdfUrl:"/chapter/pdf-preview/71817",authors:[{id:"215610",title:"Prof.",name:"Muhammad",surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz"}],corrections:null},{id:"67657",title:"Fast Motion Estimation’s Configuration Using Diamond Pattern and ECU, CFM, and ESD Modes for Reducing HEVC Computational Complexity",doi:"10.5772/intechopen.86792",slug:"fast-motion-estimation-s-configuration-using-diamond-pattern-and-ecu-cfm-and-esd-modes-for-reducing-",totalDownloads:693,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The high performance of the high efficiency video coding (HEVC) video standard makes it more suitable for high-definition resolutions. Nevertheless, this encoding performance is coupled with a tremendous encoding complexity compared to the earlier H264 video codec. The HEVC complexity is mainly a return to the motion estimation (ME) module that represents the important part of encoding time which makes several researches turn around the optimization of this module. Some works are interested in hardware solutions exploiting the parallel processing of FPGA, GPU, or other multicore architectures, and other works are focused on software optimizations by inducing fast mode decision algorithms. In this context, this article proposes a fast HEVC encoder configuration to speed up the encoding process. The fast configuration uses different options such as the early skip detection (ESD), the early CU termination (ECU), and the coded block flag (CBF) fast method (CFM) modes. Regarding the algorithm of ME, the diamond search (DS) is used in the encoding process through several video resolutions. A time saving around 46.75% is obtained with an acceptable distortion in terms of video quality and bitrate compared to the reference test model HM.16.2. Our contribution is compared to other works for better evaluation.",signatures:"Randa Khemiri, Nejmeddine Bahri, Fatma Belghith, Soulef Bouaafia, Fatma Elzahra Sayadi, Mohamed Atri and Nouri Masmoudi",downloadPdfUrl:"/chapter/pdf-download/67657",previewPdfUrl:"/chapter/pdf-preview/67657",authors:[{id:"298629",title:"Dr.",name:"Randa",surname:"Khemiri",slug:"randa-khemiri",fullName:"Randa Khemiri"},{id:"304368",title:"Dr.",name:"Nejmeddine",surname:"Bahri",slug:"nejmeddine-bahri",fullName:"Nejmeddine Bahri"},{id:"304387",title:"Prof.",name:"Mohamed",surname:"Atri",slug:"mohamed-atri",fullName:"Mohamed Atri"},{id:"304388",title:"Dr.",name:"Fatma",surname:"Belghith",slug:"fatma-belghith",fullName:"Fatma Belghith"},{id:"304390",title:"Dr.",name:"Soulef",surname:"Bouaafia",slug:"soulef-bouaafia",fullName:"Soulef Bouaafia"},{id:"304391",title:"Dr.",name:"Fatma Ezahra",surname:"Sayadi",slug:"fatma-ezahra-sayadi",fullName:"Fatma Ezahra Sayadi"},{id:"304392",title:"Prof.",name:"Nouri",surname:"Masmoudi",slug:"nouri-masmoudi",fullName:"Nouri Masmoudi"}],corrections:null},{id:"68748",title:"Digital Image Processing Applied to Optical Measurements",doi:"10.5772/intechopen.88704",slug:"digital-image-processing-applied-to-optical-measurements",totalDownloads:625,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Digital image processing is a useful tool that improves pictorial information for human interpretation and is mainly used for storage, transmission, and representation of different data. In this chapter, we want to introduce an optical technique which couples physical analysis with image processing for a measurement system. Optical methods were used to obtain the stress-strain relation by different invasive and noninvasive methods. This chapter talks about a novel noninvasive methodology to measure stress-strain evolution; this technique is based upon a single laser beam reflected on the cross section of ductile materials (steel and aluminum) while they are under a compression load. The way we measure one laser beam is by using the Gaussian beam propagation equations; we propose that the reflection area of the laser is going to change as the material surface area is compressed and we analyze these differences by using digital image processing. With this technique we are able to construct a stress-strain diagram.",signatures:"Alonso Saldaña-Heredia, Pedro Antonio Márquez-Aguilar, Álvaro Zamudio Lara and Arturo Molina-Ocampo",downloadPdfUrl:"/chapter/pdf-download/68748",previewPdfUrl:"/chapter/pdf-preview/68748",authors:[{id:"51029",title:"Dr.",name:"Pedro Antonio",surname:"Marquez Aguilar",slug:"pedro-antonio-marquez-aguilar",fullName:"Pedro Antonio Marquez Aguilar"},{id:"299407",title:"Dr.",name:"Alonso",surname:"Saldaña Heredia",slug:"alonso-saldana-heredia",fullName:"Alonso Saldaña Heredia"},{id:"299409",title:"Dr.",name:"Álvaro",surname:"Zamudio Lara",slug:"alvaro-zamudio-lara",fullName:"Álvaro Zamudio Lara"},{id:"306535",title:"Dr.",name:"Arturo",surname:"Molina Ocampo",slug:"arturo-molina-ocampo",fullName:"Arturo Molina Ocampo"}],corrections:null},{id:"67608",title:"Experimental and Theoretical Investigation on the Shear Behaviour of High Strength Reinforced Concrete Beams Using Digital Image Correlation",doi:"10.5772/intechopen.86499",slug:"experimental-and-theoretical-investigation-on-the-shear-behaviour-of-high-strength-reinforced-concre",totalDownloads:644,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In this chapter an experimental investigation is carried out on high strength concrete beams without transverse reinforcement and with transverse reinforcement. The beams were tested in bending under two concentrated loads using the technique of digital image correlation. In the test setup, the shear zone which is defined by the area of beam between the support point and the loading point was studied by the camera of high resolution. The Gom-Aramis software was used to record and analyse the numerical images by determination of the deformation of concrete in the compressed zone of the beam, to calculate the opening, the spacing and the length of the diagonal cracks. The experimental shear strength of the beams was compared with the theoretical values predicted by the different design codes, such as the American ACI 318, the British Standard BS 8110, the European Eurocode 2, the New Zealand NZS 3101 and the Indian Standard IS456. The results show that all the design codes underestimate the contribution of high strength concrete to the shear resistance of reinforced concrete beams, and greatly overestimate the contribution of transverse reinforcement. The European Eurocode 2 is the only one among the four code models that gives the best prediction of the ultimate shear strength of high strength concrete.",signatures:"Touhami Tahenni and Thibaut Lecompte",downloadPdfUrl:"/chapter/pdf-download/67608",previewPdfUrl:"/chapter/pdf-preview/67608",authors:[{id:"299556",title:"Dr.",name:"Touhami",surname:"Tahenni",slug:"touhami-tahenni",fullName:"Touhami Tahenni"}],corrections:null},{id:"69142",title:"Implementation of an Artificial Vision System for Welding in the Retrofitting Process of a Robotic Arm Industrial",doi:"10.5772/intechopen.88360",slug:"implementation-of-an-artificial-vision-system-for-welding-in-the-retrofitting-process-of-a-robotic-a",totalDownloads:612,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"An industrial approach to the use of artificial vision is worked, and we are searching for the improvement of the welding process using a robotic arm. These kinds of robots in the last years have been associated to high accuracy tasks like classification, welding, object manipulation, assembly, and so on. Generally, the artificial vision is not used in works which use manipulator arm; this is normally due to the robot programmer who plans the robot task, which is executed cyclically, however, there are some approaches where different tasks using artificial vision are implemented. In this chapter, we present a retrofitting process of a manipulator welder arm Miller MR-2000, and the development of an artificial vision system, which could be used in the positioning of the machine. The developed system is able to look for areas suitable for the welding task between two pieces of material within a workspace; this process is possible using techniques of computational vision and image processing. Subsequently, the algorithm calculates the number of welding points based on the area identified previously, and finally, it sends the respective coordinates by means of G code to the robot for welding the pieces.",signatures:"Yomin Estiven Jaramillo Munera, Jhon Edison Goez Mora, Juan Camilo Londoño Lopera and Edgar Mario Rico Mesa",downloadPdfUrl:"/chapter/pdf-download/69142",previewPdfUrl:"/chapter/pdf-preview/69142",authors:[{id:"300249",title:"M.Sc.",name:"Edgar Mario",surname:"Rico Mesa",slug:"edgar-mario-rico-mesa",fullName:"Edgar Mario Rico Mesa"},{id:"300795",title:"Prof.",name:"Jhon Edison",surname:"Goez Mora",slug:"jhon-edison-goez-mora",fullName:"Jhon Edison Goez Mora"},{id:"300796",title:"Prof.",name:"Juan",surname:"Londoño Lopera",slug:"juan-londono-lopera",fullName:"Juan Londoño Lopera"},{id:"300801",title:"Prof.",name:"Yomin Estiven",surname:"Jaramillo Múnera",slug:"yomin-estiven-jaramillo-munera",fullName:"Yomin Estiven Jaramillo Múnera"}],corrections:null},{id:"69261",title:"EBSCO Discovery Service (EDS) Usage in Israeli Academic Libraries",doi:"10.5772/intechopen.89453",slug:"ebsco-discovery-service-eds-usage-in-israeli-academic-libraries",totalDownloads:723,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Awareness to the problem that different search interfaces discourage patrons’ use of library information sources has led academic libraries to implement web-scale discovery services. These services offer the user a “Google-like” search experience of library resources. This study aims to explore library professionals’ satisfaction, patrons’ information behavior, and use of EDS discovery tool service in academic libraries in Israel. Mixed research methods were used in this study: qualitative and quantitative. Qualitative research methods are through content analysis of library directors’ interviews, and quantitative research method is through collected library metrics (from Google analytics) data analysis, regarding usage patterns and search session analysis. The study aims to gain insight regarding library implementation and patrons’ information behavior of the EDS discovery tool, in Israeli higher education institutions.",signatures:"Riki Greenberg",downloadPdfUrl:"/chapter/pdf-download/69261",previewPdfUrl:"/chapter/pdf-preview/69261",authors:[{id:"306624",title:"Ph.D.",name:"Riki",surname:"Greenberg",slug:"riki-greenberg",fullName:"Riki Greenberg"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"9965",title:"Computational Optimization Techniques and Applications",subtitle:null,isOpenForSubmission:!1,hash:"d2c7d240aed947e7780605dab6dde1c3",slug:"computational-optimization-techniques-and-applications",bookSignature:"Muhammad Sarfraz and Samsul Ariffin Abdul Karim",coverURL:"https://cdn.intechopen.com/books/images_new/9965.jpg",editedByType:"Edited by",editors:[{id:"215610",title:"Prof.",name:"Muhammad",surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10518",title:"Cybersecurity Threats with New Perspectives",subtitle:null,isOpenForSubmission:!1,hash:"de548f0f3bdfd40d0e417d04782899e6",slug:"cybersecurity-threats-with-new-perspectives",bookSignature:"Muhammad Sarfraz",coverURL:"https://cdn.intechopen.com/books/images_new/10518.jpg",editedByType:"Edited by",editors:[{id:"215610",title:"Prof.",name:"Muhammad",surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9905",title:"Biometric Systems",subtitle:null,isOpenForSubmission:!1,hash:"c730560dd2e3837a03407b3a86b0ef2a",slug:"biometric-systems",bookSignature:"Muhammad Sarfraz",coverURL:"https://cdn.intechopen.com/books/images_new/9905.jpg",editedByType:"Edited by",editors:[{id:"215610",title:"Prof.",name:"Muhammad",surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3845",title:"MATLAB",subtitle:"Applications for the Practical Engineer",isOpenForSubmission:!1,hash:"1079f9d5879db7c7c13257713a2e9710",slug:"matlab-applications-for-the-practical-engineer",bookSignature:"Kelly Bennett",coverURL:"https://cdn.intechopen.com/books/images_new/3845.jpg",editedByType:"Edited by",editors:[{id:"169605",title:"Dr.",name:"Kelly",surname:"Bennett",slug:"kelly-bennett",fullName:"Kelly Bennett"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10991",title:"Digital Image Processing Applications",subtitle:null,isOpenForSubmission:!1,hash:"e7e57bea225c50ab5ac522627afc9d93",slug:"digital-image-processing-applications",bookSignature:"Paulo E. 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The changes and advancement in the socio-economic and cultural systems globally, indicate the need for rethinking knowledge construction in schools as well as teacher education and training. The transformation of the mindset of knowledge recipients to knowledge constructors in teachers should be the main focus in the teachers’ education and training. This work contests the view of the perennial and essential philosophy to reproduce knowledge of discoveries, inventions and construction which does not inspire and challenge those who receive it. The assertion of [1] about education raises questions about education as a concept and the phenomenon thereof. If education was indeed about knowledge creation and not reproduction of knowledge, what has been learnt could not been forgotten. The Phenomenologist Psychologist describes learning as the process of creating lived experiences, from the environment and one’s surroundings. The knowledge therefore becomes part and parcel of one’s being, and the lived experiences are the basis for any further knowledge creation. If learning is about mental, emotional, and physical development, firstly, the person acquiring knowledge will have the understanding of; what knowledge, why knowledge and how knowledge? The explorations, inquiry and search for suitable and relevant information is driven by the inquest to solve problems experienced from the real-life environment, not about idealised situations. It is this sense that this work conceptualises B.F Skinner’s assertion about education. The other issue that is linked to Skinner’s assertion about education is viewed in this work to be the compartmentalised knowledge into the abstract realities, which are delinked from the real-life experience. According to [2], knowledge that is brought into the classroom as reported reality, is more relative than the actual lived experience, which is authentic practical experience and the reality of the process and results of problem solving, exploration and inquiry. The post-school education and training cannot be the continuation of the approach to knowledge acquisition at a school level. Research has highlighted that the conformist approaches to knowledge acquisition in South Africa and globally had deprived teachers the opportunity for lifelong learning, reflective thinking, and subsequently teachers have become technicians [3, 4, 5]. This work supports the trajectory of scholarship, which promotes the descriptions of educational practices as a process of engagement with the reality and surrounding environment for the purpose of creating knowledge and developing essential cognitive, affective, and psychomotor skills. According to the educational psychology, the mental growth and development is the results of the process of becoming, meaning that adaptation in the environment demands problem solving, exploration and inquiry. These are therefore cognitive skills, or the functions performed by the mind for the purpose of enabling the individuals to master the demands and challenges posed by the environment. The mind alone cannot complete the function of adaptation and mastery of the environment and surroundings, but the affective skills also play a role, for example, the decision-making processes are based on; a willingness to participate, the choice to respond or to receive, and interest. The aspect of psychomotor skills is the physical actions or movement driven by the affective and cognitive abilities to address the desire to adapt to the environment and to master the realities in the surroundings.
The argument on the necessity and importance of the learners’ perspective in knowledge construction in teacher education and training is informed by the data collected from lesson observations. The desire that manifested from teacher-learners’ interaction regarding factual knowledge, confirmed the ideas advocated by constructivist, humanist, cognitive and phenomenologist approaches, which identify the nature of the learners to rely on their interest, familiarity with context and experiences to conceptualise knowledge [6]. The findings presented in this work are the extension of this narrative, that promotes the contestations and debates in the classroom to allow learners to express their opinions, interests and experiences of what is presented to them. In addition, the findings from the data influenced this work to firstly assert that factual knowledge presented to learners in the field of Natural Science and Social Science in grade nine is irrelevant to the learners’ interests, familiar contexts and real-life experiences. Secondly, learners have no confidence in the textbook knowledge and in the teachers’ abilities to transverse knowledge and general outlooks to real-life world experiences, to assist learners to develop an in-depth understanding of scientific phenomena. The lack of opportunities for debates and reflective argumentation in Natural Science and Social Science classrooms, is perceived in this work to be incongruent with the assertion that “education is what survives when what has been learnt has been forgotten” [1]. The assimilation of raw facts deprives learners in the Natural Science and Social Sciences classes the opportunities to explore, discover, and investigate facts through deductive reasoning and logical thinking, hence learners were not complaisant with the explanations from the teachers and the textbooks in the observed lessons for this chapter.
The educational and curriculum transformation in South Africa reflects ideas and perceptions that had been advocated by international research. With regards to knowledge production, the Department of Education established the National Qualification Framework, to articulate phases in the educational system, and curriculum design and organisation. The restructuring of knowledge in the national school curriculum encapsulated ideas of the so-called mode two knowledge; the clustering of compartmentalised knowledge in a broader field of study [7, 8]. The first curriculum introduced by the new education ministry for the democratic South Africa was called, Curriculum for the 21st century, and this curriculum introduced a concept of ‘Learning Areas’, to replace subjects in the national curriculum for schools, for example, Life Sciences in a school curriculum encapsulated knowledge regarding aspects of life and sciences and it was for this reason that it changed from being a subject to being called a ‘Learning Area’.
The curriculum transformation in South Africa from 1997 to 2010 has been criticised in the works of academics and researchers [9, 10] for being vague and too broad, in the sense that the adopted design for Curriculum 2005 or Curriculum for the 21st century did not take the capacity of the current cohort of teacher into account. The criticisms were justified by the revelations and findings in the report of the ministerial task team appointed by the Department of Education to investigate the challenges and difficulties which findings are highlighted in the works of [11, 12]. According to [13] the main focus of the investigation covered; the field testing, teacher orientation and follow up training, professional support services provided within provincial systems, classroom practices, the quality, quantity, use of learning support materials in support of the Curriculum for 21st century, and the level of understanding of outcomes- based education. The findings highlighted by the task team from its review provided this work with the understanding of the background and the process that resulted in the current educational and pedagogical practices of teachers in schools. This background provides a clue about the views and the purpose of the designers of the curriculum for the 21st century concerning the transformation of a paradigm of knowledge production and pedagogy suitable for equipping citizens with skills, abilities, and knowledge of global standards. According to the task team’s report the decline in the levels of abilities and skills to read, write and to understand and perform numerical calculation in mathematics was of great concern, the levels of incapacity of teachers to comprehend the philosophical and theoretical principles and ideas underpinning the curriculum changes resulted in chaos in the learning environment. Teachers were struggling to understand and to implement curriculum guidelines due to the inability to conceptualise the new terminologies and concepts that were introduced in the Curriculum for 21st century. According to the curriculum guidelines teachers were expected to create a knowledge structure by integrating conceptual knowledge to in order to promote correlations within the Learning Area (related subjects), for example Natural Science, which is a cluster of physical science and life sciences in the General Education and training phase of the National Qualification Framework. The systemic evaluations conducted by the department in the subsequent years through the annual assessment (ANA) highlighted that curriculum transformation in spite of all various interventions by the department, implementation of the purposes and intentions of the curriculum designers were not attained in South Africa. Despite the recommendations and proposal to the department based on the continuous reviews of the curriculum to; adjust the curriculum by scrapping the new terminologies and concepts and reversing ‘Learning Areas’ in favour of subject content knowledge, supply schools with textbooks, allow teachers to utilise the traditional ways of teaching and learning, which they are familiar with, and assess learning of knowledge as they have been professionally trained to do. The reversal of the changes introduced in the Curriculum for 21st century in South African terms was aimed at getting education “back to basics” and this implied the perpetuation of traditional practices based on the absolutist and perennial view of knowledge, conceptualisation of learning and traditional behaviourist pedagogical content knowledge. This study finds it interesting that the recommendations referred to in this work were from the ministerial team whom the minister considered to be a skilled, prominent South African educationist-curriculum and evaluation specialists, school-based practitioners and department-based policy makers [13].
The recommendations of the 2000 and 2008 ministerial task teams persuaded the ministers of education to consider revising the school curriculum and indeed, in 2005 the National Revised Curriculum (NRCS) and NCS were the version of the streamlined curriculum changes, and later in 2008 the curriculum became the Curriculum and Assessment Policy Statement (CAPS). The education ministers in the education department proclaimed that the revisions in the curriculum statement for the 21st are still based on the principles of constructivism and outcome [14].
This section presents the conceptual framework drawn from the synthesis and analysis of the contesting perspectives concerning the conceptualisation of knowledge structure and knowing. Literature points to the emerging perspective advocated in the works of [15, 16, 17, 18, 19] which contest the classification of knowledge into heterogeneous subject or discipline content. Researchers who pursue the narrative of knowledge integration [20, 21] had proposed different approaches to hybridism of heterogeneous knowledge structure and those are: interdisciplinary, multi-disciplinary and cross-disciplinary. [22], in the same vein suggested that an outcomes-based curriculum model is an appropriate tool for promoting an integrated knowledge structure in the school subject curriculum. In pursuit of the relevant curriculum design for implementing hybridisation of knowledge [23, 24] proposed the consideration of two approaches to curriculum designs; first is the subject-based designs which entails: broad fields curriculum that merge several disciplines into interdisciplinary subject areas, this curriculum allows more correlation, integration, and holism, for example, Natural Sciences, Social Studies or Sciences and humanities etc. Second, is integrated the curriculum design, which encourages integration of concepts across, within and to future knowledge [25].
The opinions and ideas from the works of [26, 27, 28] informed this study regarding alternative ways to knowledge production that are recommendable for a lifelong-long process. These researchers share similar views of knowledge as a social construct; its production reflects elements of engagement of humans with reality in a specific time and context, interaction between human and environment as well as real-life problems. The understanding of knowledge established from this perspective highlights that knowledge is time and context specific and therefore knowledge is fallible and not everlasting. Similarly, the constructivism and progressive philosophical ideas support the view of knowledge as a process, which is driven by socio-economic needs and demands [29, 30]. The issue of knowledge in the classroom should be assessed in terms of relevance to the current socio-economic needs of the nation or society, worthiness to provide solutions to the current and future problems in the society. By the same token, [31, 32] argue that subject content knowledge in textbooks present the narrow and linear programmed or structured factual knowledge, which is mostly based on the unilateral world view of the author. Ideas drawn from ([31], 16) affirm the importance of questions that lead to the construction of a new set of connections and fresh perspective of knowledge structure. ([33], 5) also, alluded to composition of knowledge structure, to be both a social construct and real, while [27, 34] pointed out that knowledge comprises of commonsense, assumptions, conclusions, and hypothesis, therefore the validating and verifying of knowledge is an ongoing process. [14] supports the notion of knowledge as a fallible product and argued that knowledge is neither universal nor absolute because its production is regulated by contexts in terms of time, socio-cultural and economic advancements.
In the context of a school curriculum, [35] stated that subject content knowledge should not be confined to textbooks, instead learners and teachers should focus on current and future realities and current phenomena that affect the society. [19], extended the rhetoric of classroom-based knowledge construction when expressing the recognition and acknowledgement of learners’ perspectives of world outlooks in the process of curriculum development. [25], supports the promotion of contemporary ideas and knowledge when pointing out that the view that knowledge is generated through senses meaning, the sense of sight, hearing, touch, taste and smell. The constructivist such as John Dewey posits that knowledge is both tacit or implicit and explicit; the tacit knowledge is the collective noun for ideas, views, experiences and opinions constructed as individuals interact with reality and the environment, whereas the explicit knowledge is the expressions of the tacit knowledge, in other words the experiences and ideas an individual prefers to share with other individuals.
The opinions and ideas drawn from [24, 27] reveal contestations surrounding the philosophical and theoretical paradigms of knowledge production, which are empiricism or analytic, interpretive or hermeneutics, praxis or critical pedagogy. The empiricism paradigm pursues the scientific methods and procedures to produce knowledge, hence the countenance of knowledge is based on verification and validation of facts through scientific methods. According to [2, 13] subject content taught in classrooms is the product of scientific procedures conducted far away from the place of learning. The argument expressed by these researchers is that the main aim and the core for learning the subject content is the knowledge of the process of production rather than receiving the product. [19], also pointed out that the subject content curriculum that promotes perennial philosophical views of knowledge emphasises an absolute and universal approach to knowledge acquisition; memorisation and acceptance of facts without reflections and argumentative debates.
The discussion of different paradigms and philosophical underpinning are of importance to this work, because the main focus is on the issue of worthwhile, truthfulness and relevance of knowledge or information taught in the Natural Sciences and Social Sciences to school learners. The problem statement was to investigate the perspective of knowledge from the manner in which learners view knowledge that is taught, teachers’ perspectives of knowledge and the engagement of teachers and learners during knowledge acquisition. [28], argued that knowing is not only limited to empirical or scientific knowledge, but other ways such as intuition, revelations, reasoning, and logic, are recognised ways of knowledge construction. The data collected from classroom practices of pre-service teachers and the challenges they encounter in reproducing the traditional facts of the ancient times pointed to outdated facts and pedagogical content knowledge of the teachers.
This work draws theoretical ideas and views from constructivist, progressive and phenomenologist theories. The advocates of the constructivist theory assert that learners have their points of view and perspectives to life and reality resulting from the process of adaptation in their environment [35]. To the constructivist theory, learning is a process of becoming and it is through mastery of abilities, knowledge, and skills that the learners attain self-realisation, meaning that the learner seeks to find answers to the questions and solutions to the real-life problems [14, 24, 29, 32, 33] in the same viewpoint assert that it is in the nature of the learner to ask questions about their surroundings, and the relationships between entities that constitute their world. The researchers in theory recommend that learners should be exposed to real-world problems rather that abstract realities, for them to construct their knowledge by means of explorations, investigating, problem-solving, trial and error, and experimentation [18, 29]. In the same narrative, ([27], 7) argues that the nature of knowledge and characteristics in a progressive and pragmatic context, meaning knowledge that reflects the past, present and projecting the future possibilities are; engaging, existential, expressive, evolving, experimental, anti-entropy, and entertaining. These six aspects or characteristics provide guidelines. The constructivist theory supports the learner-centred strategies to teaching and learning; allowing learners to ask questions or identify problems that they want to solve. [32, 33, 36, 37] point out that, learners could enjoy the freedom to explore and construct their own world view if the curriculum designers perceive knowledge as a process or means to an end, not as infallible and indisputable facts. Similarly, the phenomenologist theory echoes the sentiment of the consideration of individuals’ interests, emotional and cognitive needs, freedom of choice, and their experiences, as fundamental aspects of the process of knowledge acquisition and construction [24, 25]. The recent researchers of the learning revolution [38] advise that learning for the future advancements in human life, should account for the demands of the changing times in human cultural development, and shift from the traditions of handling learners as empty vessels to be filled with insignificant and outdated factual knowledge. These researchers recommend the recognition of talents and imaginative abilities as essential meta-cognitive and intellectual abilities which are innate in learners.
This work also drew ideas from [22, 35, 39] about quality teaching and learning, as he asserted the importance of the three interactions. First is the learner-knowledge interaction, second, teacher-knowledge interaction and third, the teacher-learner interaction. The conceptualised interactions demonstrated in the diagram, indicate the worlds or dimensions from which the participants create their own meaning of the content knowledge. According to constructivist and phenomenologists’ theories, the teacher should allow learners to engage with the content knowledge and to build up new understandings, and if learners are to construct their own understanding of the content knowledge, teachers should capitalise on the learners’ prior knowledge and imaginations [18, 19, 29]. ([35], 49) proposes ways in which teachers could support and encourage learners to interact with knowledge for an in-depth understanding and creation of new knowledge, and this should be done through asking simple questions, for example, ‘How did you know about that? Did anyone approach this problem in a different way? Is there anyone with the similar view of knowledge? [35] is of the view that teachers should always establish the patterns of thoughts of the learners, be aware of and accept learners’ perspectives and to organise concepts and ideas such that learners are able to discern for themselves issues or knowledge that require more exploration and investigations.
The three interactions are the focus of this work used during the analysis of the three scenarios or case studies with the purpose of understanding the perspective of knowledge, its relevance to their cognitive abilities, emotional development, and construction of their own outlook to reality and world views. In this work the problem statement is the perennial knowledge structure promoted by the current curriculum design and its relevance to the transformation of South African learners’ world outlook. The question linked to this problem statement is: How do learners perceive school knowledge and the problem and challenges in real world systems?
The constructivist theory warns that imposing knowledge to learners as fallible and conclusive deprives learners the opportunities to develop intellectual skills; logic, evaluation, critical thinking, hypothesising and creative thinking [7, 23, 29, 33]. The Piaget theory on human cognitive development revealed that at a formal operational stage, children can think hypothetically and critically about things around them, therefore an exposition of knowledge that acts against this principle is viewed in this work to be oppressive and manipulative to the young generation.
This research is guided by the views and opinions of the critical study to expose the manipulation and oppressive approaches to knowledge acquisition in South African schools, and the purpose is to evoke a rethinking of the approach to knowledge structuring that is suitable for liberating learners’ minds in the 21st century. According to ([40], 471) critical study is a qualitative research in which the researcher is committed to exposing social manipulation and changing oppressive social structures for the purpose of finding the discourse to the current practices.
The case study design was chosen for the study and the rationale was that the researchers intended to utilise interviews and observations of the interactions in the teaching and learning processes in the classrooms. In this vein ([41], 41) refers to the case as the situation selected by the researcher in which a phenomenon is described by participants’ meanings of the process or events. The second connotation of the case study refers to the research design which enables the researcher to apply qualitative procedures and techniques to obtain an in-depth understanding of the phenomenon. In this study the first connotations describe the focus, which in this case is the interaction between learners and subject content knowledge interaction in the broad field curriculum for the 21st century in South Africa; Social Sciences and Natural Sciences.
The participants in the research were selected from the group of in-service teachers in their post-graduate teacher qualification. The purposive sampling strategy was used to select students with the highest qualifications in the knowledge of the disciplines, for example, Social Sciences students who specialised in Geography and History, and for Natural Sciences, students who specialised in Physical Science and Chemistry or Life Sciences.
The research ethics were considered during the selection of participants and the application of research instruments. Firstly, students were informed about their rights which were: to participate voluntarily, to opt out if they wish to do so, they will not be coerced to answer or provide information which they feel is confidential; their identity and personal details were to be kept anonymous. The learners were informed that the information gathered is not about them, but the observations focussed on the process of learning and teaching.
The selection of the participants in the study adopted a snowball sampling strategy. Snowball sampling is about recruiting participants from the larger sample [40, 41]. The participants in the focus group consisted of sixteen grade nine learners and two teachers who taught Natural Sciences and Social Sciences. The criteria used to recruit participants were: active participation in the class discussions, and a willingness to share opinions and ideas during the lesson.
The primary sources of data were notes developed during the observation of lessons focussed on the learner-knowledge interaction, teacher-knowledge interaction, and teacher-learner interaction. The second set of data was obtained from interview transcripts developed from the students’ reflections during face-to-face discussions after the lesson observations.
The study utilised an observation schedule focussing on the four areas of pedagogical interactions, which are learner-teacher interaction, learner-content knowledge interaction, teacher-content knowledge interaction, and teacher-learner-subject content knowledge interaction in the teaching and learning environment. The capturing and analysis of data focussed on learners’ perceptions of subject content knowledge and opinions about how best the subject content knowledge could be taught more meaningfully to them. The second set of data focussed on the appropriateness and adequacy of feedback and explanations of the teachers to learners’ questions and opinions.
“Researcher needs to live in classrooms, to see the complex forms of interaction that occur in classrooms. In this way, more accurate pictures can be got of which particular kind of students get what particular kind of knowledge and dispositions, one can also see how knowledge is actually created and used in classroom settings” ([32], 15).
The qualitative data analysis procedures were followed; first the data recorded in the observation schedule was given codes. According to [42] a code is a descriptive name for the topic of subject of a data segment. Second, the codes were organised into units focussing on the learners’ reflections, questions and comments and the category for this data was learner-knowledge interactions. The codes that highlighted teachers’ comments, explanations and feedback comprise the category of teacher- knowledge interaction and the last category was formed by actions and behaviour indicating satisfaction, doubts and confusion, and all these were classified under teacher-learner interaction.
Data coded and classified under learner-knowledge interaction were questions asked by learners during the conclusion of the Social Sciences (Geography) lesson and comments made by learners comprise the data summarised in the table.
Learner X asked: “Is earth moving or revolving from the east to the west?”
Learner T asked: “Does the sun rise and set or is it the earth rises?
Learner C asked: “Why does the teacher say the sun rises from the east and sets on the west? Is there such a thing?
Learner R: “Sir, there is something that worries me about the shape of the earth. The globe shows that earth is round, but on the chart the earth is flat. If the earth is like that globe what makes water in the oceans and rivers change position as the earth rotates?”
Learners G: “Sir, I have learned from the Natural Science textbook that the sun does not move, only the earth and other planets rotate around the sun.”
Learner K: “It is wrong to say the sun rises from the east and sets on the west. There is no rising and setting of the sun here.”
Learner F: “And then….. (
Learner J: “I believe the earth is flat, no earth round rather I can say it is round and flat.”
Learner L: “Why are [we] learning this because the Natural Science books and the teacher say something different and the Social Science books and the teacher teach us another thing. What is the truth?”
Learner N asked; “Madam, is the ocean water a soluble or solution?”
Learner Z asked; “What makes ocean water taste so much salty because there is no salt?”
Learner P asked; “Is it true, teacher that all human beings were apes, long-long ago? This information is in the Natural Science textbook.”
Learner S asked; “Who saw these changes and why are we learning about this? How is this information preparing us for jobs?”
Learners commented:
Learner C, “Learning about these things is boring to me and I see no need of knowing anything about apes and this evolution.”
Learner E, “I like to know more about cars and aeroplanes, not the apes and soluble and solvents. At home I spend time reading about cars and drawing cars.”
Learner J: “School is boring because we sit in class, listen to all these lies from the books, writing notes from the book and writing tests.”
Learner M “I am sick and tired of knowledge that does not help us to know how cell phones are made, televisions and music.”
The importance of the data from the questions asked by the learners and comments in this work, as highlighted under the section of data analysis, was to establish the holistic perspective of learners concerning firstly, their interpretation of reality and the environment, and relating knowledge that is an abstract form with their common-sense knowledge, and prior knowledge. Secondly, the comments revealed the perceptions of knowledge learned from the subjects or broad fields in the school curriculum in relation to learners’ feelings, interests, experiences, and views on the relevance of information to their actual life beyond the school. The data from the comments and questions pointed to the criteria used by learners to evaluate knowledge, teaching and learning. The data highlighted that the main premise for logic and reasoning in the learner-knowledge interaction are: (i) relevance, (ii) truthfulness, (iii) worthiness, (iv) evidence and (v) context for the content knowledge. The question asked seeking relevance was for example, “How is this information preparing us for jobs?” Whereas comments that expressed the similar sentiment were: “I am sick and tired of knowledge that does not help us to know how cell phones are made, televisions and music”. According to [2, 14], highlighted in their work, that meaningful knowledge is not just information, but its essence is in the process of production, because the process of production encapsulates the relevance in terms of time and environment contexts. These researchers contended that the only choice in knowledge production currently is between positivism, absolutist, and constructivist relativism, and this trajectory limits the insight into the multifaceted, evolving, and dialogic nature of content knowledge.
Learners distanced themselves from the confusion they identified in the information presented in the textbooks. The contradiction presented in what had been taught for so many years in the subject as factual knowledge, was considered by learners as fallible because it does not provide sense to their questions. To emphasise the importance of knowledge and knowing [10, 11] cited Maton’s legitimating theory, to reveal that knowledge structure had a knower structure, this assertion, is in congruence with the evidence highlighted in the learners’ propensities expressed in their comments and questions, for example, “school is boring because we sit in class listen to all these lies from the books, writing notes from the book and writing tests”, “I am sick and tired of knowledge that does not help us to know how cell phones are made, televisions and music.” These comments highlight that the current generation of learners are not the knower structure for the knowledge structure that is prepared for them. The perspective of the school and classroom being “boring”, was interpreted in this study to mean an oppressive and manipulative environment, because of the comparison drawn between the content knowledge and the expectations, interest and desires for the future, which are not taken care of in the knowledge structure. The argument, about the knowledge structure and knower in the works of ([32], 15) is, in whose interest is certain knowledge (facts, skills, propensities and dispositions) taught in the school curriculum? The concerns of the learners indicate blind spots in the selection and organisation of knowledge in the textbooks and in the school curriculum at large. The dimension of the learner in the selection and sequencing of learning content, from the learners’ perspective does not consider relevance, interest, future plans and desires of the learners, who are the consumers of the product. Instead, knowledge is packaged for the sake of keeping busy in the classroom, which in their view was just a waste of their time and opportunities. The definition of the term ‘education’ by the international researchers and the theorist, B.F Skinner is confirmed in the findings on learner-knowledge interaction, there are specific aspects pointed in the definition “education is what survives when what has been learnt has been forgotten.” The findings provided evidence to the definition of education in the quotation, which implies meaningless and contradictory factual knowledge taught in classroom, the survival implies awareness of the contradictory and meaningless factual knowledge, recall of factual knowledge for the purposes of marks and to obtain a certificate. The conceptualisation of the phrase, “what has been learnt has been forgotten” insinuates that some of the knowledge will be for the short while, which could be for the purposes of test and exams. The learners’ comments and questions made it clear that content knowledge that does not have value to their present and future is a waste of time at the expense of what is of significant to them. The imposed worthless knowledge to them in the school curriculum creates negative perceptions about schooling and knowledge. The phenomenologist and constructivist principles about the learner, learning and knowledge, recommends that learners should be viewed and treated as active participants in knowledge production or construction; learners have their own desires, interests and perceptions about knowledge, and skills that are learnt; learners should not be treated as empty vessels [7, 33]. Concerning knowledge and meaningful learning, [8, 22, 35] emphasise the importance of context and content, the context is the authentic world of knowledge production and its application, whereas content is the collective of conceptual, practical, procedural domains of knowledge about real life phenomena. In the context of the finding highlighting the rejection of content knowledge about the positions of the earth and the sun, the main issue was that learners wanted the practical and procedural understanding of the positions, for them to be convinced. The debate and contradictions contributed to the rejection of the factual knowledge due to the lack of evidence from practical and procedural knowledge from the authentic context where the knowledge is produced.
The ability to connect factual knowledge from Natural Sciences and Social Sciences highlighted in the data provided confirmed the Piaget theory of cognitive development, which states that learners at the age of ten and up, are able to think at an abstract level and generate hypotheses. The critical thinking and evaluation skills on the truthfulness and worthiness of scientific facts in the Natural Science and Social sciences about the positions of the sun and the earth was to learners a theme with contradictions in both fields of knowledge production.
Researcher into teachers’ professional development push the rhetoric of high-quality instruction for quality learning in classrooms [12, 13, 14, 20, 35]. The clarity seeking questions asked by the learners highlighted the deep inquest for knowledge that is not provided in the textbooks. The learners’ questions exposed the limitations in the teacher’s competence to think beyond the textbook knowledge, and as a result learners demonstrated their dissatisfaction and loss of hope and trust in their teachers. The data highlighted that teachers in the two classrooms relied on the perennial approach to knowledge and teaching strategies, which do not take heed of learners’ perspective or viewpoints, hence teachers were caught off guard when confronted by questions requiring in-depth explanation of scientific knowledge. [24, 25] highlighted that a perennial view of knowledge promotes reproduction and transmission of factual knowledge, and does not provide room for contestations, however, the behaviour demonstrated by learners confirmed John Dewey’s counter view on knowledge, which pointed out that learners are interested in knowledge that relates to their daily life experiences. The attitude of the teacher to learners’ questions dented the trust in the teacher-learner relationship, which according to [19, 28, 32] is fundamental to effective learning. The learner-knowledge interaction revealed that teachers lacked the ability to relate content knowledge to the real-life situations and context. This research exposed that learners think beyond the book’s factual knowledge and were able to challenge the teacher-knowledge interaction, which proved to be meaningless to the learners’ search for in-depth understanding.
Reflections on the lesson, according to the evaluation form, the teacher was expected to allow learners to ask questions for clarity purposes. The data presented in two columns show the learner-teacher interaction about the plane earth and the positions of the sun, east and west.
“Yes, the sun rises from the east, read your Social Science textbook”.
“The earth is round and revolves around the sun”.
“The earth is the circumference, with imaginary lines”.
“The sun is the source of energy for the biosphere”.
“The sun is static, meaning that it does not move”.
“Yes, I know it, I am a graduate meaning I have a degree in Geography”.
“The forces of nature make the sun to rise up from the east and set on the west. When you wake up in the morning you can see this for yourself.”
“Yes, the sun moves up from the east and move down in the afternoon and sets in the west”.
“I do get your point, but you should not worry about this for now”.
“The textbook is written by expects and scientists they have conducted experiments”.
“This means that what they say is true and you should believe it”.
“All what you should know is that the sun rises from the east. East is the direction on the compass”.
“In Natural Science, yes we know that the sun does not move”.
“There is only one sun. Do not be confused by these two”.
“There scientist in the Natural Science have tested this and discovered that it to be true, that the sun does not move only the planets rotates around the sun”.
Despite the proposals of the Department of Higher Education in the renewal curriculum policy guidelines, to ensure that pre-service and in-service teachers are equipped with the competence to master theoretical knowledge as well as contexts and conditions under which knowledge is produced in the field or discipline. This work revealed that teachers’ knowledge interaction lacked evidence of epistemological principles highlighted by ([33], 25) and [27] which include: logical thinking; the application of deductive reasoning or syllogism that consists of premises. The first premise is called a major premise that comprises generalised perceptions of the reality, second is, the minor premise; the particular perceptions, and third is the conclusion. The questions asked by learners about the rising and setting of the sun were based on the generally accepted fact, which was confirmed by the subject teacher and the authors of the textbooks for Social Sciences for grade nine, on the other hand learners turned the fact into a hypothesis to be verified. The teacher–learner interaction was viewed by learners to be an opportunity to test the hypothesis to verify the truthfulness of the fact about the rising and setting of the sun. The teacher was unable to assist learners to understand the scientific procedures which led to the conclusion presented in the textbook. Instead, the teacher forced learners to accept the facts as presented in the textbooks. The disposition revealed that the role of the teacher in classroom is to perpetuate traditional practices in learning that promote regurgitation and memorisation of facts, and these traditional practices applied by teachers are in contradiction to the constructivist principles underpinning the curriculum, knowledge integration and contextual construction of knowledge.
The questions from learner-knowledge interaction confirmed the view expressed by [29, 31] that priori or common sense is the basis of knowledge production. Learners’ priori exposed the dimension which the teachers were not aware of and had never expected from grade nine learners; hence the teachers were unable to address those questions.
The findings highlighted in the teachers-knowledge interaction and teacher-learner interaction pointed out that those teachers in the Social Science and Natural Science lesson show no interests in how learners internalise knowledge. Instead of adjusting the teaching techniques to acknowledge and accommodate learners’ queries and concerns, teachers defended the content knowledge, and cautioned learners about questioning knowledge generated by experts and the teachers’ knowledge of the subjects. According to [18, 20, 28, 29], the tendency to suppress learners’ points of view to knowledge and their perspectives is detrimental to meaningful and effective knowledge acquisition and learning. The learners expressed their discontent about the contradictions in the scientific knowledge presented in the textbooks and the views of the teachers. According to [27, 34] warned that the knowledge structure in textbooks is not authentic knowledge because it does not engage learners in the procedure through which that factual knowledge was produced. In the same vein, [35] expressed that factual knowledge without understanding of procedural processes involved in the production of knowledge is worthless to learners. The data presenting learners’ disgruntled dispositions confirms that learners were not satisfied with the knowledge of facts, the common interests were on how such facts were generated, and beyond that, they wanted the contradictions in the factual knowledge to be addressed.
The findings presented in this work pointed to the limitations in the development of the Natural Sciences and Social Sciences subject content knowledge. The first limitation is the promotion of the absolutist view of knowledge and traditional pedagogy. The reflections and learners’ perspectives of reality are not considered as part of knowledge interaction in the teaching and learning. According to [37, 39] constructivism, pedagogy and learner-centred teaching and learning provides learners with opportunities to engage critically with abstract reality by asking questions and developing hypotheses, to seek concrete examples that facilitate understanding of the facts. The second limitation was the teacher knowledge interaction, which pointed to the adherence of teachers to the textbook knowledge and lack of ability to relate abstract knowledge to reality. The findings of the study revealed that learners were frustrated by the teachers’ feedback and comments which indicated that teachers were unable to address the intellectual and cognitive needs of the learners. The questions asked by learners in the Natural Sciences and Social Science lessons pointed to the desire of learners to link abstract and factual knowledge presented by teachers and the textbook with the perceptual knowledge which forms learners general or prior knowledge. According to [21] prior knowledge or general knowledge forms the foundations for meaningful learning since learners use what they perceive from their surroundings to understand abstract factual knowledge.
The other limitation highlighted by the findings was the lack of research and investigating skills for science teachers, for example, questions asked by learners based on the use of the globe to teach a lesson about the structure of the earth should have been considered by the teacher as a hypothesis for investigating and research instead of suppressing the intellectual seeking questions. [8, 25, 31, 43] argued that scientific discoveries are not infallible, however, in their empirical nature, the space for further questions and hypothesis are inevitable.
This work concluded that the teacher-knowledge interaction promoted regurgitation and reproduction of factual knowledge whilst learner-knowledge interaction demanded interpretation, reasoning, deductive thinking and logic about subject content knowledge. The interpretation of this contrast is considered in this work to be an obstacle to the principles of the learner-centred approach underpinning the curriculum of the 21st century education in South Africa. According to [5, 12] teachers should encourage active learner participation of learners in the learning process, and the strategies recommended to teaching and learning are: investigation, research project, exploration, and experimentation, instead of memorisation and reproduction of knowledge. This work also concluded that learners’ intellectual capacity was suppressed by the beliefs of teachers about knowledge production, which was rigid and confined to textbook knowledge. The limitations in the teachers’ abilities to relate factual knowledge to everyday life reality, subsequently developed negative attitudes in learners towards the subject content knowledge.
The questions which this work raises for future research are: what qualities do prospective teachers require to engage learners in the process of knowledge production? Second, how is the principle of a learner-centred approach being conceptualised in the structuring of knowledge to benefit learners’ interests above those of the curriculum developers? Thirdly, how could knowledge structuring cater for differentiated interests and aspirations about life beyond the school? [14, 19, 23, 28] argue that learning and knowledge should not be confined within classroom frameworks, but it should empower learners with ideas and skills to adapt in the world beyond the school.
This work recommends the review of the knowledge structure, on the basis of findings from the comments of the learners which indicated that textbook knowledge is worthless and valueless in terms of helping them to achieve their goals. The narrative in this work serves to motivate for the recognition and acknowledgement of the importance of learners’ perspectives of subject content knowledge, and intellectual and cognitive needs of learners as well by teachers, teacher educators and national school curriculum developers. Education for the liberation of the mind can begin by equipping teachers with the competences of mastering knowledge production. In Scientific Studies knowledge production implies knowing and understanding procedures and scientific processes involved in scientific discoveries, verification of scientific knowledge, for example, investigations, experimentations, creation of hypotheses and methods of testing hypotheses, reasoning and logical thinking. Twenty-first century learners are more technologically inclined, and therefore the use of technology, as learner V indicated, that their interest as young citizens is to be knowledgeable about technology so that they can be part of the technological discoveries of the twenty-first century. The learners expressed views which indicated that they regard themselves capable or achieving their goals should they be allowed to explore their areas of interests using knowledge of modern technology. This work considered this determination and enthusiasm demonstrated by learners in the study, as an opportunity to be explored through alternative strategies to knowledge structuring, which will incorporate or apply learners’ perspective as a threshold to curriculum design, development, and implementation in practice.
The argument presented by this work confirms the definition of education in Skinner (1964) that, “education is what remains after all which has been learnt has been forgotten.” Teacher educators should think critically about this definition and begin to change the perceptions about learning and learners.
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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",metaTitle:"IntechOpen events",metaDescription:"In our mission to support the dissemination of knowledge, we travel worldwide to present our publications, authors and editors at international symposia, conferences, and workshops, as well as attend business meetings with science, academia and publishing professionals. We are always happy to host our scientists in our office to discuss further collaborations. Take a look at where we’ve been, who we’ve met and where we’re going.",metaKeywords:null,canonicalURL:"/page/events",contentRaw:'[{"type":"htmlEditorComponent","content":"May 18, 2022 | 1:00 PM - 2:00 PM CEST
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Using Salsa20/12 stream cipher, the texture images can be encrypted using bit masking and permutation procedures and as part of a new scheme for encrypting 3D objects, which complements the existing methods for 3D object encryption. 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We report on the level of student engagement and the extent to which learning outcomes were met through the introduction of such an activity.",book:{id:"11552",title:"Gamification - Analysis, Design and Development",coverURL:"https://cdn.intechopen.com/books/images_new/11552.jpg"},signatures:"Mike Mavromihales and Violeta Holmes"}],onlineFirstChaptersTotal:109},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:124,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:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"10",type:"subseries",title:"Animal Physiology",keywords:"Physiology, Comparative, Evolution, Biomolecules, Organ, Homeostasis, Anatomy, Pathology, Medical, Cell Division, Cell Signaling, Cell Growth, Cell Metabolism, Endocrine, Neuroscience, Cardiovascular, Development, Aging, Development",scope:"Physiology, the scientific study of functions and mechanisms of living systems, is an essential area of research in its own right, but also in relation to medicine and health sciences. The scope of this topic will range from molecular, biochemical, cellular, and physiological processes in all animal species. Work pertaining to the whole organism, organ systems, individual organs and tissues, cells, and biomolecules will be included. Medical, animal, cell, and comparative physiology and allied fields such as anatomy, histology, and pathology with physiology links will be covered in this topic. 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Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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